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Resume Jusqu’en 2013, la formation pratique des internes inscrits au DES/DESC de chirurgie viscerale et digestive en France n’etait pas standardisee. Depuis 2017, le troisieme cycle des etudes medicales a ete restructure autour de deux axes : connaissances theoriques et competences techniques et non-techniques. Celui-ci comporte notamment un programme de formation pratique par simulation, hors bloc operatoire, national, structure, uniformise et standardise. Le developpement de ce programme de formation est le fruit d’un travail de consensus national sous l’egide du college francais de chirurgie viscerale et digestive permettant d’offrir un guide de formation a tous les futurs chirurgiens de la specialite. Quatre seances de conference de consensus reunissant une commission de 8 membres ont abouti a la redaction du « Livret de l’Interne pour l’Enseignement Pratique en Chirurgie Viscerale et Digestive ». Ce referentiel detaille en 272 pages les objectifs (phase I), les moyens d’apprentissage de chaque competence (phase II) et enfin les methodes d’evaluation (phase III) pour les phases socles et des phases d’approfondissement du DES de chirurgie viscerale et digestive. En complement de ce livret, nous avons mene une reflexion sur la structuration et la mise en place de ce programme a l’echelle nationale a compter de novembre 2017 qui est detaille a la fin de cet article.

Up until 2013 in France, practical training for DES/DESC (advanced level) residents in visceral and digestive surgery was not standardized. Since 2017, the third cycle of medical studies has been restructured around three major thematic axes: academic knowledge, and technical and non-technical skills. The curriculum now includes a practical training program by means of simulation outside the operating theater, and it is structured, uniformized and standardized nationwide. Development of this training program is derived from the deliberations of a national consensus panel working under the umbrella of the French college of visceral and digestive surgery, program presenting a training guide to all future surgeons in the specialty. Four consensus conference sessions bringing together an eight-member commission have led to the drafting of a "Resident's manual for practical teaching in visceral and digestive surgery". As a reference document, the manual details in 272 pages the objectives (phase I), the learning resources for each skill (phase II) and, lastly, the means of evaluation for the cornerstone phases as well as the in-depth phases of an advanced degree (DES) in visceral and digestive surgery. As a complement to the manual, we have conducted a review of the structuring and implementation of the program as of November 2017 on a nationwide scale; the conclusions of the review are detailed at the end of this article.

Pancreatic adenocarcinoma has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancers are considered as unresectable because of involvement of celiac and/or mesenteric vessels. Irreversible electroporation has recently been introduced to induce permanent cell death by apoptosis. Irreversible electroporation is a nonthermal cell-destruction technique that was claimed to allow destruction of cancerous cells with less damage to surrounding supporting connective tissues with collagenic structure (such as nearby blood vessels, biliary ducts, and nerves) than other types of treatment. Applications on pancreatic adenocarcinoma seem promising, and this article is an up-to-date review of the first results.

Background: The aim of this trial was to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PMCRC). Methods: A randomised open-label phase 3 study was performed in 23 French hospitals. Eligible patients had a primary colorectal cancer with synchronous and localised PMCRC removed, resected ovarian metastases, and perforated tumor. Patients were randomised (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC after 6 months of adjuvant systemic chemotherapy with no signs of recurrence, via a web-based system with stratification by center, nodal status and factors of risk of PMCRC. The primary endpoint was 3-year disease-free survival (DFS) analysed by intention-to-treat. A sample size of 150 patients was required to achieve a power of 90% to detect a 15% improvement in 3-year DFS rate at a significance level of 0·05 (2-sided). This study was registered at ClinicalTrials.gov (NCT01226394) and recruitment is complete. Findings: Between June 2010 and March 2015, 150 patients were randomised (75 per arm). During systematic second-look (n=71), PMCRC was macroscopically described in 52·1% of patients, with a median peritoneal cancer index of 4 [IQR 2-9.50-26]. No patients died postoperatively and the complications rate was 40·8%. After a median follow-up of 50·8 months [IQR 47·0-54·8], 3-year DFS was not significantly different between arms, at 52·5% [95%CI 41-64] with surveillance and 44·3% [95%CI 33-56] with second-look. Five-year OS were also not significantly different, at 72·0% [95%CI 60-82] and 67·9% [95%CI 55-79] in the surveillance and second-look arms respectively. Interpretation: Systematic second-look surgery with oxaliplatin-HIPEC in patients at high risk of developing PMCRC did not improve survival compared to adequate surveillance. Identifying and monitoring patients with a true increased risk of PMCRC is essential for diagnosing peritoneal recurrence early enough to propose complete surgical resection. Clinical Registration Number: ClinicalTrials.gov number NCT01226394 and EudraCT number 2009-015598-11. Funding: Institut National du Cancer. Declaration of Interest: All other authors declare no competing interests. Ethical Approval: The protocol was approved by the French national health authorities, and all relevant local Ethics Committees. The study was conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent before enrollment.

International audience; Background Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. Methods We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m(2), or oxaliplatin 300 mg/m(2) plus irinotecan 200 mg/m(2), plus intravenous fluorouracil 400 mg/m(2)), or mitomycin-HIPEC (mitomycin 35 mg/m(2)) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. Findings Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50.8 months (IQR 47.0-54.8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0.97, 95% CI 0.61-1.56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. Interpretation Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. Copryright (C) 2020 Elsevier Ltd. All rights reserved.

Resume L’adenocarcinome du pancreas est l’un des cancers solides de moins bon pronostic. Le seul traitement curateur est la chirurgie d’exerese. La forme localement avancee, definie par un envahissement locoregional isole, sans metastase a distance reste egalement non chirurgicale. L’electroporation irreversible est une nouvelle technique d’ablation tumorale permettant d’obtenir une apoptose cellulaire sans effet thermique de coagulation. Cette technique respecte en effet les canaux, les vaisseaux ou les nerfs situes dans la zone de traitement. Cet article fait un point sur cette nouvelle voie therapeutique ou le radiologue interventionnel a toute sa place.

Pancreatic adenocarcinoma is one of the solid cancers associated with the poorest prognosis; the only curative treatment remains surgical resection but in most cases, this treatment is not possible because of distant metastasis or local extension. Irreversible electroporation is a new tumor ablation technique, which provides cellular apoptosis without any thermal coagulation effect. This technique helps preserve the ducts, vessels or nerves located in the treatment area. This article reviews the current knowledge regarding the use of electroporation for the treatment of pancreatic adenocarcinoma.

Resume Introduction La simulation en tant que moyen d’enseignement pratique pour les internes en chirurgie doit etre evaluee de facon objective et doit permettre de mettre en valeur l’acquisition de performance de l’etudiant. Les objectifs de cet article sont la publication de nos grilles d’evaluation et leur validation, ainsi que la mesure de satisfaction des etudiants. Methode Une plateforme d’enseignement pratique sur modele porcin a ete creee en 2009 pour 7 centres hospitaliers universitaires francais. Trois fois par an, 31 internes du DESC de chirurgie viscerale effectuaient 5 exercices chronometres : placement des trocarts (trocarts), test de convergence des instruments (convergence), nœuds intracorporels (nœuds), derouler l’intestin grele pour trouver une lesion (deroule) et realiser un surjet de fermeture du peritoine (surjet). L’evaluation etait realisee de facon prospective par 2 experts sur des grilles (HuFEG) specialement concues et validees pour ces exercices. Le temps, les scores des echelles d’evaluation, l’interet et la satisfaction des internes ont ete analyses. Resultats Les donnees pour 31 internes entre mai 2011 et mars 2012 ont ete analysees. Les echelles d’evaluation etaient statistiquement valides et correlees (K > 0,69) pour chaque exercice. Les temps realises par les internes les plus experimentes etaient significativement plus court dans tous les exercices sauf le deroule du grele (p = 0,2). Apres 4 sessions, les temps etaient significativement ameliores avec une meilleure qualite (moins de fautes et scores moyens eleves [> 88 %]), independamment de l’experience de l’interne. Parmi les apprenants, 92 % etaient satisfaits, 86 % pensaient que ces sessions amelioraient leurs qualites techniques et 74 % pensaient que cela avait un impact favorable sur leur pratique clinique. Conclusion Cette etude montre que l’amelioration des techniques chirurgicales par simulation est plebiscitee par les internes et que nos grilles HuFEG sont valides.

Background The aim of the present study is to evaluate the risk factors of endocrine and exocrine insufficiency occurring few years after pancreatic resections in a consecutive series of patients who underwent pancreatoduodenectomy (PD), left pancreatectomy (LP) or enucleation for benign neoplasms at a referral centre. Methods Pancreatic exocrine insufficiency (PEI) was defined by the onset of steatorrhea associated with weight loss, and endocrine insufficiency was determinate by fasting plasma glucose. Association between pancreatic insufficiency and clinical, pathological, and perioperative features was studied using univariate and multivariate Cox regression analysis. Results A prospective cohort of 92 patients underwent PD (48%), LP (44%) or enucleation (8%) for benign tumours, from 2005 to 2016 in the University Hospital in Poitiers (France). The median follow-up was 68.6 ± 42.4 months. During the following, 54 patients developed exocrine insufficiency whereas 32 patients presented endocrine insufficiency. In the Cox model, a BMI > 28 kg/m2, being a man and presenting a metabolic syndrome were significantly associated with a higher risk to develop postoperative diabetes. The risks factors for the occurrence of PEI were preoperative chronic pancreatitis, a BMI Conclusion Men with metabolic syndrome and obesity should be closely followed-up for diabetes, and patients with obstructive tumours, pancreatic fibrosis or chronic pancreatitis require a vigilant follow up on their pancreatic exocrine function.

International audience; Introduction Simulation as a method for practical teaching of surgical residents requires objective evaluation in order to measure the student's acquisition of knowledge and skills. The objectives of this article are to publish our evaluation and validation grids and also the measure of student satisfaction. Method A teaching platform based on practical exercises with a porcine model was created in 2009 at seven French University Hospitals. Three times a year, 31 Diplôme d’Études Spécialisées Complémentaires (DESC) surgical residents underwent timed assessment of the performance of five surgical tasks: trocar insertion (trocars) testing the convergence of instruments (convergence), intra-corporeal knot tying (knots), running of the small intestine to find a lesion (exploration), and performance of a running suture closure of the peritoneum (closure). Two experts evaluated performances prospectively on grid score sheets specifically designed and validated for these exercises. We measured time, scores on a rating scale, and the interest and satisfaction of the residents. Results Data for 31 residents between May 2011 and March 2012 were analyzed. Rating scales were statistically validated and correlated (Kappa correlation coefficient K > 0.69) for each task. The performance times of the most experienced residents decreased significantly for all tasks except for small bowel exploration (P = 0.2). After four sessions, times were significantly improved with better quality (fewer errors and higher average scores [> 88%]), regardless of the residents’ experience. Of the participants, 92% were satisfied, 86% thought that the sessions improved their technical skills and 74% thought it had a favorable impact on their clinical practice. Conclusion This study shows that the performance of surgical techniques can be improved through simulation, that HUFEG grids are valid, and that this teaching program is popular with surgical residents

PURPOSE: This study compares open Hartmann's procedure reversal (OHPR) and laparoscopic Hartmann's 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

Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241–2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495–504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1α) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.

Background It was demonstrated that postischemic kidney expresses different factors in a pattern that recapitulates expression of these factors in the developing kidney. We investigated whether peripheral-type benzodiazepine receptor (PBR), which belongs to the mitochondrial permeability transition pore and is essential during development, could be influenced by the ischemia-reperfusion injury process when compared with leukemia inhibitor factor (LIF). Study design PBR, LIF, and LIF receptor messengers and proteins were analyzed in adult normal and ischemic kidney under conditions mimicking cardiac arrest: 18 pigs were studied after 60 minutes of warm ischemia and reperfusion for 7 days and compared with sham-operated (Sham, n=12) and control (CONT, n=12) groups. The same messengers and proteins were assessed in fetal kidneys. Results In normal kidney, PBR was expressed in descending and ascending limbs of Henle and in distal tubules. After ischemia-reperfusion injury, PBR mRNA significantly increased between days 1 and 7 in cortex and outer medulla. PBR protein increased between days 1 and 7, and was transiently expressed in proximal tubules at days 1 and 3 and returned to basal level at day 7. LIF messenger and protein increased rapidly at day 1 in proximal tubules. In turn, LIF receptor messenger and protein were not changed during reperfusion. Conclusions These results suggest that PBR may be implicated in ischemia-reperfusion injury and, particularly, in the regenerative process within proximal tubules with LIF. These new insights open the possibility of novel targets for organ protection and repair.

Background: Inflammatory responses related to portal hypertension may be different in male and female rats. Most experimental studies of portal hypertension have involved male animals, and little information is available on gender differences in this setting. The aim of the present study was to compare aortic reactivity in female and male rats with and without portal hypertension. Methods: Contraction response curves to phenylephrine were studied with aortic rings, with and without endothelium. For relaxation studies, rings were precontracted with phenylephrine 10−7 mol/L and then exposed to acetylcholine 10−4 mol/L. Portal hypertension was provoked by calibrated portal stenosis performed 2 weeks before experiments. Results: In non-hypertensive conditions, the contractile response to increasing phenylephrine concentrations was significantly stronger in rings from male than female rats, both with and without endothelium. In male rats with portal hypertension, the phenylephrine concentration–response curves were lowered and shifted to the right in aortic rings both with and without endothelium. In female rats, portal hypertension did not induce significant changes in the phenylephrine concentration–response curves. In female rats, portal hypertension induced a marked increase in relaxation (157 ± 123% vs 81 ± 64% in controls); the increase was also stronger than that in male rats with portal hypertension (95 ± 6%; P

Ischemia-reperfusion injury (IRI) is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria plays a central role in this process. Using an autotransplant pig kidney model, changes in renal function and morphology were determined after different periods of cold ischemia in kidneys preserved in the University of Wisconsin solution (UW), high-Na(+) version of UW (HEH) or Celsior (CEL) a newly developed high-Na(+) solution, with or without trimetazidine (TMZ). Kidney function was better preserved in HEH after 24 hr and particularly 48- and 72-hr cold storage than in CEL and UW. TMZ improved the preservation quality when added to the different solutions tested, particularly after 48- and 72-hr cold storage. Interstitial fibrosis and tubular atrophy were reduced in HEH with TMZ. CD4(+) T-cell infiltration was also modulated by the preservation conditions. Peripheral-type benzodiazepine receptor (PBR) positive cells infiltration was also modulated by preservation conditions. TMZ was efficient to reduce IRI when added in the various preservation solutions. These results suggest that protection of the mitochondrial function should be a major target to limit IRI. In addition, this study outlines the role of CD4(+) T cells and PBR expression in inflammatory responses after IRI.

Background Proton nuclear magnetic resonance spectroscopy can be used to measure organic molecules in biological fluids. In this study, proton nuclear magnetic resonance spectroscopy of bronchoalveolar lavage was assessed to detect cellular damage in lung transplants. Also we evaluated a polyethylene glycol solution in lung preservation. Methods An isolated perfused and working pig lung was used to assess initial pulmonary function after in situ cold flush and cold storage for 6 hours in three preservation solutions: (1) Euro-Collins solution, (2) University of Wisconsin solution, and (3) low potassium solution with polyethylene glycol (PEG). Pulmonary vascular resistance and partial pressure of arterial oxygen were measured during reperfusion. Bronchoalveolar lavage was studied by proton nuclear magnetic resonance spectroscopy and a histologic study of the lungs was done at the harvest after ischemia and after reperfusion. Results Partial pressure of arterial oxygen and pulmonary vascular resistance were significantly better in PEG compared with Euro-Collins solution ( p = 0.011). Interstitial edema was significantly higher in Euro-Collins solution (2.4 ± 0.24; p = 0.02) and University of Wisconsin solution (2.7 ± 0.20; p = 0.0003) than PEG (2 ± 0.16). Mitochondria scale was better in PEG (8.1 ± 0.46) than in Euro-Collins solution (6.2 ± 0.37; p = 0.0001) or University of Wisconsin solution (5.6 ± 1.36; p = 0.0046). In bronchoalveolar lavage proton nuclear magnetic resonance spectroscopy spectra, lactate, pyruvate, citrate, and acetate were only detected after reperfusion, with a significantly reduced production of acetate in PEG. Pyruvate was reduced at the limit of significance in PEG versus University of Wisconsin solution. Conclusions Proton nuclear magnetic resonance spectroscopy seems to be a simple and suitable method for assessment of early injury to the lung transplant. In this experimental study, PEG preserved the lung better than University of Wisconsin solution and Euro-Collins solution in both the proton nuclear magnetic resonance spectroscopy study as well as the physiologic study.

The authors describe a technique of totally preperitoneal videoscopic inguinal hernia repair. This method allows, by cleavages, to obtain a preperitoneal space where can be individualised anatomical structures of the inguinofemoral area: pubis, pectineal ligament of Cooper, epigastric vessels. After squelettisation of the elements of the cord by release of the hernial bag, installation of a not fixed prosthesis largely covers the hernial rings.

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 Belzer's 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.

Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PDD) significantly contributing to post-operative morbidity. Clinical risk factors for DGE occurrence after PDD remain controversial. From January 2004 to December 2011, a total of 132 patients underwent PDD for either malignancies (73.5 %) or benign diseases (26.5 %) in one single universitary center. Post-operative mortality and morbidity were, respectively, 3 and 44.7 %. DGE has been defined in accordance with the International Study Group of Pancreatic Surgery (ISGPS) classification. DGE was distinguished in primary or secondary. Factors associated with grades B and C of DGE, based on severity and clinical impact, were assessed by means of univariate and multivariate analysis. Thirty-eight patients (28.8 %) had clinical DGE grade B or C. Post-operative complications (pancreatic fistula and/or hemorrhage or anastomotic leak) were reported in 25 out of the 38 patients (65.8 %, secondary DGE), while in 13 patients it was not associated to any other complication (34.2 %, primary DGE). Post-operative complications (pancreatic fistula and hemorrhage) appeared to be the most important predictive factor for Grade B or C DGE.

Background. Ischemia-reperfusion injury (IRI) is often responsible for graft rejection and leads to delayed graft function of cadaveric kidneys. We have shown that adding polyethylene glycol (PEG 20M) to the preservation solutions helps protect isolated perfused pig kidneys against cold ischemia and reperfusion injury. Methods. We compared the effects of adding PEG to a simplified high-K 1 perfusion solution of cold-stored kidneys to Euro-Collins or University of Wisconsin solutions on the function of reperfused autotransplanted pig kidneys. The left kidney was cold-flushed with the preservation solutions and stored for 48 hr at 4°C before reimplantation. Creatinine clearance and fractional excretion of sodium were analyzed 2 days before surgery and over 7 days after transplantation. Histological sections were obtained 40 min after reperfusion and on day 7 after surgery. Results. Adding PEG to the perfusate significantly reduced IRI from autotransplanted pig kidneys. Creatinine clearance was significantly higher and fractional excretion of sodium was significantly lower in pigs transplanted with kidneys cold-flushed with PEG-supplemented perfusate than in those flushed with Euro-Collins or University of Wisconsin solutions. PEG supplementation also better preserved the integrity of kidney cells and markedly reduced interstitial cell infiltrates. Conclusion. PEG protects against IRI and reduces early cellular inflammation. PEG may impair the recruitment and migration of leukocytes into retransplanted pig kidneys. Cold preservation of donor organs with PEG-supplemented solutions may therefore help limit IRI in human renal transplantation. Delayed graft function (DGF) is a major problem affecting kidney allografts after transplantation. DGF occurs in 30 ‐ 50% of patients given a first cadaver graft and can be exac

In organ transplantation, the determination of reliable parameters to assess ischaemic damage is essential to predict renal injury after preservation. The aim of this study was to assess renal medullary injury by 1H NMR (proton nuclear magnetic resonance) spectroscopy after preservation and reperfusion. Three experimental groups of pigs were examined during a 2-week period: control group (n = 4), Euro-Collins group (EC) (cold flushed and 48 h cold storage of kidney in EC and autotransplantation, n = 7), and University of Wisconsin (UW) group (cold flushed and 48 h cold storage of kidney in UW and autotransplantation, n = 7). Creatinine and urea were improved in the two cold stored groups. The most relevant resonances determined by 1H NMR spectroscopy after transplantation were those arising from citrate and acetate in urine and trimethylamine-N-oxide (TMAO) in urine and plasma. We demonstrate that graft dysfunction is associated with damage to the renal medulla as determined by TMAO release in urine and plasma. Conversely, citrate excretion can discriminate kidneys with favourable outcome. This study outlines the specific and beneficial impact of UW solution on renal preservation and suggests that 1H NMR spectroscopy is efficient both to detect ischaemic damage of preserved kidneys and to discriminate the preservation quality between different preservation solutions.

Background. Delayed graft function (DGF) has remained an important complication after renal transplantation. The exact causes of DGF remain to be clarified, particularly the impact of retrieval conditions and preservation factors. In the present investigation, 1HNMR spectroscopy of urine was assessed in order to detect the influence of retrieval condition on renal medulla damage. Methods. The isolated perfused pig kidney (IPK) was used to assess initial renal function from multiorgan donors (MOD) or single organ donors (SOD) after in situ cold flush and 24-h cold storage (CS) preservation with two standard preservation solutions: Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys flushed with cold heparinized saline and immediately perfused were used as the control group. Kidneys were perfused for 90 min at 37.5°C for functional evaluation. During reperfusion, renal perfusion flow rate (PF) was measured. Glomerular filtration rate (GFR), tubular reabsorption of Na+, and lactate dehydrogenase (LDH) and N-acetyl-β- d -glucosaminidase (NAG) excretions were determined. Ischemia–reperfusion impairment was also determined by histological techniques and 1HNMR spectroscopy. Results. PF, GFR, and tubular reabsorption of Na+ were significantly decreased in experimental groups when compared to the control group but there was no significant difference between experimental SOD groups. GFR was significantly greater in UW-MOD than in EC-MOD and tubular reabsorption of Na+ was significantly greater in UW-MOD than in EC-MOD after 45 min of reperfusion. The release of LDH in the effluent and the urinary excretion of NAG were not significantly different after 24-h CS in the various experimental groups. The most relevant resonances determined by 1HNMR spectroscopy were citrate, trimethylamine-N-oxide, lactate, acetate, and amino acids. Excretion of these markers was significantly different when compared to biochemical markers. A resonance (P) detected particularly in EC-MOD after 24-h CS was identified and well correlated to renal dysfunction. Histological study showed that ultrastructural damage and mitochondrial injury were more pronounced in the EC-MOD group. Conclusion. These results show that retrieval condition influences renal medullary damage. NMR spectroscopy, which is a noninvasive and nondestructive technique, is more efficient in assessing renal damage than conventional histology and biochemical analysis.

Background: Endoscopic insertion of biliary stents is a useful treatment for obstructive jaundice resulting from unresectable tumors of the pancreas and biliary tree. The main drawback is the recurrence of jaundice due to clogging. The aim of this study was to establish an experimental model of polyethylene stent clogging in large white pigs. Methods: A straight polyethylene stent of 5F (group I), 7F (group II) or 10F size (group III) was inserted in the common bile duct. Animals were killed at 2 months, or earlier if physical signs suggesting stent clogging occurred. Chemicophysical analysis of stent deposition combined stereomicroscopy and identification of the contents by means of Fourrier transform infrared spectroscopy. Bacteriologic analyses included identification of aerobic and anaerobic bacteria and measurement of β-glucuronidase, lecithinase and lipase activities. Results: Physical signs suggesting stent obstruction or death occurred in 8 of 8 animals in group I, 11 of 12 in group II, and 2 of 8 in group III ( p Clostridium species were associated with the highest enzyme activities. Conclusions: In this model the major component of early stent deposits was mucoprotein, and numerous aerobic and anaerobic bacteria were isolated. Formation of calcium bilirubinate was a late phenomenon and poorly related to bacterial enzymatic activities. (Gastrointest Endosc 2000;51:12-8.)

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 ± 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 ± 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 ± 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 ± 0.17 by the intranasal route. The terminal half-life (T1/2 λz) = 145 ± 138 min was comparable with the i.v. administration half-life (158 ± 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.

Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10 -6 M TMZ and stored for 48 h at 4°C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine- N -oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45 + and CD3 + T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.

Background. Initial ischemia-reperfusion injury is associated with organ retrieval, storage, and transplantation adversely affects early graft function and influences the development of chronic graft dysfunction. We have recently shown that the protective agent trimetazidine (TMZ) added to preservation solutions: Euro-collins (EC) and University of Wisconsin (UW) was efficient to protect kidneys from ischemia-reperfusion injury in an isolated perfused kidney model. We extended these observations to investigate the role of this drug in the development and progression of organ dysfunction in the autotransplant pig kidney model. Methods. Five experimental groups were studied. After 48-hr cold preservation, autotransplantation and immediate controlateral nephrectomy was then performed in group EC (EC+placebo (n=8), EC+TMZ (n=8), UW+placebo (n=7), and (UW+TMZ) (n=7) and compared with control group (uninephrectomized, n=4) during 14 days. Blood and urine samples were collected for the measurement of creatinine and blood urea nitrogen on postoperative days 1, 3, 5, 7, 11, and 14. Histological analysis was performed after reperfusion and at day 14. Results. Survivals were 100% in group B and D versus 42% in group A and 57% in group C. Urine production occurred earlier after autotransplantation from TMZ preserved kidneys than in placebo preserved groups. Peak creat and blood urea nitrogen was significantly greater in groups B and D than in groups A and C. TMZ was also efficient both to reduce ischemia-reperfusion injury and to decrease cellular infiltration. Conclusion. These results support the beneficial effect of TMZ against ischemia-reperfusion injury and its early effects on grafts in the form of delayed graft function and decreased graft survival. In addition, TMZ reduces inflammatory cellular infiltration in the renal parenchyma.

Background. Ischemia caused by cold storage (CS) and reperfusion of the kidney is often responsible for delayed graft function after transplantation. Significant attention has been focused on the cascade of events involved in ischemia-reperfusion injury, with the objective of identifying drugs to ameliorate the functional damage that occurs. Methods. The purpose of this study was to evaluate the renal function of isolated perfused pig kidneys after 48 hr of CS with Euro-Collins (EC) solution plus trimetazidine (EC+TMZ), standard EC solution, or University of Wisconsin (UW) solution. Normothermic isolated perfused pig kidneys were randomized into five experimental groups: (A) control group (cold flush with cold heparinized saline and immediately reperfused ; n=6); (B) cold flush with cold heparinized saline with TMZ (10 -6 M), n=6; (C) 48 hr of CS with EC and reperfusion (n=8); (D) 48 hr of CS with EC+TMZ alone and reperfusion (n=8); (E) 48 hr of CS with UW and reperfusion (n=8). Proton nuclear magnetic resonance spectroscopy and biochemical studies were performed for the functional evaluation during reperfusion. Lipid peroxidation was also determined. Histological examination (optical and electron microscopy) was performed after CS and reperfusion. Results. Using TMZ, the renal perfusate flow rate as well as the glomerular filtration rate and proximal tubular function were significantly improved. This improvement of renal function during reperfusion was correlated with a less significant cellular and interstitial edema. In addition, tubular injury markers were significantly lower in the group preserved with EC+TMZ, and TMZ reduced lipid peroxidation dramatically during reperfusion. Conclusions. The addition of TMZ to the EC solution increased the preservation quality and renal tubular function, and gave protection from reperfusion injury better than EC alone or UW. These results strongly suggest that TMZ has a cytoprotective effect and may therefore be useful for kidney preservation.

The isolated perfused pig kidney (IPK) model was used to mimic the non-heart-beating donor situation. This model was performed to assess initial renal functions after normothermic ischemia, cold flush, and 24 hr cold-storage preservation (CSP) with Euro-Collins and to determine normothermic ischemia and reperfusion impairment by biochemical, histological, and proton nuclear magnetic resonance (NMR) spectroscopy analysis. Twenty-four pig kidneys were used. There were three experimental groups: Group 1 (G1), control kidneys flushed with cold heparinized saline and immediately perfused; Group 2 (G2), cold flush followed by 24 hr CSP and reperfusion; and Group 3 (G3), 30 min of normothermic ischemia followed by cold flush and 24 hr CSP and reperfusion. Kidneys were perfused for 2 hr at 37.5 degrees C for functional evaluation. Perfusate flow rate is significantly different for G3 (P < 0.01). Glomerular filtration rate is less in G3 (P < 0.05). Fractional reabsorptions of sodium (FRNa+) and glucose (Glc) excretion in urine are different in G3 (P < 0.01 and P < 0.05, respectively). Amino acid excretion in NMR spectroscopy was higher in G3 (P < 0.05). Elevated levels of trimethylamine-N-oxide (TMAO) and lactate (Lac) were detected by proton NMR spectroscopy in G2 and particularly G3. A peak is present in G3 and related with poor glomerular and tubular functions and worse histological data. Malondialdehyde tissue level was higher in G3. This study shows that the IPK with proton NMR spectroscopy may be a useful method in the evaluation of kidneys after cold ischemia and transplantation. This model might be suitable for a variety of experimental protocols, particularly to improve functional performance after ischemia and reperfusion.

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.

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.

The potential implication of interleukin (IL) 6, tumor necrosis factor alpha (TNF-alpha), and IL-10 in the protective effect of low-dose lipopolysaccharide (LPS) administration against renal ischemia-reperfusion injury was evaluated in a rat model. Eighteen male Sprague-Dawley rats were injected intravenously with either 0.5 mg/kg of LPS (tolerant group) or saline (control group) 2 days before surgery. Ischemic renal injury was induced by clamping the left renal artery for 60 min on rats immediately after right-side nephrectomy. Reperfusion was obtained by clamp removal and was studied at R0 (no reperfusion), 2H (R2), and 24H (R24) by renal tubular disorder characterization and by plasma creatinine as well as renal cytokine (IL-6, IL-10, and TNF-alpha) studies. No differences were observed between the two groups as concerns the period immediately after renal ischemia (R0). The endotoxin-tolerant group was associated with a significantly lower creatinine level at R24 (231 +/- 28 vs 315 +/- 36 micromol/L; P = 0.007). Pretreatment with LPS significantly reduced the degree of proximal tubule necrosis and outer medulla congestion. In such tolerant animals, renal IL-6 production was decreased, whereas IL-10 production was significantly increased at R2 and R24. There were no differences in TNF-alpha renal production. In this study, we demonstrated that administration of low doses of LPS to rats had a protective effect from renal reperfusion injury, and our data suggest that IL-10 might play a role in this phenomenon.

We report the molecular cloning of the cDNA sequence for pig peripheral benzodiazepine receptor (PBR) by using RT-PCR and 5'/3' terminal extension. Three different transcripts (long, middle, and short) are identified. The open reading frame (ORF) of the longest PBR mRNA encodes a deduced polypeptide of 169 amino acids with a calculated molecular weight of 18,609 Da and an estimated pI of 9.70, which corresponds to the authentic PBR of other mammalian species. The middle transcript (PBR-M) contains a 141-codon ORF, which is consistent with that of the authentic PBR, but lacks a region of 84 bp so that its encoded polypeptide lacks a region of 28 amino acids from 35 to 62 of the authentic PBR polypeptide. The short transcript (PBR-S) contains a 104-codon ORF, which overlaps that of the authentic PBR, but lacks a region of 211 bp so that its encoded polypeptide lacks a region of 65 amino acids of the N-terminal of the authentic PBR. The pig PBR gene was mapped to the telomeric end of SSC5p. In addition, PBR mRNA was the more abundant detected form in pig tissues and in warm kidney that underwent ischemia suggesting functional implications of PBR during the renal repair process.

ALTHOUGH the success of the first cold storage solution was attributed to its intracellular composition with low sodium and high potassium,1,2 the importance of impermeant agents has been shown and the potential deleterious effects of high potassium solutions have been suggested.3–5

Inflammatory responses related to portal hypertension may be different in male and female rats. Most experimental studies of portal hypertension have involved male animals, and little information is available on gender differences in this setting. The aim of the present study was to compare aortic reactivity in female and male rats with and without portal hypertension.Contraction response curves to phenylephrine were studied with aortic rings, with and without endothelium. For relaxation studies, rings were precontracted with phenylephrine 10(-7) mol/L and then exposed to acetylcholine 10(-4) mol/L. Portal hypertension was provoked by calibrated portal stenosis performed 2 weeks before experiments.In non-hypertensive conditions, the contractile response to increasing phenylephrine concentrations was significantly stronger in rings from male than female rats, both with and without endothelium. In male rats with portal hypertension, the phenylephrine concentration-response curves were lowered and shifted to the right in aortic rings both with and without endothelium. In female rats, portal hypertension did not induce significant changes in the phenylephrine concentration-response curves. In female rats, portal hypertension induced a marked increase in relaxation (157 +/- 123% vs 81 +/- 64% in controls); the increase was also stronger than that in male rats with portal hypertension (95 +/- 6%; P0.01).Clear gender differences were observed in vasoconstrictor responsiveness of aortic rings from rats with and without portal hypertension. Contrary that in male rats, portal hypertension did not induce vascular hyporesponsiveness in female rats. Further investigations are required to explain these differences.

Abdomen can be compared in broad outline with an irregular cylinder, limited at the top by the diaphragm and below by the pond. The walls of this cylinder are musculo-aponevrotic and present "zones of weakness" seats of the hernias of the abdominal wall. We propose a topographic anatomical approach of abdominal hernias.

Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4(+), PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.

Injury during the transplant process affects the alloantigen-dependent factors and the alloantigen-independent processes of "chronic" rejection. Consequently, the determination of reliable parameters for the assessment of ischemic damage is essential for the prediction of renal changes after ischemia/reperfusion injury. The aim of this study was to assess the ability of (1)H NMR spectroscopy to predict the early graft dysfunction in an ischemia/reperfusion model after preservation in two standard preservation solutions, Euro-Collins (EC) and University of Wisconsin (UW). The second aim was to specify the role of the UW solution in preventing renal medullary injury. Urine and plasma samples from three experimental groups were examined during 2 weeks: control group (n = 5), EC group (cold flushed and 48-h cold storage of kidney in EC and autotransplantation, n = 12), and UW group (cold flushed and 48-h cold storage of kidney in UW and autotransplantation; n = 12). We also examined these kidneys 30-40 min after implantation and on the sacrifice day. Creatinine clearance was significantly reduced in the EC group during the second week. Fractional excretion of sodium and urine N-acetyl-beta-d-glucosaminidase activity were improved but not significantly different in the preserved groups. Urinary concentrations of the alpha-class glutathione S-transferase were significantly greater in the EC group during the first week after transplantation. The most relevant resonances for evaluating renal function after transplantation determined by (1)H NMR spectroscopy were those arising from citrate, dimethylamine (DMA), lactate, and acetate in urine and trimethylamine-N-oxide (TMAO) in urine and plasma. These findings suggest that graft dysfunction is associated with damage to the renal medulla determined by TMAO release in urine and plasma associated with DMA and acetate excretion. Citrate is also a urinary marker that can discriminate kidneys with a favorable evolution. Our results suggest that (1)H NMR spectroscopy is an efficient technique for detecting ischemic damage when accurate and precise data on graft injury is required. In addition, this study outlines the specific impact of the UW solution against injury to the renal medulla.

The surgery of groin hernias can be considered in two stages: the handling of the hernial sac, which necessitates dissection, resection, and reduction, and the parietal reconstruction, which calls upon the existing anatomical structures. Prosthetic material may be required to bridge a defect when the dissection is completed and the structures identified to which a prosthesis might be anchored.

The pancreas is an uncommon site of metastasis from renal cell carcinoma, comprising 2% of pancreatic tumors removed in sizable series of operations. To our knowledge the role of operative resection in the setting of metastatic malignancy to the periampullary region has not yet been defined. We reviewed the records of 6 women and 2 men who underwent pancreatic resection due to malignancy and analyzed various prognostic factors.Between 1985 and 1995, 269 patients underwent pancreatic resection for malignancy at our hospitals, including 150 (56%) for pancreatic duct cancer, 65 (24%) for carcinoma of the ampulla, 27 (10%) for distal bile duct cancer, 19 (7%) for duodenal carcinoma and 8 (3%) for renal cell carcinoma metastasis. We reviewed the records of these latter 8 cases, and analyzed demographics, primary tumor type, disease-free interval, resection type, concomitant other organ resection, histological examination of the specimen, morbidity, adjuvant therapy and survival.Pancreatic metastasis of renal cell carcinoma was managed by duodenopancreatectomy in 5 patients and total pancreatectomy in 3. There were no perioperative deaths. Mean tumor size in cases of a solitary pancreatic metastasis was 4 cm. (range 1.5 to 8). In the 3 patients treated with total pancreatectomy there were 2, 5 and 3 pancreatic metastases, respectively. Pathological examination revealed negative lymph nodes in all cases. Mean survival was 48 months. At study end 6 patients were alive at 24, 26, 30, 46, 84 and 88 months, while 2 died at 13 and 70 months, respectively.We advocate aggressive surgical resection when possible. Surgical removal of metastatic lesions prolongs survival but radical lymph node dissection is not mandatory. We also recommend careful long-term followup of patients with a history of renal cell carcinoma.

Influence of cold-storage conditions on renal function of autotransplanted large pig kidneys. Background The consequences of ischemia/reperfusion injury (IRI) on delayed graft function (DGF) and graft survival for kidney recipients remain a matter of debate. Several strategies have been proposed to reduce IRI. We have shown that adding the anti-ischemic drug trimetazidine (TMZ) to different preservation solutions had beneficial effects on the function of reperfused rat and pig kidneys. Methods We analyzed the renal parameters of reperfused, autotransplanted large pigs following transplantation. The left kidneys were first removed and cold flushed with Euro-Collins (EC) and University of Wisconsin (UW) solutions (with or without 10 -6 mol/L TMZ) and were stored for 48 hours at 4°C. The kidney was then autotransplanted, and the contralateral kidneys were removed. Creatinine clearance, natriuresis, proteinuria, the degree of interstitial fibrosis, the number of CD4, CD8, and macrophage-positive cells, and the amount of vascular cell adhesion molecule-1 were analyzed on kidney biopsies taken at 2, 4 to 5, and 10 to 12 weeks after surgery. Results The functions of the transplanted kidneys were better preserved after cold flushing with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher, and proteinuria was lower in animals transplanted with kidneys cold flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive cells. Conclusion These results indicate that the condition of cold preservation may influence long-term kidney graft functions and suggest that, to a certain extent, TMZ reduces the degree of interstitial fibrosis.

ISCHEMIA-reperfusion injury after organ transplantation is a major cause of delayed graft function. The pathogenesis of ischemia-reperfusion injury are well correlated with alterations in mitochondrial function, namely, decrease in ATP synthesis, NAD(P)H level, and mitochondrial membrane potential and generation of mitochondrial permeability transition. A previous study has demonstrated that the pretreatment with trimetazidine (TMZ) prevented these ischemia-reperfusion deleterious effects at both the cellular and mitochondrial level. The aim of this study was to assess the effect of TMZ added to University of Wisconsin Solution (UW) during cold preservation in an isolated perfused pig kidney model against lipid peroxidation and renal medulla damage. After cold preservation (CP), kidneys were perfused as previously described.

The incidence of primary dysfunction or non-function of liver grafts still occurs at an unacceptable rate and the identification of new markers of graft viability and metabolic capacity is essential. Proton nuclear magnetic resonance (H NMR) spectroscopy has previously shown potential in the evaluation of renal allograft dysfunction after ischaemia reperfusion. The aim of this study was to compare liver graft function in a rat isolated perfused liver model after 24 hours of preservation in either Euro-Collins (EC) or University of Wisconsin (UW) solutions. Livers were reperfused for 90 min with a modified Krebs-Henseleit medium. Functional parameters measured were: pressure and resistances, bile and transaminase production. The production of lactate, pyruvate, citrate and succinate, beta-hydroxybutyrate and aceto-acetate was measured by H NMR. There was a significant difference in both haemodynamics and bile production in favour of the UW group. The transaminases were similar in the two groups. Measurements of citrate, succinate and ketone bodies by H NMR were all higher in the UW group. These markers indicate better metabolic function of these grafts during reperfusion. In conclusion, discriminating different hepatic metabolic pathways is possible and easy by H NMR and can be used to assess both the preservation quality of liver grafts and their functional recovery.

The laboratory piglet is currently the preferred animal for experimental digestive surgery. In order to ensure optimal perioperative analgesic control with motor blockade during surgery together with rapid postoperative recovery, epidural anesthesia techniques were developed in this animal. We report the anatomo-radiologic studies (10 animals) and clinical experiments (51 transplantations of the liver and the small intestine) which led to the refinement of this anesthesia. In laboratory piglets, epidural anesthesia by distal transsacral (S4-S5) or sacrococcygeal approach is possible in a reproducible manner. The localization of the injection site is simple and epidural space catheterisation is easy without risk for the dural sac which ends at S1-S2.

Background: Delayed graft function has remained an important complication after renal transplantation. Methods: The purpose of this study was to evaluate Euro-Collins (EC) plus trimetazidine (TMZ) in comparison with standard EC solution after 24- or 48-hour cold storage. The normothermic isolated perfused pig kidney technique combined with proton nuclear magnetic spectroscopy was used. Results: The study verified that TMZ plus EC had a beneficial preservation effect over EC in terms of better perfusate flow rate at both 24 and 48 h (p < 0.01 and p < 0.001, respectively). In addition, TMZ also was beneficial in terms of increased glomerular filtration rate, better proximal tubular functions, and less tubular injury markers. Lipid peroxidation, evaluated by malondialdehyde renal tissue levels, was decreased in kidney homogenates preserved with TMZ, particularly after 48-hour cold storage. Citrate excretion which reflects a better intracellular pH regulation was detected in urine from kidneys preserved with TMZ. Histological data paralleled findings of the above when comparing cellular injury factors such as vacuolization, necrosis, tubular structure, and interstitial edema. Conclusion: These results indicate that, under the conditions of our experiments, the addition of TMZ to EC solution increased the preservation quality of kidneys particularly after prolonged cold ischemia.