Jean-Pierre Arnaud

Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC).

A randomized clinical trial was conducted by the European Organization for Research and Treatment for Cancer (EORTC) Gastrointestinal Cancer Cooperative Group to study the effectiveness of irradiation therapy administered in a dosage of 34.5 Gy, divided into 15 daily doses of 2.3 Gy each before radical surgery for rectal cancer (T2, T3, T4, NX, MO). Four hundred sixty-six patients were entered in the clinical trial between June 1976 and September 1981. Tolerance and side effects of pre- operative irradiation were acceptable. The overall 5-year survival rates were similar in both groups. When considering only the 341 patients treated by surgery with a curative aim, the 5-year survival rates were 59.1% and 69.1% in the control group and in the combined modality group, respectively (p = 0.08). The local recurrence rates at 5 years were 30% and 15% in the control group and the adjuvant radiotherapy group, respectively (p = 0.003). Although this study did not show preoperative radiotherapy to have a statistically significant benefit on overall survival, it does have a clear effect on local control of rectal cancer. Therefore, before performing radical surgery, this adjuvant therapy should be administered to patients who have locally extended rectal cancer.

External pancreatic duct stent decreases pancreatic fistula rate after pancreaticoduodenectomy: prospective multicenter randomized trial.

Objective: Pancreatic fistula (PF) is a leading cause of morbidity and mortality after pancreaticoduodenectomy (PD). The aim of this multicenter prospective randomized trial was to compare the results of PD with an external drainage stent versus no stent. Methods: Between 2006 and 2009, 158 patients who underwent PD were randomized intraoperatively to either receive an external stent inserted across the anastomosis to drain the pancreatic duct (n = 77) or no stent (n = 81). The criteria of inclusion were soft pancreas and a diameter of wirsung <3 mm. The primary study end point was PF rate defined as amylase-rich fluid (amylase concentration >3 times the upper limit of normal serum amylase level) collected from the peripancreatic drains after postoperative day 3. CT scan was routinely done on day 7. Results: The 2 groups were comparable concerning demographic data, underlying pathologies, presenting symptoms, presence of comorbid illness, and proportion of patients with preoperative biliary drainage. Mortality, morbidity, and PF rates were 3.8%, 51.8%, and 34.2%, respectively. Stented group had a significantly lower overall PF (26% vs. 42%; P = 0.034), morbidity (41.5% vs. 61.7%; P = 0.01), and delayed gastric emptying (7.8% vs. 27.2%; P = 0.001) rates compared with nonstented group. Radiologic or surgical intervention for PF was required in 9 patients in the stented group and 12 patients in the nonstented group. There were no significant differences in mortality rate (3.7% vs. 3.9%; P = 0.37) and in hospital stay (22 days vs. 26 days; P = 0.11). Conclusion: External drainage of pancreatic duct with a stent reduced. PF and overall morbidity rates after PD in high risk patients (soft pancreatic texture and a nondilated pancreatic duct). This study is registered at http://www.clinicaltrials.gov: Clinical trial ID# NCT01068886.

Stapled hemorrhoidopexy versus milligan-morgan hemorrhoidectomy : A prospective, randomized, multicenter trial with 2-year postoperative follow up

Purpose:The purpose of this study was to compare the outcome of stapled hemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan technique (MM group). The goals of the study were to evaluate the efficacy and reproducibility of stapled hemorrhoidopexy and define its place among conventional techniques. Methods:A series of 134 patients were included at 7 hospital centers. They were randomized according to a single-masked design and stratified by center (with balancing every 4 patients). Patients were clinically evaluated preoperatively and at 6 weeks, 1 year, and a minimum of 2 years after treatment. Patients completed a questionnaire before and 1 year after surgery to evaluate symptoms, function, and overall satisfaction. Results:The mean follow-up period was 2.21 years ± 0.26 (1.89–3.07). Nine patients (7%) could not be monitored at 1 or 2 years, but 4 of these 9 nevertheless filled in the 1-year questionnaire. The patients in the SH group experienced less postoperative pain/discomfort as scored by pain during bowel movement (P < 0.001), total analgesic requirement over the first 3 days (according to the World Health Organization [WHO] class II analgesics [P = 0.002]; class III [P = 0.066]), and per-patient consumption frequency of class III analgesics (P = 0.089). A clear difference in morphine requirement became evident after 24 hours (P = 0.010). Hospital stay was significantly shorter in the SH group (SH 2.2 ± 1.2 [0; 5.0] versus MM 3.1 ± 1.7 [1; 8.0] P < 0.001). At 1 year, no differences in the resolution of symptoms were observed between the 2 groups, and over 2 years, the overall incidence of complications was the same, specifically fecaloma (P = 0.003) in the MM group and external hemorrhoidal thrombosis (P = 0.006) in the SH group. Impaired sphincter function was observed at 1 year with no significant difference between the groups for urgency (12%), continence problems (10%), or tenesmus (3%). No patient needed a second procedure for recurrence within 2 years, although partial residual prolapse was detected in 4 SH patients (7.5%) versus 1 MM patient (1.8%) (P = 0.194). Conclusion:Stapled hemorrhoidopexy causes significantly less postoperative pain. The technique is reproducible and can achieve comparable outcomes as those of the MM technique as long as the well-described steps of the technique are followed. Like with conventional surgery, anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients. Its effectiveness in relieving symptoms is equivalent to conventional surgery, and the number of hemorrhoidal prolapse recurrences at 2 years is not significantly different. Hemorroidopexy is applicable for treating reducible hemorrhoidal prolapse.

Pancreaticoduodenectomy: superior mesenteric artery first approach.

Pancreaticoduodenectomy (PD) is the only effective treatment for cancers of the periampullary region. Many technical modifications of reconstruction after PD have been described. However, the technique of resection followed in most centers is similar.1 One of the important predictive factors of prognosis is the presence of retroperitoneal lymph node metastases, which are present in 20%–77% of resected specimens of patients with carcinoma of the head of the pancreas.2 Hence, lymph node dissection to the right of the superior mesenteric vessels is a minimum requirement. Another common technical difficulty encountered during classic PD is the presence of a replaced right hepatic artery arising from the superior mesenteric artery (SMA). This anomaly occurs in 15%–20% of patients. Inadvertent injury to this vessel can occur during the dissection of the uncinate process, especially in cases of advanced tumors. Above all, infiltration of superior mesenteric vein (SMV) and/or portal vein (PV) is encountered in a significant proportion of patients with pancreas head tumors.3 En bloc resection and reconstruction of the vein can be performed without increased morbidity and mortality.4 However, infiltration of the SMA is considered a contraindication for resection. Infiltration of these major vessels is usually identified only toward the end of the resection process, when the surgeon is committed to resection. The end result is often a “margin-positive” resection. These patients with margin-positive resection have a poor prognosis that is often not better than that of unresected patients. To overcome these technical difficulties and to achieve an oncologically acceptable lymph node clearance, we describe a technique of PD in which the SMA is dissected first and the posterior pancreatic capsule is dissected early during the operation. The

Interim analysis of a phase III study on preoperative radiation therapy in resectable rectal carcinoma. Trial of the gastrointestinal tract cancer cooperative group of the European organization for research on treatment of cancer (EORTC)

To improve surgical results of potentially operable rectal cancer (T2, T3, T4, Mo), the European Organization for Research on Treatment of Cancer (EORTC) conducted a two‐arm randomized clinical trial to evaluate the effect of administering radiotherapy before radical surgery. Four hundred ten patients were allocated to be treated either by surgery alone or by 34.5 Gy of radiotherapy (in 19 days overall) followed by surgery. The tolerance of the adjuvant radiation therapy was fairly good. The 5‐year survival rate was 65% overall and showed no difference between both therapeutic regimens. Similarly, the metastases‐free rate was the same in both groups. In contrast, the preoperative radiation therapy showed a marked effect on local control of the disease, the comparison of the time to local recurrence being highly significant between the two treatment groups (P = 0.001). The proportion of patients free of local recurrence at 5 years was 85% in the combined treatment versus 65% in the group of patients treated by surgery alone.

Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial.

OBJECTIVE To evaluate the results of a prospective multicenter randomized study of adjuvant intraperitoneal 5-fluorouracil (5-FU) administered during 6 days shortly after resection of stages II and III colon cancers. SUMMARY BACKGROUND DATA Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months. Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects. METHODS After resection, 267 patients were randomized into two groups. Patients in group 1 (n = 133) underwent resection followed by intraperitoneal administration of 5-FU (0.6 g/m2/day) for 6 days (day 4 to day 10). These patients also received intravenous 5-FU (1 g) during surgery. Patients in group 2 underwent resection alone (n = 134). RESULTS In group 1, 103 patients received the total dose, 18 received a partial dose as a result of technical or tolerance problems, and 12 did not receive the chemotherapy. Rates of surgical death and complications were similar in both groups. Tolerance to treatment was excellent or fair in 97% of the patients and poor in 3%. After a median follow-up of 58 months, 5-year overall survival rates were 74% in group 1 and 69% in group 2; disease-free survival rates were 68% and 62%, respectively. Survival curves were superimposed until 3 years after treatment and began diverging thereafter. Among patients receiving the full treatment, the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers. CONCLUSIONS Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly. However, it reduced the risk of recurrence in stage II cancers. These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences.

Colorectal Surgery in Cirrhotic Patients: Assessment of Operative Morbidity and Mortality

PurposeThe morbidity from colorectal surgery can be high and increases for patients with cirrhosis of the liver. This study was designed to assess morbidity, mortality, and prognostic factors for patients with cirrhosis undergoing colorectal surgery.MethodsFrom 1993 to 2006, 41 cirrhotic patients underwent 43 colorectal procedures and were included. Both univariate and multivariate analyses were performed to identify variables influencing morbidity and mortality.ResultsPostoperative morbidity was 77 percent (33/43). Postoperative mortality was 26 percent (11/43) among whom six patients (54 percent) underwent emergency surgery. Four factors influenced mortality on univariate analysis: presence of peritonitis (P < 0.05), postoperative complications (P < 0.04), postoperative infections (P < 0.01), and total colectomy procedures (P < 0.02). On multivariate analysis, the only factor influencing mortality was postoperative infection (P < 0.04). The only factor influencing morbidity was the existence of preoperative ascites (P < 0.04).ConclusionsColorectal surgery for cirrhotic patients has a high risk of morbidity and mortality. This risk is associated with the presence of infection, ascitic decompensation, and the urgent or extensive nature of the procedure. The optimization of patients through selection and preparation reduces operative risk.

Effect of preoperative endoscopic biliary drainage on infectious morbidity after pancreatoduodenectomy: a case-control study.

BACKGROUND The utility of preoperative endoscopic biliary drainage (PEBD) in jaundiced patients before pancreatoduodenectomy (PD) is still debated. This is in part due to the heterogeneity of the studied population, including different tumor location, drainage techniques, and surgical procedures. The aim of the current study was to report the influence of PEBD on postoperative infectious morbidity of PD. MATERIALS AND METHODS Between January 1996 and December 2004, 124 patients underwent a PD and 28. Twenty-eight (22.6%) of these patients underwent a PEBD. This group of patients was matched to 28 control patients who underwent PD without PEBD during the same period. The 2 groups were matched for age, sex, indication of surgery, and serum bilirubin levels. RESULTS The specific morbidity of PEBD before surgery was 10.7% (n = 3). The postoperative overall morbidity, medical morbidity, and surgical morbidity rates were not different between the 2 groups. At the time of surgery, 89.3% (n = 25) of the patients in the PEBD group had positive bile culture in comparison to 19.4% (n = 4) in the control group (P < .001). The number of patients with 1 or more infectious complications was higher in the PEBD group (50%; n = 14) than in the control group (21.4%; n = 6) (P = .05). CONCLUSIONS Before PD, PEBD should be routinely avoided whenever possible in patients with potentially resectable pancreatic and peripancreatic lesions. In patients with cholangitis, requiring extensive preoperative assessment (such as liver biopsy) or neoadjuvant treatment, PEBD might still be indicated.

Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II–III colorectal cancer: a multicentre randomised controlled phase III trial

BACKGROUND Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer. This study aimed to investigate whether regional chemotherapy (given by intraperitoneal or intraportal methods) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II-III colorectal cancer. The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole. METHODS During surgery, 753 patients with stage II-III colorectal cancer were randomly assigned to systemic chemotherapy alone (379 with fluorouracil and folinic acid, and 374 with fluorouracil and levamisole), and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid (n=368) or with fluorouracil and levamisole (n=380). Regional chemotherapy was given intraperitoneally (n=415) or intraportally (n=235) according to institution. The primary endpoint was 5-year overall survival. Secondary endpoints were 5-year disease-free survival and toxic effects. Analyses were by intention to treat. FINDINGS Median follow-up was 6.8 years (range 0.0-10.1). 5-year overall survival was 72.3% (95% CI 69.0-75.6) for patients assigned regional and systemic chemotherapy, compared with 72.0% (68.7-75.3) for those assigned systemic chemotherapy alone (hazard ratio [HR] 0.97 [0.81-1.15], p=0.69). 5-year overall survival for all patients assigned fluorouracil and levamisole was 72.0% (68.7-75.2) compared with 72.3% (69.0-75.6) for all those assigned fluorouracil and folinic acid (HR 0.98 [0.82-1.17], p=0.81). The hazard ratios for 5-year disease-free survival were 0.94 (0.80-1.10) for regional versus non-regional treatment, and 0.92 (0.79-1.08) for all fluorouracil and levamisole versus fluorouracil and folinic acid. Grade 3-4 toxic effects were low in all groups. INTERPRETATION Fluorouracil-based regional chemotherapy adds no further benefit to that obtained with systemic chemotherapy alone in patients with advanced colorectal cancer.

Prognostic Factors of Survival in Repeat Liver Resection for Recurrent Colorectal Metastases : Review of Sixty-Two Cases Treated at a Single Institution

PURPOSE: Liver metastases develop in 50 percent of patients with colorectal carcinoma. Recurrent liver disease is usual. Repeat liver resection remains the only curative treatment. The aim of this study was to review our data on repeat hepatectomy and to analyze potential prognostic factors of survival. METHOD: Patients who underwent repeat liver resection for metastases of colorectal carcinoma between January 1992 and August 2007 were identified from a prospective database and their medical records were analyzed. RESULTS: Of 62 patients who underwent a second hepatectomy, 15 underwent a third hepatectomy, and two underwent a fourth hepatectomy. There was no perioperative mortality. Morbidity was less than 20 percent for the first and second hepatectomies. Overall 5-year survival rate after first hepatectomy was 40 percent. Univariate analysis identified three risk factors confirmed by log-rank test and multivariate Cox regression analysis: serum carcinoembryonic antigen concentrations >5 ng/ml at first hepatectomy (HR = 2.265; CI = 1.140-4.497; P = 0.020), anatomic resection (HR = 2.124; CI = 1.069-4.218; P = 0.031), and tumors ≥3 cm at the second resection (HR = 2.039; CI = 1.013-4.103; P = 0.046). CONCLUSION: Our study shows that repeat hepatectomy for liver metastases of colorectal carcinoma may be performed with low mortality and morbidity. Preoperative concentration of carcinoembryonic antigen at first hepatectomy, tumor size, and type of anatomic resection are independent prognostic factors.