Renal graft outcome in combined heart-kidney transplantation compared to kidney transplantation alone: a single-center, matched-control study.

BACKGROUND: Renal allograft outcome in heart-kidney transplantation (HKTx) might be affected by hemodynamic instability and high levels of calcineurin inhibitor-dependent immunosuppression. METHODS: From November 1999 to March 2008, 13 patients who received HKTx were compared with a matched control group of 13 kidney transplantation (KTx) recipients with similar cardiovascular risk factors. Graft function, rejection periods, and patient survival were analyzed. RESULTS: Renal allograft rejection was noted in three patients (23%) after HKTx and in four patients (31%) after KTx. Serum creatinine levels were comparable at 1 week, 1 month, 1, 2, and 3 years after transplantation. Patient survival rates at 1, 2, and 3 years were 100% for HKTx recipients and 100, 92, and 92% for isolated KTx patients. Graft survival was 92% at 1, 2, and 3 years after HKTx and 100% at 1 year and 92% at 2 and 3 years after isolated KTx. CONCLUSIONS: Our results with excellent long-term graft function and survival after combined HKTx indicate that this procedure is a valuable option for a growing number of patients suffering from coexistent cardiac and renal failure.

Pedunculated, well differentiated liposarcoma of the oesophagus mimicking giant fibrovascular polyp.

We present a rare case of a big oesophageal liposarcoma causing dysphagia and weight loss in a 75-year-old patient. Endoscopically, a pedunculated lesion with subtotal obstruction of the oesophageal lumen had been detected and thoracoabdominal oesophageal resection with gastric sleeve reconstruction was performed. Surprisingly, a liposarcoma of the oesophagus was revealed on histopathological analysis, showing MDM2 overexpression. Oncological follow-up has been uneventful and the patient remains in good clinical shape at 15 months after surgery.

Reconstruction of ureteral necrosis in kidney transplantation using an ileum interposition.

PURPOSE: Ureteral necrosis is a serious problem in kidney transplantation. Sometimes re-ureterocystostomy is possible, while other cases require an elaborate reconstruction to maintain kidney function. We report our experience with ileum interposition for ureteral reconstruction. METHODS: After 9 years of dialysis treatment a 58-year-old patient was grafted using the left kidney of a 59-year-old donor with a cold ischemic time of 9.5 hours. The early postoperative course was uneventful apart from delayed graft function. Immunosuppression consisted of an IL-2-receptor antibody, calcineurin inhibitor, mycophenolate mofetil, and corticosteroids. Discharge serum creatinine was 2.3 mg/dL. In month 4 the patient showed a pararenal urinoma; cystoscopy revealed necrosis of the distal ureter. Operative revision showed urine leakage from the renal pelvis through the urinoma into the bladder. As the whole ureter was necrotic, a re-ureterocystostomy was not possible. The patient's own ureter had been extirpated, and the bladder was too small to do a direct anastomosis between it and the kidney. Consequently, an ileum interposition was performed. RESULTS: The postoperative course was uneventful. Kidney function was stable with a nadir creatinine concentration of 2.0 mg/dL 18 months' posttransplantation, and 14 months' post ileal interposition the kidney function was still satisfactory, with a creatinine level of 2.0 mg/dL. CONCLUSION: Ureteral necrosis is a serious complication following kidney transplantation. Whenever a re-ureterocystostomy or an uretero-ureterostomy is not possible, the interposition of the ileal segment represented a safe procedure to deal with this problem.

Acute liver failure: from bench to bedside.

Acute liver failure constitutes a challenge to clinicians and scientists alike. The course of the disease, usually unpredictable and polarizing, is associated with a high mortality unless liver transplantation is feasible, but can end in a spontaneous restitution. It poses many scientific questions regarding the mechanisms of liver cell damage and regeneration and the possibility of new therapeutic approaches. However, the performance of clinical studies in patients in acute liver failure presents problems because of the varied etiology, the small number of cases, and furthermore due to ethical and logistical difficulties. For this reason experimental investigations have gained a special importance. Arising from the improved understanding of the mechanisms of liver cell damage in acute liver failure, which may be primarily due not to the initial noxious agent alone but may also be triggered secondarily by the release of proinflammatory mediators, there are numerous options for liver cell protection, some of which have already proved successful in experimental studies. New insights into the mechanisms of regulation of liver regeneration and the physiological liver mass, gathered in particular from experimental models of partial hepatectomy and by the use of gene-manipulated animals, have contributed to the development of new therapeutic approaches for the stimulation of liver cell regeneration. Temporary liver support systems have already been successfully employed in some cases under clinical conditions. Although the systematic experimental investigation of many of the questions of acute liver failure has significantly contributed to a better understanding of liver cell damage and regeneration, the application of this new knowledge to clinical practice is to some extent made difficult by the artificial simplification that experimental studies inevitably entail and needs to be validated by controlled clinical studies.

[Timing of esophagectomy in multimodal therapy of esophageal cancer: Impact of time interval between neoadjuvant therapy and surgery on outcome and response]. / Therapiepause in der multimodalen Behandlung des Ösophaguskarzinoms : Einfluss des Intervalls zwischen neoadjuvanter Therapie und Resektion auf Outcome und Response.

BACKGROUND: Neoadjuvant radiochemotherapy [n(R)CT] has become the standard of care in the multimodal therapy concept for patients with locally advanced esophageal cancer; however, optimal timing of surgery is not clearly defined. OBJECTIVES: The study analyzed whether the length of the interval between completion of n(R)CT and surgery can affect the postoperative outcome, tumor response and long-term survival. MATERIAL AND METHODS: A total of 106 patients with adenocarcinoma and squamous cell carcinoma of the esophagus, treated between 2006 and 2013, were included in this study. On the basis of the median time interval to surgery, patients were divided into two groups [group A ≤ 40 days (n = 54) and group B > 40 days (n = 52)] and compared concerning demographic data, preoperative risk scores, morbidity, outcome, tumor response and long-term survival. RESULTS: The groups were comparable in terms of demographics, preoperative condition of the patients, complications and outcome; however, group A showed a trend towards a higher mortality risk as preoperatively assessed by the physiological and operative severity score for the enumeration of mortality and morbidity in esophagogastric surgery patients (O-POSSUM) (p = 0.064) and group B showed a trend towards a higher rate of complete responders (p = 0.097). CONCLUSION: Concerning perioperative morbidity and mortality, delayed surgery after n(R)CT showed no benefit for the patient's outcome; however, the rate of complete tumor response was higher in patients with a time interval of more than 40 days, although this did not influence long-term survival or recurrence rates.

Achilles tendon healing: long-term biomechanical effects of postoperative mobilization and immobilization in a new mouse model.

The aim of the study was to investigate the long-term effects of postoperative immobilization as opposed to mobilization on the biomechanical attributes of healing Achilles tendons in a new experimental mouse model. In 114 Balb-C-mice the left Achilles tendon was transected and sutured by the Kirchmayr-Kessler technique. The tendons healed either under postoperative immobilization effected by fixing the upper ankle joint in equinus position or under mobilization through a limited range of movement. The contralateral Achilles tendons served as internal control. All tendons were tested biomechanically at short intervals up to the 112th postoperative day in terms of load to failure [N], tendon deflection [mm] and tendon stiffness [N/mm], and were evaluated histologically after 8 and 112 days. Postoperative mobilization resulted in a continuous and significantly more rapid restoration of load to failure in comparison to the immobilization group. Tendon deflection was decreased by postoperative mobilization, whereas under immobilization it paradoxically increased still further in the later course. After 112 days the tendons of the mobilization group had regained their original tendon stiffness, whereas the tendons after immobilization reached only about half the values seen in the control tendons. Histologically, postoperative mobilization led to increased immigration of inflammatory cells in the early phase. In the late phase, as compared to immobilization, tendon structure was more mature, with fibre bundles arranged in parallel and interposed tendocytes. Tensile loading of the healing tendon by postoperative mobilization leads to fundamental changes in the biological process of tendon healing resulting in accelerated restoration of load to failure and reduced tendon deflection.

Surgical techniques of orthotopic rat liver transplantation.

Liver transplantation in rats is frequently used as a transplantation model. Although liver transplantation in larger laboratory animals such as dogs and pigs is technically easier, the rat has become the most important subject for experimental liver transplantation because of the availability of genetically defined animals. Numerous surgical techniques have been developed that permit the investigator to carry out studies with high clinical relevance. In this article the principal models of orthotopic rat liver transplantation and their technical modifications of vessel anastomoses, rearterialization, and bile duct reconstruction techniques are reviewed. More than 20 transplantation models are described in detail and demonstrated with clear illustrations. Finally, the advantages and uses of all the surgical procedures (e.g., suture and cuff anastomoses, bile duct anastomoses, and rearterialization techniques), specific problems, and survival criteria are discussed and the experiences of investigators who applied these techniques are analyzed. In conclusion, an overview and critical evaluation of all surgical techniques of orthotopic rat liver transplantation are given, together with instructions for learning these techniques.

Hepatic vein catheterization: a new technique in rats.

Blood samples taken directly from the hepatic veins are often required for evaluation of liver function or ischemia/reperfusion injury and for direct determination of metabolic products of the liver. In the rat, blood samples are usually obtained by direct puncture of the hepatic veins. Successful catheterization of these small vessels is only possible under direct vision because great dexterity is needed to persuade the catheter to enter the hepatic vein. In this report a procedure for hepatic vein catheterization under direct vision is described in the rat. After performing a median laparotomy, a flexible catheter (Buchbinder, 3.0 F/1 mm, as used in cardiology) with a bent end is inserted into the infrahepatic vena cava. Under direct vision through the thin walls of the inferior vena cava the bent end of the catheter is slowly pushed up until the tip slides into a hepatic vein, which opens into the inferior vena cava at a right angle. Selective catheterization of the desired hepatic vein is possible by rotating the catheter and changing the position of its tip. This is a reliable new technique of hepatic vein catheterization in rats, by which blood samples can be collected directly from the hepatic veins.

Liver bridging techniques in the treatment of acute liver failure.

The introduction of orthotopic liver transplantation in the management of acute liver failure has dramatically increased the survival rates of patients at the cost of removing the patient's native liver and life-long dependence on immunosuppression. However, it is well known that in many patients with acute liver failure the diseased liver has the potential to recover. Death in these patients is often due to increased intra-cranial pressure or infection. Liver bridging techniques are assigned to temporarily provide liver function and enable the native liver to recover in patients with acute liver failure. They represent an attractive alternative to conventional liver transplantation in the management of acute liver failure, since after recovery of the native liver the patient is freed from immuno-suppression with all associated side-effects and risks. Auxiliary liver transplantation, artificial liver support devices and hepatocyte transplantation represent different ways of bridging liver function in acute liver failure. The aim of this review is to present the ideas and principles of these three different liver bridging techniques. We will discuss the relative importance and the future potential of theses bridging techniques in the treatment of acute liver failure by comparing the experimental and clinical results.

Laparoscopic fluorometry: a new minimally invasive tool for investigation of the intestinal microcirculation.

The aim of this study was to develop and establish a new system of laparoscopic fluorometry for the purpose of investigating the intestinal microcirculation. In 25 pigs (German Landrace, 16-25 kg body weight), ischemia was established in two segments (A, irreversible; B, reversible ischemia; C, internal control) of the small intestine by a laparoscopic technique. Microcirculation in the segments was assessed by laparoscopy at a second-look operation 24 h later by means of the fluorescence system Endoscan. The fluorescence of the three bowel segments was measured by arbitrary dye fluorescence units (DFU) 15 min after starting reperfusion, before and after injection of sodium fluorescein (NaFlu, 0.25 mg/kg body weight). The dividing line between viable and nonviable bowel tissue was established from the inflow and outflow rates of NaFlu with the aid of ROC (receiver operating characteristic) curves. The specificity and sensitivity of the new method were evaluated by correlating the results with the viability of each intestinal segment as predicted by three laparoscopically experienced surgeons and by histological examination. By means of the calculated separation sharpness (fluorescence index at 2 min >0.5, outflow factor of NaFlu at 10 min >20%), the overall predictions of intestinal viability in all 25 animals achieved a sensitivity of 93.5% and a specificity of 94.1% by laparoscopic fluorometry, versus a sensitivity of 70.8% and a specificity of 87.5% for the prediction of bowel viability by ordinary laparoscopic technique. Used as an adjunct to conventional laparoscopy, laparoscopic fluorometry brought significant gains in sensitivity and specificity in the distinction between reversible and irreversible intestinal ischemia.

Protective effects of ambroxol in hypothermic liver preservation: a transplant study.

The bronchosecretolytic agent ambroxol added to histidine-tryptophan-ketoglutarate (HTK) solution has recently been shown to protect cold stored rat hepatocytes. The aim of the present study was to confirm these observations in a rat liver transplantation model. Before orthotopic liver transplantation, donor livers from 30 syngeneic Wistar rats were assigned to three groups (n = 10): (A) in situ flush (ISF) and 1/2-h cold storage (CS) with HTK solution, (B) ISF and 3-h CS with HTK, and (C) ISF and 3-h CS with HTK + 10(-3) mol/L ambroxol. The efficacy of the drug was evaluated by postoperative survival (> 14 days) and liver enzyme release (ALT), bile flow, histomorphological injury, and malondialdehyde (MDA) level in the grafts 15 min after reperfusion. After 1/2-h CS with HTK solution (A), 90% of the transplanted rats survived. In comparison with donor conditions, bile flow in the reperfused grafts decreased to 87 +/- 5.3%, whereas postoperative ALT levels slightly increased. After 3-h HTK preservation (B), the survival rate decreased to 60%, while ALT values markedly increased and bile flow after reperfusion declined to 82 +/- 6.6%. Ambroxol added to HTK solution (C) enhanced bile flow to 106 +/- 3.4%(p < .05), and reduced ALT and MDA levels and histomorphological injury of the transplanted livers, so that its beneficial effect in organ preservation has been confirmed in the transplant model. However, survival rate was not improved by the agent, probably because of the low cold ischemia tolerance of the Wistar rat livers used.

A new clamping technique for biomechanical testing of tendons in small animals. aprobst@uni-muenster.de.

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n = 15). When tested by the new clamping technique, 17 tendons ruptured intratendinously at a mean tensile force of 8.4 +/- 1.1 N. Three Achilles tendons (17%) tore at the site of paper fixation and had to be excluded from investigation. Data from 73% of the measurements fixed by gluing had to be excluded because slippage of the proximal tendon fibers and contamination of the tendon with glue occurred. All the conventionally clamped tendons ruptured at the site of fixation at a mean tensile force of 6.1 +/- 2.3 N (p < .05). This was 30% lower than with the new clamping technique. Thus, the newly developed clamping technique enables investigators to obtain more valid biomechanical studies of the murine Achilles tendon.

Development and evaluation of an experimental model for investigating the pathogenesis and therapeutic strategies of acute liver failure.

Because of the various etiologies of acute liver failure (ALF) a clinically relevant model must fulfill four criteria--reversibility, reproducibility, ALF-induced death, and a sufficient time interval for diagnosis and therapy between induction and death. In this study an experimental model was evaluated for these criteria. A total of 49 rats were randomized into seven groups: First, a pilot study was performed regarding the survival rate after different treatments: In group I, animals underwent a 70% liver resection. In group II, 70% liver resection was combined with ascending doses of postoperative endotoxin administration up to 400 microg/kg (group IIc). In group III, animals only underwent liver mobilization. In group IV, ALF was induced according to the protocol of group IIc, but with additional treatment of an endothelin-A-receptor (ETAR) antagonist. Animals in group V received only 400 microg endotoxin. After induction of ALF, all animals died within the first day, showing significantly elevated bilirubin and ammonium levels and severe damage to hepatocellular integrity. Application of the ETAR antagonist resulted in the survival of 6/7 animals until the 14th day; the biochemical and histomorphological changes were reversible. All other animals survived to the 14th day. A clinically relevant model of ALF in rats can be created by the combination of 70% liver resection and endotoxin application to produce an inflammatory component.

Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infection after kidney transplantation.

BACKGROUND: Urinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. METHODS: Twenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs. RESULTS: All patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n = 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected. CONCLUSIONS: The use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.

Gender and strain-specific differences in the development of steatosis in rats.

Non-alcoholic fatty liver disease (NAFLD) is a common problem with a wide variety of phenotypes. While its pathogenesis is still not fully understood, several risk factors for disease progression have been identified. Therefore, defining adequate animal models may serve to unreveal the pathogenesis in NAFLD. We studied Lewis and Sprague-Dawley rats of both genders (n = 6) fed standard (Std) or high-fat (HF) diet for three weeks. Disease stage was assessed by haematoxylin-eosin, Azan Heidenheim and Oil-Red staining, apoptosis by single-stranded DNA (ssDNA) detection and liver regeneration by Ki-67 staining. Serum markers of liver injury and lipid metabolism including adipocytokines were analysed. Livers of both strains and genders fed with HF diet demonstrated evidence of steatosis. Lewis rats developed microvesicular steatosis whereas Sprague-Dawley rats presented macrovesicular steatosis accompanied by pronounced fibrosis. Female gender of both strains was associated with lower steatosis grade and higher proliferation rate (P < 0.05). Gender-specific differences were most prominent in Lewis rats on a HF diet, where females showed lower alkaline phosphatase, cholesterol, triglyceride and leptin levels and a more favourable low-density lipoprotein/high-density lipoprotein ratio than males (P < 0.05). Reverse transcriptase-polymerase chain reaction analysis was performed to demonstrate changes in expression of various genes important for liver regeneration, fibrosis and steatosis. HF diet induced downregulation of proangiogenic genes such as vascular endothelial growth factor receptor 1 and 2 (P < 0.05) in males was not present in females. In conclusion, strain and gender served major roles in disease progression. These differences should be considered when designing studies and may offer new ways to advance therapeutic strategies.

Timing of conversion to mammalian target of rapamycin inhibitors is crucial in liver transplant recipients with impaired renal function at transplantation.

BACKGROUND: Renal dysfunction, primarily related to long-term use of calcineurin inhibitor-based immunosuppression, is the most common complication after liver transplantation. OBJECTIVE: To evaluate whether liver transplant recipients with impaired kidney function at transplantation can benefit from early conversion to mammalian target of rapamycin inhibitor therapy (mTORi) compared with patients with late induction of mTORi-based therapy. MATERIALS AND METHODS: Between 2003 and 2008, therapy was changed to an mTORi-based regimen in 57 patients. Patients were divided into 4 groups: group 1, early conversion (≤3 months after orthotopic liver transplantation) to mTORi therapy, and with impaired perioperative renal function; group 2, early conversion to mTORi therapy, and with normal perioperative renal function; group 3, late conversion to mTORi therapy, and with impaired perioperative renal function; and group 4, late conversion to mTORi therapy, and with normal perioperative renal function. RESULTS: One month after conversion, the mean (SD) increase in calculated glomerular filtration rate in groups 1 (early conversion) and 3 (late conversion) was comparable: 8 (9) mL/min vs 7 (10) mL/min. At month 3, the increase in calculated glomerular filtration rate between groups 1 and 3 was significant (15 [11] mL/min vs 9 [15] mL/min; P = .04), an effect that persisted at month 6 (16 [12] mL/min vs 10 [12] mL/min; P = .05) and month 12 (22 [14] mL/min vs 12 [15] mL/min; P = .04). CONCLUSION: In liver transplant recipients with perioperatively impaired renal function, early conversion to mTORi therapy should be performed because this approach seems to be more effective in improving long-term renal function.