Search

Background: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry. Methods: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival. Findings: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1–3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2–28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9–87·7%), and 5-year disease-specific survival was 94% (91–96%). Interpretation: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare. Funding: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.

The surgical management of rectal cancer has evolved from a disease without any possibility of cure in the early 1700s where surgical management consisted of the palliative drainage of disease related abscesses to the present day where surgical cure is not only possible but also possible with sphincter or even organ preservation. Prof Habr-Gama's lecture describes the evolution of the surgical management of rectal cancer and the current focus on organ preservation.

To estimate the improvement in surgical exposure by removal of the coccyx, during abdomino-perineal resection (APR), in rectal cancer patients. Retrospective study of 29 consecutive patients with rectal cancer was carried out. Using MR T2 sagittal series, the solid angle was estimated using the angle determined by the anterior resection margin and the tip of coccyx (no coccyx resection) or the tip of last sacral vertebra (coccyx resection). The solid angle provides an estimate of the tridimensional surface area provided by an original angle resulting in the best estimate of the surgeon’s view/exposure to the critical dissecting point of choice (anterior rectal wall). The difference (“Gain”) in surgical field exposure by removal of the coccyx was compared by the solid angle variation between the two estimates (with and without the coccyx). Routine removal of the coccyx determines an average 42% (95% CI 27–57%) gain in surgical field exposure area facing the anterior rectal wall at the level of the prostate/vagina by the surgeon. Fifteen (51%) patients had ≥30% (median) estimated gain in surgical field exposure by coccygectomy. There was no association between BMI, age or gender and estimated gain in surgical field exposure area. Routine removal of the coccyx during APR may result in an average increase in 42% in surgical field exposure during APR’s perineal dissection. Precise estimation of surgical field exposure gain by removal of the coccyx may be predicted by MR sagittal series for each individual patient.

The aim of this study was to evaluate the oncological and survival outcomes of a Watch and Wait policy in rectal cancer after a clinical complete response (cCR) following neoadjuvant chemoradiotherapy.The detection of a cCR after neoadjuvant treatment may facilitate a nonoperative approach in selected patients. However, the long-term safety of this strategy remains to be validated.This is a systematic review of the literature to determine the oncological outcomes in Watch and Wait patients. The primary outcome was the cumulative rate of local regrowth, success of salvage surgery, and incidence of metastases. We also evaluated survival outcomes. A pooled analysis of manually extracted summary statistics from individual studies was carried out using inverse variance weighting.Seventeen studies comprising 692 patients were identified; incidence of cCR was 22.4% [95% confidence interval (CI),14.3-31.8]. There were 153 (22.1%) local regrowths, of which 96% (n = 147/153) manifested in the first 3 years of surveillance. The 3-year cumulative risk of local regrowth was 21.6% (95% CI, 16.0-27.8). Salvage surgery was performed in 88% of patients, of which 121 (93%) had a complete (R0) resection. Fifty-seven metastases (8.2%) were detected, and 35 (60%) were isolated without evidence of synchronous regrowths; 3-year incidence was 6.8% (95% CI, 4.1-10.2). The 3-year overall survival was 93.5% (95% CI, 90.2-96.2).In rectal cancer patients with a cCR following neoadjuvant chemoradiotherapy, a Watch and Wait policy appears feasible and safe. Robust surveillance with early detection of regrowths allows a high rate of successful salvage surgery, without an increase in the risk of systemic disease, or adverse survival outcomes.

Neoadjuvant chemoradiation has become one of the preferred initial treatment strategies for the management of distal rectal cancer. Development of significant or even complete tumor regression following this treatment strategy may be considerably frequent depending on baseline disease stage and specific chemoradiation regimen. Management of these patients by standard radical surgery may be associated with significant postoperative morbidity, mortality, and functional consequences with no oncological benefit to other organ-preserving strategies including local excision or even nonoperative management (watch and wait strategy). This treatment strategy requires careful selection of patients and thorough evaluation of primary tumor response. In the present chapter, current key issues during the assessment of tumor response are reviewed. In addition, potential clinical and surgical consequences of these organ-preserving strategies following complete clinical response following neoadjuvant are discussed. Finally, reported outcomes of organ preservation in patients with rectal cancer avoiding radical surgery are also presented.

The incorporation of new treatment modalities has significantly increased the complexity of decision-making for patients with locally advanced rectal cancer. Neoadjuvant chemoradiation (CRT) is considered one of the preferred treatment strategies for these patients. In addition, this treatment strategy may lead to significant tumor regression, ultimately leading to complete pathological response in up to 42% of patients. The assessment of tumor response following CRT and prior to radical surgery may identify patients with complete clinical response that could be managed nonoperatively with strict follow-up (watch and wait strategy) and thus avoiding unnecessary postoperative morbidity, including long-term urinary, sexual, and fecal continence dysfunctions and the frequent need for temporary or definitive stomas.

// Paola Carpinetti 1, 2, 3 , Elisa Donnard 1, 2, 3 , Fabiana Bettoni 2 , Paula Asprino 2 , Fernanda Koyama 1 , Andrei Rozanski 2 , Jorge Sabbaga 4 , Angelita Habr-Gama 5, 6 , Raphael B. Parmigiani 2 , Pedro A.F. Galante 2 , Rodrigo O. Perez 1, 5, 6 , Anamaria A. Camargo 1, 2 1 Ludwig Institute for Cancer Research, Sao Paulo, SP, Brazil 2 Centro de Oncologia Molecular Hospital Sirio Libanes, Sao Paulo, SP, Brazil 3 Programa de Pos Graduacao em Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, SP, Brazil 4 Centro de Oncologia Clinica, Hospital Sirio Libanes, Sao Paulo, SP, Brazil 5 Angelita & Joaquim Gama Institute, Sao Paulo, SP, Brazil 6 University of Sao Paulo, School of Medicine, Sao Paulo, SP, Brazil Correspondence to: Anamaria A. Camargo, e-mail: aacamargo@mochsl.org.br Keywords: rectal cancer, liquid biopsies, ctDNA, personalized biomarkers, neoadjuvant therapy Received: June 19, 2015 Accepted: September 24, 2015 Published: October 06, 2015 ABSTRACT Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

Radiation therapy (RT) delivered preoperatively has clearly shown to improve local disease control after radical surgery in rectal cancer [1–3]. In fact different options including short-course or long-course regimens have been extensively studied with similar good long-term local disease control [4–6]. Also, the addition of chemotherapy with fluoropyrimidine to radiation led to further improvement in local disease control of these patients [7,8]. At a first glance, the issue of local recurrence in rectal cancer had been solved with widespread introduction of preoperative RT with or without concomitant chemotherapy. So why do we keep searching for alternative treatment options for the already successful neoadjuvant approach? What are we looking for? First of all, the observation that neoadjuvant chemoradiation (CRT) could result in complete tumor eradication, also known as complete pathological response is now considered one of the major advantages of neoadjuvant therapy in patients with rectal cancer [9]. Patients with complete pathological response (pCR) are associated with improved oncological outcomes [10]. Therefore, development of alternative neoadjuvant strategies that could maximize pCR rates is highly desirable. Also, even though increased rates of sphincter preservation have been considered another advantage of the neoadjuvant strategy, none of the randomized studies have demonstrated any superiority in sphincter preservation rates in experimental arms of these studies [11]. However, in select patients with clinical and radiological evidence of pCR (complete clinical response [cCR]), alternative organ-preserving treatment strategies have been suggested [12,13]. Therefore, a substantial increase in pCR and cCR rates could benefit patients by improving oncological outcomes and truly affecting sphincter or even organ preservation rates [9]. Therefore, maximization of pCR/cCR rates is an excellent reason for the search of improved neoadjuvant treatment regimens. But radiation therapy comes at a significant cost for patients, even though some

BACKGROUND:In elderly and comorbid patients with rectal cancer, radical surgery is associated with significant perioperative mortality. Data suggest that a watch-and-wait approach where a complete clinical response is obtained after neoadjuvant chemoradiotherapy might be oncologically safe.OBJECTIVE

Neoadjuvant chemoradiation (CRT) is considered one of the preferred treatment strategies for patients with locally advanced rectal cancer. This strategy may lead to significant tumor regression, ultimately leading to a complete pathologic response in up to 42% of patients. Assessment of tumor response following CRT and before radical surgery may identify patients with a complete clinical response who could possibly be managed nonoperatively with strict follow-up (watch-and-wait strategy). The present article deals with critical issues regarding appropriate selection of patients for this approach.

Background Genetic studies have largely concentrated on the impact of somatic mutations found in coding regions, and have neglected mutations outside of these. However, 3' untranslated regions (3' UTR) mutations can also disrupt or create miRNA target sites, and trigger oncogene activation or tumor suppressor inactivation. Methods We used next-generation sequencing to widely screen for genetic alterations within predicted miRNA target sites of oncogenes associated with colorectal cancer, and evaluated the functional impact of a new somatic mutation. Target sequencing of 47 genes was performed for 29 primary colorectal tumor samples. For 71 independent samples, Sanger methodology was used to screen for E2F1 mutations in miRNA predicted target sites, and the functional impact of these mutations was evaluated by luciferase reporter assays. Results We identified germline and somatic alterations in E2F1. Of the 100 samples evaluated, 3 had germline alterations at the MIR205-5p target site, while one had a somatic mutation at MIR136-5p target site. E2F1 gene expression was similar between normal and tumor tissues bearing the germline alteration; however, expression was increased 4-fold in tumor tissue that harbored a somatic mutation compared to that in normal tissue. Luciferase reporter assays revealed both germline and somatic alterations increased E2F1 activity relative to wild-type E2F1. Conclusions We demonstrated that somatic mutation within E2F1:MIR136-5p target site impairs miRNA-mediated regulation and leads to increased gene activity. We conclude that somatic mutations that disrupt miRNA target sites have the potential to impact gene regulation, highlighting an important mechanism of oncogene activation.

Background Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial treatment strategies for locally advanced rectal cancer. Responses are variable, and most patients still require surgery. The aim of this study was to identify molecular mechanisms determining poor response to CRT. Methods Global gene expression and pathway enrichment were assessed in pretreatment biopsies from patients with non-metastatic cT2–4 N0–2 rectal cancer within 7 cm of the anal verge. Downstream Akt activation was assessed in an independent set of pretreatment biopsies and in colorectal cancer cell lines using immunohistochemistry and western blot respectively. The radiosensitizing effects of the Akt inhibitor MK2206 were assessed using clonogenic assays and xenografts in immunodeficient mice. Results A total of 350 differentially expressed genes were identified, of which 123 were upregulated and 199 downregulated in tumours from poor responders. Mitochondrial oxidative phosphorylation (P < 0·001) and phosphatidylinositol signalling pathways (P < 0·050) were identified as significantly enriched pathways among the set of differentially expressed genes. Deregulation of both pathways is known to result in Akt activation, and high immunoexpression of phosphorylated Akt S473 was observed among patients with a poor histological response (tumour regression grade 0–2) to CRT (75 per cent versus 48 per cent in those with a good or complete response; P = 0·016). Akt activation was also confirmed in the radioresistant cell line SW480, and a 50 per cent improvement in sensitivity to CRT was observed in vitro and in vivo when SW480 cells were exposed to the Akt inhibitor MK2206 in combination with radiation and 5-fluorouracil. Conclusion Akt activation is a key event in the response to CRT. Pharmacological inhibition of Akt activation may enhance the effects of CRT. Surgical relevanceOrgan preservation is an attractive alternative in rectal cancer management following neoadjuvant chemoradiotherapy (CRT) to avoid the morbidity of radical surgery. Molecular steps associated with tumour response to CRT may provide a useful tool for the identification of patients who are candidates for no immediate surgery.In this study, tumours resistant to CRT were more likely to have activation of specific genetic pathways that result in phosphorylated Akt (pAkt) activation. Pretreatment biopsy tissues with high immunoexpression of pAkt were more likely to exhibit a poor histological response to CRT. In addition, the introduction of a pAkt inhibitor to cancer cell lines in vitro and in vivo led to a significant improvement in sensitivity to CRT.Identification of pAkt-activated tumours may thus allow the identification of poor responders to CRT. In addition, the concomitant use of pAkt inhibitors to increase sensitivity to CRT in patients with rectal cancer may constitute an interesting strategy for increasing the chance of a complete response to treatment and organ preservation.

Abdominal perineal excision (APE) has been associated with a high risk of positive circumferential resection margin (CRM+) and local recurrence rates in the treatment of rectal cancer. An alternative extralevator approach (ELAPE) has been suggested to improve the quality of resection by avoiding coning of the specimen decreasing the risk of tumor perforation and CRM+. The aim of this study is to compare the quality of the resected specimen and postoperative complication rates between ELAPE and “standard” APE. All patients between 1998 and 2014 undergoing abdominal perineal excision for primary or recurrent rectal cancer at a single Institution were reviewed. Between 1998 and 2008, all patients underwent standard APE. In 2009 ELAPE was introduced at our Institution and all patients requiring APE underwent this alternative procedure (ELAPE). The groups were compared according to pathological characteristics, specimen quality (CRM status, perforation and failure to provide the rectum and anus in a single specimen—fragmentation) and postoperative morbidity. Fifty patients underwent standard APEs, while 22 underwent ELAPE. There were no differences in CRM+ (10.6 vs. 13.6%; p = 0.70) or tumor perforation rates (8 vs. 0%; p = 0.30) between APE and ELAPE. However, ELAPE were less likely to result in a fragmented specimen (42 vs. 4%; p = 0.002). Advanced pT-stage was also a risk factor for specimen fragmentation (p = 0.03). There were no differences in severe (Grade 3/4) postoperative morbidity (13 vs. 10%; p = 0.5). Perineal wound dehiscences were less frequent among ELAPE (52 vs 13%; p

Local excision may offer the possibility of organ preservation for the management of select patients after neoadjuvant chemoradiation. The oncological outcomes of this strategy have been largely associated with the risk of nodal metastases. Therefore, in addition to final ypT status, baseline staging has been suggested to potentially influence the outcomes of this treatment modality.The aim of this study is to compare the pathological and oncological outcomes of patients following neoadjuvant chemoradiation and incomplete clinical response managed by transanal endoscopic microsurgery according to baseline staging.This study is a retrospective review of prospectively collected data.The study was conducted at a single center.Forty-six patients with distal rectal cancer cT2-4N0-2M0 underwent 5-fluorouracil-based neoadjuvant chemoradiation. Assessment of response was performed at least 8 weeks from radiotherapy completion. Patients with a complete clinical response were not operated on immediately. Patients with an incomplete clinical response were managed by surgery. Those with small (≤3 cm) residual cancers (ycT1-2N0M0) were managed by transanal endoscopic microsurgery.Patients undergoing local excision following chemoradiation were compared according to baseline staging.Fifteen patients (32%) were cT2N0 at baseline. Final ypT status was ypT0 in 3 (20%) patients, ypT1 in 2 (13%) patients, ypT2 in 9 (60%) patients, and ypT3 in 1 (7%) patient. There were no differences in final ypT status in comparison with patients with baseline cT3-4 or cN+ undergoing chemoradiation followed by transanal endoscopic microsurgery (p = 0.38). Local recurrence was observed in 1 patient with baseline cT2N0 (7%) and in 7 patients (23%) with stage II and III (p = 0.18).This study was limited by the short follow-up, its limited sample size, and its retrospective and nonrandomized nature.Patients with baseline cT2N0 that do not develop complete response to chemoradiation (ycT0-2N0; ≤3 cm) frequently present unfavorable pathological features for transanal local excision (ypT2 or 3 in66%). In the presence of incomplete clinical response following chemoradiation, patients with baseline cT2N0 have pathological and oncological outcomes similar to patients with baseline stage II or III and are probably not ideal candidates for local excision (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A159).

Transanal endoscopic microsurgery has become a very useful surgical tool for the management of selected cases of rectal cancer. However, the considerably high local recurrence rates led to the introduction of neoadjuvant therapies including radiation with or without chemotherapy. This treatment strategy may result in significant rates of tumor regression allowing the procedure to be offered to a significant proportion of cases. On the other hand, neoadjuvant chemoradiation (CRT) may also determine wound-healing difficulties with significant postoperative pain. In addition, salvage total mesorectal excision in the case of local recurrence may also be a challenging task. Finally, accurate selection criteria for this minimally invasive approach are still lacking and may be influenced by baseline staging, post-treatment staging and final pathology information. Ultimately, selection of patients for this treatment modality remains a significant challenge for the colorectal surgeon who should be aware of the pitfalls of this procedure in the setting of neoadjuvant CRT.

Background The main tenets of local excision of rectal cancer following neoadjuvant chemoradiation (CRT) are that the mucosal scar represents the main focus of residual disease and a solid conglomerate around this rather than being scattered (fragmented) through the bowel wall. Methods Retrospective review of a prospective cohort of patients with residual rectal ycT1-2N0 adenocarcinoma with small residual tumors (≤3 cm) following CRT who underwent transanal endoscopic microsurgery (TEM) with 1-cm margins around the residual mucosal abnormality was performed. Distribution and morphology (solid vs. fragmented) of tumor spread were studied and correlated to postoperative oncological outcomes. Results Thirty patients were included. Twenty percent (n = 6) were ypT1, 60% (n = 18) were ypT2, and 20% (n = 6) were ypT3 tumors. Fragmentation was present in 37%. The mean distance between foci of residual scattered tumor was 3.6 ± 2.0 mm. Lateral spread under normal mucosa was present in 19 specimens (53%; mean extension 4.8 ± 2.4 mm). With a median follow up of 32 months, none of these findings impacted upon development of recurrence. Conclusions Both occult lateral spread and fragmented tumor patterns are common findings after CRT. Despite the potential of occult spread to mislead surgeon choice of resection margin, its presence did not influence oncological outcome in this series. J. Surg. Oncol. 2014 109:853–858. © 2014 Wiley Periodicals, Inc.

2628 Background: We investigated whether an adaptation to rectal biopsies of the recently validated consensus Immunoscore, could predict the response to neoadjuvant treatment and delineate clinical responders that could benefit from a “Watch and Wait” (W&W) strategy with acceptable outcomes. Methods: Initial biopsies from 273 patients with locally advanced rectal cancer (LARC) treated by neoadjuvant chemoradiotherapy (nCRT) followed by Total Mesorectal Excision (TME), were immunostained for CD3+ and cytotoxic CD8+ T cells and quantified by digital pathology to determine the Immunoscore within pre-treatment Biopsy (ISB). Expression level of 44 immune related genes post-neoadjuvant treatment was investigated by Nanostring technology (n = 64 patients). Results were correlated with response to neoadjuvant treatment, disease free survival (DFS) and time to recurrence (TTR). Prognostic performance of ISB was finally assessed in 73 LARC treated by W&W strategy. Results: ISB Low, Intermediate and High were respectively observed in 23.3, 50.4 and 26.3 % of the cohort. ISB was positively and significantly correlated with the response to nCRT, as evaluated by Dworak classification (P = .0034), ypTNM (P = .0003), down-staging (P = .0014), and neoadjuvant rectal (NAR) score, (P < .0001). ISB status was also positively associated with the degree of local immune activation post-neoadjuvant treatment. ISB High patients were at low risk of relapse, with 5-year DFS rates of 81.1 % (CI, 71.3-92.1 %) as compared to 57.8 % (CI, 45.9-72.9 %) in ISB low patients. In multivariate analysis, ISB was the only significant parameter at presentation associated with DFS (High vs Low: P = .001). Among W&W patients, significant difference was observed for TTR according to ISB status (High vs Low: P = .025). Conclusions: ISB could provide a reliable estimate of the response to nCRT and risk of recurrence in LARC patients' treated by TME or W&W strategy.

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. Resumo: Um dos pilares mais importantes no tratamento do câncer de reto ainda é a ressecção cirúrgica. A amputação de reto, ou excisão abdomino-perineal do reto (APE), descrita há mais de 100 anos, continua sendo um procedimento importante para o tratamento de tumores retais distais que invadem o aparelho esfincteriano ou em casos de incontinência pré-operatória. Entretanto, os resultados oncológicos dos pacientes submetidos à APE são piores quando comparados com os pacientes submetidos a procedimentos com preservação esfincteriana. Recentemente, foi sugerido que os pacientes submetidos à APE por câncer de reto distal apresentam mais frequentemente margem radial positiva, assim como perfuração intraoperatória do tumor, fatos reconhecidamente associados à recidiva local. Uma nova técnica cirúrgica conhecida como “Amputação de reto extraelevador ou cilíndrica” tem sido descrita em um esforço para reduzir as taxas de margem radial positivas, sugerindo melhores resultados oncológicos quando comparada com o procedimento convencional. O objetivo deste trabalho é descrever a técnica deste procedimento e comparar seus resultados com os obtidos com a técnica convencional de acordo com a evidência disponível. Keywords: Rectal cancer, Total mesorectal excision, Abdominoperineal excision, Extralevator Abdominoperineal excision, Cilindric abdominoperineal excision, Palavras-chave: Câncer de reto, Excisão total do mesorreto, Amputação abdominoperineal, Amputação abdominoperineal extraelevador, Amputação cilíndrica

In the last decade, major advances have been achieved in the treatment of rectal cancer. Results of randomized controlled trials have led to the introduction of total mesorectal excision and preoperative (chemo) radiotherapy as a standard multimodal treatment approach. By combining these different treatment modalities, patients are less likely to suffer local recurrence and are more likely to maintain sphincter function and retain a reasonably good quality of life. To further improve the treatment response, many efforts have been made to integrate targeted biological agents into the conventional therapy. Anti-angiogenic treatment has been shown in preclinical and clinical studies to possibly potentiate chemoradiosensitivity. The researchers present an overview of the mechanisms of action and a summary of published results of chemoradiotherapy with anti-angiogenic drugs in the treatment of locally advanced rectal carcinoma. At present, many obstacles still have to be conquered to use this combination in daily clinical routine. Problems of resistance, invasion and metastasis as well as timing and dosing of the combination therapy when using anti-angiogenic compounds are discussed in this review. Also, attention for better response prediction and better understanding of the complexity of anti-angiogenic therapy in combination with chemoradiation is needed to lead to future improvements in the use of these agents in the clinic.

Owing to the complexity of distal rectal cancer its management requires a multidisciplinary approach. The diagnosis and the response after neoadjuvant chemoradiotherapy are not easy to assess and therefore the surgical approach is heterogeneous. The purpose of this survey is to evaluate the experiences of members of the Italian Society of Surgery in diagnosis and treatment strategies for rectal cancer and compare it with international practice. A questionnaire was devised comprising 18 questions with 11 sub-items making a total of 29 questions and submitted online to all the 2,500 members of the SIC starting from July 2010. The survey was completed in June 2011. The overall response rate was 17.8 % (444). The majority of the Italian surgeons' responses were in line with the international consensus reflecting the complex management of distal rectal cancer. Other opinions, especially those on staging, diverge from the common view of MRI being the gold standard in the assessment of loco-regional diffusion of the disease and on the superiority of FDG PET-CT versus CT for systemic staging. The timing for the re-staging and for surgery following neoadjuvant chemoradiotherapy does not reflect the international opinion. Italian surgeons are also exposed to the common difficulties encountered internationally in the management of distal rectal cancer. Probably, the implementation of an Italian rectal cancer registry and of many national and international multicentre studies may improve the management of rectal cancer in Italy.

Law, WL is one of the members of the International Rectal Cancer Study Group, BACKGROUND: Little is known regarding variations in preoperative treatment and practice for rectal cancer (RC) on an international level, yet practice variation may result in differences in recurrence and survival rates. METHODS: One hundred seventy-three international colorectal centers were invited to participate in a survey of preoperative management of rectal cancer. RESULTS: One hundred twenty-three (71%) responded, with a majority of respondents from North America, Europe, and Asia. Ninety-three percent have more than 5 years' experience with rectal cancer surgery. Fifty-five percent use CT scan, 35% MRI, 29% ERUS, 12% digital rectal examination and 1% PET scan in all RC cases. Seventy-four percent consider threatened circumferential margin (CRM) an indication for neoadjuvant treatment. Ninety-two percent prefer 5-FU-based long-course neoadjuvant chemoradiation therapy (CRT). A significant difference in practice exists between the US and non-US surgeons: poor histological differentiation as an indication for CRT (25% vs. 7.0%, p = 0.008), CRT for stage II and III rectal cancer (92% vs. 43%, p = 0.0001), MRI for all RC patients (20% vs. 42%, p = 0.03), and ERUS for all RC patients (43% vs. 21%, p = 0.01). Multidisciplinary team meetings significantly influence decisions for MRI (RR = 3.62), neoadjuvant treatment (threatened CRM, RR = 5.67, stage II + III RR = 2.98), quality of pathology report (RR = 4.85), and sphincter-saving surgery (RR = 3.81). CONCLUSIONS: There was little consensus on staging, neoadjuvant treatment, and preoperative management of rectal cancer. Regular multidisciplinary team meetings influence decisions about neoadjuvant treatment and staging methods., published_or_final_version