Showing papers by "Philippe Bachellier published in 2007"

Significance of the depth of portal vein wall invasion after curative resection for pancreatic adenocarcinoma.

Abstract: Hypothesis The depth of portal vein (PV) wall invasion is a prognostic factor for survival after curative pancreatic resection for pancreatic ductal adenocarcinoma. Design Retrospective clinical study. Setting Department of digestive surgery and transplantation. Patients From January 1, 1990, through December 31, 2002, 121 patients underwent a curative pancreatic resection for ductal adenocarcinoma of the pancreas. Among these, 37 pancreatic resections combined with PV resection were performed. Main Outcome Measures Prognostic factors for survival and predictive factors for the depth of PV wall invasion. Results The morbidity and mortality rates did not differ between patients undergoing or not undergoing PV resection (32.4% and 2.7% [1/37], respectively, vs 38.1% and 2.4% [2/84], respectively). The 3-year survival rate after curative pancreatic resection was significantly associated with the depth of PV wall invasion. Indeed, the 3-year overall survival rate was similar for patients with no PV invasion and those with superficial invasion into the tunica adventitia (40.0% vs 32.9%, respectively; P = .85). Deeper PV wall invasion into the tunica media or the tunica intima was associated with a poorer 1-year survival rate similar to that of patients undergoing noncurative resection (21.5% vs 34.4%, respectively; P = .53). Multivariate analysis showed that the depth of PV wall invasion, number of involved lymph nodes, and volume of blood transfusion were independent factors of overall and disease-free survival. Tumor size of 45 mm or more (evaluated by computed tomography) and angiographic type C or D on a portogram were significantly correlated with the depth of PV wall invasion. Patients presenting with both factors simultaneously had poor survival. Conclusions The depth of PV wall invasion significantly alters survival after curative pancreatic resection combined with PV resection. However, occasional long-term survival could be observed after curative resection in patients with deep PV wall invasion.

Impact of radiofrequency assisted hepatectomy for reduction of transfusion requirements

Abstract: Background Liver parenchyma transection technique using heat coagulative necrosis induced by radiofrequency (RF) energy is evaluated in this series. Methods Between January 2000 and October 2004, 156 consecutive patients underwent liver resection with the RF-assisted technique. Data were collected prospectively to assess the outcome, including intraoperative blood loss, blood transfusion requirement, and morbidity and mortality rates. Results There were 30 major hepatectomies and 126 minor resections. While total operative time was 241 ± 89 minutes, the actual resection time was 75 ± 51 minutes. Intraoperative blood loss was 139 ± 222 mL. Nine patients (5%) received blood transfusion, predominantly those receiving major hepatectomy ( P = .006). Thirty-six patients (23%) developed postoperative complications, and the mortality rate was 3.2%. Mean hospital stay was 12 ± 12 days. Conclusion The RF-assisted technique is associated with minimal blood loss, a low blood transfusion requirement, and reduced mortality and morbidity rates and can be used for both minor and major liver resections.

Allelotyping analyses of synchronous primary and metastasis CIN colon cancers identified different subtypes

Abstract: In colorectal cancer, the molecular alterations that lead to metastasis are not clearly established, probably because of their high genetic complexity. To identify combinations of genetic changes involved in tumor progression and metastasis, we focused on chromosome instable (CIN) colon cancers. We compared by allelotyping of 33 microsatellites, the genomic alterations of 38 primary colon tumors with the synchronously resected matched liver metastases (CLM). We observed that (i) the number of patients with alterations at certain loci did not differ significantly between the whole primary tumor and the paired CLM, (ii) a group of patients had fewer alterations in the metastasis when compared with the matched primary tumor. A 2-way hierarchical unsupervised clustering of the allelotyping data revealed 2 tumor subtypes that have different levels of CIN (CIN-High, CIN-Low). Both subtypes have a minimal common set of alterations at chromosomes 8p, 17p and 18q, but does not include alteration at 5q or mutation at K-Ras. These 2 subtypes were also observed using a collection of 104 independent primary CIN colon tumors. In addition, we found a third subtype, consisting of tumors with a very low number of alterations not associated with specific loci (CIN-Very Low). We found that colon carcinogenesis may require a minimal set of alterations and that, in contrast to the current hypothesis, the level of CIN does not correlate with tumor progression. Therefore, our results suggest that metastasis potential could be present at very early stages of tumor development.

Laparoscopic liver resection assisted with radiofrequency

Abstract: Background Radiofrequency-assisted laparoscopic liver resection is reported. Methods Patients suitable for liver resection were carefully assessed for laparoscopic resection. Patient and intraoperative and postoperative data were prospectively collected and analyzed. Results Eighteen patients underwent laparoscopic liver resection. All operations were performed without vascular clamping and consisting of tumorectomy (n = 9), multiple tumoretcomies (n = 2), segmentectomy (n = 2), and bisegmentectomies (n = 2). Mean blood loss was 121 ± 68 mL, and mean resection was time 167 ± 45 minutes. There was no need for perioperative or postoperative transfusion of blood or blood products. One patient developed pneumothorax during surgery as a result of direct puncture of pleura with the radiofrequency probe, and 1 patient had transient liver failure and required supportive care after surgery. The mean length of hospital stay was 6.0 ±1.5 days. At follow-up, those with liver cancer had no recurrence. Conclusions Radiofrequency-assist laparoscopic liver resection can decrease the risk of intraoperative bleeding and blood transfusion.

A Metabolic Screening Study of Trichostatin A (TSA) and TSA-Like Histone Deacetylase Inhibitors in Rat and Human Primary Hepatocyte Cultures

Abstract: 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-Me2 N -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, Cα-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.