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P Bachellier

Publications and source records attributed to P Bachellier.

At least 19 recordsLinked to original sources
PubMed2007

A metabolic screening study of trichostatin A (TSA) and TSA-like histone deacetylase inhibitors in rat and human primary hepatocyte cultures.

Hydroxamic acid (HA)-based histone deacetylase (HDAC) inhibitors, with trichostatin A (TSA) as the reference compound, are potential antitumoral drugs and show promise in the creation of long-term primary cell cultures. However, their metabolic properties have barely been investigated. TSA is rapidly inactivated in rodents both in vitro and in vivo. We previously found that 5-(4-dimethylaminobenzoyl)aminovaleric acid hydroxyamide or 4-Me2N-BAVAH (compound 1) is metabolically more stable upon incubation with rat hepatocyte suspensions. In this study, we show that human hepatocytes also metabolize TSA more rapidly than compound 1 and that similar pathways are involved. Furthermore, structural analogs of compound 1 (compounds 2-9) are reported to have the same favorable metabolic properties. Removal of the dimethylamino substituent of compound 1 creates a very stable but 50% less potent inhibitor. Chain lengthening (4 to 5 carbon spacer) slightly improves both potency and metabolic stability, favoring HA reduction to hydrolysis. On the other hand, Calpha-unsaturation and spacer methylation not only reduce HDAC inhibition but also increase the rate of metabolic inactivation approximately 2-fold, mainly through HA reduction. However, in rat hepatocyte monolayer cultures, compound 1 is shown to be extensively metabolized by phase II conjugation. In conclusion, this study suggests that simple structural modifications of amide-linked TSA analogs can improve their phase I metabolic stability in both rat and human hepatocyte suspensions. Phase II glucuronidation, however, can compensate for their lower phase I metabolism in rat hepatocyte monolayers and could play a yet unidentified role in the determination of their in vivo clearance.

Animals↗
PubMed2003

Simultaneous resection of colorectal primary tumour and synchronous liver metastases.

BACKGROUND: The surgical strategy for treatment of synchronous colorectal liver metastases remains controversial. The outcome and overall survival of patients presenting with such metastases, treated either by simultaneous resection or by delayed resection, were evaluated. METHODS: From 1987 to 2000, 97 patients presented with synchronous colorectal liver metastases, of whom 35 (36 per cent) underwent a simultaneous resection and 62 patients (64 per cent) a delayed resection. Simultaneous resection was considered prospectively for patients with fewer than four unilobar metastases. RESULTS: Age, blood transfusion requirements, operating time, duration of inflow occlusion, hospital stay and mortality rate were similar in the two groups. The morbidity rate did not differ significantly (23 per cent after simultaneous resection and 32 per cent after delayed resection). The location of the primary tumour and extent of liver resection did not influence the morbidity rate significantly in the simultaneous resection group. The overall survival rate was 94, 45 and 21 per cent at 1, 3 and 5 years respectively after simultaneous resection, and 92, 45 and 22 per cent after delayed resection. CONCLUSION: In selected patients, simultaneous resection of the colorectal primary tumour and liver metastases does not increase mortality or morbidity rates compared with delayed resection, even if a left colectomy and/or a major hepatectomy are required.

Colorectal Neoplasms↗
PubMed2003

Laparoscopic radiofrequency-assisted liver resection.

Laparoscopic liver resection has not yet gained wide acceptance among hepatic surgeons, mainly because of the difficulties encountered in dealing with possible intraoperative bleeding. A new technique of laparoscopic liver resection is presented. A 43-year-old man with a large and symptomatic hemangioma underwent a laparoscopic radiofrequency energy-assisted liver resection. After induction of pneumoperitoneum, four trocars were introduced and intraoperative ultrasonography and coagulative desiccation were performed along a plane of tissue 1 cm away from the edge of the lesion using the Cool-Tip radiofrequency probe and a 500-kHz, radiofrequency generator. The necrosed band of parenchyma then was divided and the specimen removed. The operative time was 300 min with a resection time of 240 min. The intraoperative blood loss was 75 ml. The postoperative course was uneventful and the patient was discharged on postoperative day 6. Laparoscopic radiofrequency-assisted liver resection is feasible, and with greater experience may contribute to the wider use of mini-invasive video-assisted liver surgery.

Adult↗
PubMed2003

[Damage control laparotomy for haemorragic abdominal trauma. A retrospective multicentric study about 109 cases].

AIM OF THE STUDY: Damage control laparotomy is a new approach to the more severe abdominal traumas. It stems from a better understanding of the physiopathology of the haemorragic shock. PATIENTS AND METHODS: A national retrospective study from 27 centers about 109 trauma patients who underwent a damage control procedure between January 1990 and December 2001, is analysed. Surgical procedures included 97 hepatic packing, 10 abdominal packing, 4 exclusive skin closure, 1 open laparotomy technique and 3 digestive stapplings. RESULTS: The mortality rate is 42%. Eleven abdominal compartment syndromes have occurred with 7 decompressive laparomy (4 deaths). CONCLUSION: This study is based on the largest series of damage control laparotomy published in France. Results in terms of mortality and morbidity are similar to those of published studies from the USA.

Abdominal Injuries↗
PubMed2002

Cryopreservation of adult human hepatocytes obtained from resected liver biopsies.

Isolated human hepatocytes have been shown to represent a valuable in vitro model to investigate the metabolism and cytotoxicity of xenobiotics. In addition, human hepatocyte transplantation and artificial liver support systems using isolated human hepatocytes are currently investigated as treatment for acute and chronic hepatic failure. In this regard, human hepatocyte banking by cryopreservation would be of great interest. In the present study, freshly isolated hepatocytes from resected liver biopsies of 28 separate donors (viability: 88 +/- 2%; plating efficiency: 79 +/- 5%) were cryopreserved using two different protocols, stepwise freezing (SF) or progressive freezing (PF), in combination (PF(+), SF(+)) or not (PF(-), SF(-)) with a 30 min preincubation in culture medium at 37 degrees C. Total recovery was higher after PF (38 +/- 3%) than after SF (12 +/- 2%). Preincubation prior to SF had no effect on plating efficiency of thawed hepatocytes (SF(-): 38 +/- 6% versus SF(+): 46 +/- 7%) while preincubation prior to PF increased plating efficiency of thawed hepatocytes (PF(-): 42 +/- 6% versus PF(+): 64 +/- 4%, p < 0.05). In attached cultured human cryopreserved/thawed hepatocytes (CH) from the PF(+) group, albumin production and glutathione content were not significantly different from those of the freshly isolated hepatocyte (FIH) cultures. Cells in CH monolayers appeared smaller than cells in FIH monolayers. In addition, the pattern of cytochrome P450- and UDP-glucuronosyl transferase-dependent isoenzyme activities and GST activity were different, suggesting a variability in the resistance to cryopreservation of the various liver hepatocyte populations. Taken all together, the results of the present study suggest that recovery of human hepatocytes after isolation prior to progressive freezing should allow human hepatocyte banking for use in pharmacotoxicology and cell therapy research purposes.

Adult↗
PubMed2001

Hepatic metastases of gastroenteropancreatic neuroendocrine tumors: safe hepatic surgery.

Liver metastases of neuroendocrine tumors are usually slow-growing, and cytoreductive hepatectomy can help reduce the effects of endocrinopathies and increase life expectancy and symptom-free survival. However, it has yet to be fully investigated how hepatectomy for metastatic neuroendocrine tumors can be performed safely. Here we report the results of 13 patients with neuroendocrine liver metastases operated on in our institution and those of a French multicentric study that included 131 patients. Preoperative patient selection and appropriate surgical technique, sometimes combined with preoperative portal embolization and local tumor destruction (radiofrequency and cryotherapy), may increase the resectability and the safety of the procedure. The mortality rate after hepatectomy was 0% (2.3% in the French study); the 3- and 6-year survival rates were 91% and 68%, respectively, in our institution (the mean survival time was 66 months in the French multicentric survey). Significant prolonged survival with complete palliation of symptoms can be obtained after liver metastases resection with low mortality.

Adult↗
PubMed2001

Surgical repair after bile duct and vascular injuries during laparoscopic cholecystectomy: when and how?

Recent collective reviews have outlined when and how surgeons should treat patients with bile duct injuries after laparoscopic cholecystectomy (LC). However, little is described about other injuries combined with bile duct injuries, for example, hepatic arterial injury and secondary biliary cirrhosis. Fifteen patients with bile duct injuries following LC were referred and surgically treated from 1990 to 1998 in our institution. We report how patients with hepatic arterial injury combined with bile duct injuries during LC were treated. The present study also reports unusual complicated situations: one patient with biliary cirrhosis referred 4 years after LC, another treated with internal biliary metallic stent referred 2.5 years after LC, and another with isolated right hepatic ductal injury. Short- and long-term surgical outcomes after biliary repair were compared between simply referred patients and those with complicated history. Patients who were referred several years after LC and who were referred after primary hepaticojejunostomy were included with patients with complicated history (n = 4, group B), and the other patients were included with patients with simple history (n = 11, group A). Simultaneous right hepatic arterial occlusion was observed in 3 of these 15 patients, and arterial reconstruction was performed in 2 of the 3 patients in addition to biliary reconstruction. No postoperative complication occurred in these three patients. The patient with isolated injury of the right hepatic duct and the other with biliary cirrhosis were successfully treated with hepaticojejunostomy. The other patient treated with biliary stent underwent hepaticojejunostomy but a second operation was required because of later stenosis. Mean hospital stay was significantly longer in group B (30.3 +/- 6.9 days) than in group A (18.5 +/- 2.5 days, p< 0.05). Rehospitalization was more frequent in group B than in group A (p < 0.01). However, long-term outcome was successful in both groups. The present results showed that arterial reconstruction should be performed when the distal right hepatic artery can be exposed and reconstructed, and suggested that patients with bile duct injuries during LC should be immediately referred to surgical institutions in which surgeons have adequate experience of bile duct repair and hepatic arterial reconstruction.

Adult↗
PubMed2001

Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases?

BACKGROUND: In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS: Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS: The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS: This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.

Analysis of Variance↗
PubMed2001

Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile?

BACKGROUND: Whether or not superior mesentericoportal venous resection (SM-PVR) associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been fully confirmed. The aim of the present study was to investigate results of this surgical procedure performed for pancreatic head and periampullary neoplasms. METHODS: As a first analysis, postoperative morbidity and mortality after PD with (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with pancreatic head and periampullary neoplasms. As a second analysis, rates of margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate was investigated in patients who did (n = 13) and did not (n = 8) undergo a margin-negative resection. RESULTS: In the first analysis, duration of surgery and volume of blood transfused perioperatively were higher in patients undergoing SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and 22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days, respectively). No postoperative death occurred in the recent part of the present study, since 1994, in patients undergoing SM-PVR. In the second analysis of pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year survival did not significantly differ between patients who did and did not undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients undergoing SM-PVR, survival rate was significantly higher for patients undergoing a margin-negative resection (n = 13) than for patients undergoing a macroscopic or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus 0%, P <0.05). CONCLUSION: PD combined with SM-PVR can be performed safely. This surgical procedure is followed by a promising survival rate and can be recommended in order to obtain a margin-negative resection; however, candidates for SM-PVR should be carefully selected.

Adenocarcinoma↗
PubMed2001

Analysis of allelic imbalance in patients with colorectal cancer according to stage and presence of synchronous liver metastases.

OBJECTIVE: To investigate the relationship between number and location of allelic imbalances (AI) and local tumor progression according to Astler-Coller classification. SUMMARY BACKGROUND DATA: Spontaneous errors in DNA replication (i.e., allelic imbalance or microsatellite instability) have been suggested to play an important role in carcinomatous transformation as reflecting alterations of gene function. METHODS: One hundred two consecutive patients with colorectal carcinoma undergoing surgical resection were included in this study. Patients were distributed according to the Astler-Coller classification as stages A (n = 7), B1 (n = 15), B2 (n = 24), C (n = 31), and D (n = 25). Fluorescent polymerase chain reaction was performed on frozen tumor, normal colon mucosa, and blood DNA at 35 microsatellite markers. Allelic imbalance frequency was compared with tumor staging. RESULTS: The percentage of AI was significantly higher in stage D than in A/B1 and B2. In addition, the percentage of AI was significantly higher in 10 synchronous colorectal liver metastases than in stage A/B1 and B2 tumors. However, the allelotyping revealed a subgroup of A/B1 tumors with a high AI frequency. Statistical analysis showed that the presence of AI at microsatellites D1S305, D2S138, D3S1282, D17S790, and D22S928 presented a significantly positive correlation with stages. CONCLUSION: The frequency of AI significantly correlates with tumor progression of colorectal cancer. Primary tumors with synchronous colorectal liver metastases showed a higher percentage of AI, suggesting that a frequency of AI greater than 35% with this selection of markers indicates a high risk of local progression and of development of metastases.

Adult↗
PubMed1999

Hepatic and pulmonary metastases from a meningeal hemangiopericytoma and severe hypoglycemia due to abnormal secretion of insulin-like growth factor: a case report.

A 42-year-old woman was hospitalized for severe hypoglycemic coma. She had a voluminous hepatic metastasis and multiple small lung metastases from a meningeal hemangiopericytoma initially operated on 11 years earlier. High blood levels of an abnormal form of insulin-like growth factor type 2 (IGF II) associated with low blood levels of insulin, growth hormone, IGF I, and IGF BP3 were observed. After surgical resection of the liver and pulmonary metastases, serum glucose levels and hormonal abnormalities returned to normal.

Adult↗
PubMed1999

[Surgical strategy in the treatment of synchronous hepatic metastases of colorectal cancers. Analysis of a series of 59 operated on patients].

AIM OF THE STUDY: The surgical strategy for the treatment of resectable synchronous hepatic metastases of colorectal cancer remains controversial. The retrospective analysis of our series of resectable synchronous hepatic metastases is focused on the percentage of simultaneous resections, the circumstances, the indications, and the results of the one-step procedure compared to the two-step strategy. METHODS: From January 1st 1982 to December 31st 1996, 146 patients were operated on for resection of hepatic metastases of colorectal cancer. Fifty-nine (40%) presented with synchronous metastases, 28 (47.5%) of whom underwent simultaneous resection of the primary tumor and of the hepatic metastases (simultaneous resection group: SR). For the other 31 patients (52.5%), the hepatic resection was delayed for a mean interval of 6 +/- 4 months (delayed resection group: DR). RESULTS: The mean age in the two groups was not significantly different (56 years vs. 60 years). The need for blood transfusion and the volume required were not significantly different between the two groups. The duration of each surgical operation was comparable between the two groups (320 +/- 76 min vs. 308 +/- 88 min). Postoperative complications were observed in 18% of patients in the SR group and in 16% of patients in the DR group (no significant difference). There was no postoperative mortality in either group. Survival was 86, 63 and 43% at 1, 2, 3 years respectively in the SR group, and 81, 51 and 36% in the DR group, with no significant difference between the groups. CONCLUSION: Simultaneous resection of the primary tumor and the hepatic metastases does not increase neither mortality nor morbidity in our series. The best candidate for a one-step procedure is a patient with a right colonic tumor, in a good status, with liver synchronous metastases resectable by mean of a minor hepatectomy.

Actuarial Analysis↗
PubMed1999

[Changes in homeostasis during surgical liver resection].

OBJECTIVES: To assess changes in haemostasis during liver resection and to discuss the indications for antifibrinolytic therapy. STUDY DESIGN: Open prospective study. PATIENTS: The study included 39 consecutive non-cirrhotic patients presenting for liver resection under portal triad clamping. METHOD: General anaesthesia was obtained with thiopentone, fentanyl, vecuronium and isoflurane. Transfusion scheme was standardized. Aprotinin (5,000 kIU.kg-1 BW) was administered in case of unexplained bleeding in the operative field. Coagulation pattern was assessed by routine tests and thrombelastrography before surgery, before portal triad clamping, 5 min after reperfusion and at completion of surgery. Patients requiring aprotinin intraoperatively were compared to others. RESULTS: In 32 patients no significant bleeding occurred. Their coagulation pattern was moderately changed and remained within the normal range. In seven patients severe bleeding occurred which was treated with aprotinin. Their coagulation tests were significantly modified, especially after reperfusion, associating an increase in aPTT, TT, FDP, DDim, r + k and a decreased platelet count. CONCLUSION: These changes were more in favour of a dilution coagulopathy or a DIC than hyperfibrinolysis. Therefore substitutive therapy with coagulation factors should be preferred to an antifibrinolytic agent. A systematic administration of the latter for liver resection in non-cirrhotic patients is debatable, considering the allergic risk (reoperation for cancer recurrence), thrombosis facilitation (pedicle clamping) and high cost.

Aged↗
PubMed1997

Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie.

AIM: The aim of this study was to analyse characteristics of patients who survived more than 5 years after liver resection of colorectal metastases. METHODS: A multicentre retrospective study collected 1818 patients who underwent curative resection of hepatic metastases between 1959 and 1991. Among the 747 patients operated on before 1987, 102 survived longer than 5 years, and were compared with patients who survived less than 5 years. RESULTS: Three risk factors proved independently significant in multivariate analysis between the two groups: serosa infiltration (P = 0.003), involvement of peritumoral lymph nodes around the primary colorectal tumour (P = 0.04), and a liver resection margin of less than 1 cm (P = 0.02). There was no significant difference for other parameters studied (location of primary tumour, location, number and size of metastases, type of resection). A trend towards a shorter survival of patients with increased carcinoembryonic antigen serum level was observed. CONCLUSION: Resection of colorectal hepatic metastases can provide long-term survival even in patients with poor prognostic factors. It seems justified to undertake resection of colorectal liver metastases whenever it may be performed safely as a curative treatment.

Carcinoembryonic Antigen↗