Molecular patterns in deficient mismatch repair colorectal tumours: results from a French prospective multicentric biological and genetic study.

BACKGROUND: To test the prognostic value of tumour protein and genetic markers in colorectal cancer (CRC) and examine whether deficient mismatch repair (dMMR) tumours had a distinct profile relative to proficient mismatch repair (pMMR) tumours. METHODS: This prospective multicentric study involved 251 stage I-III CRC patients. Analysed biomarkers were EGFR (binding assay), VEGFA, thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) expressions, MMR status, mutations of KRAS (codons 12-13), BRAF (V600E), PIK3CA (exons 9 and 20), APC (exon 15) and P53 (exons 4-9), CpG island methylation phenotype status, ploidy, S-phase, LOH. RESULTS: The only significant predictor of relapse-free survival (RFS) was tumour staging. Analyses restricted to stage III showed a trend towards a shorter RFS in KRAS-mutated (P=0.005), BRAF wt (P=0.009) and pMMR tumours (P=0.036). Deficient mismatch repair tumours significantly demonstrated higher TS (median 3.1 vs 1.4) and TP (median 5.8 vs 3.5) expression relative to pMMR (P<0.001) and show higher DPD expression (median 14.9 vs 7.9, P=0.027) and EGFR content (median 69 vs 38, P=0.037) relative to pMMR. CONCLUSIONS: Present data suggesting that both TS and DPD are overexpressed in dMMR tumours as compared with pMMR tumours provide a strong rationale that may explain the resistance of dMMR tumours to 5FU-based therapy.

Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer.

BACKGROUND: In advanced colorectal cancer, K-Ras somatic mutations predict resistance to mAbs targeting epidermal growth factor receptor (EGFR). Relationships between K-Ras mutations and EGFR status have not been examined so far. We analyzed relationships between K-Ras mutations and EGFR tumoral status based on EGFR germinal polymorphisms, gene copy number and expression. METHODS: Eighty colorectal tumors (stage 0-IV) and 39 normal mucosas were analyzed. K-Ras mutations at codons 12 and 13 were detected by a sensitive enrichment double PCR-restriction fragment length polymorphism (RFLP) assay. EGFR gene polymorphisms at positions -216G>T, -191C>A and 497Arg>Lys were analyzed (PCR-RFLP), along with CA repeat polymorphism in intron 1 (fluorescent genotyping) and EGFR gene copy number (PCR amplification). EGFR expression was quantified by Scatchard binding assay. RESULTS: The number of EGFR high-affinity sites, dissociation constant (Kd), gene copy number, intron 1, -216G>T, -191C>A or 497Lys>Arg genotypes was not different between K-Ras-mutated or K-Ras-non-mutated tumors. No relationship was observed between any of the analyzed EGFR genotypes and EGFR expression. EGFR expression was not related to gene copy number. EGFR gene copy number in tumor and normal tissue was not correlated. The mean value of the tumor/normal mucosa gene copy number ratio was 1.16. CONCLUSIONS: Present data clearly show that EGFR status is independent of K-Ras mutations in colorectal tumors.

Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect.

BACKGROUND: The cytosine deaminase gene of Escherichia coli converts the nontoxic compound 5-fluorocytosine into 5-fluorouracil (5-FU), thereby acting as a suicide gene when introduced into cancer cells, killing the cells when they are exposed to 5-fluorocytosine. We analyzed the efficacy of using cytosine deaminase-bearing cancer cells as an autologous tumor vaccine in a rat model that mimics liver metastasis from colon carcinoma. METHODS: We introduced a plasmid vector containing the E. coli cytosine deaminase gene into a BDIX rat colon carcinoma cell line. Intrahepatic injection of the modified cells in syngeneic animals generates a single experimental liver "suicide tumor." We then analyzed the effect of 5-fluorocytosine treatment in terms of regression of cytosine deaminase-expressing cells in vivo as well as protection against wild-type cancer cells. RESULTS: Treatment with 5-fluorocytosine induced regression of cytosine deaminase-expressing (CD+) tumors, with seven of 11 treated animals being tumor free at the end of 30 days and a statistically significant difference in tumor volumes between treated and control animals (two-sided P<.0001). Intrahepatic injection of CD+ cells followed by 5-fluorocytosine treatment rendered the treated animals resistant to challenge with wild-type tumor cells, with no (zero of seven) treated animals developing wild-type tumors in contrast to all (four of four) control animals. Moreover, in animals with established wild-type liver tumors, injection of CD+ tumor cells followed by 5-fluorocytosine treatment produced a statistically significant increase in survival time (two-sided P<.0001). In vivo immunodepletion and immunohistologic analysis of experimental tumors indicate that natural killer cells are the major immune component involved in this antitumor effect. CONCLUSIONS AND IMPLICATIONS: Taken together, these results suggest the potential use of suicide gene-modified tumor cells as therapeutic vaccines against liver metastasis from colon carcinoma.

Link between dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells and liver.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme of 5-fluorouracil (FU) catabolism, which occurs mainly in the liver. Several cases of severe FU-related toxicity have been reported in patients exhibiting a marked DPD deficiency measured in peripheral blood mononuclear cells (PBMCs). In addition, it has been shown that PBMC-DPD activity correlates to systemic FU clearance. The purpose of the present study was to closely evaluate the link between DPD activity measured in PBMCs and in liver samples obtained from the same patients. This prospective study was conducted on 27 patients (18 men and 9 women) who underwent laparotomy for various pathologies. Liver biopsies were performed in normal liver and immediately stored in liquid nitrogen. Biological liver function tests were within normal values for all patients. Concomitantly to the liver biopsy, a blood sample was taken and PBMCs were immediately isolated and stored at -80 degreesC. Liver-DPD and PBMC-DPD activities were measured by a radioenzymatic assay using 14C-FU as substrate (sensitivity limit, 5 pmol/min/mg protein; interassay reproducibility, 10%). Liver-DPD (mean, 178; median, 186; range, 54-290 pmol/min/mg protein) and PBMC-DPD (mean, 196; median, 205; range, 80-275 pmol/min/mg protein) exhibited the same pattern of distribution. Neither liver-DPD nor PBMC-DPD was significantly different between men and women. A significant linear correlation was demonstrated between liver- and PBMC-DPD activity (liver-DPD = 0.6 x PBMC-DPD + 59, r = 0.56, P = 0.002). Interestingly, the patient who exhibited the lowest PBMC-DPD activity (80 pmol/min/mg protein, at risk value for developing FU-related side effects) also had very low liver-DPD activity (98 pmol/min/mg protein). In conclusion, in patients with normal liver function, DPD activity measured in PBMCs reflects DPD activity expressed in the liver. The demonstrated link between liver- and PBMC-DPD activity reinforces the interest in DPD investigation in PBMCs for selecting, before FU-containing chemotherapy, patients at risk of developing severe toxicities due to impairment of FU clearance.

Decreased folylpolyglutamate synthetase activity in tumors resistant to fluorouracil-folinic acid treatment: clinical data.

Thymidylate synthase (TS) is the main target for fluorouracil (FU). Optimal cellular concentrations of reduced folates in polyglutamated forms [via folylpolyglutamate synthetase (FPGS)] are necessary for achieving maximal TS inhibition. The aim of this multicentric prospective study was to analyze the link between clinical response to FU therapy for liver metastases of colorectal carcinoma and tumoral TS and FPGS activities. Forty-four advanced colorectal cancer patients (15 women and 29 men; median age 63, range, 27-78 years) receiving a standard FU-folinic acid protocol were included. A single hepatic tumoral biopsy was obtained systematically at the time of diagnosis. For 24 patients, a biopsy in the primary colon tumor was available. TS and FPGS activities were measured by radioenzymatic assays. Clinical response on hepatic metastases was 1 complete response, 12 partial responses, 14 stabilizations, and 17 progressions. In hepatic biopsies, TS activity (median, 185; range, <10-3111 fmol/min/mg protein) and FPGS activity (median, 1270; range, <400-3730 fmol/min/mg protein) exhibited a wide variability. TS activity in primary tumors (median, 461; range, 35-2565 fmol/min/mg protein) was significantly higher than in hepatic metastases. No difference was observed between primaries and metastases for FPGS. FPGS activity expressed in liver metastases was significantly correlated to that expressed in primaries. The distribution of TS activity in liver metastases was not significantly different between responsive and nonresponsive patients. However, FPGS activity measured in liver metastases was significantly higher in responsive patients (median, 1550 fmol/min/mg protein) than in nonresponsive patients (median, 1100 fmol/min/mg protein). A discriminant analysis revealed that 24 of the 25 patients exhibiting a liver FPGS activity 320 fmol/min/mg protein were nonresponding patients. These data establish for the first time the potential importance of tumoral FPGS activity for assessing FU-folinic acid responsiveness in the clinical setting.

Relevance of tumoral folylpolyglutamate synthetase and reduced folates for optimal 5-fluorouracil efficacy: experimental data.

The purpose of this study was to investigate folate-related predictors of 5-fluorouracil (5-FU) cytotoxicity in the presence or absence of l-folinic acid (l-FA). Intracellular concentrations of the reduced folates (tetrahydrofolate + 5,10-methylenetetrahydrofolate) and folylpolyglutamate synthetase (FPGS) activity were determined in 14 human cancer cell lines expressing a spontaneous sensitivity to 5-FU. On these 14 cell lines grown without l-FA supplementation, a significant positive correlation was demonstrated between basal intracellular folate concentration and FPGS activity. 5-FU sensitivity (IC50 range 0.6-25.4 microM) was not related to the basal intracellular folate concentration, whereas, significantly, it was linked to FPGS activity (range 2.5-11.1 pmol/min/mg protein): the higher the FPGS activity, the greater the 5-FU sensitivity. Under l-FA supplementation (0.01-300 microM), intracellular reduced folates increased continuously without evidence of saturation in all cell lines; the pattern of accumulation was independent of the FPGS activity. l-FA enhanced 5-FU cytotoxicity by a factor of 1.9-6.4 in 12 of the 14 cell lines. In the 12 FA-sensitive cell lines, the l-FA concentrations allowing 90% of maximum 5-FU potentiation [l-FA]90 ranged between 0.7 and 107.9 micro M (median 1.9); in contrast, the intracellular concentrations of reduced folates allowing 90% of maximum 5-FU potentiation were much less variable (range 7.6-38.3, median 24.8 pmol/mg protein). In the presence of [l-FA]90, 5-FU sensitivity remained significantly correlated to the basal FPGS activity. In addition, reduced folates were measured in 96 tumoral samples (50 head and neck, 16 colon, 30 liver metastases from colorectal cancer) taken before treatment. Almost all investigated tumours had folate concentrations below the median concentration required for optimal 5-FU potentiation in vitro: median levels (range, pmol/mg protein) were 3.8 (0-17.7) for head and neck, 5.8 (2.3-12.0) for colon and 12.1 (1.7-118.5) for liver metastases. Above all, these data establish the relevance of FPGS activity for predicting the efficacy of 5-FU modulated by FA or not and point to the potential clinical interest of FPGS determination in human tumours.

Treatment of hepatic metastases of colorectal cancer by electrochemotherapy: an experimental study in the rat.

BACKGROUND: Electrochemotherapy, which consist of local or systemic administration of a cytotoxic agent followed by application of electric pulses to a tumor, has proved effective for various types of tumors in animals and for cutaneous and head and neck cancers in human beings. This is the first study to investigate the efficacy of electrochemotherapy for treatment of hepatic metastases of colorectal cancer in the rat. METHODS: After induction of a solitary hepatic metastasis in 36 male BDIX rats, the animals were randomized to one of four groups: B-E-(no treatment), B+E-(intratumoral bleomycin), B-E+ (application of electric pulses to the tumor), and B+E+ (electrochemotherapy: intratumoral bleomycin followed by application of electric pulses). RESULTS: Groups B-E and B-E+ had no tumor response. Group B+E had one partial response. Group B+E+ had seven partial responses and two complete responses. The difference in terms of response between group B+E+ and the other three groups was statistically significant (P < .05). Comparison of the mean posttherapy tumor volumes (B-E-, 50.6 mm3; B+E-, 58.7 mm3; B-E+, 46 mm3; and B+E+, 5.65 mm3) revealed a significantly smaller residual tumor in group B+E+ than in the other three groups (P < .05). CONCLUSIONS: Electrochemotherapy is an effective means to reduce the volume of hepatic metastases of colorectal cancer in the rat. Additional research is required to determine the optimum treatment duration, dose effects, volume of tumor that can be treated by electrochemotherapy, and impact on survival. Such experimental studies are indispensable prerequisites for clinical trials.

Infectious complications of endoscopic retrograde cholangio-pancreatography managed in a surgical unit.

The immediate infectious pancreato-biliary complications of endoscopic retrograde cholangiopancreatography (ERCP) warranting transfer to a surgical unit are analyzed, in order to evaluate their frequency and severity as well as means of treatment and prevention. Thirty complications of this type were observed in a series of 3226 ERCP performed with or without endoscopic sphincterotomy (ES) over a six year period (0.9%). ES had been performed in 12 of 30 cases, but the complication could not be attributed to the procedure. Post-ERCP complications included: acute cholangitis: 16 cases (53%); acute cholecystitis: 8 cases (26%); acute pancreatitis: 4 cases (13%); infected pancreatic pseudocyst: 2 cases (6%). The global mortality rate was 16.6% (five patients): Four of the deaths were due to septic complications. Twenty-seven of the 30 patients underwent surgery, and three of them died (11%). Acute cholangitis was responsible for most of the deaths (four of five) and the mortality appeared related to the long interval before surgery (three of four deaths). Strict adherence to good endoscopic procedures (aseptic conditions, injection without excessive pressure, antibiotic prophylaxis) and decompression of the biliary tract (nasobiliary drain or transhepatic catheter) should help reduce the frequency of post-ERCP complications, and especially cholangitis, which appears to benefit from early surgical treatment.

[Traumas of the duodenum]. / Les traumatismes du duodénum.

The aim of this study is to present current management of duodenal trauma. Duodenal lesions following penetrating injuries are rare, but more serious, than those following blunt injuries. the severity is mostly due to delay in the diagnosis and associated intraabdominal injuries. Diagnosis is based on abdominal plain film, gastroduodenography, and more recently US scan and CT-scan. Surgical procedures depend on the type of lesion. In patients operated early, a duodenal wound can be treated by suture-closure with duodenal decompression tube. If suture-closure is not available, with a wound affecting proximal or distal duodenum, resection with anastomosis can be performed. In the second portion of the duodenum, the best treatment is a jejunal plasty with a Roux-en-Y loop. When there is an associated pancreatic injury, treatment depends on whether biliary or pancreatic ducts are injured, and a pancreatico-duodenectomy could be necessary. In patients operated on later, closure with duodenal exclusion by diverticulization is associated due to the high risk of leaking.

[Video-assisted thoracic surgery: indications and limitations]. / Chirurgie thoracique vidéo-assistée: indications et limites.

From November 1990 to September 1992, 72 patients underwent a video-assisted thoracic surgery (VATS), 47 men and 25 women, of mean age 49 years. Video-assisted thoracic surgery was indicated for the following: 44 spontaneous pneumothorax, 6 benign tumors of the lung or the mediastinum, 4 pleural effusions, one broncho-pleural fistula and one sympathectomy; 17 diagnostic procedures (lung or mediastinal lymph-nodes biopsies). In one patient, it was necessary to associate a mini-thoracotomy and 5 patients went on to a formal thoracotomy. There was no mortality and the morbidity rate was 5.5%. Some conditions are required: one-lung ventilation, ability to convert to a formal thoracotomy at any moment. It is contra-indicated in cases of single lung or complete obliteration of the pleural space due to dense adhesions. The place of VATS is now well defined for the treatment of spontaneous pneumothorax. It is discussed for resection of pulmonary diseases depending on their size, location and histologic type.

[Oncological and functional results of direct colo-anal anastomosis after total resection of the rectum for cancer]. / Résultats carcinologiques et fonctionnels de l'anastomose colo-anale directe après exérèse totale du rectum pour cancer.

From january 1986 to december 1992, 71 patients underwent direct colo-anal anastomosis as described by Parks (CAA) after total rectal resection for carcinoma: 49 men and 22 women with a mean age of 64 years (range 37-82). In 67 cases, the indication was for adenocarcinoma of the mid and low rectum, and in 4 cases for carcinoma of the upper rectum associated with a low rectal benign tumour (6 Dukes A, 36 Dukes B, 21 Dukes C, 8 Dukes D). A diverting colostomy was constructed in all cases. One patient died from pulmonary embolism (mortality: 1.4%). Anastomotic leakage occurred in 6 cases (8.5%). None of these cases required reoperation and all colostomies have been closed. Local recurrence occurred in 12 cases (17%) 6 to 34 months after CAA, of whom 4 were treated by abdominoperineal resection. Eleven patients died from local recurrence (3 cases) or distant metastasis (8 cases). Actuarial survival at 1, 2, 3, 4 and 5 years was 92%, 88%, 78%, 75% and 69% respectively. From the functional point of view, one patient underwent abdomino-perineal resection for incontinence 3 years after CAA. All the other patients were fully continent, with a mean stool frequency of 2 per day, and good gas-stool discrimination. Twenty per cent of patients presented soiling, 20% with stool frequency, and 12% with urgency. Long term functional and oncological results make CAA a good alternative to abdomino-perineal resection for mid and low rectal carcinoma.

[Results of surgical treatment of complicated paraesophageal hernias]. / Résultats du traitement chirurgical des hernies para-oesophagiennes compliquées.

From January 1979 to May 1995, 18 patients (4 men, 14 women) with a mean age of 75.4 +/- 12.5 yr underwent surgery for a complicated paraesophageal hiatus hernia. In 5 patients, the complication was the first sign of the diagnosis. Thirteen patients had a history of digestive, respiratory, or cardiac symptoms (mean duration of symptoms 74 mo.; range 2-240 mo.); 9 of them were aware that they had a hiatus hernia. Ten patients presented with acute obstruction (associated with a perforation in 1 case, jaundice in 1 case, and righy lower lobe pneumonia in 1 case). Hemorrhage occurred in 6 patients (hematemesis 4 cases, melena 2 cases). One patient had a perforation and another had an abscess of the lower right lobe. Surgery was performed via a transabdominal approach in all cases (5 times as an emergency, 12 times as a delayed emergency procedure, and once as an elective procedure). The procedure was delayed in 13 cases because of successful nasogastric decompression. All patients underwent reintegration of the stomach, diaphragmatic repair and gastropexy. An antireflux procedure was performed in 14 cases. Seven patients had an ancillary procedure (including one splenectomy following decapsulation). There were no postoperative deaths. Two patients who underwent emergency surgery developed a benign complication. The outcome of 17 patients is known; none of them developed a recurrence. One patient who did not undergo an antireflux procedure presented with gastroesophageal reflux; another experienced pain during eructation. In conclusion, nearly two-thirds of all patients who present with an acute complication can benefit from medical preparation before surgery, a strategy that improves results.

[Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat]. / Vaccination par thérapie génique suicide contre un modèle de métastases hépatiques de cancer colique chez le rat.

UNLABELLED: Suicide gene therapy consists of transferring into tumor cells a viral or bacterial gene encoding for an enzyme which converts a non-toxic product into a lethal drug. STUDY AIM: To analyze the therapeutic potential of vaccination with tumor cells expressing the bacterial cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatment in a rat liver metastasis model. MATERIAL AND METHOD: We used a rat colon carcinoma cell line which, after subcapsular or intraportal injection in syngenic animals, generates single or multiple experimental liver metastases, respectively. We have shown that introduction of a vector expressing the CD gene in this colon carcinoma cell line results in 5-FC sensitivity (PRObCD). RESULTS: Intrahepatic subcapsular injection of PRObCD tumor cells, followed by 5-FC treatment, induces total regression of a wild-type tumor pre-established in the contralateral liver lobe in 45% of animals with a 96% decrease in mean volume (p < 0.0001), demonstrating the existence of a distant bystander effect. This vaccination significantly increased the survival of rats with single (log-rank p < 0.0001) or multiple (log-rank p = 0.01) liver metastasis CONCLUSIONS: These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.

[Aseptic adenitis in pyoderma gangrenosum]. / Adénites aseptiques au cours d'un pyoderma gangrenosum.

INTRODUCTION: Extra-cutaneous manifestations of neutrophilic dermatosis are rare. Symptomatic cases are usually multiform and confusing. We report a case with an aseptic lymph node abscess associated with pyoderma gangrenosum. CASE REPORT: A 28-year-old woman with past history of pyoderma gangrenosum was seen for abdominal symptoms and fever related to an epigastric mass. Due to signs indicating abscess formation, surgery was performed and led to total regression of the symptomatology. Recurrence was evidenced 3 months later with skin lesions which were negative on bacteriological examinations. The diagnosis of lymph node manifestations of pyoderma gangrenosum was retained. General corticotherapy was very effective. Relapse occurred again 6 years later and was treated with thalidomide. DISCUSSION: Lymph node involvement has been described in Sneddon-Wilkinson's disease associated with pyoderma gangrenosum. In neutrophilic dermatosis, pulmonary manifestations appear to be the least exceptional of the extra-cutaneous lesions. The pathophysiology has not been elucidated although recent hypotheses suggest that G-CSF could be involved. Corticotherapy is remarkably effective in most cases but thalidomide could be an interesting alternative treatment.

[Acute pancreatitis treated in a surgery ward. Apropos of 57 cases]. / Pancréatites aiguës traitées en milieu chirurgical. A propos de 57 cas.

The aim of this study was to examine the results of a policy in the treatment of acute pancreatitis (AP): initial abstention, management in intensive care unit, surgery in cases of complication (infection and/or failure of medical treatment). The modalities of the surgical treatment were guided by CT scan findings: transperitoneal approach for diffuse lesions, posterior approach for localized lesions. From 1986 to 1994, 57 patients (32 males, 25 females, mean age 59.2 years) were referred to our department for AP. Etiology was gallstones in 29 cases, alcohol in 14 cases (Ranson < 3), moderate in 27 cases (Ranson < or = 5) and serious in 12 cases (Ranson > or = 6). According to the initial CT scan findings (56 cases), 9 patients were classified grade A, 11 grade B, 13 grade C, 8 grade D ans 15 grade E. Thirty eight patients were managed conservatively (mean Ranson stage 3.3), while 19 patients underwent surgical treatment (mean Ranson stage 4.6), in emergency for misdiagnosis (4 cases), or secondarily because of failure of medical management (15 cases). Surgery consisted in necrosectomy with active drainage in 13 cases and drainage alone in 6 cases. Associated maneuvers included: cholecystectomy in 8 cases, cholecystostomy in 2 cases, jejunostomy in 7 cases and colic resection for necrosis in 3 cases. Two patients (5%) managed conservatively died (multiple organ failure and cardiac insufficiency) while 4 patients (21%: NS) who underwent surgery died (2 multiple organ failures, 1 septic shock, 1 myocardic infarction). Mortality was correlated with the Ranson score: 42% for serious AP, 3.7% for moderate AP and nil for mild AP (p < 0.01). It was not correlated with CT scan grade, the onset or the type of operation. These results allow us to conclude that surgical treatment should be indicated only in cases of failure of conservative management, the best indication being uncontrolled sepsis. In this situation, active drainage provides good results since only one sepsis recurred among the 14 patients who underwent this procedure.

[Para-esophageal hernias. Apropos of 42 cases]. / Les hernies para-oesophagiennes. A propos de 42 observations.

Between 1979 and May 1994, 42 patients (11 males, 31 females, mean age 72.8 +/- 12.4 years) underwent surgery for paraoesophageal hiatal hernia. In 37 cases, clinical signs had been observed for 64 months on the average: digestive (32), respiratory (15), cardiac (9). Nine patients had iron deficiency anaemia. Eighteen patients had a complication (acute obstruction: 10, haemorrhage: 6, perforation: 2, lung infection: 2). In 5 cases, the complication was the inaugural sign. Surgery was performed in a emergency situation in 5 cases and deferred emergency in 12 and surgery was elective in 25. An antireflux procedure was used in 36 cases (Lortat-Jacob (2), Toupet (5), Dor (2), Nissen-Rossetti (27)). Another procedure was also needed in 12 patients. There were no postoperative deaths and complications occurred in 6 patients (14.9%). Outcome was known in 40 patients with a mean follow-up of 40.5 months (range 3 to 140 months). Functional results was very good in 35 patients (87.5%), good in 3 (7.5%) and poor in 2 (5%). The most satisfactory immediate results were obtained for patients who had elective surgery and in those with a deferred emergency. Use of the Nissen-Rossetti procedure did not have any deleterious effect on these results and no long-term inconveniences.