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Donor-specific induction of tolerance was previously achieved in the diabetic rat by intrathymic injection of pancreatic islets. It allowed a secondary islet graft in any site without immunosuppression. Since total pancreatic graft in man is metabolically more proficient than islet graft, we attempted tolerance induction for total vascularized pancreas transplantation in diabetic BN recipient rats by an intrathymic bone marrow cell (BMC) injection from Lewis donor rats, associated to an antilymphocyte antibody (ALS) administration. Control groups consisted of isogenic grafts, allogenic grafts without tolerance induction and allogenic grafts with ALS alone. In all grafted groups, mean blood glucose and plasma insulin were normalised within 24 h. Graft rejection (clinically suggested by diabetes recurrence and later confirmed by histology) appeared at 18 ± 2 postoperative days in the absence of intrathymic BMC injection and at 36 ± 8 days in the group with BMC injection (p < 0.05). Intrathymic bone marrow graft was successful in delaying rejection in our study.

Intestinal wall motions are not easily studied and are frequently deduced from manometric and electromyographic measurements. This study aimed to establish a method of wall movement analysis based on an automatic technique of image processing. Segments of rat jejunum were fixed in an organ bath under isometric conditions. A real-time edge-detection algorithm was used to find the contours of the intestine using video imaging. After the measurement, a mapping of intestinal wall movements was performed based on diameter variations. In the 260 experiments without stimulation, intestinal wall activity was always detected. Propagated activity was found in 40% of the experiments and periodic wall motion in 60%, with 0.5-Hz activity found more frequently (41%) than 0.24-Hz activity (19%). These cyclic activities, related to intestinal slow waves, had their amplitude decreased by acetylcholine and were modified by vapreotide. Analysis of a propagated wave after cholinergic stimulation showed that it is characterized by an increase of the diameter of the intestine followed by a decrease. Moreover, this methodology allows analysis of the initiation of a propagated wave.

PURPOSE: Diversion-related colitis is an inflammatory process that affects the colon and/or rectum distal to a colostomy. Its mechanisms are unknown, and many hypotheses have been considered. The aim of the present study was to create an experimental model of diversion-related colitis in rats, so in the future it will be possible to test different hypotheses. METHODS: Three groups of ten male Wistar rats were used for the study. Two groups underwent a colostomy and were kept alive for 6 or 17 weeks. One group of rats was killed at the onset of the experiment. Specimens were taken in bypassed segments in the rats who had had a colostomy and in the sigmoid colon for the control group. Histologic analysis using standard coloration, histochemical techniques, and bacterial preparation was used to find histologic or changes of colonic histology or flora. RESULTS: Exclusion was associated with vascular congestion, a decrease in length of glandular crypts (P < 0.01), and an erosion of surface epithelium; inflammation of the mucosa was absent in all control animals and present in all test animals. In contrast, the number of goblet cells was not changed by the procedure. There was also a significant change in distribution and intensity of sulfomucins and sialomucins and quantitative and qualitative changes of the colonic flora. CONCLUSION: This experimental model of diversion colitis is characterized by histologic and bacteriologic modifications comparable with those reported in humans but with different histochemical changes.

Saliva is an important factor in neutralization of oesophageal acid exposure, clinically manifested as gastrooesophageal reflux (GOR). The aim of this study is to compare the composition and the "capacity in acid neutralization" (CAN) of saliva in controls and patients suffering of GOR. We compared the composition of saliva from 56 patients who had symptoms of GOR with that of saliva from 20 healthy control subjects. After a standardized 24-hour period of pH-monitoring, 39 patients had normal pH reflux scores (normal acid score: NAc-GOR) and 17 had abnormal pH reflux scores (pathological acid score: PAc-GOR). Then, following a 10-h fast, total saliva was collected during ten minutes in all patients and in the healthy control subjects. The composition of the saliva samples was analysed and the titration curve was determined on 200 microliters aliquots by successive addition of 5 microliters volumes of 0.1 N Hcl. The GOR patients had significantly lower salivary concentrations of Na+ and of both free and bound sialic acids and had higher salivary concentrations of inorganic phosphates than the controls. These disorders were more marked in PAc-GOR patients. Initial pH was 7.43 +/- 0.43 in controls, 7.35 +/- 0.45 in NAc-GOR patients, and 6.91 +/- 0.53 in PAc-GOR patients. In the beginning of the titration curve, PAc-GOR patients were significantly different from NAc-GOR patients and from controls. Saliva of both groups of patients presented significant differences in the acidic portion of the titrations curves, at high volumes of added HCl. These data show that the composition of saliva was modified in patients with GOR disease compared to that of normal subjects. A difference in titration curves was also observed with a higher acidic buffering capacity in these GOR patients. The modifications in saliva composition suggest a role for inorganic phosophates in the acid neutralization capacity observed in GOR, perhaps linked with a adaptation to chronic acid exposure.

To define some methodological factors that could affect the measurement of the esophageal clearance, we used three different protocols, on 41 healthy control subjects. In 20 subjects, we studied the influence of a naso-esophageal probe on the frequency of swallowing. We observed a significant (44 +/- 5%) decrease in the frequency of spontaneous swallows after 15 minutes, with stabilization after this 15 minute period of adaptation. In 11 subjects, we studied the influence of the pH of the esophageal content on esophageal clearance. We found an exponential relationship between the esophageal clearance (C) expressed in minutes and the initial pH of the lumen contents: C = 43.3 exp (-0.54 pH) In 10 other subjects, we studied the influence of the volume of the esophageal contents on esophageal clearance. We found no influence for volumes less than 30 ml and a significant increase of clearance for volumes greater than 30 ml. In summary, this study of the effects of methodological factors on esophageal clearance: Gives new information about the "accommodation phase" of the esophagus after distension by a naso-gastric probe; Allows us to propose a new quantitative method for evaluation of esophageal clearance Shows the small importance of the ingested volume.

Two hundred twenty patients were studied to investigate the chronobiological patterns of gastroesophageal reflux (GER) during a 24-h period of pH monitoring under standardized conditions. Some 204 patients met the inclusion criteria; 120 had normal values and 84 were pathologic. The hourly parameters calculated in the two groups were: the mean pH, the percentage of time during which the pH was smaller than 4, the number of reflux episodes, and the coefficient of variation of the pH. Two types of 24-h rhythms were found. There was an increase of the number of refluxes during the daytime versus the nighttime and the hourly mean pH was more acid during the night than day in subjects with normal values. All parameters differed significantly between the two groups (p < 0.001) and displayed a rhythmic pattern (p < 0.0001). The most significant difference occurred during the 3 postprandial hours after the evening meal (p < 0.001). Temporal rhythmicity of GER could also contribute to evaluation of clinical result...

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P less than 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P less than 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P less than 0.001). This may explain why a large percentage of constipated patients have been found by most authors to have "normal" colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.

Pinaverium bromide is a specific calcium channel blocker used in the treatment of irritable bowel syndrome (IBS) for its spasmolytic activity. The aim of the present study was to evaluate the effect of orally administered pinaverium bromide on jejunal motility and total and segmental colonic transit time in control subjects. Gastrointestinal studies were performed in 10 healthy volunteers (30 +/- 3 years), before and after a treatment phase of 14 days (150 mg/d). Jejunal motility was measured by prolonged manometry (14 h) and colonic transit time by a multiple ingestion, single marker technique. No significant modification of phase III of the migrating motor complexes was demonstrated. On the contrary, a significant (p < 0.01) but weak decrease of the frequency of contraction was found. Unlike previous studies, no decrease of total or segmental colonic transit time was demonstrated.

The effects of alcohol withdrawal on total and segmental transit time were evaluated in 20 chronic alcoholic subjects. After withdrawal, colorectal transit time significantly increased from 24.9 +/- 3.6 to 33.3 +/- 4.5 hours mean +/- SE (P less than 0.01). This was the result of an exclusive increase in rectosigmoid transit time from 2.8 +/- 0.7 to 9.8 +/- 2.1 hours (P less than 0.001). No variations were found in right or left colon transit time. Distal colonic motility is thus a crucial factor in the genesis of diarrhea in chronic alcoholic subjects.

Diaphragmatic hernia is a rare complication of oesophagectomy for cancer. We report a series of seven patients to determine characteristics of this entity.Seven patients (six male and one female, 61 to 68 years old) were operated on for diaphragmatic hernia following oesophagectomy for carcinoma (adenocarcinoma N =4, squamous-cell carcinoma N =3). Oesophagectomy had been performed through abdominal transhiatal approach in four patients and transthoracically in three, with hiatal enlargement in all cases.Three patients, all symptomatic, underwent emergency surgery within two years following oesophagectomy. Of the four patients operated between two and seven years after oesophagectomy, two were symptomatic. Presence of symptoms were neither related with technique of oesophagectomy, nor to type of hiatal enlargement (anterior, or by crura division). All patients with hernia containing small bowel were symptomatic. All patients were operated through abdominal approach. Hernia contained colon three times, small bowel once, and both three times. Hernia reduction needed additional phrenotomy in six patients. Two patients underwent colectomy to treat peroperative colonic ischemia. Diaphragmatic hiatus was calibrated around the gastric tube by direct suture in six patients or with absorbable mesh in one. There was no death. No recurrences occurred with a follow up ranging from one to five years.The diaphragmatic hernia after oesophagectomy is due to excessive hiatal enlargement. Hernias occurring early after oesophagectomy are badly tolerated and need urgent reoperation. To prevent this complication of oesophagectomy, we advocate calibration of diaphragmatic hiatus fit to width of gastroplasty.

The use of electrogastrography performed with cutaneous pre-gelled electrodes located in the region above the stomach to record electric control activity is discussed. A real-time spectrum analysis is used to provide a graphic representation of this activity. This study provides a method for the automatic determination of the gastric activity independently of the relative position of the stomach and the electrodes. The proposed method amplifies regular noise such as respiration. An adaptive filter is needed to suppress this noise and improve the quality of the recording. >

KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribo nucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P

Esophageal squamous cell carcinomas are frequently associated with head and neck cancers. This retrospective study was conducted to compare the long-term outcome of the patients with a double cancer and of the patients with a solitary esophageal cancer after curative management.From 1989 to 1999, 114 patients with an esophageal carcinoma were included in the study. Among them, 52 had an associated head and neck cancer (metachronous: n = 17 and synchronous: n = 35). Curative treatment was achieved in all patients. The patients were divided in "solitary" and "associated" group.Age, sex distribution, tumor location and histological findings were similar in the two groups. The esophageal resection was an esopharyngolaryngectomy (n = 13), a subtotal esophagectomy with cervical anastomosis (n = 92) and a Lewis-Santy esophagectomy with thoracic anastomosis (n = 9). Operative mortality (8 versus 7.7%), anastomotic leaks rate (14.5 versus 21%) and pneumonia rate (21 versus 9.6%) were not significantly different in the two groups. The mean hospital stay was 27 days. The mean follow-up was 85 +/- 50 months. Five-year survival rates were not significantly different in the two groups (p = 0.6411). In univariate survival analysis the only significant predictive factors were the depth of esophageal tumor invasion (p = 0.0002) and node involvement (p = 0.0373). The presence of head and neck cancer did not affect survival after esophagectomy.With an aggressive therapeutic plan, the survival of patients with an esophageal cancer associated to head and neck cancer was similar to the survival of patients with an isolated esophageal carcinoma. Long term esophageal survey seems to be useful to detect more superficial esophageal carcinomas in patients with head and neck cancer.

A local increase of interleukin-18 (IL-18) expression has been recently demonstrated in Crohn's disease (CD), suggesting a role for mature IL-18 (cleaved by ICE protease) in the induction of proinflammatory cytokines and Th1 polarization observed in CD lesions. The aim of this study was to investigate IL-18 modulation and its potential immune consequences in CD lesions. We showed increased IL-18 production in chronic CD lesions and identified epithelial cells and macrophages as IL-18-producing cells. A twofold increase in ICE alpha, beta, and/or gamma mRNA that encodes for the complete mature peptide was required for ICE activity, and a marked increase in IL-18R-positive immune cells was observed in chronic lesions compared to uninvolved areas or normal control samples. Chronic lesions also displayed intense transcription of IL-18-induced cytokines, IFN-gamma, IL-1beta, TNF-alpha, and IL-8. By contrast, when neither IL-18 nor ICE mRNAs were enhanced (early asymptomatic CD lesions), IL-18-induced cytokines were not up-regulated. These results are in accordance with a putative role of mature IL-18 in the pathogenesis of CD.

Laparoscopic gastric banding for morbid obesity is noninvasive and reversible. The aim of this prospective study was to report the preliminary results of this procedure in the first 300 patients.From April 1997 to January 2000, 300 patients were laparoscopically operated for severe obesity: 266 women, 34 men, with a mean age of 40.1 years (range: 16-66). The mean preoperative weight was 118 kg (range: 85-195) and the mean body mass index (BMI) was 43.6 kg/m2 (range: 35.1-65.8). This is a recent and complete series with a mean follow-up of 10 months (range: 3-31). The primary endpoint was excessive weight loss (EWL) and the secondary endpoints were tolerance and morbidity.There were no postoperative deaths. The mean operating time was 129 minutes (range: 50-380). A conversion to laparotomy was necessary in 11 patients. The mean hospital stay was 4.76 days (range: 3-42). There were 29 complications (9.6%), 16 among the first 50 procedures: 14 patients underwent an abdominal reoperation (2 perforations, 3 early slippages, 7 late slippages, 2 incisional hernias); 6 had respiratory complications with 2 ARDS and 9 developed a complication related to the port. At one year, BMI decreased from 43.6 to 33.7 kg/m2 and EWL reached 44.2%; 80% of the patients lost 60% of their excess weight.Our experience is encouraging with an acceptable complication rate (5%) after 50 procedures. Slippage remains the main reason for close surveillance. Half of the excess weight can be comfortably lost in one year when the whole medical and surgical staff provide close support for each patient.

The laparoscopic approach for gastroplasty is gaining widespread acceptance for morbid obesity. Less invasive and potentially reversible, this gastroplasty guarantees better quality of life. We thus evaluated perioperative complications in our consecutive series of 300 patients and followed the excessive weight loss (EWL) for the first 150.Between April 1997 and January 2000, 300 patients underwent laparoscopic gastroplasty for severe obesity according to the NIH criteria: 266 women, 34 men, mean age 40.1 years (16-66 years). Mean preoperative weight was 118 kg (85-195 kg) and mean body mass index (BMI) was 43.4 kg/m2 (31.5-65.8). Two hundred one patients had 1.3 comorbidity due to excess weight. The first 150 patients were followed 15.5 months (12-31) without any lost to follow-up. Medical, dietary and psychological data were recorded every 3 months for 18 months. The main evaluation criteria was EWL; others were tolerance and morbidity.There was no death. Mean operative time was 129 minutes (50-380), mean hospital stay was 4.76 days (3-42). There were 11 conversions (3.6%). There were 29 complications (9.6%): 11 were postoperative (5 underwent an abdominal operation for 2 perforations, 3 early slippages; and 6 respiratory problems with 2 ARDS) and 18 were late complications (7 late slippages, 2 incisional hernias and 9 port problems). Follow-up of the first 150 patients was complete: at one year, BMI fell from 43.6 to 33.8 kg/m2 and EWL reached 50.5% at 18 months.Our experience is recent, but in light of the danger of the spontaneous course of morbid obesity, the results are encouraging due to the absence of mortality and the low rate of complications after the first 50 procedures. Half of the excess weight can be lost in one and a half years. Patient comfort remains quite acceptable with the active support of the surgery and medical teams.

We report a case of pancreatitis as the first symptom of cystic fibrosis in a 22-year-old woman. The diagnosis was suspected upon the history of nasal polyposis and severe episodes of respiratory infections in infancy. The diagnosis was confirmed by sweat test. Genotyping showed a compound heterozygosity for mutations delta F508 and 5T. Acute pancreatitis is a rare manifestation of cystic fibrosis and an exceptional mode of initial presentation of the disease. It occurs in pancreatic sufficient patients, especially in young adults. This exceptional case shows that cystic fibrosis should be suspected in each case of idiopathic pancreatitis. Indications of cholecystectomy in patients with associated gallbladder lithiasis is discussed.

Segmental colectomy for complicated diverticulitis is often indicated, between attacks, in elderly patients. We report a retrospective study of operated patients over the age of 70. The aim of this retrospective study was to evaluate the age risk of consecutive patients operated between diverticular attacks by segmental colectomy, and whether such a surgical procedure is justified, as the life expectancy of these patients was 74 years for men and 81.9 years for women in 1996.From January 1990 to December 1996, 117 patients were operated, between attacks, for complicated sigmoid diverticulitis; 31% (n = 37) were over the age of 70 years. They were 16 men and 21 women with an overall mean age of 77 (range: 70-85 years). Indications for surgery were repeated attacks (n = 17), large bowel stenosis (n = 14) and colovesical fistula (n = 6). The operation was performed an average 8 weeks after the last infectious episode (3-10 weeks).Among patients over the age of 70 years, the postoperative morbidity rate was 40% and there was no mortality. One patient was reoperated for an anastomotic abscess and was managed by protective colostomy and pelvic drainage with conservation of the anastomosis.This retrospective study shows that in our experience, one third of patients operated for a complication of diverticulitis were over the age of 70 years. In this subgroup, left colectomy, when performed between attacks carries an acceptable specific morbidity and no mortality. A further study could compare the percentage and outcome of operated patients with those who were denied surgery.

Cystic dystrophy of the duodenal wall developing in heterotopic pancreas is rare. Pancreaticoduodenectomy is usually advocated in cases of symptomatic cystic dystrophy without chronic pancreatitis but little is known about long-term results. We report a case of cystic dystrophy of the duodenum wall developing in heterotopic pancreas responsible for abdominal pain and duodenal obstruction associated with chronic pancreatitis. Pancreaticoduodenectomy allowed complete relief of symptoms. Chronic pancreatitis associated with cystic dystrophy may complicate the choice of appropriate therapy.

The colonic response to food (CRF) is an integrated function of the colon that has been poorly studied in clinical practice. This study describes a new method to measure it, based on the progress of radio-opaque markers, and shows the results in healthy subjects and in patients with irritable bowel syndrome (IBS). Thirty healthy subjects and 43 patients suffering from IBS were studied. Two studies of colonic transit time (CTT), at rest and after eating a standard test meal, were performed. CRF was quantified by calculating the variation in number of markers in each zone of interest of the large bowel using X-ray films of the abdomen taken before and after eating. The results were as follows: (1) CRF is characterised by caudal propulsion of the colonic contents in the two groups. In controls, there is emptying of the cecum-ascending colon region and filling of the distal large bowel. In IBS patients, only emptying of the left transverse colon and the splenic flexure is found. (2) IBS patients have a delayed CTT because of slowing in the right and left colon, and this is both before and after a meal. The determination of the movements of markers after eating is a simple method that is useful in clinical practice to evaluate CRF.

The etiology of Crohn's disease remains unknown. A putative mycobacterial cause of the disease is still controversial.To assess the mycobacterial hypothesis in Crohn's disease using a polymerase chain reaction technique.Nested polymerase chain reaction with primers on the 16S-rRNA coding region (16S-rDNA) and with primers specific both to the insertion sequences (IS) 900, and IS 901/902 were used to amplify Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum DNA in frozen endoscopic intestinal biopsies or surgical resection specimens from patients with Crohn's disease (n = 47: 25 endoscopic biopsies and 22 surgical resection samples, +/- lymph nodes), ulcerative colitis (n = 27), and non inflammatory bowel diseases (n = 20: colonic tumors and diverticulitis). Positive as well as negative controls were used throughout the study.All strains of Mycobacterium paratuberculosis and Mycobacterium avium subsp. silvaticum tested were positive for both primer systems. Of the 94 biopsies tested, 5 (2 Crohn's disease, 1 ulcerative colitis and 2 controls) were positive with the 16S-rDNA primers but did not correspond to Mycobacterium paratuberculosis or Mycobacterium avium subsp. silvaticum. None of the specimens was positive with the IS primers.These results do not support the hypothesis that Mycobacterium paratuberculosis, or Mycobacterium avium subsp. silvaticum play a role in Crohn's disease.

Two cases of Meigs' syndrome are reported, one following an ovarian fibrothecoma and the other an ovarian fibroma. The benign condition was suggested prior to surgery in one of the two patients because of a solid tumor of the ovary without peritoneal implant on CT-scan, and no malignant cells in ascitic fluid and on a fine needle biopsy. To differentiate this benign pathology from a malignant process enables to avoid useless surgical procedures. Preoperative evaluation, including serum CA 125 level, ultrasound examination and CT-scan, allows rarely to suggest the Meigs' syndrome. Nevertheless, this syndrome may be suspected when faced with an important pleural effusion, a very elevated CA-125 serum level, a negative cytologic examination of the ascitic effusion and no peritoneal implant on CT-scan.

New technologies in molecular biology will allow the improvement of screening, diagnosis and prognosis of colorectal cancer patients. For example the determination of germline mutation in APC or in mismatch repair genes in patient with familial adenomatous polyposis or with HNPCC is now possible. The clinical surveillance can be restricted to the patients with these germline defects. More over the knowledge of somatic genetic alterations in colorectal cancer cells seems to be useful in the determination of prognosis of these patients or in order to predict the chemotherapy response.

From January 1989 to December 1996, 56 consecutive patients underwent emergency surgery for occlusive cancer of the left colon. Excepting 12 patients whose symptomatology and radiographic presentation required medial laparotomy, the elective procedure was initial colostomy. There were 11 men and 33 women, mean age 76 years (range 50-97). Two patients in poor general status (ASA III) died during the postoperative period. Among the 42 survivors, the second procedure was not performed because of poor general status or disease progression in 6. Mean delay to the second procedure for resection was 11.5 days; during the same hospitalization for 32 out of 36 patients. The second procedure was segmentary colectomy in 34 cases and limited to exploratory laparatomy because of inextricable lesions in 2. Among the 34 re-operations with segmentary colectomy, the ostomy was removed in 28 at the second procedure and a third procedure was required in 6 cases. All the anastomoses in this series were sutured manually. Mortality for re-operation was nil. Pathology results (Duke's classification) in the 36 reoperated patients was: stage B = 3, stage C = 19, stage D = 14. In this series, operative mortality only concerned those patients whose condition was incompatible with selective surgery for colostomy. This risk cannot be lowered by any, other surgical approach. For the 34 resection-anastomosis elective operations, no major complications or deaths were observed. These results led us to recommend two stage surgery as routine strategy since survival of all those patients capable of sustaining an elective colostomy in an emergency setting can be assured.

Congenital dilatation of the bile duct is an uncommon lesion requiring surgical treatment. Complete excision of the diseased bile duct prevents development of carcinoma of the bile duct. We report three cases of congenital dilatation of the biliary three, each illustrating a particular aspect of the therapeutic strategy. One patient had an unusual anomaly of the pancreaticobiliary junction that required pancreaticoduodenectomy. Another patient developed carcinoma of the bile duct 15 years after an internal derivation of a choledochal cyst. The last patient had dilatations of the common and intrahepatic bile ducts associated with congenital hepatic fibrosis.

The presence of colonic tumor cells in the circulation may predict colorectal carcinoma recurrence and metastases. We have developed a highly sensitive nested RT-PCR assay, with primers derived from the cytokeratin 20 (CK20) and the carcinoembryonic gene CGM2, to detect occult microdisseminated enterocytes in blood of colorectal cancer patients. Among 82 healthy controls analyzed, 40.2% (33/82) have a positive expression of CK20 mRNA which is not statistically different from the 45.5% (15/33) of positive results found in colon cancer patients. This sensitive method may detect non-tissue specific constitutive low level (illegitimate) expression of CK20 mRNA in peripheral nucleated blood cells (PNBC) of a significant number of healthy control as well as in a number of normal bone marrow. The low specificity of this assay therefore hampers its value to detect blood colon cancer dissemination. In 47 patients with colorectal carcinoma, CGM2 primers detected circulating enterocytes in 25 of them (53%). In disseminated Dukes' stage C disease patients, 17 out of 29 (59%) were found positive whereas in localized adenocarcinoma (Dukes's stage A and B), CGM2 primers detected enterocytes in 44% suggesting that an hematogenous spillage of colonic cells may be a relatively early event in colon cancer. None of the patients suffering from benign colonic pathologies or from diverticulitis were found positive for this assay. The analysis of 56 healthy individuals without known colorectal cancer, of 20 non-colorectal cancer patients and of 6 normal bone marrows provide evidence that this assay is highly specific and may predict an hematogenous spread of colonic cells in patients with organ-confined disease. Nevertheless, the clinical significance of enterocyte detection and the potential applications of this molecular tool merit longer term follow-up.

Severe gastric complications due to radiotherapy are uncommon, in particular hemorrhagic gastritis. A high total dose and, above all, high daily fraction appear to be the main risk factors in gastric injuries. A case of hemorrhagic gastritis induced by radiotherapy requesting a total gastrectomy is reported. The patient was treated for a primary gastric non-Hodgkin's lymphoma. Hemorrhagic gastritis occurred despite a low total dose (40 Gy) and 2 Gy daily fractions. Upper gastrointestinal endoscopy and repeated biopsies are usually insufficient to exclude a tumor recurrence. Endoscopic ultrasonography may argue for a recurrence or for radiation lesions. As the conservative treatment is usually ineffective, these gastrointestinal radiation injuries ought to be treated surgically. Besides it allows to ascertain the benign nature of radiation lesions.

Fas and Fas ligand (FasL) are implicated in programmed cell death or apoptosis. In the immunological field, they are particularly important in auto-immunity, graft rejection and anti-tumoral response. Fas ligand expression on thymocytes, activated T lymphocytes, and in sites of immune privilege, suggests the importance of Fas/FasL interactions in negative control of the immune response. The recent description of FasL expression by tumoral cells, represents a new mechanism of immune escape for different cancer, and has been well studied in colon adenocarcinoma.

Portal hypertension is characterised by the development of a collateral portocaval circulation. Among these venous reroutings, some are situated posteriorly in the left subphrenic compartment. These are the spontaneous splenorenal and gastrorenal anastomoses. Their incidence is estimated at around 16%. On the one hand, there are the direct shunts, which anastomose the spelling v. to the left renal v., of an anecdotal nature, and on the other the spontaneous indirect splenorenal shunts, characterised by the presence of a complete neurovascular pedicle traversing the gastrophrenic ligament. This relates to the gastric collateral v., which is connected to the left renal v. via the inferior v. of the left crus of the diaphragm and the middle capsular v., hence the name "gastro-phreno-capsulo-renal shunt". At an advanced stage of portal hypertension these splenorenal shunts may acquire a major caliber and behave like actual surgical shunts.

Exogenous insulin may prevent the auto-immunity of diabetes in rodents. We studied the preventive effect of a safe endogenous insulin delivery in the diabetes-prone NOD mouse by immuno-protected human insulinoma grafts. Perm-selective macrocapsules seeded with human insulinoma were implanted in 34 young NOD mice, 4 and 8 weeks old. The animals were observed 18 months and compared to 34 NOD mice grafted with empty fibers and 25 simply observed. Before grafting, the capacity of the macrocapsules to release insulin was assessed in vitro by perifusion studies and by implantation to 12 diabetic NOD mice. At perifusion, the insulin release of the macrocapsules responded to step changes in glucose. During the in vivo study, the capsules reduced the glycemia of diabetic mice from 18+/-3.5 to 7.3+/-2.1 mmol/L. In the study groups, the survival rate without diabetes (50-70%) was statistically different from controls (10-20%). Recipient's splenocytes transplanted to irradiated male NOD mice transferred the autoimmunity in 75-83% of grafted mice and 86-100% of controls. Insulitis was persistent in all, although milder in the grafted mice. Encapsulated insulinoma prevents diabetes in the NOD mouse without abolishing the auto-immunity. The quantity and quality of the tissues needed and the best moment to graft them have to be determined. The prevention of diabetes by encapsulated pancreatic tissue is appealing because of its simplicity and safety.

The effect of pancreatic transplantation on noninsulin -dependent diabetes mellitus (NIDDM) had not been evaluated in animal models. We assessed its impact by the insulin-glucose clamp study in experimental diabetic rats. NIDDM was induced in Lewis female rats by streptozocin at the age of 5 days (n5-STZ). To determine its effect on insulin sensitivity, we measured the glucose turnover rate and performed euglycemic hyperinsulinemic clamp studies, evaluating hepatic glucose production (HGP) and glucose uptake. This assessment was conducted on 5 groups of 6 female Lewis rats: 2 groups n5-STZ tested at the age of 10 and 14 weeks, respectively; 2 normal age-matched groups; and a fifth group (n5-STZ) transplanted at 10 weeks of age and tested at 14 weeks. Heterotopic pancreaticoduodenal transplantation was performed, using an end-to-side anastomosis between the donor celiac artery and portal vein to the recipient infrarenal aorta and vena cava, respectively. Pancreatic drainage was achieved by an end-to-side duodenojejunostomy. At 10 weeks of age, diabetic n5-STZ rats showed decreased body weight, hyperglycemia, moderate insulinopenia, a significantly higher basal HGP as compared with normal controls (28.5 +/- 10 vs. 10.7 +/- 4 mg/kg/minute, P0.05), and ineffective suppression of the HGP by the insulin infusion. Glycemia, body weight, and basal HGP were normalized in the transplanted group and were statistically similar to age-matched normal controls. HGP was totally suppressed by the insulin infusion. However, the blood insulin level remained significantly higher than in the normal groups (P0.05). We conclude that n5-STZ is a reliable model of NIDDM and that pancreatic transplantation, without immunosuppressive drugs in this isogenic line, corrects all tested parameters of glucose homeostasis and improves insulin sensitivity.

There is no experimental basis for transplantation of the pancreas in patients with non-insulin-dependent diabetes mellitus. We compared results in normal and grafted non-insulino-dependent Lewis rats. A heterotopic pancreatico-duodenal graft was implanted with end-to-side anastomosis of the coeliac artery and the portal vein of the donner on the infrarenal aorta and inferior vena cava of the recipient. The diabetic rats showed weight loss, high blood glucose levels (3.30 +/- 1.25 milligrams), moderate insulinopenia and significantly elevated liver production of glucose. Glycaemia, weight and liver production of glucose were the same as those in the group of normal animals. We concluded that transplantation of the pancreas in an isogenic model without immunosuppression can correct glucose levels and insulino-resistance. It could be suggested in man.

1. The aims of this study were to investigate if compartmental analysis can be used to analyse colonic transit measurements and to search for a relationship between transit time and the parameters deduced from this analysis. In addition, an attempt was made to determine if such analysis could reveal a functional abnormality in patients who complain of constipation but have normal colonic transit. 2. The subjects included 11 healthy controls, 10 patients with chronic diarrhoea and 55 constipated patients. Segmental and total colonic transit time were measured using a previously described method. Compartmental analysis was based on a three-compartment system, with k1, k2 and k3 being the coefficients of diffusion out of the right colon, the left colon and the rectosigmoid area respectively. 3. Patients complaining of constipation who had delayed transit time were the only subjects to have lower values of coefficient k1 than controls. k2 was lower than normal in all patients complaining of constipation, but this decrease was more marked in subjects with delayed colonic transit time than in subjects with normal colonic transit time. All patients complaining of constipation had lower values of k3 than control subjects. 4. This study shows that analysis of colonic transit time is feasible using a simple diffusion law, and that the results are correlated to clinical data. Moreover, this analysis permits detection of abnormalities in two groups of subjects: those who complain of constipation but are labelled as having normal colonic transit time and those who have chronic diarrhoea.

Recto-vaginal fistulas have multiple causes and a wide range of clinical and anatomical features. Simple fistulas, defined by a low situation, a traumatic origin, and a small size are accessible to simple means of cure. They can be operated from a vaginal approach, with conversion into a third degree perineal tear followed by repair of the perineal body, and the anal canal; they can be managed from a transanal approach, using endorectal flap advancement technique. Complex fistulas, defined by the etiology (IBD, radiation enteritis, cancer, postoperative), a high situation, or a large size, require larger and more sophisticated operations such as a combined abdomino-perineal approach or a muscle flap technique. Among the numerous techniques described for the cure of recto-vaginal fistulas, the authors emphasize those currently used by the most experienced teams of colo-rectal or gynecological surgeons.

A tetra-polar electrical impedance device has been constructed to permit study of gastric emptying using a microcomputer. An alternative current of 100 kHz, 4 mM peak-to-peak, is injected through a pair of surface electrodes on the upper abdomen. The voltage variations picked up across the second pair of electrodes correspond to the variations of epigastric impedance in response to the applied current. The low frequency voltage corresponding to gastric emptying and recording noise is then conditioned and digitised at a sampling frequency of 1 Hz. A parallel 8-bit signal is finally converted to standard serial form and sent, in real time, to a microcomputer via a serial port. In a process of off-line analysis, the emptying trace was extracted from measured traces by taking successive Fast Fourier Transform (FFT) of length 64 points and was then fit by three mathematical models: linear, exponential and Weibull. The rate of emptying was calculated in terms of the time needed to achieve 50% emptying (T 1/2) from the best fit model. A clinical experiment was done in 20 healthy volunteers to investigate the reproducibility of the method and compared to a scintigraphic method. Successive measurements on the same subject gave statistically similar results and were statistically independent. No correlation has been observed between impedance and scintigraphic methods.

Digestive tract cancers are infrequent during pregnancy. Prognosis is usually dismal both because diagnosis is delayed as a result of symptoms being ascribed to the pregnancy and because saving both the mother and fetus is difficult. A review of the relevant literature, focused on colorectal and gastric cancers which are the most common forms, emphasizes the need for early diagnosis and for adjusting treatment to gestational age at diagnosis.

In AIDS patients an acalculous cholecystitis may be responsible for abdominal pain subsiding after cholecystectomy. But the indications for cholecystectomy are not clear: cholecystitis is usually associated with diffuse cholangitis and this might cause the symptoms. Since 1985, 8 AIDS patients have undergone cholecystectomy for acute cholecystitis. Ultrasonography revealed a 5 to 12 mm thickening of the gallbladder wall in all of them and gallbladder stones in two; four patients had cholangitis. The decision to operate was based on persistent pain associated with fever, poor general condition and muscular rigidity at palpation. Four patients had septic shock at the time of surgery; one died in the immediate postoperative period. In all other patients pain and septic syndrome subsided. Two patients died of AIDS complications 20 days after surgery; the remaining five died of AIDS 6, 9, 10, 12 and 14 months respectively after surgery; in two of them cholestasis had reappeared due to cholangitis. To summarize, in the 8 AIDS patients studied cholecystectomy was performed for clinical deterioration. Gallbladder pathology was responsible for the abdominal pain and the febrile general condition which was relieved by cholecystectomy.

Among 126 patients operated upon for acute necrotizing pancreatitis in our department over a 10-year period starting in November 1979, 17 had a colonic resection. Colectomy was made mandatory by a necrotic or ischaemic appearance (12 cases, including 3 bowel perforations), an isolated perforation (2 cases) or extensive fat necrosis of the pericolonic atmosphere (3 cases). The hospital mortality was 5 out of the 17 cases. In 6 patients, the pathological results suggested that colonic resection was unnecessary. Since May 1988, a diverting loop ileostomy has been performed whenever colonic viability was found to be dubious at laparotomy. After this policy was introduced no case of secondary colonic complication was encountered. Nevertheless, there still are "abusive" colectomies unjustified by the pathology. Their number should be reduced by a more cautious indication of colonic resection in acute necrotizing pancreatitis.

The relationship between pancreas divisum and chronic pancreatitis is controversial. We report the cases of two patients aged 40 and 53 years suffering from recurrent pancreatitis and known to have histologically proven idiopathic chronic pancreatitis. One patient had insulin dependent diabetes. Pancreatography demonstrated in these two cases a pancreas divisum with a dilated dorsal pancreatic duct. A pancreatico-jejunostomy was performed, associated in one case with splenopancreatectomy for pseudo-cyst. With a follow-up of 32 and 78 months, both patients were free of symptoms and the diabetic patient had normal blood glucose levels with diet alone. The clinical history of the patients suggests a relationship between pancreas divisum and chronic pancreatitis and that pancreatico-jejunostomy may improve pancreatic pain and pancreatic function.

The operative diagnosis of colonic ischaemia in association with acute necrotizing pancreatitis (ANP) may be difficult in the absence of unequivocal transmural necrosis or perforation. We introduced in May 1988 a new policy whereby, when colonic viability was dubious, resection was avoided and a diverting loop ileostopy (DLI) was performed. If necrosectomy led to extensive mobilization of the splenic flexure with a capillary drainage system placed in close contact, a DLI was again performed. Colectomy was only performed for unequivocal transmural necrosis. Among 30 patients operated on for ANP, 12 underwent DLI. This policy allowed us to spare potentially ischaemic colons. No secondary colonic complication occurred and there was no rise in the mortality rate. Among patients whose colon was kept in circuit there were bouts of bowel distension and unexplained bacteriemia ultimately leading to death from multiorgan failure. When colonic viability is dubious and when drainage is brought up in close contact with the bowel wall DLI might allow colonic resection to be avoided. In our experience DLI also seemed to prevent secondary colonic complications.

The organ distribution of microsomal cytochrome P 450 isoenzymes (P 450), microsomal epoxide hydrolase (EH) and cytosolic glutathione-S-transferases was investigated by immunoblotting and enzyme measurements in rats and humans. In rats, P 450 IA1 was detected only in the duodenum, and P 450 IA2 and IIC11 were detected only in the liver. The highest concentrations of P 450 IIB1/B2 were found in the lung and in the duodenum; pentoxyresorufin-O-dealkylase activity was closely correlated with the amounts of P 450 IIB1/B2 in the different organs. P 450 IIE1 was present in liver, kidney and lung, whereas EH was found in liver, intestine and kidney. In humans, P 450 IIIA4 was detected in all tissues investigated; the highest concentrations were found in liver and intestine. The P 450 IIIA4 level was closely correlated with that of erythromycin demethylase and pentoxyresorufin-O-dealkylase activities. P 450 IIC8-10, IIE1 and IID6 were expressed in liver and intestine, P 450 9 in liver and kidney and P 450 IA2 in liver. EH was identified only in liver, intestine and kidney. In both species, concentrations and total amounts of P 450 isoenzymes and EH were much lower in all extrahepatic tissues than in the liver. Conversely, glutathione-S-transferase-pi was abundant in human intestine and colon compared to liver. Glutathione-S-transferase-mu polymorphism was confirmed in all tissues investigated. This extensive study showed that the pattern of (iso) enzymes was different in all tissues studied; consequently, xenobiotic metabolism would appear to be very different in each type of tissue.