Nonoperative management of primary colorectal cancer in patients with stage IV disease. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients. Intestinal complications after palliative treatment for asymptomatic patients with unresectable stage IV colorectal cancer. Colorectal cancer with non-resectable synchronous metastases: should the primary tumor be resected? Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Postoperative surveillance in patients with colorectal cancer who have undergone curative resection: a prospective, multicenter, randomized, controlled trial. A prospective randomized controlled trial of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.
Traditional teaching maintains that patients with primary colorectal adenocarcinoma require timely resection to prevent bleeding, perforation, or obstruction. The true benefits of primary tumor resection remain undocumented for patients presenting with metastatic disease, however. We postulated that resection of primary colorectal tumors could be avoided safely in a select population of asymptomatic colorectal cancer patients presenting with incurable stage IV disease.
                A retrospective review of the Vanderbilt University Hospital tumor registry was performed for the years 1985 to 1997. During this period, 955 patients presented for management of primary colorectal cancer. From this group, all patients with stage IV disease at the time of diagnosis were identified. Patients who initially underwent resection of their primary lesion were included in the resection group; those who underwent initial nonoperative primary tumor management were included in the nonresection group. Data were obtained regarding age, extent of disease, nonsurgical therapy, tumor-specific complications, and palliative surgical procedures. Surgery-free survival and overall survival were analyzed using the Kaplan-Meier method. For patients with liver metastases, hepatic tumor burden was defined as either H1 (<25% parenchymal replacement), H2 (25% to 50%), or H3 (>50%) disease.
                Sixty-six patients were included in the resection group, and 23 patients with intact asymptomatic primary colorectal lesions were included in the nonresection group. Among patients with hepatic metastases, most of the patients in both groups had H1 disease. Ten patients in the resection group and 3 patients in the nonresection group presented with exclusively extrahepatic metastases. In the nonresection group, primary therapy included chemotherapy in 13 patients, external beam radiation therapy in 1 patient, and combination chemoradiation in 9 patients. The median survival in the nonresection group was 16.6 months. The 2-year actuarial survival was 18%, and the surgery-free survival was 91.3%. Only 2 of 23 patients (8.7%) managed without resection eventually developed obstruction at the primary tumor site requiring emergent diversion. There were no episodes of tumor-related hemorrhage or perforation. For the resection group, the operative morbidity was 30.3%, and the perioperative mortality rate was 4.6%. The median survival in the resection group was 14.5 months (P = 0.59, log-rank test vs. nonresection group).
                Selected patients with asymptomatic primary colorectal tumors who present with incurable metastatic disease may safely avoid resection of their primary lesions, with an anticipated low rate of hemorrhage, perforation, or obstruction before death from systemic disease. No survival advantage is gained by resection of an asymptomatic primary lesion in the setting of incurable stage IV colorectal cancer. The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear.
                This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour.
                The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined.
                Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3-8.5%), 3.7% (95% CI 0.8-10.3%), and 3.7% (95% CI 0.8-10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9-22.7%) of patients in the unresected group and 13.2% (95% CI 9.2-17.2%) of patients in the resected group. More patients in the unresected group required >/=3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group.
                The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour. Surgical resection of primary colorectal cancer (CRC) in patients with stage IV disease at initial presentation remains controversial. Although bowel resection to manage symptoms such as bleeding, perforation, or obstruction has been advocated, management of asymptomatic patients has not been well defined. Patient-dependent factors (performance status, comorbid disease) and extent of distant metastases are among the considerations that impact on the decision to proceed with surgical management in asymptomatic stage IV CRC patients. We postulated that selected patients might benefit from elective resection of the asymptomatic primary CRC. The extent of distant metastases was objectively measured by several methods to identify potential prognostic variables that may help guide patient selection in this population.
                We reviewed hospital and colorectal service databases for the years 1996 to 1999. Stage IV patients who had colorectal resections with gross residual metastatic disease were identified (n = 209). Among these 209 patients, 82 patients operated on for symptoms (obstruction, perforation, bleeding, or pain) were excluded, leaving 127 patients who underwent elective resection of their asymptomatic primary CRC. Over the same time period, 103 stage IV patients who did not undergo resection were identified. Data on patient characteristics and clinical management were collected. A radiologist performed an independent review of available CT scans to assess extent of liver disease. The chi-square test was used for analysis of categoric data and Student's t-test for continuous variables. Survival was determined by the Kaplan-Meier method and distributions compared by the log rank test. Multivariate analysis was performed using Cox regression.
                The resected group could be easily distinguished from the nonresected group by a higher frequency of right colon cancers (p = 0.03) and metastatic disease restricted to the liver (p = 0.02) or one other site apart from the primary tumor (p = 0.02). Resected patients had prolonged median (16 versus 9 months, p < 0.001) and 2-year (25% versus 6%, p < 0.001) survival compared with patients never resected. Univariate analysis identified three significant prognostic variables (number of distant sites involved, metastases to liver only, and volume of hepatic replacement by tumor) in the resected group. Volume of hepatic replacement was also a significant predictor of survival in Cox multivariate regression analysis (p = 0.01). Subsequent to resection of asymptomatic primary CRC, 26 patients (20%) developed postoperative complications. Median hospital stay was 6 days. Two patients (1.6%) died within 30 days of surgery.
                Stage IV patients selected for elective palliative resection of asymptomatic primary colorectal cancers had substantial postoperative survival that was significantly better than those never having resection. Limited metastatic tumor burden and less extensive liver involvement were associated with better survival and a higher likelihood of benefit from elective bowel resection in asymptomatic patients with incurable stage IV CRC. The initial surgical management of asymptomatic patients with unresectable stage IV colorectal cancer (CRC) is still controversy. The aim of this study was to compare the incidence of major intestinal complications in asymptomatic patients who received palliative treatment for unresectable stage IV CRC, according to the type of treatment.
                Between March 2001 and January 2008, we retrospectively analyzed 227 asymptomatic patients who underwent first-line resection of the primary tumor followed by chemotherapy (144 patients, resection group) or those who underwent first-line chemotherapy (83 patients, chemotherapy group).
                In the resection group, the incidences of intestinal obstruction, peritonitis, fistula, and intestinal hemorrhage were 14.6%, 0%, 0.7%, and 4.8%, respectively. In the chemotherapy group, these incidences were 15.2%, 1.2%, 0%, and 3.5%, respectively. There were no significant differences between the two groups in terms of intestinal complications. In multivariate analysis of overall survival, treatment type (resection group vs. chemotherapy group) was not a significant prognostic factor (P = 0.076).
                In asymptomatic patients with unresectable stage IV CRC, first-line chemotherapy may be considered safe, with no increased risk of major intestinal complications compared with primary tumor resection plus chemotherapy.
                (c) 2010 Wiley-Liss, Inc. In asymptomatic patients presenting with non-resectable synchronous metastatic disease from colorectal adenocarcinoma, the beneficial effect of resecting the primary tumor remains to be documented. The aim of this study was to compare survival of patients with metastatic colorectal cancer who underwent elective resection of the primary tumor to those who did not.
                A retrospective analysis of patients with metastatic colo-rectal cancer treated between June, 1996 and December, 1999 was performed. Overall survival was compared between patients who underwent first-line resection of the primary colorectal tumor (group 1) or those who did not undergo elective resection of the primary (group 2). The probability of surgical resection of the primary tumor for gastrointestinal complications in group 2 was evaluated.
                Thirty-one and 23 patients were included in groups 1 and 2 respectively. Five patients (21.7%, 95% confidence interval CI95% 4.9-38.5%) in group 2 required surgical treatment for intestinal obstruction due to the primary tumor. Two clinical characteristics were significantly different between groups 1 and 2: rectal localization (9.7% versus 34.7%; P=0.03) and presence of fewer than three metastases (29.0% versus 4.3%; P=0.03). Survival curves were not significantly different (logrank). Median duration of survival was 21 and 14 Months, respectively (P=0.718).
                In patients with non-resectable synchronous metastatic disease, non-surgical management of the primary tumor is a rational alternative if asymptomatic. A prospective randomized trial integrating the quality-of-life factor should be organized. The aim of this case-matched study was to determine the best treatment strategy for patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases.
                Between 1997 and 2002, 27 patients with asymptomatic colorectal cancer and irresectable synchronous liver metastases were treated by chemotherapy without initial primary resection (chemotherapy group). These 27 patients were compared with 32 patients matched for age, sex, performance status, primary tumour location, number of liver metastases, nature of irresectable disease and type of chemotherapy, but who were treated initially by resection of primary tumour (resection group).
                The 2-year actuarial survival rate was 41 per cent in the chemotherapy group and 44 per cent in the resection group (P = 0.753). In the latter group, the mortality and morbidity rates for primary resection were 0 and 19 per cent (six of 32 patients) respectively. In the chemotherapy group, intestinal obstruction related to the primary tumour occurred in four of 27 patients. The mean overall hospital stay was 11 days in the chemotherapy group and 22 days in the resection group (P = 0.003).
                Systemic chemotherapy without resection of the bowel cancer is the option of choice because, for most patients, it is associated with a shorter hospital stay and avoids surgery without a detrimental effect on survival.
                Copyright 2005 British Journal of Surgery Society Ltd. About half the patients treated with curative resection for colorectal cancer do not survive long-term. Adjuvant chemotherapy given during and after surgery may prevent hepatic metastases and improve patient survival. In patients with colorectal cancer, we have done a multicentre, randomised controlled trial comparing five-year survival after intraportal infusion of fluorouracil (1 g per day) plus heparin (10,000 U per day) (130 patients) or heparin alone (123) during curative resection and for 7 days thereafter, or after resection alone (145). There was no reduction in liver metastasis or increased overall survival advantage in either active-treatment arm of the study. However, patients who had stage III, Dukes' C (lymph-node-positive) tumours resected and were treated with fluorouracil plus heparin had a significant (p less than 0.03) survival advantage of about 16% compared with surgery-only controls. Further study of intraportal infusion of chemotherapeutic agent as adjuvant treatment to surgery in patients with colorectal cancer appears worthwhile. Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability.
                Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added.
                A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm.
                A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least. A prospective randomized controlled trial (RCT) of multimodal perioperative management protocol in patients undergoing elective colorectal resection for cancer.
                This study evaluates the use of a multimodal package in colorectal cancer surgery in the context of an RCT.
                Patients for elective resection for colorectal cancer were offered trial entry. Participants were stratified by sex and requirement for a total mesorectal excision and centrally randomized. Multimodal patients received intravenous fluid restriction, unrestricted oral intake with prokinetic agents, early ambulation, and fixed regimen epidural analgesia. Control patients received intravenous fluids to prevent oliguria, restricted oral intake until return of bowel motility, and weaning regimen epidural analgesia. Adherence to both regimens was reinforced using a daily checklist and protocol guidance sheets. Discharge decision was made using pre-agreed criteria. The primary endpoint was postoperative stay, and achievement of independence milestones. Secondary endpoints were postoperative complications, readmission rates, and mortality. Analysis was by intention to treat.
                Seventy patients were recruited. Approximately one fourth underwent TME. Median ages were similar (69.3 vs. 73.0 years). The median stay was significantly reduced in the multimodal group (5 vs. 7 days; P < 0.001, Mann-Whitney U test). Patients in the control arm were 2.5 times as likely to require a postoperative stay of more than 5 days. Patients in the multimodal group had less cardiorespiratory and anastomotic complications but more readmissions. There were 2 deaths, both controls.
                This RCT provides level 1b evidence that a multimodal management protocol can significantly reduce postoperative stay following colorectal cancer surgery. Morbidity and mortality are not increased.
Resection of the primary tumour in asymptomatic patients with unresectable stage IV colorectal cancer who are managed with chemo/radiotherapy is not associated with a consistent improvement in overall survival. In addition, resection does not significantly reduce the risk of complications from the primary tumour (i.e.  obstruction, perforation or bleeding). Yet there is enough doubt with regard to the published literature to justify further clinical trials in this area. The results from an ongoing high quality randomised controlled trial will help to answer this question.