For rectal cancer with unresectable metastases, current practice favors omitting interventions directed at the primary tumor in asymptomatic patients.

This study aimed to determine the proportion of patients with primary tumor-related complications, characterize salvage outcomes, and measure survival in patients with metastatic rectal cancer who did not undergo upfront intervention for their primary tumor.

This is a retrospective analysis.

This study was conducted at a comprehensive cancer center.

Patients who presented between January 1, 2008, and December 31, 2015, with synchronous stage IV rectal cancer, an unresected primary tumor, and no prior primary tumor-directed intervention were selected.

The main outcome measured was the rate of primary tumor-related complications in the cohort that did not receive any primary tumor-directed intervention. The Kaplan-Meier method and Cox regression analysis were used to determine whether complications are associated with survival.

The cohort comprised 358 patients with a median age of 56 years (22-92). Median follow-up was 26 months (range, 1-93 months). Among the 168 patients (46.9%) who eventually underwent elective resection of the primary tumor, the surgery was performed with curative intent in 66 patients (18.4%) and preemptive intent in 102 patients (28.5%). Of the 190 patients who did not undergo an upfront or elective intervention for the primary tumor, 68 (35.8%) experienced complications. Nonsurgical intervention for complications was attempted in 34 patients with an overall success rate of 61.8% (21/34). Surgical intervention was performed in 47 patients (including 13 patients for whom nonsurgical intervention failed): diversion in 26 patients and resection in 21 patients. Of those 47 patients, 42 (89.4%) ended up with a colostomy or ileostomy.

This study was conducted at a single center.

A significant proportion of patients with metastatic rectal cancer and untreated primary tumor experience primary tumor-related complications. These patients should be followed closely, and preemptive intervention (resection, diversion, or radiation) should be considered if the primary tumor progresses despite systemic therapy. See Video Abstract at http://links.lww.com/DCR/B400. COMPLICACIONES RELACIONADAS CON EL TUMOR PRIMARIO Y RESULTADOS DE RESCATE EN PACIENTES CON CÁNCER DE RECTO METASTÁSICO Y UN TUMOR PRIMARIO NO TRATADO: Para el cáncer de recto con metástasis no resecables, la práctica actual favorece la omisión de las intervenciones dirigidas al tumor primario en pacientes asintomáticos.Determinar la proporción de pacientes con complicaciones relacionadas con el tumor primario, caracterizar los resultados de rescate y medir la supervivencia en pacientes con cáncer rectal metastásico que no se sometieron a una intervención inicial para su tumor primario.Análisis retrospectivo.Centro oncológico integral.Pacientes que se presentaron entre el 1 de enero de 2008 y el 31 de diciembre de 2015 con cáncer de recto en estadio IV sincrónico, un tumor primario no resecado y sin intervención previa dirigida al tumor primario.Tasa de complicaciones relacionadas con el tumor primario en la cohorte que no recibió ninguna intervención dirigida al tumor primario. Se utilizó el método de Kaplan-Meier y el análisis de regresión de Cox para determinar si las complicaciones están asociadas con la supervivencia.La cohorte estuvo compuesta por 358 pacientes con una mediana de edad de 56 años (22-92). La mediana de seguimiento fue de 26 meses (rango, 1 a 93 meses). Entre los 168 pacientes (46,9%) que finalmente se sometieron a resección electiva del tumor primario, la cirugía se realizó con intención curativa en 66 pacientes (18,4%) y con intención preventiva en 102 pacientes (28,5%). De los 190 pacientes que no se sometieron a una intervención inicial o electiva para el tumor primario, 68 (35,8%) experimentaron complicaciones. Se intentó una intervención no quirúrgica para las complicaciones en 34 pacientes con una tasa de éxito global del 61,8% (21 de 34). La intervención quirúrgica se realizó en 47 pacientes (incluidos 13 pacientes en los que falló la intervención no quirúrgica): derivación en 26 pacientes y resección en 21 pacientes. De esos 47 pacientes, 42 (89,4%) terminaron con una colostomía o ileostomía.Único centro.Una proporción significativa de pacientes con cáncer de recto metastásico y primario no tratado experimentan complicaciones relacionadas con el tumor primario. Se debe hacer un seguimiento estrecho de estos pacientes y considerar la posibilidad de una intervención preventiva (resección, derivación o radiación) si el tumor primario progresa a pesar de la terapia sistémica. Consulte Video Resumen en http://links.lww.com/DCR/B400.

Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short- and long-term outcomes is important.

All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients.

Median follow-up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long-term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists-score III to IV (HR: 1.51) had an impaired survival.

Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.

We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC).

We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens.

The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients.

Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.

The prognosis of patients with rectal cancer and synchronous liver metastasis has improved thanks to chemotherapy and rectal and liver surgery progresses. However, there is no consensus about optimal management and practices remain heterogeneous. A curative treatment may be considered for 20 to 30% of patients with complete resection of metastasis and primary tumor after induction chemotherapy. To this end, a primary optimal evaluation by a multidisciplinary board including hepatic and colorectal surgeons is crucial. The therapeutic strategy associates chemotherapy, radiotherapy, hepatic and rectal surgery. The most threatening site guides the sequence of treatments. If hepatic resectability is uncertain, a "liver first" strategy associating induction chemotherapy and hepatic surgery is preferred. In non-resectable metastatic cases, chemotherapies with targeted therapies might lead to secondary resection for 30% of patients (conversion). This has changed our practice and triggers reconsidering resectability after chemotherapy. When metastases remain non-resectable, additional treatment focusing on primary tumor should control pelvic symptoms otherwise hardly impacting quality of life. Rectal surgery, short-course radiotherapy (5×5Gy), conformational long-course chemoradiotherapy or intensity-modulated radiation therapy with dose escalation are options discussed in this review.

The aim of this study was to evaluate the impact of extended resection of primary tumor on survival outcome in unresectable colorectal cancer (UCRC).

A retrospective analysis was conducted for 190 patients undergoing palliative surgery for UCRC between 1998 and 2007 at a single institution. Variables including demographics, histopathological characteristics of tumors, surgical procedures, and course of the disease were examined.

Kaplan-Meier survival curve indicated a significant increase in survival times in patients undergoing extended resection of the primary tumor (P < 0.001). Multivariate analysis showed that extra-abdominal metastasis (P = 0.03), minimal resection of the primary tumor (P = 0.034), and the absence of multimodality adjuvant therapy (P < 0.001) were significantly associated poor survival outcome. The histological characteristics were significantly associated with survival times. Patients with well to moderate differentiation tumors that were extensively resected had significantly increased survival time (P < 0.001), while those with poor differentiation tumors that were extensively resected did not have increase survival time (P = 0.786).

Extended resection of primary tumors significantly improved overall survival compared to minimal resection, especially in well to moderately differentiated tumors (survival time: extended resection, 27.8 ± 2.80 months; minimal resection, 16.5 ± 2.19 months; P = 0.002).

The aim of this study is to evaluate the effect of neoadjuvant chemoradiotherapy in stage IV rectal cancer.

Primary rectal cancer patients with synchronous distant metastases between September 2001 and August 2011 were enrolled. Of 86 patients, 40 patients underwent neoadjuvant chemoradiotherapy (RTX group) and the remaining 46 patients underwent postoperative systemic chemotherapy without radiotherapy (NRTX group). Sharp mesorectal excision according to tumor location was performed. Oncologic outcomes were compared.

The lower tumor location was more common in RTX group than NRTX group (60.0 vs. 28.3%, P = 0.003). Clinical T and N status and American Society of Anesthesiologist (ASA) score were similar in both groups. The incidence of pathologic LN metastases in the NRTX group was 93.5% compared with 70.0% in RTX group (P = 0.007). Pattern of distant metastasis was similar between groups. However, metastatectomy was frequently performed in RTX group than NRTX group (57.5 vs. 30.4%, P = 0.020). There was no statistical difference in local recurrence rate between groups (10.0% in RTX vs. 15.2% in NRTX, P = 0.470). The median PFS was similar in both groups (12.00 months in RTX vs. 12.00 months in NRTX, P = 0.768). The median OS between groups was also not different (24.00 months in RTX vs. 27.00 months in NRT, P = 0.510).

Neoadjuvant chemoradiotherapy may not affect local control and overall survival in locally advanced rectal cancer with distant metastasis.

To evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC).

Primary tumour resection in this setting remains controversial.

We retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint).

Amongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n =3 32 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53-0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70-0.95]; p < 0.001).

Primary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, with a high mortality rate, particularly among patients with advanced-stage disease complicated by bowel obstruction. The present study aimed to investigate the value of different surgical procedures and potential predictors of survival for patients with stage IV CRC, with or without bowel obstruction. Between August, 1994 and December, 2005, a total of 2,950 CRC patients were diagnosed and treated at our hospital. Among these, 381 patients had stage IV disease and were divided into two groups according to the presence (n=295) or absence (n=86) of bowel obstruction. The clinical data of all the patients with stage IV CRC were retrospectively analyzed and all the patients were followed up. Our results demonstrated statistically significant differences in gender, radical resection, histological type, ascites, tumor location, peritoneal and liver metastases between the obstruction and non-obstruction groups. We also observed that hepatic metastases and radical resection were factors associated with prognosis according to the univariate and multivariate analyses. Furthermore, the mean/median survival time was 49.4/21.6 and 37.2/17.1 months in the non-obstruction and obstruction groups, respectively. In conclusion, obstruction was not found to be an independent indicator of survival for patients with stage IV CRC, with patients in the obstruction group exhibiting a worse overall survival compared to those in the non-obstruction group, whereas active radical surgery significantly improved the prognosis of patients with stage IV CRC.

The prognosis for colorectal cancer (CRC) patients with unresectable metastases is dismal. This study compared outcomes of different metastatic treatments.

We collected 653 CRC cases with unresectable metastases including 490 cases receiving primary tumor resection then chemotherapy (surgery group) and 163 patients receiving neoadjuvant chemotherapy then did or did not receive operations (chemotherapy (C/T) group) from 2004 to 2010. The statistical endpoint was overall survival from the date of diagnosis.

In the C/T group, 124 (76%) patients received an operation after 9.0 ± 6.2 months of chemotherapy, including 57 (34.9%) patients with curative surgery. The C/T group had a higher proportion of T4 lesions (37.4%) than the surgery group (26.9%). Survival of the C/T group was longer than that of the surgery group (28.8 ± 8.8 vs. 24.3 ± 7.5 months; p = 0.043). Survival of 57 patients receiving curative surgery was 36.0 ± 6.3 months, which was significantly better than that of the 67 patients receiving palliative resection (25.2 ± 5.6, p < 0.001). In the surgery group, 42 (8.6%) patients received curative metastasectomy after 8.5 ± 7.1 months of postoperative chemotherapy; survival was 30.8 ± 7.8 months, which was significantly better than that of patients who did not receive metastasectomy (22.4 ± 6.3 months). In multivariate analysis, poor differentiation, lymphovascular invasion, isolated cancer nodules, clinical risk score, and curative surgery were independent prognostic factors of overall patient survival.

Neoadjuvant chemotherapy can improve outcome of CRC patients with unresectable metastases.

Surgical resection of the primary tumour in patients with advanced colorectal cancer (crc) remains controversial. This review compares survival in patients with advanced crc who underwent surgical resection of the primary tumour with that in patients not undergoing resection, and determines rates of post-operative mortality and nonfatal complications, the primary tumour complication rate, the non-resection surgical procedures rate, and quality of life (qol).

Reports in the central, medline, and embase databases were searched for relevant studies, which were selected using pre-specified eligibility criteria. The search was also restricted to publication dates from 1980 onward, the English language, and studies involving human subjects. Screening, evaluation of relevant articles, and data abstraction were performed in duplicate, and agreement between the abstractors was assessed. Articles that met the inclusion criteria were assessed for quality using the Newcastle-Ottawa Scale. Data were collected and synthesized per protocol.

From among the 3379 reports located, fifteen retrospective observational studies were selected. Of the 12,416 patients in the selected studies, 8620 (69%) underwent surgery. Median survival was 15.2 months (range: 10-30.7 months) in the resection group and 11.4 months (range: 3-22 months) in the non-resection group. Hazard ratio for survival was 0.69 [95% confidence interval (ci): 0.61 to 0.79] favouring surgical resection. Mean rates of postoperative mortality and nonfatal complications were 4.9% (95% ci: 0% to 9.7%) and 25.9% (95%ci: 20.1% to 31.6%) respectively. The mean primary tumour complication rate was 29.7% (95% ci: 18.5% to 41.0%), and the non-resection surgical procedures rate in the non-resection group was 27.6% (95 ci: 15.4% to 39.9%). No study provided qol data.

Although this review supports primary tumour resection in advanced crc, the results have significant biases. Randomized trials are warranted to confirm the findings.

This Japanese multicenter retrospective study evaluated short- and long-term outcomes of palliative laparoscopic procedures for symptomatic stage IV colorectal cancer compared with conventional open procedures.

Of 968 eligible patients with stage IV colorectal cancer enrolled during January 2006-December 2007 from 41 participating surgical units (Japan Society of Laparoscopic Colorectal Surgery Group), we studied 409 patients who underwent palliative resection of symptomatic primary colorectal tumor.

Data from patients with laparoscopic resection (n = 98) and open colorectal resection (n = 311) were analyzed. Eleven (11.2 %) laparoscopic operations were converted to an open procedure. Fewer complications were reported for laparoscopic resections than for open procedures (13.3 vs. 26.7 %; p = 0.0042). Postoperative hospital stay was significantly shorter in the laparoscopic vs. open resection group (median, 14 vs. 17 days; p = 0.0242). Postoperative chemotherapy treatment was administered to 245 (78.9 %) patients in the open and 78 (79.6 %) patients in the laparoscopic resection group. Time from surgery to start of postoperative chemotherapy was significantly shorter in the laparoscopic vs. open resection group (median, 32 vs. 27 days; p = 0.0487). Median survival time between the two groups was not significantly different (22.0 vs. 22.2 months; p = 0.948).

Laparoscopic palliative resection results in reduced postoperative complications and earlier recovery with acceptable long-term outcomes comparable with open surgery. When performed by experienced surgeons in selected patients, it may be a safe and feasible option. Because of the potential of significant bias arising from the included studies, further randomized controlled trials should be undertaken to confirm this bias.

In a majority of patients with stage IV colorectal cancer, the metastatic disease is not resectable and the focus of management is on how best to palliate the patient. How to manage the primary tumour is an important part of palliation. A small proportion of these patients present with either obstructing or perforating cancers and require urgent surgical care. However, a majority are relatively asymptomatic from their primary cancer. Chemotherapy has been shown to prolong survival in this group of patients, and a majority of patients would be treated this way. Nonetheless, A recent meta-analysis (Stillwell 2010) suggests an improved overall survival and reduced requirement for emergency surgery in those patients who undergo primary tumour resection. This review was also able to quantify the mortality and morbidity associated with surgery to remove the primary.

To determine if there is an improvement in overall survival following resection of the primary cancer in patients with unresectable stage IV colorectal cancer and an asymptomatic primary who are treated with chemo/radiotherapy.

In January 2012 we searched for published randomised and non-randomised controlled clinical trials without language restrictions using the following electronic databases: CENTRAL (the Cochrane Library (latest issue)), MEDLINE (1966 to date), EMBASE (1980 to date), Science Citation Index (1981 to date), ISI Proceedings (1990 to date), Current Controlled Trials MetaRegister (latest issue), Zetoc (latest issue) and CINAHL (1982 to date).

Randomised controlled trials and non-randomised controlled studies evaluating the influence on overall survival of primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who are treated with palliative chemo/radiotherapy.

We conducted the review according to the recommendations of The Cochrane Collaboration and the Cochrane Colorectal Group. "Review Manager 5" software was used.

A total of 798 studies were identified following the initial search. No published or unpublished randomised controlled trials comparing primary tumour resection versus no resection in asymptomatic patients with unresectable stage IV colorectal cancer who were treated with chemo/radiotherapy were identified. Seven non-randomised studies, potentially eligible for inclusion, were identified: 2 case-matched studies, 2 CCTs and 3 retrospective cohort studies. Overall, these trials included 1.086 patients (722 patients treated with primary tumour resection, and 364 patients managed first with chemotherapy and/or radiotherapy).

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.

Patients with stage IV colorectal cancer with unresectable metastases can either receive chemotherapy or palliative resection of the primary lesion. In the absence of any randomized data the choice of initial treatment in stage IV colorectal cancer is not based on firm evidence.

A search of MEDLINE, Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010 for studies comparing palliative resection in stage IV colorectal cancer with other treatment modalities. Audits and observational studies were excluded. Median survival was the primary outcome measure. The morbidity and mortality of surgical and nonsurgical treatments were compared.

Twenty-one studies (no randomized controlled trials) were identified. Most demonstrated a survival benefit for patients who underwent palliative resection. Multivariate analysis indicates that tumour burden and performance status are both major independent prognostic variables. Selection bias, incomplete follow up and nonstandardized reporting of complications make the data difficult to interpret.

The studies indicate that there may be a survival benefit for primary resection of colorectal cancer in stage IV disease. The findings suggest that resection of the primary tumour should be based on tumour burden and performance status rather than on the presence or absence of symptoms alone.

The purpose of this study was to evaluate short-term and oncologic outcomes of laparoscopic resection (LR) for patients with symptomatic stage IV colorectal cancer compared with open resection (OR).

This study is a retrospective analysis of a prospective database. Patients with a minimum follow-up of 12 months after LR or OR for metastatic colorectal cancer were included. All analyses were performed on an "intention-to-treat" basis.

A total of 162 consecutive patients submitted to LR and 127 submitted to OR were included. In the LR group, conversion rate was 26.5 %, mostly due to locally advanced disease (88.4 %). A greater risk of conversion was observed among patients with a tumor size greater than 5 cm regardless the tumor site (P = 0.07). Early postoperative outcome was significantly better for LR group, with a shorter hospital stay (P = 0.008), earlier onset of adjuvant treatment, and similar postoperative complications (P = 0.853) and mortality rates (P = 0.958). LR for rectal cancer was associated with a higher morbidity compared with colon cancer (P = 0.058). During a median follow-up time of 72 months, there was no significant difference in overall survival between the two groups (P = 0.622).

LR for symptomatic metastatic CRC is safe and, compared with OR, is associated with a shorter hospital stay and with similar survival rates. Concerns remain about LR of bulky tumors and rectal cancers due to the increased risk of conversion and postoperative complications.

The aim of this study was to investigate the use of resection in a cohort of palliatively treated patients with stage IV rectal cancer. To avoid selection bias, particular attention was paid to correction for comorbidity and extent of disease.

Patients with stage IV rectal cancer in two hospitals in Groningen were consecutively included over a 5-year period. Comorbidity was defined as major (dementia, cardiac failure or left ventricle ejection fraction <30%, or severe chronic obstructive pulmonary disease), minor (diabetes, hypertension, mild renal disease or mild pulmonary disease) or none. The effect of patient and disease characteristics on survival was assessed using Kaplan-Meier and Cox regression analyses.

Of 88 patients, 11 (13%) underwent elective surgical resection without chemotherapy, 15 (17%) received both elective resection and chemotherapy, 21 (24%) underwent palliative chemotherapy only and 41 (47%) had supportive care only. The extent of disease (P<0.01), hospital (P=0.02) and comorbidity (P=0.04) were correlated with worse survival. Patients treated surgically survived for longer than patients treated nonsurgically, when the data were corrected for age, comorbidity, extent of disease and hospital [hazard ratio (HR)=0.4 (95% CI=0.2-0.7)]. Perioperative morbidity was seen in 38% of the patients, and 30-day mortality was 0%.

In this retrospective cohort, resection was associated with longer survival independently of the extent of distant metastases, age and comorbidity.

Optimal management of asymptomatic generalized rectal cancer is still the matter of debate. The aim of the study was to review stage IV rectal cancer patients who were treated in our clinic since 2000 till 2008 in order to evaluate the effectiveness of surgery.

Fifty-two generalized rectal cancer patients treated with elective resection of primary tumor were identified. Patients' age, sex, duration of hospital stay, modality of surgery, complications, postoperative mortality rate and survival rate were assessed.

Median survival was 16.3 months. Postoperative complications occurred in 29% patients. Postoperative mortality rate was 1.9%.

In properly selected group of patients elective resection of primary tumor may cause low mortality rate and acceptable morbidity rate. This surgical modality allows to avoid potential complications of tumor local growth.

With the improvements in newer chemotherapeutic agents, the role of primary tumour resection in patients with stage IV colorectal cancer is controversial. In many cases primary tumour resection is still favoured as first-line management. However, a detailed understanding of independent prognostic factors related to survival is necessary before making this decision.

A literature search was conducted using Medline and Embase. Studies that performed multivariate analysis on overall survival of patients with incurable stage IV colorectal cancer were included in this review.

Fourteen retrospective studies involving 3209 patients were included. Clinical variables analysed to consistently have independent prognostic significance for long-term survival included the patients' performance status (<2), volume of liver metastases (<50%), nodal stage (N0), disease-free resection margins, and treatment with chemotherapy and/or primary tumour resection. Cancer antigen (CA) 19-9, low albumin, elevated ALP levels, apical lymph node involvement, presence of ascites, and postoperative transfusion were each assessed by only one study and found to be independently associated with survival. Factors inconsistently reported to have independent prognostic significance were age, ASA score, preoperative CEA levels, primary tumour location, tumour size and differentiation, peritoneal dissemination, and extrahepatic metastases.

Each patient should be reviewed individually on the basis of the above independent prognostic factors before deciding to resect the primary tumour. Patients with a poor performance status, extensive hepatic metastases, and extensive nodal disease detected preoperatively are less likely to have a survival benefit. Nonsurgical approaches to manage these patients should be given careful consideration.

Latinos in the US experience a 60% higher death rate from primary hepatocellular carcinoma (HCC) when compared to Non-Latinos. The goal of this study was to examine risk factors that are associated with ethnic disparities among HCC patients seen at the transplant center of a metropolitan medical center in New York City. We compared HCC risk factors in 140 Non-Latino and 55 Latino patients that presented with HCC from 1995 to 2003. Surnames were used to define Latino and Non-Latino HCC patients in a retrospective analysis. Latino and Non-Latino HCC patients did not vary by gender or age at presentation (mean Latino age 60.8). Latino HCC patients had a higher frequency of presentation with advanced disease, defined as patients with unresectable HCC, than non Latino HCC patients (Latino 52.7%; 95% CI 39.1-66.3 vs. Non-Latino vs. 36.4%; 95% CI 28.3-44.4). Latinos were more likely than Non Latinos to have underlying HCV (34.5 vs. 22.1%, P < .0001; adjusted odds ratio [Siegel, 2008 #564], 3.69; 95% CI, 1.16-11.7) and cryptogenic liver diseases (7.2 vs. 3.5%, P < .0001; OR 8.86; 95% CI, 1.21-65.0) after adjusting for age, gender and alfa-fetoprotein levels. Although more advanced disease may signal delay in access to care or more aggressive disease, HCV infection and cryptogenic cirrhosis at presentation are likely key factors for the greater burden of HCC among Latinos in New York City.

Despite the encouraging results of chemotherapy in patients affected by incurable colorectal cancer (CRC), surgical resection of a primitive tumor is still a common approach worldwide. The identification of prognostic factors related to short survival (<6 months) may allow excluding from resective surgery those who may not benefit from it.

A retrospective analysis was performed of 15 variables in a population of 71 patients undergoing nonemergency palliative primary resections of incurable CRC, including patients' demographics and clinical/histopathological characteristics of the tumor.

No variables were related to perioperative mortality (8.5% overall). A multivariate analysis revealed that older age (≥80 years) and metastasis to more than 25% of the lymph nodes were associated with survival (4 and 6 months, respectively). Mucoid adenocarcinoma therefore tends to be associated with the prognosis (P = 0.070).

An elderly age tends to be a contraindication to an elective primary tumor resection in patients affected by incurable CRC. Massive lymph node involvement and mucoid adenocarcinoma should also be considered before planning major colonic surgery.

To determine the factors affecting the survival in colorectal cancer patients with synchronous liver metastases.

A total of 168 patients who had been treated colorectal cancer with synchronous liver metastases at Guangxi Medical University from January 2000 to December 2005 were identified. Criteria studied consisted of gender, age, time of symptoms, primary tumour location, primary tumour circumference, histological type, grade (tumour differentiation), T-status, N-status, large bowel obstruction, type of operation, primary tumour resection, ascities, location, number and diameter of liver lesions, preoperative CEA and chemotherapy. Survival curves were plotted using the Kaplan-Meier method. Multivariate analysis was conducted by Cox regression analysis.

The mean survival time for all patients was 18.71 (SEM = 1.59) months. The 1, 2, 3 and 5-year survival rates were 55.95%, 23.21%, 12.30%, 8.0% respectively. Univariate analysis share of grade (tumour differentiation), N-status, large bowel obstruction, operation, primary tumour resection, location, number and the most diameter of liver lesions, extrahepatic transfer, preoperative CEA level and chemotherapy to be predictors of survival. In the Cox regression analysis, the N-status, large bowel obstruction, operation, diameter of liver lesion and extrahepatic transfer were independent factors related to survival.

Tumour differentiation, N-status, bowel obstruction, operation, primary tumour resection, location of liver metastasis, number of liver metastasis, diameter of liver metastasis, extrahepatic transfer, preoperative CEA level and chemotherapy are related to the survival of patients with colorectal cancer and synchronous liver metastases.

Metastatic colorectal cancer traditionally has been considered incurable. Over the past 3 decades, however, resection of low-volume hepatic disease has been recognized as beneficial in some cases. More recently, resection of isolated pulmonary metastases has been shown to offer long-term survival in carefully selected patients. Resection of metastases to more unusual sites (ovary, brain, peritoneal cavity) is more controversial; nevertheless, retrospective data suggest that a few patients may be cured with resection of these tumors. In this article, we review the history and current status of metastasectomy in stage IV colorectal cancer.

BACKGROUND There is no consensus regarding the appropriate management of asymptomatic and minimally symptomatic patients with stage IV colorectal cancer and irresectable metastases. METHODS A literature search was conducted on Medline and Embase. Outcome measures included: survival; postoperative morbidity and mortality; complications from the primary tumor and the need for surgery to manage complications; the likelihood of curative surgery after initial response to primary therapy; and length of hospital stay. Quantitative meta-analysis was performed where appropriate. RESULTS Eight retrospective studies, including 1,062 patients, met the criteria for inclusion in this study. Meta-analysis has shown an improvement in the survival of patients managed with palliative resection of their primary tumor, with an estimated standardized median difference of 6.0 months (standardized difference, 0.55; 95% confidence interval (CI), 0.29, 0.82; p < 0.001). Patients managed with chemotherapy alone were 7.3 times more likely to have a complication from the primary tumor (95% CI, 1.7, 34.4; p = 0.008). There was no difference in the response rates to chemotherapy, making metastatic disease amendable to curative resection (0.85; 95% CI 0.40, 1.8; p = 0.662). CONCLUSIONS To date, only retrospective data are available, showing that palliative resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV colorectal cancer is associated with longer survival. Resection of the primary tumor reduces the likelihood of complications from the primary tumor and avoids the need for emergency procedures.

Here we present a concise review on the evaluation and management of locally recurrent rectal cancer, which despite marked reductions in the rate of recurrent rectal cancer remains an important problem.

This educational review discusses the diagnosis, evaluation, and management of recurrent rectal cancer.

Despite improvements in both the neoadjuvant and surgical management of rectal cancer, local recurrence is still an important problem, with documented recurrence rates of 4% to 8%. The local management of recurrence requires a team of specialist. Accurate detection and diagnosis followed by chemoradiotherapy and surgical resection may result in 5-year survival rates of up to 35%.

We discuss the diagnosis, evaluation, and management of locally recurrent rectal cancer. Locally recurrent rectal cancer can be successfully managed with multimodal therapy leading to successful palliation and often cure.

The optimal treatment strategy for rectal cancer (RC) with synchronous metastases remains an issue of debate. The aim of this study was to evaluate the impact of surgery and radiation on the control of pelvic symptoms in this setting.

Consecutive patients with RC and synchronous metastases were retrospectively assessed and divided into four treatment groups: surgical resection of rectal tumor (S); radiotherapy with/without chemotherapy followed by surgery (CRTS); chemoradiotherapy (CRT); and chemotherapy only (CT). Each group was evaluated in terms of duration of pelvic symptom-free periods (relative to overall survival).

A total of 96 patients were evaluated: S: n=30; CRTS: n=21; CRT: n=27; and CT: n=18. After treatment, pelvic symptoms persisted in 14.7% patients (S=0%, CRTS=7.1%, CRT=31.8%, CT=25%; P=0.01). The relative pelvic symptom-free periods were 93.0% in the S group, 83.1% in the CRTS group, 53.0% in the CRT group and 53.2% in the CT group (P<0.01). On multivariate analysis, only surgical treatment correlated with a significant relative pelvic symptom-free period (P<0.01), with an adjusted hazards ratio of 2.80 [95% CI: 1.79-4.39].

Our results suggest that rectal resection was the most effective therapeutic procedure in selected patients with RC and synchronous metastases, offering the patients the longest pelvic symptom-free periods.

The benefit of elective primary tumor resection for non-curable stage IV colorectal cancer (CRC) remains largely undefined. We wanted to identify risk factors for postoperative complications and short survival.

Using a prospective database, we analyzed potential risk factors in 233 patients, who were electively operated for non-curable stage IV CRC between 1996 and 2002. Patients with recurrent tumors, resectable metastases, emergency operations, and non-resective surgery were excluded. Risk factors for increased postoperative morbidity and limited postoperative survival were identified by multivariate analyses.

Patients with colon cancer (CC = 156) and rectal cancer (RC = 77) were comparable with regard to age, sex, comorbidity, American Society of Anesthesiologists score, carcinoembryonic antigen levels, hepatic spread, tumor grade, resection margins, 30-day mortality (CC 5.1%, RC 3.9%) and postoperative chemotherapy. pT4 tumors, carcinomatosis, and non-anatomical resections were more common in colon cancer patients, whereas enterostomies (CC 1.3%, RC 67.5%, p < 0.0001), anastomotic leaks (CC 7.7%, RC 24.2%, p = 0.002), and total surgical complications (CC 19.9%, RC 40.3%, p = 0.001) were more frequent after rectal surgery. Independent determinants of an increased postoperative morbidity were primary rectal cancer, hepatic tumor load >50%, and comorbidity >1 organ. Prognostic factors for limited postoperative survival were hepatic tumor load >50%, pT4 tumors, lymphatic spread, R1-2 resection, and lack of chemotherapy.

Palliative resection is associated with a particularly unfavorable outcome in rectal cancer patients presenting with a locally advanced tumor (pT4, expected R2 resection) or an extensive comorbidity, and in all CRC patients who show a hepatic tumor load >50%. For such patients, surgery might be contraindicated unless the tumor is immediately life-threatening.

According to the classification system of the Japanese Society for Cancer of the Colon and Rectum, Stage IV colorectal cancer is characterized by distant metastasis, which is defined by four factors: liver metastasis (H factor), metastasis to organs other than the liver (M factor), peritoneal dissemination (P factor), and distant lymph node metastasis (N factor). We conducted this study to investigate the postsurgical prognosis of patients with Stage IV colorectal cancer (CRC), in reference to each of these four factors.

We analyzed the medical records of 73 patients who underwent surgery for Stage IV CRC at our hospital between 1991 and 2001.

Univariate analysis revealed that P0 or P1 CRC (P < 0.001), absence of the M factor (P = 0.024), well or moderately differentiated adenocarcinoma (P < 0.001), resection of the primary tumor (P < 0.001), and curability B surgery (P < 0.0001) were associated with a better prognosis than other types of Stage IV CRC. Multivariate analysis revealed that tumor differentiation and surgical curability affected cancer-specific survival significantly.

Surgery with curative intent should be considered for patients with Stage IV CRC defined by the P1 factor or H factor.

In patients with asymptomatic colorectal cancer with irresectable metastatic disease, the optimal treatment strategy remains controversial. Resection of the primary tumor followed by chemotherapy when possible versus systemic chemotherapy followed by resection of the primary tumor when necessary are compared in this systematic review.

Seven studies reported series of patients with asymptomatic stage IV colorectal cancer and compared first-line chemotherapy with surgery for the primary tumor (n = 850 patients). Primary outcome measure was the complication rate related to the primary tumor in situ in patients receiving first-line systemic chemotherapy.

When leaving the primary tumor in situ, the mean complications were intestinal obstruction in 13.9% [95% confidence interval (CI) 9.6% to 18.8%] and hemorrhage in only 3.0% (95% CI 0.95% to 6.0%) of the patients. After resection, the overall postoperative morbidity ranged from 18.8% to 47.0%.

For patients with stage IV colorectal cancer, resection of the asymptomatic primary tumor provides only minimal palliative benefit, can give rise to major morbidity and mortality and therefore potentially delays beneficial systemic chemotherapy. When presenting with asymptomatic disease, initial chemotherapy should be started and resection of the primary tumor should be reserved for the small portion of patients who develop major complications from the primary tumor.

The time schedule for chemotherapy and primary tumor resection in patients with rectal carcinoma (RC) and unresectable synchronous metastases (USM) is not well defined. We evaluated whether response to chemotherapy is an appropriate criterion for deciding to perform surgery.

We treated 22 patients with RC and USM who received chemotherapy and were regularly evaluated. After documentation of a partial remission (PR) or stable disease (SD), patients were offered resection of the primary tumor. Results were compared with those of a historical control group of 42 patients who underwent immediate surgery.

Seven patients had a PR, four showed SD, and 11 progressed under chemotherapy. Seven patients underwent resection of the primary tumor (no perioperative mortality). The median survival for all 22 patients was 20.2 months. Patients with primary tumor resection survived 27.2 months, whereas patients without resection survived only 12.4 months (p = 0.017). The median survival in the control group was 13.5 months (perioperative mortality, 9.5%).

Chemotherapy and response-dependent resection of the primary tumor results in the same survival time as that attained with immediate surgery. Patients who face a poor prognosis due to progressive disease are thereby spared the risks of major rectal surgery.

Patients with metastatic colorectal cancer have a limited life expectancy and are at risk for life-threatening tumor-related obstruction, perforation, and hemorrhage. Though surgical resection is performed frequently in this setting, its true benefit is not well-established.

We reviewed the medical literature from 1996-2006 using the search terms metastatic colorectal cancer and primary resection to find studies that evaluated the management of primary tumors in metastatic colorectal cancer. All search results were included in our analysis and were assessed on the basis of methodologic quality.

Twelve relevant studies were identified; ten were single-institution retrospective reviews and two were population-based studies using National Cancer Institute's Surveillance, Epidemiology, and End-Results database. No prospective or randomized studies were identified. Approximately 70% of patients diagnosed with metastatic colorectal cancer in the USA undergo primary tumor resection; only a minority have this done for tumor-related symptoms or as part of potentially curative resection. The postoperative mortality ranged from 9.0-11.2% in large cancer registries but was often lower in major cancer centers. Resection of asymptomatic primary tumors was frequently associated with prolonged survival but was not found to reduce significantly the incidence of life-threatening tumor-related complications.

Retrospective data suggest that non-curative resection of asymptomatic colorectal primary tumors may prolong survival; however, selection bias and unaccounted clinical factors may explain this observation. Prospective, randomized surgical trials are needed to test the role of primary tumor resection in this setting, especially because of its current widespread use, and its associated cost, morbidity, and high postoperative mortality.

Whether resection of the primary tumour is of benefit to patients with incurable rectal cancer (RC) remains a matter of debate. In this study we analyse prospectively recorded data from a national cohort.

Among 4831 patients diagnosed with RC between 1997 and 2001, 838 (17%) patients were treated with palliative surgery. Patients were stratified according to disease stage, age and type of surgery.

A significantly longer median survival, 12 (range 10-13) months, was observed in patients treated with resection of the primary tumour compared with 5 (range 4-6) months in patients treated with nonresective procedures (P < 0.001). Median survival in months was significantly (P < 0.001) related to age (13; < 60 years of age, 10; 60 to 69 years, 7; 70 to 79 years, 6; >/= 80 years of age). In patients over 80 years, survival was similar regardless of the treatment. Thirty-day mortality varied from 2.5% to 20%, according to age groups.

The longer survival observed in patients with resection of the primary tumour may partly be explained by patient selection. Elderly patients (>/= 80 years) had a similar survival, irrespective of resection of the primary tumour or not. Careful consideration of the individual patient, extent of disease and treatment-related factors are important in decision-taking for palliative treatment for patients with advanced RC.

It is still a matter of debate as to whether resective surgery of the primary tumor may prolong the survival of patients affected by incurable colorectal cancer (CRC). The main goal of this retrospective study, carried out on patients not undergoing any therapy other than surgery, was to quantify the benefit of primary tumor removal in patients with differently presenting incurable CRC.

One hundred and thirty consecutive patients were operated on for incurable CRC (83 undergoing resective and 47 non-resective procedures). With the purpose of comparing homogenous populations and of identifying patients who may benefit from primary tumor resection, the patients were classified according to classes of disease, based on the "metastatic pattern" and the "resectability of primary tumor."

In patients with "resectable" primary tumors, resective procedures are associated with longer median survival than after non-resective ones (9 months vs 3). Only patients with distant spread without neoplastic ascites/carcinosis benefit from primary tumor removal (median survival: 9 months vs 3). Morbidity and mortality of resective procedures is not significantly different from that of non-resective surgery, either in the population studied or in any of the groups considered.

Palliative resection of primary CRC should be pursued in patients with unresectable distant metastasis (without carcinomatosis), and, intraoperatively, whenever the primary tumor is technically resectable.

About 50% of patients with colorectal cancer (CCR) are destined to develop hepatic metastases during the course of the disease. Surgery is currently the only potentially curative treatment with a five year survival rate after hepatectomy from 26% to 49%. The criteria for resectability are now less rigid than in the past and the tendency to adopt a more aggressive treatment of metastatic lesions is the rule. Systemic infusion chemotherapies based on 5-fluorouracil (5-FU), oxaliplatin (OHP) and irinotecan (CPT-11) are well tolerated and have been shown to be effective in non-operable patients. These regimens allow surgery for patients who are initially not suitable for resection, giving them a probability of survival at five years similar to that of patients operated on at diagnosis. Intra-arterial infusion chemotherapy (HAI) is very effective in inducing objective responses, but is costly, difficult to manage and encumbered by major side effects, so that its application is necessarily limited to centres with specific experience. However, despite the broader criteria and recent advances of chemotherapy, surgery is not possible in most patients. The role of other local therapeutic techniques like cryosurgery (CS) and radiofrequency ablation (RF), alone or combined with surgery or chemotherapy, is not yet established in a multidisciplinary therapeutic approach. Roughly two thirds of patients relapse during the first two years after surgery suggesting appropriate post-operative chemotherapy treatment after hepatic resection may be indicated, but no randomised studies have been published to date. In case of relapse, another hepatectomy should be considered. The role of novel targeted therapies in pre-operative, post-operative and palliative management has yet to be evaluated.

There is no consensus as to the management of the primary rectal cancer in the presence of distant metastasis and data on the outcomes of radical resection in stage IV rectal cancer are limited. This study aims to evaluate the results of resection of rectal cancer in the patients with stage IV disease and to analyze the factors that might affect the survival of these patients.

Of the 744 patients with radical resection of primary rectal and rectosigmoid cancer during the study period from August 1993 to July 2002, 70 had stage IV disease on the initial presentation. The demographics, the operative details, the tumor characteristics, the postoperative outcomes and survival of the patients were collected prospectively. Factors influencing the survival were analyzed with univariate and multivariate analysis.

Fifty-three men and 17 women with a median age of 66 years (range: 31-90 years) were included. The median level of the tumor from the anal verge was 10 cm (range 3-20 cm). The operations included abdominoperineal resection (n = 5), anterior resection (n = 53), and Hartmanns operation (n = 11). The operation mortality was 4.3%. The overall morbidity was 42.7% while the surgical morbidity and the reoperation rates were 15.7% and 5%, respectively. The local recurrence rate was 4.3% and the 2-year actuarial rate was 7.8%. All the patients who had local recurrences also had disseminated peritoneal metastasis. The median cancer-specific survival of the patients who survived the surgery was 15.2 months. Multivariate analysis showed that the presence of gross residual local disease, lymph node metastasis, liver involvement of over 50%, the absence of surgical management of liver metastasis and those without chemotherapy were independent factors associated with poor survival.

Postoperative mortality and morbidity were acceptable in patients with stage IV rectal cancer. The local disease can be controlled effectively with radical resection. However, in patients with extensive liver involvement and advanced local disease, resection is not worthwhile because of the poor survival. Surgical management of the metastasis and the administration of chemotherapy are associated with better survival. However, the optional treatment regimes are yet to be defined.

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.

Surgical management of patients with metastatic or recurrent rectal cancer remains controversial. Self-expanding metal stents are increasingly used for palliative treatment of advanced tumors, although long-term results are not yet available.

Between 1996 and 2003, 521 patients underwent surgery for rectal neoplasms. In the same time period, self-expanding metal stents were used for palliation of 34 patients with malignant rectal obstruction and incurable disease. The outcome of the patients was analyzed retrospectively.

Rectal stents were successfully placed in 33 of 34 patients (97%) without major complications. Early failure occurred in 7 patients (21%) because of stent migration, pain, or incontinence. Long-term success with a mean patency of 5.3 months was observed in 26 patients (79%), but restenting was required in 2 patients. Despite the initial success of stenting, a colostomy was created in 2 other patients after 3.4 months and 9.2 months because of incontinence and rectovesical fistula. Overall, 6 of 33 patients (18%) underwent palliative surgery because of early complications (n = 4) or long-term failure of stent treatment (n = 2).

Self-expanding metal stents are useful to avoid a colostomy in selected patients with incurable rectal cancer and limited life expectancy. Nonetheless, a considerable number (18%) of patients will require surgical palliation because of failure of stent treatment.

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.