Colon and Rectal

All stage IV colorectal cancer patients should be screened for Lynch syndrome, according to Dr. Douglas J. Hartman, and his colleagues at the University of Pittsburgh.

Published pathology models for predicting high microsatellite instability failed to identify up to 13% of Lynch syndrome–associated colorectal carcinomas in a study conducted by Dr. Hartman and his associates.

Current predictive pathology models for the detection of high microsatellite instability (MSI-H) colorectal cancers, including PREDICT and MSPath, rely primarily on right-sided tumor detection; however, Dr. Hartman and his associates determined that MSI-H tumors within the left colon and rectum were associated with Lynch syndrome in 57% of cases. In addition, revised Bethesda Guidelines for Lynch syndrome screening in colorectal cancer patients do not call for microsatellite instability testing in patients over age 60 years, yet 32% of left-sided tumors were identified in patients over age 60 years (Hum Pathol. 2013 Sep 10 [doi: 10.1016/j.humpath.2013.06.012]).

The researchers used MSI polymerase chain reaction (MSI-PCR) and DNA mismatch repair protein immunohistochemistry to prospectively analyze 1,292 colorectal cancers between January 2009 and July 2012. During 2009-2011, cases were evaluated using MSI-PCR only. In 2012, cases were first evaluated with immunohistochemistry. MSI-PCR was performed if there were any equivocal findings in the first round of testing.

MSI-H was found in 150 tumors; 112 were sporadic and 38 were probable Lynch syndrome as determined by BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H tumors were analyzed for their grade, location, and histology; left-sided MSI-H tumors (n = 12; 57%) were more likely to be Lynch syndrome–related than were right-sided tumors (n = 26; 20%).

Neither PREDICT nor MSPath identified all Lynch syndrome–related tumors: PREDICT found 87% (33 of the 38), while MSPath identified 92% (35 of the 38). The researchers attributed these shortcomings to current predictive models’ "reliance on right-sided location."

"At our institution, we employ a universal screening approach for all resected colorectal carcinomas and biopsies from stage IV colorectal carcinomas regardless of patient age, tumor histology, and tumor location. Patients with tumors exhibiting loss of MSH2 and/or MSH6 and isolated loss of PMS2 are referred for further genetic counseling. Tumors with loss of MLH1 and PMS2 protein expression are further evaluated with BRAF mutation analysis and MLH1 promoter hypermethylation analysis before referral to genetic counseling," the authors wrote.

Contrary to some previously published data, the researchers also found that sporadic MSI-H tumors shared similar morphologies with tumors associated with probable Lynch syndrome, with the exception of a slightly higher proportion of sporadic MSI-H tumors (81%) demonstrating tumor infiltrating lymphocytes as compared with Lynch syndrome–associated tumors (61%).

The authors wrote that this is the "largest study" to date of consecutively identified Lynch syndrome–associated and sporadic tumors. As previous reports were based on retrospective data of primarily Lynch syndrome–associated tumors, those results were "vastly enriched for patients selected for analysis based on cancer-related personal or family history."

The failure of current predictive pathology models to predict all MSI-H and Lynch syndrome–related tumors, particularly left-sided ones, is a strong argument for universal screening, which "does not require widespread application of clinicopathologic criteria by clinicians and pathologists in order to select patients for testing." Further, universal screening is cost effective, and provides useful predictive and prognostic data in reducing cancer risks for patients and relatives who may or may not benefit from genetic counseling, particularly in patients over 60 years, for whom most of the MSI-H tumors were sporadic (91.5%), requiring no additional genetic counseling or testing.

Dr. Hartman and his associates reported no relevant disclosures.

[email protected]

All stage IV colorectal cancer patients should be screened for Lynch syndrome, according to Dr. Douglas J. Hartman, and his colleagues at the University of Pittsburgh.

Published pathology models for predicting high microsatellite instability failed to identify up to 13% of Lynch syndrome–associated colorectal carcinomas in a study conducted by Dr. Hartman and his associates.

Current predictive pathology models for the detection of high microsatellite instability (MSI-H) colorectal cancers, including PREDICT and MSPath, rely primarily on right-sided tumor detection; however, Dr. Hartman and his associates determined that MSI-H tumors within the left colon and rectum were associated with Lynch syndrome in 57% of cases. In addition, revised Bethesda Guidelines for Lynch syndrome screening in colorectal cancer patients do not call for microsatellite instability testing in patients over age 60 years, yet 32% of left-sided tumors were identified in patients over age 60 years (Hum Pathol. 2013 Sep 10 [doi: 10.1016/j.humpath.2013.06.012]).

The researchers used MSI polymerase chain reaction (MSI-PCR) and DNA mismatch repair protein immunohistochemistry to prospectively analyze 1,292 colorectal cancers between January 2009 and July 2012. During 2009-2011, cases were evaluated using MSI-PCR only. In 2012, cases were first evaluated with immunohistochemistry. MSI-PCR was performed if there were any equivocal findings in the first round of testing.

MSI-H was found in 150 tumors; 112 were sporadic and 38 were probable Lynch syndrome as determined by BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H tumors were analyzed for their grade, location, and histology; left-sided MSI-H tumors (n = 12; 57%) were more likely to be Lynch syndrome–related than were right-sided tumors (n = 26; 20%).

Neither PREDICT nor MSPath identified all Lynch syndrome–related tumors: PREDICT found 87% (33 of the 38), while MSPath identified 92% (35 of the 38). The researchers attributed these shortcomings to current predictive models’ "reliance on right-sided location."

"At our institution, we employ a universal screening approach for all resected colorectal carcinomas and biopsies from stage IV colorectal carcinomas regardless of patient age, tumor histology, and tumor location. Patients with tumors exhibiting loss of MSH2 and/or MSH6 and isolated loss of PMS2 are referred for further genetic counseling. Tumors with loss of MLH1 and PMS2 protein expression are further evaluated with BRAF mutation analysis and MLH1 promoter hypermethylation analysis before referral to genetic counseling," the authors wrote.

Contrary to some previously published data, the researchers also found that sporadic MSI-H tumors shared similar morphologies with tumors associated with probable Lynch syndrome, with the exception of a slightly higher proportion of sporadic MSI-H tumors (81%) demonstrating tumor infiltrating lymphocytes as compared with Lynch syndrome–associated tumors (61%).

The authors wrote that this is the "largest study" to date of consecutively identified Lynch syndrome–associated and sporadic tumors. As previous reports were based on retrospective data of primarily Lynch syndrome–associated tumors, those results were "vastly enriched for patients selected for analysis based on cancer-related personal or family history."

The failure of current predictive pathology models to predict all MSI-H and Lynch syndrome–related tumors, particularly left-sided ones, is a strong argument for universal screening, which "does not require widespread application of clinicopathologic criteria by clinicians and pathologists in order to select patients for testing." Further, universal screening is cost effective, and provides useful predictive and prognostic data in reducing cancer risks for patients and relatives who may or may not benefit from genetic counseling, particularly in patients over 60 years, for whom most of the MSI-H tumors were sporadic (91.5%), requiring no additional genetic counseling or testing.

Dr. Hartman and his associates reported no relevant disclosures.

[email protected]

All stage IV colorectal cancer patients should be screened for Lynch syndrome, according to Dr. Douglas J. Hartman, and his colleagues at the University of Pittsburgh.

Published pathology models for predicting high microsatellite instability failed to identify up to 13% of Lynch syndrome–associated colorectal carcinomas in a study conducted by Dr. Hartman and his associates.

Current predictive pathology models for the detection of high microsatellite instability (MSI-H) colorectal cancers, including PREDICT and MSPath, rely primarily on right-sided tumor detection; however, Dr. Hartman and his associates determined that MSI-H tumors within the left colon and rectum were associated with Lynch syndrome in 57% of cases. In addition, revised Bethesda Guidelines for Lynch syndrome screening in colorectal cancer patients do not call for microsatellite instability testing in patients over age 60 years, yet 32% of left-sided tumors were identified in patients over age 60 years (Hum Pathol. 2013 Sep 10 [doi: 10.1016/j.humpath.2013.06.012]).

The researchers used MSI polymerase chain reaction (MSI-PCR) and DNA mismatch repair protein immunohistochemistry to prospectively analyze 1,292 colorectal cancers between January 2009 and July 2012. During 2009-2011, cases were evaluated using MSI-PCR only. In 2012, cases were first evaluated with immunohistochemistry. MSI-PCR was performed if there were any equivocal findings in the first round of testing.

MSI-H was found in 150 tumors; 112 were sporadic and 38 were probable Lynch syndrome as determined by BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H tumors were analyzed for their grade, location, and histology; left-sided MSI-H tumors (n = 12; 57%) were more likely to be Lynch syndrome–related than were right-sided tumors (n = 26; 20%).

Neither PREDICT nor MSPath identified all Lynch syndrome–related tumors: PREDICT found 87% (33 of the 38), while MSPath identified 92% (35 of the 38). The researchers attributed these shortcomings to current predictive models’ "reliance on right-sided location."

"At our institution, we employ a universal screening approach for all resected colorectal carcinomas and biopsies from stage IV colorectal carcinomas regardless of patient age, tumor histology, and tumor location. Patients with tumors exhibiting loss of MSH2 and/or MSH6 and isolated loss of PMS2 are referred for further genetic counseling. Tumors with loss of MLH1 and PMS2 protein expression are further evaluated with BRAF mutation analysis and MLH1 promoter hypermethylation analysis before referral to genetic counseling," the authors wrote.

Contrary to some previously published data, the researchers also found that sporadic MSI-H tumors shared similar morphologies with tumors associated with probable Lynch syndrome, with the exception of a slightly higher proportion of sporadic MSI-H tumors (81%) demonstrating tumor infiltrating lymphocytes as compared with Lynch syndrome–associated tumors (61%).

The authors wrote that this is the "largest study" to date of consecutively identified Lynch syndrome–associated and sporadic tumors. As previous reports were based on retrospective data of primarily Lynch syndrome–associated tumors, those results were "vastly enriched for patients selected for analysis based on cancer-related personal or family history."

The failure of current predictive pathology models to predict all MSI-H and Lynch syndrome–related tumors, particularly left-sided ones, is a strong argument for universal screening, which "does not require widespread application of clinicopathologic criteria by clinicians and pathologists in order to select patients for testing." Further, universal screening is cost effective, and provides useful predictive and prognostic data in reducing cancer risks for patients and relatives who may or may not benefit from genetic counseling, particularly in patients over 60 years, for whom most of the MSI-H tumors were sporadic (91.5%), requiring no additional genetic counseling or testing.

Dr. Hartman and his associates reported no relevant disclosures.

[email protected]

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

[email protected]

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

[email protected]

Early dual therapy with infliximab and an immunomodulator significantly decreased the 1-year risk of hospitalization and surgery in patients with inflammatory bowel disease, in a cohort study of almost 20,500 patients.

The improvements in hospitalization and surgery rates became apparent as quickly as 5 months after therapy initiation. By 9 months after dual therapy began, there was an 86% decrease in hospitalization and a 92% decrease in surgery compared with the rates in those who had not taken these medications.

The study shows that aggressive treatment of inflammatory bowel disease can reap robust results, Dr. Neena S. Abraham and colleagues reported in the Aug. 29 issue of Clinical Gastroenterology and Hepatology (doi:10.1016/j.cgh.2013.04.051).

The results probably underestimate the potential benefits of dual therapy, wrote Dr. Abraham of the Mayo Clinic, Scottsdale, Ariz., and associates. Only 11% of patients in the database took one of the studied treatment regimens, and of those, most (85%) got an immunomodulator only.

"Given the paucity prescribed dual therapy (8.5%), the dose-response data are even more impressive and suggest that if dual therapy had been initiated earlier, greater benefit may have been observed," the investigators wrote.

The study examined 1-year hospitalization and surgical rates in 20,474 patients with either ulcerative colitis or Crohn’s disease. The patients were all included in a database that covered 176 U.S. Department of Veteran Affairs facilities.

Three treatment protocols were examined: immunomodulator monotherapy, anti–tumor necrosis factor (TNF)-alpha monotherapy with infliximab, and dual therapy with an immunomodulator and infliximab.

Most of the patients (12,432) had ulcerative colitis (UC); the remainder had Crohn’s disease (CD). Most (94%) were male; the mean age was 72 years.

The most common strategy was the anti–TNF-alpha alone (8%). Among patients receiving infliximab, 63% had evidence of induction therapy preceding a maintenance regimen.

"Despite their clear therapeutic benefit, less than 15% of patients with inflammatory bowel disease receive anti-TNF monotherapy, and 40% of patients with active CD receive anti-TNF agents in combination with immunomodulator agents (thiopurines or methotrexate)," they commented.

Most patients (66%) were taking other drugs, including steroids (14%), nonsteroidal anti-inflammatory agents (39%), aspirin (21%), cyclosporine (0.21%), antimetabolites (0.67%), and antibiotics (29%).

A 50% relative reduction in hospitalization occurred at 7.7 months with dual therapy compared with 9 months with immunomodulator monotherapy and 8 months with anti–TNF-alpha therapy. All of these differences were statistically significant after the model was adjusted for diagnosis (UC or CD), smoking status, race/ethnicity, and other medications that could modify the treatment effect.

By 1 year, there was a 45% relative reduction in hospitalization for immunomodulator therapy and a 78% relative reduction with anti–TNF-alpha monotherapy. But patients taking dual therapy reached a similar reduction of 73% by 9 months.

"Results suggested that, if dual therapy had been initiated earlier, perhaps a greater response in the outcome may have been observed," the investigators wrote.

There was a similar beneficial effect on surgeries related to the disorders. In the first year of treatment, there were 276 procedures. By 9 months, there was a 28% risk reduction associated with immunomodulator monotherapy, a 90% reduction associated with anti–TNF-alpha monotherapy, and a 92% reduction associated with dual therapy.

This also suggests that a "greater response may have been observed with earlier initiation of dual therapy," the authors said.

Safety concerns may be one reason for the dearth of these treatment protocols, the authors noted. However, recent long-term safety data suggest that there is a very low risk of mortality associated with them.

"[Five-year] outcome data on infliximab use has failed to demonstrate increased risk of mortality, and, although increased risk of infection was observed, the presence of severe disease and use of prednisone or narcotics carried higher risks," they said, referring to a 2012 study (Am. J. Gastroenterol. 2012;107:1409-22).

A 2011 study also suggested that the benefits of dual therapy outweigh the risks of developing a serious infection or cancer (Clin. J. Gastroenterol. Hepatol. 2012;10:46-51).

Janssen Biotech funded the study. None of the authors reported having any relevant financial disclosures.

[email protected]

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

PHOENIX – Applying continuous negative pressure to the incisional wound sharply reduces the incidence of surgical site infection after open colorectal surgery, according to results from a retrospective study.

A team led by Dr. Allison M. Bonds, a general surgery resident at the University of Texas Southwestern Medical Center at Dallas, studied 254 patients who underwent open colorectal surgery, whether planned or converted from a laparoscopic procedure.

In 13% of the patients, surgeons used incisional negative-pressure wound therapy, which entails standard wound closure followed by placement of a wound vacuum device over the completed stapled skin closure.

Study results, reported at the annual meeting of the American Society of Colon and Rectal Surgeons, showed that relative to the group receiving usual wound care, patients receiving incisional negative-pressure wound therapy were two-thirds less likely to develop a surgical site infection.

"Our study, although a retrospective chart review, does seem to show that the use of incisional negative-pressure wound therapy is associated with a decreased risk of surgical site infection," Dr. Bonds asserted. "This finding is significant enough that we feel it further needs a randomized controlled trial to see if there is actually a significant effect in the colorectal population."

Several attendees wondered about the cost of the negative-pressure wound therapy and how that was covered in the study population.

"We didn’t do an official cost analysis," Dr. Bonds replied. "Normally, the device that we used is associated with about $200 extra initially and then ... another $500 a day to use. So it is a fairly expensive addition to the care of the patients." She said she did not have data on how this cost was covered.

Dr. Jason Hall of the Lahey Clinic in Burlington, Mass., asked, "What was the indication to use the vac in those 32 patients?" and further wondered whether the patients receiving this therapy differed in ways that may have confounded the results.

"Placement of the vacuum wound device was left to the discretion of the surgeons," Dr. Bonds replied. "It’s hard to know exactly which patients would have been chosen for the study. There is some chance that the surgeons would have chosen the patients that they didn’t think would have a high rate of infection risk. But from our talking with the surgeons who use this, we believe that most of the vacuum devices were placed on patients who they had a high suspicion were going to get surgical site infections."

She agreed that there might have been selection bias at play, despite the study’s use of multivariate analysis. "That’s exactly why we believe that a randomized controlled trial is really the only way to show whether this is going to be a good technique to use or not," she said.

Cost of the therapy and its coverage will be major issues going forward, according to session comoderator Dr. Mark Welton of Stanford (Calif.) University. "Any time you are talking about downstream benefit to the insurer, they really need to see robust data before they are going to start to pay for that. So, especially in today’s health care environment, it’s going to come back to the patient paying for it. If you could talk about driving the cost associated with the wound infection down significantly, then the insurance companies would pay for it."

"Interestingly, there are companies coming out producing less expensive and less cumbersome devices. So I think it’s actually a very exciting idea, it’s intriguing. But we have a long way to go, and we do get to this cost-benefit question, and who’s going to pay for it," he said in an interview.

Dr. Kim Rhoads, the other session comoderator, also of Stanford University, said that "it’s an interesting concept," but she would like to see a standardized protocol detailing, for example, whether the vacuum and dressing are changed at some point and how long it has to be used for benefit; additionally, the indication for use should be worked out.

Also, "what we didn’t hear is how much fluid actually comes out ... because if nothing is coming out, you have to ask, what’s happening here and would that patient not have otherwise been wound infection free," she said. "We don’t know."

Incisional negative-pressure wound therapy has been used in orthopedic surgery for several years, according to Dr. Bonds. "At UT Southwestern, we began using this in 2010 [in colorectal surgery], and anecdotally saw that it seemed to be decreasing the rate of infections in our patients, so we thought that this warranted further study," she explained.

With this therapy, surgeons close the incision with standard staples, apply a strip of bridge dressing (GranuFoam, made by KCI), and cover the area with clear occlusion tape. The vacuum device (V.A.C. Therapy, made by KCI) is then applied at 75 mm Hg of continuous suction; in patients having a stoma, the stoma is returned after the device is in place.

In the study, the vacuum device was left on until postoperative day 5 or 7, and was removed before patients were discharged, according to Dr. Bonds.

Overall, 27.2% of the patients developed a surgical site infection. The rate was 12.5% in the group given incisional negative-pressure wound therapy, compared with 29.3% in the group given standard care.

In a multivariate analysis, patients in the negative-pressure wound therapy group were 68% less likely to develop a surgical site infection (odds ratio, 0.32; P = .04).

The only other independent predictor of this outcome was diabetes mellitus, which was associated with roughly a doubling of risk (OR, 1.98; P = .03).

"There are several proposed mechanisms for why this therapy would work," Dr. Bonds noted. The device prevents the incision from coming into contact with the surrounding environment, and decreases patient mobility and shear forces on the wound.

"In addition, the continuous suction seems to remove infectious material and the interstitial fluid, thereby decreasing the wound edema. Studies have also shown that the wound vacuum device increases vascularity to the wound, which would seem to help it heal as well," she said.

Dr. Bonds disclosed no relevant conflicts of interest. One coinvestigator has an affiliation with KCI.

PHOENIX – Two differing surgical approaches for early rectal cancer – radical resection and local resection—appear to be essentially equivalent treatment options, finds a systematic review and meta-analysis.

The conclusion is based on an analysis of morbidity and mortality data from 13 studies with a total of 2,855 patients with stage T1N0M0 rectal adenocarcinoma. All of the studies were published after 1979, when total mesorectal excision and modern local resection techniques were being used.

There are "improved results with the newer techniques of TEMS [transanal endoscopic microsurgery] and TAMIS [transanal minimally invasive surgery], as well as comparable outcomes when we adjust for the fact that there is a bit of a selection bias in the literature for lower-third lesions to be performed by local resection," lead investigator Dr. Sami A. Chadi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

"We know that quality of life data is better with local resection," he commented. Relative to radical resection, local resection was associated with an 87% lower risk of postoperative complications, a 69% lower risk of perioperative mortality, and an 83% lower risk of permanent ostomy.

On the other hand, local resection also was associated with a 46% higher likelihood of death at 5 years. Survival no longer differed significantly, however, when analyses took into account the greater use of local resection for cancers located in the lower third of the rectum.

"The implication is that we have established clinical equipoise between groups with T1N0M0 adenocarcinoma of the rectum, thus prompting the need for a prospective randomized, controlled trial on these two procedures," he maintained. "We do need further data to assess whether or not there is a role for neoadjuvant or adjuvant therapy in these groups." Ongoing studies are assessing the role of therapy, as well as the potential for local resection to be performed for T2 lesions.

Dr. Chadi, a surgeon with the University of Western Ontario in London, and his colleagues analyzed data from 12 observational studies and one randomized, controlled trial among patients with T1N0M0 cancer.

The 5-year rate of overall survival was poorer with local resection (relative risk, 1.46), with the difference between groups corresponding to 72 more deaths per 1,000 patients in the local resection group, according to Dr. Chadi, who disclosed no conflicts of interest related to the research.

However, this difference was largely driven by transanal excision (TAE) local procedures. There was no significant difference in this outcome for TEMS local procedures as compared with radical resection.

The researchers also repeated the survival analysis with an adjustment for cancers in the lower third of the rectum. In these patients, the surgical choice is more often local resection, potentially leading to selection bias.

When the ratio of lower-third cancers was equal in both the radical and local resection groups, there was no longer a significant difference in 5-year overall survival.

Compared with radical resection, local resection yielded a lower risk of postoperative complications (rate ratio, 0.13), with the difference corresponding to 129 fewer complications per 1,000 patients in the local resection group. The difference was significant for both TAE and TEMS individually as compared with radical resection.

Local resection also was associated with a lower risk of perioperative mortality (rate ratio, 0.31), with the difference corresponding to 11 fewer deaths per 1,000 patients in the local resection group, and a lower risk of permanent ostomy (risk ratio, 0.17), with the difference corresponding to 225 fewer permanent ostomies per 1,000 patients in the local resection group.

PHOENIX – Two differing surgical approaches for early rectal cancer – radical resection and local resection—appear to be essentially equivalent treatment options, finds a systematic review and meta-analysis.

The conclusion is based on an analysis of morbidity and mortality data from 13 studies with a total of 2,855 patients with stage T1N0M0 rectal adenocarcinoma. All of the studies were published after 1979, when total mesorectal excision and modern local resection techniques were being used.

There are "improved results with the newer techniques of TEMS [transanal endoscopic microsurgery] and TAMIS [transanal minimally invasive surgery], as well as comparable outcomes when we adjust for the fact that there is a bit of a selection bias in the literature for lower-third lesions to be performed by local resection," lead investigator Dr. Sami A. Chadi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

"We know that quality of life data is better with local resection," he commented. Relative to radical resection, local resection was associated with an 87% lower risk of postoperative complications, a 69% lower risk of perioperative mortality, and an 83% lower risk of permanent ostomy.

On the other hand, local resection also was associated with a 46% higher likelihood of death at 5 years. Survival no longer differed significantly, however, when analyses took into account the greater use of local resection for cancers located in the lower third of the rectum.

"The implication is that we have established clinical equipoise between groups with T1N0M0 adenocarcinoma of the rectum, thus prompting the need for a prospective randomized, controlled trial on these two procedures," he maintained. "We do need further data to assess whether or not there is a role for neoadjuvant or adjuvant therapy in these groups." Ongoing studies are assessing the role of therapy, as well as the potential for local resection to be performed for T2 lesions.

Dr. Chadi, a surgeon with the University of Western Ontario in London, and his colleagues analyzed data from 12 observational studies and one randomized, controlled trial among patients with T1N0M0 cancer.

The 5-year rate of overall survival was poorer with local resection (relative risk, 1.46), with the difference between groups corresponding to 72 more deaths per 1,000 patients in the local resection group, according to Dr. Chadi, who disclosed no conflicts of interest related to the research.

However, this difference was largely driven by transanal excision (TAE) local procedures. There was no significant difference in this outcome for TEMS local procedures as compared with radical resection.

The researchers also repeated the survival analysis with an adjustment for cancers in the lower third of the rectum. In these patients, the surgical choice is more often local resection, potentially leading to selection bias.

When the ratio of lower-third cancers was equal in both the radical and local resection groups, there was no longer a significant difference in 5-year overall survival.

Compared with radical resection, local resection yielded a lower risk of postoperative complications (rate ratio, 0.13), with the difference corresponding to 129 fewer complications per 1,000 patients in the local resection group. The difference was significant for both TAE and TEMS individually as compared with radical resection.

Local resection also was associated with a lower risk of perioperative mortality (rate ratio, 0.31), with the difference corresponding to 11 fewer deaths per 1,000 patients in the local resection group, and a lower risk of permanent ostomy (risk ratio, 0.17), with the difference corresponding to 225 fewer permanent ostomies per 1,000 patients in the local resection group.

PHOENIX – Two differing surgical approaches for early rectal cancer – radical resection and local resection—appear to be essentially equivalent treatment options, finds a systematic review and meta-analysis.

The conclusion is based on an analysis of morbidity and mortality data from 13 studies with a total of 2,855 patients with stage T1N0M0 rectal adenocarcinoma. All of the studies were published after 1979, when total mesorectal excision and modern local resection techniques were being used.

There are "improved results with the newer techniques of TEMS [transanal endoscopic microsurgery] and TAMIS [transanal minimally invasive surgery], as well as comparable outcomes when we adjust for the fact that there is a bit of a selection bias in the literature for lower-third lesions to be performed by local resection," lead investigator Dr. Sami A. Chadi reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

"We know that quality of life data is better with local resection," he commented. Relative to radical resection, local resection was associated with an 87% lower risk of postoperative complications, a 69% lower risk of perioperative mortality, and an 83% lower risk of permanent ostomy.

On the other hand, local resection also was associated with a 46% higher likelihood of death at 5 years. Survival no longer differed significantly, however, when analyses took into account the greater use of local resection for cancers located in the lower third of the rectum.

"The implication is that we have established clinical equipoise between groups with T1N0M0 adenocarcinoma of the rectum, thus prompting the need for a prospective randomized, controlled trial on these two procedures," he maintained. "We do need further data to assess whether or not there is a role for neoadjuvant or adjuvant therapy in these groups." Ongoing studies are assessing the role of therapy, as well as the potential for local resection to be performed for T2 lesions.

Dr. Chadi, a surgeon with the University of Western Ontario in London, and his colleagues analyzed data from 12 observational studies and one randomized, controlled trial among patients with T1N0M0 cancer.

The 5-year rate of overall survival was poorer with local resection (relative risk, 1.46), with the difference between groups corresponding to 72 more deaths per 1,000 patients in the local resection group, according to Dr. Chadi, who disclosed no conflicts of interest related to the research.

However, this difference was largely driven by transanal excision (TAE) local procedures. There was no significant difference in this outcome for TEMS local procedures as compared with radical resection.

The researchers also repeated the survival analysis with an adjustment for cancers in the lower third of the rectum. In these patients, the surgical choice is more often local resection, potentially leading to selection bias.

When the ratio of lower-third cancers was equal in both the radical and local resection groups, there was no longer a significant difference in 5-year overall survival.

Compared with radical resection, local resection yielded a lower risk of postoperative complications (rate ratio, 0.13), with the difference corresponding to 129 fewer complications per 1,000 patients in the local resection group. The difference was significant for both TAE and TEMS individually as compared with radical resection.

Local resection also was associated with a lower risk of perioperative mortality (rate ratio, 0.31), with the difference corresponding to 11 fewer deaths per 1,000 patients in the local resection group, and a lower risk of permanent ostomy (risk ratio, 0.17), with the difference corresponding to 225 fewer permanent ostomies per 1,000 patients in the local resection group.

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

CHICAGO – Long-term intensive blood and computed tomography follow-up offered no significant advantage over minimal follow-up for detecting colorectal cancer recurrences in the phase III FACS trial.

The proportion of patients with recurrence treated surgically with curative intent was 6.7% with intensive carcinoembryonic antigen (CEA) testing, 8% with monthly computed tomography imaging and 6.6% with combination CEA plus CT, compared with 2.3% with minimal follow-up involving a single CT scan.

After adjustment, it was about three times more likely that patients would have a recurrence with CEA (adjusted odds ratio, 2.70; P = .035), monthly CT imaging (OR, 3.45; P = .007) and CEA plus CT (OR, 2.95; P = .021) than with minimal follow-up.

"This result appeared to be quite robust" and was independent of cancer stage, co-primary investigator Dr. David Mant said at the annual meeting of the American Society of Clinical Oncology.

There was virtually no deviation in protocol by patients, however, the desire for unscheduled CT scans by surgeons meant that up to 30% in the minimal follow-up arm had 1 or more additional CTs, he noted. Still, in a per protocol analysis, the absolute differences in recurrence were 3.8- to 5.4-times higher with intensive follow-up. Again, there was no evidence of an additive effect of CEA plus CT.

Guidelines in the United States and Europe stress intensive follow-up including routine history and physical examination, CEA monitoring, yearly colonoscopy and repeated CT scans in those at high risk of recurrence.

The FACS (Follow-Up After Colorectal Surgery) trial looked at whether long-term intensive follow-up was worthwhile. Though commonplace after curative surgery, economic modeling suggests intensive followup may not be cost-effective and claims of a substantial overall survival benefit are inconsistent with the reported frequency and effectiveness of treatment for recurrence, explained Dr. David Mant, emeritus professor of general practice, Oxford University.

"As a long-term family physician, I’d seen many patients being followed-up for cancer and watched their cycle of deep anxiety, followed usually by relief, but sometimes with misery, as they waited for their follow-up appointments," he added. "It seemed to me that it was a very bad idea to carry on with this practice, unless it was to their benefit."

FACS involved 1,202 patients who were disease free on colonoscopy and CT imaging and had a blood CEA level of 10 mcg/L or less (Dukes’ stages A-C) after treatment for primary colorectal cancer. Their median age was 70 years.

Patients were randomly assigned to one of four follow-up regimens: "minimal" follow-up based mainly on symptoms and a single CT scan at 12-18 months; "CEA," which included minimal follow-up, plus 3 monthly blood CEA tests for 2 years then 6 monthly tests in years 3-5; "CT," which included minimal follow-up plus intensive CT imaging involving 6 monthly scans of the chest, abdomen, and pelvis for 2 years, and then annually for another 3 years; and "CEA plus CT," which included the CEA regimen in group 2 and the CT measures in group 3.

If during monitoring, a patient’s CEA level was 7 mcg/L or more above their baseline level at trial entry, the test was repeated as soon as possible. If the second test was also above the threshold, the patient’s physician was asked to refer the patient urgently to the local hospital.

Overall, 6% of patients (71/1,202) developed a recurrence treated surgically with curative intent. There was little difference between patients according to Duke’s staging (stage A, 5.1%; stage B, 6.1%; stage C, 6.2%), reported Dr. Mant and coprincipal investigator Dr. John Primrose of University of Southhampton, U.K.

"You actually do need rigorous initial staging to detect residual disease before you embark on any follow-up," Dr. Mant stressed. "I think both John and I are convinced that the reason why we have a 6% overall recurrence rate is because the people in this trial were appropriately staged. The survival curves don’t suggest they were any less sick than patients in other trials."

At the time of the analysis, 59% of patients with a recurrence treated with curative intent were still alive, but there was no statistical difference in colorectal cancer deaths (P = .66) or total deaths (P = .45) between the minimum and intensive follow-up arms, he said.

In a meta-analysis that integrated the FACS data with that from three previous trials, the overall effect of intensive follow-up was not significant (OR, 0.96; P = .56), Dr. Mant said. The number needed to treat to detect potentially curable recurrence with intensive follow-up is about 20 to 25 and that predicts a number-needed-to-treat of about 40 to 50 for 5-year post-recurrence survival.

Dr. Maughan said the disparity between the current meta-analysis and the Cochrane review may be because the latter included six studies, not three, and that the survival data from FACS may not be fully mature. A further analysis of the FACS data is planned in about 18 months.

Dr. Mant and his coauthors reported having no financial disclosures.

Mant, D., et al. "Effect of 3-5 years of scheduled CED and CT follow-up to detect recurrence of colorectal cancer: FACS randomized controlled trial." Ab. 3500.

[email protected]

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

PHOENIX – The longer a laparoscopic colectomy for cancer takes, the less its advantages over an open colectomy in terms of morbidity and mortality, researchers reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

A team led by Dr. Matthew Bailey, a surgery resident at the University of Kentucky in Lexington, queried the National Surgical Quality Improvement Program (NSQIP) database to identify more than 4,000 patients undergoing right colectomy because of colorectal malignancy.

Results showed that compared with their peers having an open operation lasting 3 hours or less, patients having a laparoscopic operation of this duration were less likely to develop complications and to die. However, when the operations lasted more than 3 hours, there was no longer any significant difference.

Within the laparoscopic group, patients were more likely to have a procedure lasting longer than 3 hours if they had recently received radiation therapy, were morbidly obese, or had peripheral vascular disease.

"We recommend that surgeons consider an open approach if the patient has risk factors for an operative duration greater than 3 hours," Dr. Bailey said. "We also recommend surgeons consider conversion to an open approach when it is anticipated that a laparoscopic right colectomy will exceed 3 hours."

Dr. Walter Peters of Columbia (Mo.) Surgical Associates, who comoderated the session, asked, "Were the laparoscopic procedures lasting more than 3 hours concentrated in a few institutions, or were they spread across the entire NSQIP database?"

The investigators did not assess the institutional distribution, and it may not be possible to tease that information out of NSQIP, Dr. Bailey replied.

Session attendee Dr. Eric Haas, of Colorectal Surgical Associates in Houston asked what percentage of patients had a conversion from laparoscopic to open procedures and whether analyses were conducted according to intention to treat.

"NSQIP unfortunately does not allow you to discern that, there’s no CPT [Current Procedural Terminology] code for conversion," Dr. Bailey said. "We can only assume that cases that were converted laparoscopic to open were most likely ultimately coded as open. So there was no way to perform an intent-to-treat analysis."

Dr. Haas also noted that surgeon experience with laparoscopy may have played a role. "In my own experience, certainly at the beginning of the learning curve phase, I would take 3, maybe 4 hours. And the one risk factor that you can’t put [in analyses] is surgeon," he said. "So were these 3-hour cases because of the learning curve, or were they true 3-hour cases because of the patient factors?"

The NSQIP database captures the surgeon who dictates the operative report and the level of training, the highest-level resident involved, and the specialty of the surgeon (although colorectal surgery is not among the options), according to Dr. Bailey. Still, it is generally not possible to determine who did all or most of the operation.

"We did look at operative time, and it was around 138 minutes, plus-minus, for a laparoscopic right colectomy, with the reported literature being around 187 minutes. So I’m not sure if the reported literature is dated or if, in these over 200 hospitals across the nation, this is realistic of current practice trends," he said.

"The study shows that patients are probably going to have increased complications with longer surgery, whether it’s laparoscopic or open," Dr. Timothy Geiger of Vanderbilt University Medical Center, Nashville, Tenn., the session’s other comoderator, said in an interview. "It was a good study, but it needs a little bit more in-depth look, especially at things like redosing of antibiotics, whether that is done in an appropriate manner. But otherwise, it’s a great kind of intro for us to look at this."

Giving some background to the research, Dr. Bailey noted, "The use of laparoscopy in colon cancer has been shown to be equivalent to open surgery in survival and oncologic outcomes. The question of whether operative time negatively impacts laparoscopic outcomes compared to open surgery outcomes requires further investigation if we are to endorse a laparoscopic approach regardless of procedure length. We postulated that there is an operative duration where the benefits of a laparoscopic approach are negated."

The investigators analyzed data from the NSQIP database for the years 2005 through 2010, identifying patients who had a right colectomy for cancer and excluding those treated on an emergent basis, or having secondary procedures other than enterolysis or mobilization of the splenic flexure.

Analyses were based on 2,141 patients in the laparoscopic group and 2,132 patients in the open group. Procedures lasted longer than 3 hours in 18% of the former and 11% of the latter.

Compared with the open group, the laparoscopic group was younger and had lower American Society of Anesthesiologists scores, higher serum albumin levels, and lower prothrombin time and platelet count.

In unadjusted analysis among patients whose operations lasted 3 hours or less, the laparoscopic group fared better than did the open group in terms of 30-day mortality (1.1% vs 2.6%, P less than .001), cardiopulmonary and cerebrovascular complications (5.4% vs. 8.4%, P less than .001), and infectious complications (9.2% vs. 13.3%, P less than .001).

In contrast, among patients whose operations lasted more than 3 hours, differences in these outcomes were not significant. If anything, there was a trend toward a higher rate of infectious complications with laparoscopy.

To assess the role of preoperative risk factors, the investigators looked at NSQIP estimates of morbidity and mortality for all gastrointestinal and abdominal surgery by operative duration and including 37 preoperative risk factors, and found patterns differing from those in the study cohort.

Specifically, these estimates suggested mortality was consistently lower for procedures lasting more then 3 hours, whether laparoscopic or open. And the risk of infectious complications was constant for each type and less for laparoscopy, regardless of the operative duration.

Thus, "there is something other than preoperative risk factors causing an increase in mortality" with longer operative time for laparoscopic procedures in the study cohort, said Dr. Bailey, who disclosed no conflicts of interest related to the research. Also, "the increased infectious complications that we demonstrated are not related to the morbidity risk."

Patients in the laparoscopic group had a significantly higher risk of surgery lasting more than 3 hours if they had recently received radiation therapy (odds ratio, 6.5), were morbidly obese (3.0), or had peripheral vascular disease (2.5).

Hospital length of stay was consistently shorter with the laparoscopic approach, regardless of how long the operation lasted, according to Dr. Bailey.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

PHOENIX – Improving cancer-specific survival after resection for colorectal cancer may be as simple as ordering preoperative mechanical bowel preparation, according to an analysis of data from a randomized trial conducted in Sweden and Germany.

Roughly half of the 841 patients studied had such preparation before their operation. The actuarial 5-year rate of cancer-specific survival was about 8% higher in this group, first author Dr. Åsa Collin of Uppsala University reported at the annual meeting of the American Society of Colon and Rectal Surgeons.

An analysis of cancer stage at the time of surgery suggested that the two groups were well matched on this measure. Preparation did not significantly decrease the rate of recurrence or increase the rate of overall survival.

Session attendee Dr. J. Daniel Stanley of University Surgical Associates in Chattanooga, Tenn., questioned whether the patients might have differed on other factors that influenced whether they underwent mechanical bowel preparation.

"Were some of them obstructed, which might indicate a different tumor biology than was reflected in the staging?" he asked.

"These were all elective surgeries, and there was no patient who we actually decided that they shouldn’t have preparation," Dr. Collin replied.

In an interview, session comoderator Dr. David Maron, a colorectal surgeon at the Cleveland Clinic in Weston, Fla., said, "What was interesting was that they didn’t show a significant difference in cancer recurrence, although it was close to significance. So the question remains, is it in fact the mechanical bowel prep, or could there be differences in the postoperative follow-up and even the postoperative treatment of those patients who developed recurrence?"

Guidelines leave preparation up to the treating surgeon, and several studies have found no benefit at least in the short term, he noted. "This is one of the first studies that have shown that perhaps from a long-term standpoint in patients with cancer, that there may be some benefit to preoperative preparation of the bowel, although again, it’s preliminary and there’s a lot of unknowns out there."

Dr. Collin and her colleagues analyzed data from a trial among patients who underwent an elective resection for cancer, adenoma, or diverticular disease of the colon at 21 hospitals in Sweden and Germany between 1999 and 2005.

Earlier results for the entire trial population, previously reported, showed no significant reduction in 30-day rates of complications with mechanical bowel preparation (Br. J. Surg. 2007;94:689-95).

The new, long-term results for just the 841 patients with colorectal cancer – 53% of whom had a mechanical bowel preparation before their surgery – indicated those undergoing this preparation had a higher actuarial 5-year rate of cancer-specific survival (90% vs. 82%; P = .03).

The two groups were similar in terms of the 5-year rate of recurrence (80% vs. 89%, P = .08) and overall survival, Dr. Collin said.

"We looked at tumor stage to see if the explanation for patients having no mechanical bowel preparation having poorer cancer-specific survival was that they had more advanced tumors, and there was no difference in the stages" between groups, she said, with the majority of patients in both groups having stage II or III disease.

Dr. Collin disclosed no conflicts of interest related to the research.

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.

Data show that African Americans present with colon cancer at an earlier age than whites. But there's debate about the appropriate screening age. Should all African American patients be screened at age 40? Dr. Byron Cryer, professor of medicine at the University of Texas Southwestern Medical Center, discusses the pros and cons of earlier screening and shares his opinion on the issue.