Yann Parc

Efficacy of sacral nerve stimulation for fecal incontinence : Results of a multicenter double-blind crossover study

Background and Aims:This is the first double-blind multicenter study examining the effectiveness of sacral nerve stimulation in a significant number of fecally incontinent patients. Methods:A total of 34 consecutive patients (31 women), median age 57 years (range, 33–73 years), underwent sacral nerve stimulation for fecal incontinence. After implantation, 27 of 34 patients were randomized in a double-blind crossover design to stimulation ON or OFF for 1-month periods. While still blinded, the patients chose the period of stimulation (ON or OFF) that they had preferred. The mode of stimulation corresponding to the selected period was continued for 3 months (final period). Outcome measures were frequency of fecal incontinence and urgency episodes, delay in postponing defecation, score severity, feeling of improvement, preference for ON or OFF, quality of life, and manometric measurements. Results:In the crossover portion of the study, the self-reported frequency of fecal incontinence episodes was significantly reduced during the ON versus the OFF period (P = 0.03), and this symptomatic improvement was consistent: 1) with the patients feeling of greater improvement during the ON versus OFF period (P = 0.02); 2) with the significant preference of patients (P = 0.02) for the ON versus OFF period. In the final period of the study, the frequency of fecal incontinence episodes decreased significantly (P = 0.005) in patients with the stimulator ON. The ability to postpone defecation (P = 0.01), the score for symptom severity (P = 0.0004), and the quality of life (P < 0.05) as well as anal sphincter function significantly improved. Conclusions:The significant improvement in FI during the ON versus OFF period indicated that the clinical benefit of sacral nerve stimulation was not due to placebo.

Long-term results of intersphincteric resection for low rectal cancer.

Introduction:In the treatment of very low rectal cancer, a distal resection margin of more than 1 cm can be obtained by partial internal sphincteric resection, allowing a sphincter preserving surgery. Thus, intersphincteric resection (ISR) has been proposed as an alternative to abdominoperineal resection for selected low rectal cancer. Objective:The aim of our study was to assess the morbidity, mortality, and the long-term oncologic and functional results of ISR. Methods:Charts of patients who had ISR between 1992 and 2004 were reviewed. Cancer-related survival and locoregional recurrence rates were calculated using the Kaplan–Meier method. Functional outcome was assessed by using a standardized gastrointestinal functional questionnaire. Incontinence was assessed by the continence score of Wexner. Results:Ninety patients (59 males, 31 females) with a tumor at a median distance of 35 mm (range, 22–52) from the anal verge had an ISR. Thirty-seven patients (41%) had preoperative radiotherapy. Histologically complete remission after neoadjuvant radiotherapy (ypT0) was observed in 7 patients (8%), 12 patients (13%) were pT1, 35 patients (39%) pT2, 32 patients (36%) pT3, and 4 patients (4%) pT4. Five patients (5.5%) had synchronous liver metastases. R0 resection was obtained in 85 patients (94.4%). The median distal resection margin on the fixed specimen was 12 mm (range, 5–35) and was positive in 1 case. The circumferential margin was positive (≤1 mm) in 4 patients (4.4%). There was no mortality. Complication rate was 18.8%: anastomotic leakage occurred in 8 patients (8.8%) and 1 patient had an anovaginal fistula. Five patients (5.6%) underwent secondary abdominoperineal resection: 1 for positive distal margin, 1 for colonic J-pouch necrosis, and 3 for local recurrence. Oncologic Results:After a median follow-up of 56.2 months (range, 13.3–168.4), local, distant, and combined recurrence occurred in 6 (6.6%), 8 (8.8%), and 2 patients, respectively. Thirteen patients (14.4%) died of cancer recurrence. Five-year overall and disease-free survival was 82% (80–97) and 75% (64–86), respectively. In univariate analysis, overall survival was significantly influenced by pTNM stage and T stage (pT 1–2 vs. 3–4: P = 0.008 and stage I–II vs. III–IV: P = 0.03). In multivariate analysis, we did not find any impact on local recurrence-free survival for the investigated prognostic variables. Functional Results:For a total of 83 patients the mean stool frequency was 2.3 ± 1.3 per 24 hours. Forty-one percent of patients had stool fragmentation, one-third nocturnal defecation, 19% fecal urgency, and 36% followed low fiber diet. Thirty-four patients (41%) were fully continent, 29 patients (35%) had minor continence problems, and 20 patients (24%) were incontinent. After adjustment for age, gender, tumor level, and pTNM stage, preoperative radiotherapy was the only factor associated with a risk of fecal incontinence [OR (IC 95%) = 3.1 (1.0–9.0), P = 0.04]. Conclusion:In selected patients, ISR is a safe operation with good oncologic results. It achieves good functional results in 76% of patients. Functional results are significantly altered by preoperative radiotherapy.

Microsatellite instability and hMLH1/hMSH2 expression in young endometrial carcinoma patients: Associations with family history and histopathology

Endometrial cancer is the second most common malignancy in patients with hereditary nonpolyposis colorectal cancer (HNPCC). The age at diagnosis of HNPCC‐associated endometrial cancer is approximately 15 years younger than for sporadic endometrial cancer. Our current study was undertaken to determine the frequency of microsatellite instability (MSI) and absence of hMLH1 or hMSH2 protein expression in young patients with endometrial carcinoma and to correlate these findings with histopathologic and clinical features. Endometrial carcinoma from 62 women (23–52 years, median age 46) were assessed for MSI. Twenty‐one of the 62 (34%) tumors demonstrated MSI. Of the 21 tumors demonstrating MSI, 12 showed an absence of hMLH1 expression, 4 showed an absence of hMSH2 expression, and 5 demonstrated normal expression of both proteins. All 41 tumors without MSI demonstrated normal hMLH1 and hMSH2 expression. Two patients with MSI tumors fulfilled the Amsterdam criteria for HNPCC, while 2 had histories suggestive of HNPCC. None of the patients with tumors without MSI had a personal or family cancer history suggestive of HNPCC. The MSI phenotype was associated (p < 0.05) with high FIGO stage and grade, cribriform growth pattern, mucinous differentiation and necrosis. Our findings suggest that the frequency of HNPCC in young endometrial cancer patients is relatively low when compared with the frequency of HNPCC in young colorectal cancer patients. Defects of the MMR proteins hMSH2 or hMLH1 account for MSI in most but not all endometrial cancers from young patients. Int. J. Cancer 86:60–66, 2000.

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6)

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes [8.5%]). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum [I] 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.

Long-term outcome of familial adenomatous polyposis patients after restorative coloproctectomy.

Background:Restorative proctocolectomy (RPC) eliminates the risk of colorectal adenocarcinoma in familial adenomatous polyposis (FAP) patients, but desmoid tumors, duodenal, and ileal adenomas can still develop. Our aim was to assess the long-term outcome of FAP patients after RPC. Patients and Methods:FAP patients who had RPC between 1983 and 1990 were contacted for interview and upper gastrointestinal (GI) and ileal pouch endoscopy. Results:Sixty-two males and 48 females had undergone hand-sewn RPC during this period. One patient died postoperatively (0.9%). Among 96 patients available for a minimal follow-up of 11 years, 7 patients died: 3 from causes unrelated to FAP, 2 from metastatic colorectal cancer, and 2 from mesenteric desmoid tumor (MDT). Thirteen patients had a symptomatic MDT (13.5%). Of 73 patients who had an upper GI endoscopy, 52 developed duodenal and/or ampullary adenomas. Four patients required surgical treatment of their duodenal lesions. Among 54 patients who underwent ileal pouch endoscopy, pouch adenomas were noted in 29. No invasive duodenal or ileal pouch carcinoma were detected. Functional results of RPC were significantly worse in MDT patients. Conclusions:RPC eliminates the risk of colorectal cancer, and close upper GI surveillance may help prevent duodenal malignancy. MDTs are the principal cause of death, once colorectal cancer has been prevented, and the main reason for worsening functional results.

Sacral nerve stimulation in faecal incontinence: position statement based on a collective experience

Objective  Since the first paper published by Matzel et al., in 1995, on the efficacy of sacral nerve stimulation (SNS) in patients with faecal incontinence, the indications, the contraindications, the stimulation technique and follow up of implanted patients have changed. The aim of this article was to provide a consensus opinion on the management of patients with faecal incontinence treated with SNS.

Preoperative radiotherapy is associated with worse functional results after coloanal anastomosis for rectal cancer.

PURPOSE: This study was designed to evaluate functional outcome in patients treated with preoperative radiotherapy after low anterior resection and a coloanal anastomosis for low rectal cancer. METHODS: Functional outcome data from patients enrolled in a prospective randomized trial comparing 3 reconstructive procedures were evaluated with respect to administration of preoperative radiotherapy. Incontinence was assessed with a questionnaire on bowel function including the Fecal Incontinence Severity Index; sexual function was assessed with the Sexual Health Inventory for Men and a gender-specific questionnaire for women. Quality of life was assessed with SF-36 scores. RESULTS: Of 364 patients enrolled, 153 (42%) had no radiotherapy or chemotherapy, and 211 (58%) had preoperative radiotherapy; 186 (51%) had chemotherapy in addition to radiotherapy. Comparison of irradiated vs. nonirradiated patients showed no significant differences in postoperative morbidity (29.9% vs. 35.3%; P = 0.27). Two-year follow-up of 297 patients showed greater impairment of bowel function in irradiated patients (n = 170) vs. nonirradiated patients (n = 127): e.g., mean number of daily bowel movements at 12 months, 4.2 ± 3.5 vs. 3.5 ± 2.6, P = 0.032; urgency, 85% vs. 67%, P = 0.002). Antidiarrheal use was significantly higher in irradiated patients vs. nonirradiated patients at 4 (P = 0.043), 12 (P = 0.002), and 24 (P = 0.001) months. Sexual Health Inventory for Men scores indicated poorer function in irradiated patients at 24 months (P = 0.039). Preoperative radiotherapy had no deleterious effects on quality of life. Multivariate analyses showed that negative effects of preoperative radiotherapy on urgency at 4 months (P = 0.002) and antidiarrheal use at 24 months were independent of reconstruction technique, but a positive effect of reconstruction with a J-pouch was still observed in patients who received radiotherapy. CONCLUSION: Preoperative radiotherapy does not increase overall morbidity but is associated with poorer functional outcome after low anterior resection with coloanal anastomosis. Preoperative radiotherapy and the J-pouch are nonconfounding predictors of functional outcome up to 24 months after surgery.

Morbidity risk factors after low anterior resection with total mesorectal excision and coloanal anastomosis: a retrospective series of 483 patients.

Objective:To report postoperative morbidity after low anterior resection (LAR) and coloanal anastomosis (CAA) for rectal cancer and identify possible risk factors of complications. Background:Coloanal anastomosis after total mesorectal excision (TME) is associated with significant morbidity. Precise data on the specific morbidity and the risk factors are lacking. Methods:We analyzed retrospectively 483 consecutive LARs with TME and CAA carried out in a single center between 1996 and 2005. All complications occurring up to 3 months after LAR and up to 3 months after closure of the diverting stoma were graded according to the Dindo classification. Results:Of 483 patients, 164 (33.9%) suffered at least 1 complication, leading to death in 2 (0.4%) patients. Grade III/IV complications occurred in 69 of 483 (14.2%) patients. Thirty-four (7.0%) patients developed leakage of the CAA and 3 patients had leakage of the small bowel anastomosis after stoma closure. Ileostomy closure was carried out after a mean of 88.7 days (36–630) after LAR. The stoma was not closed in 4 of 456 (0.6%) patients. In multivariate analysis, male sex (P = 0.0216) and postoperative transfusion (P = 0.0025) were associated with complications. Medical complications were furthermore associated with previous thrombembolic events (P = 0.0012) and associated surgery at the time of LAR (P = 0.0010). Circumferential tumor localization was predictive of surgical complications (P = 0.0015). The only factor associated with a risk of leakage was transfusion (P = 0.0216). Conclusions:In this series morbidity occurred in 34% and dehiscence of the CAA in 7.0%. Transfusion requirement was an independent risk factor for postoperative complications and anastomotic leakage.

Outcome and Cost Analysis of Sacral Nerve Modulation for Treating Urinary and/or Fecal Incontinence

Background:Sacral nerve modulation (SNM) is an established treatment for urinary and fecal incontinence in patients for whom conservative management has failed. Objective:This study assessed the outcome and cost analysis of SNM compared to alternative medical and surgical treatments. Methods:Clinical outcome and cost-effectiveness analyses were performed in parallel with a prospective, multicenter cohort study that included 369 consecutive patients with urge urinary and/or fecal incontinence. The duration of follow-up was 24 months, and costs were estimated from the national health perspective. Cost-effectiveness outcomes were expressed as incremental costs per 50% of improved severity scores (incremental cost-effectiveness ratio). Results:The SNM significantly improved the continence status (P < 0.005) and quality of life (P < 0.05) of patients with urge urinary and/or fecal incontinence compared to alternative treatments. The average cost of SNM for urge urinary incontinence was &OV0556; 8525 (95% confidence interval, &OV0556; 6686–&OV0556; 10,364; P = 0.001) more for the first 2 years compared to alternative treatments. The corresponding increase in cost for subjects with fecal incontinence was &OV0556; 6581 (95% confidence interval, &OV0556; 2077–&OV0556; 11,084; P = 0.006). When an improvement of more than 50% in the continence severity score was used as the unit of effectiveness, the incremental cost-effectiveness ratio for SNM was &OV0556; 94,204 and &OV0556; 185,160 at 24 months of follow-up for urinary and fecal incontinence, respectively. Conclusions:The SNM is a cost-effective treatment for urge urinary and/or fecal incontinence.

Implication of MYH in Colorectal Polyposis

Objective:The aim of this study was to determine the frequency of MYH mutations in one large population of polyposis patients without APC mutation identified. Summary Background Data:Familial adenomatous polyposis (FAP) is the most known inherited colorectal cancer syndrome. In 70% to 80% of polyposis patients, an APC mutation is found. Patients with polyposis but no APC mutation are considered as APC-muted patients and followed as their relatives accordingly. Biallelic mutation of MYH has been found to responsible of colorectal polyposis and cancer in an autosomal recessive pattern of inheritance. Methods:Between 1978 and 2004, 433 patients were operated for polyposis. A mutation on APC was identified in 322 patients. Among the remaining patients, 44 were identified as possible MYH-muted patients and contacted, and 31 signed informed consent. Clinical data were obtained from the patients’ medical notes. Germline mutation of MYH was searched by sequencing the whole gene. To confirm the deleterious effects of biallelic MYH mutation, transversions on K-ras and APC were searched. Results:There were 9 women and 22 men with a mean age of 53.9 years (range, 22–68 years) at the time of diagnosis. The mean number of polyps was 62.8 (range, 11–266). Eighteen patients (58.1%) had a colorectal cancer. We found biallelic MYH mutation in 6 patients (19.3%; 95% confidence interval, 5.2%–33.5%) and 5 (83.3%) had transversions in K-ras and/or APC. Conclusion:MYH is a new gene responsible for about 1.4% of all adenomatous polyposis and about 20% of adenomatous polyposis without APC mutation identified. Search for MYH biallelic mutation in these patients should be systematic as it changes their and relativessurveillance.