Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

BACKGROUND: Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. OBJECTIVES: We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). SEARCH METHODS: CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* SELECTION CRITERIA: Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. DATA COLLECTION AND ANALYSIS: Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy) and the control arm (no adjuvant chemotherapy). The survival data were either entered directly in RevMan or extrapolated from Kaplan-Meier plots and then entered in RevMan. Due to expected clinical heterogeneity a random effects model was used for creating the pooled estimates of treatment efficacy. MAIN RESULTS: A total of 21 eligible RCTs were identified and used for meta-analysis purposes. Overall, 16,215 patients with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma. Considering patients with rectal cancer only, 4,854 cases were randomized to receive potentially curative surgery of the primary tumour plus adjuvant chemotherapy and 4,367 to receive surgery plus observation. The mean number of patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in Western countries and 10 in Japan. All trials used fluoropyrimidine-based chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological agents - were tested).Overall survival (OS) data were available in 21 RCTs and the data available for meta-analysis regarded 9,221 patients: of these, 4854 patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367 patients did not receive adjuvant chemotherapy (control arm). The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to those undergoing observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I-squared=30%) but significant (P=0.09) at the 10% alpha level.Disease-free survival (DFS) data were reported in 20 RCTs, and the data suitable for meta-analysis included 8,530 patients. Of these, 4,515 patients were randomized to postoperative chemotherapy (treatment arm) and 4,015 patients received no postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed a reduction in the risk of disease recurrence (25%) among patients undergoing adjuvant chemotherapy as compared to those undergoing observation (HR=0.75, CI: 0.68-0.83). Between-study heterogeneity was moderate (I-squared=41%) but significant (P=0.03).While analyzing both OS and DFS data, sensitivity analyses did not find any difference in treatment effect based on trial sample size or geographical region (Western vs Japanese). Available data were insufficient to investigate on the effect of adjuvant chemotherapy separately in different TNM stages in terms of both OS and DFS. No plausible source of heterogeneity was formally identified, although variability in treatment regimens and TNM stages of enrolled patients might have played a significant role in the difference of reported results. AUTHORS' CONCLUSIONS: The results of this meta-analysis support the use of 5-FU based postoperative adjuvant chemotherapy for patients undergoing apparently radical surgery for non-metastatic rectal carcinoma. Available data do not allow us to define whether the efficacy of this treatment is highest in one specific TNM stage. The implementation of modern anti-cancer agents in the adjuvant setting is warranted to improve the results shown by this meta-analysis. Randomized trials of adjuvant chemotherapy for patients receiving preoperative neoadjuvant therapy are also needed in order to define the role of postoperative chemotherapy in the multimodal treatment of resectable rectal cancer.

Preoperative mechanical bowel preparation in elective colorectal surgery: an update of systematic review of the literature and meta-analysis

The belief that mechanical bowel preparation is related to the reduction of complications in elective colorectal surgery is based on observational studies and expert opinion. This question led the authors to a systematic literature review, with the completion of meta-analysis, followed by three updates. METHOD: The sources of information were EMBASE, LILACS, MEDLINE, IBECS, the Cochrane Controlled Trials Register and letters to the authors. The studies were included according to the randomization criteria. The studied variables were: anastomotic dehiscence, mortality and operatory wound infection. The analysis was divided into two comparisons: one group with mechanical preparation (Group A) compared with a group without preparation (Group B) (Comparison I) and a group submitted to rectal enema (Comparison II). RESULTS: We analyzed 5,805 patients in 20 clinical trials. In comparison I, anastomotic leak occurred in 4.4% (101/2,275 patients) in Group A and 4.5% (103/2,258 patients) in Group B. In comparison II, anastomotic leak occurred in 4.4% (27/601 patients) in Group A and 3.4% (21/609 patients) in Group B. CONCLUSION: Despite the inclusion of more studies, evidences found in studies did not show any benefit obtained from the use of preoperative mechanical bowel preparation or rectal cleansing enemas in elective colorectal surgery. (AU)

A crença de que o preparo mecânico do cólon está relacionado à diminuição de complicações na cirurgia colorretal eletiva é baseada em estudos observacionais e opinião de especialistas. Seu questionamento motivou os autores na busca sistemática da literatura, com a realização de meta-análise, seguida de três atualizações. MÉTODO: Fontes de informação foram EMBASE, LILACS, MEDLINE, IBECS, Registros de Ensaios Clínicos Casualizados da Colaboração Cochrane e cartas para os autores. Os estudos foram incluídos de acordo com os critérios de casualização. Os desfechos clínicos estudados foram: deiscência anastomótica, mortalidade e infecção da ferida operatória. A análise dos grupos foi dividida em duas comparações: comparação I, grupo submetido a preparo mecânico do cólon (Grupo A) comparado ao grupo sem preparo (Grupo B); comparação II, Grupo A, submetido a preparo do cólon e Grupo B, realizado apenas enema retal. RESULTADOS: Foram analisados 5.805 doentes em 20 ensaios clínicos. Na comparação I, deiscência anastomótica ocorreu em 4,4% (101/2.275 doentes) no Grupo A e 4,5% (103/2.258 doentes) no Grupo B. Na comparação II, deiscência anastomótica ocorreu em 4,4% (27/601 doentes) no Grupo A e 3,4% (21/609 doentes) no Grupo B. CONCLUSÃO: Apesar da inclusão de mais estudos, as evidências encontradas não demonstraram benefício no uso do preparo mecânico pré-operatório do cólon, assim como de enemas de limpeza do reto em cirurgia colorretal eletiva. (AU)

Mechanical bowel preparation for elective colorectal surgery.

BACKGROUND: The presence of bowel contents during colorectal surgery has been related to anastomotic leakage, but the belief that mechanical bowel preparation (MBP) is an efficient agent against leakage and infectious complications is based on observational data and expert opinions only.An enema before the rectal surgery to clean the rectum and facilitate the manipulation for the mechanical anastomosis is used for many surgeons. This is analysed separately OBJECTIVES: To determine the security and effectiveness of MBP on morbidity and mortality in colorectal surgery. SEARCH STRATEGY: Publications describing trials of MBP before elective colorectal surgery were sought through searches of MEDLINE, EMBASE, LILACS, IBECS and The Cochrane Library; by handsearching relevant medical journals and conference proceedings, and through personal communication with colleagues.Searches were performed December 1, 2010. SELECTION CRITERIA: Randomised controlled trials (RCTs) including participants submitted for elective colorectal surgery. Eligible interventions included any type of MBP compared with no MBP. Primary outcomes included anastomosis leakage - both rectal and colonic - and combined figures. Secondary outcomes included mortality, peritonitis, reoperation, wound infection, extra-abdominal complications, and overall surgical site infections. DATA COLLECTION AND ANALYSIS: Data were independently extracted and checked. The methodological quality of each trial was assessed. Details of randomisation, blinding, type of analysis, and number lost to follow up were recorded. For analysis, the Peto-Odds Ratio (OR) was used as the default (no statistical heterogeneity was observed). MAIN RESULTS: At this update six trials and a new comparison (Mechanical bowel preparation versus enema) were added. Altogether eighteen trials were analysed, with 5805 participants; 2906 allocated to MBP (Group A), and 2899 to no preparation (Group B), before elective colorectal surgery.For the comparison Mechanical Bowel Preparation Versus No Mechanical Bowel Preparation results were:1. Anastomotic leakage for low anterior resection: 8.8% (38/431) of Group A, compared with 10.3% (43/415) of Group B; Peto OR 0.88 [0.55, 1.40].2. Anastomotic leakage for colonic surgery: 3.0% (47/1559) of Group A, compared with 3.5% (56/1588) of Group B; Peto OR 0.85 [0.58, 1.26].3. Overall anastomotic leakage: 4.4% (101/2275) of Group A, compared with 4.5% (103/2258) of Group B; Peto OR 0.99 [0.74, 1.31].4. Wound infection: 9.6% (223/2305) of Group A, compared with 8.5% (196/2290) of Group B; Peto OR 1.16 [0.95, 1.42].Sensitivity analyses did not produce any differences in overall results.For the comparison Mechanical Bowel Preparation (A) Versus Rectal Enema (B) results were:1. Anastomotic leakage after rectal surgery: 7.4% (8/107) of Group A, compared with 7.9% (7/88) of Group B; Peto OR 0.93 [0.34, 2.52].2. Anastomotic leakage after colonic surgery: 4.0% (11/269) of Group A, compared with 2.0% (6/299) of Group B; Peto OR 2.15 [0.79, 5.84].3. Overall anastomotic leakage: 4.4% (27/601) of Group A, compared with 3.4% (21/609) of Group B; Peto OR 1.32 [0.74, 2.36].4. Wound infection: 9.9% (60/601) of Group A, compared with 8.0% (49/609) of Group B; Peto OR 1.26 [0.85, 1.88]. AUTHORS' CONCLUSIONS: Despite the inclusion of more studies with a total of 5805 participants, there is no statistically significant evidence that patients benefit from mechanical bowel preparation, nor the use of rectal enemas. In colonic surgery the bowel cleansing can be safely omitted and induces no lower complication rate. The few studies focused in rectal surgery suggested that mechanical bowel preparation could be used selectively, even though no significant effect was found. Further research on patients submitted for elective rectal surgery, below the peritoneal verge, in whom bowel continuity is restored, and studies with patients submitted to laparoscopic surgeries are still warranted.

[Acute treatment of colon cancer]. / Akut behandling af coloncancer.

The primary treatment of left-sided colonic ileus due to cancer is after localisation of the tumor with water-soluble contrast enema placement of an intraluminal, self-expanding metal stent. If this treatment is unsuccessful, open resection with primary anastomosis is the treatment of choice. In the case of a perforated tumor, resection and primary anastomis may be performed if the patient s general condition is acceptable.

Clinical value of preoperative mechanical bowel cleansing in elective colorectal surgery: a systematic review.

PURPOSE: This study was designed to establish scientific evidence for and clinical results of preoperative mechanical bowel cleansing before elective colorectal surgery. METHODS: Systematic literature searches in electronic databases, conference proceedings, and hand searches of reference lists of previously retrieved literature without any language restrictions were used. Only randomized trials were included. A quality assessment of each retrieved trial was performed. Outcome measures were surgical infections, mortality, and anastomotic dehiscence. Meta-analyses of the selected trials were performed using the Peto odds ratio. RESULTS: The results of each outcome were as follows. 1). Overall anastomotic leakage-six studies: 5.5 percent with cleansing compared with 2.9 percent without cleansing; odds ratio 1.94, 95 percent confidence interval: 1.09 to 3.43 (P = 0.02). 2). Peritonitis-three studies: 5.1 percent with cleansing compared with 2.8 percent without cleansing; odds ratio 1.90, 95 percent confidence interval: 0.78 to 4.64 (not significant). 3). Wound infection-six studies: 7.4 percent with cleansing compared with 5.7 percent without cleansing; odds ratio 1.34, 95 percent confidence interval: 0.85 to 2.13 (not significant). CONCLUSIONS: There is no evidence in the literature for beneficial effects from the use of bowel cleansing before elective colorectal surgery. Cleansing seems to be associated with an increased risk of more anastomotic dehiscence. Further studies stratifying between rectal and colonic surgery are warranted.