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Biomedical subjects

B Nordlinger

Publications and source records attributed to B Nordlinger.

At least 109 records · Page 6Linked to original sources

High-dose folinic acid, 5-fluorouracil bolus and continuous infusion in poor-prognosis patients with advanced measurable gastric cancer.

Twenty-five patients with advanced measurable gastric cancer were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. Fourteen patients over 65 yr old and/or with a poor general status received first-line treatment, and eleven younger patients second-line. The response rate was 43.5% in 23 evaluable patients. There were 2 complete responses (8.7%) and 8 partial responses (34.8%). Median survival was 6 months in first-line and 8 months, calculated from start of folinic acid-5FU, in second-line. Toxicity was mild without WHO Grade greater than 2 events. This combination is effective for advanced gastric cancer in poor-prognosis patients and requires further studies.

Adenocarcinoma↗

[Experimental models for hepatic metastases from colorectal tumors].

Over recent years, the interest in the development of experimental models of colorectal liver metastases has increased due to the need for new adjuvant therapies to improve the treatment of both colorectal cancer and liver metastases. The induction of colon cancer by carcinogens in the rat with spontaneous liver metastases fairly closely mimicks the natural history of colon cancer but a low yield of both colonic cancer (less than 50%) and liver metastases (approx. 25%) is obtained after 6 months of latency. Direct intraportal injection of cells derived from a colon carcinoma cell line is the experimental model most often used. Although it bypasses the natural history of cancer this simple model produces up to 100% of liver metastases 6 weeks after injection of cells. These two models have been used for several studies of liver metastases concerning their morphology, their modulating factors and their vascularisation. They have been used to test new adjuvant therapies for colorectal cancer.

Animals↗

Experimental colorectal liver metastases. Influence of sex, immunological status and liver regeneration.

The liver is the most frequent site of metastases from colon cancer. To improve our knowledge of liver metastases and to develop new adjuvant therapies, a good animal model is necessary. The aims of this study were to obtain a model of liver metastases with intraportal injection of colon adrenocarcinoma cell aggregates (DHDK12 cell line) and to study the effect of various factors, i.e., sex, liver regeneration and immunosuppression, on the development of liver metastasis. Cell aggregates were injected into the portal vein of 59 syngenic male and female BD IX rats following randomization into three groups. Group 1, (control 12 males and 10 females) received only cell aggregates; group 2 (12 males and 10 females) underwent a 70% hepatectomy before cell injection; group 3 (15 males and 10 females) received cyclosporin A injections at a dose of 10 mg/kg per day for 28 days following cell injection. Autopsy was performed at 10 weeks. Liver metastases were more frequent in the male rats in group 3 than in those in group 1 (80% vs. 30%, p less than 0.04). The rate of liver metastases in females was not increased by immunosuppression (22.2% vs. 12.5%, N.S.). Liver resection (group 2) did not significantly modify the incidence of liver metastasis. No female had liver metastases in this group. This relatively simple model rapidly produces liver metastasis with a high yield, but only in male rats. Besides sexual factors, immunosuppression also increased the rate of experimental liver metastasis, while liver regeneration failed to do so.

Adenocarcinoma↗

[Hepatocyte transplantation. Treatment of hepatic encephalopathy. An experimental study in the rat].

The aim of this work was to assess the effect of intrasplenic liver cell transplantation (ILCT) on hepatic insufficiency induced by a terminolateral portocaval shunt (PCS) in rats. Thirty syngenic Wistar Furth rats were divided up into three groups: (a) rats with PCS (n = 10); (b) rats with PCS then ILCT of 10(7) liver cells isolated from the livers of syngenic rats (n = 10); (c) operated control rats (n = 10). Double-blind behavior tests were carried out two weeks, two months and six months after surgery. The spontaneous motor activity and the exploring activity of each rat were studied in automated cages fitted with infrared diodes. Each interruption of the infrared beam was automatically recorded by a computer and converted into an activity score (number/hour). The spontaneous motor activity and the exploring activity were poor in the rats with PCS. The ILCT significantly increased the spontaneous motor activity and the exploring activity 2 months and 3 weeks after transplantation, respectively. Three months after transplantation, the spontaneous motor activity and the exploring activity in the PCS/ILCT group were not significantly different from those of the control rats. This study shows that ILCT can correct the neurological signs of hepatic encephalopathy in an experimental model of chronic hepatic insufficiency, and suggests that ILCT may produce therapeutic benefits in chronic hepatic insufficiency.

Animals↗

Repeat hepatic resection for primary and metastatic carcinoma of the liver.

During the last 15 years, 19 patients underwent repeated hepatic resections for malignant lesions of the liver. The first hepatic resection had been performed four to 40 months earlier for treatment of hepatocellular carcinoma (nine patients) or hepatic metastases (ten patients), eight of which were of colorectal origin. Repeat resection was an extensive hepatectomy in six, a segmentectomy in six and a local excision in seven. In one patient, three wedge resections and, finally, hepatic transplantation were subsequently performed after an initial extended right lobectomy. The operative mortality rate was 5.2 per cent. The three year actuarial survival rate was 64 per cent after the second resection.

Adult↗

[Hepatectomy with total vascular exclusion. Anatomical principles based on 64 dissections].

Intra-operative hemorrhage is the main surgical risk during liver resections. Nowadays hepatectomies for large or posterior liver tumors close to the hepatocaval junction can benefit from total hepatic vascular exclusion (HVE) involving portal triad exclusion and clamping of the inferior vena cava (IVC) below and above the liver. Anatomical aspects of HVE have been studied in 64 subjects by segmental occlusive phlebographies of the IVC, injection of corrosive substances into the hepatocaval network, biometry of the retrohepatic IVC and serial sections of injected livers. A total HVE should exclude the right suprarenal and phrenic veins. Clamping of the suprahepatic IVC depends on the termination of the left inferior phrenic vein. Clamping of the subhepatic IVC must be retrohepatic: the right lobe of the liver has to be mobilized to free the right border of the retrohepatic IVC into which flows the right suprarenal vein 40 +/- 20 mm above the right renal vein and under the superior right hepatic vein. Both suprahepatic and retrohepatic clamps excluding the retrohepatic portion of the IVC (46.6 +/- 13 mm) and the hepatocaval junction should come in contact behind the IVC without overlapping.

Constriction↗

[Reoperation in severe hepatic trauma. 30 cases].

From 1978 to 1987, thirty patients were secondarily referred to Saint-Antoine Hospital for the treatment of their hepatic trauma. Seventeen were referred because of a postoperative complication (group I) and thirteen after peri-hepatic packing (group II). In group I, transfer was decided because of hemorrhage (8 patients), sepsis (6 patients) and haemobilia (3 patients). The lesions observed in this group (hemoperitoneum, hepatic sequestrum, intrahepatic hematoma, choleperitoneum and subphrenic abscess) were often related to an incomplete assessment of hepatic damage due to an inadequate exploration and the absence of operative cholangiography. In group II, peri-hepatic packing was effective in eleven patients. The overall mortality was 16.6% (17.6% in group I and 15.4% in group II). Postoperative complications occurred in 50% of the patients (64.6% in group I and 30.7% in group II). Good exposure of the liver, operative cholangiography and, in selected cases, a direct approach to the lacerated liver with suture ligation of severed blood vessels and bile ducts are mandatory for the complete exploration and the treatment of severe hepatic trauma. Peri-hepatic packing and the transfer of the patient to a specialized center is a reliable method when the injury cannot be treated locally.

Adolescent↗

The isolated perfused rat spleen. An original method for studying the function of hepatocytes transplanted into the spleen.

The aim of this study was to assess directly the function of isolated hepatocytes 1 year after transplantation into the spleen, using an original model of isolated rat-spleen perfusion. Three specific liver functions, albumin synthesis, indocyanine-green clearance, and antipyrine oxidation, were studied. Five x 10(6) isolated hepatocytes were injected into the spleen of syngenic Wistar-Furth rats. One year later, splenectomy was performed, and the splenic pedicle was carefully isolated in order to allow a selective ex vivo perfusion for 3 hr. De novo albumin synthesis was studied by qualitatively using immunoelectrophoresis and autoradiography, and quantitatively using (35S)-methionine incorporation in albumin. De novo albumin synthesis was observed in spleens containing transplanted hepatocytes but not in controls (P less than 0.001); (35S)-methionine incorporation was significantly higher in spleens containing transplanted hepatocytes than in controls (132 +/- 67 cpm/spleen/hr vs. 14 +/- 6 cpm/spleen/hr, P less than 0.001). Antipyrine clearance was significantly higher in spleens with transplanted hepatocytes than in controls (67.4 +/- 4.9 microliters/min/g vs. 0.2 +/- 0.4 microliters/min/g, P less than 0.01). No statistically significant difference was observed with indocyanine-green clearance (4.2 +/- 6.0 microliters/min/g, vs. 5.2 +/- 5.1 microliters/min/g, P greater than 0.05); this was probably due to the absence of compartmentation between the sinusoid and biliary sectors in this model. In conclusion, using this original isolated rat-spleen perfusion model, it was directly observed that 1 year after transplantation, intrasplenic hepatocytes can perform two liver-specific functions, i.e., de novo albumin synthesis and antipyrine clearance.

Albumins↗

Adjuvant therapy of poor prognosis colon cancer with levamisole: results of an EORTC double-blind randomized clinical trial.

From 1978 to 1985, 297 patients were entered in a double-blind randomized trial comparing levamisole to placebo as adjuvant therapy of Dukes' C carcinoma of the colon. Therapy consisted of from two to five tablets of 50 mg levamisole (or placebo) twice a week, depending on bodyweight for 1 year. Levamisole was generally well tolerated, with only four reversible cases of agranulocytosis reported among 129 patients. The trial failed to show a benefit of levamisole on disease-free survival (P = 0.53) or on survival (P = 0.35). There was no difference between the two treatment groups in terms of number of disease relapses, sites of relapse, or time to relapse. The proportion of patients still alive at 5 years was 51 per cent (standard error, 5.5 per cent) in the levamisole group versus 39 per cent (standard error, 5.4 per cent) in the placebo group.

Adjuvants, Immunologic↗

Cytogenetic characterization of a colon adenocarcinoma from a familial polyposis coli patient.

We report on the cytogenetic findings in a fresh biopsy of a colorectal adenocarcinoma in a patient with familial polyposis coli (FAP). The stemline had 45 chromosomes with several clonal chromosome aberrations including a der(17)t(17;?), and -18, which are the two most recurrent aberrations in sporadic colorectal carcinomas. This finding is discussed in relation to the chromosomal changes described in sporadic colorectal carcinomas and in FAP cell lines.

Adenocarcinoma↗

Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases.

The intra- and early postoperative courses of 142 consecutive patients who underwent liver resections using vascular occlusions to reduce bleeding were reviewed. In 127 patients, the remnant liver parenchyma was normal, and 15 patients had liver cirrhosis. Eighty-five patients underwent major liver resections: right, extended right, or left lobectomies. Portal triad clamping (PTC) was used alone in 107 cases. Complete hepatic vascular exclusion (HVE) combining PTC and occlusion of the inferior vena cava below and above the liver was used for 35 major liver resections. These 35 patients had large or posterior liver tumors, and HVE was used to reduce the risks of massive bleeding or air embolism caused by an accidental tear of the vena cava or a hepatic vein. Duration of normothermic liver ischemia was 32.3 +/- 1.2 minutes (mean +/- SEM) and ranged from 8 to 90 minutes. Amount of blood transfusion was 5.5 +/- 0.5 (mean +/- SEM) units of packed red blood cells. There were eight operative deaths (5.6%). Overall, postoperative complications occurred in 46 patients (32%). The patients who experienced complications after surgery had received more blood transfusion than those with an uneventful postoperative course (p less than 0.001). The length of postoperative hospital stay was also correlated with the amount of blood transfused during surgery (p less than 0.001). On the other hand, there was no correlation between the durations of liver ischemia of up to 90 minutes and the lengths of postoperative hospital stay. The longest periods of ischemia were not associated with increased rates of postoperative complications, liver failures, or deaths. There was no difference in mortality or morbidity after major liver resections performed with the use of HVE as compared with major liver resections carried out with PTC alone, although the lesions were larger in the former group. It is concluded that the main priority during liver resections is to reduce operative bleeding. Vascular occlusions aim at achieving this goal and can be extended safely for up to 60 minutes.

Aged↗

[Acute necroticohemorrhagic pancreatitis. Why, when and how to drain? Apropos of 106 cases].

The heavy toll of necrotizing acute pancreatitis led the authors to start developing a new method of treatment in experimental and clinical conditions in 1979. This was aimed on one hand at creating a large channel for the centrifugal drainage of pancreatic or peri-pancreatic foci, and on the other hand at maintaining this draining channel during the first 5 weeks of acute evolution of the acute necrotizing pancreatitis in order to allow the permanent evacuation of purulent or necrotic fragments. From 1979 to 1989, 106 patients were treated with this method, ie. 71 men and 35 women with an average age of 47.9 years. 73 (74%) of these patients had been referred by other hospitals, and 64 only had been initially operated at Saint-Antoine hospital. All patients presented with extensive peripancreatic necrosis. The average Ranson score was 4.8 (not taking the fluid sequestration during the first few hours into account). Visceral failure was observed in 76% of the patients before surgery. The necrosis of the pancreatic gland was focal in 6 cases, extensive in 47 cases and total or subtotal in 25 cases. Out of the 70 CT studies, 64 showed a Ranson grade of E. All patients received enteral feeding on a jejunal site postoperatively. The mortality rate was 16%. The stay of the surviving patients in the intensive care unit averaged 50 days. 29 patients (27%) were reoperated on for complications or insufficient drainage.

Adult↗

Single-layer anastomosis in surgery of the large bowel. A prospective study on 316 cases in a university hospital.

A prospective study was undertaken to evaluate the results of a single layer appositional technique for large bowel anastomoses used in a University Hospital. 316 patients were entered during an 18-month period. Anastomoses were situated within the peritoneal cavity in 277 patients and below the peritoneal reflection in 39. No covering stoma was made. The incidence of clinical leakage was 1.6% and of wound infection 1.9%. These results compare favourably with those obtained by stapling. For intraperitoneal anastomoses and high anterior resection manual suture remains the standard technique and is less expensive than stapling. For low rectal tumours, there is still debate on the relative merits of stapling and various manual techniques of colo-anal anastomosis in terms of morbidity, tumour clearance and functional results.

Adolescent↗