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Background Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. Methods An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. Results In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). Conclusions Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

BACKGROUND Neoadjuvant chemoradiotherapy followed by tumor resection and postoperative chemotherapy is the standard of care for patients with clinical stage II or III adenocarcinoma of the rectum. Significant variation exists in the receipt of postoperative chemotherapy after resection in this population. The objective of this study was to determine the demographic and clinicopathologic factors associated with the initiation of postoperative chemotherapy in elderly patients with rectal cancer and to identify potential targets for reducing treatment variation. METHODS A retrospective cohort study was performed of patients with rectal cancer ages 66 to 80 years who received neoadjuvant chemoradiotherapy and underwent radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007). Multivariate logistic regression was used to assess chemotherapy use in relation to patient, tumor, and treatment response characteristics. RESULTS Among 1492 patients who met the study criteria, 61.5% received adjuvant therapy with 5-fluorouracil. Pathologic stage was the strongest determinant of whether patients received postoperative chemotherapy (48.3% of patients with stage I disease, 59.6% of patients with stage II disease, and 77.6% of patients with stage III disease). Increasing age and postoperative readmission also were associated significantly with a decreased rate of adjuvant therapy initiation. CONCLUSIONS Although standard treatment guidelines for locally advanced rectal cancer include postoperative chemotherapy for all patients after neoadjuvant chemoradiotherapy and radical resection, greater than 1 in 3 patients failed to receive adjuvant therapy. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology. Cancer 2014;120:1162–1170. © 2014 American Cancer Society.

BACKGROUND The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer. METHODS The authors studied 251 patients with rectal adenocarcinoma who were treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated percentage of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near-complete, ≤ 5% residual cancer cells; major, > 5%, and

BACKGROUND Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based chemoradiation was evaluated for patients with locally advanced squamous cell carcinoma (SCC) of the anal canal treated at a single institution over a 20-year period. METHODS A retrospective, single-institution analysis was conducted of patients receiving concurrent 5-FU/cisplatin and radiotherapy for locally advanced SCC from 1989 to 2009. Endpoints included clinical complete response rate, local recurrence rate, colostomy-free survival, disease-free survival (DFS), overall survival, and treatment-related toxicity. RESULTS A total of 197 patients were evaluable. The majority had American Joint Committee on Cancer stage II (41%) or stage III (46%) disease; most were T2 (44%) or T3 (27%); bulky nodal disease (N2-N3) was noted in 24% of patients. Patients received weekly (20 mg/m2) or daily (4 mg/m2) cisplatin during radiotherapy. Median radiation dose was 55 Gy. Clinical complete response was observed in 185 patients (94%). After a median follow-up of 8.6 years, local recurrence rate was 11%. Sixteen patients (8%) developed distant metastases. The 5-year DFS was 81%, the 5-year overall survival was 86%, and the 5-year colostomy-free survival was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-year DFS (P = .02, 95% confidence interval = 1.17-2.01) and distant metastases (P = .046, 95% confidence interval = 1.09-2.13). Increased T-stage correlated with the necessity for salvage surgery (P = .01). CONCLUSIONS The combination of weekly/daily cisplatin and 5-FU–based chemotherapy with concurrent radiotherapy is an effective regimen, and our long-term results indicate that cisplatin is an alternative to mitomycin C and may be considered for the treatment of locally advanced SCC of the anal canal. Cancer 2013;119:3769–3775. © 2013 American Cancer Society.

Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR.An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used.In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06).Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

BACKGROUND: Preoperative chemoradiation for rectal cancer can decrease the number of evaluable lymph nodes. Hence, the prognostic role of lymph node evaluation in patients with rectal cancer who receive preoperative chemoradiation is unclear. The authors of this report evaluated the prognostic impact of the number of lymph nodes examined in patients with rectal cancer who had negative lymph nodes based on the pathologic extent of disease (ypN0) after they received preoperative chemoradiation. METHODS: Between 1990 and 2004, 372 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation followed by mesorectal excision and had ypN0 disease. The median radiation dose was 45 gray, and 68% of patients received adjuvant chemotherapy. RESULTS: Patients had a median of 7 lymph nodes examined after preoperative chemoradiation. Compared with patients who had ≤7 lymph nodes examined, patients who had >7 lymph nodes had higher 5-year rates of freedom from relapse (86% vs 72%; log-rank P = .005) and cancer-specific survival (95% vs 86%; log-rank P = .0004), but no significant difference was observed in the overall survival rate (87% vs 81%; log-rank P = .07). Multivariate Cox proportional models demonstrated that patients who had >7 lymph nodes examined had a significantly lower risk of relapse (hazard ratio [HR], 0.39; P = .003) and death from rectal cancer (HR, 0.45; P = .04) but a similar risk of all-cause mortality (HR, 0.75; 95% CI, 0.46-1.20; P = .23) compared with patients who had ≤7 lymph nodes examined. CONCLUSIONS: The number of lymph nodes examined was associated independently with disease relapse and cancer-specific survival in patients with rectal cancer who had ypN0 disease after receiving preoperative chemoradiation. Hence, the authors concluded that the number of negative lymph nodes examined may be a prognostic factor in patients with rectal cancer who receive preoperative chemoradiation. Cancer 2011;. © 2011 American Cancer Society.

BACKGROUND The objective of this study was to identify predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. METHODS Between 1989 and 2004, 562 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation and underwent mesorectal excision. The median radiation dose was 45 Gray (Gy) (range, 19.8–58.6 Gy), 77% of patients received concurrent infusional 5-fluorouracil, 20% of patients received concurrent capecitabine, and 3% of patients received other regimens. RESULTS Nineteen percent of patients achieved a pathologic complete response (CR), whereas 20% of patients had only microscopic residual disease at surgery, and 61% of patients had macroscopic residual disease at surgery. Downstaging of the tumor stage occurred in 57% of patients. The results from a univariate analysis indicated that tumor circumferential extent >60% (P = .033) and pretreatment carcinoembryonic antigen (CEA) level >2.5 ng/mL (P = .015) were associated significantly with lower pathologic CR rates. The univariate analysis also indicated that tumor circumferential extent >60% (P = .001), pretreatment CEA level >2.5 ng/mL (P = .006), and distance from the anal verge >5 cm (P = .035) were associated significantly with lower downstaging rates. The results from a multivariate logistic regression analysis indicated that greater circumferential extent of tumor (odds ratio [OR], 0.43; P = .033) independently predicted a lower pathologic CR rate. The multivariate logistic regression analysis also indicated that greater circumferential extent of tumor (OR, 0.49; P = .020) and greater distance from the anal verge (OR, 0.46; P = .010) independently predicted a lower downstaging rate. CONCLUSIONS Circumferential extent of tumor, CEA level, and distance from the anal verge predicted for the pathologic response to preoperative chemoradiation for patients with rectal cancer. Therefore, these factors may be used to predict outcomes for patients, to develop risk-adapted treatment strategies, and to target patients who participate in trials of newer therapies. Cancer 2007. © 2007 American Cancer Society.

BACKGROUND Although controversial, some believe that preoperative chemoradiation increases the use of sphincter-preserving surgery in low rectal carcinoma patients. This article investigates the relationship between objective tumor response and sphincter preservation in low rectal carcinoma patients. METHODS The authors reviewed the records of 238 patients with T3 or T4 low rectal carcinoma (≤ 6 cm from the anal verge) who underwent preoperative pelvic chemoradiation (45 Gy/25 fractions/5 weeks, n = 182 or 52.5 Gy/30 fractions/5 weeks, n = 56 with continuous infusion 5-fluorouracil at 300 mg/m2, Monday to Friday) followed by mesorectal (n = 223) or local excision (n = 15). A logistic regression analysis was used to analyze the influence of objective tumor response (defined as complete clinical response) and other prognostic factors on sphincter preservation. Because degrees of partial response could not be objectively defined retrospectively, the influence of partial response on sphincter preservation could not be evaluated. RESULTS Overall, 49% of patients (117 of 238) had sphincter-preserving surgery. The clinical complete response rate was 47%. Independent predictors of sphincter preservation included the year of surgery, tumor distance from the anal verge, circumferential tumor involvement, and response to chemoradiation. The sphincter preservation rate increased over the period of the study (from 28% [December 1989 to December 1992] to 44% [January 1993 to December 1996] to 67% [January 1997 to December 2000]). The difference in the rates of sphincter preservation according to response was most striking among patients with tumors 3 cm or less from the anal verge (44% vs. 22%, P = 0.01). The pelvic disease recurrence rate among patients undergoing sphincter-preserving surgery has been less than 10% since January 1993 and was not statistically different between the groups treated from January 1993 to December 1996 and from January 1997 to December 2000. CONCLUSIONS There has been an increase in the use of sphincter-preserving surgery without an increase in pelvic disease recurrence over the past decade. Although not necessary for sphincter preservation, clinical response to preoperative chemoradiation independently contributed to sphincter-preserving surgery, particularly in patients with low rectal tumors. Cancer 2003;97:517–24. © 2003 American Cancer Society. DOI 10.1002/cncr.11075

BACKGROUND Mutations of the p53 tumor suppressor gene play an integral role in sporadic colorectal carcinogenesis but prior studies have failed to show their prognostic significance consistently. METHODS Fifty-six consecutive sporadic colorectal tumors were analyzed for their p53 status. Polymerase chain reaction amplification with primers for exons 5–9 was conducted and these products were subjected to single strand conformation polymorphism analysis. Suspected mutations were confirmed with DNA sequencing. p53 status was entered into a colorectal clinical database and these patients then were followed prospectively. Patient status with regard to disease recurrence and survival was updated every 6 months. Survival and disease free survival were calculated according to the method of Kaplan and Meier. The association between p53 status and clinical and pathologic factors with survival and recurrence was statistically determined using univariate analysis and the Cox proportional hazards model for multivariate analysis. RESULTS p53 mutations were detected in 28 of 56 patients (50%). The median follow-up time was 45 months (range, 3–72 months). There were 33 patients (59%) who were alive at last follow-up. Fifteen of the 23 patients who died (65%) had p53 mutations and 8 (35%) had wild-type p53. Thirteen patients developed a disease recurrence, 9 of whom (69%) had tumors with p53 mutations. Overall 4-year survival rates for patients with wild-type p53 and mutant p53 were 71% and 54%, respectively (P = 0.05). The 4-year disease free survival rates for patients with wild-type p53 and mutant p53 were 83% and 62%, respectively (P = 0.09). p53 status and stage were found to be independent significant predictors for survival (p53 negative: P = 0.02; stage: P = 0.0002.) Stage was found to be the sole significant predictor for disease free survival (P = 0.006). CONCLUSIONS In this group of colorectal carcinoma patients, p53 mutations were a significant negative prognostic indicator for overall survival. This finding holds prognostic and therapeutic implications for the management of colorectal carcinoma patients. Cancer 2000;88:1814–9. © 2000 American Cancer Society.

BACKGROUND, Small bowel carcinoma is uncommon. However, hereditary nonpolyposis colorectal carcinoma (HNPCC) patients are at increased risk of small bowel carcinoma. The purpose of this study was to characterize small bowel tumors in HNPCC patients. METHODS. A questionnaire was mailed to the members of International Collaborative Group on HNPCC (ICG-HNPCC) requesting clinicopathologic data in their registries on HNPCC patients with small bowel carcinoma. Survival was estimated utilizing the Kaplan-Meier method. RESULTS. Forty-two individuals from 40 HNPCC families developed 42 primary and 7 metachronous small bowel tumors. There were 46 adenocarcinomas and 3 carcinoid tumors. The median age at diagnosis of the index small bowel tumor was 49 years. Mismatch repair gene mutations were present in 15 of 42 patients (36%). There were nine hMLH1 and six hMSH2 mutations. The small bowel was the first site of carcinoma in 24 patients (57%). The median survival for the 42 patients was 47 months (range, 0-447 months). The overall 5- and 10-year survival rates were 44% and 33%, respectively. CONCLUSIONS. Small bowel tumors can be the presenting neoplasms in HNPCC patients. Similar to colorectal carcinoma in HNPCC, small bowel adenocarcinomas in HNPCC patients occur at an earlier age and appear to have a better prognosis than those occurring in the general population.

BACKGROUND Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. METHODS This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. RESULTS Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. CONCLUSIONS A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease. Cancer 1998;82:1244-9. © 1998 American Cancer Society.

Neoadjuvant chemoradiotherapy followed by tumor resection and postoperative chemotherapy is the standard of care for patients with clinical stage II or III adenocarcinoma of the rectum. Significant variation exists in the receipt of postoperative chemotherapy after resection in this population. The objective of this study was to determine the demographic and clinicopathologic factors associated with the initiation of postoperative chemotherapy in elderly patients with rectal cancer and to identify potential targets for reducing treatment variation.A retrospective cohort study was performed of patients with rectal cancer ages 66 to 80 years who received neoadjuvant chemoradiotherapy and underwent radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007). Multivariate logistic regression was used to assess chemotherapy use in relation to patient, tumor, and treatment response characteristics.Among 1492 patients who met the study criteria, 61.5% received adjuvant therapy with 5-fluorouracil. Pathologic stage was the strongest determinant of whether patients received postoperative chemotherapy (48.3% of patients with stage I disease, 59.6% of patients with stage II disease, and 77.6% of patients with stage III disease). Increasing age and postoperative readmission also were associated significantly with a decreased rate of adjuvant therapy initiation.Although standard treatment guidelines for locally advanced rectal cancer include postoperative chemotherapy for all patients after neoadjuvant chemoradiotherapy and radical resection, greater than 1 in 3 patients failed to receive adjuvant therapy. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology.

Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based chemoradiation was evaluated for patients with locally advanced squamous cell carcinoma (SCC) of the anal canal treated at a single institution over a 20-year period.A retrospective, single-institution analysis was conducted of patients receiving concurrent 5-FU/cisplatin and radiotherapy for locally advanced SCC from 1989 to 2009. Endpoints included clinical complete response rate, local recurrence rate, colostomy-free survival, disease-free survival (DFS), overall survival, and treatment-related toxicity.A total of 197 patients were evaluable. The majority had American Joint Committee on Cancer stage II (41%) or stage III (46%) disease; most were T2 (44%) or T3 (27%); bulky nodal disease (N2-N3) was noted in 24% of patients. Patients received weekly (20 mg/m2) or daily (4 mg/m2) cisplatin during radiotherapy. Median radiation dose was 55 Gy. Clinical complete response was observed in 185 patients (94%). After a median follow-up of 8.6 years, local recurrence rate was 11%. Sixteen patients (8%) developed distant metastases. The 5-year DFS was 81%, the 5-year overall survival was 86%, and the 5-year colostomy-free survival was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-year DFS (P = .02, 95% confidence interval = 1.17-2.01) and distant metastases (P = .046, 95% confidence interval = 1.09-2.13). Increased T-stage correlated with the necessity for salvage surgery (P = .01).The combination of weekly/daily cisplatin and 5-FU-based chemotherapy with concurrent radiotherapy is an effective regimen, and our long-term results indicate that cisplatin is an alternative to mitomycin C and may be considered for the treatment of locally advanced SCC of the anal canal.

Background. Sporadic desmoid tumors occur mainly in the abdominal wall and in extraabdominal sites. Desmoid tumors in patients with familial adenomatous polyposis (FAP) usually occur in the abdominal wall and in the bowel mesentery. Surgical resection of desmoids in patients with FAP has been controversial. Methods. A retrospective review of patients with FAP and desmoid tumors treated from 1950 to 1991 was performed. Patients were evaluated for gender, age, site of desmoid tumors, treatment, recurrence, and survival. Results. Twenty-one of 24 patients underwent 60 surgical procedures related to the desmoid tumors. Seven of nine patients who underwent potentially curative surgery had recurrences; three were reresected. Major morbidity after palliative or curative surgery was 47%. Five patients were alive with no evidence of disease at a median of 198 months, 10 patients were alive with disease at a median of 102 months, and 5 patients died with disease at a median of 31 months after diagnosis. Conclusions. Desmoid tumors are common in patients with FAP. Unresectability and recurrence are more common than cure. Palliative and curative resections have a high morbidity. Surgery should be reserved for those patients with symptomatic mesenteric desmoids.

BACKGROUND Isolation of Inoue-Melnick virus (IMV) Type 1 from tumor tissues of patients with colorectal carcinoma in Japan was reported. A high prevalence of IMV antibodies has been found among patients with colorectal carcinoma in Buffalo, New York. METHODS IMV was isolated from homogenates of colorectal carcinoma and other tissues, inoculated into MRC-5 human fibroblast cultures. IMV-specific cytopathic effects were detected and titrated following 7 days of incubation in a roller-tube apparatus. RESULTS IMV was isolated from all nine (100%) colorectal carcinoma tissues tested and all four (100%) normal parts of colon mucosa tissues obtained from patients with cancer. Biopsy specimens of normal colon mucosa from 10 patients without colon carcinoma were negative for IMV (0%). Average infectious titers of IMV in these tissue homogenates were 4.41 for tumor tissue and 2.55 log10 tissue culture infectious dose by 50% (TCID50)/0.1 ml for colon mucosa, respectively. Most of the isolates were the IMV intermediate type. CONCLUSIONS Our results confirmed the production of infectious IMV in colorectal carcinoma tissues, as reported recently in Japan. The role of IMV in colorectal carcinogenesis is currently unknown.

BACKGROUND: Adjusting to cancer requires effective cognitive and emotional processing. Written and verbal disclosure facilitate processing and have been studied independently in cancer survivors. Combined written and verbal expression may be more effective than either alone, particularly for patients with difficult to discuss or embarrassing side effects. Thus, the authors developed and tested the efficacy of a 12-session combined written and verbal expression group program for psychologically distressed colorectal cancer (CRC) patients. METHODS: Forty post-treatment patients with CRC (stages I-III) identified as psychologically distressed using the Brief Symptom Inventory (BSI) were randomized to an intervention group (Healthy Expressions; n = 25) or standard care (control group; n = 15). Assessments were completed at baseline, Month 2, and Month 4 (postintervention). Primary outcomes were psychological functioning and quality of life (QOL). RESULTS: Most participants were women (63%), white (63%), and non-Hispanic (75%). The Healthy Expressions group demonstrated significantly greater changes in distress compared with the control group at Month 2 on the BSI Global Severity Index (GSI) and the Centers for Epidemiologic Studies Depression scale (CES-D) scores (P < .05 for each); differences in the European Organization for Research and Treatment of Cancer (EORTC) global QOL scores approached significance (P = .063). The BSI GSI and Positive Symptom Total, CES-D, and EORTC emotional functioning subscale scores were all significant at Month 4 (P < .05 for each). CONCLUSIONS: The Healthy Expressions program improved psychological functioning in CRC patients who reported experiencing distress. Findings demonstrate the program's feasibility and provide strong support for conducting a larger randomized trial. Cancer 2011;. © 2011 American Cancer Society.