Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers: A Phase II Multicenter Randomized Controlled Trial (PRODIGE 22).

BACKGROUND: Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC). OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC. METHODS: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery. RESULTS: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group. CONCLUSIONS: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.

Prognostic factors of hemorrhagic complications after oxaliplatin-based hyperthermic intraperitoneal chemotherapy: Toward routine preoperative dosage of Von Willebrand factor?

BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC-ox) induces specific morbidity with hemorrhagic complications (HC). The aim of this study was to identify preoperative, intraoperative and postoperative HC predictive factors after HIPEC-ox. METHODS: A prospective single center study that included all consecutive patients treated with curative-intent HIPEC-ox, whatever the origin of peritoneal disease, was conducted. All patients underwent systematic blood tests exploring primary hemostasis and endothelial activation before surgical incision (D0) and on postoperative days 2 (POD2) and 5 (POD5). RESULTS: Between May 2012 and August 2015, 47 patients were enrolled in the study. The overall HC rate was 38%. Major morbidity was significantly higher in patients with HC. Patients presenting HC were significantly more often affected with pseudomyxoma peritonei and had less preoperative chemotherapy. Multivariate analysis showed that a higher plasmatic level of Von Willebrand factor antigen at D0 (D0 VWF:Ag) was a protective predictive factor for HC (p = 0.049, HR: 0.97 CI 95% [0.94-1.00]). A D0 VWF:Ag level below 138% had a sensitivity of 87.5%, a specificity of 67% and an area under the curve of 80.3% (CI 95% [66.5-94], p < 0.01) for predicting HC. CONCLUSIONS: Through the identification of prognostic factors, this study highlighted a subgroup of patients with low risk of HC after HIPEC-ox. Based on these results, we propose a routine preoperative dosage of VWF that would help the surgeon to select the most suitable patients for HIPEC-ox.

Outcomes of hypnosis combined with local anesthesia during inguinal repair: a pilot study.

PURPOSE: To evaluate the usefulness and outcomes of hypnosis associated with local anesthesia during inguinal hernia repair procedure, notably on post-operative pain. METHODS: A prospective study included patients operated on inguinal hernia repair according to Lichtenstein technique from January 2013 to September 2014. The cohort was divided into three groups (group 1: local anesthesia; group 2: hypnosis and local anesthesia; and group 3: general anesthesia). A questionnaire was filled by each participant before and after surgery. Pre-operative apprehension, pain at hospital discharge, surgeon comfort during procedure, immediate satisfaction after hospital discharge, and satisfaction at 1 month after surgery were evaluated. RESULTS: A total of 103 patients were included in this study (group 1: n = 55; group 2: n = 35; and group 3: n = 13). Pre-operative apprehension and pain at hospital discharge's scores were significantly higher in the group 3 than in the groups 1 and 2 (p < 0.001). Pain at hospital discharge was significantly lower in the group 2 than in the group 1 (p = 0.03). Pre-operative apprehension, surgeon comfort during procedure, immediate satisfaction after hospital discharge, and satisfaction at 1 month after surgery were similar between groups 1 and 2. CONCLUSION: Hypnosis combined with local anesthesia is a feasible technique which allows extending inguinal hernia repair to a large population. There is no complication associated with its use.

Routine second-look after surgical treatment of colonic peritoneal carcinomatosis.

BACKGROUND: Surgical procedures that combine both complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved the survival of patients with peritoneal carcinomatosis (PC). Current imaging and laboratory investigations are not very useful to diagnose PC. This prospective study sought to determine the usefulness of routine second-look surgery (RSLS) combined with HIPEC in the diagnosis and treatment of patients with PC at high-risk for recurrence. METHODS: From 2007 to 2011, RSLS was performed on 14 patients who had undergone a complete initial oncological resection for synchronous colonic PC and/or ovarian metastasis with PC discovered during primary colon cancer surgery after a course of 12 cycles of intravenous chemotherapy, eventually associated with HIPEC. RESULTS: Pathology confirmed PC in 71% of patients during RSLS, with a median peritoneal carcinomatosis index (PCI) of 10. There was no post-operative mortality, while 7% of patients exhibited Dindo Grade III-IV complications. The 2-year overall survival and disease-free survival rates were 91% and 38%, respectively. Following RSLS and CCRS, peritoneal recurrence was observed in only 8% of patients who had undergone HIPEC. CONCLUSION: RSLS combined with HIPEC after initial resection of synchronous colonic PC allows diagnosis and treatment of low-score PC, with limited post-operative complications and increased overall survival rates.