Colon and Rectal

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the U.S.^1-3 Only 40% of cases are diagnosed in a localized stage with an estimated 5-year survival of 90%, whereas 20% of cases present with metastatic disease with a 5-year survival of about 12.5%.¹ With recent advances in cancer genetics and immunology as well as approval of targeted agents by the FDA, different treatment options are now available, even for progressive disease.

This article presents a brief review of CRC with a special focus on targeted therapies in metastatic CRC (mCRC). Colorectal cancers exhibit certain mutations, which affect the tumor responsiveness to various treatment options. This article describes the role of targeted therapies in various well-established mutations.

Epidemiology

The most common tumor location is the proximal colon (42%), followed by the rectum (28%). More than 90% of patients with CRCs are aged > 50 years at diagnosis.
Women have a higher percentage of proximal tumors compared with men (46% vs 38%) and a lower percentage of rectal tumors (24% vs 31%).ŽAmong both sexes, incidence and mortality are highest in African Americans and lowest in Asian/Pacific Islanders. The estimated 5-year survival is slightly higher for rectal cancer (66.5%) than for colon cancer (64.2%), although the stage-specific survival is similar. The difference in 5-year overall survival (OS) is attributed to the higher percentage of rectal tumors diagnosed at a localized stage (44% vs 38%). Patients aged < 65 years have higher 5-year survival rates than do those aged • 65 years (68.9% vs 62.0%).¹

Risk Factors

Like most human cancers, multiple genetic and environmental factors are believed to play a role in the development of colorectal carcinomas, with environmental factors playing the dominant role.⁴

Environmental risk factors include a low-fiber diet,⁵ red and processed meat intake,⁶ a high-fat diet,⁷ smoking,⁸ heavy alcohol consumption,⁹ obesity,¹⁰ physical inactivity,¹¹ alteration in intestinal flora,¹² and chronic inflammation.¹³ Aspirin (at doses > 300 mg/d), nonsteroidal anti-inflammatory drugs, and folic acid are believed to protect against colon cancer.¹⁴

Some of the genetic factors involved in colorectal cancers include (1) the loss of tumor suppressor genes, such as APC (most common tumor suppressor mutation), p53, SMAD4 pathways, or TGF-ß pathways; (2) DNA mismatch repair defects: mutations in MLH1, MSH2 in hereditary nonpolyposis colon cancer or methylation of MLH1 in sporadic cases; and (3) CpG island methylation (CIMP pathway), methylation of MLH1, MINT1, MINT2, MINT3; and (4) activation of oncogenes such as RAS and BRAF.¹⁵

Pathogenesis

The colonic mucosa consists of epithelial cells arranged in cylindrical structures called crypts. The human colon contains about 10 millionŽcrypts. The cellular proliferation and migration in each of the crypts is believed to be tightly regulated, with the majority of cells arising from a small number of stem cells (around 4-6) at the bottom of the crypt, which migrate upward after division and are eventually shed into the lumen.¹⁶ Each crypt is renewed in 2 to 8 days, which makes colonic mucosa one of the organs with the most cell proliferation in the human body and, hence, a target for various genetic and epigenetic alterations as well as environmental mutagenesis.⁷

Traditionally, the majority of colorectal carcinomas were believed to evolve from adenomatous polyps, which transform into an advanced adenoma with high-grade
dysplasia and then progress to an invasive cancer often referred to as the adenoma-to-carcinoma sequence.¹⁵ However, 2 other pathways, alternative and serrated,
have been described, and CRCs are now regarded as complex malignancies with a wide array of genetic and epigenetic mutations.¹⁷

About 70% to 85% of CRCs generally develop from chromosomal instability resulting from inactivation of tumor suppressor genes (APC gene, p53, etc). About 15% of cases are attributed to the failure of the DNA mismatch repair system either by germline/somatic mutations or by epigenetic silencing of gene transcription by CpG island methylation.¹⁸ Mutation in the BRAF or K-ras oncogenes are also believed to promote carcinogenesis.¹⁵ All these changes are believed to give rise to a precursor microscopic mucosal lesion that precedes the development of macroscopic adenomas.¹⁷

Clinical Features

The clinical features of CRCs can be widely variable, from incidental findings during screening colonoscopy to intestinal obstruction. The most common clinical presentation is rectal bleeding, followed by weight loss, abdominal pain, constipation, or diarrhea.¹⁹ The likelihood of CRC is higher with the combination of rectal bleeding and weight loss as well as rectal bleeding and change in bowel habits. Other clinical features may include bloating, abdominal pain, or anemia.²⁰ (See Table 1.)

Targeted Therapy in CRC

The targeted therapies in CRC include (1) the antivascular endothelial growth factor-A (anti–VEGF-A) antibody bevacizumab; (2) the VEGF-A, VEGF-B, and placental growth factor inhibitor aflibercept; (3) the multikinase inhibitor regorafenib; and (4) the anti-epidermal growth factor receptor (anti-EGFR) antibodies cetuximab and panitumumab.

Bevacizumab is an anti-VEGF monoclonal antibody. Vascular endothelial growth factor promotes angiogenesisnecessary for tumor growth. Bevacizumab was approved by the FDA in February 2004 as a first-line treatment in combination with IFL (irinotecan plus 5-fluorouracil [5-FU]/leucovorin) regimen and in June 2006 as a second-line treatment in combination with 5-FU–based chemotherapy for patients with mCRC. In January 2013, bevacizumab was approved for use in combination with fluoropyrimidine–irinotecan- or fluoropyrimidine–oxaliplatin-based chemotherapy for the treatment of patients with mCRC whose disease has progressed while on first-line treatment with a bevacizumab-containing regimen.²¹ (See Table 2.)

Aflibercept is a recombinant fusion protein, containing VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2, fused to the Fc portion of human immunoglobulin IgG1 that blocks the activity of VEGF-A, VEGF-B, and placental growth factor by acting as a high-affinity ligand trap to prevent these ligands from binding to their endogenous receptors.²² It was approved by the FDA in August 2012 for use in combination with FOLFIRI (5-FU, leucovorin, irinotecan) for the treatment of patients with mCRC that is resistant to or has progressed following an oxaliplatin‑containing regimen.²³

Cetuximab (a chimeric IgG1 anti-EGFR monoclonal antibody) and panitumumab (a human IgG2 anti-EGFR monoclonal antibody) have been shown to improve OS
and progression-free survival (PFS) in up to 20% of cases, either alone or in combination with chemotherapy.^24,25 The FDA approved cetuximab in July 2012 for use in
combination with FOLFIRI for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFRexpressing mCRC.²⁶ The FDA approved panitumumab in
September 2006 for the treatment of patients with EGFRexpressing metastatic colorectal carcinoma with disease progression on or following FOLFOX (5-FU, leucovorin, oxaliplatin)/FOLFIRI.27 (See Table 3.)

KRAS, a member of the rat sarcoma virus (ras) gene family of oncogenes, encodes for a small G protein downstream of EGFR. KRAS is mutated in CRC in up to 37% cases, resulting in activation of the different downstream signaling pathways.^15,28 Therefore, KRAS mutations predict resistance to anti-EGFR therapy.^28,29 Testing for KRAS mutation prior to treatment with cetuximab or panitumumab leads to targeted us of the very costly monoclonal antibodies and hence is considered a cost-effective practice.³⁰

Even in cases with wild-type KRAS mutation, response to anti-EGFR therapies is seen in only less than half of patients.³¹ Up to 17% of tumors with wild-type for KRAS exon 2 at codons 12 and 13 can have a mutation in another of the ras pathway genes (eg, KRAS exon 3, 4 and NRAS exon 2, 3, 4).²⁵ Mutations in the BRAF oncogene have been described in up to 13% of colorectal carcinoma cases.¹⁵ The data to suggest a lack of antitumor activity from anti-EGFR therapies in the presence of BRAF V600E mutation are still limited, but BRAF mutation is considered a poor prognostic factor.

A recent trial involving 1,137 patients with KRAS exon 2 wild-type mCRC randomly assigned to cetuximab or bevacizumab with standard chemotherapy (FOLFOX or FOLFIRI) found OS of 29.9 vs 29.0 months and median PFS 10.4 vs 10.8 months for cetuximab and bevacizumab, respectively.32 The OS for 5-FU–based therapies was about 11 months.³³

Regorafenib is an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor protein kinases, including those involved in the regulation of tumor angiogenesis (eg, VEGFR1-3 and TIE2 [tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2]), tumor microenvironment (plateletderived growth factor receptor-β and fibroblast growth factor receptor 1), as well as tumor oncogenesis (KIT, RET, RAF1, BRAF, BRAF V600E).34 A randomized phase 3 study involving 760 patients with documented progressive mCRC found a higher median OS with regorafenib vs placebo (6.4 mo vs 5.0 mo, P = .0052) and a
higher PFS (2.0 mo vs 1.7 mo, P < .0001).³⁵ The FDA approved regorafenib in September 2012 for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with an anti-VEGF therapy and, if KRAS wild-type, with an anti-EGFR therapy.³⁶

Conclusion

Targeted therapies in conjunction with newer chemotherapies have improved outcomes in metastatic colorectal carcinoma compared with those of conventional therapy (29 mo vs 11 mo).

Author disclosures
Peter T. Silberstein, MD, reports receiving payment for lectures from Bristol Myers and Celgene in the past. Drs. Khanal and Upadhyay report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Click here to read the digital edition.

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the U.S.^1-3 Only 40% of cases are diagnosed in a localized stage with an estimated 5-year survival of 90%, whereas 20% of cases present with metastatic disease with a 5-year survival of about 12.5%.¹ With recent advances in cancer genetics and immunology as well as approval of targeted agents by the FDA, different treatment options are now available, even for progressive disease.

This article presents a brief review of CRC with a special focus on targeted therapies in metastatic CRC (mCRC). Colorectal cancers exhibit certain mutations, which affect the tumor responsiveness to various treatment options. This article describes the role of targeted therapies in various well-established mutations.

Epidemiology

The most common tumor location is the proximal colon (42%), followed by the rectum (28%). More than 90% of patients with CRCs are aged > 50 years at diagnosis.
Women have a higher percentage of proximal tumors compared with men (46% vs 38%) and a lower percentage of rectal tumors (24% vs 31%).ŽAmong both sexes, incidence and mortality are highest in African Americans and lowest in Asian/Pacific Islanders. The estimated 5-year survival is slightly higher for rectal cancer (66.5%) than for colon cancer (64.2%), although the stage-specific survival is similar. The difference in 5-year overall survival (OS) is attributed to the higher percentage of rectal tumors diagnosed at a localized stage (44% vs 38%). Patients aged < 65 years have higher 5-year survival rates than do those aged • 65 years (68.9% vs 62.0%).¹

Risk Factors

Like most human cancers, multiple genetic and environmental factors are believed to play a role in the development of colorectal carcinomas, with environmental factors playing the dominant role.⁴

Environmental risk factors include a low-fiber diet,⁵ red and processed meat intake,⁶ a high-fat diet,⁷ smoking,⁸ heavy alcohol consumption,⁹ obesity,¹⁰ physical inactivity,¹¹ alteration in intestinal flora,¹² and chronic inflammation.¹³ Aspirin (at doses > 300 mg/d), nonsteroidal anti-inflammatory drugs, and folic acid are believed to protect against colon cancer.¹⁴

Some of the genetic factors involved in colorectal cancers include (1) the loss of tumor suppressor genes, such as APC (most common tumor suppressor mutation), p53, SMAD4 pathways, or TGF-ß pathways; (2) DNA mismatch repair defects: mutations in MLH1, MSH2 in hereditary nonpolyposis colon cancer or methylation of MLH1 in sporadic cases; and (3) CpG island methylation (CIMP pathway), methylation of MLH1, MINT1, MINT2, MINT3; and (4) activation of oncogenes such as RAS and BRAF.¹⁵

Pathogenesis

The colonic mucosa consists of epithelial cells arranged in cylindrical structures called crypts. The human colon contains about 10 millionŽcrypts. The cellular proliferation and migration in each of the crypts is believed to be tightly regulated, with the majority of cells arising from a small number of stem cells (around 4-6) at the bottom of the crypt, which migrate upward after division and are eventually shed into the lumen.¹⁶ Each crypt is renewed in 2 to 8 days, which makes colonic mucosa one of the organs with the most cell proliferation in the human body and, hence, a target for various genetic and epigenetic alterations as well as environmental mutagenesis.⁷

Traditionally, the majority of colorectal carcinomas were believed to evolve from adenomatous polyps, which transform into an advanced adenoma with high-grade
dysplasia and then progress to an invasive cancer often referred to as the adenoma-to-carcinoma sequence.¹⁵ However, 2 other pathways, alternative and serrated,
have been described, and CRCs are now regarded as complex malignancies with a wide array of genetic and epigenetic mutations.¹⁷

About 70% to 85% of CRCs generally develop from chromosomal instability resulting from inactivation of tumor suppressor genes (APC gene, p53, etc). About 15% of cases are attributed to the failure of the DNA mismatch repair system either by germline/somatic mutations or by epigenetic silencing of gene transcription by CpG island methylation.¹⁸ Mutation in the BRAF or K-ras oncogenes are also believed to promote carcinogenesis.¹⁵ All these changes are believed to give rise to a precursor microscopic mucosal lesion that precedes the development of macroscopic adenomas.¹⁷

Clinical Features

The clinical features of CRCs can be widely variable, from incidental findings during screening colonoscopy to intestinal obstruction. The most common clinical presentation is rectal bleeding, followed by weight loss, abdominal pain, constipation, or diarrhea.¹⁹ The likelihood of CRC is higher with the combination of rectal bleeding and weight loss as well as rectal bleeding and change in bowel habits. Other clinical features may include bloating, abdominal pain, or anemia.²⁰ (See Table 1.)

Targeted Therapy in CRC

The targeted therapies in CRC include (1) the antivascular endothelial growth factor-A (anti–VEGF-A) antibody bevacizumab; (2) the VEGF-A, VEGF-B, and placental growth factor inhibitor aflibercept; (3) the multikinase inhibitor regorafenib; and (4) the anti-epidermal growth factor receptor (anti-EGFR) antibodies cetuximab and panitumumab.

Bevacizumab is an anti-VEGF monoclonal antibody. Vascular endothelial growth factor promotes angiogenesisnecessary for tumor growth. Bevacizumab was approved by the FDA in February 2004 as a first-line treatment in combination with IFL (irinotecan plus 5-fluorouracil [5-FU]/leucovorin) regimen and in June 2006 as a second-line treatment in combination with 5-FU–based chemotherapy for patients with mCRC. In January 2013, bevacizumab was approved for use in combination with fluoropyrimidine–irinotecan- or fluoropyrimidine–oxaliplatin-based chemotherapy for the treatment of patients with mCRC whose disease has progressed while on first-line treatment with a bevacizumab-containing regimen.²¹ (See Table 2.)

Aflibercept is a recombinant fusion protein, containing VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2, fused to the Fc portion of human immunoglobulin IgG1 that blocks the activity of VEGF-A, VEGF-B, and placental growth factor by acting as a high-affinity ligand trap to prevent these ligands from binding to their endogenous receptors.²² It was approved by the FDA in August 2012 for use in combination with FOLFIRI (5-FU, leucovorin, irinotecan) for the treatment of patients with mCRC that is resistant to or has progressed following an oxaliplatin‑containing regimen.²³

Cetuximab (a chimeric IgG1 anti-EGFR monoclonal antibody) and panitumumab (a human IgG2 anti-EGFR monoclonal antibody) have been shown to improve OS
and progression-free survival (PFS) in up to 20% of cases, either alone or in combination with chemotherapy.^24,25 The FDA approved cetuximab in July 2012 for use in
combination with FOLFIRI for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFRexpressing mCRC.²⁶ The FDA approved panitumumab in
September 2006 for the treatment of patients with EGFRexpressing metastatic colorectal carcinoma with disease progression on or following FOLFOX (5-FU, leucovorin, oxaliplatin)/FOLFIRI.27 (See Table 3.)

KRAS, a member of the rat sarcoma virus (ras) gene family of oncogenes, encodes for a small G protein downstream of EGFR. KRAS is mutated in CRC in up to 37% cases, resulting in activation of the different downstream signaling pathways.^15,28 Therefore, KRAS mutations predict resistance to anti-EGFR therapy.^28,29 Testing for KRAS mutation prior to treatment with cetuximab or panitumumab leads to targeted us of the very costly monoclonal antibodies and hence is considered a cost-effective practice.³⁰

Even in cases with wild-type KRAS mutation, response to anti-EGFR therapies is seen in only less than half of patients.³¹ Up to 17% of tumors with wild-type for KRAS exon 2 at codons 12 and 13 can have a mutation in another of the ras pathway genes (eg, KRAS exon 3, 4 and NRAS exon 2, 3, 4).²⁵ Mutations in the BRAF oncogene have been described in up to 13% of colorectal carcinoma cases.¹⁵ The data to suggest a lack of antitumor activity from anti-EGFR therapies in the presence of BRAF V600E mutation are still limited, but BRAF mutation is considered a poor prognostic factor.

A recent trial involving 1,137 patients with KRAS exon 2 wild-type mCRC randomly assigned to cetuximab or bevacizumab with standard chemotherapy (FOLFOX or FOLFIRI) found OS of 29.9 vs 29.0 months and median PFS 10.4 vs 10.8 months for cetuximab and bevacizumab, respectively.32 The OS for 5-FU–based therapies was about 11 months.³³

Regorafenib is an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor protein kinases, including those involved in the regulation of tumor angiogenesis (eg, VEGFR1-3 and TIE2 [tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2]), tumor microenvironment (plateletderived growth factor receptor-β and fibroblast growth factor receptor 1), as well as tumor oncogenesis (KIT, RET, RAF1, BRAF, BRAF V600E).34 A randomized phase 3 study involving 760 patients with documented progressive mCRC found a higher median OS with regorafenib vs placebo (6.4 mo vs 5.0 mo, P = .0052) and a
higher PFS (2.0 mo vs 1.7 mo, P < .0001).³⁵ The FDA approved regorafenib in September 2012 for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with an anti-VEGF therapy and, if KRAS wild-type, with an anti-EGFR therapy.³⁶

Conclusion

Targeted therapies in conjunction with newer chemotherapies have improved outcomes in metastatic colorectal carcinoma compared with those of conventional therapy (29 mo vs 11 mo).

Author disclosures
Peter T. Silberstein, MD, reports receiving payment for lectures from Bristol Myers and Celgene in the past. Drs. Khanal and Upadhyay report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Click here to read the digital edition.

Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in the U.S.^1-3 Only 40% of cases are diagnosed in a localized stage with an estimated 5-year survival of 90%, whereas 20% of cases present with metastatic disease with a 5-year survival of about 12.5%.¹ With recent advances in cancer genetics and immunology as well as approval of targeted agents by the FDA, different treatment options are now available, even for progressive disease.

This article presents a brief review of CRC with a special focus on targeted therapies in metastatic CRC (mCRC). Colorectal cancers exhibit certain mutations, which affect the tumor responsiveness to various treatment options. This article describes the role of targeted therapies in various well-established mutations.

Epidemiology

The most common tumor location is the proximal colon (42%), followed by the rectum (28%). More than 90% of patients with CRCs are aged > 50 years at diagnosis.
Women have a higher percentage of proximal tumors compared with men (46% vs 38%) and a lower percentage of rectal tumors (24% vs 31%).ŽAmong both sexes, incidence and mortality are highest in African Americans and lowest in Asian/Pacific Islanders. The estimated 5-year survival is slightly higher for rectal cancer (66.5%) than for colon cancer (64.2%), although the stage-specific survival is similar. The difference in 5-year overall survival (OS) is attributed to the higher percentage of rectal tumors diagnosed at a localized stage (44% vs 38%). Patients aged < 65 years have higher 5-year survival rates than do those aged • 65 years (68.9% vs 62.0%).¹

Risk Factors

Like most human cancers, multiple genetic and environmental factors are believed to play a role in the development of colorectal carcinomas, with environmental factors playing the dominant role.⁴

Environmental risk factors include a low-fiber diet,⁵ red and processed meat intake,⁶ a high-fat diet,⁷ smoking,⁸ heavy alcohol consumption,⁹ obesity,¹⁰ physical inactivity,¹¹ alteration in intestinal flora,¹² and chronic inflammation.¹³ Aspirin (at doses > 300 mg/d), nonsteroidal anti-inflammatory drugs, and folic acid are believed to protect against colon cancer.¹⁴

Some of the genetic factors involved in colorectal cancers include (1) the loss of tumor suppressor genes, such as APC (most common tumor suppressor mutation), p53, SMAD4 pathways, or TGF-ß pathways; (2) DNA mismatch repair defects: mutations in MLH1, MSH2 in hereditary nonpolyposis colon cancer or methylation of MLH1 in sporadic cases; and (3) CpG island methylation (CIMP pathway), methylation of MLH1, MINT1, MINT2, MINT3; and (4) activation of oncogenes such as RAS and BRAF.¹⁵

Pathogenesis

The colonic mucosa consists of epithelial cells arranged in cylindrical structures called crypts. The human colon contains about 10 millionŽcrypts. The cellular proliferation and migration in each of the crypts is believed to be tightly regulated, with the majority of cells arising from a small number of stem cells (around 4-6) at the bottom of the crypt, which migrate upward after division and are eventually shed into the lumen.¹⁶ Each crypt is renewed in 2 to 8 days, which makes colonic mucosa one of the organs with the most cell proliferation in the human body and, hence, a target for various genetic and epigenetic alterations as well as environmental mutagenesis.⁷

Traditionally, the majority of colorectal carcinomas were believed to evolve from adenomatous polyps, which transform into an advanced adenoma with high-grade
dysplasia and then progress to an invasive cancer often referred to as the adenoma-to-carcinoma sequence.¹⁵ However, 2 other pathways, alternative and serrated,
have been described, and CRCs are now regarded as complex malignancies with a wide array of genetic and epigenetic mutations.¹⁷

About 70% to 85% of CRCs generally develop from chromosomal instability resulting from inactivation of tumor suppressor genes (APC gene, p53, etc). About 15% of cases are attributed to the failure of the DNA mismatch repair system either by germline/somatic mutations or by epigenetic silencing of gene transcription by CpG island methylation.¹⁸ Mutation in the BRAF or K-ras oncogenes are also believed to promote carcinogenesis.¹⁵ All these changes are believed to give rise to a precursor microscopic mucosal lesion that precedes the development of macroscopic adenomas.¹⁷

Clinical Features

The clinical features of CRCs can be widely variable, from incidental findings during screening colonoscopy to intestinal obstruction. The most common clinical presentation is rectal bleeding, followed by weight loss, abdominal pain, constipation, or diarrhea.¹⁹ The likelihood of CRC is higher with the combination of rectal bleeding and weight loss as well as rectal bleeding and change in bowel habits. Other clinical features may include bloating, abdominal pain, or anemia.²⁰ (See Table 1.)

Targeted Therapy in CRC

The targeted therapies in CRC include (1) the antivascular endothelial growth factor-A (anti–VEGF-A) antibody bevacizumab; (2) the VEGF-A, VEGF-B, and placental growth factor inhibitor aflibercept; (3) the multikinase inhibitor regorafenib; and (4) the anti-epidermal growth factor receptor (anti-EGFR) antibodies cetuximab and panitumumab.

Bevacizumab is an anti-VEGF monoclonal antibody. Vascular endothelial growth factor promotes angiogenesisnecessary for tumor growth. Bevacizumab was approved by the FDA in February 2004 as a first-line treatment in combination with IFL (irinotecan plus 5-fluorouracil [5-FU]/leucovorin) regimen and in June 2006 as a second-line treatment in combination with 5-FU–based chemotherapy for patients with mCRC. In January 2013, bevacizumab was approved for use in combination with fluoropyrimidine–irinotecan- or fluoropyrimidine–oxaliplatin-based chemotherapy for the treatment of patients with mCRC whose disease has progressed while on first-line treatment with a bevacizumab-containing regimen.²¹ (See Table 2.)

Aflibercept is a recombinant fusion protein, containing VEGF-binding portions from the extracellular domains of human VEGF receptors 1 and 2, fused to the Fc portion of human immunoglobulin IgG1 that blocks the activity of VEGF-A, VEGF-B, and placental growth factor by acting as a high-affinity ligand trap to prevent these ligands from binding to their endogenous receptors.²² It was approved by the FDA in August 2012 for use in combination with FOLFIRI (5-FU, leucovorin, irinotecan) for the treatment of patients with mCRC that is resistant to or has progressed following an oxaliplatin‑containing regimen.²³

Cetuximab (a chimeric IgG1 anti-EGFR monoclonal antibody) and panitumumab (a human IgG2 anti-EGFR monoclonal antibody) have been shown to improve OS
and progression-free survival (PFS) in up to 20% of cases, either alone or in combination with chemotherapy.^24,25 The FDA approved cetuximab in July 2012 for use in
combination with FOLFIRI for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFRexpressing mCRC.²⁶ The FDA approved panitumumab in
September 2006 for the treatment of patients with EGFRexpressing metastatic colorectal carcinoma with disease progression on or following FOLFOX (5-FU, leucovorin, oxaliplatin)/FOLFIRI.27 (See Table 3.)

KRAS, a member of the rat sarcoma virus (ras) gene family of oncogenes, encodes for a small G protein downstream of EGFR. KRAS is mutated in CRC in up to 37% cases, resulting in activation of the different downstream signaling pathways.^15,28 Therefore, KRAS mutations predict resistance to anti-EGFR therapy.^28,29 Testing for KRAS mutation prior to treatment with cetuximab or panitumumab leads to targeted us of the very costly monoclonal antibodies and hence is considered a cost-effective practice.³⁰

Even in cases with wild-type KRAS mutation, response to anti-EGFR therapies is seen in only less than half of patients.³¹ Up to 17% of tumors with wild-type for KRAS exon 2 at codons 12 and 13 can have a mutation in another of the ras pathway genes (eg, KRAS exon 3, 4 and NRAS exon 2, 3, 4).²⁵ Mutations in the BRAF oncogene have been described in up to 13% of colorectal carcinoma cases.¹⁵ The data to suggest a lack of antitumor activity from anti-EGFR therapies in the presence of BRAF V600E mutation are still limited, but BRAF mutation is considered a poor prognostic factor.

A recent trial involving 1,137 patients with KRAS exon 2 wild-type mCRC randomly assigned to cetuximab or bevacizumab with standard chemotherapy (FOLFOX or FOLFIRI) found OS of 29.9 vs 29.0 months and median PFS 10.4 vs 10.8 months for cetuximab and bevacizumab, respectively.32 The OS for 5-FU–based therapies was about 11 months.³³

Regorafenib is an oral multikinase inhibitor of angiogenic, stromal, and oncogenic receptor protein kinases, including those involved in the regulation of tumor angiogenesis (eg, VEGFR1-3 and TIE2 [tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2]), tumor microenvironment (plateletderived growth factor receptor-β and fibroblast growth factor receptor 1), as well as tumor oncogenesis (KIT, RET, RAF1, BRAF, BRAF V600E).34 A randomized phase 3 study involving 760 patients with documented progressive mCRC found a higher median OS with regorafenib vs placebo (6.4 mo vs 5.0 mo, P = .0052) and a
higher PFS (2.0 mo vs 1.7 mo, P < .0001).³⁵ The FDA approved regorafenib in September 2012 for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, with an anti-VEGF therapy and, if KRAS wild-type, with an anti-EGFR therapy.³⁶

Conclusion

Targeted therapies in conjunction with newer chemotherapies have improved outcomes in metastatic colorectal carcinoma compared with those of conventional therapy (29 mo vs 11 mo).

Author disclosures
Peter T. Silberstein, MD, reports receiving payment for lectures from Bristol Myers and Celgene in the past. Drs. Khanal and Upadhyay report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Click here to read the digital edition.

Childhood cancer survivors are at an increased risk for developing an intestinal obstruction requiring surgery (IOS) 5 or more years after the initial cancer diagnosis, according to a study based on data from the Childhood Cancer Survivor Study.

The risk was greater among those who had a pelvic or abdominal tumor and had been exposed to pelvic or abdominal radiotherapy, reported the authors, who pointed out that no study has “rigorously” investigated the incidence of intestinal obstruction in childhood cancer survivors. The study appeared online in the Journal of Clinical Oncology (2015 Aug 10 doi: 10.1200/JCO.2015.61.5070).

The subjects in the study had been diagnosed with cancer before age 21 years between 1970 and 1986 and were followed longitudinally in the CCSS. The sample included 12,316 childhood cancer survivors who had survived at least 5 years from the time they were diagnosed with cancer and 4,023 of their siblings.

The cumulative incidence of “late” IOS (occurring at least 5 years after the cancer diagnosis) was 5.8% among those who had an abdominopelvic tumor and 1% among those who had other types of cancer, compared with 0.3% among siblings, who served as controls in the study. After adjusting for year of diagnosis, age at diagnosis, cancer type, radiotherapy, surgery, and other confounding factors, the risk of late IOS was significantly increased among those who had an abdominopelvic tumor (3.6 times greater) and those who had received abdominal/pelvic radiotherapy (2.4 times greater). Mortality was also almost twofold higher among those who developed late IOS when adjusted for the same factors, but there was no association with chemotherapy, cyclophosphamide equivalent dose, or platinum agent score and late IOS.

“The risk of IOS extends for decades beyond cancer diagnosis, implying the need for long-term vigilance, especially among survivors with abdominal or pelvic tumors and survivors who have undergone treatment with abdominal or pelvic surgery or radiotherapy,” concluded lead author Dr. Arin Madenci of Boston Children’s Hospital and his coauthors.

“Widespread awareness of the signs and symptoms of IOS will facilitate timely presentation and effective management of this complication. Although prevention of IOS is not currently possible, education of survivors of cancer, their families, and their health care providers is critical,” they added.

The study was supported by grants from the National Cancer Institute and Cancer Center Support (Centers of Research Excellence) and by the American Lebanese Syrian Associated Charities. Dr. Madenci and nine other authors had no disclosures. The remaining three authors had disclosures that included receiving honoraria, travel, and expenses from Sandoz, holding stock or other ownership in Pfizer and Novartis, serving as a consultant or advisor to United Therapeutics, and having an immediate family member with stock or other ownership in several pharmaceutical companies.

[email protected]

Childhood cancer survivors are at an increased risk for developing an intestinal obstruction requiring surgery (IOS) 5 or more years after the initial cancer diagnosis, according to a study based on data from the Childhood Cancer Survivor Study.

The risk was greater among those who had a pelvic or abdominal tumor and had been exposed to pelvic or abdominal radiotherapy, reported the authors, who pointed out that no study has “rigorously” investigated the incidence of intestinal obstruction in childhood cancer survivors. The study appeared online in the Journal of Clinical Oncology (2015 Aug 10 doi: 10.1200/JCO.2015.61.5070).

The subjects in the study had been diagnosed with cancer before age 21 years between 1970 and 1986 and were followed longitudinally in the CCSS. The sample included 12,316 childhood cancer survivors who had survived at least 5 years from the time they were diagnosed with cancer and 4,023 of their siblings.

The cumulative incidence of “late” IOS (occurring at least 5 years after the cancer diagnosis) was 5.8% among those who had an abdominopelvic tumor and 1% among those who had other types of cancer, compared with 0.3% among siblings, who served as controls in the study. After adjusting for year of diagnosis, age at diagnosis, cancer type, radiotherapy, surgery, and other confounding factors, the risk of late IOS was significantly increased among those who had an abdominopelvic tumor (3.6 times greater) and those who had received abdominal/pelvic radiotherapy (2.4 times greater). Mortality was also almost twofold higher among those who developed late IOS when adjusted for the same factors, but there was no association with chemotherapy, cyclophosphamide equivalent dose, or platinum agent score and late IOS.

“The risk of IOS extends for decades beyond cancer diagnosis, implying the need for long-term vigilance, especially among survivors with abdominal or pelvic tumors and survivors who have undergone treatment with abdominal or pelvic surgery or radiotherapy,” concluded lead author Dr. Arin Madenci of Boston Children’s Hospital and his coauthors.

“Widespread awareness of the signs and symptoms of IOS will facilitate timely presentation and effective management of this complication. Although prevention of IOS is not currently possible, education of survivors of cancer, their families, and their health care providers is critical,” they added.

The study was supported by grants from the National Cancer Institute and Cancer Center Support (Centers of Research Excellence) and by the American Lebanese Syrian Associated Charities. Dr. Madenci and nine other authors had no disclosures. The remaining three authors had disclosures that included receiving honoraria, travel, and expenses from Sandoz, holding stock or other ownership in Pfizer and Novartis, serving as a consultant or advisor to United Therapeutics, and having an immediate family member with stock or other ownership in several pharmaceutical companies.

[email protected]

Childhood cancer survivors are at an increased risk for developing an intestinal obstruction requiring surgery (IOS) 5 or more years after the initial cancer diagnosis, according to a study based on data from the Childhood Cancer Survivor Study.

The risk was greater among those who had a pelvic or abdominal tumor and had been exposed to pelvic or abdominal radiotherapy, reported the authors, who pointed out that no study has “rigorously” investigated the incidence of intestinal obstruction in childhood cancer survivors. The study appeared online in the Journal of Clinical Oncology (2015 Aug 10 doi: 10.1200/JCO.2015.61.5070).

The subjects in the study had been diagnosed with cancer before age 21 years between 1970 and 1986 and were followed longitudinally in the CCSS. The sample included 12,316 childhood cancer survivors who had survived at least 5 years from the time they were diagnosed with cancer and 4,023 of their siblings.

The cumulative incidence of “late” IOS (occurring at least 5 years after the cancer diagnosis) was 5.8% among those who had an abdominopelvic tumor and 1% among those who had other types of cancer, compared with 0.3% among siblings, who served as controls in the study. After adjusting for year of diagnosis, age at diagnosis, cancer type, radiotherapy, surgery, and other confounding factors, the risk of late IOS was significantly increased among those who had an abdominopelvic tumor (3.6 times greater) and those who had received abdominal/pelvic radiotherapy (2.4 times greater). Mortality was also almost twofold higher among those who developed late IOS when adjusted for the same factors, but there was no association with chemotherapy, cyclophosphamide equivalent dose, or platinum agent score and late IOS.

“The risk of IOS extends for decades beyond cancer diagnosis, implying the need for long-term vigilance, especially among survivors with abdominal or pelvic tumors and survivors who have undergone treatment with abdominal or pelvic surgery or radiotherapy,” concluded lead author Dr. Arin Madenci of Boston Children’s Hospital and his coauthors.

“Widespread awareness of the signs and symptoms of IOS will facilitate timely presentation and effective management of this complication. Although prevention of IOS is not currently possible, education of survivors of cancer, their families, and their health care providers is critical,” they added.

The study was supported by grants from the National Cancer Institute and Cancer Center Support (Centers of Research Excellence) and by the American Lebanese Syrian Associated Charities. Dr. Madenci and nine other authors had no disclosures. The remaining three authors had disclosures that included receiving honoraria, travel, and expenses from Sandoz, holding stock or other ownership in Pfizer and Novartis, serving as a consultant or advisor to United Therapeutics, and having an immediate family member with stock or other ownership in several pharmaceutical companies.

[email protected]

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

CHICAGO – Oral antibiotics alone or in combination with mechanical bowel preparation were independently associated with reduced surgical site infections after elective colorectal resection in a large national patient sample.

Oral antibiotics (OA) alone significantly reduced the rate of any surgical site infection (SSI) by 44% (odds ratio, 0.56; 95% confidence interval, 0.36-0.87) and wound SSI by 59% (OR, 0.41; 95% CI, 0.23-0.72), compared with no bowel preparation in propensity-adjusted multivariate analysis.

Patrice Wendling/Frontline Medical News

OA combined with mechanical bowel preparation (MBP) was independently associated with significant reductions of 54%, 58%, and 41%, respectively, for any SSI (OR, 0.46; 95% CI, 0.38-0.55), wound SSI (OR, 0.42; 95% CI, 0.33-0.53), and organ space SSI (OR, 0.59; 95% CI, 0.44-0.78).

In contrast, MBP, which was used in 40.8% of cases, was not independently associated with reduced rates of any SSI (OR, 0.95; 95% CI, 0.82-1.10), wound SSI (OR, 0.91; 95% CI, 0.76-1.09), or organ space SSI (OR, 1.0; 95% CI, 0.79-1.27), according to Dr. Sarah Koller of Temple University Hospital in Philadelphia and her associates.

A limitation of the study was the lack of information on type of OA or MBP used, patient compliance, and use of parenteral antibiotic prophylaxis.

“Randomized clinical trials are needed to determine the true benefits of oral antibiotics alone versus combined oral antibiotics and mechanical bowel prep prior to elective colorectal resection,” Dr. Koller said at the American College of Surgeons/National Surgery Quality Improvement Program National Conference.

Session comoderator Dr. E. Patchen Dellinger, of the University of Washington in Seattle, commented, “Logically, it’s hard for me to believe that oral antibiotics would affect a couple of kilograms of stool in the colon and yet here are these tantalizing data. So we do need the prospective trial you mention.

Patrice Wendling/Frontline Medical News

“But, the other thing that blows my mind every time I see these data is 49% of people getting a mechanical bowel prep without oral antibiotics, which has conclusively been shown to be useless for anything but torture of the patient.”

Significant variability in the use of bowel preparation exists within the surgical community, with a recent survey of colorectal surgeons revealing that 76% routinely used MBP and only 36% routinely used oral antibiotics, Dr. Koller observed.

In the current analysis, just 3.3% of patients received OA, 30.4% OA plus MBP, 40.8% MBP, and 25.5% no bowel preparation.

Physicians have been slow to abandon MBP, despite multiple studies showing that MBP alone does not reduce SSIs in elective colon and rectal surgery. There also have been reports of higher rates of anastomotic leak, increased cardiac or metabolic complications, and a slower return of bowel function with MBP.

Several studies, including a recent Cochrane Database Review, have shown that oral or intravenous antibiotic prophylaxis reduces surgical wound infection after colorectal surgery. The comparison groups are not uniform across the studies, however, and the controversy persists as to which type of bowel prep best reduces SSI after colorectal surgery, she said.

To explore this issue, the investigators identified all patients who underwent elective, nonemergent colorectal resections in both the ACS NSQIP Participant Use Data File (PUF) and the Procedure Targeted PUF for colectomy from 2012 to 2013. The cohort included 19,372 patients with complete preoperative bowel preparation data. Patients who were ventilator dependent or had infections or open wounds at the time of surgery were excluded.

The overall rates of any SSI, wound SSI (superficial and/or deep), and organ space SSI were 9.5%, 6.4%, and 3.5%, respectively.

With regard to adverse outcomes cited in previous studies, only OA plus MBP was shown to independently reduce anastomotic leak (OR, 0.57; 95% CI, 0.42-0.78) and postoperative ileus (OR, 0.79; 95% CI, 0.68-0.92), compared with no bowel prep, Dr. Koller reported.

Both OA and OA plus MBP, however, decreased length of stay by 0.83 days.

None of the bowel preparations were independently associated with increased rates of cardiac or renal complications, she said.

The investigators were not able to track rates of Clostridium difficile colitis after administration of the oral antibiotics. Dr. Koller acknowledged this is a concern when using oral antibiotics and may contribute to why they aren’t used frequently.

Dr. Koller reported having no conflicts of interest. A coauthor disclosed consulting for Intuitive Surgical.

[email protected]

Clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) were similar enough to outcomes of younger patients that doctors may want to reconsider using age alone for determining eligibility for nCRT and surgery, investigators reported online in the Annals of Oncology.

Dr. D. M. Jiang of the University of Ottawa (Ont.) and associates collected data from 1,172 patients with LARC who received nCRT and curative intent surgery, 25% (n = 295) of whom were 70 years old or older, from five major Canadian cancer centers between 2005 and 2012. When compared with younger patients, elderly patients were less likely to receive adjuvant chemotherapy (ACT) (60% vs. 79%; P less than .0001), oxaliplatin-based ACT (12% vs. 31%; P less than .0001), less likely to complete nCT (76% vs. 86%; P less than .001), and more likely to be anemic at initiation of nCRT (42% vs. 30%; P = .0004).

The investigators found that increasing age was not predictive of disease-free survival (hazard ratio, 1.00; 95% confidence interval, 0.99-1.02; P = .49) or cancer-specific survival (HR, 1.002; 95% CI, 0.98-1.02; P = .88) among LARC patients; however, advanced age correlated with an inferior overall survival (HR, 1.02; 95% CI, 1.00-1.03; P = .04).

Read the full article here.

[email protected]

Clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) were similar enough to outcomes of younger patients that doctors may want to reconsider using age alone for determining eligibility for nCRT and surgery, investigators reported online in the Annals of Oncology.

Dr. D. M. Jiang of the University of Ottawa (Ont.) and associates collected data from 1,172 patients with LARC who received nCRT and curative intent surgery, 25% (n = 295) of whom were 70 years old or older, from five major Canadian cancer centers between 2005 and 2012. When compared with younger patients, elderly patients were less likely to receive adjuvant chemotherapy (ACT) (60% vs. 79%; P less than .0001), oxaliplatin-based ACT (12% vs. 31%; P less than .0001), less likely to complete nCT (76% vs. 86%; P less than .001), and more likely to be anemic at initiation of nCRT (42% vs. 30%; P = .0004).

The investigators found that increasing age was not predictive of disease-free survival (hazard ratio, 1.00; 95% confidence interval, 0.99-1.02; P = .49) or cancer-specific survival (HR, 1.002; 95% CI, 0.98-1.02; P = .88) among LARC patients; however, advanced age correlated with an inferior overall survival (HR, 1.02; 95% CI, 1.00-1.03; P = .04).

Read the full article here.

[email protected]

Clinical outcomes of elderly patients treated with neoadjuvant chemoradiation (nCRT) for locally advanced rectal cancer (LARC) were similar enough to outcomes of younger patients that doctors may want to reconsider using age alone for determining eligibility for nCRT and surgery, investigators reported online in the Annals of Oncology.

Dr. D. M. Jiang of the University of Ottawa (Ont.) and associates collected data from 1,172 patients with LARC who received nCRT and curative intent surgery, 25% (n = 295) of whom were 70 years old or older, from five major Canadian cancer centers between 2005 and 2012. When compared with younger patients, elderly patients were less likely to receive adjuvant chemotherapy (ACT) (60% vs. 79%; P less than .0001), oxaliplatin-based ACT (12% vs. 31%; P less than .0001), less likely to complete nCT (76% vs. 86%; P less than .001), and more likely to be anemic at initiation of nCRT (42% vs. 30%; P = .0004).

The investigators found that increasing age was not predictive of disease-free survival (hazard ratio, 1.00; 95% confidence interval, 0.99-1.02; P = .49) or cancer-specific survival (HR, 1.002; 95% CI, 0.98-1.02; P = .88) among LARC patients; however, advanced age correlated with an inferior overall survival (HR, 1.02; 95% CI, 1.00-1.03; P = .04).

Read the full article here.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

CHICAGO – Implementing an enhanced recovery after surgery (ERAS) protocol at Canada’s second largest hospital significantly reduced morbidity and surgical site infections after elective colorectal surgery.

Rates of postoperative morbidity declined 48.7% from 27.3% before implementation to 14% after full ERAS implementation (P less than .05), while total surgical site infections fell 45% (20.2% vs. 11%; P less than .05).

Nonsignificant reductions were also seen in superficial surgical site infections (11.1% vs. 7.3%), deep SSIs (2% vs. 0.6%), and organ space SSIs (7.1% vs. 3.4%).

“Our results illustrate that using a multidisciplinary team, with attention to details and small multiple changes, aggregation of marginal gains can result in dramatic improvements in patient outcomes,” primary author Tracey Hong, R.N., said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference.

The ERAS protocol was implemented at Vancouver General Hospital, after ACS NSQIP risk-adjusted reports showed the 743-bed hospital had a high odds ratio of 1.50 for colorectal operative mortality.

Patrice Wendling/Frontline Medical News

“We had a problem,” Ms. Hong, the hospital’s quality and patient safety coordinator, said.

ERAS documents were developed, staff were educated on the protocol, intraoperative components were implemented and audited, and the full protocol was initiated in November 2013.

To explore the effects of ERAS implementation, chart reviews were conducted on 278 general surgery patients undergoing elective colorectal surgery: 99 patients before ERAS implementation (July 2011 through June 2013) and 179 patients in the first 10 months after full implementation (November 2013 through August 2014).

Laparoscopic colon resections were performed in 53% of the pre-ERAS group and 62% of the post-ERAS group, laparoscopic anterior and abdominoperineal resections in 10% and 23%, and open anterior and abdominoperineal resections in 23% and 18%, respectively. The median American Society of Anesthesiologists classification in both groups was 2.

After ERAS implementation, there was a trend for less postoperative pneumonia, unplanned intubation, ventilator use greater than 48 hours, and urinary tract infections (data not presented).

The median length of stay was reduced from 7 to 5 days, while readmissions increased from 7.1% to 11.7% (both changes were nonsignificant), according to Ms. Hong, who won the conference’s 2015 Surgical Clinical Reviewers Abstract Competition.

The reason for the increased readmissions is unclear, but opportunities to avoid preventable readmissions have been identified and are currently being worked on, she said.

Process measures showed that the goal of achieving a minimum 80% compliance from August 2014 to March 2015 was met within 4 months and sustained for the preoperative and intraoperative ERAS components, in aggregate. The aggregate postoperative components, which include early oral nutrition, early ambulation, early catheter removal, use of chewing gum, and defined discharge criteria, were the slowest to change, but are trending in the right direction, Ms. Hong said.

The key to achieving better outcomes with ERAS lies in involving a multidisciplinary team in all stages of planning and implementation, ongoing communication and sharing of results with stakeholders to foster commitment and ownership, and real-time auditing and use of plan-do-study-act cycles to enhance the rate of improvement, she said.

“It takes time to change culture; tenacity is important,” Ms. Hong added.

In a separate poster presentation, Ms. Hong and her colleagues reported compliance of ERAS components under the control of the anesthesiologist. The highest rate of compliance was seen in practices with few barriers to implementation such as active pre- and intraoperative warming (96%) and appropriate admission of antibiotics (92%) and antiemetics (86%). Conversely, rates were lower for multimodal analgesia (72%) and goal-directed fluid therapy (50%), which can be more labor intensive. Also, there is controversy around goal-directed fluid therapy’s benefit in low-risk patients, which may contribute to the lower compliance rates, the study authors noted. Overall, just under three-quarters of patients received at least four out of five components in their care.

On the basis of the success of the protocol, ERAS is now used for patients undergoing radical cystectomy, with plans to expand its use to all emergent and urgent cases within general surgery at Vancouver General as well as bariatric surgery at Richmond Hospital, also a member of Vancouver Coastal Health, Andrea Bisaillon, operations director of surgical services at Vancouver General Hospital, said in an interview.

“We’re rolling out ERAS to all the surgical patients because it’s best practice for all of surgery, not just colorectal surgery anymore,” she said.

[email protected]

Patients who have just had surgery for colorectal cancer may not be getting enough information at discharge, say researchers from Lund University in Sweden.

The researchers conducted 31 interviews with 16 patients during their first 7 weeks at home after surgery. A theme emerged from the interviews: trying to regain control in life by using information. That had several subthemes, such as needing more information on how to manage symptoms and self-care.

Related: Do Age and Gender Matter in Colorectal Cancer?

Patients lacked information on how long recovery would take, how to improve physical fitness, what to eat and drink, how bowel function and weight would be affected, and how to remove the sutures and care for the wound. Some patients were concerned about how to take medications and painkillers, and some received incorrect prescriptions.

Related: Colonoscopy Bowel Preparation Instructions

Researchers also found that patients wanted to take part in planning and preparation. Some patients compared the discharge process unfavorably with the preoperative preparation, which they described as being calmer, with easier-to-follow information. Patients also wanted straightforward information given as part of a mutual meeting, which was important in part because they closely observed health care practitioners’ facial expressions and intonation to determine whether anything was being withheld.

Lack of information added to patient worry about treatment and about their future. And having to wait without being told anything worsened worry for some patients. Even things like not having a promised appointment take place on time added to the anxiety and insecurity.

Related: Oxaliplatin-Induced Lhermitte Sign

The researchers acknowledge that not all patients want information, or they want it later in the trajectory of the disease and recovery stages. But when patients do seek information, they may choose untrustworthy sources. The onus is on the health care professionals, the researchers say, to provide person-centered care with easily accessible information for all patients, even those who might wish to avoid it.

Source
Lithner M, Klefsgard R, Johannson J, Andersson E. BMC Nurse. 2015;14:36.
doi: 10.1186/s12912-015-0086-6.

Patients who have just had surgery for colorectal cancer may not be getting enough information at discharge, say researchers from Lund University in Sweden.

The researchers conducted 31 interviews with 16 patients during their first 7 weeks at home after surgery. A theme emerged from the interviews: trying to regain control in life by using information. That had several subthemes, such as needing more information on how to manage symptoms and self-care.

Related: Do Age and Gender Matter in Colorectal Cancer?

Patients lacked information on how long recovery would take, how to improve physical fitness, what to eat and drink, how bowel function and weight would be affected, and how to remove the sutures and care for the wound. Some patients were concerned about how to take medications and painkillers, and some received incorrect prescriptions.

Related: Colonoscopy Bowel Preparation Instructions

Researchers also found that patients wanted to take part in planning and preparation. Some patients compared the discharge process unfavorably with the preoperative preparation, which they described as being calmer, with easier-to-follow information. Patients also wanted straightforward information given as part of a mutual meeting, which was important in part because they closely observed health care practitioners’ facial expressions and intonation to determine whether anything was being withheld.

Lack of information added to patient worry about treatment and about their future. And having to wait without being told anything worsened worry for some patients. Even things like not having a promised appointment take place on time added to the anxiety and insecurity.

Related: Oxaliplatin-Induced Lhermitte Sign

The researchers acknowledge that not all patients want information, or they want it later in the trajectory of the disease and recovery stages. But when patients do seek information, they may choose untrustworthy sources. The onus is on the health care professionals, the researchers say, to provide person-centered care with easily accessible information for all patients, even those who might wish to avoid it.

Source
Lithner M, Klefsgard R, Johannson J, Andersson E. BMC Nurse. 2015;14:36.
doi: 10.1186/s12912-015-0086-6.

Patients who have just had surgery for colorectal cancer may not be getting enough information at discharge, say researchers from Lund University in Sweden.

The researchers conducted 31 interviews with 16 patients during their first 7 weeks at home after surgery. A theme emerged from the interviews: trying to regain control in life by using information. That had several subthemes, such as needing more information on how to manage symptoms and self-care.

Related: Do Age and Gender Matter in Colorectal Cancer?

Patients lacked information on how long recovery would take, how to improve physical fitness, what to eat and drink, how bowel function and weight would be affected, and how to remove the sutures and care for the wound. Some patients were concerned about how to take medications and painkillers, and some received incorrect prescriptions.

Related: Colonoscopy Bowel Preparation Instructions

Researchers also found that patients wanted to take part in planning and preparation. Some patients compared the discharge process unfavorably with the preoperative preparation, which they described as being calmer, with easier-to-follow information. Patients also wanted straightforward information given as part of a mutual meeting, which was important in part because they closely observed health care practitioners’ facial expressions and intonation to determine whether anything was being withheld.

Lack of information added to patient worry about treatment and about their future. And having to wait without being told anything worsened worry for some patients. Even things like not having a promised appointment take place on time added to the anxiety and insecurity.

Related: Oxaliplatin-Induced Lhermitte Sign

The researchers acknowledge that not all patients want information, or they want it later in the trajectory of the disease and recovery stages. But when patients do seek information, they may choose untrustworthy sources. The onus is on the health care professionals, the researchers say, to provide person-centered care with easily accessible information for all patients, even those who might wish to avoid it.

Source
Lithner M, Klefsgard R, Johannson J, Andersson E. BMC Nurse. 2015;14:36.
doi: 10.1186/s12912-015-0086-6.

There are several relevant strategies for patients with cancer who have malignant bowel obstruction. According to Jocelyn White, MD, strategies for management must be based on patient characteristics, current cancer treatment, and care goals.

“For hospice and palliative patients, we start by treating the reversible causes,” Dr. White said. “The first thing you do when you suspect obstruction is to try to treat for pseudo-obstruction. I can’t tell you how many times we have gotten patients referred to us for complete malignant bowel obstruction who actually are constipated or obstipated.”

There are several relevant strategies for patients with cancer who have malignant bowel obstruction. According to Jocelyn White, MD, strategies for management must be based on patient characteristics, current cancer treatment, and care goals.

“For hospice and palliative patients, we start by treating the reversible causes,” Dr. White said. “The first thing you do when you suspect obstruction is to try to treat for pseudo-obstruction. I can’t tell you how many times we have gotten patients referred to us for complete malignant bowel obstruction who actually are constipated or obstipated.”

There are several relevant strategies for patients with cancer who have malignant bowel obstruction. According to Jocelyn White, MD, strategies for management must be based on patient characteristics, current cancer treatment, and care goals.

“For hospice and palliative patients, we start by treating the reversible causes,” Dr. White said. “The first thing you do when you suspect obstruction is to try to treat for pseudo-obstruction. I can’t tell you how many times we have gotten patients referred to us for complete malignant bowel obstruction who actually are constipated or obstipated.”

For adults with advanced ulcerative colitis (UC) older than 50 years of age, elective colectomy offered a significantly higher survival rate than did medical therapy, according to a retrospective study of 8,371 patients.

Dr. Meenakshi Bewtra of the University of Pennsylvania, Philadelphia, and her coinvestigators matched 830 UC patients seeking elective colectomy for treatment with 7,541 UC patients opting for more traditional medical therapy, all recruited using data from Medicaid and Medicare from 2000 to 2011 (Ann. Intern. Med. July 14, 2015 [doi:10.7326/M14-0960]).

In total, 63 patients who received elective colectomy died, compared with 783 patients in the medical therapy cohort. Mortality rates per cohort were 34 and 54 per 1,000 person-years, respectively. Furthermore, patients were more likely to respond more favorably to elective colectomy than to medical therapy, with an adjusted hazard ratio of 0.67. Additional post hoc analysis revealed higher survival odds with colectomy for patients age 50 years or older (HR, 0.60; P = .032). “These findings warrant discussion with patients when one is weighing the risks and benefits of different medical therapies and total colectomy,” the investigators said.

The authors noted that the study had several limitations, such as potential residual confounding and the possibility of reduced statistical power in subsequent analyses because several databases were used to cull data.

The study was funded by grants from the National Institutes of Health and the Agency for Healthcare Research and Quality. Dr. Bewtra disclosed receiving a grant from NIH and accepting speaking engagements for Imedex and the Crohn’s & Colitis Foundation of America/Robert Michael Educational Institute outside the submitted work.

[email protected]

For adults with advanced ulcerative colitis (UC) older than 50 years of age, elective colectomy offered a significantly higher survival rate than did medical therapy, according to a retrospective study of 8,371 patients.

Dr. Meenakshi Bewtra of the University of Pennsylvania, Philadelphia, and her coinvestigators matched 830 UC patients seeking elective colectomy for treatment with 7,541 UC patients opting for more traditional medical therapy, all recruited using data from Medicaid and Medicare from 2000 to 2011 (Ann. Intern. Med. July 14, 2015 [doi:10.7326/M14-0960]).

In total, 63 patients who received elective colectomy died, compared with 783 patients in the medical therapy cohort. Mortality rates per cohort were 34 and 54 per 1,000 person-years, respectively. Furthermore, patients were more likely to respond more favorably to elective colectomy than to medical therapy, with an adjusted hazard ratio of 0.67. Additional post hoc analysis revealed higher survival odds with colectomy for patients age 50 years or older (HR, 0.60; P = .032). “These findings warrant discussion with patients when one is weighing the risks and benefits of different medical therapies and total colectomy,” the investigators said.

The authors noted that the study had several limitations, such as potential residual confounding and the possibility of reduced statistical power in subsequent analyses because several databases were used to cull data.

The study was funded by grants from the National Institutes of Health and the Agency for Healthcare Research and Quality. Dr. Bewtra disclosed receiving a grant from NIH and accepting speaking engagements for Imedex and the Crohn’s & Colitis Foundation of America/Robert Michael Educational Institute outside the submitted work.

[email protected]

For adults with advanced ulcerative colitis (UC) older than 50 years of age, elective colectomy offered a significantly higher survival rate than did medical therapy, according to a retrospective study of 8,371 patients.

Dr. Meenakshi Bewtra of the University of Pennsylvania, Philadelphia, and her coinvestigators matched 830 UC patients seeking elective colectomy for treatment with 7,541 UC patients opting for more traditional medical therapy, all recruited using data from Medicaid and Medicare from 2000 to 2011 (Ann. Intern. Med. July 14, 2015 [doi:10.7326/M14-0960]).

In total, 63 patients who received elective colectomy died, compared with 783 patients in the medical therapy cohort. Mortality rates per cohort were 34 and 54 per 1,000 person-years, respectively. Furthermore, patients were more likely to respond more favorably to elective colectomy than to medical therapy, with an adjusted hazard ratio of 0.67. Additional post hoc analysis revealed higher survival odds with colectomy for patients age 50 years or older (HR, 0.60; P = .032). “These findings warrant discussion with patients when one is weighing the risks and benefits of different medical therapies and total colectomy,” the investigators said.

The authors noted that the study had several limitations, such as potential residual confounding and the possibility of reduced statistical power in subsequent analyses because several databases were used to cull data.

The study was funded by grants from the National Institutes of Health and the Agency for Healthcare Research and Quality. Dr. Bewtra disclosed receiving a grant from NIH and accepting speaking engagements for Imedex and the Crohn’s & Colitis Foundation of America/Robert Michael Educational Institute outside the submitted work.

[email protected]