Positive Circumferential Margin Research Articles

Rectal outcomes after a liver-first treatment of patients with stage IV rectal cancer.

The treatment of patients with metastatic rectal cancer remains controversial. We developed a reverse strategy, the liver-first approach, to optimize the chance of a curative resection. The aim of this study was to assess rectal outcomes after reverse treatment of patients with metastatic rectal cancer. From May 2000 to November 2013, a total of 34 consecutive selected patients with histology-proven adenocarcinoma of the rectum and liver metastases were prospectively entered into a dedicated computerized database. All patients were treated via our reverse strategy. Rectal and overall survival outcomes were analyzed. Most patients presented with advanced disease (median Fong clinical risk score of 3; range 2-5). One patient failed to complete the whole treatment (3%). Rectal surgery was performed after a median of 3.9 months (range 0.4-17.8 months). A total of 73.3% patients received preoperative radiotherapy. Perioperative mortality and morbidity rates were 0 and 27.3% after rectal surgery. Severe complications were reported in two patients (6.1%): one anastomotic leak and one systemic inflammatory response syndrome. The median hospital stay was 11 days (range 5-23 days). Complete local pathological response was observed in three patients (9.1%). The median number of lymph nodes collected was 14. The R0 rate was 93.9%. There was no positive circumferential margin. After a mean follow-up of 36 months after rectal surgery, 5-year overall survival was 52.5%. Five patients experienced pelvic recurrence. In our cohort of selected patients with stage IV rectal cancer, the reverse strategy was not only safe and effective, but also oncologically promising, with a low morbidity rate and high long-term survival.

583P - Impact of Adjuvant Chemotherapy (Ac) on Relapse-Free Survival (Rfs) is Different According to Post-Chemoradiation Pathologic Stage (Ypstage) in Rectal Cancer

ABSTRACT Aim: In contrast with colon cancer, survival benefit from adjuvant chemotherapy (AC) in rectal cancer is still unclear. For patients (pts) who are treated with preoperative chemoradiation (preop CRT), post-chemoradiation pathologic stage (ypStage) is known to be a major determinant of long term outcome. We aimed to describe clinical benefit from AC in terms of relapse-free survival (RFS) according to ypStage in rectal cancer. Methods: Retrospective analysis was done for data which were derived from prospective database of preop CRT - treated pts in National Cancer Center, Korea. Pts with initially nonmetastatic rectal cancer who received preop CRT followed by surgery (Jan 2001–Dec 2009) were included. Completeness of AC schedule was reviewed: undergoing chemotherapy cycles covering at least 16 weeks was considered completion. Results: Among a total of 743 pts, ypT0N0 or ypTisN0 (ypStage 0) / ypStage I/ ypStage II/ ypStage III/ ypStage IV were 119 (16.0%), 192 (25.9%), 203 (27.3%), 219 (29.5%), 10 (1.4%), respectively. 625 (84.1%) completed scheduled AC (fluoropyrimidine monotherapy in 95%), and 88 (11.8%) omitted or stopped AC, while 30 (4.0%) were excluded due to follow-up loss or disease progression. Completing AC was not associated with RFS in all pts (5-yr RFS 75.9% vs 73.6%, hazard ratio for relapse (HR) 0.95, p = 0.84), but significantly affected RFS in ypStage III (5-yr RFS 56.6% vs 21.4%, HR 0.45, p = 0.014). Among ypStage 0, I, and II, completing AC was not related to RFS (5-yr RFS 85.0% v 84.1%, HR 1.01, p = 0.969). Multivariate analysis revealed completion of AC was still a significant predictor of RFS after adjustment to initial carcinogembryonic antigen (CEA) level, nodal stage, and circumferential margin (CRM) status (table). HR (95% confidence interval) p value initial CEA 1.83 (1.22 - 2.76) 0.004 ypN2 2.08 (1.38 - 3.16) 0.001 completion of AC 0.37 (0.20 - 0.70) 0.002 positive CRM 2.21 (1.18 - 4.15) 0.014 Conclusions: Completion of AC affected RFS in ypstage III rectal cancer, while it did not in earlier stages. This study suggests survival benefit from AC could be limited to ypStage III in preop CRT treated rectal cancer. Disclosure: All authors have declared no conflicts of interest.

Perineal reconstruction after extralevator abdominoperineal excision(ELAPE) for carcinoma at the lower rectum

Extralevator abdominoperineal excision (ELAPE) has been described to improve the outcomes of advanced low rectal cancer, probably because of more pelvic dissection and less positive circumferential resection margin (CRM). Recent improvements of ELAPE have focused on the reconstruction of the large pelvic defect. Different approaches have been focused on the reconstruction including primary closure, uterus retroversion, omentoplasty, myocutaneous flaps, and biological mesh. The optimal method is still controversial. Recent reviews showed that the perineal wound complications of biological mesh reconstruction were comparable to those of myocutaneous flaps. Moreover reviews suggested the use of biologic materials to close the perineal defect because it offers a significant cost saving mostly attributable to reduction in hospital length of stay. The combination of different techniques may be the best way to reconstruct the pelvic defect following ELAPE.

Neoadjuvant chemoradiation with concomitant boost radiotherapy associated to capecitabine in rectal cancer patients.

The primary end-points were complete pathological response and local control. Secondary end-points were survivals, anal sphincter preservation, and toxicity profile. Patients with T3/T4 and or N+ rectal cancer (n = 65) were treated with preoperative concomitant boost radiotherapy (55 Gy/25 fractions) associated to concurrent chemotherapy with oral capecitabine. All patients completed the programmed treatment. The complete pathological response was achieved by 17 % of the patients. Anal sphincter preservation surgery was possible for 86 % of the patients with low rectal cancer (≤ 5 cm from the anal verge). The T-stage and N-stage downstaging were achieved by 40 and 58 % of the patients, respectively. Circumferential radial margin was involved (close/positive) in eight patients. After a median follow-up of 26 months, local and distant recurrence occurred in two and 11 patients, respectively. The 3-year overall survival and disease-free survival were 86.8 and 81 %, respectively. Non-hematological ≥ grade 3 toxicities were observed in 15 % of the patients. On univariate analysis N-downstaging and positive circumferential radial margin were significantly associated with worse overall survival (p = 0.003 and p = 0.023, respectively), disease-free survival (p = 0.001 and p = 0.036, respectively), and metastasis-free survival (MFS) (p = 0.001 and p = 0.038, respectively).On multivariate analysis, the N-downstaging were significantly associated with better overall survival (OS) (p = 0.022). Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Radiation treatment intensification may have a biological rationale; longer follow-up is needed.

Comparaison de deux schémas de radiochimiothérapie neo-adjuvante pour les cancers du rectum localement avancés. Résultats de la phase III ACCORD 12/0405-PRODIGE 2

PurposeNeoadjuvant chemoradiotherapy is considered a standard approach for T3–4 M0 rectal cancer. In this situation, we compared neoadjuvant radiotherapy plus capecitabine with dose-intensified radiotherapy plus capecitabine and oxaliplatin.Patients and methodsWe randomly assigned patients to receive 5 weeks of treatment with radiotherapy 45 Gy/25 fractions with concurrent capecitabine 800 mg/m2 twice daily 5 days per week (Cap 45) or radiotherapy 50 Gy/25 fractions with capecitabine 800 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m2 once weekly (Capox 50). The primary end point was complete sterilization of the operative specimen (ypCR).ResultsFive hundred ninety-eight patients were randomly assigned to receive Cap 45 (n = 299) or Capox 50 (n = 299). More preoperative grade 3 to 4 toxicity occurred in the Capox 50 group (25 v 1%; P <.001). Surgery was performed in 98% of patients in both groups. There were no differences between groups in the rate of conservative surgery (75%) or postoperative deaths at 60 days (0.3%). The ypCR rate was 13.9% with Cap 45 and 19.2% with Capox 50 (P =.09). When ypCR was combined with yp few residual cells, the rate was respectively 28.9% with Cap 45 and 39.4% with Capox 50 (P =.008). The rate of positive circumferential rectal margins (between 0 and 2 mm) was 19.3% with Cap 45 and 9.9% with Capox 50 (P =.02).ConclusionThe benefit of oxaliplatin was not demonstrated and this drug should not be used with concurrent irradiation. Cap 50 merits investigation for T3–4 rectal cancers.

Integration of open and laparoscopic approaches for rectal cancer resection: oncologic and short-term outcomes

Laparoscopy is increasingly used for rectal cancer surgery. Laparoscopic surgery is not attempted for some suitable patients because of concerns for conversion or technical difficulty. This study aimed to evaluate oncologic and short-term outcomes for patients undergoing curative resection for rectal cancer via laparoscopic and open approaches. A prospective database was reviewed to identify rectal cancer resections from 2005 to 2011. Patients who had primary rectal cancer within 15 cm of the anal verge were included in the study. Those with recurrent or metastatic disease were excluded. Patients were assigned to laparoscopic or open approaches preoperatively based on clinical criteria and imaging. All patients underwent a standard total mesorectal excision and followed a standardized enhanced recovery pathway. The oncologic and clinical outcomes were evaluated by approach. The analysis included 81 patients. The preoperative assignments consisted of 62 laparoscopic (77%) and 19 open (23%) procedures. Nine laparoscopic procedures (14.5%) were converted to open procedures. After a median follow-up period of 25 months, all oncologic outcomes were comparable. Three patients (two laparoscopic, one open) had a positive circumferential margin (≤1 mm). The laparoscopic and open groups were similar in terms of their 3-year disease-free periods (93.6 vs. 88.2%; P = 0.450) and overall survival periods (93.5 vs. 90.9%; P = 0.766). The local recurrence rate was 2.5%. Laparoscopic resection for rectal cancer can be attempted for most patients. Conversion to open procedure does not compromise clinical or oncologic outcomes. In practice, combining laparoscopic and open surgery optimizes resource use and results in at least equivalent outcomes.

Robotic-laparoscopic rectal cancer excision versus traditional laparoscopy.

Background and Objectives:Robotic surgery has been advocated for the radical excision of rectal cancer. Most data supporting its use have been reported from European and Asian centers, with a paucity of data from the United States documenting clear advantages of the robotic technique. This study compares the short-term outcome of robotic versus laparoscopic surgery.Methods:Consecutive patients who underwent laparoscopic (group 1) or robotic (group 2) rectal cancer excision at a single institution over a 2-year period were retrospectively reviewed. The main outcome measures were operative time, blood loss, conversion rates, number of lymph nodes, margin positivity, length of hospital stay, complications, and readmission rates.Results:Forty-two patients were analyzed. The median operative time was shorter in group 1 than that in group 2 (240 minutes vs 260 minutes, P = .04). No difference was noted in blood loss, transfusion rates, intraoperative complications, or conversion rates. There was no difference in circumferential or distal margin positivity. The median length of stay was shorter in group 1 (5 days vs 6 days, P = .05). The 90-day complication rate was similar in both groups (33% vs 43%, P = .75), but there was a trend toward more anastomotic leaks in group 1 (14% vs 0%, P = .23). Similarly, a non–statistically significant trend toward a higher readmission rate was noted in group 1 (24% vs 5%, P = .18).Conclusion:Robotic rectal cancer excision yielded a longer operative time and hospital length of stay, although immediate oncologic results were comparable. The need for randomized data is critical to determine whether the added resource utilization in robotic surgery is justifiable.

Robotic surgery for rectal cancer: current immediate clinical and oncological outcomes.

Laparoscopic rectal surgery continues to be a challenging operation associated to a steep learning curve. Robotic surgical systems have dramatically changed minimally invasive surgery. Three-dimensional, magnified and stable view, articulated instruments, and reduction of physiologic tremors leading to superior dexterity and ergonomics. Therefore, robotic platforms could potentially address limitations of laparoscopic rectal surgery. It was aimed at reviewing current literature on short-term clinical and oncological (pathological) outcomes after robotic rectal cancer surgery in comparison with laparoscopic surgery. A systematic review was performed for the period 2002 to 2014. A total of 1776 patients with rectal cancer underwent minimally invasive robotic treatment in 32 studies. After robotic and laparoscopic approach to oncologic rectal surgery, respectively, mean operating time varied from 192-385 min, and from 158-297 min; mean estimated blood loss was between 33 and 283 mL, and between 127 and 300 mL; mean length of stay varied from 4-10 d; and from 6-15 d. Conversion after robotic rectal surgery varied from 0% to 9.4%, and from 0 to 22% after laparoscopy. There was no difference between robotic (0%-41.3%) and laparoscopic (5.5%-29.3%) surgery regarding morbidity and anastomotic complications (respectively, 0%-13.5%, and 0%-11.1%). Regarding immediate oncologic outcomes, respectively among robotic and laparoscopic cases, positive circumferential margins varied from 0% to 7.5%, and from 0% to 8.8%; the mean number of retrieved lymph nodes was between 10 and 20, and between 11 and 21; and the mean distal resection margin was from 0.8 to 4.7 cm, and from 1.9 to 4.5 cm. Robotic rectal cancer surgery is being undertaken by experienced surgeons. However, the quality of the assembled evidence does not support definite conclusions about most studies variables. Robotic rectal cancer surgery is associated to increased costs and operating time. It also seems to be associated to reduced conversion rates. Other short-term outcomes are comparable to conventional laparoscopy techniques, if not better. Ultimately, pathological data evaluation suggests that oncologic safety may be preserved after robotic total mesorectal excision. However, further studies are required to evaluate oncologic safety and functional results.

Robotic colorectal surgery: summary of the current evidence

Several studies have confirmed that laparoscopic colorectal surgery results in improved early post-operative outcomes. Nevertheless, conventional laparoscopic approach and instruments have several limitations. Robotic approach could potentially address of many of these limitations. This review aims to present a summary of the current evidence on the role of robotic colorectal surgery. A comprehensive search of electronic databases (Pubmed, Science Direct and Google scholar) using the key words "rectal surgery", "laparoscopic", "colonic" and "robotic." Evidence from these data was critically analysed and summarised to produce this article. Robotic colorectal surgery is both safe and feasible. However, it has no clear advantages over standard laparoscopic colorectal surgery in terms of early postoperative outcomes or complications profile. It has shorter learning curve but increased operative time and cost. It could offer potential advantage in resection of rectal cancer as it has a lower conversion rates even in obese individuals, distal rectal tumours and patients who had preoperative chemoradiotherpy. There is also a trend towards better outcome in anastomotic leak rates, circumferential margin positivity and perseveration of autonomic function, but there was no clear statistical significance to support this from the currently available data. The use of robotic approach seems to be capable of addressing most of the shortcomings of the standard laparoscopic surgery. The technique has proved its safety profile in both colonic and rectal surgery. However, the cost involved may restrict its use to patients with challenging rectal cancer and in specialist centres.

Cylindrical abdominoperineal resection rationale, technique and controversies

Surgery remains the cornerstone in rectal cancer treatment. Abdominoperineal excision (APE), described more than 100 years ago, remains as an important procedure for the treatment of selected advanced distal tumors with direct invasion of the anal sphincter or preoperative fecal incontinence. Historically, oncological outcomes of patients undergoing APE have been worse when compared to sphincter preserving operations. More recently, it has been suggested that patients undergoing APE for distal rectal cancer are more likely to have positive circumferential resection margins and intraoperative perforation, known surrogate markers for local recurrence. Recently, an alternative approach known as “Extralevator Abdominoperineal Excision” has been described in an effort to improve rates of circumferential margin positivity possibly resulting in better oncological outcomes compared to the standard procedure. The objective of this paper is to provide a technical description and compare available data of both Extralevator and Standard abdominal perineal excision techniques.

Early Outcomes for Rectal Cancer Surgery in the Republic of Ireland Following a National Centralization Program

Following a national audit of rectal cancer management in 2007, a national centralization program in the Republic of Ireland was initiated. In 2010, a prospective evaluation of rectal cancer treatment and early outcomes was conducted. A total of 29 colorectal surgeons in 14 centers prospectively collated data on all patients with rectal cancer who underwent curative surgery in 2010. Data were available on 447 patients who underwent proctectomy with curative intent for rectal cancer in 2010; 23.7% of patients underwent abdominoperineal excision. The median number of lymph nodes identified was 12. The 30-day mortality rate was 1.1%. Compared with 2007, there was a reduction in positive circumferential margin rate (15.8 vs 4.5%, P<0.001), clinical anastomotic leak rate (10.8 vs 4.3%, P=0.002), and postoperative radiotherapy use (17.8 vs 4.0%, P<0.001). Also, 53.9% received preoperative radiotherapy in 2010. Four centers gave statistically more patients (high-administration), and four centers gave fewer patients (low-administration) preoperative radiotherapy for T2/T3 tumors (P<0.05). On multivariate analysis, being treated in a "high-administration center" increased the likelihood (likelihood ratio [LR], 2.9; 95% CI 1.7-4.8; P<0.001) while attending a "low-administration center" (LR, 0.3; 95% CI 0.2-0.5; P<0.001) reduced the likelihood of receiving preoperative radiotherapy for a T2/T3 rectal cancer. Patients undergoing rectal cancer surgery in hospitals following a national centralization initiative received high-quality surgery. Significant heterogeneity exists in radiotherapy administration, and evidence-based guidelines should be developed and implemented.

Multidisciplinary Treatment of Rectal Cancer

Russell et al1 have addedmore information to thedebate over the treatment of rectal cancer in institutions focused on the treatment of rectal cancer. Although the treatment of patients with rectal cancer in higher-volume academic centers with neoadjuvant protocols does not guarantee good surgical outcomes, it seems to help. Because no type of hospital (even a high-volume academic hospital) was immune to high outlier status for circumferentialmargins positive for cancer, the need for quality assurance and improvement in processes is extremely important for anyhospital/institution that treatspatients with rectal cancer. TheAmericanSocietyofColonandRectalSurgeons, inconjunctionwith the Society of Surgical Oncology, the American College of Surgeons, the Society for Surgery of the Alimentary Tract, and the Society of American Gastrointestinal and EndoscopicSurgeons,has initiated a project to optimize treatment of rectal cancer; OSTRiCh (Optimizing Surgical Treatment of Rectal Cancer) is a group of interested institutionsand individuals attempting todevelopaprogramin the United States similar to that in the United Kingdom, Scandinavia, and Europe. Out of this effort, a set of criteria for centers of excellence should become available. Rather than focusing solely on surgeon credentialing, the OSTRiCh group is embracing the institution with a multidisciplinary approach to rectal cancer. Someof the criteria includeddedicatedhighvolumesurgeonsusing totalmesorectal excisionof rectal cancer; radiologists experienced in magnetic resonance imaging stagingof rectal cancer;medical and radiationoncologistswho understand the nuances of neoadjuvant chemoradiation and adjuvant chemotherapy for rectal cancer; pathologists focused on macroscopic specimen grading, circumferential radial margin reporting, and whole-specimen processing for cross-sectionmounts; gastroenterologistswithhigh-level endoscopic intervention skills; and genetic counselors, asmembers of a multidisciplinary team, whomanage, evaluate, and assesseseverypatient treatedwithcolorectal cancer.Thesecriteria should improve the outcomes of patients treated for rectal cancer. Russell et al1 havealso shownus that apatient’s awareness of theappropriate treatmentof rectal cancer is important.Older individuals and those without private insurance had a higher likelihood of choosing low-volume, nonteaching hospitals, which have a greater likelihood of high outlier status for radial margins positive for cancer. As patients become more aware and/or educated about rectal cancer, this trend should change. This study1 has some issues that may never be resolved, even with the use of a database as sophisticated as the NationalCancerDataBase.Thepatientpopulation includedyoung patientswhomust,bydefinition,beconsideredhighrisk forhereditary cancer, which behaves differently from sporadic cancer. The inclusionof rectosigmoid cancers, simplybecause the patients underwent irradiation, may bias or negatively influence the outcomes because only the most advanced rectosigmoid cancers would require neoadjuvant therapy. The change in the awareness of the requirements for the pathologicevaluationofa rectal cancerspecimenbegan in2007 and seems to be associatedwith the increase in circumferentialmarginpositivity. Similarly, surgeonsaremoreawareof the need for total mesorectal excision and the avoidance of circumferential radial margin positivity. The use of a 9% to 10% baseline level of circumferential radial positivity and a 100% complete total mesorectal specimen can become an objectivemeasureof surgicalquality forhospitals treating rectal cancer.On thewhole,Russell et al1 are tobecongratulated for their superb effort to improve the surgical procedure for and the treatment of rectal cancer.

The impact of positive circumferential margin on survival following oesophagectomy using the new 7th TNM classification†

Previous studies looking at the influence of positive circumferential margin (CRM) on survival after oesophagectomy are conflicting. This may be due to the fact that older versions of the TNM classification were used, which do not predict survival as accurately as the new 7th edition. We examine whether CRM involvement has an impact on survival when the 7th TNM classification is used. Over a 10-year period, 199 patients who had undergone potentially curative resection for oesophageal cancer with postoperative histopathological T3 were identified. A total of 151 (75.9%) were found to have CRM involvement (<1 mm), and these were compared with patients in whom the CRM was free of tumour. Cancers were staged according to the International Union against Cancer TNM 7th edition. First, univariate and then multivariate Cox regression analysis were performed to assess the factors influencing survival. Potentially significant predictors (P < 0.1) from the univariate analysis were inserted in the forward-stepwise Cox regression model and was allowed to remain in the final model if a P-value of <0.05 was achieved. A sub-group analysis was also performed for different N-stages (N0-N3). After all analyses were performed, CRM involvement was found to have no effect on survival following oesophagectomy [hazard ratio 1.28 (95% CI: 0.82-2.01) (P = 0.28)]. This was seen for all N-stages. Stage of disease, age at operation, % predicted forced expiratory volume in 1 second and shortness of breath [(according to New York Heart Association classification)] were all significant predictors of survival. With this study, it became clear that CRM involvement does not affect long-term survival of patients after oesophagectomy. Patients with CRM involvement should not necessarily be considered to have had an incomplete resection.

A 12‐year experience of the Trendelenburg perineal approach for abdominoperineal resection

The abdominoperineal resection (APR) is the current accepted surgical technique for low rectal cancers. Negative circumferential surgical margins are an important prognostic indicator and are best obtained by producing a cylindrical specimen. The 'ideal' approach to produce such specimen is debated between a standard lithotomy position and turning the patient in the prone position in the later stages of the procedure. We aimed to assess results of perineal morbidity and oncological outcomes following the lithotomy approach at a single institution. Data were collected retrospectively at a single institution. All patients undergoing the APR for low rectal cancers were included in the current study. Patients underwent this procedure in the standard lithotomy position and a mucocutaneous flap was not routinely used for closure of the perineal wound. The primary outcome measures in this study were local and systemic tumour recurrence and overall patient survival. Fifty-three patients undergoing APR were included in the current study. Majority of patients (87%) received neoadjuvant therapy. Perineal morbidity was observed in 11% of patients loco-regional recurrence occurred in 4% at 5 years. One-, 3- and 5-year survival was 87, 75 and 66%, respectively. Patients with T3/4 disease and positive circumferential surgical margins had significantly poorer survival outcomes. APR can be performed in the lithotomy position with acceptable perineal morbidity and oncological safety. Negative circumferential margins can be achieved reliably by producing a cylindrical specimen with this position.

Pre-operative hypoalbuminaemia predicts poor overall survival in rectal cancer: a retrospective cohort analysis

BackgroundSerum albumin is a marker of nutrition and inflammation. It has recently emerged as a predictor of outcome after surgery for rectal cancer. Our aim was to evaluate if pre-operative serum albumin would predict survival after resection for rectal cancer.Method226 Patients with rectal cancer of all stages undergoing resection with curative intent were studied. Kaplan-Meier curves analysed survival based on a pre-operative albumin level of <35 g/L vs. >35 g/L. We sought for significant associations of survival with age, sex, stage, tumour site, use of neoadjuvant chemoradiation, microscopic positive resection margins, differentiation, angio, peri-neural, and lymphovascular invasion using individual variable analysis. Multifactorial analysis was performed using type III analysis with Weibull hazard model and Cox-proportional hazard model. Significance was assigned to a P value <0.05.ResultsOf 226 patients (median age- 59 years; range 19 – 88, Male - 54%), forty five (20%) had an albumin level < 35 g/L and was associated with a poor overall survival (P = 0.02). Mean survival in months for <35 g/L vs. >35 g/L was 64.7 (SE - 9.3) vs. 95.8 (SE – 7.0) and 5 year overall survival rates were 49% and 69%. Individual variable analysis revealed age, circumferential margin, stage, perineural, lympho-vascular and angio invasion to be also significant. With multifactorial analysis hypoalbuminaemia (HR = 0.58; 95% CI: 0.35 - 0.95, P = 0.03), advanced stage (HR = 2.0; 95% CI: 1.26 - 3.23, P < 0.01) and positive circumferential margin (HR = 2.2; 95% CI: 1.26 - 3.89, P < 0.01) remained significant.ConclusionPreoperative hypoalbuminaemia is an independent risk factor for poor overall survival in rectal cancer. Advanced tumour stage and circumferential margin positivity were the other associations with poor survival.

Multicentre study of circumferential margin positivity and outcomes following abdominoperineal excision for rectal cancer

Rectal cancer outcomes following abdominoperineal excision (APE) have been inferior to those for anterior resection, including more positive circumferential resection margins (CRMs). An erroneously conservative interpretation of APE (rather than a radical resection termed 'extralevator') has been proposed as the cause. In this multicentre study, factors contributing to CRM positivity were examined following APE according to its original description. Data were collected from five hospital databases up to June 2011 including small- and larger-volume units (3 hospitals had 5 or fewer and 2 hospitals had more than 5 APE procedures per year). Primary outcome measures were CRM status; secondary outcomes were local recurrence and death. Of 327 patients, 302 patients had complete data for analysis. Some 50·0 per cent of patients had neoadjuvant chemoradiotherapy. Histopathological examination showed that 62·9 per cent had tumour category T3 or T4 cancers, 42·1 per cent had node-positive disease and the CRM positivity rate was 13·9 per cent. Multivariable analysis showed only pathological tumour category pT4 (odds ratio 19·92, 95 per cent confidence interval 6·48 to 68·61) and node positivity (odds ratio 3·04, 1·32 to 8·05) to be risk factors for a positive circumferential margin. CRM positivity was a risk factor for local recurrence (P = 0·022) and decreased overall survival (P = 0·001). Hospital volume had no impact on the likelihood of CRM positivity (P = 0·435). In patients undergoing APE by appropriately trained surgeons using a standardized approach, margin positivity was dictated by tumour stage, but not by centre or surgeon.

P36. Low positive circumferential margins can be achieved by standard APR with careful MRI assessment and neo-adjuvant treatment

Aims: Recent moves towards wider resection of low rectal tumours using techniques such as ELAPe have been based on data reporting high rates of circumferential margin (CRM) involvement and inadvertent bowel perforation in standard abdomio-perineal resections (APR). This has been associated with worse outcome. We aimed to demonstrate the rate of CRM involvement in a small district general hospital to determine whether ELAPe should be adopted as our standard technique for low rectal tumours.

Abdominoperineal resection and low anterior resection: comparison of long-term oncologic outcome in matched patients with lower rectal cancer

The current study aimed to compare the oncologic outcome and pattern of metastasis after abdominoperineal resection (APR) and low anterior resection (LAR) treating lower rectal cancer. A total of 804 patients undergoing curative resection (R0) were enrolled prospectively. The APR and LAR groups (n = 402, respectively) were matched for gender, age, and stage, for a retrospectively comparative analysis. In a multivariate analysis with potential variables, APR itself was not a risk factor for increased local recurrence (LR) or reduced survival (P = 0.243-0.994). Circumferential resection margin (CRM) involvement as an operation-related risk was 1.6-fold more frequent in the APR group and was significantly associated with LR and systemic recurrence (OR, 2.487-4.017; P < 0.01). Circumferential margin positivity (CRM+) was concurrently correlated with advanced stage, larger tumor (long diameter, >4 cm), and longer sagittal midpelvic diameter (>10 cm) in a multivariate analysis (P < 0.001-0.05). The site of metastasis did not differ between the two groups, with the exception of lung metastasis which was more frequent in the APR group (APR vs. LAR: 15.9 vs. 10 %, P = 0.015). In the APR group, CRM+ and the presence of an infiltrating tumor were correlated with disease-free survival (hazard ratio (HR), 1.644 and 1.654, respectively), whereas elevated serum carcinoembryonic antigen and LVI+ were correlated with overall survival (HR, 1.57 and 1.671, respectively), in a multivariate analysis with potential variables (P < 0.05). When performed with appropriate skill to achieve R0 resection, APR can be used safely without impairing oncological outcome, although sphincter-preserving surgery should remain the preferred option.

Research progress of cylindrical abdominoperineal resection/extralevator abdominoperineal excision for advanced low rectal cancer

Cylindrical abdominoperineal resection (CAPR), also known as extralevator abdominoperineal excision (ELAPE), has been described as a method for improving the outcome of APR for advanced low rectal cancer, probably because of more pelvic dissection and less positive circumferential resection margin (CRM). Recently, there have been some hot issues associated with CAPR/ELAPE, such as pelvic floor reconstruction methods, prone or lithotomy positioning during pelvic procedure, postoperative chronic perineal pain, postoperative sexual and urinary nerves damage, etc. Individual cylindrical procedure based on clinical and anatomic research may be as effective as CAPR/ELAPE while minimizing the operative trauma and the damage to the nerves of the genital and urinary organs.

567P - Neoadjuvant Multidisciplinary Phase II Study (BRANCH) of an Early Bevacizumab Schedule Plus Chemo-Radiation Therapy in Rectal Cancer: Efficacy, Safety, and Biomarkers

ABSTRACT Background In BRANCH study we assess the safety and efficacy of an experimental schedule of early (4 days before) bevacizumab (BEV) added to neoadjuvant chemotherapy (CT) and radiotherapy (RT) in poor-risk locally advanced rectal cancer (pLARC) patients (pts) and explore the potential of circulating endothelial cells (CECs) and tumor lesion glycolysis (TLG) as surrogate markers of pathological response(PR). Patients and methods 46 pts (cT4, cN + , cT3≤ 5 cm from the anal verge and/or positive circumferential margin, M1 resectable) received 3 biweekly courses of oxaliplatin (100 mg/m2)/raltitrexed (2.5 mg/m2) on day 1, and 5-FU (800 mg/m2)/folinic acid (250 mg/m2) on day 2 during pelvic RT (45 Gy). BEV (5 mg/kg) was given biweekly 4 days before beginning of CT/RT for 2 courses. Toxicity was graded with NCI-CTC v.3. PR was defined using Mandard tumor regression grade (TRG). According to the Simon's two-stage design, assuming an hypothesis of a 50% TRG1 (complete tumor regression) (α error = 0.05, β error = 0.20), at least 6/16 TRG1 should be obtained to continue accrual to 46 pts. CECs and TLG were evaluated at baseline (BL) on day 10 and before surgery, by flow cytometry and FDG-PET, respectively. Statistical analysis was by Mann-Whitney test. Results We obtained 23 TRG1 (50%), 14 TRG2 (30%) and 8 TRG3-4 (17%). Grade ¾ neutropenia was the most common adverse event (13/46 pts, 28%). TLG reduction on day 10 vs BL was significantly higher in responders TRG1-2 compared to non-responders TRG3-4 pts (median -72%, range -90% + 31% vs -38%, range -45% + 25%; p Conclusions Current scheme of BEV plus CT and RT appears safe and active, yielding high rate of TRG1 and TRG2 responses in pLARC. Early FDG-PET and CECs evaluation emerged as potential biomarkers for treatment selection to be incorporated in design of future studies with this regimen. CEP and citochine data will be provided at the meeting. Disclosure All authors have declared no conflicts of interest.