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Biomedical subjects

B Nordlinger

Publications and source records attributed to B Nordlinger.

At least 19 recordsLinked to original sources

Dormant liver metastases: an experimental study.

Experimental work was undertaken to evaluate whether intrahepatic recurrences, observed after resection of colorectal liver metastases in humans, could be due to the activation of dormant cancer cells already present within the liver at liver resection. About 250 cell aggregates (DHDK12 colon carcinoma cell line) were injected into the portal vein of 70 BD IX rats. Eight weeks later, 43 rats with no apparent liver metastases were divided randomly into three groups: group 1 (n = 15) served as control; group 2 (n = 15) were given cyclosporin A (10 mg kg body-weight-1 day-1) for 28 days; and group 3 (n = 13) underwent a 70 per cent hepatectomy. Twelve weeks after the injection of cells, when the animals were killed, 20 per cent of rats in group 1 had liver metastases, 80 per cent in group 2 (P less than 0.01) and 62 per cent in group 3 (P less than 0.05). Undetectable liver micrometastases may have been present at 8 weeks and had not developed until stimulation by cyclosporin A-induced immunosuppression or by liver regeneration after hepatectomy. A similar mechanism may occur clinically and explain some of the recurrences observed after resection of liver metastases.

Animals

Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.

Animals

Tumours of Oddi: diagnosis and surgical treatment.

A retrospective review of 56 patients operated upon for tumours of Oddi was performed in order to determine optimal diagnostic and therapeutic procedures. Common presenting symptoms were jaundice (86%) and anemia (21%). Mean size of the tumour was 2.3 cm. Five tumours were benign and 51 were malignant. According to the classification of Martin, five were grade I: 10 grade II; 18 grade III; and 18 grade IV. Forty-seven patients underwent resection of the tumour: three local excisions for small benign tumors, six ampullectomies (followed in three by a Whipples' procedure for recurrence) and 41 Whipples' procedures. The hospital mortality was 5.3%, minor complications appeared in 21%. The overall five years survival was 41%. It was 75% in grade I, 50% in grade II, 40% in grade III and 10% in grade IV. The patients who received ampullectomies were alive with a follow-up of one, two and three years. All patients operated upon for a benign tumour were alive except one who died of cardiac failure. Ultrasonography and duodenoscopy are the most useful tests for the diagnosis of tumours of Oddi. Prognosis depends on the degree of infiltration of the duodenal wall and the presence of positive lymph nodes. Whipples' procedure is best but ampullectomy can be used in elderly or poor risk patients. Malignant tumours of the ampullary region are infrequent and reported to constitute between 0.02 and five percent of all cancers of the digestive tract. With wider application of endoscopic techniques, there has been an increasing interest in this group of tumours during recent years. In the literature tumours of Oddi are usually reported in the group of periampullary tumours, including tumours of the ampulla itself, duodenal wall surrounding the ampulla, the distal part of the common bile duct and head of the pancreas. We have wanted to distinguish specifically the tumours of the ampulla of Vater and have adopted the term tumour of Oddi introduced by Marchal and Hureau.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholestasis

[What role is left to surgery in portal hypertension?].

The place of surgery in the treatment of gastrointestinal haemorrhage in cirrhotic patients remains controversial. Emergency surgery may be considered when other haemostatic techniques fail. In this situation, the decision to operate must be taken rapidly, as the prognosis depends on the patient's preoperative status and the degree of hepatocellular failure (HCF). Elective surgery for portal hypertension completes with long-term sclerotherapy, and randomised prospective comparative studies have not been able to clearly distinguish between the two methods. The objective of the various operations proposed is to prevent recurrent haemorrhage without inducing any mortality or major morbidity (particularly encephalopathy). Partial, selective anastomoses and devascularisations appear to satisfy these objectives. The choice of technique depends on the portal flow rate, the type of varices, the degree of HCF and the surgeon's experience. Lastly, liver transplantation should be considered when portal surgery is decided in order to select a procedure which does not compromise the possibility of future transplantation and also as an alternative to portal surgery, particularly in young subjects with already severely impaired liver function.

Anastomosis, Surgical

[Comparison of functional results of ileorectal and ileo-anal anastomoses in familial adenomatous polyposis. Conversions of ileorectal anastomoses into ileo-anal anastomoses].

The aim of this study was to compare the functional results of ileo-rectal anastomosis and ileal pouch-anal anastomosis in a group of patients with familial adenomatous polyposis who had conversion of a ileorectostomy into a ileal pouch-anal anastomosis. In 2 cases (8.3 percent), the conversion was impossible because of abdominal desmoid tumors. For the remaining 21 patients, with more than 1 year follow-up, the number of bowel movements per 24 hours was 3.8 +/- 0.2 before and 4.6 +/- 0.3 after conversion. Daytime and nighttime continence and sensation of the need to defecate were unchanged. The number of patients having nocturnal bowel movements were higher after the pouch procedure (40 vs 10.5 percent). After ileorectostomy and after conversion, 89.5 and 80 percent of the patients had good functional results respectively. Ninety percent of the patients said that results were unchanged or improved after the conversion. In familial adenomatous polyposis the functional results of ileal pouch-anal anastomosis are similar to those of ileorectostomy but the first procedure eradicates the risk of rectal cancer. A conversion to ileal pouch-anal anastomosis should to be proposed to patients with ileorectostomy and at high risk for rectal cancer.

Adenomatous Polyposis Coli

[Diverting loop ileostomy, effective prevention of colonic complications in necrotizing acute pancreatitis].

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.

Acute Disease

Cholestasis induces major histocompatibility complex class I expression in hepatocytes.

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However, aberrant expression occurs in cholestatic diseases such as primary biliary cirrhosis. The aim of this work was to assess the effect of cholestasis itself on hepatocyte MHC expression and to determine if immunosuppressive drugs might modulate this expression. Liver fragments taken from six patients with extrahepatic cholestasis and eight control patients were analyzed for MHC expression by direct immunofluorescence. MHC class I expression by hepatocytes was present in six of six cholestatic patients and zero of eight control subjects. Hepatocytes did not express MHC class II in either group. In further studies, cholestasis was induced in rats by ligation-section of the bile duct. Five groups of rats were studied: control, 3-day cholestasis, 5-day cholestasis, 5-day cholestasis plus cyclosporine, and 5-day cholestasis plus corticosteroids. Hepatocyte MHC class I expression was detected by immunofluorescence in bile duct-ligated rats but not in control animals. Flow-cytofluorimetric analysis of isolated hepatocytes showed that the percentage of hepatocytes expressing MHC class I increased from day 0 (9.9%) to days 3 (50.2%) and 5 (82.9%); this hyperexpression was not modified by cyclosporine (79.7%) or corticosteroids (77.9%). The percentage of hepatocytes spontaneously expressing MHC class II was low (0.05%) and was not significantly modified by cholestasis or immunosuppressive drugs. Thus, a nonimmunological factor such as cholestasis is able to modulate MHC expression. The liver may become more vulnerable to immune destruction in the presence of cholestasis, and immunosuppressive treatment has no effect on this phenomenon.

Aged

[Total pharyngolaryngoesophagectomy. Indications and results apropos of 17 cases].

Pharyngolaryngoesophagectomy (PLO) allows one-stage treatment of synchronous tumors involving both esophagus and hypopharynx and may also be advocated when the pharyngo-esophageal junction (PEJ) is involved. Less radical surgery may be advocated in the case of hypopharyngeal malignancy sparing the pharyngoesophageal junction. The authors report the results of 17 PLO carried out in 11 cases for a tumor involving the PEJ, and in 4 cases for synchronous tumors involving esophagus and hypopharynx. In 2 instances, PLO was performed for primary hypopharyngeal malignancy requiring total circular excision (i.e. which did not involve the PEJ). Five patients had previously received chemotherapy and 6 had had an association of chemotherapy and radiation therapy as initial treatment before surgery. Reconstructive procedure used the stomach and colon in 12 and 5 cases respectively. Hospital mortality was 4 cases out of 17. There was 1 cervical fistula secondary to pharyngogastric anastomosis necrosis. One and 2 year actuarial survival rates were 73% and 37%. Tumor recurrence and a remote new tumor were noted in 6 and 4 cases respectively, despite extensive surgical procedures and the use of chemotherapy and/or radiotherapy. When esophagectomy was added to total circular excision in case of hypopharyngeal tumor sparing the PEJ, no significant benefit was noted. Good functional results obtained by means of PLO shall lead to therapeutic trials including surgery, chemotherapy and radiotherapy with the aim of improving long-term results.

Adult

[Thyroid cancer revealed by a suppressive hot nodule].

We report the case of a 62-year old woman in euthyroidism who presented with a thyroid cancer located within a hot nodule. The nodule was partially extinctive, and the triiodothyronine test showed incomplete suppression. Fine needle cytology showed no malignant cells. Systematic lobectomy was performed, and the diagnosis of cancer was made at pathology. This rare situation does not mean that all non-toxic hot nodules must be removed, but if surgery is decided an extemporaneous histological examination is mandatory. Besides, such cases provide an additional argument in favour of surgery or treatment of toxic adenomas.

Female

Experimental model of colon cancer: recurrences after surgery alone or associated with intraperitoneal 5-fluorouracil chemotherapy.

The liver is the most frequent site of metastases in colon cancer. No good animal model has been available to help improve the treatment of liver metastases or their prevention after resection of a primary colon cancer. The aim of this study was to develop a model of colon cancer induced by azoxymethane in the rat and to study the outcome after surgical resection alone or in association with intraperitoneal chemotherapy (5-fluorouracil (5-FU). Three hundred male Wistar rats received subcutaneous azoxymethane (10 mg/kg body weight/week) for 12 weeks. Eighty-three rats with isolated colon cancer underwent total colectomy; 40 of these rats with no metastases were randomized into two groups: surgery alone or surgery plus 5-FU (5 mg/kg body weight/day) for 5 days after surgery. Thirty rats were able to be evaluated. At autopsy, peritoneal carcinomatosis and liver metastases were more frequent in the control group than after adjuvant treatment with 5-FU (27.7 percent vs. 0, P less than 0.05; and 22.2 percent vs. 0, P less than 0.05, respectively). The rates of peritoneal and hepatic recurrence after resection of the primary cancer indicate that the model mimics the natural history of human colon cancer. In this model, 5-FU reduced the rate of peritoneal carcinomatosis and liver metastases but did not influence survival.

Adenocarcinoma

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