A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

INTRODUCTION: Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. PATIENTS AND METHODS: The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. RESULTS: Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. CONCLUSION: Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Tumor size, tumor location, and antitumor inflammatory response are associated with lymph node size in colorectal cancer patients.

Lymph node size affects lymph node retrieval in surgical specimen and is used as criterion for pre-operative radiological estimation of metastatic disease. However, factors determining lymph node size remain to be established. Therefore, the association between lymph node size and presence of metastatic cancer deposits as well as different primary tumor characteristics was analyzed in a prospective cross-sectional study. Visible and palpable nodes were harvested, and conventional histology, immunohistochemistry, and molecular analysis were performed. The study cohort comprised 148 patients (median age 69 years, range 36-92). Lymph node dissection rendered 4167 nodes. Mean lymph node count was 28 (median 26, range 9-67). Metastatic disease was detected in 320 (8%) nodes and was associated with lymph node size (P<0.001). Positive nodes measuring ≤2 mm caused upstaging within the N category in one third of cases, but did not identify patients as node-positive as all patients also had positive larger nodes. Large tumor size (P=0.001), right tumor location (P<0.001), and deep tumor penetration (P=0.024) were all independently associated with lymph node size, whereas high lymphocytic antitumor reaction just missed statistical significance (P=0.053) in multivariable analysis. Microsatellite instability had no influence on lymph node size when analysis was restricted to right-sided tumors. In conclusion, analysis of small lymph nodes may lead to upstaging within the N category, but they do not identify a patient as node-positive and do therefore not influence clinical decision-making in the adjuvant setting. The majority of enlarged lymph nodes, including those measuring >1 cm, are not involved by cancer. Different tumor characteristics, such as large primary tumor size, right tumor location, and deep tumor penetration are independently associated with lymph node size and need to be considered when interpreting enlarged nodes detected by radiological imaging.

Impact of postoperative complications on long-term survival after resection for rectal cancer.

BACKGROUND: The relevance of type and severity of postoperative complications after curative resection for rectal cancer on survival and recurrence rates is a matter of controversy. OBJECTIVE: The aim of this study was to investigate the impact of postoperative complications on long-term outcome after resection for rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: The study was conducted at a university teaching hospital by a specialized colorectal team. PATIENTS: Between January 1984 and October 2008, 811 patients with rectal cancer underwent curative resection. Patients who experienced postoperative complications were divided into a minor complication group (grades I and II) and a major complications group (grades III and IV) according to the Clavien classification. MAIN OUTCOME MEASURES: The influence of several pathological and clinical factors, including complications in terms of overall and disease-free survival, was tested and compared in univariate and multivariate analyses. RESULTS: Curative resection was performed in 811 patients; median age was 65 years. The Kaplan-Meier estimates (± SE) for 5- and 10-year overall cumulative survival were 70.3% ± 1.8% and 54.5% ± 2.4%; Kaplan-Meier estimates for 5- and 10-year disease-free survival were 64.0% ± 1.8% and 50.9% ± 2.3%. One hundred sixty-five patients (20.3%) had minor complications, and 103 patients (12.7%) had major complications. Twelve patients (1.48%) died within 30 days after surgery. There was no significant difference between patients with no complications, patients with minor complications, and patients with major complications in terms of overall (p = 0.41) or disease-free survival (p = 0.32). LIMITATIONS: A possible limitation of our study is that the data represent a cohort study from a single center. CONCLUSION: Following resection for rectal cancer, the severity of postoperative complications (minor or major) according to a standardized classification system does not demonstrate a statistically significant effect on either overall or disease-free survival.

Pre- and Postoperative Levels of Carcinoembryonic Antigen in Microsatellite Stable Versus Instable Colon Cancer: a Retrospective Analysis.

PURPOSE: The prognosis of microsatellite stable (MSS) versus instable (MSI) tumors is an ongoing matter of debate, with differences in expression of carcinoembryonic antigen (CEA) in these two tumor subsets being inconsistently reported to date. The aim of this study was to investigate CEA expression in the context of clinical parameters in MSS and MSI tumors. METHODS: Clinical, pathological, and biochemical parameters of colon cancer patients who underwent curative surgery were documented in a database and compared between MSS and MSI cases. The pre- to postoperative trend of CEA was analyzed. Survival was assessed using the Kaplan-Meier (log rank) test. RESULTS: One hundred sixty-nine patients were included in the study. Compared to those with MSS tumors, there was a higher proportion of preoperatively elevated CEA among those with MSI tumors (p = 0.067). Median CEA values decreased over the pre- to postoperative course with MSS (p = 0.01) but not MSI (p = 0.093) tumors. The distribution of N classification differed between MSS and MSI tumors (p = 0.014). Patients with MSI tumors had superior survival. CONCLUSION: Despite the better prognosis, MSI tumors are associated with increases in CEA. Our findings shed light on discrepancies related to the prognostic evaluation of MSI tumors. Furthermore, in follow-up of colorectal cancers, CEA measurements should be interpreted differently for MSI and MSS tumors.

Influence of body mass index on postoperative complications after rectal resection for carcinoma.

OBJECTIVES: The influence of obesity on postoperative complications after various surgical interventions remains controversial. The aim of this study was to evaluate the impact of overweight and obesity on the occurrence of postoperative complications for patients undergoing elective resection for rectal carcinoma. METHODS: We conducted a retrospective data analysis of 676 patients undergoing surgical treatment for rectal carcinoma. Depending on their body mass index (BMI), patients were grouped as follows: group I, patients up to BMI 24.9 kg/m; group II patients, with a BMI between 25 and 29.9 kg/m; and group III, all patients with a BMI >30 kg/m. Complications were classified as minor and major with regard to severity grades (1-5). Statistical analysis was performed to evaluate the difference in complication rates between the different BMI groups. RESULTS: A total of 444 patients were included for analysis. Overall, 300 (67.6%) of the 444 patients did not develop postoperative complications, 82 (18.4%) patients had minor complications (grade 1 + 2), and 56 patients (12.6%) had major (grade 3 + 4) complications. Six (1.4%) patients died (grade 5). The Fisher exact test indicated no statistically significant difference of complication rates between the different BMI groups (P = 0.3716). CONCLUSIONS: Compared with nonobese or normal-weight patients, obese patients do not have a statistically significant higher risk of developing postoperative complications after rectal resection for carcinoma.

INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn's Disease Treated in the ADMIRE-CD Trial.

BACKGROUND: The efficacy of a single administration of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells) for treating complex perianal fistulas in patients with Crohn's disease was demonstrated in a randomized, double-blind trial (ADMIRE-CD [Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn\'s Disease] trial). The current chart review study (INSPECT [A retrospectIve chart review study evaluatINg the longer-term effectiveneSs of darvadstrocel in PatiEnts who CompleTed ADMIRE-CD]) evaluated the longer-term effectiveness and safety of darvadstrocel. METHODS: Eligible patients had completed at least 52 weeks in the ADMIRE-CD trial. Data on clinical remission and fistula relapse outcomes were collected retrospectively at 104 and 156 weeks after treatment. Adverse events of special interest (tumorigenicity and ectopic tissue formation) were collected up to 208 weeks after treatment. RESULTS: Eighty-nine patients were included (43 darvadstrocel patients, 46 control subjects). At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively. In patients with clinical remission at week 52, this remission was sustained at 104 and 156 weeks after treatment in 19 (65.5%) of 29 and 16 (55.2%) of 29 darvadstrocel-treated patients and in 17 (70.8%) of 24 and 13 (54.2%) of 24 control subjects, respectively. Time to fistula relapse and incidence of fistula relapse or new fistula occurrence were not significantly different between groups. Tumorigenicity was reported for 1 (2.2%) patient in the control group (malignant epidermoid carcinoma). No ectopic tissue formation was reported. CONCLUSIONS: Real-world follow-up of patients from the ADMIRE-CD trial indicates that clinical remission of complex perianal fistulas can be sustained in the long term irrespective of whether it is achieved through darvadstrocel administration or maintenance treatment regimens and confirms a favorable long-term safety profile of darvadstrocel.

This retrospective chart review of patients treated with darvadstrocel indicates sustained remission and confirms a favorable safety profile up to 156 weeks after a single administration of stem cells for treatment of complex perianal fistulas in patients with Crohn's disease.

Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT3NxM0, low rectal cancer: a phase II study.

PURPOSE: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy. PATIENTS AND METHODS: Patients with LARC of the mid and lower rectum, T3NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m² twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m² intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level. RESULTS: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%). CONCLUSIONS: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.

Influence of pT3 subgroups on outcome of R0-resected colorectal tumors.

OBJECTIVE: Evaluate whether depth of infiltration within T3 colorectal tumors influences long-term oncologic outcome. PATIENTS AND METHODS: Patients with stage pT3 colon and rectal tumors were divided into four subgroups according to the depth of infiltration. The influence on overall and disease-free survival was tested for each subgroup and compared in univariate and multivariate analyses. RESULTS: A total of 368 patients were evaluated, with a median follow-up time of 92.5 months. In 181 patients with colon cancer 5- and 10-year overall survival rates were 82.7% and 65.0%, respectively, and 5- and 10-year disease-free survival rates were 80.9% and 64.4%, respectively. For 187 patients, rectal cancer 5- and 10-year overall survival rates were 69.0% and 50.5%, respectively, and disease-free survival rates were 61.3% and 47.5%, respectively. In either colon or rectal cancer, different pT3 categories showed neither a statistically significant influence on survival nor the occurrence of local or distant recurrence in univariate and multivariate analyses; however, higher pT3 subgroups had a significant influence on lymph node involvement and vessel invasion in patients with rectal cancer. CONCLUSIONS: Subdivision of pT3 tumors in colon cancer based on depth of infiltration does not provide additional information about prognosis. In rectal cancer, T3 substages were associated with lymph node involvement; however, we could not demonstrate an impact on recurrence or survival.

Heterotopic pancreatic tissue in the cystic duct: complicating factor or coexisting pathology.

The case of a 75-year-old female suffering from recurrent abdominal pain and nausea is presented. Ultrasound showed gallstones without inflammation of the gallbladder. The patient underwent laparoscopic cholecystectomy and her symptoms resolved. Histological examination of the operation specimen disclosed heterotopic pancreatic tissue within the cystic duct. An accurate clinical diagnosis of pancreatic heterotopia is difficult. The deep submucosal or intramural location of the lesion may hamper retrieval of representative biopsy material. Indications for surgery or endoscopic resection include symptomatic lesions as well as cases of unclear histological examination in order to distinguish pancreatic heterotopia from other tumors.

The long-term influence of hospital and surgeon volume on local control and survival in the randomized German Rectal Cancer Trial CAO/ARO/AIO-94.

BACKGROUND: The association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers. METHODS: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with stage II/III rectal cancers were evaluated. LR-rates and OS were stratified by hospital recruitment volume (≤20 vs. 21-90 vs. >90 patients) and by surgeon volume (≤10 vs. 11-50 vs. >50 procedures). RESULTS: Patients treated in high-volume hospitals had a longer OS than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was adversely associated with LR (p = 0.01) but had no influence on overall survival. The positive effect of neoadjuvant chemoradiation (CRT) on local control was the strongest in patients being operated by medium-volume surgeons, less in patients being operated by high-volume surgeons and missing in those being operated by low-volume surgeons. CONCLUSIONS: Patients with locally advanced rectal cancers might benefit from treatment in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on long-term local tumour control. The effect of neoadjuvant CRT on local tumour control may likewise depend on the surgeon volume.

Solitary giant splenic metastasis in a patient with metachronous gastric cancers.

Splenic metastases from solid tumors are uncommon. They may be observed in a context of multivisceral dissemination or as a solitary lesion. We report the case of an 80-year-old woman with a history of two metachronous gastric cancers treated with distal gastrectomy and resection of the gastric remnant within a period of 15 years, who presented with a huge splenic tumor mass three years after the second operation. Splenectomy was performed. The resection specimens showed a well-circumscribed solid lesion measuring 15 cm in the largest diameter. Histology revealed metastatic gastric cancer. The differential diagnosis and clinical significance of this rare condition is discussed.

Ileocecal intussusception caused by lung cancer metastasis.

Intussusception is a rare clinical finding in adults. Most cases occur in the distal small bowel or large intestine. We report the case of a 65-year-old woman with known non-small-cell lung cancer (NSCLC) who presented with acute abdomen and ileus-like symptoms. Abdominal computed tomography suggested ileocecal intussusception. The patient underwent right hemicolectomy and the histopathological workup showed ileal NSCLC metastasis as the lead lesion of intussusception. The classic triad of cramping abdominal pain, bloody diarrhea and a palpable tender mass, which is present in the majority of pediatric patients, is only infrequently observed in adults. Thus, symptoms are often nonspecific and the clinical presentation may be inconspicuous. Because of the large proportion of structural anomalies, adult intussusception requires definitive treatment, of which surgical resection is the treatment of choice. In patients with colocolonic or ileocolonic intussusception, malignancy should be considered and therefore en bloc resection rather than reduction is the recommended surgical technique, whereas cases of enteric intussusceptions may be reduced by limited resection of the small intestine.

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

BACKGROUND: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies. METHOD: Biomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study. RESULTS: From 2007-2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%. CONCLUSION: Due to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

Preoperative versus postoperative chemoradiotherapy for rectal cancer.

BACKGROUND: Postoperative chemoradiotherapy is the recommended standard therapy for patients with locally advanced rectal cancer. In recent years, encouraging results with preoperative radiotherapy have been reported. We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer. METHODS: We randomly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy. The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day, five days per week, and fluorouracil, given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy. Surgery was performed six weeks after the completion of chemoradiotherapy. One month after surgery, four five-day cycles of fluorouracil (500 mg per square meter per day) were given. Chemoradiotherapy was identical in the postoperative-treatment group, except for the delivery of a boost of 540 cGy. The primary end point was overall survival. RESULTS: Four hundred twenty-one patients were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy. The overall five-year survival rates were 76 percent and 74 percent, respectively (P=0.80). The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group (P=0.006). Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group, as compared with 40 percent of the patients in the postoperative-treatment group (P=0.001); the corresponding rates of long-term toxic effects were 14 percent and 24 percent, respectively (P=0.01). CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, improved local control and was associated with reduced toxicity but did not improve overall survival.

Neoadjuvant Chemotherapy with Capecitabine, Oxaliplatin and Bevacizumab Followed by Concomitant Chemoradiation and Surgical Resection in Locally Advanced Rectal Cancer with High Risk of Recurrence - A Phase II Study.

AIM: To evaluate feasibility and safety of neoadjuvant chemotherapy with capecitabine, oxaliplatin and bevacizumab followed by concomitant standard chemoradiation and surgical resection in patients with high-risk locally advanced rectal cancer. PATIENTS AND METHODS: Magnetic resonance imaging (MRI)-defined high-risk cT3/4 rectal cancer patients were treated with 3 cycles of neoadjuvant chemotherapy with capecitabine (1,000 mg/m2 twice daily days 1-14, 22-35, 43-56), oxaliplatin (130 mg/sqm on days 1, 22, 43) and bevacizumab (7.5 mg/kg on days 1, 22, 43) followed by capecitabine (825 mg/m2 twice daily on radiotherapy days week 1-4) concomitantly with radiotherapy (1.8 Gy daily up to 45 Gy in 5 weeks) and surgical resection by total mesorectal excision. Feasibility, safety, response rate and postoperative morbidity were evaluated. RESULTS: Twenty-five patients were recruited. Median age was 62 years (range=24-78 years) and all patients had Eastern Cooperation Oncology Group (ECOG) performance status 0. From all patients, 79.2% finished neoadjuvant chemotherapy. Twenty patients underwent surgery. Pathologic complete remission rate, R0 resection and T-downstaging were achieved in 25%, 95% and 54.2% of the "intention to treat" (ITT) patients. The most common grade 3 adverse events (AEs) during neoadjuvant chemotherapy were diarrhea (16.6%) and mucositis (12.5%). In one patient, a grade 4 acute renal failure occurred (4.2%). During chemoradiation, skin reactions (5.3%) were the most common grade 3 AEs. Two major perioperative complications required re-intervention. CONCLUSION: Neoadjuvant chemotherapy with bevacizumab, capecitabine and oxaliplatin followed by concomitant standard chemoradiation is feasible in patients with high-risk locally advanced rectal cancer (LARC) and resulted in complete pathologic remission (pCR) rate of 25% and neoadjuvant chemotherapy completion rate of 80%.

Diverting ileostomy versus no diversion after low anterior resection for rectal cancer: A prospective, randomized, multicenter trial.

BACKGROUND: This study sought to determine whether a protective diverting ileostomy improves short-term outcomes in patients with rectal resection and colonic J-pouch reconstruction for low anastomoses. Criteria for the use of a proximal stoma in rectal resections with colonic J-pouch reconstruction have not been defined sufficiently. METHODS: In a multicenter prospective study, rectal cancer patients with anastomoses below 8 cm treated with low anterior resection and colonic J-pouch were randomized to a defunctioning loop ileostomy or no ileostomy. The primary study endpoint was the rate of anastomotic leakage, and the secondary endpoints were surgical complications related to primary surgery, stoma, or stoma closure. RESULTS: From 2004 to 2014, a total of 166 patients were randomized to 1 of the 2 study groups. In the intention-to-treat analysis, the overall leakage rate was 5.8% in the stoma group and 16.3% in the no stoma group (P = .0441). However, some patients were not treated according to randomization and only 70% of our patients with low anastomoses received a pouch. Therefore, we performed a second analysis as to actual treatment. In this analysis, as well, leakage rates (P = .044) and reoperation rates for leakage (P = .021) were significantly higher in patients without a stoma. In multivariate analysis, male gender (P = .0267) and the absence of a stoma (P = .0092) were significantly associated with anastomotic leakage. CONCLUSION: Defunctioning loop ileostomy should be fashioned in rectal cancer patients with anastomoses below 6 cm, particularly in male patients, even if reconstruction was done with a J-pouch.

TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI: 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

Randomized clinical trials in colon cancer.

Prospective randomized trials involving the surgical and chemotherapeutic treatment of resectable colon cancer are reviewed. Emphasis is placed on those trials that have impacted the current management of primary colon cancer.