Carole Doucet

Protective roles of polyethylene glycol and trimetazidine against cold ischemia and reperfusion injuries of pig kidney graft.

Ischemia‐reperfusion injury (IRI) represents an allo‐independent risk factor which favors chronic allograft nephropathy (CAN). Here we analyzed the influence of preservation solutions on the function of autotransplanted pig kidneys over 1–16 weeks after surgery. Kidneys were cold‐flushed and cold‐stored for 24 or 48 h either in University of Wisconsin (UW), modified‐UW Hôpital Edouard Herriot, polyethylene glycol 20 kDa (PEG)‐supplemented preservation solutions with low K+ (ECPEG) or high K+ (ICPEG) content. Animals autotransplanted with kidneys cold‐stored for 24 h in ECPEG exhibited the greatest levels of creatinine clearance (Ccr: 161 ± 12 mL/min, n = 10) and the lowest levels of proteinuria (0.5 ± 0.03 mg/mL) 16 weeks after surgery as compared with pigs autotransplanted with kidneys cold‐stored in the other solutions tested (Ccr ranging from 80 and 140 mL/min). Similar differences, but with lower Ccr levels, were achieved after a prolonged period of cold‐storage(48 h). ECPEG better preserved the kidneys from monocytes/macrophages and CD4+ T cells infiltrations, VCAM‐1 and MHC class II overexpressions and occurrence of renal interstitial fibrosis (2%) as compared with the other preservation solutions (5%–20%). Adding the anti‐ischemic drug trimetazidine (TMZ) to the preservation solutions, particularly ECPEG, further improved the quality of the week‐16 post‐transplanted kidneys (Ccr: 182 ± 12 mL/min, n = 10). These findings demonstrated that adding PEG to extracellular‐like (with low K+ content) preservation solutions in combination with TMZ significantly improved the long‐term outcome of kidney grafts in this model of autotransplanted pig kidney.

A modified University of Wisconsin preservation solution with high-NA+ low-K+ content reduces reperfusion injury of the pig kidney graft.

Background. Ischemia‐reperfusion injury has been associated with both early and late effects on allografts in the form of delayed graft function and decreased graft survival. Recent studies demonstrated that functional parameters were influenced by cold storage conditions and particularly the ratio of Na+:K+ of the preservation solution. Methods. We have extended this study to examine whether the high‐Na+ low‐K+ formulation of Belzers solution (HEH) was efficient in an autotransplanted pig kidney model when compared with the classical low‐Na+ high‐K+ University of Wisconsin solution and the new high‐Na+ low‐K+ Celsior solution. Kidneys were harvested, cold flushed, and preserved for 24, 48, or 72 hr with HEH, Celsior solution, or University of Wisconsin solution and autotransplanted. Renal function was determined on days 1, 3, 7, and 14, and at 4 to 16 weeks after autotransplantation. Histologic changes and cell infiltration were assessed on kidney biopsy specimens taken after reperfusion (30‐40 min), at days 5 and 14, and at 4 to 5 and 10 to 12 weeks after surgery. Peripheral benzodiazepine receptor (PBR), a structural mitochondrial protein, was also studied. Results. Cold storage in HEH resulted in reduction of delayed graft function and renal damage, with a decrease in interstitial inflammation. HEH reduced interstitial fibrosis, tubular atrophy, and improved PBR expression. Conclusion. This study suggests that cold preservation in HEH has a beneficial action in in vivo renal preservation and reduces tubular necrosis, interstitial inflammation, and fibrosis in these groups. In addition, PBR detection was correlated to the level of preservation integrity.

Comparison of conventional and laparoscopic Hartmann's procedure reversal.

Purpose This study compares open Hartmanns procedure reversal (OHPR) and laparoscopic Hartmanns procedure reversal (LHPR) in patients first treated for peritonitis (Henchey III or IV). Methods Fourteen patients who underwent LHPR during a 2-year period were compared with 20 patients who had previously undergone an open procedure at the same institution. Results Conversion rate was 14.28%. Operating time was shorter for the laparoscopic group [143 (90 to 240) vs. 180 (90 to 350) min, P<0.05]. Hospital length of stay was shorter for the laparoscopic group [9.5 (4 to 18) vs. 11 (6 to 39)]. Use of patient-controlled analgesia was not significantly shorter in the laparoscopic group [3 (0 to 4) vs. 3.5 (0 to 8)]. Morbidities observed in the LHPR group include a parietal abscess and an anastomotic stenosis without surgical treatment. The OHPR group had 6 complications: 1 anastomotic leak and 5 incisional hernias. Conclusions LHPR with a conversion rate of 14.28% seems to be a method with shorter operating time and less morbidity compared with OHPR.

A p38 mitogen-activated protein kinase inhibitor protects against renal damage in a non-heart-beating donor model

Ischemia-reperfusion injury is one of the central nonimmunologic processes involved in renal allograft dysfunction. Kidneys from non-heart beating donors (NHBD) exhibit higher rates of delayed graft function (DGF) than those from other donors. Primary nonfunction and DGF are the main barriers to the use of kidneys from NHBD. Using a pig model of NHBD transplantation, we studied the effect of FR167653 (a p38 MAP kinase inhibitor) on the recovery and reparation of kidneys exposed to both warm (WI: 1 h) and cold ischemia (24 h). Our results demonstrate that the addition of FR167653 increases the kinetics of proximal tubule cell regeneration after 60 min of WI. Hypoxia-inducible factor and vascular endothelial growth factor expression was also more important in FR167653-treated kidneys compared with those in nontreated groups. Also, expression of peripheral-type benzodiazepine receptor, involved in tissue repair, was increased in the FR167653-treated groups. At 3 mo, the protective effects of FR167653 were accompanied by a reduction of long-term inflammation process and tubulointerstitial fibrosis development associated with a limitation of ischemia-induced remodeling. This study suggests that such treatment may be useful in protocols aimed at improving the quality of renal transplants from NHBD. In addition, the beneficial role of FR167653 in limiting early injury is associated with secondary reduction in development of tubular atrophy and interstitial fibrosis which are together the hallmark of failing renal transplants. The more efficient effect was observed when FR167653 was added in combination before WI, during cold storage and reperfusion.

Abnormalities of the gallbladder, clinical effects.

The aim of this review of the literature was to present and discuss the anatomical and embryological basis of congenital abnormalities of the gallbladder, based on a case of volvulus. In the rare cases of ectopic gallbladder, diagnosis of a biliary disease could be difficult. In such cases surgery can also be dangerous, especially when it is associated with abnormalities of the intra-hepatic biliary and vascular tree. This study, based on the embryology of the extra hepatic bile duct, focused on the most frequent gallbladder abnormalities to keep them in mind.

Influence of Warm Ischemia Time on Peripheral-Type Benzodiazepine Receptor: A New Aspect of the Role of Mitochondria

The peripheral benzodiazepine receptor (PBR) is located mainly in the outer mitochondrial membrane and many functions are associated directly or indirectly with the PBR. We have studied the influence of different durations of warm ischemia (WI) on renal function, tissue damage and PBR expression in a Large Whitepig model. After a midline incision, the renal pedicle was clamped for 10 (WI10), 30 (WI30), 45 (WI45), 60 (WI60) or 90 min (WI90), and blood and renal tissue samples were collected between 1 day and 2 weeks after reperfusion for assessment of renal function. Metabolite excretion associated with renal ischemia reperfusion injury such as trimethylamine-N-oxide (TMAO) was quantified in blood by magnetic resonance spectroscopy. PBR mRNA and protein expression were determined in renal tissue. TMAO levels rose progressively and significantly with increasing duration of WI. PBR mRNA expression was upregulated between 3 h and 1 day after reperfusion in WI30, WI45 and WI60. Its upregulation was noted 3 days after reperfusion in WI90. At day 14, PBR transcript expression was not different from basal level in any group. PBR protein followed the same pattern. These findings suggest a new role for PBR which could be a major target in the regeneration process during ischemia reperfusion.

Anatomical pitfalls in the technique for total extra peritoneal laparoscopic repair for inguinal hernias

PurposeThe totally extraperitoneal laparoscopic approach for the treatment of inguinal hernia is a well-recognized technique with proven efficacy, low failure rate, and reduced post-operative pain. This laparoscopic technique is reputed to be a more difficult procedure to learn and practice than a laparoscopic trans-abdomino-pre-peritoneal procedure: we hope this is because many surgeons don’t well know extra-peritoneal anatomy of groin. So we proposed a “step by step” anatomical analysis, with pitfalls to avoid, of a totally extraperitoneal laparoscopic approach for treatment of inguinal hernia.MethodsOur experience with totally extraperitoneal laparoscopic inguinal hernia repair with regard to the morphology of the inguinal-femoral region concerns 23 cadaver dissection and more than 400 surgical procedures, now permits clarification of a surgical technique that has hitherto not been well known.ConclusionPhotographic representations of surgical views are displayed, and detailed descriptions applicable to anatomical structures are presented.

Development of the right colon and the peritoneal surface during the human fetal period: human ontogeny of the right colon

BackgroundDevelopment of the digestive tract during the human fetal period has been the subject of many studies, but there are no works that study the ontogeny of both the right colon and the peritoneum.MethodsBased on the dissections of adult male cadavers and human fetuses, the aim of this anatomical study was to demonstrate the rules of the morpho-functional group, consisting of the right colon and its peritoneum surface, in human ontogeny.ResultsThe morphology of the right colon results from a rotational motion, inducting the migration of the cecum in the right iliac fossa and formation of the hepatic flexure. This intestinal migration is based on the axis of rotation of the spreading area of the colon at the ventral side of the lower pole of the right kidney, which becomes visible after the 17th week.ConclusionOur different observations plead in favor of the peritoneal fusion theory. A few variations of this fusion can explain all the disorders in the position of the cecum–appendix that are encountered in current surgery, as well as the possibility of internal hernias.