Bernard Saint-Aubert

Perioperative Chemotherapy Compared With Surgery Alone for Resectable Gastroesophageal Adenocarcinoma: An FNCLCC and FFCD Multicenter Phase III Trial

PURPOSE After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma. PATIENTS AND METHODS Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS. RESULTS Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio [HR] for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups. CONCLUSION In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.

Transanal endoscopic proctectomy: an innovative procedure for difficult resection of rectal tumors in men with narrow pelvis.

BACKGROUND: In rectal surgery, some situations can be critical, such as anterior topography of locally advanced low tumors with a positive predictive radial margin, especially in a narrow pelvis of men who are obese. Transanal proctectomy is a new laparoscopic technique that uses the transanal endoscopic microsurgery device. OBJECTIVE: The aim of this study is to evaluate the technical feasibility of laparoscopic transanal proctectomy in patients with unfavorable features. DESIGN AND PATIENTS: This is a single-center, prospective analysis of selected patients with rectal cancer operated on from January 2009 to June 2011. MAIN OUTCOME MEASURES: Intraoperative details and short-term postoperative outcome were described. RESULTS: Thirty men with advanced or recurrent low rectal tumors associated with unfavorable anatomical and/or tumor characteristics underwent a sphincter-sparing transanal endoscopic proctectomy. Twenty-nine patients had received preoperative treatment. We report a 6% conversion rate, no postoperative mortality, and a 30% morbidity rate. At the beginning of our experience, a urethral injury was diagnosed in 2 patients and easily sutured intraoperatively, without postoperative after-effect. The mesorectal resection was graded as “good” in all patients. R0 resection was achieved in 26 patients (87%). The short-term stoma closure rate was 85%. After a median follow-up of 21 months, 4 patients experienced locoregional recurrence alone. Overall survival rates at 12 and 24 months were 96.6% (95% CI, 78.0–99.5) and 80.5% (95% CI, 53.0–92.9). Relapse-free survival rates at 12 and 24 months were 93.3% (95% CI, 75.9–98.3) and 88.9% (95% CI, 69.0–96.3). LIMITATIONS: Although the transanal endoscopic proctectomy was performed by trained surgeons, we report a slight increase in early postoperative morbidity and relatively poor early outcome. There was a clear selection bias related to the study cohort exclusively composed of high-risk patients, but we need to be cautious before generalizing this technique. CONCLUSION: The transanal endoscopic proctectomy is a feasible alternative surgical option to conventional laparoscopy for radical rectal resection in selected cases with unfavorable characteristics. Further investigations with larger cohorts are required to validate its safety and to clarify its best indication.

Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis.

Objective: To assess the perioperative and long-term results of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) using oxaliplatin+irinotecan (ox-irino) versus oxaliplatin alone (ox-alone). Background: Treatment of peritoneal carcinomatosis (PC) of colorectal origin with CRS+HIPEC using mitomycin-C or oxaliplatin monotherapy has shown encouraging survival results. This bi-centric study evaluates an intensified intraperitoneal combination of ox-irino and compares it with ox-alone. Patients and Methods: All consecutive patients with PC undergoing CRS+HIPEC using either ox-alone or ox-irino between1998 and 2007 were evaluated. Results: One hundred forty-six patients underwent CRS+HIPEC for PC, 103 received ox-irino and 43 received ox-alone. The median peritoneal carcinomatosis index (PCI) was 11 in both groups. 90.4% had complete cytoreduction. Overall mortality rate was 4.1%. The overall morbidity rate was 47.2% and was significantly lower with ox-alone (34.9% vs. 52.4%, P = 0.05). After a median follow-up of 48.5months, the median overall survival (OS) was 41months (95% CI, 32–60) and median relapse-free survival (RFS) was 15.7 months (95% CI, 12–18). The median RFS of ox-alone (16.8 months; 95% CI, 11-25) was not significantly different from ox-irino (15.7 months; 95% CI, 11—18; P = 0.93). There was no significant difference between median OS of ox-alone (40.83 months; 95%CI, 29–61) and ox-irino (47 months; 95%CI, 32–61; P = 0.94). At 5 years, OS and RFS rates were 41.8% and 13.8% in ox-alone and 42.4% and 14.2% in ox-irino, respectively. Prognostic factors confirmed on multivariate analysis were lymph node metastasis and PCI. Conclusion: Our study showed no advantage of intensification of HIPEC by adding irinotecan, contrary to the results obtained with IV combination. Ox-alone HIPEC should continue as one of the standard HIPEC regimens for PC.

Intraoperative Radiotherapy in Early-Stage Breast Cancer: Results of the Montpellier Phase II Trial

PURPOSE We recently presented the intraoperative radiotherapy (IORT) technique given as a reliable alternative to conventional boost radiation after breast-conserving surgery. The low crude numbers of recurrence in elderly patients led us to investigate the feasibility and the efficacy of this procedure as a sole treatment. METHODS AND MATERIALS We included 94 patients older than 65 years in this phase II trial. Among them, 42 patients presented with all the inclusion criteria, i.e., stages pT0 to pT1 and pN0, ductal invasive unifocal carcinoma, and tumor-free margin of >2 mm. IORT was delivered using a dedicated linear accelerator. One 21-Gy fraction was prescribed and specified at the 90% isodose, using electrons. In vivo dosimetry was performed for all patients. The primary endpoint was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, and specific and overall rates of survival. RESULTS The median follow-up was 30 months (range, 12-49 months), and median age was 72 years (range, 66-80 years). The median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Endpoints for all but one patient corresponded to acceptable quality index criteria. Pretreatment quality-of-life scores were maximal, and no significant decrease was observed during follow-up. Cosmesis was good to excellent at 6 months. Two patients experienced recurrence but underwent salvage mastectomy. CONCLUSION Our results confirm that exclusive partial-breast IORT is feasible for treating early-stage breast cancer in the elderly. IORT may be considered an alternative treatment for a selected population and offers a safe one-step treatment.

Restorative and nonrestorative surgery for low rectal cancer after high-dose radiation: long-term oncologic and functional results.

AbstractPURPOSE: This prospective, nonrandomized study evaluates, with a seven-year median follow-up, the morbidity and the functional and oncologic results of conservative surgery after high-dose radiation for cancer of the lower third of the rectum of patients who would otherwise have undergone abdominoperineal resection. METHODS: Between June 1990 and June 1996, 43 patients with distal rectal adenocarcinoma were treated by preoperative radiotherapy (40 + 20 Gy delivered with three fields) and curative surgery. The mean distance from the anal verge was 50 (range, 25–60) mm, and none of the tumors was fixed (15 percent T2N0, 53 percent T3N0, 32 percent T3N1). RESULTS: Postoperative mortality (2 percent) and morbidity (35 percent) were not increased by high-dose preoperative radiation. Conservative surgery was done in 30 patients (70 percent: 26 coloanal anastomoses and 4 low stapled anastomoses). After conservative surgery, long-term functional results showed 30 percent complete continence and 20 percent serious incontinence. Four patients had local recurrence as first development (13 percent). The seven-year overall survival rate was 53 percent, 62 percent after conservative surgery and 31 percent after abdominoperineal resection. The univariate analysis underscores the tumor response impact on long-term survival (pT<3 = 81 percent; pT3 = 35 percent; P = 0.0008). CONCLUSIONS: These long-term results confirm the feasibility of conservative surgery for low rectal carcinoma after high-dose radiation. A prospective multicentric trial began in France in June 1996 to evaluate the reproducibility of these results.

Intra-operative radiotherapy of rectal cancer: Results of the French multi-institutional randomized study

PURPOSE To assess efficacy and tolerance of intra-operative radiation therapy (IORT) in patients suffering from locally advanced rectal cancer, treated with preoperative radiotherapy followed by surgical resection. METHODS AND MATERIALS In this French, multicenter, comparative, phase III study, 142 patients with locally advanced rectal cancer (T3 or T4 or N+, and M0), treated with a 4-week preoperative radiotherapy (40 grays) were randomly assigned to either surgical resection alone ( CONTROL GROUP n=69) or combined to 18-gray intra-operative radiation therapy (IORT group: n=73) between 1993 and 2001. RESULTS The 5-year cumulative incidence of local control was 91.8% with IORT and 92.8% with surgery alone (p=0.6018); the mean duration without local relapse (Kaplan-Meier method) was 107 versus 126 months, respectively. No statistically significant difference was demonstrated for overall survival (p=0.2578) disease-free survival (p=0.7808) and probability of metastatic relapse (p=0.6037) with 5-year cumulative incidences of 69.8% versus 74.8%, 63.7% versus 63.1%, and 26.1% versus 30.2%, respectively. 48 patients of the IORT group and 53 patients of the control group were alive with a median follow-up of 60.1 and 61.2 months, respectively. Post-operative complications were observed in the IORT group in 21 patients (29.6%) and in the control group in 13 patients (19.1%) (p=0.15), with an acceptable tolerance profile. CONCLUSIONS Although this randomized study did not demonstrate any significant improvement in local control and disease-free survival in rectal cancer patients treated with preoperative radiation therapy receiving IORT or not, it confirmed the technical feasibility and the necessity for evaluating IORT for rectal carcinoma in further clinical studies.

Intra-operative radiotherapy in soft tissue sarcomas

We treated 31 soft tissue sarcoma bearing patients with intraoperative radiation therapy (IORT) with ages ranging from 26 to 71: first curative intent treatment, 16 patients; and recurrent tumors, 15 patients. The tumor site was the pelvis and the retroperitoneal spaces in 13 patients and the limbs or the trunk in 18 patients. The histological type was: malignant histiocytofibroma, 14 patients; liposarcomas, 10 patients; malignant schwanoma, 1 patient; leiomyosarcoma, 2 patients; hemangiopericytoma, 1 patient; embryonic rhabdomyosarcoma, 2 patients; and synovialosarcoma, 1 patient. All the patients were diagnosed without any distant metastatic evolution at the moment of the treatment. All the patients except one underwent a complete surgical excision without any gross residual disease and received an intraoperative radiation single dose of 10 Gy in one case, 12.5 Gy in one case, 13 Gy in one case, 15 Gy in 17 cases, 18 Gy in three cases, 20 Gy in seven cases and 25 Gy in one case. Thereafter the treatment was completed by a postoperative X-ray dose of 45-50 Gy in 4.5-5 weeks for 16 patients. Local control (LC) was obtained in 27 out of 31 patients (87%), with a minimal follow-up duration of 2 years. Eleven out of 31 patients died: seven with local control (one from an intercurrent disease, six from distant metastasis) and four with local failure inside the IORT fields. Twenty patients are alive with no evolutive disease in 19 cases and with a distant metastasis in one case.(ABSTRACT TRUNCATED AT 250 WORDS)

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 ∼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.

Experimental Model of Extended Repeated Partial Hepatectomy in the Dog

The model of extended repeated partial hepatectomy without vascular shunt in dogs is presented. It consisted of 65% initial hepatectomy and after liver regeneration (6-10 weeks) repeated hepatectomy. Finally, only the papillary process of the caudate lobe (PPC), which constitutes 5% of the initial hepatic mass, was left intact. The most important finding was an ability of PPC to reconstitute the liver mass which enabled survival without the vascular shunt. After repeated hepatectomy the need for artificial hepatic assistance (parenteral nutritional support with frozen plasma) was imperative to offset the effects of acute hepatic failure and to support PPC regeneration.

Autotransplantation of the pylorus sphincter at the terminal abdominal colostomy

A method for constructing a continent colostomy has been tried in dogs. The pylorus sphincter with blood supply by the left gastroepiploic vessels was transposed around or anastomosed to the terminal abdominal colostomy in five dogs. One dog had a colostomy without pylorus transplantation. Evaluation was by clinical (consistency and weight of fecal material and number of defecations per day), radiologic, and manometry studies. There was no difference in the clinical data. In all the dogs, the radiologic study demonstrated emptying of the contrast medium to the peristomal skin. By manometry one high-pressure zone was demonstrated, and, in all dogs with a transposed or anastomosed pyloric segment, the average resting pressure was superior to that of the control dog. However, the transposed pylorus sphincter alone was not sufficient to control continence.