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How should urine electrolytes be ordered and interpreted in acute kidney injury and electrolyte abnormalities?
The case
A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.
Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.
Which urine electrolytes should be ordered in various clinical contexts?
Introduction
Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.
Acute kidney injury
Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.
FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.
Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.3 Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.2
Many of the limitations of the FENa also apply to the FEUrea, including interpretation in the elderly and use in acute volume changes. However, the FEUrea has unique limitations, particularly in patients with sepsis, as cytokines released in sepsis may interfere with urea transporters in the kidney and colon.2 Its interpretation also relies on intact functioning of the proximal tubule, which can be altered in many conditions including uncontrolled diabetes. Overall, the FENa and FEUrea can be helpful to determine the etiology of AKI, but only in certain clinical scenarios.
Hyponatremia
Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.4 It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.
Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.
Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.
Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.
Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.
In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).5
In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
Hypokalemia
About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.6
The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.
Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.
Hyperkalemia
Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).
CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.
Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.6
Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
Normal anion gap metabolic acidosis
The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.
The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.9
Additional considerations
Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.
Back to the case
Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.
Bottom line
Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.
Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.
References
1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.
2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.
3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.
4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.
5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.
6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.
7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.
8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.
9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.
Key Points:
• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.
• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.
• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.
• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad
Additional Reading:
Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.
Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.
Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.
The case
A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.
Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.
Which urine electrolytes should be ordered in various clinical contexts?
Introduction
Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.
Acute kidney injury
Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.
FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.
Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.3 Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.2
Many of the limitations of the FENa also apply to the FEUrea, including interpretation in the elderly and use in acute volume changes. However, the FEUrea has unique limitations, particularly in patients with sepsis, as cytokines released in sepsis may interfere with urea transporters in the kidney and colon.2 Its interpretation also relies on intact functioning of the proximal tubule, which can be altered in many conditions including uncontrolled diabetes. Overall, the FENa and FEUrea can be helpful to determine the etiology of AKI, but only in certain clinical scenarios.
Hyponatremia
Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.4 It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.
Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.
Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.
Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.
Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.
In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).5
In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
Hypokalemia
About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.6
The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.
Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.
Hyperkalemia
Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).
CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.
Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.6
Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
Normal anion gap metabolic acidosis
The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.
The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.9
Additional considerations
Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.
Back to the case
Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.
Bottom line
Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.
Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.
References
1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.
2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.
3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.
4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.
5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.
6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.
7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.
8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.
9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.
Key Points:
• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.
• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.
• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.
• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad
Additional Reading:
Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.
Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.
Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.
The case
A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.
Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.
Which urine electrolytes should be ordered in various clinical contexts?
Introduction
Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.
Acute kidney injury
Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several limitations.
FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.
Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.3 Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.2
Many of the limitations of the FENa also apply to the FEUrea, including interpretation in the elderly and use in acute volume changes. However, the FEUrea has unique limitations, particularly in patients with sepsis, as cytokines released in sepsis may interfere with urea transporters in the kidney and colon.2 Its interpretation also relies on intact functioning of the proximal tubule, which can be altered in many conditions including uncontrolled diabetes. Overall, the FENa and FEUrea can be helpful to determine the etiology of AKI, but only in certain clinical scenarios.
Hyponatremia
Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.4 It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.
Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.
Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.
Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.
Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.
In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).5
In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.
Hypokalemia
About 20% of patients are hypokalemic during an inpatient hospitalization. There is a broad differential for hypokalemia, including medical, nutritional, and medication-related causes. Exogenous insulin administration or endogenous production in cases of refeeding syndrome drives potassium intracellularly via the N+/K+ ATPase. Increased sympathetic activity from alcohol withdrawal, acute myocardial infarction, head injury, or thyroid imbalance, as well as iatrogenic causes such as albuterol administration, also drive potassium intracellularly. Diarrhea and nasogastric tube suction lead to gastrointestinal (GI) potassium losses, while antibiotics, chemotherapeutic agents, and diuretics can cause hypokalemia through renal potassium wasting. Hyperaldosteronism and renal tubular acidosis are less common causes.6
The history, review of medications, physical exam, and initial basic laboratory testing (electrolytes, BUN, creatinine, magnesium) should assess for pseudohypokalemia, poor oral intake, diuretic use, acid-base disturbances, or GI losses.
Measuring urine potassium is useful in the work-up of the hypokalemic patient when these conditions are not evident. Urine potassium – either 24-hour or spot urine potassium-to-creatinine ratio – can help determine if urinary potassium wasting is a factor. Potassium is excreted at a near constant rate throughout the day. A urine potassium-to-creatinine ratio corrects for variations in urine volume. When this ratio is greater than 13 mEq/g, renal potassium losses should be suspected. If the ratio is less than 13 mEq/g, hypokalemia is likely due to transcellular potassium shifts, GI losses, diuretics, or poor intake.
Hyperkalemia
Several concepts in hypokalemia are relevant to hyperkalemia. Redistribution of potassium into the extracellular fluid can cause hyperkalemia when the body tries to counterbalance low extracellular pH by potassium-hydrogen exchange. Medications may cause an extracellular shift of potassium (e.g. digoxin) or induce diminished potassium excretion (e.g. NSAIDs, spironolactone, ACE/ARBs).
CKD and end-stage kidney disease are common causes of hyperkalemia in the hospitalized patient – as functioning nephrons decrease, poor Na-K exchange ensues. Hypoaldosteronism and type 4 renal tubular acidosis are also on the differential diagnosis. Pseudohyperkalemia secondary to thrombocytosis, erythrocytosis, or activated platelets should be considered and evaluated.
Appropriate renal excretion of potassium is mediated by the connecting segment between the distal tubule and the collecting duct, and the cortical collecting duct itself. There are four major causes of hyperkalemia due to reduced urinary potassium secretion: reduced aldosterone secretion, reduced response to aldosterone, reduced distal sodium and water delivery (often related to low effective arterial blood volume), and kidney injury.6
Measurement of 24-hour urinary potassium excretion is of limited utility in patients with persistent stable hyperkalemia because urinary potassium excretion is related to potassium intake. The TTKG was previously used to assess the degree of aldosterone activity by estimating the potassium concentration in the cortical collecting tubule. However, some assumptions upon which this calculation was based have been considered invalid by the original studies’ authors, and the TTKG to evaluate potassium abnormalities is no longer uniformly recommended.7,8 Ultimately, if patients have persistent hyperkalemia, work-up for hypoaldosteronism should be considered.
Normal anion gap metabolic acidosis
The urine anion gap (UAG) is used to determine the cause of normal anion gap hyperchloremic metabolic acidosis by indirectly measuring urinary excretion of ammonium. To maintain a normal acid/base balance, hydrogen ions are excreted in the urine with simultaneous reabsorption of bicarbonate. Hydrogen ions are bound to ammonia (NH3) to form ammonium (NH4+), which is excreted as NH4Cl in the urine.
The UAG is calculated by adding urine sodium and urine potassium and subtracting urine chloride (see Table 1). In a patient without an acid/base disturbance, the UAG is positive because more Na and K is absorbed in the gastrointestinal system compared to Cl, and thus more Na and K is excreted in the urine. In a normal anion gap metabolic acidosis through an acid load or bicarbonate loss, the normal response of the kidney is to excrete more hydrogen ions, resulting in more chloride excretion as NH4Cl. This leads to a negative urine anion gap, as Cl excretion outweighs Na and K excretion. When NH4+ excretion is impaired, such as in distal renal tubular acidosis (RTA), the urine anion gap will remain positive despite the metabolic acidosis. Thus, a positive UAG points to renal causes of the normal anion gap metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.9
Additional considerations
Urine studies can also be useful for assessment of proteinuria and albuminuria in a patient with CKD or diabetes, diagnosis of plasma cell dyscrasias, the diagnosis and prevention of nephrolithiasis, and a wide variety of other conditions.
Back to the case
Our patient was admitted with an elevated creatinine of unclear chronicity, and subacute symptoms of uremia. Because she was oliguric, urine and serum sodium and creatinine were measured before intravenous fluids were administered. Her FENa was 2%, which was not consistent with prerenal azotemia or ATN. She was found to have CKD secondary to previously undiagnosed diabetes. Upon further questioning, she had been taking high-dose NSAIDs for her chronic knee pain. Her renal function improved mildly by withholding NSAIDs, and she was discharged with appropriate nephrology follow-up.
Bottom line
Urine electrolytes have specific indications and utilities for different clinical scenarios, and should be ordered in a targeted manner that can aide in diagnosing AKI, hyponatremia, hypokalemia, and normal anion gap metabolic acidosis.
Dr. Tummalapalli, Dr. Krouss, and Dr. Goetz are hospitalists in the department of medicine at the Icahn School of Medicine at Mount Sinai in New York City.
References
1. Brosius FC, Lau K. Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. Am J Nephrol. 1986;6(6):450-7.
2. Gottfried J, Weisen J, Raina R, Nally J. Finding the cause of acute kidney injury: Which index of fractional excretion is better? Cleve Clin J Med. 2012;79(2):121-6.
3. Steiner, RW. Interpreting the fractional excretion of sodium. Am J Med. 1984;77(4):699-702.
4. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM. Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol. 1990;34(4):163-6.
5. Shepshelovich D, Leibovitch C, Klein A, et al. The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. Eur J Int Med. 2015;26(10):819-24.
6. Mount DB. Fluid and Electrolyte Disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.
7. Kamel KS. Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens. 2011 Sep;20(5):547-54.
8. Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-45.e2. Philadelphia, PA: Elsevier; 2016.
9. Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: a clinically useful index of ammonium excretion. Am J Med Sci. 1986;198-202.
Key Points:
• In acute kidney injury, the FENa and FEUrea may be calculated to distinguish prerenal azotemia from ATN; however, FENa and FEUrea may be low in a wide variety of conditions other than prerenal azotemia.
• Urine sodium and osmolality values are helpful in diagnosing the cause of hyponatremia, but have a number of limitations in nonoliguric patients and those with CKD.
• An elevated transtubular potassium gradient (TTKG) may indicate renal loss of potassium in patients with hypokalemia.
• A positive urine anion gap (UAG) in the setting of a normal anion gap metabolic acidosis points to renal causes of the metabolic acidosis, whereas a negative UAG points to extrarenal causes such as bicarbonate losses in the GI tract.Ad
Additional Reading:
Goldstein MB, Bear R, Richardson RMA, Marsden PA, Halperin ML. The Urine Anion Gap: A Clinically Useful Index of Ammonium Excretion. Am J Med Sci. 1986;198-202.
Gotfried J, Wiesen J, Raina R, Nally Jr JV. Finding the cause of acute kidney injury: which index of fractional excretion is better. Cleve Clin J Med. 2012;79(2):121-126.
Kamel KS, Davids MR, Lin S-H, Halperin ML. Interpretation of Electrolyte and Acid-Base Parameters in Blood and Urine. In: Brenner and Rector’s The Kidney, 27, 804-845.e2. Philadelphia, PA: Elsevier; 2016.
Sneak Peek: Journal of Hospital Medicine
Background: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital.
Objective: To study the association of frailty (≥six points in the Clinical Frailty Scale [CFS]), HoD, and ACS with hospital outcomes, controlling for age, gender, acute illness severity (measured by a Modified Early Warning Score in the emergency department), comorbidity (Charlson Comorbidity Index), and discharging specialty (general medicine, geriatric medicine, surgery).
Design: Retrospective, observational study.
Setting: Large university hospital in England.
Patients: We analyzed 8,202 first nonelective inpatient episodes of people ages 75 years and older between October 2014 and October 2015.
Measurements: The outcomes studied were prolonged length of stay (LOS 10 days), inpatient mortality, delayed discharge, institutionalization, and 30-day readmission. Statistical analyses were based on multivariate regression models.
Results: Independently of controlling variables, prolonged LOS was predicted by CFS greater than or equal to 6: odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.36-1.77; P less than .001; HOD: OR = 2.16; 95% CI, 1.79-2.61; P less than .001; and ACS: OR = 3.31; 95% CI, 2.64-4.15; P less than .001. Inpatient mortality was predicted by CFS greater than or equal to 6: OR = 2.29; 95% CI, 1.79-2.94, P less than .001. Delayed discharge was predicted by CFS greater than or equal to 6: OR = 1.46; 95% CI, 1.27-1.67; P less than .001; HOD: OR = 2.17; 95% CI, 1.80-2.62; P less than .001, and ACS: OR = 2.29; 95% CI: 1.83-2.85; P less than .001. Institutionalization was predicted by CFS greater than or equal to 6: OR=2.56; 95% CI, 2.09-3.14; P less than .001; HOD: OR = 2.51; 95% CI, 2.00-3.14; P less than .001; and ACS: OR = 1.93; 95% CI, 1.46-2.56; P less than .001. Readmission was predicted by ACS: OR = 1.36; 95% CI, 1.09-1.71; P = .006.
Conclusion: Routine screening for frailty, HoD, and ACS in hospitals may aid the development of acute care pathways for older adults.
Read the full article at journalofhospitalmedicine.com.
Also in JHM this month…
- Screening for Depression in Hospitalized Medical Patients
AUTHORS: Waguih William IsHak, MD, FAPA, Katherine Collison, Itai Danovitch, MD, MBA, Lili Shek, MD, Payam Kharazi, Tae Kim, DO Candidate, Karim Y. Jaffer, MD Candidate, Lancer Naghdechi, DO Candidate, Enrique Lopez, PsyD, Teryl Nuckols, MD, MSHS, FHM
- Patient-Level Exclusions from mHealth in a Safety-Net Health System
AUTHORS: Keiki Hinami, MD, MS, Bhrandon A. Harris, MD, Ricardo Uriostegui, MD, Wilnise Jasmin, MD, MBA, Mario Lopez, MD, William E. Trick, MD
- Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study
AUTHORS: Ranjan Pathak, MD, Vijaya Raj Bhatt, MD, Paras Karmacharya, MD, Madan Raj Aryal, MD, Anthony A. Donato, MD, MHPE
- Assessment of the Readability, Understandability and Completeness of Pediatric Hospital Medicine Discharge Instructions
AUTHORS: Ndidi I. Unaka, MD, Med, Angela Statile, MD, Med, Julianne Haney, Andrew F. Beck, MD, MPH, Patrick W. Brady, MD, MSc, Karen E. Jerardi, MD, MEd
- Impact of Patient-Centered Discharge Tools: A Systematic Review
AUTHORS: Karen Okrainec, MD, MSc, Davina Lau, BSc, Howard B Abrams, MD, Shoshanna Hahn-Goldberg, PhD, Ronak Brahmbhatt, MBBS, MPH, Tai Huynh, MBA, Kenneth Lam, MD, Chaim M Bell, MD, PhD
Background: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital.
Objective: To study the association of frailty (≥six points in the Clinical Frailty Scale [CFS]), HoD, and ACS with hospital outcomes, controlling for age, gender, acute illness severity (measured by a Modified Early Warning Score in the emergency department), comorbidity (Charlson Comorbidity Index), and discharging specialty (general medicine, geriatric medicine, surgery).
Design: Retrospective, observational study.
Setting: Large university hospital in England.
Patients: We analyzed 8,202 first nonelective inpatient episodes of people ages 75 years and older between October 2014 and October 2015.
Measurements: The outcomes studied were prolonged length of stay (LOS 10 days), inpatient mortality, delayed discharge, institutionalization, and 30-day readmission. Statistical analyses were based on multivariate regression models.
Results: Independently of controlling variables, prolonged LOS was predicted by CFS greater than or equal to 6: odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.36-1.77; P less than .001; HOD: OR = 2.16; 95% CI, 1.79-2.61; P less than .001; and ACS: OR = 3.31; 95% CI, 2.64-4.15; P less than .001. Inpatient mortality was predicted by CFS greater than or equal to 6: OR = 2.29; 95% CI, 1.79-2.94, P less than .001. Delayed discharge was predicted by CFS greater than or equal to 6: OR = 1.46; 95% CI, 1.27-1.67; P less than .001; HOD: OR = 2.17; 95% CI, 1.80-2.62; P less than .001, and ACS: OR = 2.29; 95% CI: 1.83-2.85; P less than .001. Institutionalization was predicted by CFS greater than or equal to 6: OR=2.56; 95% CI, 2.09-3.14; P less than .001; HOD: OR = 2.51; 95% CI, 2.00-3.14; P less than .001; and ACS: OR = 1.93; 95% CI, 1.46-2.56; P less than .001. Readmission was predicted by ACS: OR = 1.36; 95% CI, 1.09-1.71; P = .006.
Conclusion: Routine screening for frailty, HoD, and ACS in hospitals may aid the development of acute care pathways for older adults.
Read the full article at journalofhospitalmedicine.com.
Also in JHM this month…
- Screening for Depression in Hospitalized Medical Patients
AUTHORS: Waguih William IsHak, MD, FAPA, Katherine Collison, Itai Danovitch, MD, MBA, Lili Shek, MD, Payam Kharazi, Tae Kim, DO Candidate, Karim Y. Jaffer, MD Candidate, Lancer Naghdechi, DO Candidate, Enrique Lopez, PsyD, Teryl Nuckols, MD, MSHS, FHM
- Patient-Level Exclusions from mHealth in a Safety-Net Health System
AUTHORS: Keiki Hinami, MD, MS, Bhrandon A. Harris, MD, Ricardo Uriostegui, MD, Wilnise Jasmin, MD, MBA, Mario Lopez, MD, William E. Trick, MD
- Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study
AUTHORS: Ranjan Pathak, MD, Vijaya Raj Bhatt, MD, Paras Karmacharya, MD, Madan Raj Aryal, MD, Anthony A. Donato, MD, MHPE
- Assessment of the Readability, Understandability and Completeness of Pediatric Hospital Medicine Discharge Instructions
AUTHORS: Ndidi I. Unaka, MD, Med, Angela Statile, MD, Med, Julianne Haney, Andrew F. Beck, MD, MPH, Patrick W. Brady, MD, MSc, Karen E. Jerardi, MD, MEd
- Impact of Patient-Centered Discharge Tools: A Systematic Review
AUTHORS: Karen Okrainec, MD, MSc, Davina Lau, BSc, Howard B Abrams, MD, Shoshanna Hahn-Goldberg, PhD, Ronak Brahmbhatt, MBBS, MPH, Tai Huynh, MBA, Kenneth Lam, MD, Chaim M Bell, MD, PhD
Background: Frailty, history of dementia (HoD), and acute confusional states (ACS) are common in older patients admitted to hospital.
Objective: To study the association of frailty (≥six points in the Clinical Frailty Scale [CFS]), HoD, and ACS with hospital outcomes, controlling for age, gender, acute illness severity (measured by a Modified Early Warning Score in the emergency department), comorbidity (Charlson Comorbidity Index), and discharging specialty (general medicine, geriatric medicine, surgery).
Design: Retrospective, observational study.
Setting: Large university hospital in England.
Patients: We analyzed 8,202 first nonelective inpatient episodes of people ages 75 years and older between October 2014 and October 2015.
Measurements: The outcomes studied were prolonged length of stay (LOS 10 days), inpatient mortality, delayed discharge, institutionalization, and 30-day readmission. Statistical analyses were based on multivariate regression models.
Results: Independently of controlling variables, prolonged LOS was predicted by CFS greater than or equal to 6: odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.36-1.77; P less than .001; HOD: OR = 2.16; 95% CI, 1.79-2.61; P less than .001; and ACS: OR = 3.31; 95% CI, 2.64-4.15; P less than .001. Inpatient mortality was predicted by CFS greater than or equal to 6: OR = 2.29; 95% CI, 1.79-2.94, P less than .001. Delayed discharge was predicted by CFS greater than or equal to 6: OR = 1.46; 95% CI, 1.27-1.67; P less than .001; HOD: OR = 2.17; 95% CI, 1.80-2.62; P less than .001, and ACS: OR = 2.29; 95% CI: 1.83-2.85; P less than .001. Institutionalization was predicted by CFS greater than or equal to 6: OR=2.56; 95% CI, 2.09-3.14; P less than .001; HOD: OR = 2.51; 95% CI, 2.00-3.14; P less than .001; and ACS: OR = 1.93; 95% CI, 1.46-2.56; P less than .001. Readmission was predicted by ACS: OR = 1.36; 95% CI, 1.09-1.71; P = .006.
Conclusion: Routine screening for frailty, HoD, and ACS in hospitals may aid the development of acute care pathways for older adults.
Read the full article at journalofhospitalmedicine.com.
Also in JHM this month…
- Screening for Depression in Hospitalized Medical Patients
AUTHORS: Waguih William IsHak, MD, FAPA, Katherine Collison, Itai Danovitch, MD, MBA, Lili Shek, MD, Payam Kharazi, Tae Kim, DO Candidate, Karim Y. Jaffer, MD Candidate, Lancer Naghdechi, DO Candidate, Enrique Lopez, PsyD, Teryl Nuckols, MD, MSHS, FHM
- Patient-Level Exclusions from mHealth in a Safety-Net Health System
AUTHORS: Keiki Hinami, MD, MS, Bhrandon A. Harris, MD, Ricardo Uriostegui, MD, Wilnise Jasmin, MD, MBA, Mario Lopez, MD, William E. Trick, MD
- Medical and Economic Burden of Heparin-Induced Thrombocytopenia: A Retrospective Nationwide Inpatient Sample (NIS) Study
AUTHORS: Ranjan Pathak, MD, Vijaya Raj Bhatt, MD, Paras Karmacharya, MD, Madan Raj Aryal, MD, Anthony A. Donato, MD, MHPE
- Assessment of the Readability, Understandability and Completeness of Pediatric Hospital Medicine Discharge Instructions
AUTHORS: Ndidi I. Unaka, MD, Med, Angela Statile, MD, Med, Julianne Haney, Andrew F. Beck, MD, MPH, Patrick W. Brady, MD, MSc, Karen E. Jerardi, MD, MEd
- Impact of Patient-Centered Discharge Tools: A Systematic Review
AUTHORS: Karen Okrainec, MD, MSc, Davina Lau, BSc, Howard B Abrams, MD, Shoshanna Hahn-Goldberg, PhD, Ronak Brahmbhatt, MBBS, MPH, Tai Huynh, MBA, Kenneth Lam, MD, Chaim M Bell, MD, PhD
From the Washington Office: ACS Works to Establish Joint Trauma System in NDAA
I am frequently asked for examples of successes from the College’s advocacy efforts in DC. While many of our successes come in the form of legislation or regulation we are either able to significantly modify into more favorable form or to outright prevent from being enacted, this month’s topic provides an example of how our advocacy efforts are equally successful in obtaining specific provisions in legislation.
Over a year ago, staff of the Division of Advocacy and Health Policy were approached by members and staff of the Military Health System Strategic Partnership American College of Surgeons to assist them in their effort toward the establishment of both a Joint Trauma System (JTS) within the Defense Health Agency (to promote continuous improvement of trauma care provided to members of the Armed Forces) and a Joint Trauma Education and Training Directorate (JTETD) (to ensure military traumatologists maintain readiness with regard to critical surgical skills). I am pleased and proud to report that when the U.S. House of Representatives, on December 2, and the Senate, on December 8, passed the National Defense Authorization Act (NDAA), provisions for both the JTS and the JTETD, in nearly the precise wording as was proposed by ACS, were included in the legislation.
Our success in this effort was strongly supported by both Rep. Joe Heck, DO (R-Nev.), Chairman of the House Armed Services Subcommittee on Military Personnel, and Rep. Brad Wenstrup, DPM (R-Ohio). Rep. Heck, who is a Brigadier General in the Army Reserve, ensured that the language establishing the JTS within the U.S. Department of Defense and the JTETD were included in the House version of the NDAA. Rep. Wenstrup, who also serves in the Army Reserve, was key to securing language providing for review of the military trauma system under the JTS by a “non-government entity with subject matter experts.” This is an activity that the ACS Committee on Trauma Verification, Review, and Consultation Program conducts on a regular basis.
The Joint Trauma System will standardize trauma care in the military by establishing uniform standards for all military medical treatment facilities. The Joint Trauma Education and Training Directorate is charged with ensuring that trauma providers of the U.S. Armed Forces maintain a state of readiness. Under this provision, partnerships will be established with level one trauma centers in civilian academic medical centers and large metropolitan teaching hospitals where combat casualty care teams will embed to provide military surgeons with regular exposure to critically injured patients.
The Senate version of the NDAA did not contain language specifically outlining provisions for either the JTS or the JTETD. Because the House and Senate versions of the NDAA were different, a conference committee from both legislative bodies was appointed to settle the differences between the two versions of the legislation. Over the several months duration of the conference committee process, members of the ACS legislative affairs team met regularly with the offices of several key senators who serve on the Senate Armed Services Committee as well as with committee staff for both the Republican and Democrat members of the committee. During these meetings, we repeatedly “made the case” relative to the critically important nature of these provisions and were able to answer questions and address concerns relative to why ACS felt it was vitally important to include the House language in the final version of the bill. No doubt, these efforts were key in the decision of the Senate negotiators to recede their position and agree to the House language in the final version of the bill relative to these specific provisions.
Prior to the final House vote on the conference committee language of the NDAA, Rep. Wenstrup spoke on the House floor in support of the JTETD.
As I write, the legislation is awaiting signature by President Obama and it is expected he will do so in the coming days.
ACS’ successful efforts toward the establishment of the Joint Trauma System and the Joint Trauma Education and Training Directorate represent a significant achievement toward ensuring that our soldiers, sailors, airmen, Marines and guardsmen continue to receive the best of the best in trauma care while in the service of our nation.
Until next month ….
Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.
I am frequently asked for examples of successes from the College’s advocacy efforts in DC. While many of our successes come in the form of legislation or regulation we are either able to significantly modify into more favorable form or to outright prevent from being enacted, this month’s topic provides an example of how our advocacy efforts are equally successful in obtaining specific provisions in legislation.
Over a year ago, staff of the Division of Advocacy and Health Policy were approached by members and staff of the Military Health System Strategic Partnership American College of Surgeons to assist them in their effort toward the establishment of both a Joint Trauma System (JTS) within the Defense Health Agency (to promote continuous improvement of trauma care provided to members of the Armed Forces) and a Joint Trauma Education and Training Directorate (JTETD) (to ensure military traumatologists maintain readiness with regard to critical surgical skills). I am pleased and proud to report that when the U.S. House of Representatives, on December 2, and the Senate, on December 8, passed the National Defense Authorization Act (NDAA), provisions for both the JTS and the JTETD, in nearly the precise wording as was proposed by ACS, were included in the legislation.
Our success in this effort was strongly supported by both Rep. Joe Heck, DO (R-Nev.), Chairman of the House Armed Services Subcommittee on Military Personnel, and Rep. Brad Wenstrup, DPM (R-Ohio). Rep. Heck, who is a Brigadier General in the Army Reserve, ensured that the language establishing the JTS within the U.S. Department of Defense and the JTETD were included in the House version of the NDAA. Rep. Wenstrup, who also serves in the Army Reserve, was key to securing language providing for review of the military trauma system under the JTS by a “non-government entity with subject matter experts.” This is an activity that the ACS Committee on Trauma Verification, Review, and Consultation Program conducts on a regular basis.
The Joint Trauma System will standardize trauma care in the military by establishing uniform standards for all military medical treatment facilities. The Joint Trauma Education and Training Directorate is charged with ensuring that trauma providers of the U.S. Armed Forces maintain a state of readiness. Under this provision, partnerships will be established with level one trauma centers in civilian academic medical centers and large metropolitan teaching hospitals where combat casualty care teams will embed to provide military surgeons with regular exposure to critically injured patients.
The Senate version of the NDAA did not contain language specifically outlining provisions for either the JTS or the JTETD. Because the House and Senate versions of the NDAA were different, a conference committee from both legislative bodies was appointed to settle the differences between the two versions of the legislation. Over the several months duration of the conference committee process, members of the ACS legislative affairs team met regularly with the offices of several key senators who serve on the Senate Armed Services Committee as well as with committee staff for both the Republican and Democrat members of the committee. During these meetings, we repeatedly “made the case” relative to the critically important nature of these provisions and were able to answer questions and address concerns relative to why ACS felt it was vitally important to include the House language in the final version of the bill. No doubt, these efforts were key in the decision of the Senate negotiators to recede their position and agree to the House language in the final version of the bill relative to these specific provisions.
Prior to the final House vote on the conference committee language of the NDAA, Rep. Wenstrup spoke on the House floor in support of the JTETD.
As I write, the legislation is awaiting signature by President Obama and it is expected he will do so in the coming days.
ACS’ successful efforts toward the establishment of the Joint Trauma System and the Joint Trauma Education and Training Directorate represent a significant achievement toward ensuring that our soldiers, sailors, airmen, Marines and guardsmen continue to receive the best of the best in trauma care while in the service of our nation.
Until next month ….
Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.
I am frequently asked for examples of successes from the College’s advocacy efforts in DC. While many of our successes come in the form of legislation or regulation we are either able to significantly modify into more favorable form or to outright prevent from being enacted, this month’s topic provides an example of how our advocacy efforts are equally successful in obtaining specific provisions in legislation.
Over a year ago, staff of the Division of Advocacy and Health Policy were approached by members and staff of the Military Health System Strategic Partnership American College of Surgeons to assist them in their effort toward the establishment of both a Joint Trauma System (JTS) within the Defense Health Agency (to promote continuous improvement of trauma care provided to members of the Armed Forces) and a Joint Trauma Education and Training Directorate (JTETD) (to ensure military traumatologists maintain readiness with regard to critical surgical skills). I am pleased and proud to report that when the U.S. House of Representatives, on December 2, and the Senate, on December 8, passed the National Defense Authorization Act (NDAA), provisions for both the JTS and the JTETD, in nearly the precise wording as was proposed by ACS, were included in the legislation.
Our success in this effort was strongly supported by both Rep. Joe Heck, DO (R-Nev.), Chairman of the House Armed Services Subcommittee on Military Personnel, and Rep. Brad Wenstrup, DPM (R-Ohio). Rep. Heck, who is a Brigadier General in the Army Reserve, ensured that the language establishing the JTS within the U.S. Department of Defense and the JTETD were included in the House version of the NDAA. Rep. Wenstrup, who also serves in the Army Reserve, was key to securing language providing for review of the military trauma system under the JTS by a “non-government entity with subject matter experts.” This is an activity that the ACS Committee on Trauma Verification, Review, and Consultation Program conducts on a regular basis.
The Joint Trauma System will standardize trauma care in the military by establishing uniform standards for all military medical treatment facilities. The Joint Trauma Education and Training Directorate is charged with ensuring that trauma providers of the U.S. Armed Forces maintain a state of readiness. Under this provision, partnerships will be established with level one trauma centers in civilian academic medical centers and large metropolitan teaching hospitals where combat casualty care teams will embed to provide military surgeons with regular exposure to critically injured patients.
The Senate version of the NDAA did not contain language specifically outlining provisions for either the JTS or the JTETD. Because the House and Senate versions of the NDAA were different, a conference committee from both legislative bodies was appointed to settle the differences between the two versions of the legislation. Over the several months duration of the conference committee process, members of the ACS legislative affairs team met regularly with the offices of several key senators who serve on the Senate Armed Services Committee as well as with committee staff for both the Republican and Democrat members of the committee. During these meetings, we repeatedly “made the case” relative to the critically important nature of these provisions and were able to answer questions and address concerns relative to why ACS felt it was vitally important to include the House language in the final version of the bill. No doubt, these efforts were key in the decision of the Senate negotiators to recede their position and agree to the House language in the final version of the bill relative to these specific provisions.
Prior to the final House vote on the conference committee language of the NDAA, Rep. Wenstrup spoke on the House floor in support of the JTETD.
As I write, the legislation is awaiting signature by President Obama and it is expected he will do so in the coming days.
ACS’ successful efforts toward the establishment of the Joint Trauma System and the Joint Trauma Education and Training Directorate represent a significant achievement toward ensuring that our soldiers, sailors, airmen, Marines and guardsmen continue to receive the best of the best in trauma care while in the service of our nation.
Until next month ….
Dr. Bailey is a pediatric surgeon, and Medical Director, Advocacy, for the Division of Advocacy and Health Policy in the ACS offices in Washington, D.C.
From the Editors: One pebble at a time
This is a story about Sarah Prince, FRCS, and thousands of others here and abroad who are surgeons. Only a few of you may have heard of Miss Prince, consultant surgeon from Fort William, Scotland; but she represents to me one of thousands of stories that make surgery such a rich subject that spans more than pure science. Sarah achieved immortality in what she accomplished in 43 short years.
Sarah was trained in the United Kingdom system, attaining specialty training in hepatobiliary disease. While she loved that sort of work she decided, with her internist husband Patrick Byrne, to work in a rural town in northern Scotland. In nine years she built up the hospital there and its training paradigm. She went on to work toward creating a better rural surgical system in Scotland, eventually becoming an expert who spoke all over the world about rural surgery and allocating resources to build surgical capacity in rural areas. She understood the volume debate and the need for rural surgeons to have a connection that was substantive with a larger center in a collaborative way benefiting both locales.
I bring her up because she represents something we all can do. A few surgeons become academic giants known far and wide, but all surgeons have the ability to be local giants, unknown but immortal and essential in their own way. Sarah’s accomplishments confirm that.
Unlike surgery in the United States, the U.K. system is more regimented in many ways and even more political than what the average U.S. surgeon experiences. It is a single-payer system that was there long before Sarah became a surgeon and will be there long after. The fact that the system into which she was born was not of her making did not deter Sarah from taking on that very system to make her corner of the world a better place. I was always surprised when speaking with her that the problems she faced in Scotland were much the same as what I’ve seen in rural surgery in the United States and in other countries. She didn’t bend the whole system but she made a significant dent in how things were done. Isn’t that the challenge for us all?
Recently on the ACS Communities and elsewhere, the debate on single-payer, multitier, and market-driven health care is being argued. In light of the current political environment, the path forward seems bewilderingly tangled. Most surgeons just want to operate. The OR may be the last bastion of control we surgeons have in our professional lives. There may be a barrage of obstacles getting to the OR and hordes of explanations and details postoperatively, but in the OR we still get to do what we think is best at the moment using all those skills we so painfully acquired during a career of learning and practice. To despair is easy until one takes a look at what so many surgeons achieve in their lives.
Like Sarah, most of us try to make the profession a little better. In small town Iowa, that may be getting sonography privileges for FAST exams that improves the lot of trauma patients in that town. In an exburbia hospital, the surgeon may bring new expertise not previously available. It goes on and on with each of us contributing one pebble at a time to a mountain of effort. Any one pebble seems so insignificant in itself and sometimes just placing it on the mountain takes enormous effort, but each is worth the toil to put it there.
Which brings us back to Miss Prince (it is a faux pas to call a consultant surgeon in the U.K. by the honorific doctor). Sarah faced just as many challenges and perhaps more than surgeons elsewhere. Yet she brought her best every day to her hospital until cruel fate delivered her a fatal blow at a young age. Even then facing her imminent death, Sarah made sure that her patients and trainees would be well cared for after her passing. Her indomitable approach to surgical life shows that no matter what the opposition, a surgeon can with grit and wit make life better in his or her town, region, and maybe even the world.
As we face 2017 with all its potential for defeat or victory for our patients, let us remember surgeons like Sarah Prince who made a difference and commit ourselves to the same goal. We can do it one pebble at a time until we’ve created a mountain of accomplishment.
Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.
This is a story about Sarah Prince, FRCS, and thousands of others here and abroad who are surgeons. Only a few of you may have heard of Miss Prince, consultant surgeon from Fort William, Scotland; but she represents to me one of thousands of stories that make surgery such a rich subject that spans more than pure science. Sarah achieved immortality in what she accomplished in 43 short years.
Sarah was trained in the United Kingdom system, attaining specialty training in hepatobiliary disease. While she loved that sort of work she decided, with her internist husband Patrick Byrne, to work in a rural town in northern Scotland. In nine years she built up the hospital there and its training paradigm. She went on to work toward creating a better rural surgical system in Scotland, eventually becoming an expert who spoke all over the world about rural surgery and allocating resources to build surgical capacity in rural areas. She understood the volume debate and the need for rural surgeons to have a connection that was substantive with a larger center in a collaborative way benefiting both locales.
I bring her up because she represents something we all can do. A few surgeons become academic giants known far and wide, but all surgeons have the ability to be local giants, unknown but immortal and essential in their own way. Sarah’s accomplishments confirm that.
Unlike surgery in the United States, the U.K. system is more regimented in many ways and even more political than what the average U.S. surgeon experiences. It is a single-payer system that was there long before Sarah became a surgeon and will be there long after. The fact that the system into which she was born was not of her making did not deter Sarah from taking on that very system to make her corner of the world a better place. I was always surprised when speaking with her that the problems she faced in Scotland were much the same as what I’ve seen in rural surgery in the United States and in other countries. She didn’t bend the whole system but she made a significant dent in how things were done. Isn’t that the challenge for us all?
Recently on the ACS Communities and elsewhere, the debate on single-payer, multitier, and market-driven health care is being argued. In light of the current political environment, the path forward seems bewilderingly tangled. Most surgeons just want to operate. The OR may be the last bastion of control we surgeons have in our professional lives. There may be a barrage of obstacles getting to the OR and hordes of explanations and details postoperatively, but in the OR we still get to do what we think is best at the moment using all those skills we so painfully acquired during a career of learning and practice. To despair is easy until one takes a look at what so many surgeons achieve in their lives.
Like Sarah, most of us try to make the profession a little better. In small town Iowa, that may be getting sonography privileges for FAST exams that improves the lot of trauma patients in that town. In an exburbia hospital, the surgeon may bring new expertise not previously available. It goes on and on with each of us contributing one pebble at a time to a mountain of effort. Any one pebble seems so insignificant in itself and sometimes just placing it on the mountain takes enormous effort, but each is worth the toil to put it there.
Which brings us back to Miss Prince (it is a faux pas to call a consultant surgeon in the U.K. by the honorific doctor). Sarah faced just as many challenges and perhaps more than surgeons elsewhere. Yet she brought her best every day to her hospital until cruel fate delivered her a fatal blow at a young age. Even then facing her imminent death, Sarah made sure that her patients and trainees would be well cared for after her passing. Her indomitable approach to surgical life shows that no matter what the opposition, a surgeon can with grit and wit make life better in his or her town, region, and maybe even the world.
As we face 2017 with all its potential for defeat or victory for our patients, let us remember surgeons like Sarah Prince who made a difference and commit ourselves to the same goal. We can do it one pebble at a time until we’ve created a mountain of accomplishment.
Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.
This is a story about Sarah Prince, FRCS, and thousands of others here and abroad who are surgeons. Only a few of you may have heard of Miss Prince, consultant surgeon from Fort William, Scotland; but she represents to me one of thousands of stories that make surgery such a rich subject that spans more than pure science. Sarah achieved immortality in what she accomplished in 43 short years.
Sarah was trained in the United Kingdom system, attaining specialty training in hepatobiliary disease. While she loved that sort of work she decided, with her internist husband Patrick Byrne, to work in a rural town in northern Scotland. In nine years she built up the hospital there and its training paradigm. She went on to work toward creating a better rural surgical system in Scotland, eventually becoming an expert who spoke all over the world about rural surgery and allocating resources to build surgical capacity in rural areas. She understood the volume debate and the need for rural surgeons to have a connection that was substantive with a larger center in a collaborative way benefiting both locales.
I bring her up because she represents something we all can do. A few surgeons become academic giants known far and wide, but all surgeons have the ability to be local giants, unknown but immortal and essential in their own way. Sarah’s accomplishments confirm that.
Unlike surgery in the United States, the U.K. system is more regimented in many ways and even more political than what the average U.S. surgeon experiences. It is a single-payer system that was there long before Sarah became a surgeon and will be there long after. The fact that the system into which she was born was not of her making did not deter Sarah from taking on that very system to make her corner of the world a better place. I was always surprised when speaking with her that the problems she faced in Scotland were much the same as what I’ve seen in rural surgery in the United States and in other countries. She didn’t bend the whole system but she made a significant dent in how things were done. Isn’t that the challenge for us all?
Recently on the ACS Communities and elsewhere, the debate on single-payer, multitier, and market-driven health care is being argued. In light of the current political environment, the path forward seems bewilderingly tangled. Most surgeons just want to operate. The OR may be the last bastion of control we surgeons have in our professional lives. There may be a barrage of obstacles getting to the OR and hordes of explanations and details postoperatively, but in the OR we still get to do what we think is best at the moment using all those skills we so painfully acquired during a career of learning and practice. To despair is easy until one takes a look at what so many surgeons achieve in their lives.
Like Sarah, most of us try to make the profession a little better. In small town Iowa, that may be getting sonography privileges for FAST exams that improves the lot of trauma patients in that town. In an exburbia hospital, the surgeon may bring new expertise not previously available. It goes on and on with each of us contributing one pebble at a time to a mountain of effort. Any one pebble seems so insignificant in itself and sometimes just placing it on the mountain takes enormous effort, but each is worth the toil to put it there.
Which brings us back to Miss Prince (it is a faux pas to call a consultant surgeon in the U.K. by the honorific doctor). Sarah faced just as many challenges and perhaps more than surgeons elsewhere. Yet she brought her best every day to her hospital until cruel fate delivered her a fatal blow at a young age. Even then facing her imminent death, Sarah made sure that her patients and trainees would be well cared for after her passing. Her indomitable approach to surgical life shows that no matter what the opposition, a surgeon can with grit and wit make life better in his or her town, region, and maybe even the world.
As we face 2017 with all its potential for defeat or victory for our patients, let us remember surgeons like Sarah Prince who made a difference and commit ourselves to the same goal. We can do it one pebble at a time until we’ve created a mountain of accomplishment.
Dr. Hughes is clinical professor in the department of surgery and director of medical education at the Kansas University School of Medicine, Salina Campus, and Co-Editor of ACS Surgery News.
FDA approves ibrutinib for refractory MZL
The Food and Drug Administration has approved ibrutinib for the treatment of patients with relapsed or refractory marginal zone lymphoma (MZL), the drug’s manufacturers report.
The approval marks the fifth indication for ibrutinib (Imbruvica) in just over 4 years, and ibrutinib is the first agent specifically approved for relapsed/refractory MZL, according to press releases issued by Janssen Biotech and Pharmacyclics, the two manufacturers that jointly developed and marketed the Bruton tyrosine kinase inhibitor.
After receiving various fast-track, breakthrough therapy, priority review, and accelerated approval designations from the FDA, ibrutinib was previously approved to treat mantle cell lymphoma; refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); CLL/SLL with 17p deletion; and Waldenstrom’s macroglobulinemia, another rare form of non-Hodgkin lymphoma. The MCL and MZL approvals are based on overall response rates, and full approval is likely to require additional confirmatory data.
The new indication is based on data from a phase II, open-label, single-arm manufacturer-sponsored study that showed a 46% overall response rate (95% confidence interval, 33.4-59.1) in a cohort of 63 MZL patients who had failed one or more prior therapies. Of these, 3.2% had a complete response and 42.9% had a partial response. The median duration of response was not reached (NR) (range, 16.7 months–NR), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (2.3-16.4 months).
All three MZL subtypes were represented in the cohort, and ibrutinib appeared to be effective across subtypes. Thrombocytopenia, fatigue, anemia, diarrhea, bruising, and musculoskeletal pain were commonly reported adverse events.
[email protected]
On Twitter @HematologyNews1
The Food and Drug Administration has approved ibrutinib for the treatment of patients with relapsed or refractory marginal zone lymphoma (MZL), the drug’s manufacturers report.
The approval marks the fifth indication for ibrutinib (Imbruvica) in just over 4 years, and ibrutinib is the first agent specifically approved for relapsed/refractory MZL, according to press releases issued by Janssen Biotech and Pharmacyclics, the two manufacturers that jointly developed and marketed the Bruton tyrosine kinase inhibitor.
After receiving various fast-track, breakthrough therapy, priority review, and accelerated approval designations from the FDA, ibrutinib was previously approved to treat mantle cell lymphoma; refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); CLL/SLL with 17p deletion; and Waldenstrom’s macroglobulinemia, another rare form of non-Hodgkin lymphoma. The MCL and MZL approvals are based on overall response rates, and full approval is likely to require additional confirmatory data.
The new indication is based on data from a phase II, open-label, single-arm manufacturer-sponsored study that showed a 46% overall response rate (95% confidence interval, 33.4-59.1) in a cohort of 63 MZL patients who had failed one or more prior therapies. Of these, 3.2% had a complete response and 42.9% had a partial response. The median duration of response was not reached (NR) (range, 16.7 months–NR), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (2.3-16.4 months).
All three MZL subtypes were represented in the cohort, and ibrutinib appeared to be effective across subtypes. Thrombocytopenia, fatigue, anemia, diarrhea, bruising, and musculoskeletal pain were commonly reported adverse events.
[email protected]
On Twitter @HematologyNews1
The Food and Drug Administration has approved ibrutinib for the treatment of patients with relapsed or refractory marginal zone lymphoma (MZL), the drug’s manufacturers report.
The approval marks the fifth indication for ibrutinib (Imbruvica) in just over 4 years, and ibrutinib is the first agent specifically approved for relapsed/refractory MZL, according to press releases issued by Janssen Biotech and Pharmacyclics, the two manufacturers that jointly developed and marketed the Bruton tyrosine kinase inhibitor.
After receiving various fast-track, breakthrough therapy, priority review, and accelerated approval designations from the FDA, ibrutinib was previously approved to treat mantle cell lymphoma; refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); CLL/SLL with 17p deletion; and Waldenstrom’s macroglobulinemia, another rare form of non-Hodgkin lymphoma. The MCL and MZL approvals are based on overall response rates, and full approval is likely to require additional confirmatory data.
The new indication is based on data from a phase II, open-label, single-arm manufacturer-sponsored study that showed a 46% overall response rate (95% confidence interval, 33.4-59.1) in a cohort of 63 MZL patients who had failed one or more prior therapies. Of these, 3.2% had a complete response and 42.9% had a partial response. The median duration of response was not reached (NR) (range, 16.7 months–NR), with median follow-up of 19.4 months. The median time to initial response was 4.5 months (2.3-16.4 months).
All three MZL subtypes were represented in the cohort, and ibrutinib appeared to be effective across subtypes. Thrombocytopenia, fatigue, anemia, diarrhea, bruising, and musculoskeletal pain were commonly reported adverse events.
[email protected]
On Twitter @HematologyNews1
Left ventricle dose predicts heart events after BC radiation
The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.
The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).
The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.
For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).
“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.
The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.
Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.
The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.
ACE incidence was not significantly associated with the maximum dose of radiation to the heart.
LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.
There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
The limitations of this study are substantial. As the authors note, their work was based on only a small number of events, and their length of follow-up prevented them from being able to examine risk in the period of 10 years and beyond.
Also, the likelihood is high that the risk of radiation-induced heart disease can be reduced below that seen in the study. Cardiac exposure in many recent studies has been lower. Techniques such as deep inspiration breath holding or treatment in the prone position often can further decrease this exposure. Several randomized trials comparing partial-breast with whole-breast irradiation have found equal local control rates with both approaches, strongly suggesting that judicious individualization of field borders and cardiac blocks are unlikely to compromise outcome for selected patients treated with partial mastectomy.
Nonetheless, at some point, compromising coverage of the breast, chest wall, or nodal target volumes because an arbitrary threshold of a cardiac dose-volume parameter has been exceeded may be dangerous. Computer programs can likely be created to perform calculations of an individual’s excess risk of cardiac events or death in relation to dose-volume and clinical parameters, although I suspect it will be some years before they provide sufficiently validated, narrow estimates of risk to be clinically useful. Perhaps by then we will also have better ways to explain such sobering decisions to patients.
Abram Recht, MD , is a professor of radiation oncology at Harvard Medical School, Boston. He is also an advisor for CareCore and US Oncology, and receives institutional research funding form Genomic Health. He made his comments in an editorial (J Clin Oncol. 2017 Jan 17. doi: 0.1200/JCO.2016.71.4113 ).
The limitations of this study are substantial. As the authors note, their work was based on only a small number of events, and their length of follow-up prevented them from being able to examine risk in the period of 10 years and beyond.
Also, the likelihood is high that the risk of radiation-induced heart disease can be reduced below that seen in the study. Cardiac exposure in many recent studies has been lower. Techniques such as deep inspiration breath holding or treatment in the prone position often can further decrease this exposure. Several randomized trials comparing partial-breast with whole-breast irradiation have found equal local control rates with both approaches, strongly suggesting that judicious individualization of field borders and cardiac blocks are unlikely to compromise outcome for selected patients treated with partial mastectomy.
Nonetheless, at some point, compromising coverage of the breast, chest wall, or nodal target volumes because an arbitrary threshold of a cardiac dose-volume parameter has been exceeded may be dangerous. Computer programs can likely be created to perform calculations of an individual’s excess risk of cardiac events or death in relation to dose-volume and clinical parameters, although I suspect it will be some years before they provide sufficiently validated, narrow estimates of risk to be clinically useful. Perhaps by then we will also have better ways to explain such sobering decisions to patients.
Abram Recht, MD , is a professor of radiation oncology at Harvard Medical School, Boston. He is also an advisor for CareCore and US Oncology, and receives institutional research funding form Genomic Health. He made his comments in an editorial (J Clin Oncol. 2017 Jan 17. doi: 0.1200/JCO.2016.71.4113 ).
The limitations of this study are substantial. As the authors note, their work was based on only a small number of events, and their length of follow-up prevented them from being able to examine risk in the period of 10 years and beyond.
Also, the likelihood is high that the risk of radiation-induced heart disease can be reduced below that seen in the study. Cardiac exposure in many recent studies has been lower. Techniques such as deep inspiration breath holding or treatment in the prone position often can further decrease this exposure. Several randomized trials comparing partial-breast with whole-breast irradiation have found equal local control rates with both approaches, strongly suggesting that judicious individualization of field borders and cardiac blocks are unlikely to compromise outcome for selected patients treated with partial mastectomy.
Nonetheless, at some point, compromising coverage of the breast, chest wall, or nodal target volumes because an arbitrary threshold of a cardiac dose-volume parameter has been exceeded may be dangerous. Computer programs can likely be created to perform calculations of an individual’s excess risk of cardiac events or death in relation to dose-volume and clinical parameters, although I suspect it will be some years before they provide sufficiently validated, narrow estimates of risk to be clinically useful. Perhaps by then we will also have better ways to explain such sobering decisions to patients.
Abram Recht, MD , is a professor of radiation oncology at Harvard Medical School, Boston. He is also an advisor for CareCore and US Oncology, and receives institutional research funding form Genomic Health. He made his comments in an editorial (J Clin Oncol. 2017 Jan 17. doi: 0.1200/JCO.2016.71.4113 ).
The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.
The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).
The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.
For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).
“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.
The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.
Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.
The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.
ACE incidence was not significantly associated with the maximum dose of radiation to the heart.
LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.
There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.
The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).
The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.
For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).
“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.
The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.
Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.
The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.
ACE incidence was not significantly associated with the maximum dose of radiation to the heart.
LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.
There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Replacing the mean heart dose with the volume of the left ventricle receiving 5 Gy improves the predictive c-statistic to 0.80.
Data source: Investigation of 910 women who underwent radiation treatment following breast-conserving surgery.
Disclosures: There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
ASCO offers practice guidance on small renal masses
All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.
The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.
Not too long ago, nearly all patients with small renal masses would have undergone radical nephrectomy for lesions of any size. Today, however, partial nephrectomy and percutaneous thermal ablation are safe and less debilitating surgical options for many patients, the authors point out. The purpose of the guideline, therefore, is to help clinicians manage patients with clinically localized small renal masses with evidence-based clinical recommendations.
Recommendations summarized
The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:
- All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
- For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
- For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
- Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
- Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
- If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m2, or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.
The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.
“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.
They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.
The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.
All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.
The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.
Not too long ago, nearly all patients with small renal masses would have undergone radical nephrectomy for lesions of any size. Today, however, partial nephrectomy and percutaneous thermal ablation are safe and less debilitating surgical options for many patients, the authors point out. The purpose of the guideline, therefore, is to help clinicians manage patients with clinically localized small renal masses with evidence-based clinical recommendations.
Recommendations summarized
The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:
- All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
- For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
- For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
- Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
- Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
- If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m2, or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.
The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.
“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.
They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.
The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.
All patients with small renal masses detected on imaging should be considered for renal tumor biopsy when there is a likelihood that the results may affect management of the patient, says a new clinical oncology practice guideline from the American Society of Clinical Oncology.
The guideline defines small renal masses as incidentally image-detected, contrast-enhancing renal tumors 4 cm in diameter or less that are usually consistent with stage T1a renal cell carcinoma (RCC). Approximately one-fourth of all small renal masses turn out to be benign lesions such as oncocytoma or metanephric adenoma, and another 25% may be indolent tumors that can be managed more conservatively, the guidelines note.
Not too long ago, nearly all patients with small renal masses would have undergone radical nephrectomy for lesions of any size. Today, however, partial nephrectomy and percutaneous thermal ablation are safe and less debilitating surgical options for many patients, the authors point out. The purpose of the guideline, therefore, is to help clinicians manage patients with clinically localized small renal masses with evidence-based clinical recommendations.
Recommendations summarized
The guideline, developed with consensus from a multidisciplinary panel, includes six evidence-based recommendations, all based on intermediate quality sources, with recommendation strengths running from moderate to strong. In summary, the guideline recommends:
- All patients with a small renal mass should be considered for renal tumor biopsy “when the results may alter management.”
- For patients with significant comorbidities and a limited life expectancy, active surveillance should be one of the initial management options. Absolute indications for active surveillance include if the patient is at high risk for anesthesia and intervention or has a life expectancy of less than 5 years. Active surveillance is a relative indication for those patients with significant risk of end-stage renal disease if treated, small renal masses less than 1 cm, or a life expectancy of less than 10 years.
- For all patients for whom an intervention is indicated and who have a tumor amenable to limited resection, partial nephrectomy should be the standard treatment offered.
- Percutaneous thermal ablation can be considered as an option for patients whose tumors can be completely ablated. A biopsy should be performed either prior to or at the time of ablation.
- Radical nephrectomy for small renal masses should be reserved only for patients whose tumors are significantly complex to allow for successful partial nephrectomy or for whom or where partial nephrectomy “may result in unacceptable morbidity even when performed at centers with expertise. Referral to a surgeon and a center with experience in partial nephrectomy should be considered.”
- If the patient has chronic kidney disease (CKD), defined as an estimated glomerular filtration rate less than 45 mL/min per 1.73 m2, or develops progressive CKD after treatment, he or she should be considered for referral to a nephrologist, especially if the CKD is associated with proteinuria.
The guideline also offers advice for clinicians on communicating with patients and coordinating all aspects of care in a complex care environment.
“To begin, remember that today’s empowered patient will expect a greater role in his or her care. This means taking steps to ensure the patient is well educated and informed. Clinicians should take the time to orient the patient to his or her care but also make available recommended sources for information, including both print materials and online information,” the guideline authors advise.
They also recommend that clinicians share the details of pathology reports and test results with patients, families, and caregivers using terminology they can understand, including a thorough explanation of cancer staging, tumor types, and clinical options. Patients should also be informed, if appropriate, about the availability of clinical trials.
The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The guideline recommends renal tumor biopsy for most patients with incidentally detected renal masses 4 cm or smaller.
Major finding: Approximately 25% of patients with incidental small renal masses will have benign lesions.
Data source: Evidence-based clinical guideline developed by a multidisciplinary panel.
Disclosures: The guideline is sponsored by ASCO, Dr. Finelli and multiple coauthors disclosed relationships with various drug and/or device companies.
Expert panel reaches consensus on hernia management recommendations
Those are key conclusions from a consensus statement based on a systematic review of existing evidence in the medical literature about ventral hernia management that were published in the January 2017 issue of the Annals of Surgery.
“Despite ventral hernias (VH) being one of the most common pathologies seen by clinicians, significant variability in management exists,” wrote the researchers, led by Mike K. Liang, MD, of the University of Texas Health Science Center at Houston. “Surveys of clinicians and review of nationwide databases of patients undergoing elective ventral hernia repair (VHR) demonstrate substantial heterogeneity in patient selection and clinical practice.”
The panelists agreed that complications with VHR increase in obese patients (grade A evidence), current smokers (grade A), and in patients with glycosylated hemoglobin A1c (HbA1c) of 6.5% or greater (grade B). They did not recommend elective VHR in patients with a body mass index of 50 kg/m2 or greater (grade C), in current smokers (grade A), or patients with an HbA1c of 8.0% or greater (grade B). They also agreed that patients with a BMI of 30-50 kg/m2 or an HbA1c level of 6.5%-8.0% require individualized interventions to reduce surgical risk (grade C, grade B, respectively). The panelists considered nonoperative management to have a low risk of short-term morbidity (grade C) and they recommended mesh reinforcement for repair of hernias 2 cm or greater in size (grade A).
The panelists failed to reach agreement on several areas where high-quality data were limited, including mesh type. “Categories include ultra-light weight, light-weight, mid-weight, heavy-weight, and super-heavy weight, though precise definitions for each category are variable,” authors of the consensus statement wrote. “Randomized controlled trials are needed to compare synthetic, biological, and bioabsorbable meshes in all VH types and clinical settings.”
The authors of the consensus statement also called for further high-quality studies to better assess the management of VH in complex patients, which they defined as those presenting acutely, patients with cirrhosis, patients with inflammatory bowel disease, and patients who are pregnant.
The authors acknowledged certain limitations of the statement, including the fact that not all VH experts were included on the consensus panel. “However, the panel consisted of a large group of national experts with a primary practice focus of VHR,” they wrote. “The panelists have diverse views and unique areas of knowledge in the realm of hernia repair. The differing backgrounds among panelists was intended to make the guidelines that were developed more generalizable, as there is a wide variety of experience and skill level in the surgical community. In addition, there are no objective criteria to define an ‘expert’ in VH management.”
This work was supported by the Center for Clinical and Translational Sciences. The authors reported having no financial disclosures.
[email protected]
Those are key conclusions from a consensus statement based on a systematic review of existing evidence in the medical literature about ventral hernia management that were published in the January 2017 issue of the Annals of Surgery.
“Despite ventral hernias (VH) being one of the most common pathologies seen by clinicians, significant variability in management exists,” wrote the researchers, led by Mike K. Liang, MD, of the University of Texas Health Science Center at Houston. “Surveys of clinicians and review of nationwide databases of patients undergoing elective ventral hernia repair (VHR) demonstrate substantial heterogeneity in patient selection and clinical practice.”
The panelists agreed that complications with VHR increase in obese patients (grade A evidence), current smokers (grade A), and in patients with glycosylated hemoglobin A1c (HbA1c) of 6.5% or greater (grade B). They did not recommend elective VHR in patients with a body mass index of 50 kg/m2 or greater (grade C), in current smokers (grade A), or patients with an HbA1c of 8.0% or greater (grade B). They also agreed that patients with a BMI of 30-50 kg/m2 or an HbA1c level of 6.5%-8.0% require individualized interventions to reduce surgical risk (grade C, grade B, respectively). The panelists considered nonoperative management to have a low risk of short-term morbidity (grade C) and they recommended mesh reinforcement for repair of hernias 2 cm or greater in size (grade A).
The panelists failed to reach agreement on several areas where high-quality data were limited, including mesh type. “Categories include ultra-light weight, light-weight, mid-weight, heavy-weight, and super-heavy weight, though precise definitions for each category are variable,” authors of the consensus statement wrote. “Randomized controlled trials are needed to compare synthetic, biological, and bioabsorbable meshes in all VH types and clinical settings.”
The authors of the consensus statement also called for further high-quality studies to better assess the management of VH in complex patients, which they defined as those presenting acutely, patients with cirrhosis, patients with inflammatory bowel disease, and patients who are pregnant.
The authors acknowledged certain limitations of the statement, including the fact that not all VH experts were included on the consensus panel. “However, the panel consisted of a large group of national experts with a primary practice focus of VHR,” they wrote. “The panelists have diverse views and unique areas of knowledge in the realm of hernia repair. The differing backgrounds among panelists was intended to make the guidelines that were developed more generalizable, as there is a wide variety of experience and skill level in the surgical community. In addition, there are no objective criteria to define an ‘expert’ in VH management.”
This work was supported by the Center for Clinical and Translational Sciences. The authors reported having no financial disclosures.
[email protected]
Those are key conclusions from a consensus statement based on a systematic review of existing evidence in the medical literature about ventral hernia management that were published in the January 2017 issue of the Annals of Surgery.
“Despite ventral hernias (VH) being one of the most common pathologies seen by clinicians, significant variability in management exists,” wrote the researchers, led by Mike K. Liang, MD, of the University of Texas Health Science Center at Houston. “Surveys of clinicians and review of nationwide databases of patients undergoing elective ventral hernia repair (VHR) demonstrate substantial heterogeneity in patient selection and clinical practice.”
The panelists agreed that complications with VHR increase in obese patients (grade A evidence), current smokers (grade A), and in patients with glycosylated hemoglobin A1c (HbA1c) of 6.5% or greater (grade B). They did not recommend elective VHR in patients with a body mass index of 50 kg/m2 or greater (grade C), in current smokers (grade A), or patients with an HbA1c of 8.0% or greater (grade B). They also agreed that patients with a BMI of 30-50 kg/m2 or an HbA1c level of 6.5%-8.0% require individualized interventions to reduce surgical risk (grade C, grade B, respectively). The panelists considered nonoperative management to have a low risk of short-term morbidity (grade C) and they recommended mesh reinforcement for repair of hernias 2 cm or greater in size (grade A).
The panelists failed to reach agreement on several areas where high-quality data were limited, including mesh type. “Categories include ultra-light weight, light-weight, mid-weight, heavy-weight, and super-heavy weight, though precise definitions for each category are variable,” authors of the consensus statement wrote. “Randomized controlled trials are needed to compare synthetic, biological, and bioabsorbable meshes in all VH types and clinical settings.”
The authors of the consensus statement also called for further high-quality studies to better assess the management of VH in complex patients, which they defined as those presenting acutely, patients with cirrhosis, patients with inflammatory bowel disease, and patients who are pregnant.
The authors acknowledged certain limitations of the statement, including the fact that not all VH experts were included on the consensus panel. “However, the panel consisted of a large group of national experts with a primary practice focus of VHR,” they wrote. “The panelists have diverse views and unique areas of knowledge in the realm of hernia repair. The differing backgrounds among panelists was intended to make the guidelines that were developed more generalizable, as there is a wide variety of experience and skill level in the surgical community. In addition, there are no objective criteria to define an ‘expert’ in VH management.”
This work was supported by the Center for Clinical and Translational Sciences. The authors reported having no financial disclosures.
[email protected]
FROM ANNALS OF SURGERY
Esophageal cancers: Apples and oranges wrongly lumped together
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
This article published in Nature summarizes an integrated genomic analysis of esophageal cancer with careful comparisons to other cancers in the neighborhood (head and neck, lung, and gastric cancer). While clinically apparent to physicians taking care of esophageal cancer throughout the world, these analyses confirm that esophageal squamous cell cancer and esophageal adenocarcinoma are essentially two different diseases with distinct genomic characteristics. This has an important implication in clinical trial design: These pathologies should not be analyzed together, but instead should be studied distinctly.
In addition to the above major conclusion, several other features deserve to be noted. First, esophageal cancer does not seem to be associated with HPV as the HPV transcript levels in these tumors resemble those in HPV-negative head and neck cancers. Second, there are significant differences in the genomic characteristics of esophageal squamous cell cancer depending on geographic location. Third, esophageal adenocarcinoma is most like one particular molecular variant of gastric cancer (chromosomal instability type) and as one moves from the gastric antrum to the esophagus, there is an enrichment of this type of cancer. Such a gradient is found in methylation patterns as well, suggesting a similar cell of origin between gastric and esophageal cancers.
This study brings into focus the overarching theme that cancers may soon be treated based on molecular characteristics rather than anatomic location and clinical trials may have to be grouped based on genetic changes rather than organ systems.
Sai Yendamuri, MD, FACS, is an attending surgeon at the department of thoracic surgery, and director, Thoracic Surgery Research Laboratory, and an associate professor of oncology at Roswell Park Cancer Institute, Buffalo, N.Y.
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
Genomic analysis suggests that esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are two separate diseases that should not be combined in clinical trials and may benefit from different treatments, according to the results of a molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
The comprehensive molecular analysis comprised 164 esophageal tumors, 359 gastric adenocarcinomas, and 36 additional adenocarcinomas spanning the gastroesophageal junction.
The results of their analysis “call into question the premise of envisioning esophageal carcinoma as a single entity” and “argue against approaches that combine EAC and ESCC for clinical trials of neoadjuvant, adjuvant, or systemic therapies,” wrote the members of The Cancer Genome Atlas Research Network under the coordination of the National Cancer Institute and the National Human Genome Research Institute project.
The researchers evaluated the 164 esophageal carcinomas using integrated clustering of somatic copy number aberrations, DNA methylation, mRNA, and microRNA expression.
Gene expression analysis showed EACs had increased E-cadherin (CDH1) signaling and upregulation of ARF6 and FOXA pathways, which regulate E-cadherin. In contrast, ESCCs showed upregulation of Wnt, syndecan; p63 pathways, which are essential for squamous epithelial cell differentiation, were also upregulated. “These data suggest the presence of lineage-specific alterations that drive progression in EACs and ESCCs,” according to the researchers.
Somatic genome alterations showed that many of the same genetic pathways were altered in both EAC and ESCC, but the specific genes affected were dissimilar, suggesting distinct pathophysiologies between the two types of cancer. This could signal the need for different treatment approaches and led the researchers to caution against lumping EAC and ESCC in the same clinical trials.
Molecular subtype analysis of the ESCC cancers showed three molecular subtypes: ESCC1 (50 tumors), ESCC2 (36) and ESCC3 (4), distinguished by their mutation types. ESCC1, for example, was characterized by alterations in the NRF2 pathway, mutations in which are associated with poor prognosis and resistance to chemotherapy.
The three subtypes also showed trends for geographic associations, with Vietnamese patients (the only Asian population studied) showing a predominance of ESCC1 (27/41), and all 4 ESCC3 tumors being derived from United States patients.
The researchers also evaluated the molecular association between ESCC and human papillomavirus (HPV), which has been shown to have a pathogenic role in cervical SCC and head and neck (HN)SCC. They found that ESCC mRNA sequencing showed that ESCC-HPV transcript levels were similar to HPV-negative HNSCC tumors, diminishing the likelihood of an etiological role for HPV in ESCC.
In evaluating EACs in comparison to chromosomal instability (CIN) gastric cancers, the researchers found “clear similarity between chromosomal aberrations” in the two cancer types, with a stronger similarity between EAC and CIN gastric cancers than between EAC and ESCC, further differentiating the two esophageal cancers.
“The notable molecular similarity between EACs and CIN gastric cancers provides indirect support for gastric origin of Barrett’s esophagus and EAC and indicates that we may view GEA [gastroesophageal adenocarcinoma] as a singular entity, analogous to colorectal adenocarcinoma,” the authors added.
A notable anatomic gradient showed up in the progression of DNA methylation as seen from proximal to distal GEA-CIN tumors, with the most frequent hypermethylation seen in EACs, compared with gastric CIN cancers, a significant difference.
“These molecular data show that EAC and ESCC are distinct in their molecular characteristics across all platforms tested. ESCC emerges as a disease more reminiscent of other SCCs than of EAC, which itself bears striking resemblance to CIN gastric cancer,” the researchers concluded.
The authors reported that they had no competing financial interests.
FROM NATURE
Key clinical point:
Major finding: Molecular analysis showed esophageal squamous cell carcinoma is more like other squamous cell carcinomas than esophageal adenocarcinoma, which itself resembles chromosomal-instability gastric cancer.
Data source: A molecular study of 559 esophageal and gastric carcinoma tumors obtained from around the world.
Disclosures: The authors reported that they had no competing financial interests.
Scleroligation procedure proposed for gastroesophageal varices
In the treatment of gastroesophageal varices, scleroligation – a hybrid procedure that combines sclerotherapy and band ligation – performed as well as did band ligation, but required fewer sessions and had a shorter overall treatment duration. Sclerotherapy involves the injection of sclerosant to prompt occlusion of the varices, while ligation involves banding the varices to cut off blood flow.
The new approach combines them. The researchers ligated the varix 3-5 cm from the gastroesophageal junction and injected the sclerosant into the varix, below the ligated section. They reasoned that ligation should increase the contact time between the sclerosant and endothelial cells, and thus improve efficacy.
He noted that in the United States, band ligation is the standard of therapy, and the new study won’t change that. “These preliminary results from a single center are quite promising, and if they can be confirmed in a larger, multicenter trial, then this is something that can be added to our therapeutic armamentarium,” said Dr. Kwo.
Band ligation replaced sclerotherapy as the preferred treatment for gastroesophageal varices because it has equal efficacy but fewer severe side effects. However, it also suffers from a higher rate of recurrence because the bands cannot destroy deeper varices and perforating veins.
The combination technique, scleroligation, has been demonstrated in the treatment of esophageal varices, which prompted the authors’ investigation into gastroesophageal varices.
At a single center, the researchers recruited 120 patients with cirrhosis and acute gastroesophageal variceal bleeding above the gastroesophageal junction. They were randomized 1:1 to undergo endoscopic band ligation (EBL) or scleroligation (SL).
On average, 15.6 weeks were required to obliterate the varices in the EBL group versus 8.64 weeks in the SL group (P less than .001). The EBL group required an average of 3.43 sessions to reach that endpoint, compared with 2.22 sessions in the SL group (P less than .001). The EBL group required an average of 13.72 bands per patient, compared with 8.88 bands in the SL group (P less than .001). The EBL group also had a higher average number of units of blood transfused (2.30 vs 1.53; P less than .001).
No patients in either group experienced perforation, chest empyema, pericardial effusion, or strictures.
The good safety outcomes may be related to the small volume of sclerosant used, just 2 mL. “It’s probably because of their meticulous approach that they were able to reduce the complications that we have historically seen with sclerotherapy alone,” said Dr. Kwo.
There was no difference in the number of rebleeds or recurrences at follow-up, total cost, mortality due to rebleeding, or 12-month survival.
No funding source was disclosed. The authors reported no financial disclosures.
In the treatment of gastroesophageal varices, scleroligation – a hybrid procedure that combines sclerotherapy and band ligation – performed as well as did band ligation, but required fewer sessions and had a shorter overall treatment duration. Sclerotherapy involves the injection of sclerosant to prompt occlusion of the varices, while ligation involves banding the varices to cut off blood flow.
The new approach combines them. The researchers ligated the varix 3-5 cm from the gastroesophageal junction and injected the sclerosant into the varix, below the ligated section. They reasoned that ligation should increase the contact time between the sclerosant and endothelial cells, and thus improve efficacy.
He noted that in the United States, band ligation is the standard of therapy, and the new study won’t change that. “These preliminary results from a single center are quite promising, and if they can be confirmed in a larger, multicenter trial, then this is something that can be added to our therapeutic armamentarium,” said Dr. Kwo.
Band ligation replaced sclerotherapy as the preferred treatment for gastroesophageal varices because it has equal efficacy but fewer severe side effects. However, it also suffers from a higher rate of recurrence because the bands cannot destroy deeper varices and perforating veins.
The combination technique, scleroligation, has been demonstrated in the treatment of esophageal varices, which prompted the authors’ investigation into gastroesophageal varices.
At a single center, the researchers recruited 120 patients with cirrhosis and acute gastroesophageal variceal bleeding above the gastroesophageal junction. They were randomized 1:1 to undergo endoscopic band ligation (EBL) or scleroligation (SL).
On average, 15.6 weeks were required to obliterate the varices in the EBL group versus 8.64 weeks in the SL group (P less than .001). The EBL group required an average of 3.43 sessions to reach that endpoint, compared with 2.22 sessions in the SL group (P less than .001). The EBL group required an average of 13.72 bands per patient, compared with 8.88 bands in the SL group (P less than .001). The EBL group also had a higher average number of units of blood transfused (2.30 vs 1.53; P less than .001).
No patients in either group experienced perforation, chest empyema, pericardial effusion, or strictures.
The good safety outcomes may be related to the small volume of sclerosant used, just 2 mL. “It’s probably because of their meticulous approach that they were able to reduce the complications that we have historically seen with sclerotherapy alone,” said Dr. Kwo.
There was no difference in the number of rebleeds or recurrences at follow-up, total cost, mortality due to rebleeding, or 12-month survival.
No funding source was disclosed. The authors reported no financial disclosures.
In the treatment of gastroesophageal varices, scleroligation – a hybrid procedure that combines sclerotherapy and band ligation – performed as well as did band ligation, but required fewer sessions and had a shorter overall treatment duration. Sclerotherapy involves the injection of sclerosant to prompt occlusion of the varices, while ligation involves banding the varices to cut off blood flow.
The new approach combines them. The researchers ligated the varix 3-5 cm from the gastroesophageal junction and injected the sclerosant into the varix, below the ligated section. They reasoned that ligation should increase the contact time between the sclerosant and endothelial cells, and thus improve efficacy.
He noted that in the United States, band ligation is the standard of therapy, and the new study won’t change that. “These preliminary results from a single center are quite promising, and if they can be confirmed in a larger, multicenter trial, then this is something that can be added to our therapeutic armamentarium,” said Dr. Kwo.
Band ligation replaced sclerotherapy as the preferred treatment for gastroesophageal varices because it has equal efficacy but fewer severe side effects. However, it also suffers from a higher rate of recurrence because the bands cannot destroy deeper varices and perforating veins.
The combination technique, scleroligation, has been demonstrated in the treatment of esophageal varices, which prompted the authors’ investigation into gastroesophageal varices.
At a single center, the researchers recruited 120 patients with cirrhosis and acute gastroesophageal variceal bleeding above the gastroesophageal junction. They were randomized 1:1 to undergo endoscopic band ligation (EBL) or scleroligation (SL).
On average, 15.6 weeks were required to obliterate the varices in the EBL group versus 8.64 weeks in the SL group (P less than .001). The EBL group required an average of 3.43 sessions to reach that endpoint, compared with 2.22 sessions in the SL group (P less than .001). The EBL group required an average of 13.72 bands per patient, compared with 8.88 bands in the SL group (P less than .001). The EBL group also had a higher average number of units of blood transfused (2.30 vs 1.53; P less than .001).
No patients in either group experienced perforation, chest empyema, pericardial effusion, or strictures.
The good safety outcomes may be related to the small volume of sclerosant used, just 2 mL. “It’s probably because of their meticulous approach that they were able to reduce the complications that we have historically seen with sclerotherapy alone,” said Dr. Kwo.
There was no difference in the number of rebleeds or recurrences at follow-up, total cost, mortality due to rebleeding, or 12-month survival.
No funding source was disclosed. The authors reported no financial disclosures.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point:
Major finding: Scleroligation required 2.22 sessions on average, compared with 3.43 for endoscopic band ligation.
Data source: Single-center randomized trial of 120 patients.
Disclosures: No funding source was disclosed. The authors reported no financial disclosures.