[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Rapidly progressive hepatic alveolar echinococcosis in an ABO-incompatible renal transplant recipient.

We report on the case of an ABO-incompatible renal re-transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work-up, the lesions revealed alveolar echinococcosis, a rare but potentially life-threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti-CD20 treatments. Retrospectively performed serological studies with enzyme-linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B-cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.

[Timing of resection in patients with colorectal carcinoma and synchronous liver metastases]. / Zeitlicher Ablauf von Leber- und Darmresektion bei Patienten mit kolorektalem Karzinom und synchronen Lebermetastasen.

Timing of surgical therapy in patients with synchronous colorectal liver metastases is becoming more complex. The standard therapy for most of the patients remains resection of the colorectal cancer first followed 6 weeks later by liver resection. Simultaneous colon and liver resection is safe and advisable in cases of minor liver resections and right-sided colon tumours. Major liver resections in combination with resection of the colorectal cancer carry the risk of increased postoperative morbidity and mortality. They should be considered for selected patients only. A pre-requisite is, in addition, special expertise of the operating surgeon in colorectal as well as in hepatobiliary surgery. If the synchronous liver metastases are near to essential anatomic structures, the liver resection should be performed before the bowel resection. The same holds if the metastases are technically resectable, but the future liver remnant seems to be too small. Using well known techniques, the future liver remnant should be increased and the liver metastases resected before treatment of the colonic primary tumour. The risk for local complications is very low when leaving the colorectal tumour in situ during treatment of liver metastases. When synchronous liver metastases are technically not resectable or carry a high risk of an R1 resection, patients should be treated first with systemic neo-adjuvant chemotherapy. If sufficient down-sizing of the metastases can be achieved, liver resection should be performed before bowel resection. A close cooperation between the oncologist and the hepatobiliary surgeon is most important, since the window for curative surgery is rather limited in these patients. In patients with resectable synchronous liver metastases, the advantage of a neoadjuvant chemotherapy has not been proven yet.

[Diagnosis of and therapy for gastric cancer--work-flow]. / Diagnostik und Therapie des Magenkarzinoms--Workflow.

AIM: This review comments on the diagnosis and treatment of gastric cancer in the classical meaning--excluding adenocarcinoma of the -oesophagogastric junction. Algorithms of diagnosis and care with respect to tumour stage are presented. PREOPERATIVE DIAGNOSIS: Besides oesophagogastroduodenoscopy, endoscopic ultrasonography is necessary for the accurate diagnosis of T categories and as a selection criterion for neoadjuvant chemotherapy. Computed tomography is recommended for preoperative evaluation of tumours > T1, laparoscopy has become an effective stag-ing tool in T3 and T4 tumours avoiding unnecessary laparotomies and improving the detection of small -liver and peritoneal metastases. TREATMENT: Endoscopic mucosal resection and submucosal dissection are indicated in superficial cancer confined to the mucosa with special characteristics (T1 a / no ulcer / G1, 2 / Laurén intestinal / L0 / V0 / tumour size < 2 cm). In all other cases total gastrectomy or distal subtotal gastric resection are indicated, the latter in cases of tumours located in the distal two-thirds of the stomach. Standard lymphadenectomy (LAD) is the D2 LAD without distal pancreatectomy and splenectomy. The Roux-en-Y oesophagojejunostomy is still the preferred type of reconstruction. An additional pouch reconstruction should be considered in -patients with favourable prognosis, this also -applies for the preservation of the duodenal passage by jejunum interposition. Extended organ resections are only indicated in cases where a R0-resection is possible. Hepatic resection for metachronous or synchronous liver metastases is rarely advised since 50 % of patients with liver metastases show concomitant peritoneal dissemination of the disease. DISCUSSION AND CONCLUSIONS: Undergoing gastrectomy at a high-volume centre is associated with lower in-hospital mortality and a better prognosis, however, clear thresholds for case load cannot be given. Perioperative chemotherapy and postoperative chemoradiotherapy are based on the MAGIC and MacDonald trials. Perioperative chemotherapy should be performed in patients with T3 and T4 tumours with the aim to increase the likelihood of curative R0-resection by downsizing the tumour. Adjuvant postoperative chemotherapy cannot be recommended since its benefit has so far not been proven in randomised trials. In selected patients with incomplete lymph-node dissection and questionable R0-resection postoperative chemoradiotherapy may be debated.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Glucagon expression shift in a syngeneic single-donor intrahepatic rat islet transplantation model.

In the native rat pancreas glucagon is expressed by alpha cells in the outer layer of the spheroid islet, producing a circular immunohistochemical staining pattern. We asked whether this pattern would remain unchanged after short-term and long-term intrahepatic islet transplantation. Islets of inbred Lewis rats were isolated with liberase, purified by discontinuous density gradients, handpicked, and cultured for 24 hours. After rats were rendered diabetic with streptozotocin, islets were implanted intraportally. Transplanted animals were sacrificed at 1 to 2 days (n = 5) or 100 days (n = 6). Islet clusters were detected by hematoxylen-and-eosin staining. Serial slides were stained for glucagon and insulin with the alkaline phosphatase and alkaline phosphate method at 1 to 2 days after transplantation islets with strong insulin expression were found within the portal vein branches. However, glucagon staining showed an incomplete circular staining pattern. After 100 days insulin expression remained strong, whereas only few glucagon-expressing cells were detected. Intrapancreatic islets showed inversion of the ratio of insulin- to glucagon-positive cells in favor of the glucagon-expressing cells that now composed the major part of the islet. Streptozotocin had selectively damaged beta cells in the recipient. In transplanted islets glucagon expression faded over time, possibly due to a functional involution process or to stress/inflammatory mechanisms during the isolation, transplantation, and the posttransplantation periods.

High levels of C-reactive protein after simultaneous pancreas-kidney transplantation predict pancreas graft-related complications and graft survival.

BACKGROUND: Although pancreas graft-related complications are frequent after simultaneous pancreas-kidney transplantation (SPK), there are no parameters predicting the risk for these complications. METHOD: A two-center retrospective study was performed in 97 patients who underwent SPK to investigate the peak serum value of c-reactive protein (CRP) during the first 72 hr after SPK in view of graft-related complications and graft survival. RESULTS: Mean peak CRP was 115.6 +/- 71.5 mg/L. Mean peak CRP was higher in patients needing relaparotomy (n=31) (136.4 vs. 105.8 mg/L, P=0.048), especially when postoperative bleeding was excluded (P=0.015); in patients with graft pancreatitis (P=0.03); and in patients with graft loss (n=19; P<0.001) compared with patients without these complications. With a cut-off of peak CRP at the level of mean plus 1 SD (187.05 mg/L), there was a significantly higher incidence of relaparotomies (P=0.01; bleedings excluded: P=0.003), graft pancreatitis (P=0.03), and pancreas graft loss (P<0.0001) in patients with high peak CRP compared with patients with low peak CRP. No differences were noticed with regard to rejection rate, mortality, and kidney graft loss. CONCLUSION: Our findings suggest that peak CRP is a helpful parameter in predicting pancreas graft-related complications and pancreas graft survival after SPK. Our results also stress the importance of early graft damage in pancreas transplantation.

Apoptosis is caused by prolonged organ preservation and blocked by apoptosis inhibitor in experimental rat pancreatic grafts.

UNLABELLED: Apoptosis is a major mode of cell death after ischemia/reperfusion injury in several organs. The aims of this study were to evaluate apoptosis induction after different conditions of pancreas preservation and to investigate the impact of a caspase inhibitor on apoptosis induction in pancreatic grafts. METHODS: Inbred male Lewis rats served as donors and recipients. Apoptosis was detected using an in situ cell death detection kit and an apoptotic DNA ladder kit (Roche, Germany). An apoptotic index (AI) was defined as the number of apoptotic cells per field (400x) under a light microscope. The five groups included: group 1 (n = 5), normal pancreata; group 2 (n = 7), pancreata stored in University of Wisconsin (UW) solution (4 degrees C) for 6 hours (hr); group 3 (n = 7), pancreata preserved in UW solution (4 degrees C) for 18 hr; group 4 (n = 7), pancreata preserved in 0.9% saline (4 degrees C) for 6 hours; and group 5 (n = 5), pancreata preserved in 0.9% saline (4 degrees C) for 6 hours with Z-Asp-2,6-dichlorobenzoyloxymethylketone (caspase inhibitor) treatment. The pancreatic grafts in all experimental groups underwent a 2-hr period of reperfusion after transplantation. RESULTS: The results in this study showed that the AI was not significantly increased among pancreatic grafts in group 2 compared to group 1 (P >.05). However, AI in group 3 was significantly higher than that in group 2 (P <.05). The highest AI was observed in group 4. Interestingly, AI in group 5 was significantly lower than that in group 4 (P <.01), and not significantly different from group 1 (P >.05). Apoptotic DNA ladders were detected in the pancreatic grafts in group 2, 3, and 4, but not in group 1 and 5. CONCLUSIONS: Prolonged preservation of pancreata in cold UW solution induces a dramatic increase in apoptotic cell death among the pancreatic grafts following Tx. This observation may well be an important mechanism of graft damage. A caspase inhibitor might be useful to inhibit apoptosis induction in pancreatic grafts.

[Primary aortoduodenal fistula as a late complication of para-aortic radiation therapy. A case report]. / Primäre aortoduodenale Fistel als Spätkomplikation nach paraaortaler Radiatio. Ein Fallbericht.

Primary aortoenteric fistulae (AEFs) are rare vascular entities. More than 75% of primary AEFs involve the duodenum, with the overwhelming majority located in the third or fourth portion. Atherosclerosis, leading to formation of an aortic aneurysm, remains the most common etiology, accounting for more than 3/4 of the cases reported. Primary aortoenteric fistulae following radiotherapy are rare. The case of a 49-year-old man with aortoduodenal fistula 22 years after para-aortic radiation is presented. In November 1997, the patient suddenly developed hematemesis and melena. Endoscopy suggested the presence of an ulcus but no definitive bleeding source could be seen. Bleeding stopped spontaneously. Six hours later he developed massive hematemesis and was transferred to our department. An emergency operation was performed. We found an aorto-duodenal fistula in the third portion of the duodenum without an aortic aneurysm. We directly sutured the aortic wall laceration and resected the third and fourth part of the duodenum. Histology revealed typical signs of radiation damage. The patient is alive and well 2 years after surgery. To our knowledge, this is the sixth case of a primary aorto-duodenal fistula following radiotherapy ever to be reported in world literature.

[The surgical technique of laparoscopic right hemihepatectomy. Technical aspects and results]. / Chirurgische Technik der laparoskopischen Hemihepatektomie rechts. Machbarkeit und Ergebnisse.

INTRODUCTION: This study compared the technical aspects and results for two different techniques of total laparoscopic anatomical right hemihepatectomy. PATIENTS AND METHODS: From September 2010 to February 2013 a total of 16 patients underwent total laparoscopic right hemihepatectomy at the University Hospital of Freiburg. Of the patients 8 received an intraglissonian approach (IGA) and the other 8 patients an extraglissonian approach (EGA). In the patients of the IGA group, vascular inflow control of the right liver was accomplished by dissection and dividing the right hepatic artery, the right portal vein and the right bile duct separately before parenchymal dissection. In contrast, vascular control for patients in the EGA group was performed by enclosure and transsection of the whole right pedicle using a vascular linear stapler. RESULTS: Indications for right hemihepatectomy were benign tumors in 2 and malignancies in 14 cases. The average maximum tumor diameter was 5.5 cm (range 1.5-10.0 cm). Adequate tumor-free surgical margins (R0) were confirmed in all patients with malignancies. The perioperative mortality rate was 0 %, surgical complications according to Clavien's classification were grade I (n = 1 trocar site superficial wound infection), grade II (n = 2 cholangitis) and grade IIIb (n = 1 wound dehiscence after conversion to open procedure). The median operating time was 366 min (range 265-422 min) and 313 min (range 247-417 min) in the IGA and EGA groups, respectively. Conversion from laparoscopic to open minimal access procedure was necessary in three patients in the IGA group and two patients in the EGA group. Mean intraoperative blood loss was 644 ml (200-1000 ml) and 518 ml (200-1500 ml) in the IGA and EGA groups, respectively. Transfusion of two units of packed red blood cells was necessary for one patient in group EGA. No patient in either group needed a Pringle maneuver. Mean postoperative hospital stay was 11 days (range 7-23 days) and 13 days (range 7-31 days) in the IGA and EGA groups, respectively. CONCLUSIONS: Total laparoscopic anatomical right hemihepatectomy is a feasible procedure. The extraglissonian technique can provide shorter operating times by correctly facilitating vascular control of the right liver.

[Hepatic resection for hepatocellular carcinoma--results and analysis of the current literature]. / Leberresektion beim Hepatozellulären Karzinom - Eigene Ergebnisse und Literaturübersicht.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth-leading cause of cancer death world-wide. Although less frequent in Western Europe, its incidence is increasing in this region. Causes involved in the pathogenesis of HCC are, besides viral hepatitis, metabolic and nutritional factors (alcohol, diabetes, obesity). The therapeutic management depends strongly on the initial extent of disease and includes hepatic resection, liver transplantation and local ablation. In this context, we present our results on liver resection for HCC and a discussion of the current literature about (potentially curative) treatment for HCC. PATIENTS: From 1999 until 2008 93 patients [83 % male, median age 64 (range: 39-94) years] underwent hepatic resection for HCC. Postoperative follow-up was available in 85 patients [median follow-up: 1.2 (0.25-8) years]. RESULTS: In contrast to data, especially from Asia, a viral hepatitis as the origin of HCC was found in only 28 % of the patients in our series. Half of the patients had proven liver cirrhosis. The median number of intrahepatic tumours was one (1-11), median size of the largest tumour was 55 mm (5-250 mm). 58 % of the HCC were removed by atypical or segmental resection, 42 % of the patients underwent hemihepatectomy or extended -hemihepatectomy. Tumor-free resection margins were -achieved in 95 %. Total postoperative morbidity was 61 %. A reoperation for complications was -necessary in 10 %. Hospital mortality was 8.6 % in the entire study period but decreased from 14.9 % in 1999-2004 to 2.2 % in 2005 to 2008 (p = 0.03). Actuarial survival was 81 % after 1 year, 58 % after 3 years and 26 % after 5 years. The T-stage could be identified tendentially as a prognostic factor influencing survival. CONCLUSION: With the proper selection of patients, liver resection for HCC may be performed with a curative intention (i. e., free resection margins) in over 90 %. Although it decreased during the study period peri-operative mortality was higher than after resection of other hepatic tumours. Long-term survival in our series was comparable to reports from other European centres.

ABO-incompatible kidney transplantation with antigen-specific immunoadsorption and rituximab - insights and uncertainties.

Several protocols have been developed to effectively overcome the blood group barrier in renal transplantation. In the evolution of these protocols, one of the latest steps was the combination of anti-CD20 treatment with antigen-specific immunoadsorptions. Over the last years we have learned that these relatively new protocols carry very promising short-term and intermediate-term results which compare favorably to the outcome of ABO-compatible living donor transplantations. Latest reports suggest that combining immunoadsorptions with rituximab does not result in an increased risk of infectious complications or tumors in the first years after transplantation compared to ABO-compatible living donor transplantations. We recently demonstrated that a majority of patients with isoagglutinin titers >1:128 can be safely transplanted using rituximab and immunoadsorptions without an added risk of early antibody-mediated rejections. We have also shown that a cost saving 'on-demand strategy' of postoperative immunoadsorptions based on careful titer monitoring can be used as an alternative to preemptively scheduled immunoadsorptions. Although rituximab and antigen-specific immunoadsorptions are significantly less invasive than splenectomy and plasma-pheresis, long-term follow-up of patients treated with a combination of anti-CD20 antibody and antigen-specific immunoadsorption will be needed to benchmark this therapeutic option in relation to more established protocols.

Release of vancomycin and teicoplanin from a plasticized and resorbable gelatin sponge: in vitro investigation of a new antibiotic delivery system with glycopeptides.

BACKGROUND: The aim of this study was to evaluate the efficacy of sustained release of vancomycin and teicoplanin from a resorbable gelatin glycerol sponge, in order to establish a new delivery system for local anti-infective therapy. MATERIALS AND METHODS: 60 plasticized glycerol gelatin sponges containing either 10 or 20% gelatin (w/v) were incubated in vancomycin or teicoplanin solution at 20 degrees C for either 1 or 24 h. In vitro release properties of the sponges were investigated over a period of 1 week by determining the levels of vancomycin and teicoplanin eluted in plasma using fluorescent polarization immunoassay. The rate constant and the half-life for the antibiotic release of each group were calculated by linear regression assuming first order kinetics. RESULTS: Presoaking for 24 h was associated with a significant increase in the total antibiotic release in all groups opposed to 1 h of incubation, except for the 10% sponges presoaked in teicoplanin. Doubling the gelatin content of the sponges from 10 to 20% significantly increased the total release of antibiotic load only in teicoplanin-containing sponges after 24 h incubation. In all corresponding groups investigated, release of vancomycin was more prolonged compared to teicoplanin, which allowed a gradual release beyond 5 days. The half-life (h +/- SEM) of both types of vancomycin-containing sponges was significantly prolonged by 24 h incubation in comparison to 1 h incubation (29.1 +/- 5.9 vs 5.9 +/- 1.0; p < 0.001, 30.0 +/- 2.1 vs 11.1 +/- 1.9; p < 0.001). However, neither doubling the gelatin content of the sponges nor a prolonged incubation was associated with a significantly prolonged delivery of teicoplanin. CONCLUSION: This study demonstrated a better diffusion-controlled release of vancomycin-impregnated glycerol gelatin sponges compared to those pretreated with teicoplanin. The plasticized glycerol gelatin sponge may be a promising carrier for the application of vancomycin to infected wounds for local anti-infective therapy.

[Pancreas transplantation: a survey on indications, surgical techniques, immunosuppression, complications and outcome]. / Aktueller Stand der Pankreastransplantation: Indikation, operative Technik, Immunsuppression, Komplikationen und Ergebnisse.

Since its introduction in 1966, pancreas transplantation has undergone considerable progress. Refinements in surgical technique, better organ preservation solutions, and more potent immunosuppressive therapies have improved patient and graft-survival rates dramatically. Survival rates for patient and pancreas at 1 year approach 95 and 83 %, resp., for simultaneous pancreas and kidney transplantation, and 97 and 78 %, resp., for pancreas alone. US pancreas graft and patient survival rates do not significantly differ from the results of the European centers. However, there is still a hesitant acceptance of combined pancreas-kidney transplantation in Germany. Combined pancreas-kidney transplantation is nowadays the treatment of choice in carefully selected patients with type 1 insulin-dependent diabetes mellitus and end-stage renal failure. Many US centers even advocate combined transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation significantly improves quality of life and provides excellent long-term glycemic control which halts or even ameliorates secondary diabetic complications such as microangiopathy and neuropathy. In addition, there is increasing evidence that successful pancreas transplantation significantly prolongs patient survival mainly by a reduction of cardiovascular-related mortality. Current 10-year patient survival rate after SPK exceeds 70 %. For diabetics with end-stage renal disease there is no alternative treatment available with comparable live expectancy. However, morbidity and mortality after SPK is still higher than for kidney transplantation alone in the first year. Outcome of isolated pancreas transplantation is also improving but this technique is still restricted to non-uremic patients with severe diabetic complications or with brittle diabetes and severe impairment of quality of life.

[Stomach and rectum replacement with pouches--is less more?]. / Magen- und Rektumersatz mit Pouches--ist weniger mehr?

The effects of pouch reconstruction on long term are dependent not only on the capacity of the pouch, but also on its motility and contractibility. Problems with evacuation of the pouches in the upper and lower abdominal tract may become a major problem in a significant part of the patients. Thus the length of the pouches should be limited to 5 cm at the most in patients with complete rectal resection and to 10-15 cm after gastrectomy. The evacuation profile of the pouches is influenced in addition by the outlet characteristics of the pouch. Finally one should take into consideration that the beneficial effects of pouch reconstruction disappear with time due to adaptation of the bowel after straight reconstruction procedures, while on the other hand the evacuation problems persist.

Pancreas organ transplantation. Short and long-term results in terms of diabetes control.

Diabetes mellitus is a very common and dreadful disease which cannot be cured by exogenous insulin substitution. Many of the patients suffer from recurrent, and sometimes rather dangerous, hypo- or hyperglycemias and, in the long term, from the well-known secondary diabetic complications. At the moment, pancreas transplantation is the only known therapy to reliably reestablish endogenous insulin secretion responsive to normal feed back controls. Within the last decade, pancreas transplantation has evolved as a clinically well-established procedure. Nevertheless, the perioperative risk after pancreas/kidney transplantation is still higher than after isolated kidney transplantation. However, the benefits of a functioning pancreas graft for the patients are enormous. Ten-year survival of type-I diabetic patients with combined pancreas/ kidney grafts is dramatically better than of those with an isolated kidney graft. Long-term function of the pancreas grafts is excellent, reaching more than 60% after 10 years. Contrary to kidney transplantation, chronic rejection does not seem to be a major problem. Blood glucose levels in the fasting state, after glucose challenge, and in the postprandial state are completely normalized. A significant peripheral hyperinsulinemia, however, is found when the pancreas graft is connected to the systemic venous circulation. Thus, portal venous drainage of the pancreas graft, which is already being performed by a few transplant centers routinely, might be the procedure of choice for the future. Beneficial effects on secondary diabetic lesions can only be expected after a rather long observation period. In addition, for all secondary diabetic complications, there is a point of no return. Nevertheless, significant improvement of diabetic polyneuropathy, diabetic nephropathy, and the disturbed microcirculation has been convincingly demonstrated. The effect on diabetic retinopathy, however, is still controversial. One of the most impressive effects for the pancreas graft recipients seems to be the enormous improvement in quality of life, which is reported unanimously by almost all patients. Thus, simultaneous pancreas/kidney transplantation can be regarded as the optimal and only causal therapy for type-I diabetic patients with end-stage renal disease.

Ischemic preconditioning attenuates capillary no-reflow and leukocyte adherence in postischemic pancreatitis.

BACKGROUND AND AIMS: Ischemic preconditioning (IPC) has been shown to protect several organs from ischemia-reperfusion injury. Postischemic microvascular dysfunction is considered to be the key mechanism of early graft pancreatitis after transplantation. The aim of the study was to determine whether brief ischemia and reperfusion before prolonged ischemia followed by reperfusion is protective in respect to microcirculatory derangement in postischemic pancreatitis. METHODS: In an in-situ model of ischemia-reperfusion was induced in the isolated pancreatic tail segment. Wistar rats were randomized to one group ( n=7/group) with 2-h ischemia and reperfusion (I/R) and another group with 10-min ischemia and 10-min reperfusion (IPC) before the prolonged ischemia time. Microcirculation was observed for 2 h by intravital-fluorescence microscopy that analyzed functional capillary density and leukocyte adherence in postcapillary venules. Histological damage was quantified by a semiquantitative score (edema, vacuolization, PMN infiltration, necrosis). RESULTS: IPC resulted in a significant improvement of functional capillary density (248+/-20 vs 372+/-8 cm(-1), P<0.001), a significant reduction in leukocyte adherence in postcapillary venules (476+/-79 vs 179+/-15 cells/mm(2), P<0.001) and in significantly lower histological damage (score 9+/-0.8 vs 5+/-1.4, P<0.001), when compared with the ischemia-reperfusion group. CONCLUSION: IPC reduces pancreatic inflammatory reaction by preservation of postischemic microcirculation. Therefore, it might become a useful procedure before organ procurement in pancreas transplantation.

Characterization of microcirculatory disturbance in a novel model of pancreatic ischemia-reperfusion using intravital fluorescence-microscopy.

INTRODUCTION: Microcirculatory disturbances caused by ischemia-reperfusion injury (IRI) are the crucial hallmarks of pancreatitis following pancreas transplantation. AIMS: To develop a novel rodent model of normothermic in situ ischemia of a pancreatic tail-segment that simulates the clinical situation of pancreas transplantation by flushing the organ via an inserted microcatheter and thus enables selective treatment of the organ via this access. METHODOLOGY: Four experimental groups were investigated (n = 7 Wistar rats/group): sham animals without ischemia and dissection of the pancreas; control animals with dissection of a pancreatic tail segment pedunculated on the splenic vessels and flushing od this segment with saline via a microcatheter; and two groups of animals treated like controls with a pancreatic ischemia time of 1 hour or 2 hours. With use of intravital epifluorescence microscopy, the microcirculatory damage was characterized by investigation of functional capillary density (FCD) and leukocyte adherence in postcapillary venules (LAV) before ischemia and during a reperfusion time of 2 hours. Dry:wet ratio determinations, light microscopy, and electron microscopic investigations were performed to characterize the histologic organ damage. RESULTS: FCD decreased significantly (p < 0.05) 2 hours after reperfusion in the groups of 1-hour (-29.21%) and 2-hour ischemia (-42.73%), in comparison with baseline values. LAV increased significantly (p < 0.05), 4.3- and 5.8-fold, after 1-hour and 2-hour ischemia during the observation time. The histologic damage was similar to posttransplantation pancreatitis in humans 1 hour after reperfusion. In sham and control animals these alterations were not significant. CONCLUSIONS: The rodent in situ model of pancreatic IRI showed standardized microcirculatory damage dependent on the ischemia time. Offering the possibility of selective treatment by the direct artery access to the ischemic pancreatic area, the model enables investigations of questions related to human pancreas transplantation.