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Aim: To develop a simplified and quick protocol to induce cirrhosis and standardize models of partial liver resection in rats., Methods: In Fischer F344 rats two modified protocols of phenobarbital-carbon tetrachloride (CCl4) (dilution 50%) gavage to induce cirrhosis (frequency adjusted according to weight, but each subsequent dose was systematically administered) were tested, i.e. the rapid and slow protocols. Prothrombin time (PT) and total bilirubin (TB) were also evaluated. Animals from the rapid group underwent 15% hepatectomy and animals from the slow group underwent 70% hepatectomy., Results: Rapid protocol: This corresponded to 1 gavage/4 d over 6 wk (mortality 30%). Mean PT was 35.2+/-2.8 s (normal: 14.5 s), and mean TB was 1.8+/-0.2 mg/dL (normal: 0.1 mg/dL). Slow protocol: This corresponded to 1 gavage/6 d over 9 wk (mortality 10%). Mean PT was 11.8+/-0.2 s (normal: 14.5 s), and mean TB was 0.4+/-0.04 mg/dL (normal: 0.1 mg/dL). Pathological analyses were performed in both protocols which showed persistent cirrhosis at 3 mo. Rat mortality in the rapid gavage group who underwent 15% hepatectomy and in the slow gavage group who underwent 70% hepatectomy was 50% and 70%, respectively., Conclusion: Our modified model is a simplified method to induce cirrhosis which is rapid (6 to 9 wk), efficient and stable up to 3 mo. Using this method, "Child Pugh A" or "Child Pugh BC" cirrhotic rats were obtained. Our models of cirrhosis and hepatectomy can be used in various situations focusing on postoperative survival.

Objective: The aim of this prospective study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis (PC) at an early stage in a series of patients at high risk of developing PC from colorectal cancer., Background: The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS), and could be further improved if PC could be treated at an early stage. But, currently, the diagnosis of early PC is not accessible to imaging., Patients and Methods: From 1999 to 2006, 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor. Patients were selected according to primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 16), synchronous ovarian metastases (n = 4), perforated primary tumor (n = 9)., Results: PC was found and treated with CCRS plus HIPEC in 16 of 29 (55%) cases, corresponding to 10 of 16 patients with initial PC, 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor. There was no postoperative mortality, and morbidity (grade III/IV) occurred in 14% of cases. After a median follow-up of 27 months (range, 6-96), 8 of 16 patients treated with CCRS and HIPEC are free of disease, 4 relapsed in the peritoneum, and 4 developed isolated visceral metastases., Conclusion: Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55% of cases. Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospective multicenter trial.

Background: Peritoneal carcinomatosis (PC), which has hitherto been regarded as a lethal entity, can now be cured with surgery (treating macroscopic tumor seeding) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) (treating residual microscopic disease). The purpose of this study was to analyze the morbidity and mortality of a particular approach associating optimal (R0-R1) cytoreduction, optimal HIPEC combining oxaliplatin and irinotecan, and an optimal homogeneous intraperitoneal temperature of 43 degrees C., Methods: A total of 106 consecutive patients were included in this prospective phase 2 study. After complete resection of the PC, HIPEC was performed by the Coliseum technique with oxaliplatin (360 mg/m2) combined with irinotecan (360 mg/m2) in 2 L/m2 of 5% dextrose, over 30 minutes at a real intraperitoneal temperature of 43 degrees C. During the hour preceding HIPEC, patients received 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) intravenously, resulting in tritherapy., Results: Postoperative mortality and morbidity rates were 4% and 66%, respectively. The most frequent complications were digestive fistula (24%), lung infection (16%), and severe hematological toxicity (11%). Statistical correlation was evidenced between morbidity and the carcinomatosis score (P = .0008), the number of resected organs (P = .0001), the duration of surgery (P = .0001), and blood loss (P = .0001)., Conclusions: This new approach, optimized in three respects (complete cytoreduction, combination oxaliplatin with irinotecan, and high temperature) has resulted in a relatively high but acceptable incidence of adverse events considering the expected advantage for survival.

Objectives: The aim of this study was to determine the potential of bone marrow derived cells to participate in liver repopulation. In this model, the injected cells had a "selective growth advantage" compared to the native hepatocytes whose proliferation was blocked by retrorsine., Methods: Total bone marrow cells were isolated from male Fisher 344 rats not deficient in dipeptidyl peptidase activity (F344, DPP IV+). The animals were given an injection of retrorsine and were divided in 2 groups: 1/group R (N=13): female F344 rats received 4.106 male cells at day 0 (labeled by chromosome Y). 2/group RH (N=19): Male F344 DPP IV- rats received 4.106 male DPP IV+ cells after hepatectomy at day 0 (labelled by DPP IV activity)., Results: Group R: no male cell was detected by PCR at day 14, 28, 56 and 84. Group RH: isolated DPP IV+ transplanted cells were observed at days 14 and 28 in the periportal areas. Later, these cells were no longer visible. Liver regeneration occurred by proliferation of small clusters of hepatocytes., Conclusions: In this experimental model the capacity of transplanted bone marrow cells to repopulate the liver was tested against the same capacity of native liver stem cells. Liver regeneration occurred via native liver cells seen as small hepatocytes. In this model the small hepatocytes may be considered as hepatic stem cells.