A hepatoid carcinoma of the pancreatic head.

Hepatoid carcinoma (HC) is an extremely rare form of neoplasm. Its cellular structure resembles that of a hepatocellular carcinoma (HCC). To date, only 26 cases of hepatoid carcinoma of the pancreas have been reported in the literature. We report the diagnosis of a hepatoid carcinoma of the pancreatic head in a 78-year-old male patient. The tumor was detected incidentally during routine abdominal ultrasound scanning. Laboratory tests did not show any abnormalities except for a monoclonal gammopathy of undetermined significance. After CT, MRI, and laparoscopic biopsy that failed to obtain the diagnosis, the patient underwent a Whipple procedure. The final pathology report described a hepatoid carcinoma of the pancreatic head (pathological T3, N0 (0/10), L0, V0, R0, M0). After the patient recovered, no further therapy was recommended by the tumor board and he was discharged. Regular follow-up was suggested; however, the patient suddenly died of acute coronary artery disease 2 months after surgery.

A patient with a hyperechoic band-shaped structure in the right hepatic vein.

Cement (polymethylmethacrylat) is frequently and increasingly used in vertebral surgery. Complications can occur by spillage of this material; however the vast majority of the patients remain free of symptoms and do not require any specific therapy.Internists, gastroenterologists and radiologists regularly performing abdominal ultrasound and computed tomography should be aware of this complication.A case of spillage of cement in the right hepatic vein is presented.

Endoscopic procedures in patients under clopidogrel or dual antiplatelet therapy: a survey among German gastroenterologists and current guidelines.

BACKGROUND: Because of the higher risk of bleeding, guidelines recommend cessation of clopidogrel seven days prior to high-risk endoscopic procedures. However, premature cessation of clopidogrel may lead to catastrophic cardiovascular sequelae due to stent thrombosis. We aimed to assess the current clinical practice among German gastroenterologists regarding endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy. METHODS: A 10-item questionnaire on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy was sent by e-mail to all 220 members of the ALGK. RESULTS: 73 (33 %) chief gastroenterologists returned completed questionnaires, 35 (48 %) of whom conduct high-volume endoscopic units performing more than 4000 procedures per annum. 62 (85 %) endoscopic units perform endoscopic biopsies under clopidogrel alone, while just in 30 (41 %) departments biopsies are carried out under dual antiplatelet therapy. In 36 (49 %) GI-units endoscopic polypectomy under clopidogrel monotherapy is performed, in contrast to only 4 (5.5 %) in the case of combined antiplatelet therapy. However, in emergency situations more than 60 % of all participants do perform endoscopic sphincterotomy in patients under clopidogrel/dual antiplatelet therapy. Percutaneous endoscopic gastrostomy is carried out in 32 endoscopic units (44 %) under clopidogrel monotherapy, but only in 4 (5.5 %) under dual antiplatelet therapy. CONCLUSION: Current guidelines on endoscopic procedures in patients under clopidogrel/dual antiplatelet therapy are mainly based on expert opinion and therefore, backed by only weak evidence. Our survey shows that in this setting the clinical decision making takes place on an individual basis, as there are no data to support the recommendations of the present guidelines.

Spontaneous intramural small-bowel hematoma secondary to anticoagulant therapy: a case series.

Spontaneous small-bowel hematomas most commonly involve the jejunum, followed by the ileum and duodenum, and occur in patients who receive excessive anticoagulation with phenprocoumon/warfarin or who have additional risk factors for bleeding. We report three cases of intramural small-bowel hematoma, all complications of treatment with phenprocoumon, which nowadays is used extensively for therapeutic and prophylactic purposes. Diagnosis can be readily attained by sonography and confirmed using computed tomography. Early diagnosis is crucial because most patients can be treated successfully without surgery. Based on this experience and data from the literature, conservative treatment is recommended for intramural intestinal hematomas, when other complications needing laparotomy have been excluded.

[Partial thrombosis of the inferior vena cava in a patient with non-Hodgkin lymphoma and history of lumbar spine surgery]. / V.-cava-inferior-Thrombose bei Patientin mit Non-Hodgkin-Lymphom und stattgefundener Wirbelsäulenoperation.

Complete or partial thrombosis of the inferior vena cava is usually due to pre-existing malformation of the vessel, malignant tumors, ascending thrombosis, or thrombophilic disorders. We report the case of an 81-year-old woman, in whom a partial thrombosis of the vena cava was observed in the CT scan when re-staging was performed after six cycles of R-CHOP because of high-grade malignant non-Hodgkin lymphoma. Before chemotherapy was started, the patient had undergone an operation of the lumbar spine using cement augmentation. Retrospective analysis showed that cement had penetrated a segmental vein and spilled into the vena cava leading to formation of an adhering blood thrombus. The patient was free of symptoms and anticoagulation was started. Spillage of cement frequently occurs in the process of vertebroplasty and kyphoplasty and may result in serious sequelae. As these procedures are increasingly being used, physicians should be aware of these complications if a patient presents with thrombosis of the caval vein or signs of pulmonary embolism.

[Acute haemoperitoneum due to spontaneous tumour rupture as first manifestation of hepatocellular carcinoma]. / Akutes Hämoperitoneum bei einer spontanen Tumorruptur als Erstmanifestation eines hepatozellulären Karzinoms.

HCC rupture with potentially fatal haemoperitoneum is not an infrequent complication of primary hepaotcellular carcinoma with a prevalence between 2.9 and 26 % and must be considered in the differential diagnosis in all patients with acute haemoperitoneum. Spontaneous tumour rupture is the most common cause, although the pathogenesis of it is not completely understood. Because of the high mortality of an emergency tumour resection, it appears that a two-stage treatment approach with emergency TAE and subsequent elective hepatic resection is the safest and most effective strategy for the management of this life-threatening situation. Despite all therapeutic efforts, the prognosis of this severe complication still remains poor. We report on a 82-year-old patient with spontaneous tumour rupture as the first manifestation of liver cell carcinoma. Our patient represents an exception because his spontaneous HCC rupture occurred without concomitant liver cirrhosis. According to our knowledge this case report is the first publication on spontaneous HCC rupture without pre-existing liver cirrhosis.

[Clinical usefulness and diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin]. / Klinischer Nutzen und diagnostische Bedeutung der Leberbiopsie bei chronisch erhöhten Leberwerten nicht viraler Genese.

BACKGROUND: In the context of increasing non-invasive diagnostic techniques the purpose of the present study was to determine the clinical usefulness and the diagnostic value of percutaneous liver biopsy in patients with chronically elevated liver enzymes of non-viral origin. PATIENTS AND METHODS: 100 patients from the outpatient clinic of the department of gastroenterology and hepatology who had a liver biopsy in the years 1996 to 1998 because of chronically elevated alanine-aminotransferase (ALT) and/or gamma-glutamyltransferase (gamma-GT) levels were included. Exclusion criteria were as follows: chronic hepatitis B or C infection, focal liver disease and clinical signs of hepatic decompensation. Retrospectively gained clinical data were independently evaluated by two experienced hepatologists. Initially, both examiners made a preliminary clinical diagnosis prior to knowing results from liver histology. With the results from liver histology both examiners were asked to make a final diagnosis. For each patient, the preliminary clinical diagnoses of both examiners were then correlated with the corresponding final diagnoses. RESULTS: Liver histology led in 71 % respectively 74 % of the patients to confirmation or specification of the clinical diagnosis. Liver biopsy was particularly helpful in differentiating non-decompensated liver cirrhosis, cryptogenic hepatitis, auto-immune hepatitis and biliary diseases. CONCLUSION: Despite improved non-invasive diagnostic tools including a broad spectrum of serologic tests liver biopsy is often indispensable for differentiating primary liver from biliary diseases and for the early detection of patients with liver cirrhosis.

Progressive sclerosing cholangitis after septic shock: a new variant of vanishing bile duct disorders.

BACKGROUND: We present nine patients with progressive sclerosing cholangitis after septic shock. PATIENTS: All nine patients had previously required long term treatment in an intensive care unit for septic shock: two patients with polytrauma, five with burn injury, and two with extensive surgery. They were admitted to our hospital because of cholangitis. Endoscopic retrograde cholangiography revealed severe intrahepatic stenoses in all patients and liver biopsies showed typical signs of sclerosing cholangitis. No patient had pre-existing liver disease. RESULTS: Mean follow up time was 35 months. In patients with major bile duct stenoses (3/9), 12 endoscopic dilations were performed in total. In one patient, concrements were extracted and intermittent stenting was necessary. To date, 4/9 patients have rapidly developed liver cirrhosis. During follow up, 5/9 patients died: two after fulminant cholangitis, one after liver failure, one due to liver transplantation associated problems, and one after cerebral ischaemia. One patient has been registered for transplantation and the remaining three patients show no acute signs of liver failure. CONCLUSIONS: Patients with sclerosing cholangitis, following septic shock, represent a new variant of vanishing bile duct disorders. In such patients liver disease rapidly progresses to cirrhosis. Endoscopic treatment may only transiently improve the course of the disease. Orthotopic liver transplantation is indicated in end stage disease.

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study.

BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Expression of apoptosis and apoptosis-related peptides in various stages of rejection in the human transplanted liver.

BACKGROUND/AIMS: In the transplanted liver, the role of apoptosis and apoptosis-related proteins are largely unknown. This study addresses the question whether hepatocyte or leukocyte apoptosis plays an important role in acute rejection of the transplanted human liver and which pathways are involved. METHODOLOGY: Cryosections from liver biopsies with acute rejection were stained with the TUNEL technique for detection of apoptosis and labeled immunohistochemically with antibodies against CD95, bcl-2, TGF-beta and iNOS. A double-labeling protocol was developed for simultaneous detection of iNOS and apoptosis. Liver tissue with chronic viral hepatitis, with hepatitis reinfection and tissue without pathological findings served as a control. RESULTS: Leukocyte apoptosis was markedly reduced in severe compared to mild or moderate acute rejection. Hepatocyte apoptosis is detected rarely in acute rejection with a slight increase from mild to severe despite a strong expression of CD95 and TGF-beta on hepatocytes. The hepatocyte expression of iNOS is weak in acute rejection but strong in control slides with hepatitis B/C reinfection. In acute rejection, simultaneous expression of iNOS and apoptosis could be demonstrated in Kupffer-cells. CONCLUSIONS: Severe acute rejection in the human transplanted liver is characterized by a lack of apoptosis of infiltrating portal lymphocytes probably caused by a reduced downregulation of lymphocyte function. Secondly, in spite of the strong expression of CD95 and TGF-alpha, hepatocyte apoptosis plays a limited role for liver damage in acute rejection. Finally, Kupffer cell apoptosis is increased in acute rejection and seems to be induced by nitric oxide.

[Angiomyolipoma of the liver]. / Angiomyolipom der Leber.

HISTORY AND ADMISSION FINDINGS: A 66-year-old woman, known for 4 years to have a space-occupying lesion in the liver thought to be a lipoma, was admitted because the increasing size of the mass. She was hypertensive and had recurrent supraventricular tachycardia, but was otherwise asymptomatic and physical examination was unremarkable. INVESTIGATIONS: Laboratory tests were within normal limits. Abdominal ultrasound demonstrated a well-circumscribed, echodense space-occupying lesion. Magnetic resonance imaging revealed a hyperintense encapsulated tumour with contrast-medium enhancement. DIAGNOSIS AND TREATMENT: Because the imaging tests were equivocal, a segmental liver resection was performed to exclude malignancy. Histological examination revealed an angiomyolipoma of the liver. CONCLUSION: Angiolipoma is a benign mixed-cell tumour that very rarely affects the liver but must be included in the differential diagnosis of hepatic space-occupying lesions. Its manifestations may be highly variable and histological examination is required if there is any uncertainty about possible malignancy. If the biopsy is diagnostic of a benign lesion, expectant observation with regular monitoring is indicated.

Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.

An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease. Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems. A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons. Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins. This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies of HCV and the development of antiviral drugs.

Clinical relevance of hepatitis G virus (HGV) infection in heart transplant patients.

To investigate whether the recently discovered hepatitis G virus (HGV) influences the clinical outcome of heart transplant recipients under immunosuppression, we determined the prevalence of HGV infections correlated with liver function and survival in 51 patients. Presence of HGV RNA and anti-E2, a marker for resolved HGV infection, were serially tested in sera from patients before and after heart transplantation (HTX) by nested RT-PCR and ELISA. Four of 51 (7.8%) patients before transplantation, and 22 of 50 patients (44%) after transplantation showed signs of persistent or resolved HGV infection. HGV infection was not associated with impairment of liver function or with patient survival. In summary, presence of HGV infection does not influence the clinical outcome in heart transplant patients.

Hepatotropism of GB virus C (GBV-C): GBV-C replication in human hepatocytes and cells of human hepatoma cell lines.

BACKGROUND/AIMS: Recently, GB virus C (GBV-C) has been identified as another virus potentially causing viral hepatitis. However, its hepatotropism and pattern of infection in humans is still unknown. To elucidate the presence and replication of GBV-C in the human liver, we investigated tissue samples of six explanted livers from five GBV-C mono- or GBV-C/HCV co-infected patients for GBV-C RNA plus- and minus-strand RNA. METHODS: These tissues were examined using nested RT-PCR followed by Southern blot hybridization as well as fluorescence in situ hybridization on liver cryosections. To further substantiate susceptibility of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C mono-infected serum was performed. RESULTS: By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 liver specimens (4/5 patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA could be detected in 4 of 6 liver specimens (4/5 patients). One liver sample was negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in situ hybridization. Virus infection appeared to be restricted to hepatocytes and detection of minus-strand RNA showed viral replication in a few highly infected liver cells. In vitro infection of HepG2 or HuH7 cells confirmed these findings by a release of virions into supernatant. CONCLUSION: In conclusion, our results establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin in vivo and in vitro.