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Biomedical subjects

M Pocard

Publications and source records attributed to M Pocard.

67 records · Page 4Linked to original sources

[Two colons--two cancers? Proximal or distal adenocarcinoma: arguments for a different carcinogenesis].

The purpose of this review is to study the literature concerning normal colon and colorectal cancer for evidencing that the location of the primary proximal or distal tumor may determine two categories of carcinogenesis. The proximal or distal normal colon can be considered as two different organs. Their embryologic origins are different, the splenic flexure starts the distal segment. Antigenic pattern as well as the use of metabolic pathways, such as that of glucose, butyrate and polyamines differ. Epidemiologic, macroscopic and histological features and the inherited and acquired genetic abnormalities allow in some cases to distinguish between two types of cancer according to their proximal or distal location. These two forms are not entirely different and these features can overlap. However the recognition of these two different forms of colon cancer, must be taken in account for clinical or basic research and evaluation of data.

Adenocarcinoma↗

[Orthotopic implantation of human colon cancers into nude mice. Methodology and physiopathological value].

OBJECTIVE: The xenograft of human cancers into athymic nude mice makes it possible to obtain abundant tumour material and deepen biological characterization. Usually, the tumours are grafted into the subcutaneous tissue whose environment is indeed different from that of original colon cancer. METHODS: In order to transplant tumours into an orthotopic environment, intra-caecal implantation of colon cancers was performed. A tumour fragment (30 mm3) was deposited at the surface of serous membrane of the caecum, previously scrapped, fixed with a thread and recovered with biologic glue. Six different types of colon tumour, previously adapted to transplantation in nude mice, were similarly grafted. RESULTS: Twenty to forty days after transplantation, tumour takes were observed with a similar rate by the subcutaneous or intra-caecal graft (93% of 115 and 96.8% of 154 transplantations, respectively). Tumour growth varied between the tumours implanted into the two sites. Moreover, only the tumours intracaecally transplanted developed nodal and liver metastases. Histological examination revealed the invasion of the muscle layer, submucosal tissue and mucosal membrane by tumour cells and the mixture of normal glands and neoplastic glands. CONCLUSIONS: This technique of orthotopic implantation of colon cancer samples will contribute to obtain an experimental model for colon cancer research.

Animals↗

[Peri-operative chemotherapy during resection of pulmonary metastases of sarcoma].

The objective of this prospective study was to evaluate the mortality and morbidity of sarcoma pulmonary metastasis resection with continuous chemotherapy. Ifosfamide was administered at the daily dose of 1200 mg/m2/24 h. Twenty-six resections of pulmonary sarcoma were performed from December 1990 to April 1992. The primary lesion was already resected in all patients. Peri-operatory chemotherapy was started 30 minutes before surgery and continued for 6 days. Chemotherapy was associated with an uroprotector, antiemetic drugs and adequate hydration. Patients had a mean age of 30.6 years. The delay between initial and thoracic surgery was 81 months. The following was performed: tumorectomy (32), wedge (18), lobectomy (7), diaphragm resection (1), left pneumectomy (1). All patients had the 6-days chemotherapy course. None of the patients died. Respiratory failure following superinfection, but not necessitating assisted ventilation, was observed in one case. The following adverse events were noted: nausea (34.6%), uncomplicated cystitis (15.4%), leucopenia (7.6%), fever (3.8%). Mean duration of hospitalization was 11.8 days. Chemotherapy adverse effects did not result in significant morbidity. Bronchial fistula was not observed. Following the results of this pilot study, we feel that perioperatory chemotherapy can be added to sarcoma pulmonary metastasis resection surgery without increasing patient morbidity and mortality.

Adult↗

Hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis of digestive and peritoneal origin: rationale.

Up to a few years ago peritoneal carcinomatosis was considered as an "incurable" disease. The aim of this paper is to review the surgical approach with curative intent to carcinomatosis: it consists of complete resection of macroscopic disease (R1), associated with hyperthermic intraperitoneal chemotherapy (HIPEC) to treat residual microscopic disease, and to evaluate its indications. Overall 5-year survival of patients with peritoneal carcinomatosis treated by HIPEC is similar to that of patients with hepatic metastases treated with curative intent. Those patients should no longer be considered as patients with a terminal disease but as patients with a potentially treatable localized disease.

Antineoplastic Agents↗

Response to 5-fluorouracil of orthotopically xenografted human colon cancers with a microsatellite instability: influence of P53 status.

Response to 5-FU of 5 different human colon cancers (hCC) with a DNA microsatellite instability (MSI), xenografted into nude mice, was analysed according to their p53 status. Two hCC (TC82 and TC71) had a mutated p53 (mutp53), while two others (TC33 and LoVo) had a wild type p53 (wtp53); the fifth tumour (X17LoVo) originated from the stable transfection of LoVo cells with a dominant mutp53 (273his) vector. All tumours were implanted onto the caecum of nude mice to induce orthotopic growth of hCC. 5-FU was administered at 40 mg/kg per day for 5 consecutive days. A significant growth inhibition of TC82 and TC71 tumours (of 68 and 60%, p < 0.05 and < 0.01 respectively) was observed, whereas 5-FU had no effect on TC33 and LoVo. Moreover, the mutp53 transfected tumour, X17LoVo, displayed significant sensitivity to 5-FU (p < 0.05). This suggests that distinct genetic alterations influence differently the response of hCC to this antimetabolite.

Adenocarcinoma↗

A new etiology of acute abdominal emergencies in cirrhotic patient: secondary pneumococcal peritonitis with jejunitis.

We report the first case of secondary pneumococcal peritonitis associated with acute jejunitis in a 52-year-old homeless Child-Pugh C cirrhotic man without ascitis. The patient was admitted with clinical signs of peritonitis, and jaundice. Morphologic examination was unremarkable. A laparotomy revealed a diffuse peritonitis, and an acute jejunitis with prenecrotic lesion. The lesion was located within the first centimeters of the jejunum, immediately after the duodeno-jejunal angle, extented on 15 cm. A resection of the first 15 cm of the jejunum was performed with duodeno-jejunal side-to-side manual anastomosis. Gram-stain and cultures of blood, peritoneal pus, and jejunal mucosa revealed a penicillin-sensitive Streptococcus pneumoniae. Appropriate parenteral antibiotic treatment was initiated (aminopenicillin). The postoperative course was marked by a transient hepatic failure associated with an ascitis controlled by diuretics. The patient was discharged on the 26th day after surgery. This case reports a new etiology of acute abdominal emergencies in cirrhotic patients.

Abdomen, Acute↗

Effects of preoperative chemotherapy on liver function tests after hepatectomy.

BACKGROUND/AIMS: Surgical resection of liver metastases is performed increasingly frequently after chemotherapy, which can induce fatty degeneration, possibly modifying the postoperative course after hepatectomy. This study evaluated the effect of chemotherapy on postoperative liver function tests according to the use of preoperative chemotherapy or not. METHODOLOGY: Thirty-two patients were operated on for isolated breast cancer hepatic metastases, after stabilization or complete response to systemic therapy. The first group included 20 patients operated on after chemotherapy (9 major and 11 minor hepatic resections). The second group included 12 patients operated on without chemotherapy (3 major and 9 minor hepatic resections). RESULTS: Histological examination after chemotherapy confirmed micronodular fatty degeneration in 85% of cases, versus none in the control group (P = 0.05). Fall in prothrombin time on day 1 (D1) was more marked in the chemotherapy group (58%) versus control group (74%) (P = 0.001). gamma-glutamyl transpeptidase did not rise on D7 in the chemotherapy group (1.4 x N), even after major hepatectomy (1.6 x N), in contrast with the control group, in which the mean gamma-glutamyl transpeptidase on D7 was 4.6 x N after major hepatectomy and 2 x N after minor hepatectomy (P = 0.05). CONCLUSIONS: Chemotherapy induces almost constant fatty degeneration of the liver. Hepatic regeneration in the postchemotherapy liver is delayed, as reflected by a later and lower elevation of gamma-glutamyl transpeptidase. The predictive risk of liver failure, reflected by prothrombin time, following minor hepatectomy on postchemotherapy liver is similar to that of major hepatectomy to healthy liver.

Antineoplastic Combined Chemotherapy Protocols↗

Sinistroposition of the gallbladder and the common bile duct.

A left lateral bisegmentectomy was performed in a 29-year-old man presenting a primary lymphoma of the liver. Surgical exploration revealed a left-side gallbladder, located under the left lobe of the liver. During hepatic parenchyma dissection, performed strictly at the left of the round ligament and the umbilical portion of the left portal vein, common bile duct was injured. Complete separation of hepatic pedicle structures showed that the upper biliary convergence passed on the left side of the umbilical portion of the left portal vein before reaching the hepatoduodenal ligament. This case report discusses the embryological mechanism that could explain this uncommon bile duct abnormality, focusing on its consequences during left ruled lobectomy.

Adult↗

Efficiency of orthotopic xenograft models for human colon cancers.

It is feasible to graft human colon cancer tissue into immuno-deficient nude mice, in order to maintain these tumors in vivo. Analysis of the properties tumors under such conditions might increase our knowledge of their biological characteristics. Xenografts are usually implanted into subcutaneous tissue, a site easily accessible for both graft procedure and observation of tumor growth. However these subcutaneous tumors are usually non-invasive and fail to metastasize. To override these limitations we, as others, have tried to improve the tumor xenograft model by transplanting tumors into their original location, designated as the orthotopic site. Transplanted into the cecum of nude mice, human colon cancers were frequently locally invasive and developed liver metastases. These transplantations may be done by injection of colon cancer cell suspensions into the cecal wall. Alternatively, orthotopic implantations of histologically intact tissue were performed and the thus-obtained tumors were more metastatic than tumors obtained after tumor cell injections. The chemosensibility of tumors xenografted into their orthotopic site was different from that of their subcutaneously implanted counterpart. This, added to the enhancement of invasive and metastatic properties, leads us to conclude that colon cancer xenografted into the caecum might be more representative of the clinical situation. We have reviewed the literature and report on the possibilities and limitations different models of colon cancer in vivo.

Animals↗

Growth dependency of human colon cancer xenograft on organ environment is related with their original clinical stage.

The ability of cancer cells to metastasize might depend on their reduced dependency on the originating tissue. To test this hypothesis, 10 human colorectal carcinomas (CRC) were implanted either onto nude mouse caecum wall (orthotopic site), or into the subcutaneous tissue (ectopic site), and their growth in these sites compared. Prognostic factors were studied: Astler-Coller modified Dukes's stage, loss of chromosome 17p and/or 18q, and their TP53 gene. Early stage CRC [B2 (n = 3) and C1 (n = 1)] were found to grow 1.7 to 3.6 times (p < 0.05, p < 0.008 respectively) more rapidly in the caecum than in subcutaneous tissue. Metastatic stage CRC [C1 (n = 1), C2 (n = 2) or D (n = 3)] grew similarly in both sites, and more slowly than those of the first group. No relationship was found between growth rates, TP53 mutations or karyotypes. Growth rate of non metastatic cancers was slowed down by implantation in a foreign tissue whereas growth of metastatic tumours was similar in both sites, indicating that they do not recognize or need tissue growth factors.

Animals↗