ACS Surgery News

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

PHOENIX – Seeing is not always believing when it comes to determining whether pancreatic adenocarcinomas are resectable.

In patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy with the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin), presurgical imaging was not a reliable determinant of resectability, said Dr. Cristina R. Ferrone from the department of general and gastrointestinal surgery at Massachusetts General Hospital in Boston.

Neil Osterweil/Frontline Medical News

"It really is a paradigm shift that we can’t rely on CT scans and MRIs the way we did before," she said at the annual Society of Surgical Oncology Cancer Symposium.

An important case

For her team, the paradigm shift was sparked by the case of a 41-year-old woman who presented with a 3.6-cm pancreatic adenocarcinoma involving the superior mesenteric artery (SMA), and a cancer antigen 19-9 (CA 19-9) level of 985 U/mL (normal values for the nonspecific biomarker range from 0 to 37 U/mL, according to National Comprehensive Cancer Network guidelines).

Following 4 months of FOLFIRINOX and 50.4 Gy of chemoradiation, her CA 19-9 level normalized to 37 U/mL. But her postchemotherapy imaging studies appeared identical to her prechemotherapy studies, with no apparent evidence of tumor regression and apparent continued involvement of the SMA following FOLFIRINOX.

"We had a big debate about this woman, because she had a normalized CA 19-9. Do we attempt to resect a patient like this?" Dr. Ferrone said.

After considerable discussion, the decision was made to take the patient into the operating room, approach the pancreas from the left side, and perform intraoperative biopsies on the SMA. If the biopsies were positive, the surgical team would either perform intraoperative radiation therapy (IORT) or use a soft-tissue ablation system (Nanoknife). If the biopsies were negative, the team would proceed to resection.

The patient went on to resection, and was found to have only minimal residual tumor on postoperative pathology samples, Dr. Ferrone reported.

Case comparisons

To see whether other patients could benefit from a similar approach, the investigators compared outcomes for 87 patients who underwent upfront resection for presumed organ-confined disease and 38 patients who received neoadjuvant FOLFIRINOX before surgery. Of the latter group, 5 received FOLFIRINOX chemotherapy only; 16 received FOLFIRINOX and 50.4 Gy of radiation; 10 received FOLFIRINOX, radiation, and IORT; 4 received FOLFIRINOX and proton-beam therapy; and 3 had FOLFIRINOX with other drug therapies.

The median CA 19-9 level fell from 169 U/mL before FOLFIRINOX to 16 U/mL after (P = .003), and more than twice as many patients had levels below 40 U/mL after therapy (31% vs. 72%; P = .03)

Median tumor diameter on CT also decreased after chemotherapy, from 3.6 cm to 2.2 cm (P = .001).

Pathology review of images from 20 cases with the observer blinded to treatment status showed 14 cases judged to be locally advanced disease and 6 borderline pre-FOLFIRINOX, and 12 locally advanced cases, 3 borderline, and 5 cases deemed resectable post-FOLFIRINOX.

When the investigators compared clinical and operative results in the surgery-only patients vs. results in those who had neoadjuvant FOLFIRINOX, they found that the latter group had higher mean operative times (300 minutes for surgery-only patients vs. 393 minutes for FOLFIRINOX-treated patients; P less than .001) and higher mean blood loss (400 mL vs. 600 mL, respectively; P = .01).

However, patients who received neoadjuvant therapy had significantly fewer postoperative complications (63% vs. 35% of patients; P = .004) and fewer pancreatic fistulas (29% vs. 0%; P less than .001).

Patients who received FOLFIRINOX also had a lower proportion of readmissions within 90 days (30% vs. 21%); shorter lengths of stay (7 days vs. 6 days); and no deaths, compared with 1 in the up-front surgery group, but these differences were not significant.

Pathology results showed that 79% of the surgery-only patients had positive lymph nodes, compared with only 37% of those in the neoadjuvant group (P less than .001). The neoadjuvant group also had lower proportions of both lymphatic invasion (70% vs. 37%, P less than .001) and perineural invasion (P less than .001).

There were proportionally more R0 (clean margin) resections in the FOLFIRINOX group, but the difference was not significant.

After a median follow-up of 10 months for the up-front surgery patients and 12 months for the FOLFIRINOX-treated patients, there have been no differences in local or distant progression or deaths from pancreatic cancer. Dr. Ferrone acknowledged that a larger patient sample and longer follow-up may be needed to detect significant differences.

However, Kaplan-Meier overall survival estimates from the time of diagnosis out to 34 months significantly favor the FOLFIRINOX-treated patients (P = .02).

"With this therapeutic modality and intensive surgical interventions, we hope that we are making an impact in these patients’ lives and improving their survival," she said.

The study was internally supported. Dr. Ferrone reported having no financial disclosures.

To answer the question proposed in the title above – no. However, in an era of increasing specialization, it is not unexpected to respond to challenges in surgery with increased training. One challenge that is confronted on an almost daily basis at cancer centers is the patient who experiences a complication requiring surgical evaluation during treatment of an advanced or incurable malignancy.

These complications come in many forms and include bowel perforation, bowel obstruction, gastrointestinal bleeding, and wound problems. These complications are also notable in that they often represent a sharp turn in the intent of the patient’s care, from improving length of life to improving quality of life. It also will not come as a surprise to any surgeon who is called upon to evaluate a patient with a metastatic incurable malignancy with bowel perforation while on systemic chemotherapy that the surgeon may even be the first health care provider who attempts to address prognosis and end-of-life issues with the patient and/or family members.

Palliative surgery can account for 1,000 or more procedures per year and as much as 20% of a surgeon’s practice at major cancer centers. In addition, up to 40% of all inpatient surgical consultations at cancer centers meet the criteria for palliative care. In understanding the scope, volume, and complexity of acute care surgical oncology, it is important to define palliative surgical care as distinct from palliative medical care, as there are clear differences that are not always recognized. Palliative medical care expertise can be obtained through a palliative care fellowship, and focuses on the treatment of problems such as cachexia, delirium, fatigue, dyspnea, pain, and end-of-life psychosocial issues. Palliative surgical care is specifically surgery for which the major intent is improvement in symptoms or quality of life. As the population ages and the “silver tsunami” of aging patients with cancer washes over our surgical practice, palliative surgical concepts will become an increasingly important aspect of surgical training. Palliative surgical training is not a pasture upon which surgeons are put to keep them out of the operating room. On the contrary, palliative surgical procedures are some of the highest-risk procedures that are performed and often require a lengthy preoperative discussion of the anticipated risk-benefit ratio. This ratio is often very narrow, and the increased risks of palliative surgery must be balanced against the difficult task of estimating the remaining length of a patient’s life or the potential for future cancer-directed treatment options.

So how do we respond to the challenge of palliative surgery in cancer patients? Actually, we do need new and improved training, but it can and should be included as part of general surgery residency and the new ACGME certification in complex general surgical oncology. Our local response at M.D. Anderson has included the creation of an Acute and Palliative Surgical Oncology Service modeled after the acute care surgery model. Acute care surgery has been recognized as providing more timely consultation and improved quality of care, and minimizing disruption of elective practice and research efforts for other faculty. In response to our current demand of one to two palliative surgical consults per day, in addition to other acute inpatient consults, we are attempting to focus the care of these patients on a smaller group of faculty in an effort to develop better algorithms of care and improved clinical expertise. Surgical oncologists may not have the best reputation for acute care clinical expertise. I can think back to my own residency experience where the surgical oncologists did not take call in response to their belief that “there are no emergency surgical oncology problems.”

Cancer care is becoming more complex; even targeted agents can create life-threatening surgical problems, and our current level of palliative surgical training can be improved. My hope is that through acceptance of surgical oncology as a specialty within the Board of Surgery, we will be recognized not only for our expertise in elective cancer surgery but for acute and palliative cancer surgery as well.

Dr. Badgwell is an ACS Fellow and an associate professor of surgery at M.D. Anderson Cancer Center in Houston. He specializes in gastric cancer and palliative surgical oncology.

To answer the question proposed in the title above – no. However, in an era of increasing specialization, it is not unexpected to respond to challenges in surgery with increased training. One challenge that is confronted on an almost daily basis at cancer centers is the patient who experiences a complication requiring surgical evaluation during treatment of an advanced or incurable malignancy.

These complications come in many forms and include bowel perforation, bowel obstruction, gastrointestinal bleeding, and wound problems. These complications are also notable in that they often represent a sharp turn in the intent of the patient’s care, from improving length of life to improving quality of life. It also will not come as a surprise to any surgeon who is called upon to evaluate a patient with a metastatic incurable malignancy with bowel perforation while on systemic chemotherapy that the surgeon may even be the first health care provider who attempts to address prognosis and end-of-life issues with the patient and/or family members.

Palliative surgery can account for 1,000 or more procedures per year and as much as 20% of a surgeon’s practice at major cancer centers. In addition, up to 40% of all inpatient surgical consultations at cancer centers meet the criteria for palliative care. In understanding the scope, volume, and complexity of acute care surgical oncology, it is important to define palliative surgical care as distinct from palliative medical care, as there are clear differences that are not always recognized. Palliative medical care expertise can be obtained through a palliative care fellowship, and focuses on the treatment of problems such as cachexia, delirium, fatigue, dyspnea, pain, and end-of-life psychosocial issues. Palliative surgical care is specifically surgery for which the major intent is improvement in symptoms or quality of life. As the population ages and the “silver tsunami” of aging patients with cancer washes over our surgical practice, palliative surgical concepts will become an increasingly important aspect of surgical training. Palliative surgical training is not a pasture upon which surgeons are put to keep them out of the operating room. On the contrary, palliative surgical procedures are some of the highest-risk procedures that are performed and often require a lengthy preoperative discussion of the anticipated risk-benefit ratio. This ratio is often very narrow, and the increased risks of palliative surgery must be balanced against the difficult task of estimating the remaining length of a patient’s life or the potential for future cancer-directed treatment options.

So how do we respond to the challenge of palliative surgery in cancer patients? Actually, we do need new and improved training, but it can and should be included as part of general surgery residency and the new ACGME certification in complex general surgical oncology. Our local response at M.D. Anderson has included the creation of an Acute and Palliative Surgical Oncology Service modeled after the acute care surgery model. Acute care surgery has been recognized as providing more timely consultation and improved quality of care, and minimizing disruption of elective practice and research efforts for other faculty. In response to our current demand of one to two palliative surgical consults per day, in addition to other acute inpatient consults, we are attempting to focus the care of these patients on a smaller group of faculty in an effort to develop better algorithms of care and improved clinical expertise. Surgical oncologists may not have the best reputation for acute care clinical expertise. I can think back to my own residency experience where the surgical oncologists did not take call in response to their belief that “there are no emergency surgical oncology problems.”

Cancer care is becoming more complex; even targeted agents can create life-threatening surgical problems, and our current level of palliative surgical training can be improved. My hope is that through acceptance of surgical oncology as a specialty within the Board of Surgery, we will be recognized not only for our expertise in elective cancer surgery but for acute and palliative cancer surgery as well.

Dr. Badgwell is an ACS Fellow and an associate professor of surgery at M.D. Anderson Cancer Center in Houston. He specializes in gastric cancer and palliative surgical oncology.

To answer the question proposed in the title above – no. However, in an era of increasing specialization, it is not unexpected to respond to challenges in surgery with increased training. One challenge that is confronted on an almost daily basis at cancer centers is the patient who experiences a complication requiring surgical evaluation during treatment of an advanced or incurable malignancy.

These complications come in many forms and include bowel perforation, bowel obstruction, gastrointestinal bleeding, and wound problems. These complications are also notable in that they often represent a sharp turn in the intent of the patient’s care, from improving length of life to improving quality of life. It also will not come as a surprise to any surgeon who is called upon to evaluate a patient with a metastatic incurable malignancy with bowel perforation while on systemic chemotherapy that the surgeon may even be the first health care provider who attempts to address prognosis and end-of-life issues with the patient and/or family members.

Palliative surgery can account for 1,000 or more procedures per year and as much as 20% of a surgeon’s practice at major cancer centers. In addition, up to 40% of all inpatient surgical consultations at cancer centers meet the criteria for palliative care. In understanding the scope, volume, and complexity of acute care surgical oncology, it is important to define palliative surgical care as distinct from palliative medical care, as there are clear differences that are not always recognized. Palliative medical care expertise can be obtained through a palliative care fellowship, and focuses on the treatment of problems such as cachexia, delirium, fatigue, dyspnea, pain, and end-of-life psychosocial issues. Palliative surgical care is specifically surgery for which the major intent is improvement in symptoms or quality of life. As the population ages and the “silver tsunami” of aging patients with cancer washes over our surgical practice, palliative surgical concepts will become an increasingly important aspect of surgical training. Palliative surgical training is not a pasture upon which surgeons are put to keep them out of the operating room. On the contrary, palliative surgical procedures are some of the highest-risk procedures that are performed and often require a lengthy preoperative discussion of the anticipated risk-benefit ratio. This ratio is often very narrow, and the increased risks of palliative surgery must be balanced against the difficult task of estimating the remaining length of a patient’s life or the potential for future cancer-directed treatment options.

So how do we respond to the challenge of palliative surgery in cancer patients? Actually, we do need new and improved training, but it can and should be included as part of general surgery residency and the new ACGME certification in complex general surgical oncology. Our local response at M.D. Anderson has included the creation of an Acute and Palliative Surgical Oncology Service modeled after the acute care surgery model. Acute care surgery has been recognized as providing more timely consultation and improved quality of care, and minimizing disruption of elective practice and research efforts for other faculty. In response to our current demand of one to two palliative surgical consults per day, in addition to other acute inpatient consults, we are attempting to focus the care of these patients on a smaller group of faculty in an effort to develop better algorithms of care and improved clinical expertise. Surgical oncologists may not have the best reputation for acute care clinical expertise. I can think back to my own residency experience where the surgical oncologists did not take call in response to their belief that “there are no emergency surgical oncology problems.”

Cancer care is becoming more complex; even targeted agents can create life-threatening surgical problems, and our current level of palliative surgical training can be improved. My hope is that through acceptance of surgical oncology as a specialty within the Board of Surgery, we will be recognized not only for our expertise in elective cancer surgery but for acute and palliative cancer surgery as well.

Dr. Badgwell is an ACS Fellow and an associate professor of surgery at M.D. Anderson Cancer Center in Houston. He specializes in gastric cancer and palliative surgical oncology.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

PHOENIX – Hope remains for patients with advanced cancers, even after curative-intent surgery fails them, investigators reported at the annual Society of Surgical Oncology Cancer Symposium.

A study of the effects of an online decision aid for advance care planning showed that patients whose cancers had advanced despite initial curative-intent surgery had degrees of hope and desires for the aggressiveness of additional therapy similar to those of patients who had undergone palliative therapy only, said Dr. Niraj J. Gusani, FACS, of Penn State College of Medicine, Hershey, Pa.

"As we do more advance care planning, stratify patients, and get them into these programs to help them figure out what their wishes really are, we should treat everybody the same , and they should all have a durable advance care planning process, maybe using a decision aid such as this," he said.

The results show that outcomes beyond whether a patient lives or dies also matter, commented Dr. Steven Chen, FACS, from City of Hope Medical Center, Duarte, Calif.

"The thing that patients care about at least as much as how long they’re going to live is how well they’re going to live until they die," he said in an interview. Dr. Chen was not involved in the study, but comoderated the poster discussion session where it was presented.

"Almost all of my patients have very advanced cancers with poor prognosis, and it’s all about their quality of life and how they’re going to feel," Dr. Gusani agreed. "They intuitively get that they have a poor prognosis, but if we can get them through with a better experience with their time and they are able to maintain their hope, then it makes a world of difference for the patient and the family as well."

Multimedia advance care planning

Dr. Gusani and his colleagues looked at data from a clinical trial evaluating the effects of an online multimedia decision aid tool for patients with advanced-stage disease. The program, called Making Your Wishes Known: Planning Your Medical Future, was developed by two of the authors.

The program "provides tailored education, values-clarification exercises, and a decision-making tool that translates an individual’s values and preferences into a specific medical plan than can be implemented by a health care team," they wrote.

The investigators hypothesized that patients who went into surgery hoping for or expecting a cure might opt for more aggressive treatment at the end of life and have more hope and/or less hopelessness than patients who underwent treatments that they knew would not be curative.

The researchers administered the advance care planning program to 159 patients from the parent clinical trial, in which 200 patients with stage IV cancers who were judged to have less than 12 months to live were randomly assigned to receive either standard advance care planning or the decision aid. All of the patients had non–central nervous system and nonhematologic malignancies and were classified as having had initial curative-intent surgery or treatment without curative intent (e.g., palliative therapy and tumor debulking).

Making patients’ wishes known

Both at baseline and after the intervention, the patients were rated for hope on the 12-item Herth Hope Index, with scores from 12 (low hope) to 48 (high hope), and for hopelessness on the 7-item Beck Hopelessness Scale, in which 0 is no hopelessness and 7 is the highest level of despair.

The patients were also asked to rate their desires for aggressiveness of additional therapy by choosing one of six general wishes statements. For this scale, questions 1-4 were deemed to be more aggressive, and 5-6 less aggressive.

Additionally, patients who used the decision aid were rated on a treatment aggressiveness scale scored from 0 (least aggressive) to 40 (most) based on their responses to questions within the decision aid that asked about their wishes for eight different treatments (such as mechanical ventilation or cardiopulmonary resuscitation) under five clinical scenarios (such as stroke or dementia).

In all, 46 of 95 patients (48%) who had originally had curative-intent surgery received the control intervention, and 49 (52%) received the decision aid. Of the 64 patients who had non–curative-intent therapy, 35 (52%) received standard advance care planning and 31 (48%) received the Making Your Wishes Known aid.

After either intervention, patients who had curative-intent surgery had a slight but not significant increase in hope, and patients in the non–curative-intent group had a slight but not significant decrease. There was no significant between-group difference.

Similarly, each group had a slight decrease in hopelessness scores, with no significant differences between the groups.

There were also no significant variations in the distribution of the general wishes statements between the curative and noncurative groups or between the decision-aid and control groups, nor were there differences in the median treatment aggressiveness score of patients who used the decision aid, regardless of whether they had initially had curative-intent surgery.

"Regardless of what they choose in terms of their level of aggressiveness, the patients are more satisfied with their decision, they feel more informed, and caregiver satisfaction has improved with the decision aid compared with traditional materials," Dr. Gusani said.

"This is really important work," commented Dr. Sandra L. Wong of the University of Michigan Medical Center, Ann Arbor, who comoderated the poster discussion session.

The study was supported by Penn State College of Medicine. Dr. Gusani, Dr. Chen, and Dr. Wong reported having no financial conflicts of interest.

Will you get paid for the care you provide to patients who have gained insurance coverage through the Affordable Care Act’s health insurance claims? You’ll soon find out.

Under the health reform law, patients must pay their first month’s premium to be considered enrolled; they then have 90 days to pay the next premium.

If the patient doesn’t pay his or her premiums for the second month, the insurer can hold or "pend" all claims. By the third month, if the patient still has not paid, the insurer can terminate his or her policy. The physician is left to collect whatever is owed for all outstanding claims from the patient.

The Centers for Medicare and Medicaid Services (CMS) clarified the grace period policy in a letter to insurers last year.

The first ripples could come in April. Patients who started and paid for coverage in January, but who did not pay in February or March, might get dropped from coverage. That could leave physicians scrambling to cover the unreimbursed care.

Physicians’ organizations including the American Medical Association, the American College of Physicians, and the American Academy of Family Physicians have been working to reverse this provision of the Affordable Care Act, to no avail so far.

In a March 5 letter to the CMS, dozens of organizations and state medical societies urged the agency to require insurers to tell physicians whether patients had up-to-date coverage during the verification of eligibility. As the law and current regulations are written, insurers can notify physicians on their own timeline whether a patient’s coverage has lapsed.

The organizations also asked the CMS to "require issuers to assume full financial responsibility if an issuer provides inaccurate eligibility information during the last 60 days of the grace period."

"Managing risk is typically a role for insurers, but the grace period rule transfers two-thirds of that risk from the insurers to physicians and health care providers," Dr. Ardis Dee Hoven, president of the American Medical Association, said in a statement.

She added that the AMA is now offering some resources to help physicians manage the "potential negative impact" from having unwittingly given uncompensated care.

Among the resources is a sample letter for patients that explains the 90-day grace period and the importance of paying premiums on a timely basis and in full. The AMA also provides a step-by-step outline suggesting how to collect from patients whose coverage has lapsed.

It is unclear how many individuals have paid for coverage under the Affordable Care Act. The Health and Human Services department said on March 17 that 5 million Americans have signed up for coverage through the state and federal exchanges since Oct. 1. But the department continues to say that it does not know how many have paid their premiums.

[email protected]

On Twitter @aliciaault

Will you get paid for the care you provide to patients who have gained insurance coverage through the Affordable Care Act’s health insurance claims? You’ll soon find out.

Under the health reform law, patients must pay their first month’s premium to be considered enrolled; they then have 90 days to pay the next premium.

If the patient doesn’t pay his or her premiums for the second month, the insurer can hold or "pend" all claims. By the third month, if the patient still has not paid, the insurer can terminate his or her policy. The physician is left to collect whatever is owed for all outstanding claims from the patient.

The Centers for Medicare and Medicaid Services (CMS) clarified the grace period policy in a letter to insurers last year.

The first ripples could come in April. Patients who started and paid for coverage in January, but who did not pay in February or March, might get dropped from coverage. That could leave physicians scrambling to cover the unreimbursed care.

Physicians’ organizations including the American Medical Association, the American College of Physicians, and the American Academy of Family Physicians have been working to reverse this provision of the Affordable Care Act, to no avail so far.

In a March 5 letter to the CMS, dozens of organizations and state medical societies urged the agency to require insurers to tell physicians whether patients had up-to-date coverage during the verification of eligibility. As the law and current regulations are written, insurers can notify physicians on their own timeline whether a patient’s coverage has lapsed.

The organizations also asked the CMS to "require issuers to assume full financial responsibility if an issuer provides inaccurate eligibility information during the last 60 days of the grace period."

"Managing risk is typically a role for insurers, but the grace period rule transfers two-thirds of that risk from the insurers to physicians and health care providers," Dr. Ardis Dee Hoven, president of the American Medical Association, said in a statement.

She added that the AMA is now offering some resources to help physicians manage the "potential negative impact" from having unwittingly given uncompensated care.

Among the resources is a sample letter for patients that explains the 90-day grace period and the importance of paying premiums on a timely basis and in full. The AMA also provides a step-by-step outline suggesting how to collect from patients whose coverage has lapsed.

It is unclear how many individuals have paid for coverage under the Affordable Care Act. The Health and Human Services department said on March 17 that 5 million Americans have signed up for coverage through the state and federal exchanges since Oct. 1. But the department continues to say that it does not know how many have paid their premiums.

[email protected]

On Twitter @aliciaault

Will you get paid for the care you provide to patients who have gained insurance coverage through the Affordable Care Act’s health insurance claims? You’ll soon find out.

Under the health reform law, patients must pay their first month’s premium to be considered enrolled; they then have 90 days to pay the next premium.

If the patient doesn’t pay his or her premiums for the second month, the insurer can hold or "pend" all claims. By the third month, if the patient still has not paid, the insurer can terminate his or her policy. The physician is left to collect whatever is owed for all outstanding claims from the patient.

The Centers for Medicare and Medicaid Services (CMS) clarified the grace period policy in a letter to insurers last year.

The first ripples could come in April. Patients who started and paid for coverage in January, but who did not pay in February or March, might get dropped from coverage. That could leave physicians scrambling to cover the unreimbursed care.

Physicians’ organizations including the American Medical Association, the American College of Physicians, and the American Academy of Family Physicians have been working to reverse this provision of the Affordable Care Act, to no avail so far.

In a March 5 letter to the CMS, dozens of organizations and state medical societies urged the agency to require insurers to tell physicians whether patients had up-to-date coverage during the verification of eligibility. As the law and current regulations are written, insurers can notify physicians on their own timeline whether a patient’s coverage has lapsed.

The organizations also asked the CMS to "require issuers to assume full financial responsibility if an issuer provides inaccurate eligibility information during the last 60 days of the grace period."

"Managing risk is typically a role for insurers, but the grace period rule transfers two-thirds of that risk from the insurers to physicians and health care providers," Dr. Ardis Dee Hoven, president of the American Medical Association, said in a statement.

She added that the AMA is now offering some resources to help physicians manage the "potential negative impact" from having unwittingly given uncompensated care.

Among the resources is a sample letter for patients that explains the 90-day grace period and the importance of paying premiums on a timely basis and in full. The AMA also provides a step-by-step outline suggesting how to collect from patients whose coverage has lapsed.

It is unclear how many individuals have paid for coverage under the Affordable Care Act. The Health and Human Services department said on March 17 that 5 million Americans have signed up for coverage through the state and federal exchanges since Oct. 1. But the department continues to say that it does not know how many have paid their premiums.

[email protected]

On Twitter @aliciaault

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

[email protected]

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

[email protected]

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

[email protected]

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Mortality related to severe sepsis steadily and substantially declined between 2000 and 2012 across Australia and New Zealand, contrary to the pervasive sense that little progress has been made in achieving that goal, according to a report presented at the International Symposium on Intensive Care and Emergency Medicine.

The report was simultaneously published online March 18 in JAMA.

In a retrospective analysis of information in the Australian and New Zealand Intensive Care Society adult ICU database, which covers more than 90% of all ICU admissions in both countries, researchers examined time trends in mortality among 101,064 patients who had severe sepsis, both with and without septic shock. Even though the incidence of severe sepsis increased during the study period, sepsis-related mortality steadily declined from 35.0% in 2000 to 18.4% in 2012, said Dr. Kirsi-Maija Kaukonen of the Australian and New Zealand Intensive Care Research Centre, department of epidemiology and preventive medicine, Monash University, Melbourne, and her associates.

At the same time, the rate of discharge to home increased and that of discharge to rehabilitation facilities dropped, indicating that the decreased in-hospital mortality wasn’t a statistical artifact resulting from transferring out the sickest patients who were most likely to die imminently, the investigators said.

The decreased mortality extended across all subgroups of patients and remained robust in several sensitivity analyses and after numerous adjustments of the data for factors such as illness severity, hospital size, length of stay, and patient age and comorbidities. "Similar decreases in mortality over time have been reported in other retrospective studies" in the United States and elsewhere, Dr. Kaukonen and her associates said (JAMA 2014 March 18 [doi:101001/jama.2014.2637]).

A similar decline in mortality occurred among nonseptic ICU patients during this time interval. "It is unclear whether any improvements in diagnostic procedures, earlier and broader-spectrum antibiotic treatment, or more aggressive supportive therapy" contributed to the decrease in sepsis mortality. But the observation that "an equivalent improvement occurred in nonseptic patients supports the view that overall changes in ICU practice rather than in the management of sepsis explain most of our findings," they wrote.

During the study period, many treatments to improve survival in severe sepsis, including activated protein C, low-dose hydrocortisone, antithrombin III, tifacogin, vasoactive agents, fludrocortisone, intensive insulin therapy, large-molecular-size hydroxyethyl starch, and eritoran, showed initial promise in animal and phase 2 trials but have ultimately failed to do so in real world practice. "These failures have led to a sense that little progress has been made in decreasing the mortality of severe sepsis," but the findings of this study challenge that view, Dr. Kaukonen and her associates said.

Dr. Kaukonen reported no financial conflicts of interest; one of her associates reported receiving support from Gambro, Baxter, Philips, and Braun.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

The House of Representatives on March 14 approved a bill to repeal the Medicare Sustainable Growth Rate formula; the Senate is not likely to take up the bill.

The House voted mostly along party lines, with 226 Republicans and 12 Democrats voting in favor of approving H.R. 4015 and sending it to the Senate. Many Democrats who voted against it objected to the bill’s financing, which was achieved through a 5-year delay of the Affordable Care Act’s individual health insurance mandate.

Alicia Ault/ Frontline Medical News

The Congressional Budget Office estimated that delaying the mandate would save about $170 billion over 10 years, while the Sustainable Growth Rate (SGR) fix would cost $130 billion in the same period. But the CBO also said that the plan would increase the number of uninsured by 13 million and lead to 10%-20% premium increases.

"Political games are threatening to derail months of bipartisan, bicameral progress" on implementing the Affordable Care Act, House Minority Leader Nancy Pelosi (D-Calif.) said in a speech before the vote.

"We shouldn’t be wasting time on this foolishness and this recklessness," she added, noting that securing a permanent fix before a 24% physician pay cut takes effect on April 1 was increasingly less likely as the Senate was not likely to approve the plan with the accompanying financing.

The House now is on break until March 25.

Dr. Ardis Dee Hoven, president of the American Medical Association, said that she was disappointed at the House action, given that the House and Senate had already agreed on the fundamentals of replacing the SGR. "It would be a shame for lawmakers to have done all of that hard work only to have it overcome by partisan politics over budgetary issues," she said in a statement.

"We thank all members who spoke on the floor in support of a return to bipartisan negotiations and encourage the United States Senate to proceed in a timely and bipartisan manner to advance legislation in that body," she said, adding that the AMA would continue to try to help forge a compromise.

"Continuing the cycle of kicking the can down the road through temporary patches in the months ahead simply wastes more taxpayer money to preserve a bad policy of Congress’ own making," Dr. Hoven said.

Leaders at other physicians’ organizations echoed Dr. Hoven’s disappointment.

"We’re dismayed that Congress sabotaged their own work by linking this legislation to unrelated, ideological issues – particularly in light of the nearly universal opposition to such action from patients, insurers, and the medical community," Dr. Reid Blackwelder, president of the American Academy of Family Physicians, said in a statement.

"It’s imperative that both parties come together to reach agreement on the budgetary payment that will pass both the House and the Senate before April 1," Dr. Blackwelder said.

Ms. Molly Cooke, president of the American College of Physicians, said the ACP stands by its statement from March 7. At that time, she said, "Congress knows that it is counterproductive for either the House or the Senate, Republicans or Democrats, to tie the bipartisan, bicameral SGR repeal bill to other policies that do not have the bipartisan support needed to pass both chambers, and be signed into law by the President."

Dr. Cooke added, "We cannot support linking SGR repeal to changes in current law that will result in fewer people getting health insurance coverage."

House Republican leaders called on the Senate to act.

"We have never come this far in finding a permanent solution," House Energy and Commerce Committee Chairman Fred Upton (R-Mich.) said in a statement. "But there is still much work to be done after today’s vote, and I call on my good friend Sen. Ron Wyden [D-Ore.] to pick up the torch and work with Majority Leader Harry Reid [D-Nev.] to put politics aside, stand up for our seniors and doctors, and solve SGR this year."

[email protected]

On Twitter @aliciaault

The House of Representatives on March 14 approved a bill to repeal the Medicare Sustainable Growth Rate formula; the Senate is not likely to take up the bill.

The House voted mostly along party lines, with 226 Republicans and 12 Democrats voting in favor of approving H.R. 4015 and sending it to the Senate. Many Democrats who voted against it objected to the bill’s financing, which was achieved through a 5-year delay of the Affordable Care Act’s individual health insurance mandate.

Alicia Ault/ Frontline Medical News

The Congressional Budget Office estimated that delaying the mandate would save about $170 billion over 10 years, while the Sustainable Growth Rate (SGR) fix would cost $130 billion in the same period. But the CBO also said that the plan would increase the number of uninsured by 13 million and lead to 10%-20% premium increases.

"Political games are threatening to derail months of bipartisan, bicameral progress" on implementing the Affordable Care Act, House Minority Leader Nancy Pelosi (D-Calif.) said in a speech before the vote.

"We shouldn’t be wasting time on this foolishness and this recklessness," she added, noting that securing a permanent fix before a 24% physician pay cut takes effect on April 1 was increasingly less likely as the Senate was not likely to approve the plan with the accompanying financing.

The House now is on break until March 25.

Dr. Ardis Dee Hoven, president of the American Medical Association, said that she was disappointed at the House action, given that the House and Senate had already agreed on the fundamentals of replacing the SGR. "It would be a shame for lawmakers to have done all of that hard work only to have it overcome by partisan politics over budgetary issues," she said in a statement.

"We thank all members who spoke on the floor in support of a return to bipartisan negotiations and encourage the United States Senate to proceed in a timely and bipartisan manner to advance legislation in that body," she said, adding that the AMA would continue to try to help forge a compromise.

"Continuing the cycle of kicking the can down the road through temporary patches in the months ahead simply wastes more taxpayer money to preserve a bad policy of Congress’ own making," Dr. Hoven said.

Leaders at other physicians’ organizations echoed Dr. Hoven’s disappointment.

"We’re dismayed that Congress sabotaged their own work by linking this legislation to unrelated, ideological issues – particularly in light of the nearly universal opposition to such action from patients, insurers, and the medical community," Dr. Reid Blackwelder, president of the American Academy of Family Physicians, said in a statement.

"It’s imperative that both parties come together to reach agreement on the budgetary payment that will pass both the House and the Senate before April 1," Dr. Blackwelder said.

Ms. Molly Cooke, president of the American College of Physicians, said the ACP stands by its statement from March 7. At that time, she said, "Congress knows that it is counterproductive for either the House or the Senate, Republicans or Democrats, to tie the bipartisan, bicameral SGR repeal bill to other policies that do not have the bipartisan support needed to pass both chambers, and be signed into law by the President."

Dr. Cooke added, "We cannot support linking SGR repeal to changes in current law that will result in fewer people getting health insurance coverage."

House Republican leaders called on the Senate to act.

"We have never come this far in finding a permanent solution," House Energy and Commerce Committee Chairman Fred Upton (R-Mich.) said in a statement. "But there is still much work to be done after today’s vote, and I call on my good friend Sen. Ron Wyden [D-Ore.] to pick up the torch and work with Majority Leader Harry Reid [D-Nev.] to put politics aside, stand up for our seniors and doctors, and solve SGR this year."

[email protected]

On Twitter @aliciaault

The House of Representatives on March 14 approved a bill to repeal the Medicare Sustainable Growth Rate formula; the Senate is not likely to take up the bill.

The House voted mostly along party lines, with 226 Republicans and 12 Democrats voting in favor of approving H.R. 4015 and sending it to the Senate. Many Democrats who voted against it objected to the bill’s financing, which was achieved through a 5-year delay of the Affordable Care Act’s individual health insurance mandate.

Alicia Ault/ Frontline Medical News

The Congressional Budget Office estimated that delaying the mandate would save about $170 billion over 10 years, while the Sustainable Growth Rate (SGR) fix would cost $130 billion in the same period. But the CBO also said that the plan would increase the number of uninsured by 13 million and lead to 10%-20% premium increases.

"Political games are threatening to derail months of bipartisan, bicameral progress" on implementing the Affordable Care Act, House Minority Leader Nancy Pelosi (D-Calif.) said in a speech before the vote.

"We shouldn’t be wasting time on this foolishness and this recklessness," she added, noting that securing a permanent fix before a 24% physician pay cut takes effect on April 1 was increasingly less likely as the Senate was not likely to approve the plan with the accompanying financing.

The House now is on break until March 25.

Dr. Ardis Dee Hoven, president of the American Medical Association, said that she was disappointed at the House action, given that the House and Senate had already agreed on the fundamentals of replacing the SGR. "It would be a shame for lawmakers to have done all of that hard work only to have it overcome by partisan politics over budgetary issues," she said in a statement.

"We thank all members who spoke on the floor in support of a return to bipartisan negotiations and encourage the United States Senate to proceed in a timely and bipartisan manner to advance legislation in that body," she said, adding that the AMA would continue to try to help forge a compromise.

"Continuing the cycle of kicking the can down the road through temporary patches in the months ahead simply wastes more taxpayer money to preserve a bad policy of Congress’ own making," Dr. Hoven said.

Leaders at other physicians’ organizations echoed Dr. Hoven’s disappointment.

"We’re dismayed that Congress sabotaged their own work by linking this legislation to unrelated, ideological issues – particularly in light of the nearly universal opposition to such action from patients, insurers, and the medical community," Dr. Reid Blackwelder, president of the American Academy of Family Physicians, said in a statement.

"It’s imperative that both parties come together to reach agreement on the budgetary payment that will pass both the House and the Senate before April 1," Dr. Blackwelder said.

Ms. Molly Cooke, president of the American College of Physicians, said the ACP stands by its statement from March 7. At that time, she said, "Congress knows that it is counterproductive for either the House or the Senate, Republicans or Democrats, to tie the bipartisan, bicameral SGR repeal bill to other policies that do not have the bipartisan support needed to pass both chambers, and be signed into law by the President."

Dr. Cooke added, "We cannot support linking SGR repeal to changes in current law that will result in fewer people getting health insurance coverage."

House Republican leaders called on the Senate to act.

"We have never come this far in finding a permanent solution," House Energy and Commerce Committee Chairman Fred Upton (R-Mich.) said in a statement. "But there is still much work to be done after today’s vote, and I call on my good friend Sen. Ron Wyden [D-Ore.] to pick up the torch and work with Majority Leader Harry Reid [D-Nev.] to put politics aside, stand up for our seniors and doctors, and solve SGR this year."

[email protected]

On Twitter @aliciaault

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]