[Gastric ulcer suspected of being a carcinoma]. / Karzinomverdächtiges Magenulkus.

Following hepatic penetration by a gastric ulcer a pitfall diagnosis of gastric adenocarcinoma can result from a biopsy of the ulcer base. In cases of suspicious "hepatoid" epithelial cells in a gastric biopsy, the possibility of regular liver tissue from a gastric ulcer penetrating the liver should be kept in mind and verified, e.g. by immunohistochemistry.

Colonic ischaemia as a severe Shiga toxin/verotoxin producing Escherichia coli O104:H4 complication in a patient without haemolytic uraemic syndrome, Germany, June 2011.

An increasing rate of infections with Shiga toxin/verotoxin-producing Escherichia coli (STEC/VTEC) O104:H4 has been observed in Germany since May 2011, with unusually high numbers of patients suffering from haemolytic uraemic syndrome (HUS). We report a STEC/VTEC O104:H4 case without HUS, presenting with colonic ischaemia demanding surgery. This atypical clinical presentation of STEC O104:H4 infection might indicate new severe complications associated with this uncommon strain, and highlights the importance of immediate interdisciplinary assessment of STEC/VTEC patients.

[Lambliasis as differential diagnosis of MARSH type 3b]. / Lamblieninfektion als Differenzialdiagnose der Zöliakie in der Duodenalbiopsie.

Giardia lamblia is the most common human parasite with a worldwide distribution and fecal-oral way of transmission. Diagnostic procedures include stool examination and gastroduodenoscopy with biopsy or secret aspiration. In most cases histology reveals a dense accumulation of the parasites on the surface of the duodenal mucosa with no or only slight inflammation. In rare cases, a dense inflammatory infiltrate with severe mucosal atrophy and increased count of intraepithelial lymphocytes may be seen. If in such cases the amount of parasites is low, the histological picture may mimic celiac disease. The two presented cases demonstrate the close morphological relationship and show the importance of considering giardiasis in the differential diagnosis in patients with suspected celiac disease.

Stability changes after cryosurgery in long tubular bones in correlation to histological results: an animal trial.

STUDY QUESTION: Pathologic bone fractures in cryosurgery of bone tumors have been described in literature. This study utilizing a sheep model should prove the possible reduction of potential fracture while using a new miniature cryoprobe minimizing tissue damage and providing accurate control of the ablation process. Furthermore, postoperative histological changes should be investigated and the results correlated with the stability trials. METHODS: In 24 sheep, ablation of the femur and the tibial bone on one side was carried out. Ablation of the right femur was limited to an area of 2 cm(2) with single cortical bone, whereas at the left tibia the whole proximal tibial plateau was included. The other side served as a control entity without cryoablation. After a period of 2, 4, and 6 months postoperative investigation of bending resistance of the femoral bone and of compression resistance of the tibial bone as well as histological findings were done in eight animals each. RESULTS: After 2 months there was a significant difference (P < 0.05) regarding compression resistance between the treated and the contralateral tibia, whereas the bending resistance in the treated femur was slightly lower than on the contralateral side. After 4 and 6 months the cryo-treated part showed a tendency towards weakness. Histological findings showed bone necrosis with slight beginning repair after 2 months. Four and six months later, bone necrosis still existed with increasing development of woven bone and conversion into lamellar bone. DISCUSSION: A thorough control of the freezing process and the low iatrogenous weakening of the bone due to placing the probe when modern miniature cryoprobes are used can minimize the risk of pathological postoperative fractures. However, at least 2 months after operation there is histological proof of bone healing with appropriate reduction of bone stability, which should be considered for the clinical application of this new technique.

Competition between native liver and graft in auxiliary liver transplantation in a rat model.

The competition between the native and the grafted liver in heterotopic auxiliary liver transplantation (HALT) with portal vein arterialization (PVA) was investigated in a rat model. The experimental groups were: HALT with flow-regulated PVA and 70% resection of a native liver and graft (n = 32; group I) versus 70% liver resection (n = 32; group II). After HALT, the weight of the native liver increased until the sixth postoperative week (431% +/- 55% of the intraoperative weight), whereas, the graft weight was only 76% +/- 31% of the intraoperative weight at this time. In group II, liver weight increased continuously to 529% +/- 30% of the intraoperative weight after 6 weeks. On postoperative day 2, there was significantly increased proliferative hepatocellular activity in all groups. This was highest in the resected livers of group II, followed by the native livers of group I, and the grafts of group I (301 +/- 126 vs 262 +/- 97 vs 216 +/- 31 Ki-67-positive hepatocytes/10 visual fields). However, the differences between the groups were not significant. With regard to hepatocellular apoptosis, the livers were similar among all groups and at all time points, M30-positive hepatocyte counts were

Postoperative fulminant varicella zoster virus hepatitis with fatal outcome: a case report.

INTRODUCTION: Fulminant hepatitis due to varicella zoster virus (VZV) infection has a poor prognosis although an effective treatment is available. CASE REPORT: We present a case of fulminant hepatic failure (FHF) as a result of disseminated VZV infection in a long-term alcoholic patient who underwent laryngectomy and radical neck dissection due to squamous cell carcinoma of the larynx. Post-mortem examination revealed the diagnosis of fulminant hepatitis and infection with VZV. Viral inclusion bodies were found in the hypopharyngeal mucosa as well as in the liver tissue. In these tissues VZV was detected by PCR. The clinical presentation is suggestive for a reactivation of VZV without cutaneous signs of herpes zoster during a state of immunosuppression. DISCUSSION: Differential diagnosis comprises hepatitis by other Herpes group viruses and toxic hepatic injury.

Induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant viruses.

Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)-cloned virus constructs [MCMV-SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)-promoter control, MCMV-GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV-ie promoter control, MCMV-HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40-promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter-gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post-infection in immunocompetent mice. In situ, the reporter-gene products beta-galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV-induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct.

[Primary cholangiocarcinoma in a case of Caroli's disease: case report and literature review]. / Primäres Cholangiokarzinom auf dem Boden einer Caroli-Erkrankung. Fallbericht und Literaturübersicht.

Caroli's disease is a liver disease with segmental cystic dilatation of the intrahepatic bile ducts. It belongs to the group of congenital ductal plate malformations. With an incidence of only 0.05% of all liver cases in the Liver Registry of the University of Cologne, it is a very rare disorder. Caroli's disease is usually combined with cholangitis and bile duct stones. Control of these infections and maintenance of biliary drainage are the main therapeutic aims. The development of intra epithelial neoplasia and invasive carcinoma are rare complications. We report a case of Caroli's disease with the development of cholangiocarcinoma and review the literature.

[Primary infection with Epstein-Barr virus in a 77-year-old patient with B symptoms and hepatitis -- a case report]. / 77-jähriger Patient mit Epstein-Barr-Virus-Erstinfektion mit B-Symptomatik und Hepatitis -- ein Fallbericht.

Epstein-Barr virus (EBV) infection has a prevalence of 90 % and is - depending on the immune status of the host - associated with a broad spectrum of clinical manifestations. By presenting a case report we would like to demonstrate an unusual clinical course of a primary infection with EBV in an elderly patient. A 77-year-old patient was admitted to hospital in reduced health condition because of a persisting bronchopulmonary infection with B symptoms. The patient had already been treated with antibiotics. Because of elevated liver enzymes, a liver biopsy was performed. Histopathology revealed moderate acute hepatitis with cholangitis und endothelialitis, pointing to an EBV-induced hepatitis. Serological examinations confirmed the diagnosis, revealing a primary infection with positive EBV VCA IgM and IgG. EBV PCR of the liver tissue was positive, viral genome could be demonstrated within lymphocytes. A short period later the patient was discharged to reconvalescence. This case report demonstrates an unusual primary infection with EBV at the age of 77 with atypical clinical symptoms and hepatitis. The relevance of EBV in the differential diagnosis of atypical infectious diseases with hepatitis of unknown aetiology is strengthened on taking data reports from the literature into consideration.

Portal hyperperfusion causes disturbance of microcirculation and increased rate of hepatocellular apoptosis: investigations in heterotopic rat liver transplantation with portal vein arterialization.

Clinical results of portal vein arterialization (PVA) in liver transplantation are controversial. One reason for this is the lack of a standardized flow regulation. Our experiments in rats compared PVA with blood-flow regulation to PVA with hyperperfusion in heterotopic auxiliary liver transplantation (HALT). In group I (n = 19), the graft's portal vein was completely arterialized via the right renal artery in-stent technique, using a 0.3-mm stent, leading to a physiological average portal blood flow. In group II (n = 19), a 0.5-mm stent was used. In group II, the average portal blood flow after reperfusion was significantly elevated (group II: 6.4 +/- 1.5; group I: 1.7 +/- 0.4 mL/min/g of liver weight; P < .001). The sinusoidal diameter after reperfusion was significantly greater in group II (9.8 +/- 0.5 microm) than in group I (5.5 +/- 0.2 microm; P < .001). Red blood cell velocity in the dilated sinusoids was significantly lower in group II (171 +/- 18 microm/s) than in group I (252 +/- 13 microm/s). Stasis of erythrocytes occurred; consequently, the functional sinusoidal density was significantly reduced in group II (38 +/- 7%) compared with group I (50 +/- 3%; P < .01). Two hours after reperfusion of the portal vein, the number of apoptotic hepatocytes was significantly higher in group II than in group I (I: 0 +/- 0 vs II: 7 +/- 9 M30-positive hepatocytes/10 high-power fields). The 6-week survival rate was 9 of 11 in both groups. In group II, 6 of 9 grafts showed massive hepatocellular necroses after 6 weeks, whereas in group I, only 1 of 9 presented a slight hepatocellular necrosis. Finally, our results demonstrate negative effects of portal hyperperfusion in transplanted livers, which are correctable by adequate flow regulation.

[Morphology of drug induced liver damage]. / Morphologische Veränderungen der medikamenteninduzierten Leberschädigung.

Hepatotoxicity is a significant complication of therapeutic drug use. As ist can imitate nearly all hepatopathies, the diagnosis of drug-induced liver disease is difficult. Most often, it is a diagnosis of exclusion. The following morphological changes are known, dependent on the target cell type: acute and chronic hepatitis, granuloma formation, and fatty liver disease, cholestatic type acute and chronic liver damage with or without inflammation,or mixed forms of liver injury. Portal or perisinusoidal fibrosis can occur following each type of liver damage. Vascular changes or neoplasms are rare. Drug induced liver injuries are more likely induced by type B damage, which is not expected and cannot be reproduced in animal testing. Type A damage, which is known from toxicity assays, is less likely. A specific therapeutic regime is not available. Therefore, early recognition and cessation of the use of the drug is necessary.

Intratumoral application of standardized mistletoe extracts down regulates tumor weight via decreased cell proliferation, increased apoptosis and necrosis in a murine model.

The cytotoxic in vitro activity of standardized mistletoe extracts (ME) was examined by established assays towards the human ductal breast carcinoma cell line BT474. A dose-dependent (optimum 25 mg/mL medium) and significantly (p < 0.05) enhanced cytotoxic activity towards the BT474 cells was demonstrated. In vivo experiments on the antitumor activity of ME-A and ME-M were performed in a BALB/c-mouse / BT474 ductal breast carcinoma model. ME-A and ME-M were intratumorally administered according to an application schedule which was found to be optimal concerning dosage and time of administration. Standardized intratumoral application of ME-A and ME-M induced a significantly (p < 0.05) decreased tumor weight in experimental mice. Histological investigations were performed comprising analysis of mitosis and proliferation rates (Ki67 expression), as well as necrosis and apoptosis induction (ssDNA detection). As compared to tumors of control mice with intratumoral phosphate-buffered saline (PBS) injections, tumors of the ME-A and ME-M treated groups showed a decreased cell proliferation rate, as well as an increased cell necrosis and apoptosis rate. Standardized mistletoe extracts, interfering with defined tumor cell functions, e.g., proliferation, necrosis and apoptosis, may have an impact on local cancer treatment.

[Liver metastases: incidence and histogenesis]. / Lebermetastasen: Inzidenz und histogenetische Einordnung.

Metastases are the most common malignant tumors of the liver. In the files of the Institute of Pathology of the University of Cologne 12,161 liver tissue cases are registered. Of them, 1,357 cases (11.2%) showed tumors or tumor like masses. Liver metastases of solid tumors were the largest group of the neoplasias with 611 cases (5.0%) followed by hepatocellular carcinoma (380 cases; 3.1%). Other entities were rare and include cholangiolar carcinoma (0.5%), vascular tumors (0.4%), lymphomas (0.4%), focal nodular hyperplasias (0.36%) and liver cell adenomas (0.23%). Adenocarcinomaa are the largest group of metastases with 400 cases (65.5%). 48.2% of this group were metastases of colorectal cancer, 13.5% of pancreatic cancer, 13% of breast cancer, 6.2% of gastric cancer, 4.5% of lung cancer and 3.7% of esophageal cancer. Neuroendocrine carcinomas are the second largest group with 16% of liver filiae. Other entities were rarely found. Metastases in cirrhotic livers are seldom. The gross findings, the histology, the differential diagnosis including immunohistochemistry and the value of the liver biopsy is discussed.

Successful use of sirolimus in a patient with bulky ovarian metastasis of hepatocellular carcinoma after liver transplantation.

This 44-year-old woman developed multifocal hepatocellular carcinoma (HCC) within hepatitis B-induced liver cirrhosis. At the time of listing for transplantation the HCC had progressed beyond the Milan criteria. Due to her young age, high grade of histological differentiation according to biopsy, and lack of therapeutic alternatives, she was listed for transplantation. She received an organ from the Eurotransplant marginal liver list. Immunosuppression was reduced to tacrolimus monotherapy within 4 months. Five months after transplantation bilateral bulky ovarian metastases were seen on computed tomography (CT) scan. A bilateral salphingo-oophorectomy was performed and immunosuppression switched to sirolimus monotherapy. Fourteen months after this procedure and 19 months after transplantation, the patient is asymptomatic with stable liver function. She is free of recurrence as judged by CT scan, bone scan, and alpha-fetoprotein. In conclusion, radical surgical treatment and immunosuppression using sirolimus may achieve tumor-free survival in selected patients with advanced or recurrent HCC.

[Report of a spindle cell myoepithelialioma of the minor salivary glands with extensive lipomatous component]. / Spindelzelliges Myoepitheliom der kleinen Speicheldrüsen mit ausgeprägter lipomatöser Komponente.

Myoepitheliomas of the salivary glands are rare benign tumors composed of spindle-shaped myoepithelial cells, but may show plasmacytoid, epitheloid and clear cell-types that principally exhibit myoepithelial but not ductal differentiation. These tumors are mainly located in the major salivary glands and have sometimes abundant, acellular, mucoid or hyaline stroma but lack chondroid and myxochondroid foci, probably representing the one end of the spectrum of pleomorphic adenoma. Lipomatosis in the form of isolated small islands or scattered single lipocytes, is quite uncommon, and a large amount of adipose tissue in a pleomorphic adenoma and myoepithelioma is a rarity and only described in major salivary glands. We present the case report of a 38-year old man with a myoepithelioma of the minor palatinal salivary glands with extensive lipomatosis as an example of this rare phenomena.

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

BACKGROUND: The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA. METHODS: Twelve pigs underwent RFA adjacent to the right bile duct. After placement of an intraductal cooling catheter and a RFA probe, pigs were randomized to cooling or no cooling. Intraductal temperature was measured in all animals. The bile ducts were assessed by magnetic resonance imaging (MRI) and cholangiography 1 and 28 days after the procedure. RESULTS: Intraductal cooling abolished the increase of intraductal temperature seen in the absence of cooling. Concurrent cholangiography and MRI showed a biliary lesion in one of six pigs subjected to intraductal cooling and in five of six without cooling (P = 0.040). The biliary injuries were barely visible by MRI on day 1 but were clearly visible on day 28. CONCLUSION: Intraductal cooling can prevent biliary injury induced by RFA. The exact parameters for intraductal cooling require further investigation to establish the best compromise between bile duct protection and complete ablation of surrounding tissue.

[Magnetic resonance tomogography after cryotherapy of long bones in an animal model]. / Magnetresonanztomographie nach Kryoablation langer Röhrenknochen im Tiermodell.

PURPOSE: To describe the MR findings following cryoablation of long bones. MATERIALS AND METHOD: Cryoablation was performed in femoral and tibial bones of 24 sheep under general anesthesia. MRI of the treated and untreated contralateral bones was performed immediately thereafter and at 2, 4 and 6 months after the cryosurgical procedure. RESULTS: On the MRI performed immediately after cryotherapy, the lesions showed low signal intensities relative to the normal bone marrow on unenhanced T1- and T2-weighted images. At 2, 4 and 6 months after cryoablation, the lesions showed high signal intensities on STIR images, low signal intensities on T1-weighted and heterogeneous enhancement on contrast-enhanced T1-weighted MR images. The femoral lesions decreased in size from 31 +/- 3 mm immediately after the cryotherapy to 13 +/- 4 mm 6 month later and the tibial lesions from 29 +/- 7 mm to 19 +/- 4 mm. CONCLUSION: MRI shows bone marrow lesions immediately after cryotherapy and can easily monitor healing lesions. MR imaging is suitable for following cryotherapy.

[Clear cell tumor of the lung]. / Klarzelltumor der Lunge. Problem der Schnellschnittdiagnostik.

Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45 positive tumor cells. It has been proposed that clear cell tumors generate from perivascular epithelioid cells which are also found in renal angiomyolipoma. Due to its morphologic epithelioid features with clear cytoplasm the distinction from either primary or metastatic clear cell carcinoma is difficult. Usually clinical investigations do not lead to the final diagnosis so that only subsequent histological examination and immunophenotyping can establish the correct tumor classification. We describe the case of a 52 year old woman who underwent exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen sections a solid trabecular tumor was diagnosed, paraffin histology and immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of the correct diagnosis of the clear cell tumor of the lung in frozen sections is discussed as well as the differential diagnosis.