Francis Michot

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy.

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

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.

The safety and efficacy of the artificial bowel sphincter for fecal incontinence: results from a multicenter cohort study.

AbstractPURPOSE: The aim of this trial was to evaluate the safety, efficacy, and impact on quality of life of the Acticon™ artificial bowel sphincter for fecal incontinence. METHODS: A multicenter, prospective, nonrandomized clinical trial was conducted under a common protocol. Patients were evaluated with anal physiology, endoanal ultrasonography, a fecal incontinence scoring system, fecal incontinence quality of life assessment, and overall health evaluation. Patients with a fecal incontinence score of 88 or greater (scale, 1–120) were considered candidates for the study. Implanted patients underwent identical reevaluation at 6 and 12 months postimplant. RESULTS: One hundred twelve of 115 patients (86 females) enrolled were implanted. Mean age was 49 (range, 18–81) years. A total of 384 device-related or potentially device-related adverse events were reported in 99 enrolled patients. Of these events, 246 required no intervention or only noninvasive intervention. Seventy-three revisional operations were required in 51 (46 percent) of the 112 implanted patients. Infection rate necessitating surgical revision was 25 percent. Forty-one patients (37 percent) have had their devices completely explanted, of which 7 have had successful reimplantations. In patients with a functioning neosphincter, improvement in quality of life and anal continence was documented. Mean matched fecal incontinence scores in 63 patients at 6 months follow-up was improved from 105 preimplant to 51 postimplant. In 55 patients at 12 months follow-up, mean matched fecal incontinence scores were 105 preimplant vs. 48 postimplant. A successful outcome was achieved in 85 percent of patients with a functioning device. Intention to treat success rate was 53 percent. CONCLUSIONS: Although morbidity and the need for revisional surgery are high, the artificial bowel sphincter can improve anal incontinence and quality of life in patients with severe fecal incontinence.

Life-threatening postoperative pancreatic fistula (grade C) after pancreaticoduodenectomy: incidence, prognosis, and risk factors.

BACKGROUND Pancreatic fistula (PF) is one of the most common postoperative complications of pancreatoduodenectomy (PD). A recent International Study Group on Pancreatic Fistula (ISGPF) definition grades the severity of PF according to the clinical impact on the patients hospital course. Although PF is generally treated conservatively (grade A), some cases may require interventional procedures (grade B) or may be life-threatening and necessitate emergency reoperation (grade C). The aim of the present study was to evaluate the incidence of postoperative grade C PF after PD and to assess the prognosis and risk factors for this life-threatening condition. STUDY DESIGN Between January 2000 and December 2006, 680 consecutive patients underwent PD in 5 digestive surgery departments in the northwest region of France (Lille, Amiens, Rouen, and Caen). PF was defined as drain output of any measurable volume of fluid on or after postoperative day 3 with amylase content greater than 3 times the serum amylase activity (ISGPF guidelines). To identify possible risk factors for grade C PF, we reviewed the records of 111 (16.3%) patients with postoperative PF and compared grade C cases with grade A+B cases. RESULTS The median age was 59 years (range 22-87). The male-to-female ratio was 1.6:1. Fifty-six (50.4%) PDs were performed via pancreaticogastrostomy and 55 via pancreaticojejunostomy. Overall mortality was 2% (n = 14). Grade C PF was observed in 36 (32%) patients, of whom 17 (47%) had sepsis due to an abdominal collection, 16 (44%) had postoperative bleeding, 10 (27.7%) had bleeding associated with abdominal collection, and 3 (9%) had multi-organ failure due to other causes. Of these 36 patients, 35 (97%) underwent reoperation. The mortality rate in grade C PF patients was 38.8%. The major causes of death were sepsis (n = 6) and recurrent bleeding after reoperation (n = 5). Grade C PF increased the duration of postoperative hospitalization (46 vs 29 days, P < .001). Univariate analysis showed that peroperative soft pancreatic parenchyma, peroperative blood transfusion, and postoperative bleeding were significant risk factors for grade C PF, with P values of .011, .003, and .001, respectively. No risk factors for grade C PF were identified in a multivariate analysis. The sensibility, specificity, positive predictive value, and negative predictive value of the presence of the 3 risk factors for grade C PF were 13.89%, 100%, 100%, and 70.75%, respectively. CONCLUSION Sixteen percent of patients had PF after PD. Among them, 30% had grade C PF, with a mortality rate of about 40%. Achievement of a 100% predictive positive value for grade C PF after PD in individuals with 3 discriminant risk factors (peroperative soft pancreatic parenchyma, peroperative transfusion, and postoperative bleeding) is a first step towards the identification of high-risk patients who should be managed differently from other patients with PF during or after PD.

Results of artificial sphincter in severe anal incontinence

PURPOSE AND METHODS: Fourteen AMS 800® (American Medical Systems, Minneapolis, MN) urinary artificial sphincters have been consecutively implanted in 13 patients with total incontinence for stool of various causes (traumatic or postoperative, 7; congenital, 3; neurologic, 2; idiopathic, 1). No proximal stoma was constructed but was already present in one patient before implantation. RESULTS: Sepsis occurred in two patients. Removal of sphincter and colostomy was necessary in three patients: one of these two had developed sepsis, one had perineal ulceration before activation of the sphincter in a severely scarred perineum, and one had severe pain in a radiation-injured anorectum. Sphincter-related failure occurred once by rupture of the cuff in a constipated woman after two years of satisfactory function. Reimplantation of a new cuff restored normal continence in this patient. After median follow-up of 20 (range, 4–60) months, nine of ten patients with a functioning sphincter were continent for stool, and five were also continent for gas. Failure occurred in one patient because the cuff was too large to occlude the anal canal. This patient is awaiting reimplantation. Four patients experienced easily controlled difficulties with evacuation of feces. Anal pressure with inflated cuff varied from 43 to 94 (mean, 58±12) cm H2O. CONCLUSION: These results show that an artificial sphincter has a role in the treatment of severe anal incontinence when local therapies are not applicable or have failed.

Sacral nerve stimulation in fecal incontinence: are there factors associated with success?

PurposeSacral nerve stimulation has been used successfully in treating fecal incontinence. This study was designed to evaluate the proportion of patients with unsuccessful implantation despite positive test stimulation and to examine and compare factors associated with the success of the transitory and permanent sacral nerve stimulation.MethodsA total of 61 patients (55 females; median age, 56 (range, 33–77) years) with refractory fecal incontinence underwent temporary stimulation. A 50 percent or greater improvement in the number of episodes of fecal incontinence or urgency was required to proceed to permanent implantation and was the criteria of success of permanent sacral nerve stimulation at the last follow-up visit in implanted patients. The factors compared between the success and the failure groups during temporary and permanent stimulation were patients’ age and gender, diagnosis and characteristics of fecal incontinence, previous surgery, quality of life scores, anorectal manometry, endoanal ultrasound, and electrophysiologic tests performed before stimulation.ResultsTemporary stimulation was successful in 35 patients (57.4 percent). A permanent neurostimulation device was implanted in 33 patients. Age was the only factor related to success of the temporary stimulation (P=0.03). After permanent implantation, 31 percent of patients did not attain screening phase results for the number of episodes of fecal incontinence or urgency. A neurologic disorder was more frequently the origin of fecal incontinence in the success group compared with others (P=0.03). The left bulbocavernosus reflex was more frequently delayed in the success group than in the others (P=0.03), and a prolonged or absent bulbocavernosus reflex was more frequent in the success group than in the failure group (P=0.03).ConclusionsPatients with fecal incontinence from neurologic origins could be good candidates for sacral nerve stimulation.

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.

Long-Term Outcomes of Transanal Rectocele Repair

PURPOSE:This study was designed to assess the risk of rectocele recurrence after transanal repair and identify its predictive factors.METHODS:A series of 71 females who had undergone transanal repair of low isolated rectocele was retrospectively reviewed. The functional outcome was assessed by a standard questionnaire. The follow-up varied from 30 to 128 (mean, 74 ± 30) months. Recurrences were evaluated by survival-analysis methods, and Cox’s proportional hazard model was used to determine the optimal predictive factor for recurrence.RESULTS:Twenty-nine of 71 patients had isolated low rectocele recurrence, and 6 had a rectocele recurrence associated to an enterocele occurrence. The optimal predictive factor for rectocele recurrence was the persistence of symptoms two months after surgery. Although correlated to recurrences, preoperative manual pressure during defecation was not an independent predictive factor for recurrences. Preoperative defecographic parameters do not seem to influence clinical outcome of surgery, and preoperative manometric values did not determine which females could develop anal incontinence several years after surgery.CONCLUSIONS:The results of the transanal rectocele repair might progressively be worse during the length of the follow-up with a high recurrence rate (50 percent). Preoperative clinic, defecographic, or manometric parameters are not useful to identify females at risk for recurrence.

Predictive factors for successful sacral nerve stimulation in the treatment of faecal incontinence: results of trial stimulation in 200 patients.

Aim  Sacral nerve stimulation (SNS) has a place in the treatment algorithm for faecal incontinence (FI). However, after implantation, 15–30% of patients with FI fail to respond for unknown reasons. We investigated the effect of SNS on continence and quality of life (QOL) and tried to identify specific predictive factors of the success of permanent SNS in the treatment of FI.

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.