Hannes P. Neeff

Solitary fibrous tumour of the liver: case report and review of the literature

BackgroundSolitary fibrous tumours (SFTs) of the liver are very rare entities. Although firstly described to be tumours of pleural origin, SFTs have been reported in various organs such as the meninges, orbit, upper respiratory tract, thyroid, peritoneum, retroperitoneum and soft tissues. Histologically, this tumour often shows alternating cellular and relatively acellular areas. The cellular areas show a wide variety of patterns, making it difficult for it to be differentiated from other mesenchymal tumours. Its immunohistochemical positivity for CD34 and vimentin is believed to be unique. Histiogenesis of SFTs, however, is not yet fully understood. They are known to be usually benign, with only few reports indicating their ability to metastasize.Patients and methodsWe review the literature on SFTs of the liver and report on the case of a 63-year-old female patient with a large SFT of the right liver.ConclusionsSurgical resection seems to be the treatment of choice. Local recurrence is scarce. Due to the very limited number of cases, data regarding the long-term survival of patients are lacking.

Effects of Organ Preservation, Ischemia Time and Caspase Inhibition on Apoptosis and Microcirculation in Rat Pancreas Transplantation

This study was undertaken to examine the impact of ischemia‐reperfusion (I/R) injury on microcirculation and apoptosis in experimental pancreas transplantation. Pancreatic grafts were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6‐h CITs (group U6); UW, 18‐h CITs (group U18); normal saline, 6‐h CITs (group S6); and normal saline, 6‐h CITs with Z‐Asp‐2,6‐dichlorobenzoyloxymethylketone (pan‐caspase inhibitor; group S6 & CI). Nontransplanted animals served as controls. At 1‐ and 2‐h reperfusion microcirculation was assessed by means of intravital microscopy. Apoptosis was detected by in situ nick end‐labeling method (TUNEL) at 2‐h reperfusion. Deterioration of microcirculation was lowest in group U6 and highest in groups S6 and S6 & CI compared with controls. The apoptotic index (cells per high power fields) of groups U6, U18 and S6 correlated well with functional capillary density (r=− 0,70, p < 0.0001) and leucocyte sticking (r= 0,69, p < 0.0001) at 1‐h reperfusion. Caspase inhibition had no impact on microcirculation but significantly reduced AI compared with group S6 (p < 0.001). These data suggest that pancreatic I/R injury‐induced apoptotic cell death well predicts the extent microcirculatory impairment. Caspase inhibition might be a promising strategy in reducing I/R injury in pancreas transplantation.

Autosomal Dominant Polycystic Kidney Disease: Prevalence of Renal Neoplasias in Surgical Kidney Specimens

Background: The role of autosomal dominant polycystic kidney disease (ADPKD) as a risk factor for renal cell carcinoma (RCC) is still under discussion. Data on prevalence of RCC in ADPKD are limited, especially on a large population scale. The aim of this study was to analyze the prevalence of RCC in ADPKD kidneys and characterize the clinical features of this coincidence. Methods: Based on our histopathological registry for ADPKD and the Else Kröner-Fresenius Registry, we retrospectively reviewed malignant and benign renal lesions in patients with ADPKD who had undergone renal surgery from 1988 to 2011. Results: 240 ADPKD patients underwent 301 renal surgeries. Mean age at surgery was 54 years. Overall, 16 malignant and 11 benign lesions were analyzed in 301 kidneys (5.3%; 3.7%), meaning that 12/240 (5%; 1:20) patients presented with malignant renal lesions. 66.7% (8/12) of these patients had undergone dialysis prior to surgery. We found 10/16 (63%) papillary RCC, 5/16 (31%) clear cell RCC, and 1/16 (6%) papillary noninvasive urothelial cancer. Regarding all renal lesions, 6/17 (35.3%) patients had more than one histological finding in their kidneys. In 2 cases, metachronous metastases were removed. Mean follow-up was 66.7 months. Conclusion: Kidney-related prevalence of RCC in ADPKD kidneys was surprisingly high. Whether or not this is due to chronic dialysis or due to the underlying disease is still speculative. Like other cystic renal diseases with an increased risk for RCC, the attending physician should be aware of the malignant potential of ADPKD, especially with concomitant dialysis.

[Hepatic resection for hepatocellular carcinoma--results and analysis of the current literature].

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.

One hundred consecutive kidney transplantations with simultaneous ipsilateral nephrectomy in patients with autosomal dominant polycystic kidney disease

PURPOSE Surgical management of autosomal dominant polycystic kidney disease (ADPKD) in patients awaiting renal transplantation is a challenging task. METHODS From 1998 to 2009, a total of 100 consecutive renal transplantations with simultaneous unilateral nephrectomy were performed in 59 men and 41 women with ADPKD and end-stage renal failure. About 38% received kidney allografts from living donors. The ipsilateral polycystic kidney was removed at the time of renal transplantation. Immunosuppressive therapy was not modified. Cold ischaemia time was 155 (38-204 min) versus 910 min (95-2760 min) for living versus deceased donor transplantation. Mean weight of removed kidneys was 2002 g (414-8850 g). Mean follow-up was 3.0 years (0.8-10.0 years). RESULTS Overall patient and graft survival were 97 and 96% at 1 year and 93 and 80% at 5 years, respectively. Serum creatinine at current follow-up was 1.49 (0.8-2.8) mg/dL. Surgical complications, which might be associated with simultaneous nephrectomy requiring re-operation, occurred in 12% (lymphocele 4%, hernia 4%, post-operative haematoma or bleeding 4%). None of the patients died peri-operatively. CONCLUSION Renal transplantation with simultaneous unilateral nephrectomy in ADPKD is a reasonable procedure for patients suffering from massively enlarged native kidneys.

Characterization of ischemia/reperfusion-induced gene expression in experimental pancreas transplantation.

Background. The aim of this study was to identify genes that are differentially expressed in the early period after pancreatic cold ischemia/reperfusion (I/R) injury. Methods. Grafts of isogeneic rat pancreaticoduodenal transplantation were subjected to different preservation solutions and cold ischemia times (CITs): University of Wisconsin (UW), 6-hour CIT; UW, 18-hour CIT; and physiologic saline solution, 6-hour CIT. Animals that did not receive transplants served as controls. At 2-hour reperfusion, grafts were removed and pancreatic RNA was isolated, pooled, and hybridized to Affymetrix RG-U34A arrays. Quantitative reverse-transcription polymerase chain reaction was used to confirm the results of microarray technology. Results. A total of 49 genes were consistently upregulated (more than threefold) in all three groups of transplant recipient animals. Prominent genes include transcription factors; cytoskeletal factors; heat-shock proteins (e.g. Hsp27, Hsp90); molecules involved in inflammation (e.g. PAPIII), immunology, signal transduction, and translation; and genes that have not been associated with I/R injury so far (e.g. Best5). Messenger RNA levels of some genes were exclusively downregulated in response to the different conditions applied to the pancreatic grafts: Cybb, Reg3a, Per2, BMAL1, MAP, and Isl2. Conclusions. These results provide new insight in I/R–induced gene expression after experimental pancreas transplantation. The reported upregulation of heat shock proteins, Best5, and PAPIII may play a pathologic role in pancreatic cold I/R injury and could therefore provide a promising perspective for further investigations.

Heterotopic Pancreatitis with Obstruction of the Major Duodenal Papilla - A Rare Trigger of Obstructive Orthotopic Pancreatitis

Background: Heterotopic pancreas appears in 0.5 to 13% of autopsies. The most frequent locations are stomach, duodenum or upper jejunum. Pancreatitis in heterotopic pancreas is rarely described, and clinical symptoms caused by this heterotopic inflammation are uncommon. Method: We report a case of heterotopic pancreatitis localized in the major duodenal papilla causing biliary obstruction and mimicking a pancreatic head tumor. Clinically and radiologically, malignancy was suspected. Preoperative biopsies showed only fibrosis. A pylorus preserving resection of the pancreatic head was performed followed by an uneventful postoperative course. Result: Macroscopically, in the periampullary region on the pancreatic side a thickened duodenal wall with multiple lobules and cysts was found, compressing the common bile duct. Microscopic examination showed heterotopic pancreas with inflammatory lesions surrounding the ampulla. In the orthotopic pancreas a diffuse chronic pancreatitis with marked inflammation, fibrosis and atrophy of exocrine tissue was found. Conclusion: In our case it was impossible to differentiate between chronic pancreatitis and pancreas carcinoma preoperatively. Radiological findings and endoscopic biopsies were not sufficient to distinguish heterotopic pancreatitis from other tumors of the pancreatic head. Clear diagnosis could only be made by complete histological examinations after pancreatic head resection, being the treatment of choice for pancreatic head tumors of unclear dignity. The differential diagnosis of heterotopic pancreatitis as trigger of unclear enlargement of the pancreatic head is very seldom.

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.

In vivo quantification of oxygen‐free radical release in experimental pancreas transplantation

Reactive oxygen species (ROS) were drawn to the attention in the setting of organ transplantation when the ‘injury hypothesis’ postulated a link between oxidative stress and the activation of the innate immunity of the recipient. While the occurrence of ROS during organ transplantation is undoubted, their onset and magnitude remain largely unknown. We therefore measured ROS using a novel cyclic hydroxylamine spin probe CMH (1‐hydroxy‐3‐ methoxycarbonyl‐2,2,5,5‐tetramethylpyrrolidine) during syngeneic experimental pancreas transplantation in rats in vivo. Organs were subjected to two different cold preservation methods [University of Wisconsin preservation solution (UW) or normal saline] for 18 h. During the first 90 min of reperfusion, samples were collected and analysed using electron paramagnetic resonance signalling. Isolated blood‐free perfused organs (IPO) were used for comparison. Analysis showed that it is feasible to detect ROS using CMH spin probes. While IPO organs displayed a very early ROS release, there was no ROS increase in the UW preserved group compared to NaCl. These findings were in line with conventional markers of organ damage such as serum lactate, glucose, potassium as well as tissue ATP levels. CMH spin probes might become a useful tool for the in vivo animal testing of antioxidative substances in models of solid organ transplantation.

Organ procurement in experimental pancreas transplantation with minimal microcirculatory impairment.

Background: Ischemia-reperfusion injury has been shown to deteriorate microcirculation in experimental pancreas transplantation. However, minor concern was taken on the impact of organ procurement in this condition. We examined the impact of a standardized technique of organ procurement on microcirculation and apoptosis in experimental pancreas transplantation. Methods: Male Lewis rats were divided into three groups: sham-operated animals without dissection of the pancreas served as controls (n = 5); animals undergoing nearly total process of organ procurement with the pancreas pedunculated on the aorta and the hepatoduodenal ligament (n = 7), and animals receiving pancreaticoduodenal transplantation. Pancreatic grafts were preserved for 6 h in cold University of Wisconsin solution (n = 7). At 1 and 2 h reperfusion and in time-matched controls, microcirculation was assessed by means of intravital fluorescence microscopy. Tissue samples were obtained after 2 h measurement and DNA breaks of acinar cells were detected by in situ nick end-labeling (TUNEL assay). The apoptotic index (apoptotic cells per high- power fields; hpf) was quantified by microscopic counting of at least 50 hpf. Results: Assessment of functional capillary density (FCD) in animals undergoing subtotal process of organ procurement revealed a slight non-significant decrease at 1 and 2 h compared with controls. In addition, leukocyte sticking to postcapillary venules (LAV) as well as the apoptotic index were found slightly increased after organ procurement compared with controls (p > 0.05). However, after pancreas transplantation the apoptotic index and the LAV were significantly increased and the FCD significantly decreased compared with both groups of non-transplanted animals (p < 0.01). Conclusions: Our validated technique of organ procurement does not negatively impact microcirculation and apoptosis in experimental pancreas transplantation.