Total Mesorectal Excision Surgery Research Articles

Modern rectal cancer surgery—Total mesorectal excision—The standard of care

The literature has repeatedly shown the superiority of total mesorectal excision (TME) for rectal cancer in reducing the incidence of local recurrence (LR) and improving long-term survival compared to conventional blunt rectal dissection. This article reviews the history of surgery for rectal cancer, supports TME as the standard of care in obtaining a negative circumferential margin (CRM) for mid- and lower-third rectal cancers, discusses the drawbacks of TME, the role of tumor-specific mesorectal excision for upper-third rectal cancers and laparoscopic TME, and emphasizes the need for a selective role of chemoradiation with TME for rectal cancer. The need for standardizing TME in the United States with pathological specimen quality analysis and reporting of the completeness of the TME specimen is also emphasized.

Robotic-assisted transanal surgery for total mesorectal excision (RATS-TME): a description of a novel surgical approach with video demonstration

A new era has emerged in rectal cancer surgery--transanal total mesorectal excision (TME). Various platforms have been used to facilitate this novel approach, including transanal minimally invasive surgery (TAMIS) and transanal endoscopic microsurgery. We have previously reported the use of TAMIS-TME. This is a report of the first human case of robotic-assisted transanal surgery for TME.

Abstract 668: DNA methylation of apoptosis-related genes as clinical biomarker in rectal cancer.

Abstract Background: To prevent over- and undertreatment of rectal cancer patients, there is a need for the development of new biomarkers that can complement the current staging system. We have previously shown that apoptosis plays an important role in local tumor recurrence after TME surgery. We studied the epigenetic regulation of several key apoptosis genes in rectal cancer tissues, using methylation-sensitive restriction enzymes. Materials and methods: DNA was obtained from frozen specimens of 138 patients representative for the non-irradiated arm of the Dutch Total Mesorectal Excision (TME) trial. Isoschizomers HpaII (CpG methylation sensitive) and MspI (not sensitive) were used for restriction enzyme digestion of tumor DNA, followed by real-time PCR for apoptosis genes Apaf1, Bcl2, TrailR2, Fas and p53. A pilot series consisted of 50 patients with tumor stages I-III and 10 normal rectal tissues. For the validation study stage III patients (n=88) and 18 normal rectal tissues were selected. Results: Single marker analyses showed a significant correlation between methylation status and apoptotic status (measured by immunohistochemical staining of M30) of Fas (p=0.005) and Apaf1 (p=0.052). Combining intrinsic pathway markers Apaf1, Bcl2 and p53, significant differences were observed between the methylation groups in survival and recurrence analyses (log rank test), with overall survival (p=0.054), cancer specific survival (p=0.014) and distant recurrence free survival (p=0.006). Conclusion: Methylation of apoptosis genes is representative for the apoptotic status of a tumor and is correlated to survival and recurrence in rectal cancer patients. The apoptotic status of a tumor may be used to guide treatment strategies for individual patients. [A.B. and E.C.M.Z contributed equally to this work.] Citation Format: Anne Benard, Eliane C.M. Zeestraten, Inès J. Goossens-Beumer, Hein Putter, Christine Kuo, Cornelis J.H. van de Velde, Peter J.K. Kuppen, Dave S.B. Hoon. DNA methylation of apoptosis-related genes as clinical biomarker in rectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 668. doi:10.1158/1538-7445.AM2013-668

Transanal minimally invasive surgery for total mesorectal excision (TAMIS–TME): a stepwise description of the surgical technique with video demonstration

Transanal minimally invasive surgery (TAMIS), which can provide high-quality local excision for rectal neoplasia, has emerged as an important alternative to transanal endoscopic microsurgery. The role of TAMIS beyond local excision has also been explored, and it has been shown that this platform can be used for complete rectal resection with total mesorectal excision (TME). The stepwise approach to TAMIS for TME is described and illustrated in video format.

Laparoscopic total mesorectal excision with natural orifice specimen extraction

To introduce transvaginal or transanal specimen extraction in laparoscopic total mesorectal excision surgery to avoid an abdominal incision. Between January 2009 and December 2011, 21 patients with rectal cancer underwent laparoscopic radical resection and the specimen was retrieved by two different ways: transvaginal or transanal rectal removal. Transvaginal specimen extraction approach was strictly limited to elderly post-menopausal women who need hysterectomy. Patients aged between 30 and 80 years, with a body mass index of less than 30 kg/m², underwent elective surgery. The surgical technique and the outcomes related to the specimen extraction, such as duration of surgery, length of hospital stay, and the complications were retrospectively reviewed. Laparoscopic resection using a natural orifice removal approach was successful in all of the 21 patients. Median operating time was 185 min (range, 122-260 min) and the estimated blood loss was 48 mL. The mean length of hospital stay was 7.5 d (range, 2-11 d). One patient developed postoperative ileus and had an extended hospital stay. The patient complained of minimal pain. There were no postoperative complications or surgery-associated death. The mean size of the lesion was 2.8 cm (range, 1.8-6.0 cm), and the mean number of lymph nodes harvested was 18.7 (range, 8-27). At a mean follow-up of 20.6 mo (range, 10-37 mo), there were no functional disorders associated with the transvaginal and transanal specimen extraction. Transvaginal or transanal extraction in L-TME is a safe and effective procedure. Natural orifice specimen extraction can avoid the abdominal wall incision and its potential complications.

Multidisciplinary Management of Early-Stage Rectal Cancer

Because patients with locally advanced rectal cancer are at high risk for both recurrence and distant disease, they require adjuvant therapy. In the United States, the current standard of care is neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. Neoadjuvant chemoradiation has been shown to improve local recurrence rates and decrease toxicity. However in the era of total mesorectal excision surgery, no study has shown a survival benefit to either chemoradiation or postoperative chemotherapy. Newer biologic therapies, although promising in initial early trials, have yet to show a significant benefit in adjuvant therapy for rectal cancer.

Volume and outcome in rectal cancer surgery: the importance of quality management

For many years, the impact of the surgeon volume on short- and long-term outcome after rectal carcinoma surgery is controversially discussed. Literature and own department data were reviewed in order to clarify the impact of surgeon volume in the current era of total mesorectal excision surgery, multimodal therapy, quality management, and centralization of cancer care. Uni- and multivariate analysis of data from 1,028 patients with solitary rectal carcinoma, treated between 1995 and 2010 at the Department of Surgery, University Hospital, Erlangen, Germany, was performed. Surgeons were subdivided according to the number of operations/year into high- (at least seven/year), medium- (three to six), and low- (less than three) volume surgeons. Of 1,028 patients, 800 (77.8 %) were operated by five high-volume surgeons, 193 (18.8 %) by seven medium-volume surgeons, and 35 (3.4 %) by 12 low-volume surgeons. Surgeon volume was significantly associated with postoperative mortality and the rate of positive pathological circumferential resection margin. In risk-adjusted analysis, after primary surgery, surgeon volume had a significant impact on observed overall survival and disease-free survival, but not on locoregional recurrence. After neoadjuvant radiochemotherapy, only observed overall survival was significantly influenced by surgeon volume. In surgical departments with special interest in rectal carcinoma, surgeon volume has some influence on short- and long-term outcome. Irrespective of this fact, specialization, experience, individual skill, hospital organization, and regular quality assurance are essential prognostic factors ensuring good results in rectal carcinoma surgery.

Quality Assurance in Rectal Cancer Treatment

Colorectal cancer is the cancer with the second highest cancer incidence in Europe. Roughly, 1 out of 3 patients with a colorectal malignancy has a rectal carcinoma. Surgery is the cornerstone in the curative treatment of rectal cancer. In the 1980s with conventional surgery, the 5-year local recurrence rate was over 20% and the 5-year overall survival rate around 50%. In the Swedish Rectal Cancer trial, in which 1,168 patients were included, preoperative radiotherapy in addition to conventional surgery resulted in a reduction of more than 50% in the 5-year local recurrence rate in comparison to conventional surgery alone (11 vs. 27%; p < 0.001). In addition, the 5-year overall survival rate improved from 48 to 58% if patients were treated with preoperative radiotherapy in addition to conventional surgery (p = 0.004). With total mesorectal excision (TME), by which the rectum with its mesorectum and visceral fascia are dissected sharply and under direct vision, local recurrence rates dropped and overall survival improved. In the Dutch TME trial, 5 × 5 Gy preoperative radiotherapy in combination with TME surgery was compared to TME surgery alone (1,861 patients). In this trial, the 5-year local recurrence rate for patients treated with TME surgery alone was similar to patients treated in the Swedish Rectal Cancer trial with blunt dissection in combination with preoperative 5 × 5 Gy radiotherapy (11%). If preoperative radiotherapy was added to TME surgery, the 5-year local recurrence rate was reduced to 5.6%. The overall survival rate at 5 years was 64% for both patients treated with TME surgery alone and patients treated with preoperative radiotherapy followed by TME surgery, compared to 48% for patients treated with blunt dissection alone in the previously mentioned Swedish trial. TME surgery is now considered the standard surgical procedure for rectal cancer. However, even if TME surgery is performed, surgical quality varies. First, these results indicate that improvements in the surgical procedure itself can result in major progress regarding long-term oncological outcome, such as decreased local recurrence rates and improved overall survival. Second, it illustrates that variation in surgical quality could lead to large differences in outcome. Recently, it was shown that surgical variation is not only important for patients with rectal cancer, but also plays an important role for the outcome of patients with colon cancer.

612P - Are Patients with Resectable Rectal Cancer Better Off in the Era of Multidisciplinary Care?

ABSTRACT Introduction The management of rectal cancer (RC) has evolved with the introduction of Total Mesorectal Excision Surgery (TME), use of Magnetic Resonance Imaging (MRI) for staging, changes in chemotherapy and radiotherapy and multidisciplinary meetings (MDTs). The timing of therapy for T3/4 and/or node positive RC has also changed with neoadjuvant chemoradiotherapy (CRT) becoming standard based on lower local recurrence rates. Given these changes in management over time, we assessed disease free survival (DFS), overall survival (OS) and rates of local and distant recurrences of patients treated at The Queen Elizabeth Hospital (TQEH) between 1992 to 2006. Method Demographic and outcome data of patients diagnosed with early stage RC from TQEH Cancer Registry from 2 different time cohorts 1992-99 (A) and 2000-06 (B) were analysed. Survival analysis was by Kaplan-Meier method and prognostic factors were analysed using cox proportional hazards regression. Results 423 patients were identified; 235 in A, 188 in B. Patient characteristics were generally similar. Median age A 68.1 yrs (range 32-94), B was 67.4 yrs (range 25-92). More patients had stage B in cohort A (47%) v B (39%). 56% of patients had surgery alone in cohort A compared to 47% in cohort B. Rates of any “adjuvant” therapy was similar (A = 41% v B = 46%), although there was a doubling in proportion of patients who received neoadjuvant CRT in the latter cohort (A= 7.2% v B= 16%). There was a significant improvement in rate of 5 year local/distal recurrence; A 87%/71% v B 95%/81%, p Conclusion There has been significant improvement in DFS, OS and local and distant recurrence rates in patients diagnosed with early stage RC. The trend to greater use of neoadjuvant CRT in the latter cohort is consistent with changes in practice, and this may be a factor in improved local control, but does not appear to impact on survival. Other factors likely to have improved overall outcomes include: increased TME rates, improved preoperative staging including use of MRI and potentially the introduction of MDTs. Disclosure All authors have declared no conflicts of interest.

607P - Efficacy and Safety of Two Neoadjuvant Strategies with Bevacizumab in Locally Advanced Resectable Rectal Cancer: Interim Results of a Randomized, Non-Comparative Phase II Study

ABSTRACT Background Current therapy of locally advanced resectable rectal cancer (LARC) involves a combination of chemotherapy (CT), radiation therapy, (RT) and total mesorectal excision (TME) surgery. Two neoadjuvant strategies with bevacizumab (Bv) were assessed in a randomized, open-label, multicentre, phase II study. Method Patients (pts) were treated with a sequential strategy including induction Bv/6 cycles (5mg/2weeks) + Folfox4, followed by CT-RT (Bv/6 cycles + 5-FU/5 cycles) + RT(45Gy) then TME in Arm A and the same CT-RT, then TME in Arm B. Primary end-point was tumor sterilization rate (pCR) - at least 10% in each arm. Efficacy and safety were reviewed by an independent committee. Results at 8 weeks post-surgery are presented. Results Pts characteristics in Arm A (n = 46) and in Arm B (n= 45) were: men 67%, age 60 ± 9 years, ECOG score 0 (85%), mid-rectum (60%), low-rectum (40%), MRI stage: T3N0M0/T3N1M0/T3N2M0 (20%/65%/15%). In Arm A, 94% pts completed induction and 91% had CT-RT and surgery; in Arm B 100% had CT-RT and 98% surgery. Resection was macroscopically complete in 91% pts. Median post-surgery hospitalization duration was 15 [0-84] days. In the ITT population, pCR (ypT0-N0) rate was 23.8% [12.1%-39.5%] in Arm A (p = 0.015) and 11.4% [3.8%-24.6%] in Arm B (p = 0.91), both compared to the 10% pCR initial hypothesis. Central review found similar results for pCR. At surgery and 4 weeks post-surgery grade 3/4 adverse events (AE) were reported in 10 (22%) of pts in both arms. At 8 weeks post-surgery, grade 3/4 adverse events (AE) were reported in 59% of pts in Arm A and 36% in Arm B. Grade 3/4 AEs of special interest for bevacizumab were reported in 20% of pts in Arm A and 22% in Arm B. No death was reported at 8 weeks post-surgery follow-up. Conclusions Interim results in patients with LARC treated with 2 neoadjuvant strategies showed that bevacizumab combination to neoadjuvant CT-RT did not significantly increase pCR in Arm B. The neoadjuvant strategy assessed in Arm A seems promising and deserves further investigation. Safety was comparable in Arms A and B at 8 weeks post-surgery. Disclosure T. Andre: Consultant: Roche Honoraries: Amgen, Merck, Sanofi. F. Boudghene: Honoraries : Roche. M. Piutti: Employment: Roche. All other authors have declared no conflicts of interest.

P-0296 Could Pre-Treatment Cea be an Effective Predictor of Relapse in High Risk Rectal Cancer?

ABSTRACT Introduction Over 14,000 cases of rectal cancer occur per year in the UK. Radical surgery with total mesorectal excision (TME) is the main curative treatment for disease localised to the pelvis. Some cases are judged on pelvic MRI to be at high risk of positive margins from surgery alone. They are offered pre-operative chemo-radiotherapy (CRT) before surgery with TME. This hopes to downsize and downstage tumors to provide clear circumferential resection margins and reduce the likelihood of relapse. Good pathological responses to CRT are associated with improved cancer outcomes. We investigated whether carcinoembryonic antigen (CEA) levels at presentation could act as a simple predictor of relapse when using CRT followed by TME for patients with high-risk rectal cancers. Methods Retrospective data was collected on high-risk rectal cancer patients treated radically with pre-op CRT and TME surgery at Ipswich Hospital between March 2005 and Jan 2012. All received at least 45 Gy in 25 fractions of radiotherapy using a three-field CT plan and 5 weeks of oral capecitabine chemotherapy. CEA levels were obtained prior to radiotherapy. Following surgery, rectal specimens were assessed by our pathologists to evaluate response to treatment and whether complete pathological response (pCR) was achieved. Follow-up was by our oncology department and colorectal surgeons with annual CT scanning, 1-3 yearly colonoscopies and clinical surveillance for 5 years. Results 56 patients met inclusion criteria. Male to female ratio: 1.8:1. 96% (n=54) patients received pre-op chemotherapy alongside radiotherapy: 2 patients were considered too high-risk for this component of treatment. Mean follow-up from commencing radiotherapy was 33 months (range 7-69). Mean time from last dose of radiotherapy to surgery was 11 weeks (range 5-18). 93% (n=52) had (R0) resection margins following surgery. 7.1% (n=4) had (R1) incomplete resection margins following surgery; 2 of these 4 suffered local relapse in the pelvis. 30% (n=17) achieved a pCR following CRT, none of the patients who achieved a pCR have relapsed. 77% (n=43) presented with a normal CEA (≤5, range 5, range 6-54). Normal CEA group: 35%, (n=15) achieved pCR following CRT and 14% (n=6) relapsed. High CEA group: 15% (n=2) achieved pCR following CRT and 46%, (n=6) relapsed. There was a significant between group difference in relapse (Fisher's exact test p=0.02). Further survival analysis for relapse revealed a statistically significant hazard ratio of 4.5 (95% CI 1.04 to 19.4). Conclusion 1. High CEA on presentation was associated with an estimated relative risk of relapse 4.5 times greater than presenting with a normal CEA. 2. Therefore high CEA at presentation could be a useful biomarker to identify patients with the highest risk of relapse who may benefit from more intensive treatment. 3. Our high rates of R0 resection margin (93%) and pCR (30%) could be due to a relatively prolonged time from radiotherapy to surgery in our cohort.

Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial

Preoperative chemoradiotherapy, total mesorectal excision surgery, and adjuvant chemotherapy with fluorouracil is the standard combined modality treatment for rectal cancer. With the aim of improving disease-free survival (DFS), this phase 3 study (CAO/ARO/AIO-04) integrated oxaliplatin into standard treatment. This was a multicentre, open-label, randomised, phase 3 study in patients with histologically proven carcinoma of the rectum with clinically staged T3-4 or any node-positive disease. Between July 25, 2006, and Feb 26, 2010, patients were randomly assigned to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (1000 mg/m(2) days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) days 1-5 and 29; fluorouracil group); and an experimental group receiving preoperative radiotherapy of 50·4 Gy plus infusional fluorouracil (250 mg/m(2) days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) days 1, 8, 22, and 29), followed by surgery and eight cycles of adjuvant chemotherapy with oxaliplatin (100 mg/m(2) days 1 and 15), leucovorin (400 mg/m(2) days 1 and 15), and infusional fluorouracil (2400 mg/m(2) days 1-2 and 15-16; fluorouracil plus oxaliplatin group). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-4 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. DFS is the primary endpoint. Secondary endpoints, including toxicity, compliance, and histopathological response are reported here. Safety and compliance analyses included patients as treated, efficacy endpoints were analysed according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT00349076. Of the 1265 patients initially enrolled, 1236 were evaluable (613 in the fluorouracil plus oxaliplatin group and 623 in the fluorouracil group). Preoperative grade 3-4 toxic effects occurred in 140 (23%) of 606 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 127 (20%) of 624 patients who actually received fluorouracil chemoradiotherapy. Grade 3-4 diarrhoea was more common in those who received fluorouracil and oxaliplatin during chemoradiotherapy than in those who received fluorouracil during chemoradiotherapy (73 patients [12%] vs 52 patients [8%]), as was grade 3-4 nausea or vomiting (23 [4%] vs nine [1%]). 516 (85%) of the 606 patients who received fluorouracil and oxaliplatin-based chemoradiotherapy had the full dose of chemotherapy, and 571 (94%) had the full dose of radiotherapy; as did 495 (79%) and 601 (96%) of 624 patients who received fluorouracil-based chemoradiotherapy, respectively. A pathological complete response was achieved in 103 (17%) of 591 patients who underwent surgery in the fluorouracil and oxaliplatin group and in 81 (13%) of 606 patients who underwent surgery in the fluorouracil group (odds ratio 1·40, 95% CI 1·02-1·92; p=0·038). In the fluorouracil and oxaliplatin group, 352 (81%) of 435 patients who began adjuvant chemotherapy completed all cycles (with or without dose reduction), as did 386 (83%) of 463 patients in the fluorouracil group. Inclusion of oxaliplatin into modified fluorouracil-based combined modality treatment was feasible and led to more patients achieving a pathological complete response than did standard treatment. Longer follow-up is needed to assess DFS. German Cancer Aid (Deutsche Krebshilfe).

Midcourse neoadjuvant chemoradiation for locally advanced rectal cancer.

e14121 Background: Neoadjuvant chemoradiotherapy is considered a standard approach for locally advanced rectal cancer. Many studies have showed that short-course radiation (25Gy in 5 fractions) and long-course chemoradiotherapy (50.4-55Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days) have similar long-term survival, local recurrence, and late morbidity. The aim of this study is to show the efficacy and safety of a newly modulated mid-course chemoradiotherapy with capecitabine in locally advanced rectal cancer. Methods: 252 patients with low lying (within 7cm from anal verge) locally advanced rectal cancer were recruited. All patients received a total irradiation dose of 30 Gy with conventional fractions for 3 weeks (2 Gy on weekdays). Capecitabine was administered 1000mg/m2 twice a day on 21 days during radiotherapy, followed total mesorectal excision surgery in a week without resting period. Results: The mean patients age was 60.2 years, and 57.9% (146/252) were men. The mean location of cancer was at 4.7cm from anal verge (1-7cm). There were 8 patients (3.2%) with pathologic complete response. 32 patients (12.7%) underwent abdominoperineal resection or Hartmann's operation. Among other 220 patients, 163 patients (74.1%) concomittent diverting ileostomy. Anastomotic leakage was confirmed in 32 patients (14.5%) in the patients with sphincter-saving surgery. There was one case of septicemia, which was recovered. The postoperative mortality was none. Eight patients (3.2%) experienced locoregional recurrence of pelvic cavity. 3-year overall survival rate was 84.1%. Conclusions: Preoperative mid-course chemoradiotherapy using oral capecitabine 2,000 mg/m2/day on 21 days during 2 Gy radiation of each 15 weekdays is seemed to be a tolerable and effective modality, in patients with low lying, locally advanced rectal cancer.

Preoperative Versus Postoperative Chemoradiotherapy for Locally Advanced Rectal Cancer: Results of the German CAO/ARO/AIO-94 Randomized Phase III Trial After a Median Follow-Up of 11 Years

Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival. Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival. There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.

Defining Quality in Colon Cancer Surgery

Defining Quality in Colon Cancer Surgery

The Importance of the Pathologist’s Role in Assessment of the Quality of the Mesorectum

Total mesorectal excision (TME) is considered standard of care for rectal cancer treatment. Failure to remove the mesorectal fat envelope entirely may explain part of observed local and distant recurrences. Several studies suggest quality of the mesorectum after TME surgery as determined by pathological evaluation may influence prognosis. We aimed to determine the prognostic value of the plane of surgery as well as factors influencing the likelihood of a high-quality specimen by reviewing the literature. A pooled meta-analysis of relevant outcome data was performed where appropriate. A muscularis propria resection plane was found to increase the risk of local recurrence (RR 2.72 [95 % CI 1.36 to 5.44]) and overall recurrence (RR 2.00 [95 % CI 1.17 to 3.42]) compared to an (intra)mesorectal plane. Plane of surgery is an important factor in rectal cancer treatment and the documentation by pathologists is essential for the improvement of TME quality and patient outcome.

Laparoscopic total mesorectal excision can be performed on a nonselective basis in patients with rectal cancer with excellent medium-term results

Concerns exist regarding laparoscopic rectal cancer surgery due to increased rates of open conversion, complications and circumferential resection margin positivity. This study reports medium-term results from consecutive unselected cases in a single surgeon series. The results of laparoscopic total mesorectal excision (TME) for rectal cancer over a 9-year period within the context of an evolving 'enhanced recovery protocol' (ERP) were reviewed from analysis of a prospectively maintained database. One hundred and fifty patients (91 male, median age 69 years, median BMI 26) underwent laparoscopic TME over 9 years. Median follow up was 28.5 months (range 0-88). Sixteen (10.6%) patients underwent neoadjuvant radiotherapy. Six (4.0%) required open conversion and 13 (9.0%) had an anastomotic leakage. The proportion of Dukes stages were: A, 33.3%; B, 30.7%; C, 31.3%; D, 4.7%. Five (3.3%) patients had an R1 and one an R2 resection. Median length of postoperative stay was 6 days. Three (2.0%) patients died within 30 days. Four (2.7%) developed local recurrence and 14 (9.3%) developed distant metastases. Predicted 5-year disease-free and overall survival rates by Kaplan-Meier analysis were 85.8% and 78.7%, respectively. Laparoscopic TME surgery can safely be offered to unselected patients with rectal cancer with excellent medium-term results.

Diagnostic Sequence of MRI and PET/CT in a Case of Bone Metastases by Hypopharyngeal Squamous Cell Carcinoma

Magnetic resonance imaging (MRI) has gained increasing importance in the management of rectal cancer over the last two decades. The role of MRI in patients with rectal cancer has expanded beyond the tumor-node-metastasis (TNM) system in both staging and restaging scenarios and has contributed to identifying “high” and “low” risk features that can be used to tailor and personalize patient treatment; for instance, selecting the patients for neoadjuvant chemoradiation (NCRT) before the total mesorectal excision (TME) surgery based on risk of recurrence. Among those features, the status of the circumferential resection margin (CRM), extramural vascular invasion (EMVI), and tumor deposits (TD) have stood out. Moreover, MRI also has played a role in surgical planning, especially when the tumor is located in the low rectum, when the relationship between tumor and the anal canal is important to choose the best surgical approach, and in cases of locally advanced or recurrent tumors invading adjacent pelvic organs that may require more complex surgeries such as pelvic exenteration. As approaches using organ preservation emerge, including transanal local excision and “watch-and-wait”, MRI may help in the patient selection for those treatments, follow up, and detection of tumor regrowth. Additionally, potential MRI-based prognostic and predictive biomarkers, such as quantitative and semi-quantitative metrics derived from functional sequences like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE), and radiomics, are under investigation. This review provides an overview of the current role of MRI in rectal cancer in staging and restaging and highlights the main areas under investigation and future perspectives.

Preoperative chemoradiation with oral capecitabine in locally advanced rectal cancers: An impact on sphincter preservation and pathologic response‏

Background: Preoperative chemorradiotherapy with concurrent 5-flourouracil (5-FU) has shown superior results as compared to postoperative chemoradiation. Capecitabine, an oral flouropyrimidine, is converted to 5-FU in the body. Our aim was to evaluate the efficacy of capecitabine as radiosensitizer in preoperative chemoradiation of locally advanced rectal cancer. Methods: From November 2008 to December 2009, 20 patients with locally advanced rectal cancers (≥ T3 or N+), were treated after written consent with concurrent capecitabine (825 mg/m 2 oral twice daily) with pelvic radiotherapy (dose 5040 cGy in 28 fractions), followed by total mesorectal excision surgery and adjuvant chemotherapy. Primary endpoints were pathologic response rates, efficacy of capecitabine and its toxicity. Pathologic response rates and toxicities were summarized with 95% confidence intervals (95% CI). Results: The predominant radiological stage was T3 N+ in 40% followed by T4N0 in 35%. The complete pathologic response (pCR) was achieved in 3 patients (15%), the downstaging was observed in 17 patients (85%). Sphincter preservation was reported in 65% cases. The Grade 3 hematological toxicities were lymphopenia (30%) and neutropenia (10%). The Grade 3 non hematological toxicities observed were; diarrhea/proctitis (25%) and nausea/vomiting (25%). No hand foot syndrome or Grade 3 skin toxicity was seen. Conclusions: The capecitabine as radiosensitizer was well tolerated, more convenient than intravenous 5-FU and with similar response rates in locally advanced rectal cancer.

Lymph node distribution and pattern of metastases in the mesorectum following total mesorectal excision using the modified fat clearing technique

AimTo define the distribution, size, location and metastasis of lymph nodes (LNs) within the mesorectum from rectal cancer specimens following total mesorectal excision (TME) surgery without neoadjuvant therapy.MethodsSpecimens from 60...