Enteral versus parenteral nutrition in the conservative treatment of upper gastrointestinal fistula after surgery: a multicenter, randomized, parallel-group, open-label, phase III study (NUTRILEAK study).

BACKGROUND: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality. METHODS/DESIGN: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled. DISCUSSION: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial.

OBJECTIVE: To assess with a single-blinded, multicenter, randomized trial, the postoperative results in patients undergoing sphincter-saving rectal resection for cancer without preoperative mechanical bowel preparation (MBP). BACKGROUND: The collective evidence from literature strongly suggests that MBP, before elective colonic surgery, is of no benefit in terms of postoperative morbidity. Very few data and no randomized study are available for rectal surgery and preliminary results conclude toward the safety of rectal resection without MBP. METHODS: From October 2007 to January 2009, patients scheduled for elective rectal cancer sphincter-saving resection were randomized to receive preoperative MBP (ie, retrograde enema and oral laxatives) or not. Primary endpoint was the overall 30-day morbidity rate. Secondary endpoints included mortality rate, anastomotic leakage rate, major morbidity rate (Dindo III or more), degree of discomfort for the patient, and hospital stay. RESULTS: A total of 178 patients (103 men), including 89 in both groups (no-MBP and MBP groups), were included in the study. The overall and infectious morbidity rates were significantly higher in no-MBP versus MBP group, 44% versus 27%, P = 0.018, and 34% versus 16%, P = 0.005, respectively. Regarding both anastomotic leakage and major morbidity rates, there was no significant difference between no-MBP and MBP group: 19% versus 10% (P = 0.09) and 18% versus 11% (P = 0.69), respectively. Moderate or severe discomfort was reported by 40% of prepared patients. Mortality rate (1.1% vs 3.4%) and mean hospital stay (16 vs 14 days) did not differ significantly between both groups. CONCLUSIONS: This first randomized trial demonstrated that rectal cancer surgery without MBP was associated with higher risk of overall and infectious morbidity rates without any significant increase of anastomotic leakage rate. Thus, it suggests continuing to perform MBP before elective rectal resection for cancer.

Adjuvant radioimmunotherapy trial with iodine-131-labeled anti-carcinoembryonic antigen monoclonal antibody F6 F(ab')2 after resection of liver metastases from colorectal cancer.

PURPOSE: To evaluate the feasibility of radioimmunotherapy (RIT) with radiolabeled anti-carcinoembryonic antigen antibodies after complete resection of liver metastases (LM) from colorectal cancer. PATIENTS AND METHODS: Twenty-two patients planned for surgery of one to four LM received a preoperative diagnostic dose of a 131I-F(ab')2-labeled anti-carcinoembryonic antigen monoclonal antibody F6 (8-10 mCi/5 mg). 131I-F(ab')2 uptake was analyzed using direct radioactivity counting, and tumor-to-normal liver ratios were recorded. Ten patients with tumor-to-normal liver ratios of >5 and three others were treated with a therapeutic injection [180-200 mCi 131I/50 mg F(ab')2] 30 to 64 days after surgery. RESULTS: Median 131I-F(ab')2 immunoreactivity in patient serum remained at 91% of initial values for up to 96 hours after injection. The main and dose-limiting-toxicity was hematologic, with 92% and 85% grades 3 to 4 neutropenia and thrombocytopenia, respectively. Complete spontaneous recovery occurred in all patients. No human anti-mouse antibody response was observed after the diagnosis dose; however, 10 of the 13 treated patients developed human anti-mouse antibody approximately 3 months later. Two treated patients presented extrahepatic metastases at the time of RIT (one bone and one abdominal node) and two relapsed within 3 months of RIT (one in the lung and the other in the liver). Two patients are still alive, and one of these is disease-free at 93 months after resection. At a median follow-up of 127 months, the median disease-free survival is 12 months and the median overall survival is 50 months. CONCLUSION: RIT is feasible in an adjuvant setting after complete resection of LM from colorectal cancer and should be considered for future trials, possibly in combination with chemotherapy, because of the generally poor prognosis of these patients.

Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial.

BACKGROUND: We have previously described gene-expression signatures that predict growth inhibitory and cytotoxic effects of common chemotherapeutic drugs in vitro. The aim of this study was to confirm the validity of these gene-expression signatures in a large series of patients with oestrogen-receptor-negative breast tumours who were treated in a phase III neoadjuvant clinical trial. METHODS: This trial compares a non-taxane regimen (fluorouracil, epirubicin, and cyclophosphamide [FEC] for six cycles) with a taxane regimen (docetaxel for three cycles followed by epirubicin plus docetaxel [TET] for three cycles) in women with oestrogen-receptor-negative breast cancer. The primary endpoint of the study is the difference in progression-free survival based on TP53 status and will be reported later. Predicting response with gene signatures was a planned secondary endpoint of the trial and is reported here. Pathological complete response, defined as complete disappearance of the tumour with no more than a few scattered tumour cells detected by the pathologist in the resection specimen, was used to assess chemosensitivity. RNA was prepared from sections of frozen biopsies taken at diagnosis and hybridised to Affymetrix X3P microarrays. In-vitro single-agent drug sensitivity signatures were combined to obtain FEC and TET regimen-specific signatures. This study is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00017095. FINDINGS: Of 212 patients with oestrogen-receptor-negative tumours assessed, 87 patients were excluded. 125 oestrogen-receptor-negative tumours (55 that showed pathological complete responses) were tested: 66 in the FEC group (28 that showed pathological complete responses) and 59 in the TET group (27 that showed pathological complete responses). The regimen-specific signatures significantly predicted pathological complete response in patients treated with the appropriate regimen (p<0.0001). The FEC predictor had a sensitivity of 96% (27 of 28 patients [95% CI 82-99]), specificity of 66% (25 of 38 patients [50-79]), positive predictive value (PPV) of 68% (27 of 40 patients [52-80]), and negative predictive value (NPV) of 96% (25 of 26 patients [81-99]). The TET predictor had a sensitivity of 93% (25 of 27 patients [77-98]), specificity 69% (22 of 32 patients [51-82]), PPV of 71% (25 of 35 patients [55-84]), and NPV of 92% (22 of 24 patients [74-98]). Analysis of tumour size, grade, nodal status, age, and regimen-specific signatures showed that the genomic signatures were the only independent variables predicting pathological complete response at p<0.01. Selection of patients with these signatures would increase the proportion of patients with pathological complete responses from 44% to around 70% in the patients studied here. INTERPRETATION: We have validated the use of regimen-specific drug sensitivity signatures in the context of a multicentre randomised trial. The high NPV of both signatures may allow early selection of patients with breast cancer who should be considered for trials with new drugs.

[Rectal cancer Information dedicated to cancer patients and relatives]. / Comprendre le cancer du rectum Information à l'usage des personnes malades et de leurs proches.

In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives, the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals, the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbook SOR SAVOIR PATIENT Understanding rectal cancer is an adapted version of the clinical practice guidelines (CPG) Standards, Options and Recommendations for rectal cancer. It is meant to provide a basis for the explanation of the disease and treatments and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 Paris, Tel. (0033) 1 44 23 04 68, www.fnclcc.fr). This document has been validated at the end of 2004 and published in 2005. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. Information leaflets, extracted from the handbook SOR SAVOIR PATIENT Understanding rectal cancer and published in this edition of the Bulletin du cancer, allow patients to better understand colonoscopy and colostomy, which represent an important patient information need. These articles are meant to inform patients and relatives about the disease and its treatments. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.

Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results.

PURPOSE: The standard radiotherapy (RT) of breast cancer consists of 50 Gy external beam RT (EBRT) to the whole breast followed by an electron boost of 10-16 Gy to the tumor bed, but this has several cosmetic disadvantages. Intraoperative radiotherapy (IORT) could be an alternative to overcome these. METHODS AND MATERIALS: We evaluated 50 women with early breast cancer operated on in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy fractions). Late toxicity and cosmetic results were assessed independently by two physicians according to the Common Terminology Criteria for Adverse Event v3.0 grading system and the European Organization for Research and Treatment of Cancer questionnaires. RESULTS: After a median follow-up of 9.1 years (range, 5-15 years), two local recurrences were observed within the primary tumor bed. At the time of analysis, 45 patients are alive with (n = 1) or without disease. Among the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous fibrosis within the boost area. Overall, the scores indicated a very good quality of life and cosmesis was good to excellent in the evaluated patients. CONCLUSION: Our results confirm that IORT given as a boost after breast-conserving surgery is a reliable alternative to conventional postoperative fractionated boost radiation.