Colon and Rectal

The use of a large-pore polypropylene mesh in colorectal surgery can reduce incidence of incisional hernias without contributing to wound complication risk, according to results from a randomized controlled trial.

While prophylactic polypropylene meshes have been used successfully in other types of surgeries to prevent hernias, they have been little studied in series of patients undergoing colorectal surgeries, a group for which incidence of IH is high, and particularly so with emergency procedures.

STEFANOLUNARDI/thinkstockphotos.com

For their research, published ahead of print in Annals of Surgery (Ann. Surg.2015 Jan 8 [doi: 10.1097/SLA.0000000000001116]), Dr. Miguel Ángel García-Ureña of Henares University Hospital in Madrid, and his colleagues, recruited 107 patients with elective or emergency colorectal surgeries using a midline laparotomy approach.

Patients were randomized to either standard care (n = 54, 20 emergency) or the addition of an overlay large-pore polypropylene mesh after the closure of the abdominal wall (n = 53, 17 emergency). All operations took place at the same hospital, with 12 surgeons participating.

At 24 months’ follow-up, the control group saw 17 incisional hernias (31.5%), compared with 6 (11.3%) in the study group (P = .011). No statistically significant differences were seen for incidence of surgical site infection, seroma, evisceration, or systemic complications, and no mesh rejection was seen.

Dr. García-Ureña and colleagues used a very low-weight, large-pore polypropylene mesh after initial studies suggested large-pore meshes were better tolerated in contaminated fields, and that these could be salvaged even in the case of site infection.

The study “confirms the safe use of large-pore polypropylene meshes even in contaminated and emergency surgical procedures,” the investigators wrote in their analysis, adding that the use of mesh overlay “was cost-effective due to the number needed to treat obtained: 1 IH was prevented for every 5 prophylactic meshes that were used.”

Dr. García-Ureña and colleagues cited as limitations of their study the fact that deaths and reoperations occurred in 28% of patients before follow-up ended, the inclusion of both elective and emergency cases, and that wound length was not recorded. Further studies will be needed, they said, to determine the ideal positioning of the mesh and the best type of mesh for these procedures.

The study authors declared no conflicts of interest.

The use of a large-pore polypropylene mesh in colorectal surgery can reduce incidence of incisional hernias without contributing to wound complication risk, according to results from a randomized controlled trial.

While prophylactic polypropylene meshes have been used successfully in other types of surgeries to prevent hernias, they have been little studied in series of patients undergoing colorectal surgeries, a group for which incidence of IH is high, and particularly so with emergency procedures.

STEFANOLUNARDI/thinkstockphotos.com

For their research, published ahead of print in Annals of Surgery (Ann. Surg.2015 Jan 8 [doi: 10.1097/SLA.0000000000001116]), Dr. Miguel Ángel García-Ureña of Henares University Hospital in Madrid, and his colleagues, recruited 107 patients with elective or emergency colorectal surgeries using a midline laparotomy approach.

Patients were randomized to either standard care (n = 54, 20 emergency) or the addition of an overlay large-pore polypropylene mesh after the closure of the abdominal wall (n = 53, 17 emergency). All operations took place at the same hospital, with 12 surgeons participating.

At 24 months’ follow-up, the control group saw 17 incisional hernias (31.5%), compared with 6 (11.3%) in the study group (P = .011). No statistically significant differences were seen for incidence of surgical site infection, seroma, evisceration, or systemic complications, and no mesh rejection was seen.

Dr. García-Ureña and colleagues used a very low-weight, large-pore polypropylene mesh after initial studies suggested large-pore meshes were better tolerated in contaminated fields, and that these could be salvaged even in the case of site infection.

The study “confirms the safe use of large-pore polypropylene meshes even in contaminated and emergency surgical procedures,” the investigators wrote in their analysis, adding that the use of mesh overlay “was cost-effective due to the number needed to treat obtained: 1 IH was prevented for every 5 prophylactic meshes that were used.”

Dr. García-Ureña and colleagues cited as limitations of their study the fact that deaths and reoperations occurred in 28% of patients before follow-up ended, the inclusion of both elective and emergency cases, and that wound length was not recorded. Further studies will be needed, they said, to determine the ideal positioning of the mesh and the best type of mesh for these procedures.

The study authors declared no conflicts of interest.

The use of a large-pore polypropylene mesh in colorectal surgery can reduce incidence of incisional hernias without contributing to wound complication risk, according to results from a randomized controlled trial.

While prophylactic polypropylene meshes have been used successfully in other types of surgeries to prevent hernias, they have been little studied in series of patients undergoing colorectal surgeries, a group for which incidence of IH is high, and particularly so with emergency procedures.

STEFANOLUNARDI/thinkstockphotos.com

For their research, published ahead of print in Annals of Surgery (Ann. Surg.2015 Jan 8 [doi: 10.1097/SLA.0000000000001116]), Dr. Miguel Ángel García-Ureña of Henares University Hospital in Madrid, and his colleagues, recruited 107 patients with elective or emergency colorectal surgeries using a midline laparotomy approach.

Patients were randomized to either standard care (n = 54, 20 emergency) or the addition of an overlay large-pore polypropylene mesh after the closure of the abdominal wall (n = 53, 17 emergency). All operations took place at the same hospital, with 12 surgeons participating.

At 24 months’ follow-up, the control group saw 17 incisional hernias (31.5%), compared with 6 (11.3%) in the study group (P = .011). No statistically significant differences were seen for incidence of surgical site infection, seroma, evisceration, or systemic complications, and no mesh rejection was seen.

Dr. García-Ureña and colleagues used a very low-weight, large-pore polypropylene mesh after initial studies suggested large-pore meshes were better tolerated in contaminated fields, and that these could be salvaged even in the case of site infection.

The study “confirms the safe use of large-pore polypropylene meshes even in contaminated and emergency surgical procedures,” the investigators wrote in their analysis, adding that the use of mesh overlay “was cost-effective due to the number needed to treat obtained: 1 IH was prevented for every 5 prophylactic meshes that were used.”

Dr. García-Ureña and colleagues cited as limitations of their study the fact that deaths and reoperations occurred in 28% of patients before follow-up ended, the inclusion of both elective and emergency cases, and that wound length was not recorded. Further studies will be needed, they said, to determine the ideal positioning of the mesh and the best type of mesh for these procedures.

The study authors declared no conflicts of interest.

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.

SAN FRANCISCO – Resecting the primary tumor in patients with metastatic colon or colorectal cancer may prolong survival. But then again, it may not.

This was the overarching take-home message from a trio of cohort studies presented at the Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. Results were reported in a poster session.

“Whereas surgery is the primary treatment of localized colorectal cancer, resection of the primary tumor in patients with incurable metastatic disease is usually recommended for palliative purposes to manage obstruction, perforation, or bleeding,” Dr. Shahid Ahmed, lead investigator of one of the studies, noted in comments provided by e-mail. “The role of surgical resection of the primary tumor in patients with newly diagnosed incurable stage IV colorectal cancer remains controversial.”

In earlier research, he and colleagues found a survival benefit of primary resection among Canadian patients whose cancer was diagnosed between 1992 and 2005 (Cancer 2014;120:683-91). But the majority did not receive systemic therapy, and those who did were often given older regimens.

In a new study aimed at testing the association in the contemporary treatment era, the researchers analyzed data from 569 patients with stage IV colorectal cancer diagnosed between 2006 and 2010 who had a median follow-up of 11 months. Overall, 55% had resection of the primary tumor.

Among the 57% of patients who received systemic therapy, 91% received FOLFIRI or FOLFOX, 65% received bevacizumab (Avastin), and 10% received cetuximab (Erbitux) or panitumumab (Vectibix), according to Dr. Ahmed, professor of medicine, University of Saskatchewan, Canada.

Results for the entire cohort showed that median overall survival was 18 months in patients who had resection of their primary versus 4 months in those who did not (multivariate hazard ratio, 0.44; P less than .001).

Among the subgroup of patients who received chemotherapy, median survival was 27 months with primary resection versus 14 months without it (P less than .0001). And among the subgroup that specifically received FOLFIRI or FOLFOX and a biologic agent, it was 35 months with primary resection and 23 months without it (P less than .001).

“Surgical resection of primary tumor improves survival of patients with stage IV colorectal cancer, independent of other prognostic variables including age, performance status, comorbid illness, and chemotherapy,” maintained Dr. Ahmed. “The current study validates our findings and supports surgical resection of primary tumor in patients with stage IV colorectal cancer who are treated with modern chemotherapy and biologics.

“A well-designed prospective randomized trial is warranted to confirm the survival benefit conferred by the primary tumor resection,” he added, noting that two such trials in Europe – SYNCHRONOUS and CAIRO4 – are underway.

“If the magnitude of survival benefit is confirmed in these future randomized studies, surgical resection of the primary tumor could potentially be a more cost-effective intervention compared with novel systemic therapy in the management of metastatic colorectal cancer,” he concluded.

Susan London/Frontline Medical News

In a second study, Dr. Aaron Lewis, a surgical oncology fellow at the City of Hope, Duarte, Calif., and colleagues analyzed data from patients with stage IV colon cancer in the Surveillance, Epidemiology, and End Results (SEER) database for the years 1998 through 2011. They excluded those who died within 30 days of diagnosis or had resection of metastases. Overall, 70% of the 28,068 included patients had resection of their primary.

In multivariate analyses, patients who underwent resection had half the risk of death when compared with peers who did not have this surgery (hazard ratio, 0.49), reported Dr. Lewis.

Findings were essentially the same when the analysis was repeated in a subset of matched patients: Median survival was 17 months with resection versus 9 months without it (hazard ratio, 0.48; P less than .0001). Estimated 3-year survival was 23% and 6%, respectively.

“There are limitations, factors that we couldn’t completely control for. For example, there is no chemotherapy data in the SEER database. We didn’t know the timing of surgery in relation to chemotherapy. And we didn’t know whether these patients were asymptomatic or symptomatic,” Dr. Lewis noted in an interview. “But analysis of this huge group of patients in the United States that are getting treated shows that there is a survival benefit.”

Possible reasons why surgery might prolong life in this setting are unknown but may include the effects of tumor debulking or some enhancement of the immune response, he proposed.

To definitively confirm a survival benefit, a randomized controlled trial is needed, he agreed. “This seems to be a popular question in the literature in the last couple of years, so maybe somebody will be willing to take it on.”

In a third study, a team led by Dr. Zeinab Alawadi, a surgeon and postdoctoral fellow at the University of Texas MD Anderson Cancer Center, Houston, analyzed data from 14,399 patients in the National Cancer Data Base. They had been diagnosed with stage IV colon cancer between 2003 and 2005. The researchers excluded patients who had nonelective resection or surgery at other sites, such as metastasectomy.

The primary tumor was resected in 55% of all patients studied and in 74% of patients included in a 1-year landmark analysis done to account for early deaths related to comorbidity or disease burden, reported Dr. Alawadi.

In the entire cohort, primary resection conferred a significant survival benefit after standard multivariate adjustment (hazard ratio, 0.39) that persisted after propensity score weighting to account for treatment selection bias (hazard ratio, 0.41). The benefit was also significant, but much attenuated, in an instrumental variable analysis, another method for accounting for treatment selection bias (relative mortality rate, 0.88).

In the 1-year landmark population, primary resection conferred a smaller significant survival benefit after standard multivariate adjustment (hazard ratio, 0.60) that persisted after propensity score weighting (hazard ratio, 0.59). But there was no longer a significant benefit in the instrumental variable analysis here.

“Among the entire cohort of patients with stage 4 colon cancer, primary tumor resection offered no survival benefit over systemic chemotherapy alone when the [instrumental variable] method was applied at the 1 year landmark,” the investigators write.

“Subject to selection and survivor treatment bias, standard regression analysis may overestimate the benefit of [primary tumor resection],” they concluded.

Postoperative NSAIDs appear to raise the risk for anastomotic complications among patients undergoing nonelective colorectal resection, according to a report in JAMA Surgery.

“Given that other analgesic regimens are effective and well tolerated, these data may be enough from some surgeons to alter practice patterns,” said Dr. Timo W. Hakkarainen of the department of surgery at the University of Washington, Seattle, and his associates.

The recent development of intravenous formulations of NSAIDs has expanded their use in postoperative patients, chiefly because the drugs don’t carry the adverse effects of opioid analgesia, which include impaired GI motility. However, several small and single-institution studies have suggested that NSAIDs used in this setting may impair anastomotic healing and may raise the rates of leakage.

Dr. Hakkarainen and his associates examined this issue using data from a statewide surveillance system for surgical quality. They analyzed 90-day complications among 13,082 adults (mean age, 58 years) who underwent surgery of the GI tract with anastomosis at 47 participating hospitals throughout Washington State during a 5-year period. The investigators tracked the use of ibuprofen, naproxen, ketorolac tromethamine, Caldolor, celecoxib, and diclofenac during the first 24 hours after surgery; they assumed that in most cases, this involved IV NSAIDs because such patients don’t take oral medications within that time period.

Postoperative NSAIDs were given to 24% of the study population. This use was associated with a significantly increased risk for anastomotic leakage during the next 90 days, with an OR of 1.24. Further analysis showed that this association was largely restricted to the subgroup of patients who had nonelective colorectal surgery, in whom the relationship was even stronger, with an OR of 1.70. Among patients who had nonelective colorectal surgery, those who received postoperative NSAIDs had a 12.3% rate of anastomotic leakage, compared with an 8.3% rate among those who did not receive NSAIDs, the investigators said (JAMA Surg. 2015 Jan. 21 [doi:10.1001/jamasurg.2014.2239]).

This study was limited in that the records didn’t specify the dose or duration of NSAID use, didn’t take into account preoperative NSAID use, and didn’t include the timing of anastomotic leakage (immediately following surgery vs. weeks or months later). “We believe that [these] results are sufficient to suggest caution in the use of NSAIDs in the postoperative treatment of patients undergoing nonelective colorectal surgery, and highlight the importance of further evaluation of this association,” the investigators added.

Postoperative NSAIDs appear to raise the risk for anastomotic complications among patients undergoing nonelective colorectal resection, according to a report in JAMA Surgery.

“Given that other analgesic regimens are effective and well tolerated, these data may be enough from some surgeons to alter practice patterns,” said Dr. Timo W. Hakkarainen of the department of surgery at the University of Washington, Seattle, and his associates.

The recent development of intravenous formulations of NSAIDs has expanded their use in postoperative patients, chiefly because the drugs don’t carry the adverse effects of opioid analgesia, which include impaired GI motility. However, several small and single-institution studies have suggested that NSAIDs used in this setting may impair anastomotic healing and may raise the rates of leakage.

Dr. Hakkarainen and his associates examined this issue using data from a statewide surveillance system for surgical quality. They analyzed 90-day complications among 13,082 adults (mean age, 58 years) who underwent surgery of the GI tract with anastomosis at 47 participating hospitals throughout Washington State during a 5-year period. The investigators tracked the use of ibuprofen, naproxen, ketorolac tromethamine, Caldolor, celecoxib, and diclofenac during the first 24 hours after surgery; they assumed that in most cases, this involved IV NSAIDs because such patients don’t take oral medications within that time period.

Postoperative NSAIDs were given to 24% of the study population. This use was associated with a significantly increased risk for anastomotic leakage during the next 90 days, with an OR of 1.24. Further analysis showed that this association was largely restricted to the subgroup of patients who had nonelective colorectal surgery, in whom the relationship was even stronger, with an OR of 1.70. Among patients who had nonelective colorectal surgery, those who received postoperative NSAIDs had a 12.3% rate of anastomotic leakage, compared with an 8.3% rate among those who did not receive NSAIDs, the investigators said (JAMA Surg. 2015 Jan. 21 [doi:10.1001/jamasurg.2014.2239]).

This study was limited in that the records didn’t specify the dose or duration of NSAID use, didn’t take into account preoperative NSAID use, and didn’t include the timing of anastomotic leakage (immediately following surgery vs. weeks or months later). “We believe that [these] results are sufficient to suggest caution in the use of NSAIDs in the postoperative treatment of patients undergoing nonelective colorectal surgery, and highlight the importance of further evaluation of this association,” the investigators added.

Postoperative NSAIDs appear to raise the risk for anastomotic complications among patients undergoing nonelective colorectal resection, according to a report in JAMA Surgery.

“Given that other analgesic regimens are effective and well tolerated, these data may be enough from some surgeons to alter practice patterns,” said Dr. Timo W. Hakkarainen of the department of surgery at the University of Washington, Seattle, and his associates.

The recent development of intravenous formulations of NSAIDs has expanded their use in postoperative patients, chiefly because the drugs don’t carry the adverse effects of opioid analgesia, which include impaired GI motility. However, several small and single-institution studies have suggested that NSAIDs used in this setting may impair anastomotic healing and may raise the rates of leakage.

Dr. Hakkarainen and his associates examined this issue using data from a statewide surveillance system for surgical quality. They analyzed 90-day complications among 13,082 adults (mean age, 58 years) who underwent surgery of the GI tract with anastomosis at 47 participating hospitals throughout Washington State during a 5-year period. The investigators tracked the use of ibuprofen, naproxen, ketorolac tromethamine, Caldolor, celecoxib, and diclofenac during the first 24 hours after surgery; they assumed that in most cases, this involved IV NSAIDs because such patients don’t take oral medications within that time period.

Postoperative NSAIDs were given to 24% of the study population. This use was associated with a significantly increased risk for anastomotic leakage during the next 90 days, with an OR of 1.24. Further analysis showed that this association was largely restricted to the subgroup of patients who had nonelective colorectal surgery, in whom the relationship was even stronger, with an OR of 1.70. Among patients who had nonelective colorectal surgery, those who received postoperative NSAIDs had a 12.3% rate of anastomotic leakage, compared with an 8.3% rate among those who did not receive NSAIDs, the investigators said (JAMA Surg. 2015 Jan. 21 [doi:10.1001/jamasurg.2014.2239]).

This study was limited in that the records didn’t specify the dose or duration of NSAID use, didn’t take into account preoperative NSAID use, and didn’t include the timing of anastomotic leakage (immediately following surgery vs. weeks or months later). “We believe that [these] results are sufficient to suggest caution in the use of NSAIDs in the postoperative treatment of patients undergoing nonelective colorectal surgery, and highlight the importance of further evaluation of this association,” the investigators added.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.

Although significantly fewer patients with stage IV colorectal cancer have undergone primary tumor resection (PTR) since 1988, overall rates of patient survival have improved over that period, according to the results of a study published in JAMA.

“The role of PTR for asymptomatic patients remains controversial. Some physicians advocate PTR to prevent the development of symptoms associated with an intact primary tumor,” wrote lead author Chung-Yuan Hu, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and his associates. “Approximately 10%-25% of patients with intact primary tumors will develop symptoms, but there is considerable morbidity (4%-30%) and mortality (2%-10%) associated with noncurative PTR” (JAMA Surg. [doi:10.1001/jamasurg.2014.2253]).

Courtesy Wikimedia Commons/Nephron /Creative Commons License

In a retrospective cohort study, Dr. Hu and his colleagues used data on 64,157 patients diagnosed with stage IV colon or rectal cancer between Jan. 1, 1988, and Dec. 31, 2010, from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) CRC registry. The primary outcome measured was difference in PTR rates over the study period. Included subjects had either undergone PTR or not, and investigators calculated rates of PTR and median relative survival for each year. Joinpoint regression analyses were used to determine when a “significant change” in PTR rate had occurred, while logistic regression analyses were used to assess factors associated with PTR.

Findings indicated that 43,273 (67.4%) of the patients analyzed for the study had undergone PTR; overall, between 1988 and 2010, annual PTR rates declined from 74.5% to 57.4%, respectively (P < .001). “Significant change” was noted between 1998 and 2001 and from 2001 to 2010: –0.41% and –2.39%, respectively (P < .001 in both cases). However, median annual survival rates improved substantially from 1988 to 2009, changing from 8.6% to 17.8%, respectively (P < .001).

“Despite the availability of more effective chemotherapeutic options, a considerable number of patients with stage IV CRC continue to undergo PTR,” wrote the authors. “Our findings indicate potential overuse of PTR among these patients and highlight a need to better understand the clinical decisions and outcomes associated with that treatment.”

This study was supported in part by grants from the National Institute of Health’s National Cancer Institute, and the American Society of Clinical Oncology Foundation Career Development Award. Authors reported no financial conflicts of interest.

[email protected]

Although significantly fewer patients with stage IV colorectal cancer have undergone primary tumor resection (PTR) since 1988, overall rates of patient survival have improved over that period, according to the results of a study published in JAMA.

“The role of PTR for asymptomatic patients remains controversial. Some physicians advocate PTR to prevent the development of symptoms associated with an intact primary tumor,” wrote lead author Chung-Yuan Hu, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and his associates. “Approximately 10%-25% of patients with intact primary tumors will develop symptoms, but there is considerable morbidity (4%-30%) and mortality (2%-10%) associated with noncurative PTR” (JAMA Surg. [doi:10.1001/jamasurg.2014.2253]).

Courtesy Wikimedia Commons/Nephron /Creative Commons License

In a retrospective cohort study, Dr. Hu and his colleagues used data on 64,157 patients diagnosed with stage IV colon or rectal cancer between Jan. 1, 1988, and Dec. 31, 2010, from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) CRC registry. The primary outcome measured was difference in PTR rates over the study period. Included subjects had either undergone PTR or not, and investigators calculated rates of PTR and median relative survival for each year. Joinpoint regression analyses were used to determine when a “significant change” in PTR rate had occurred, while logistic regression analyses were used to assess factors associated with PTR.

Findings indicated that 43,273 (67.4%) of the patients analyzed for the study had undergone PTR; overall, between 1988 and 2010, annual PTR rates declined from 74.5% to 57.4%, respectively (P < .001). “Significant change” was noted between 1998 and 2001 and from 2001 to 2010: –0.41% and –2.39%, respectively (P < .001 in both cases). However, median annual survival rates improved substantially from 1988 to 2009, changing from 8.6% to 17.8%, respectively (P < .001).

“Despite the availability of more effective chemotherapeutic options, a considerable number of patients with stage IV CRC continue to undergo PTR,” wrote the authors. “Our findings indicate potential overuse of PTR among these patients and highlight a need to better understand the clinical decisions and outcomes associated with that treatment.”

This study was supported in part by grants from the National Institute of Health’s National Cancer Institute, and the American Society of Clinical Oncology Foundation Career Development Award. Authors reported no financial conflicts of interest.

[email protected]

Although significantly fewer patients with stage IV colorectal cancer have undergone primary tumor resection (PTR) since 1988, overall rates of patient survival have improved over that period, according to the results of a study published in JAMA.

“The role of PTR for asymptomatic patients remains controversial. Some physicians advocate PTR to prevent the development of symptoms associated with an intact primary tumor,” wrote lead author Chung-Yuan Hu, Ph.D., of the University of Texas M.D. Anderson Cancer Center in Houston, and his associates. “Approximately 10%-25% of patients with intact primary tumors will develop symptoms, but there is considerable morbidity (4%-30%) and mortality (2%-10%) associated with noncurative PTR” (JAMA Surg. [doi:10.1001/jamasurg.2014.2253]).

Courtesy Wikimedia Commons/Nephron /Creative Commons License

In a retrospective cohort study, Dr. Hu and his colleagues used data on 64,157 patients diagnosed with stage IV colon or rectal cancer between Jan. 1, 1988, and Dec. 31, 2010, from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) CRC registry. The primary outcome measured was difference in PTR rates over the study period. Included subjects had either undergone PTR or not, and investigators calculated rates of PTR and median relative survival for each year. Joinpoint regression analyses were used to determine when a “significant change” in PTR rate had occurred, while logistic regression analyses were used to assess factors associated with PTR.

Findings indicated that 43,273 (67.4%) of the patients analyzed for the study had undergone PTR; overall, between 1988 and 2010, annual PTR rates declined from 74.5% to 57.4%, respectively (P < .001). “Significant change” was noted between 1998 and 2001 and from 2001 to 2010: –0.41% and –2.39%, respectively (P < .001 in both cases). However, median annual survival rates improved substantially from 1988 to 2009, changing from 8.6% to 17.8%, respectively (P < .001).

“Despite the availability of more effective chemotherapeutic options, a considerable number of patients with stage IV CRC continue to undergo PTR,” wrote the authors. “Our findings indicate potential overuse of PTR among these patients and highlight a need to better understand the clinical decisions and outcomes associated with that treatment.”

This study was supported in part by grants from the National Institute of Health’s National Cancer Institute, and the American Society of Clinical Oncology Foundation Career Development Award. Authors reported no financial conflicts of interest.

[email protected]

Patients with locally advanced rectal cancer who have a complete response to neoadjuvant therapy can skip surgery with little compromise in outcomes, according to a retrospective review that will be reported this week at the annual Gastrointestinal Cancers Symposium.

Investigators at the Memorial Sloan-Kettering Cancer Center in New York studied 145 patients with stage I to III rectal cancer who received neoadjuvant therapy there between 2006 and 2013. The meeting was cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology

After a median follow-up of 3.5 years, there were no significant differences in disease-specific or overall survival between patients who had a clinical complete response to neoadjuvant therapy of radiation and chemotherapy and skipped surgery, and patients who underwent rectal resection (the current standard strategy in the United States) with a pathologic complete response. Additionally, more than three-fourths of the group skipping surgery had preservation of rectal function.

“Nonoperative management appears to be a safe and effective treatment strategy and achieves a high rate of rectal preservation,” senior investigator Dr. Philip B. Paty, a surgical oncologist at Memorial Sloan-Kettering Cancer Center, New York, commented in a press briefing held before the symposium.

Ideally, the findings would be tested in a randomized trial, he said; however, “there’s too many factors and too much patient autonomy involved here, so that no one really believes asking people to sign up for a randomized trial where rectal resection is decided by a flip of the coin would ever accrue patients.” Short of that, rigorous prospective studies, such as a phase II trial now open at the center, will provide critical information.

Press briefing moderator Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, commented, “These are important findings for patients with rectal cancer because removal of the rectum can result in altered bowel habits or the need for permanent colostomy. This study set the bar very high, comparing the results of nonoperative management to the results seen in patients who had no cancer left under the microscope at the time of surgery, and in this study, the nonoperative management appears to compare favorably.”

“We do need longer follow-up though, to be sure that these patients will have disease-specific survival that equals what is achieved with surgery in the long term,” she cautioned, such as the conventional 5 years of observation patients typically receive. “And then of course a prospective study also would be helpful to see the effects of this approach.”

In the study, Dr. Paty and colleagues identified 73 patients who had a clinical complete response (no cancer detected on physical exam, endoscopy, or imaging) to neoadjuvant therapy of radiation and chemotherapy and—by mutual agreement of physician and patient—had nonoperative management (watchful waiting), consisting initially of follow-up at 3- to 4-month intervals by digital rectal and endoscopic exams and at 6-month intervals by imaging. They used as a comparison group 72 patients who underwent standard total mesorectal excision and had a pathologic complete response (no viable cancer cells found microscopically in the resected tissue).

Results showed that 74% of the patients who did not have surgery had a sustained clinical complete response, with no regrowth of tumor during follow-up, reported Dr. Paty. Among the other 26% whose tumors regrew, most of the recurrences were clinically detectable and all patients had successful resections with clean margins. Overall, 77% of the nonsurgical patients had rectal preservation and 98% had local control.

The nonsurgical group did not differ significantly from the surgical group with respect to 4-year rates of disease-specific survival (91% vs. 96%) and overall survival (91% vs. 95%).

The investigators plan to report quality of life data in the future, Dr. Paty said. “But I think it’s pretty obvious to everyone who’s managed these patients that if you can avoid rectal surgery, the quality of life and particularly bowel function is far superior to those who have had rectal resection.”

Successful nonoperative management hinges critically on careful patient selection, close follow-up, and use of salvage surgery, he stressed. Additionally, “the informed consent process in nonoperative management is extremely important, and I always tell patients that they are taking a slight risk. It’s hard to imagine that not operating is going to have 100% equivalent cancer outcomes as operating. That is hard to believe. So we never sell it as being absolutely as good, but …with good follow-up, the results seem to be very close if not equivalent.”

In his experience, most patients are willing to accept this option. “In fact, I have only had two patients [out of more than 100] decline nonoperative management when I thought they were candidates—both young, both with young children, both not wanting to take even the slightest risk of leaving cancer in the rectal wall or their body,” he commented.

Adoption of nonoperative management has been slow in the United States for a variety of reasons, according to Dr. Paty. “I think the bottom line is that practicing watch and wait, nonoperative management is more difficult for the surgeon. It requires first the judgment that the cancer’s gone. You have to follow the patient longer after radiation; sometimes the complete response will take up to 3 months. And there is also the medical-legal issue of deviating from the standard of care. … So I think it was operationally a difficult thing to do, it didn’t fit with the existing paradigm very well.”

But that is changing as more data roll in. “What’s happened in the last I will say 2-3 years is that there are centers publishing their experience, ours being the largest outside Brazil and the first in North America. Another group in the Netherlands has published a group of about 25 patients,” he explained. “Talking with people at meetings around the world, centers are adopting it, and I think that many leaders in clinical trials in rectal cancer recognize that this option is not only reasonable, but perhaps it’s necessary to inform patients that it is an option.”

Patients with locally advanced rectal cancer who have a complete response to neoadjuvant therapy can skip surgery with little compromise in outcomes, according to a retrospective review that will be reported this week at the annual Gastrointestinal Cancers Symposium.

Investigators at the Memorial Sloan-Kettering Cancer Center in New York studied 145 patients with stage I to III rectal cancer who received neoadjuvant therapy there between 2006 and 2013. The meeting was cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology

After a median follow-up of 3.5 years, there were no significant differences in disease-specific or overall survival between patients who had a clinical complete response to neoadjuvant therapy of radiation and chemotherapy and skipped surgery, and patients who underwent rectal resection (the current standard strategy in the United States) with a pathologic complete response. Additionally, more than three-fourths of the group skipping surgery had preservation of rectal function.

“Nonoperative management appears to be a safe and effective treatment strategy and achieves a high rate of rectal preservation,” senior investigator Dr. Philip B. Paty, a surgical oncologist at Memorial Sloan-Kettering Cancer Center, New York, commented in a press briefing held before the symposium.

Ideally, the findings would be tested in a randomized trial, he said; however, “there’s too many factors and too much patient autonomy involved here, so that no one really believes asking people to sign up for a randomized trial where rectal resection is decided by a flip of the coin would ever accrue patients.” Short of that, rigorous prospective studies, such as a phase II trial now open at the center, will provide critical information.

Press briefing moderator Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, commented, “These are important findings for patients with rectal cancer because removal of the rectum can result in altered bowel habits or the need for permanent colostomy. This study set the bar very high, comparing the results of nonoperative management to the results seen in patients who had no cancer left under the microscope at the time of surgery, and in this study, the nonoperative management appears to compare favorably.”

“We do need longer follow-up though, to be sure that these patients will have disease-specific survival that equals what is achieved with surgery in the long term,” she cautioned, such as the conventional 5 years of observation patients typically receive. “And then of course a prospective study also would be helpful to see the effects of this approach.”

In the study, Dr. Paty and colleagues identified 73 patients who had a clinical complete response (no cancer detected on physical exam, endoscopy, or imaging) to neoadjuvant therapy of radiation and chemotherapy and—by mutual agreement of physician and patient—had nonoperative management (watchful waiting), consisting initially of follow-up at 3- to 4-month intervals by digital rectal and endoscopic exams and at 6-month intervals by imaging. They used as a comparison group 72 patients who underwent standard total mesorectal excision and had a pathologic complete response (no viable cancer cells found microscopically in the resected tissue).

Results showed that 74% of the patients who did not have surgery had a sustained clinical complete response, with no regrowth of tumor during follow-up, reported Dr. Paty. Among the other 26% whose tumors regrew, most of the recurrences were clinically detectable and all patients had successful resections with clean margins. Overall, 77% of the nonsurgical patients had rectal preservation and 98% had local control.

The nonsurgical group did not differ significantly from the surgical group with respect to 4-year rates of disease-specific survival (91% vs. 96%) and overall survival (91% vs. 95%).

The investigators plan to report quality of life data in the future, Dr. Paty said. “But I think it’s pretty obvious to everyone who’s managed these patients that if you can avoid rectal surgery, the quality of life and particularly bowel function is far superior to those who have had rectal resection.”

Successful nonoperative management hinges critically on careful patient selection, close follow-up, and use of salvage surgery, he stressed. Additionally, “the informed consent process in nonoperative management is extremely important, and I always tell patients that they are taking a slight risk. It’s hard to imagine that not operating is going to have 100% equivalent cancer outcomes as operating. That is hard to believe. So we never sell it as being absolutely as good, but …with good follow-up, the results seem to be very close if not equivalent.”

In his experience, most patients are willing to accept this option. “In fact, I have only had two patients [out of more than 100] decline nonoperative management when I thought they were candidates—both young, both with young children, both not wanting to take even the slightest risk of leaving cancer in the rectal wall or their body,” he commented.

Adoption of nonoperative management has been slow in the United States for a variety of reasons, according to Dr. Paty. “I think the bottom line is that practicing watch and wait, nonoperative management is more difficult for the surgeon. It requires first the judgment that the cancer’s gone. You have to follow the patient longer after radiation; sometimes the complete response will take up to 3 months. And there is also the medical-legal issue of deviating from the standard of care. … So I think it was operationally a difficult thing to do, it didn’t fit with the existing paradigm very well.”

But that is changing as more data roll in. “What’s happened in the last I will say 2-3 years is that there are centers publishing their experience, ours being the largest outside Brazil and the first in North America. Another group in the Netherlands has published a group of about 25 patients,” he explained. “Talking with people at meetings around the world, centers are adopting it, and I think that many leaders in clinical trials in rectal cancer recognize that this option is not only reasonable, but perhaps it’s necessary to inform patients that it is an option.”

Patients with locally advanced rectal cancer who have a complete response to neoadjuvant therapy can skip surgery with little compromise in outcomes, according to a retrospective review that will be reported this week at the annual Gastrointestinal Cancers Symposium.

Investigators at the Memorial Sloan-Kettering Cancer Center in New York studied 145 patients with stage I to III rectal cancer who received neoadjuvant therapy there between 2006 and 2013. The meeting was cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology

After a median follow-up of 3.5 years, there were no significant differences in disease-specific or overall survival between patients who had a clinical complete response to neoadjuvant therapy of radiation and chemotherapy and skipped surgery, and patients who underwent rectal resection (the current standard strategy in the United States) with a pathologic complete response. Additionally, more than three-fourths of the group skipping surgery had preservation of rectal function.

“Nonoperative management appears to be a safe and effective treatment strategy and achieves a high rate of rectal preservation,” senior investigator Dr. Philip B. Paty, a surgical oncologist at Memorial Sloan-Kettering Cancer Center, New York, commented in a press briefing held before the symposium.

Ideally, the findings would be tested in a randomized trial, he said; however, “there’s too many factors and too much patient autonomy involved here, so that no one really believes asking people to sign up for a randomized trial where rectal resection is decided by a flip of the coin would ever accrue patients.” Short of that, rigorous prospective studies, such as a phase II trial now open at the center, will provide critical information.

Press briefing moderator Dr. Smitha S. Krishnamurthi of Case Western Reserve University, Cleveland, commented, “These are important findings for patients with rectal cancer because removal of the rectum can result in altered bowel habits or the need for permanent colostomy. This study set the bar very high, comparing the results of nonoperative management to the results seen in patients who had no cancer left under the microscope at the time of surgery, and in this study, the nonoperative management appears to compare favorably.”

“We do need longer follow-up though, to be sure that these patients will have disease-specific survival that equals what is achieved with surgery in the long term,” she cautioned, such as the conventional 5 years of observation patients typically receive. “And then of course a prospective study also would be helpful to see the effects of this approach.”

In the study, Dr. Paty and colleagues identified 73 patients who had a clinical complete response (no cancer detected on physical exam, endoscopy, or imaging) to neoadjuvant therapy of radiation and chemotherapy and—by mutual agreement of physician and patient—had nonoperative management (watchful waiting), consisting initially of follow-up at 3- to 4-month intervals by digital rectal and endoscopic exams and at 6-month intervals by imaging. They used as a comparison group 72 patients who underwent standard total mesorectal excision and had a pathologic complete response (no viable cancer cells found microscopically in the resected tissue).

Results showed that 74% of the patients who did not have surgery had a sustained clinical complete response, with no regrowth of tumor during follow-up, reported Dr. Paty. Among the other 26% whose tumors regrew, most of the recurrences were clinically detectable and all patients had successful resections with clean margins. Overall, 77% of the nonsurgical patients had rectal preservation and 98% had local control.

The nonsurgical group did not differ significantly from the surgical group with respect to 4-year rates of disease-specific survival (91% vs. 96%) and overall survival (91% vs. 95%).

The investigators plan to report quality of life data in the future, Dr. Paty said. “But I think it’s pretty obvious to everyone who’s managed these patients that if you can avoid rectal surgery, the quality of life and particularly bowel function is far superior to those who have had rectal resection.”

Successful nonoperative management hinges critically on careful patient selection, close follow-up, and use of salvage surgery, he stressed. Additionally, “the informed consent process in nonoperative management is extremely important, and I always tell patients that they are taking a slight risk. It’s hard to imagine that not operating is going to have 100% equivalent cancer outcomes as operating. That is hard to believe. So we never sell it as being absolutely as good, but …with good follow-up, the results seem to be very close if not equivalent.”

In his experience, most patients are willing to accept this option. “In fact, I have only had two patients [out of more than 100] decline nonoperative management when I thought they were candidates—both young, both with young children, both not wanting to take even the slightest risk of leaving cancer in the rectal wall or their body,” he commented.

Adoption of nonoperative management has been slow in the United States for a variety of reasons, according to Dr. Paty. “I think the bottom line is that practicing watch and wait, nonoperative management is more difficult for the surgeon. It requires first the judgment that the cancer’s gone. You have to follow the patient longer after radiation; sometimes the complete response will take up to 3 months. And there is also the medical-legal issue of deviating from the standard of care. … So I think it was operationally a difficult thing to do, it didn’t fit with the existing paradigm very well.”

But that is changing as more data roll in. “What’s happened in the last I will say 2-3 years is that there are centers publishing their experience, ours being the largest outside Brazil and the first in North America. Another group in the Netherlands has published a group of about 25 patients,” he explained. “Talking with people at meetings around the world, centers are adopting it, and I think that many leaders in clinical trials in rectal cancer recognize that this option is not only reasonable, but perhaps it’s necessary to inform patients that it is an option.”

The incidence of colorectal cancers (CRCs) increases with age, and gender plays a part, yet age- and gender-related changes have not been fully investigated, say researchers from University of Tokyo in Japan.

They aimed to clarify gender-specific, age-related changes in the clinicopathologic features of CRCs. The researchers evaluated data on 632 men and 427 women with CRC admitted to the University of Tokyo Hospital from February 2005 to June 2012. Of those patients, 1,036 underwent surgery. Patients with ulcerative colitis, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer were excluded from the study.  Of the 1,059 patients whose data were analyzed, 98 had ≥ 2 primary CRCs. In those cases, the histopathologic features of the dominant lesion (defined as the largest or deepest) were analyzed. The researchers also assessed the number of concomitant adenomas ≥ 5 mm in diameter.

Among patients aged < 70 years, the female-to-male ratio was relatively low, but increased with age. Male patients with proximal CRC, without distant metastasis and more concomitant adenomas tended to be older. The histologic type was the only variable significantly associated with age in women, but not in men (P = .026).

In the univariate analysis, tumor location was associated with age in both men and women. The shift of tumor location to the proximal colon with increasing age was more prominent in women: Only 11.1% of women aged < 50 years had right-sided CRC, compared with 48.3% of those aged > 80 years. In a multivariate analysis, right-sided CRC was the only independent variable that correlated with age in women aged > 70 years.

The correlation between number of concomitant adenomas and age was stronger in men. In men, the number of concomitant adenomas gradually increased with age, and among those aged > 70 years, 43.2% had ≥ 1 concomitant adenomas, compared with 30.7% of women aged > 70 years.

With increasing age, the proportion of proximal CRC gradually increased in women, whereas that of rectal cancer gradually decreased. To the best of their knowledge, the researchers say, this gradual age-related change of CRC distribution in women has not been previously reported. They don’t know the cause of the connection, but they note that some research has suggested a link between reduced endogenous secretion of female hormones and CRCs in elderly women. Other research has indicated higher expression of estrogen receptor in the epithelium of the right colon compared with that of the left colon; thus, they speculate, the drop in female hormones postmenopause might promote CRC, especially in the right-sided colon.

The higher incidence of concomitant adenomas and the shift for the proximal predominance are the age-related characteristics of CRC in elderly patients, the researchers conclude. They note that chromosomal instability (CIN) is predominantly associated with the adenoma-carcinoma sequence, and microsatellite instability (MSI) with the serrated neoplastic pathway. The results of their study suggest, they say, the importance of CIN in the colorectal carcinogensis of elderly men and, on the other hand, of MSI in that of elderly women.

Source
Iida Y, Kawai K, Tsuno NH, et al. Clin Colorect Canc. 2014;13(4):213-218.
doi: 10.10156/j.clcc.2014.06.005.

The incidence of colorectal cancers (CRCs) increases with age, and gender plays a part, yet age- and gender-related changes have not been fully investigated, say researchers from University of Tokyo in Japan.

They aimed to clarify gender-specific, age-related changes in the clinicopathologic features of CRCs. The researchers evaluated data on 632 men and 427 women with CRC admitted to the University of Tokyo Hospital from February 2005 to June 2012. Of those patients, 1,036 underwent surgery. Patients with ulcerative colitis, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer were excluded from the study.  Of the 1,059 patients whose data were analyzed, 98 had ≥ 2 primary CRCs. In those cases, the histopathologic features of the dominant lesion (defined as the largest or deepest) were analyzed. The researchers also assessed the number of concomitant adenomas ≥ 5 mm in diameter.

Among patients aged < 70 years, the female-to-male ratio was relatively low, but increased with age. Male patients with proximal CRC, without distant metastasis and more concomitant adenomas tended to be older. The histologic type was the only variable significantly associated with age in women, but not in men (P = .026).

In the univariate analysis, tumor location was associated with age in both men and women. The shift of tumor location to the proximal colon with increasing age was more prominent in women: Only 11.1% of women aged < 50 years had right-sided CRC, compared with 48.3% of those aged > 80 years. In a multivariate analysis, right-sided CRC was the only independent variable that correlated with age in women aged > 70 years.

The correlation between number of concomitant adenomas and age was stronger in men. In men, the number of concomitant adenomas gradually increased with age, and among those aged > 70 years, 43.2% had ≥ 1 concomitant adenomas, compared with 30.7% of women aged > 70 years.

With increasing age, the proportion of proximal CRC gradually increased in women, whereas that of rectal cancer gradually decreased. To the best of their knowledge, the researchers say, this gradual age-related change of CRC distribution in women has not been previously reported. They don’t know the cause of the connection, but they note that some research has suggested a link between reduced endogenous secretion of female hormones and CRCs in elderly women. Other research has indicated higher expression of estrogen receptor in the epithelium of the right colon compared with that of the left colon; thus, they speculate, the drop in female hormones postmenopause might promote CRC, especially in the right-sided colon.

The higher incidence of concomitant adenomas and the shift for the proximal predominance are the age-related characteristics of CRC in elderly patients, the researchers conclude. They note that chromosomal instability (CIN) is predominantly associated with the adenoma-carcinoma sequence, and microsatellite instability (MSI) with the serrated neoplastic pathway. The results of their study suggest, they say, the importance of CIN in the colorectal carcinogensis of elderly men and, on the other hand, of MSI in that of elderly women.

Source
Iida Y, Kawai K, Tsuno NH, et al. Clin Colorect Canc. 2014;13(4):213-218.
doi: 10.10156/j.clcc.2014.06.005.

The incidence of colorectal cancers (CRCs) increases with age, and gender plays a part, yet age- and gender-related changes have not been fully investigated, say researchers from University of Tokyo in Japan.

They aimed to clarify gender-specific, age-related changes in the clinicopathologic features of CRCs. The researchers evaluated data on 632 men and 427 women with CRC admitted to the University of Tokyo Hospital from February 2005 to June 2012. Of those patients, 1,036 underwent surgery. Patients with ulcerative colitis, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer were excluded from the study.  Of the 1,059 patients whose data were analyzed, 98 had ≥ 2 primary CRCs. In those cases, the histopathologic features of the dominant lesion (defined as the largest or deepest) were analyzed. The researchers also assessed the number of concomitant adenomas ≥ 5 mm in diameter.

Among patients aged < 70 years, the female-to-male ratio was relatively low, but increased with age. Male patients with proximal CRC, without distant metastasis and more concomitant adenomas tended to be older. The histologic type was the only variable significantly associated with age in women, but not in men (P = .026).

In the univariate analysis, tumor location was associated with age in both men and women. The shift of tumor location to the proximal colon with increasing age was more prominent in women: Only 11.1% of women aged < 50 years had right-sided CRC, compared with 48.3% of those aged > 80 years. In a multivariate analysis, right-sided CRC was the only independent variable that correlated with age in women aged > 70 years.

The correlation between number of concomitant adenomas and age was stronger in men. In men, the number of concomitant adenomas gradually increased with age, and among those aged > 70 years, 43.2% had ≥ 1 concomitant adenomas, compared with 30.7% of women aged > 70 years.

With increasing age, the proportion of proximal CRC gradually increased in women, whereas that of rectal cancer gradually decreased. To the best of their knowledge, the researchers say, this gradual age-related change of CRC distribution in women has not been previously reported. They don’t know the cause of the connection, but they note that some research has suggested a link between reduced endogenous secretion of female hormones and CRCs in elderly women. Other research has indicated higher expression of estrogen receptor in the epithelium of the right colon compared with that of the left colon; thus, they speculate, the drop in female hormones postmenopause might promote CRC, especially in the right-sided colon.

The higher incidence of concomitant adenomas and the shift for the proximal predominance are the age-related characteristics of CRC in elderly patients, the researchers conclude. They note that chromosomal instability (CIN) is predominantly associated with the adenoma-carcinoma sequence, and microsatellite instability (MSI) with the serrated neoplastic pathway. The results of their study suggest, they say, the importance of CIN in the colorectal carcinogensis of elderly men and, on the other hand, of MSI in that of elderly women.

Source
Iida Y, Kawai K, Tsuno NH, et al. Clin Colorect Canc. 2014;13(4):213-218.
doi: 10.10156/j.clcc.2014.06.005.

A combination of a cephalosporin and a beta-lactamase inhibitor in an intravenous formulation has been approved for treating complicated intra-abdominal infections and complicated urinary tract infections in adults, the Food and Drug Administration announced on Dec. 19.

The cephalosporin is ceftolozane and the beta-lactamase inhibitor is tazobactam; it will be marketed as Zerbaxa by Cubist Pharmaceuticals.

This is the fourth antibacterial drug product approved by the FDA in 2014 and, like the other three, it was designated as a Qualified Infectious Disease Product (QIDP) and was given priority review, according to the FDA statement. Zerbaxa was granted a QIDP designation under the Generating Antibiotic Incentives Now (GAIN) Act of the FDA Safety and Innovation Act, “because it is an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection,” the statement said.

As part of the QIDP program, the manufacturer has also been granted an extra 5 years of “exclusivity” – exclusive marketing rights – by the FDA.

Ceftolozane-tazobactam was approved for treating complicated intra-abdominal infections in combination with metronidazole; approval for this indication was based on a study of 979 adults, randomized to the combination or to meropenem.

Approval for complicated urinary tract infections, including pyelonephritis, was based on a study of 1,068 adults, randomized to treatment with ceftolozane-tazobactam or levofloxacin.

The prescribing information includes a warning about decreased efficacy in patients with renal impairment (a baseline creatinine clearance of 30-50 mL/min or less, and the recommendation to monitor creatinine clearance “at least daily in patients with changing renal function,” and to adjust dose accordingly. Nausea, diarrhea, headache, and fever were the most common adverse events in studies, according to the FDA statement.

The other antibacterials approved by the FDA in 2014 were approved for treating acute bacterial skin and skin structure infections caused by certain susceptible bacteria. They were dalbavancin (Dalvance), approved in May; tedizolid (Sivextro), approved in June; and oritavancin (Orbactiv), approved in August.

Serious adverse events associated with Zerbaxa should be reported to the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

A combination of a cephalosporin and a beta-lactamase inhibitor in an intravenous formulation has been approved for treating complicated intra-abdominal infections and complicated urinary tract infections in adults, the Food and Drug Administration announced on Dec. 19.

The cephalosporin is ceftolozane and the beta-lactamase inhibitor is tazobactam; it will be marketed as Zerbaxa by Cubist Pharmaceuticals.

This is the fourth antibacterial drug product approved by the FDA in 2014 and, like the other three, it was designated as a Qualified Infectious Disease Product (QIDP) and was given priority review, according to the FDA statement. Zerbaxa was granted a QIDP designation under the Generating Antibiotic Incentives Now (GAIN) Act of the FDA Safety and Innovation Act, “because it is an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection,” the statement said.

As part of the QIDP program, the manufacturer has also been granted an extra 5 years of “exclusivity” – exclusive marketing rights – by the FDA.

Ceftolozane-tazobactam was approved for treating complicated intra-abdominal infections in combination with metronidazole; approval for this indication was based on a study of 979 adults, randomized to the combination or to meropenem.

Approval for complicated urinary tract infections, including pyelonephritis, was based on a study of 1,068 adults, randomized to treatment with ceftolozane-tazobactam or levofloxacin.

The prescribing information includes a warning about decreased efficacy in patients with renal impairment (a baseline creatinine clearance of 30-50 mL/min or less, and the recommendation to monitor creatinine clearance “at least daily in patients with changing renal function,” and to adjust dose accordingly. Nausea, diarrhea, headache, and fever were the most common adverse events in studies, according to the FDA statement.

The other antibacterials approved by the FDA in 2014 were approved for treating acute bacterial skin and skin structure infections caused by certain susceptible bacteria. They were dalbavancin (Dalvance), approved in May; tedizolid (Sivextro), approved in June; and oritavancin (Orbactiv), approved in August.

Serious adverse events associated with Zerbaxa should be reported to the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

A combination of a cephalosporin and a beta-lactamase inhibitor in an intravenous formulation has been approved for treating complicated intra-abdominal infections and complicated urinary tract infections in adults, the Food and Drug Administration announced on Dec. 19.

The cephalosporin is ceftolozane and the beta-lactamase inhibitor is tazobactam; it will be marketed as Zerbaxa by Cubist Pharmaceuticals.

This is the fourth antibacterial drug product approved by the FDA in 2014 and, like the other three, it was designated as a Qualified Infectious Disease Product (QIDP) and was given priority review, according to the FDA statement. Zerbaxa was granted a QIDP designation under the Generating Antibiotic Incentives Now (GAIN) Act of the FDA Safety and Innovation Act, “because it is an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection,” the statement said.

As part of the QIDP program, the manufacturer has also been granted an extra 5 years of “exclusivity” – exclusive marketing rights – by the FDA.

Ceftolozane-tazobactam was approved for treating complicated intra-abdominal infections in combination with metronidazole; approval for this indication was based on a study of 979 adults, randomized to the combination or to meropenem.

Approval for complicated urinary tract infections, including pyelonephritis, was based on a study of 1,068 adults, randomized to treatment with ceftolozane-tazobactam or levofloxacin.

The prescribing information includes a warning about decreased efficacy in patients with renal impairment (a baseline creatinine clearance of 30-50 mL/min or less, and the recommendation to monitor creatinine clearance “at least daily in patients with changing renal function,” and to adjust dose accordingly. Nausea, diarrhea, headache, and fever were the most common adverse events in studies, according to the FDA statement.

The other antibacterials approved by the FDA in 2014 were approved for treating acute bacterial skin and skin structure infections caused by certain susceptible bacteria. They were dalbavancin (Dalvance), approved in May; tedizolid (Sivextro), approved in June; and oritavancin (Orbactiv), approved in August.

Serious adverse events associated with Zerbaxa should be reported to the FDA’s MedWatch program at 800-332-1088 or http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm.

[email protected]

SAN FRANCISCO – Patients who did not undergo elective surgical resection after successful percutaneous drainage of a diverticular-associated abscess had low rates of recurrent diverticulitis in a retrospective study, a finding that suggests nonoperative management is a reasonable option in such patients, Dr. Tarek K. Jalouta said.

Percutaneous drainage of diverticular-associated abscess resolved symptoms in 118 of 165 (72%) patients who underwent the procedure at two teaching hospitals in 2001-2013. Sixty of the patients with successful drainage did not undergo elective surgical resection, and eight of these died within a year of the drainage procedure.

Among the remaining 52 patients who had nonoperative management, 72% remained free of diverticulitis after 5 years, Dr. Jalouta and his associates reported at the annual clinical congress of the American College of Surgeons.

“A significant number of patients successfully recover from complicated diverticulitis following percutaneous drainage,” Dr. Jalouta said. “Subsequent nonoperative management carries an acceptable risk for recurrent episodes and may be considered as a reasonable management option.”

All patients diagnosed with diverticular-associated abscess received IV antibiotics within 24-48 hours of diagnosis. The decision to perform percutaneous drainage was at the discretion of the consulting surgeon and the interventional radiologist.

Practice parameters issued by the American Society of Colon and Rectal Surgeons in 2014 suggest that elective colectomy “should typically be advised” following successful medical treatment of diverticular-associated abscess with or without percutaneous drainage, noted Dr. Jalouta of Spectrum Health System, Grand Rapids, Mich. Separate guidelines from the Association of Coloproctology of Great Britain and Ireland state that there is not sufficient evidence to make a formal recommendation on this topic, he added.

For the cohort of 165 patients, the abscesses averaged 6 cm in diameter and were pelvic in 73% of patients, abdominal in 22%, and in both locations in 5%. Multiple abscesses were present in 17%. Patients had a mean age of 61 years and a mean body mass index of 21 kg/m², and 52% were female.

The patients who did not undergo surgery after successful percutaneous drainage were significantly older than those who had surgery – 62 years vs. 55 years. Those subgroups did not differ in other respects.

An estimated 130,000 U.S. hospitalizations each year are due to diverticulitis, with 10%-20% of cases complicated by an associated intra-abdominal abscess, he said. Most diverticular-associated abscesses smaller than 5 cm in diameter will respond to antibiotic therapy, but patients with larger abscesses or associated sepsis often get percutaneous drainage.

The results were slightly better than those seen in two previous studies. In one study of 511 patients admitted for acute diverticulitis in 1994-2003, 5 of 12 patients (42%) who did not undergo surgery after percutaneous drainage of abscesses averaging 7 cm in size had a recurrence of diverticulitis (Am. J. Gastroenterol. 2005;100:910-7), Dr. Jalouta said. A separate study of 32 patients managed without surgery after percutaneous drainage of diverticular-associated abscesses found a recurrence-free survival rate of 58% after 7 years (Dis. Colon Rectum 2013;56:622-6).

Dr. Jalouta reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients who did not undergo elective surgical resection after successful percutaneous drainage of a diverticular-associated abscess had low rates of recurrent diverticulitis in a retrospective study, a finding that suggests nonoperative management is a reasonable option in such patients, Dr. Tarek K. Jalouta said.

Percutaneous drainage of diverticular-associated abscess resolved symptoms in 118 of 165 (72%) patients who underwent the procedure at two teaching hospitals in 2001-2013. Sixty of the patients with successful drainage did not undergo elective surgical resection, and eight of these died within a year of the drainage procedure.

Among the remaining 52 patients who had nonoperative management, 72% remained free of diverticulitis after 5 years, Dr. Jalouta and his associates reported at the annual clinical congress of the American College of Surgeons.

“A significant number of patients successfully recover from complicated diverticulitis following percutaneous drainage,” Dr. Jalouta said. “Subsequent nonoperative management carries an acceptable risk for recurrent episodes and may be considered as a reasonable management option.”

All patients diagnosed with diverticular-associated abscess received IV antibiotics within 24-48 hours of diagnosis. The decision to perform percutaneous drainage was at the discretion of the consulting surgeon and the interventional radiologist.

Practice parameters issued by the American Society of Colon and Rectal Surgeons in 2014 suggest that elective colectomy “should typically be advised” following successful medical treatment of diverticular-associated abscess with or without percutaneous drainage, noted Dr. Jalouta of Spectrum Health System, Grand Rapids, Mich. Separate guidelines from the Association of Coloproctology of Great Britain and Ireland state that there is not sufficient evidence to make a formal recommendation on this topic, he added.

For the cohort of 165 patients, the abscesses averaged 6 cm in diameter and were pelvic in 73% of patients, abdominal in 22%, and in both locations in 5%. Multiple abscesses were present in 17%. Patients had a mean age of 61 years and a mean body mass index of 21 kg/m², and 52% were female.

The patients who did not undergo surgery after successful percutaneous drainage were significantly older than those who had surgery – 62 years vs. 55 years. Those subgroups did not differ in other respects.

An estimated 130,000 U.S. hospitalizations each year are due to diverticulitis, with 10%-20% of cases complicated by an associated intra-abdominal abscess, he said. Most diverticular-associated abscesses smaller than 5 cm in diameter will respond to antibiotic therapy, but patients with larger abscesses or associated sepsis often get percutaneous drainage.

The results were slightly better than those seen in two previous studies. In one study of 511 patients admitted for acute diverticulitis in 1994-2003, 5 of 12 patients (42%) who did not undergo surgery after percutaneous drainage of abscesses averaging 7 cm in size had a recurrence of diverticulitis (Am. J. Gastroenterol. 2005;100:910-7), Dr. Jalouta said. A separate study of 32 patients managed without surgery after percutaneous drainage of diverticular-associated abscesses found a recurrence-free survival rate of 58% after 7 years (Dis. Colon Rectum 2013;56:622-6).

Dr. Jalouta reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Patients who did not undergo elective surgical resection after successful percutaneous drainage of a diverticular-associated abscess had low rates of recurrent diverticulitis in a retrospective study, a finding that suggests nonoperative management is a reasonable option in such patients, Dr. Tarek K. Jalouta said.

Percutaneous drainage of diverticular-associated abscess resolved symptoms in 118 of 165 (72%) patients who underwent the procedure at two teaching hospitals in 2001-2013. Sixty of the patients with successful drainage did not undergo elective surgical resection, and eight of these died within a year of the drainage procedure.

Among the remaining 52 patients who had nonoperative management, 72% remained free of diverticulitis after 5 years, Dr. Jalouta and his associates reported at the annual clinical congress of the American College of Surgeons.

“A significant number of patients successfully recover from complicated diverticulitis following percutaneous drainage,” Dr. Jalouta said. “Subsequent nonoperative management carries an acceptable risk for recurrent episodes and may be considered as a reasonable management option.”

All patients diagnosed with diverticular-associated abscess received IV antibiotics within 24-48 hours of diagnosis. The decision to perform percutaneous drainage was at the discretion of the consulting surgeon and the interventional radiologist.

Practice parameters issued by the American Society of Colon and Rectal Surgeons in 2014 suggest that elective colectomy “should typically be advised” following successful medical treatment of diverticular-associated abscess with or without percutaneous drainage, noted Dr. Jalouta of Spectrum Health System, Grand Rapids, Mich. Separate guidelines from the Association of Coloproctology of Great Britain and Ireland state that there is not sufficient evidence to make a formal recommendation on this topic, he added.

For the cohort of 165 patients, the abscesses averaged 6 cm in diameter and were pelvic in 73% of patients, abdominal in 22%, and in both locations in 5%. Multiple abscesses were present in 17%. Patients had a mean age of 61 years and a mean body mass index of 21 kg/m², and 52% were female.

The patients who did not undergo surgery after successful percutaneous drainage were significantly older than those who had surgery – 62 years vs. 55 years. Those subgroups did not differ in other respects.

An estimated 130,000 U.S. hospitalizations each year are due to diverticulitis, with 10%-20% of cases complicated by an associated intra-abdominal abscess, he said. Most diverticular-associated abscesses smaller than 5 cm in diameter will respond to antibiotic therapy, but patients with larger abscesses or associated sepsis often get percutaneous drainage.

The results were slightly better than those seen in two previous studies. In one study of 511 patients admitted for acute diverticulitis in 1994-2003, 5 of 12 patients (42%) who did not undergo surgery after percutaneous drainage of abscesses averaging 7 cm in size had a recurrence of diverticulitis (Am. J. Gastroenterol. 2005;100:910-7), Dr. Jalouta said. A separate study of 32 patients managed without surgery after percutaneous drainage of diverticular-associated abscesses found a recurrence-free survival rate of 58% after 7 years (Dis. Colon Rectum 2013;56:622-6).

Dr. Jalouta reported having no financial disclosures.

[email protected]

On Twitter @sherryboschert