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H Lobeck

Publications and source records attributed to H Lobeck.

At least 37 records · Page 2Linked to original sources
PubMed1998

p53 mutagenesis in Klatskin tumors.

Mutagenesis of the p53 tumor-suppressor gene represents the most common genetic alteration in human malignancies but has not yet been investigated in Klatskin tumors. Cancerous and normal liver tissues were obtained from 12 patients after surgical resection of Klatsin tumors. Genomic DNA was extracted and served as a template for PCR amplification and sequencing of a 1,574-bp fragment of the p53 gene comprising the exons 5 through 8. Immunohistochemical expression analysis was performed using five different antibodies. Missense mutations were detected in 2 of 12 patients--one transversion on codon 273 (Arg --> Leu) and a transition on codon 168 (His --> Arg). In all specimens, immunohistochemistry was negative regarding a nuclear overexpression. An apparent clinicopathologic impact of p53 mutations was not observed. This report on mutagenesis of the p53 gene in Klatskin tumors shows that the most commonly mutated tumor suppressor gene in human cancers is also mutated in a subset of patients with Klatskin tumors. Assessment of a clinical or pathological impact of p53 mutagenesis on Klatskin tumors requires evaluation in larger studies.

Adult↗
PubMed1998

Biphasic spiral computed tomography for detection of hepatocellular carcinoma before resection or orthotopic liver transplantation.

RATIONALE AND OBJECTIVES: The authors correlate computed tomography (CT) findings in biphasic spiral technique with histopathology in patients with hepatocellular carcinoma (HCC) who had undergone liver resection (LR) or orthotopic liver transplantation (OLT). METHODS: Preoperative biphasic spiral CT findings in 33 consecutive patients (23 men, 10 women, aged 43-74 years; LR group: n = 17; OLT group; n = 16) with liver cirrhosis and HCC were reviewed retrospectively by consensus of two radiologists and correlated with pathology from liver specimens. RESULTS: Of the 16 patients in the OLT group with 1 to 5 confirmed HCC lesions (total lesions: 29; mean lesion diameter: 2 cm; range: 0.6-5.0 cm), CT before OLT depicted 22 lesions in 15 patients (sensitivity for lesions with a diameter of 0.5-1.0 cm, 20%; for lesions 1.1-2.0 cm, 82%; and for lesions 2.1-3.0 cm and > 3.0 cm, 86% and 100%, respectively). Among the 17 patients in the LR group (total lesions: 21; mean lesion diameter: 5.4 cm; range: 1.0-11.0 cm), CT detected 18 lesions. Lesion-by-lesion sensitivity, as correlated with pathology, was calculated at 76% and 86% in the OLT and LR groups, respectively (overall sensitivity, 80%). The diameter of CT detected lesions, compared with liver specimens, corresponded in 90% of lesions (maximum deviation, 15%). Characteristic CT findings of HCC included unenhanced hypoattenuating focal liver lesions (32 lesions), with hyperattenuation (38 lesions) in the arterial phase of contrast material administration. CONCLUSIONS: Biphasic spiral CT for preoperative HCC detection correlated with pathology in 80%, thus proving this technique to represent a sensitive imaging modality for pretherapeutic evaluation of HCC.

Adult↗
PubMed1998

[L-arginine administration improves mucosal structure in the early phase of reperfusion of small intestine transplants].

L-arginine and molsidomine application prior to reperfusion significantly reduced the preservation and reperfusion-related injury after small bowel transplantation. The architecture of the mucosa was best preserved after treatment with L-arginine and methylprednisolone. The macroscopic appearance of the mucosa was improved (less watery and less thin than after reperfusion of non-treated recipients). The histological appearance was improved. But the most prominent changes were observed by antilaminin staining showing an almost normal architecture of the basement membrane compared with compressed and thickened basement membrane structures in non-treated recipients. This was accompanied by a decrease in CD44-expression within the villi cores and crypts 20 minutes and 24 hours after reperfusion. The release of hyaluronic acid into the plasma was also lower after treatment with L-arginine and molsidomine in combination with methylprednisolone than in non-treated recipients. These improvements may result from increased NO-production by L-arginine which may scavenge superoxid anions. The latter are known intermediates that cause significant injury at the endothelial level and at the extracellular matrix including the basement membrane.

Animals↗
PubMed1998

A randomized, placebo-controlled trial with anti-interleukin-2 receptor antibody for immunosuppressive induction therapy after liver transplantation.

The introduction of quadruple induction therapy after liver transplantation with the murine anti-interleukin-2 receptor (IL-2R) antibody (BT563) has decreased the incidence of serious side effects, such as tachycardia, hypertension, rash, fever and nausea since it does not lyse its target cell. To investigate the immunosuppressive efficacy of BT563, a placebo-controlled trial was performed and BT563 was added to the standard triple induction after liver transplantation. Forty consecutive recipients of primary orthotopic liver transplants (OLT) (median age 47 yr [range 18-65]) were randomized. All patients received triple immunosuppression with cyclosporine A (CyA), prednisolone (PRED) and azathioprine (AZA). In addition, 19 patients received BT563 (Biotest, Dreieich, Germany) at a dose of 10 mg/d from day 0 until day 12. The remaining 21 patients received a placebo infusion at the same days after transplantation. Minimal follow-up for all patients was 3 yr. Patient survival at 3 yr was 74% in the BT563 group and 90% in placebo group. Similar results were observed for graft survival. Two acute rejection episodes were detected in the BT563 group and 9 acute rejections (5 steroid-resistant) were observed in the placebo group (p < 0.034). The incidences of sepsis, pneumonia, cholangitis, urinary tract infections as well as cytomegalo-virus (CMV) infections were similar in both groups. Side effects of the BT563 therapy and/or post-transplant lymphoproliferative disease (PTLD) were not detected. Quadruple induction therapy with BT563 significantly reduces the incidence of rejection episodes after liver transplantation, while infectious complications and/or PTLD is not increased. Therefore, the anti-IL2 receptor antibody BT563 constitutes a safe and efficient addition to the immunosuppressive induction regimen following OLT.

Acute Disease↗
PubMed1997

[Stenosis of the terminal ileum. Endometriosis as the differential diagnosis of Crohn's disease].

HISTORY AND CLINICAL FINDINGS: A 25-year-old woman had for 5 years complained of lower and mid-abdominal pain, at first monthly but later continuous and gradually increasing in severity. At the same time she had diarrhoea associated with nausea, vomiting and weight loss. Physical examination showed a markedly distended abdomen, diffuse pain on pressure over the whole abdomen, most marked in the left middle and lower part, and high pitched peristalsis, but was otherwise unremarkable. INVESTIGATIONS: Abdominal radiography indicated small-intestinal ileus, while ultrasound revealed absent peristalsis in the small intestine and a 10 cm stenosis in the terminal ileum. Coloscopy demonstrated a fibrosed stenosis of the terminal ileum but a biopsy showed no specific changes. TREATMENT AND COURSE: Under suspicion of Crohn's disease with stenosis of the terminal ileum a partial resection of the ileum was performed. The ileum was on inspection thickened with scar tissue but no inflammation. Histology revealed florid chronic mucosal and submucosal inflammation, haemorrhages and ulcers, as well as numerous islands of endometriosis in the subserosa and muscularis propria. CONCLUSION: Endometriosis is a rare disease in women of the reproductive age, but should be considered in the differential diagnosis of Crohn's disease of the terminal ileum.

Adult↗
PubMed1997

A prospective randomized trial comparing interleukin-2 receptor antibody versus antithymocyte globulin as part of a quadruple immunosuppressive induction therapy following orthotopic liver transplantation.

BACKGROUND: Quadruple immunosuppressive induction therapy has been shown to markedly reduce the incidence of acute rejection episodes without increasing the incidence of infectious complications after liver transplantation. However, the use of polyclonal antibody preparations (e.g. antithymocyte globulin [ATG]) is associated with side effects such as fever and tachycardia. To evaluate the efficacy and the safety of a monoclonal antibody directed against the interleukin-2 receptor (BT563) in comparison with ATG as part of a quadruple induction regimen, a prospective, randomized study was conducted. METHODS: Eighty consecutive adult recipients of primary orthotopic liver transplants were randomized to receive either BT563 (10 mg/day; days 0-12; n=39) or ATG (5 mg/kg/day; days 0-6; n=41) in addition to the standard immunosuppressive protocol consisting of cyclosporine, and prednisolone, and azathioprine. RESULTS: Patients treated with BT563 had a significantly lower incidence of steroid-sensitive rejection episodes (3 vs. 11; P<0.025) and also significantly fewer drug-related side effects (4 vs. 18, P<0.038) when compared with patients treated with ATG. The incidence of infectious complications was not different between the two groups. Patient survival did not differ significantly between the two groups (84.6% at 1, 2, and 3 years in the BT563 group and 90.2% at 1 year and 87.8% at 2 and 3 years for the ATG group). Analysis of graft function showed an advantage for the BT563 group in terms of postoperative bilirubin levels. However, no differences were observed in long-term follow-up between the two groups. CONCLUSIONS: Our results indicate that treatment with anti-interleukin-2 receptor antibody as part of quadruple induction therapy after orthotopic liver transplantation is safe and effective and shows fewer steroid-sensitive rejection episodes as well as fewer side effects when compared with quadruple induction therapy including ATG.

Adult↗
PubMed1997

A pretransplant infection with precore mutants of hepatitis B virus does not influence the outcome of orthotopic liver transplantation in patients on high dose anti-hepatitis B virus surface antigen immunoprophylaxis.

Hepatitis B virus (HBV) infection of the liver graft is a major complication after orthotopic liver transplantation (OLT) for HBV-related cirrhosis. A high viral load before OLT is a known risk factor, whereas the relevance of precore mutants of HBV is a subject of controversy. The aim of this study was to correlate the pretransplantation viral load and a pretransplantation infection with precore mutant HBV (pmHBV) or wildtype HBV (wtHBV) with allograft damage, graft failure, and survival after OLT. Sixty-nine patients with HBV cirrhosis underwent OLT under high dose immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulins (HBIg). A pretransplantation infection with pmHBV and wtHBV was detected by polymerase chain reaction (PCR) and direct sequencing in 30 patients each (pmHBV and wtHBV group). Nine of 69 patients were PCR-negative (noHBV group). Median pretransplantation levels of HBV DNA assessed by hybridization assay were 42 pg/mL for pmHBV and 54 pg/mL for wtHBV patients. HBV recurred in 17 of 30 (57%) of pmHBV and in 14 of 30 (47%) of wtHBV patients and graft failure occurred in 6 of 30 (20%) of pmHBV and 7 of 30 (23%) of wtHBV patients. Neither HBV recurrence nor graft failure occurred in patients in whom no HBV DNA could be detected by PCR using primers flanking the HBV precore region (noHBV) patients. Allograft damage assessed by histology activity index (HAI) scoring was median 6 for pmHBV and 7 for wtHBV patients. Cumulative survival after 5 years was 72% for pmHBV, 74% for wtHBV, and 100% for noHBV patients. In this study, we provide evidence that pretransplantation viral load, but not infection with pmHBV, determines the outcome after OLT in patients on high dose HBIg prophylaxis.

Adult↗
PubMed1997

[HIV-associated salivary gland diseases. Review of the literature and 3 case reports].

HIV-associated salivary gland disease (HIV-SGD) includes lymphoepithelial lesions and cysts involving the salivary gland tissue and/or intraglandular lymph nodes, and Sjögren-like conditions. Three cases of salivary gland disease occurring in HIV-infected patients are reported. Histopathological examination showed squamous epithelium-lined cysts. In the walls of the cysts lymphoid tissue, epitheloid granulomas and giant cells were found. The clinical and histopathological criteria as well as magnetic resonance imaging and therapy are discussed.

AIDS-Related Opportunistic Infections↗
PubMed1997

[Intra-abdominal schwannoma. Diagnosis and surgical therapy].

We report three patients who were operated on because of an intraabdominal schwannoma between February 1991 and October 1994 in our department. In the first case, a benign gastric schwannoma was treated by a distal gastric resection (Billroth II); the main symptom was gastric bleeding. In the second case, a malignant duodenal schwannoma with liver metastasis was treated by wide en-bloc resection of the tumor including retroperitoneal lymphadenectomy and an anatomical resection of the right lobe of the liver. A metachronous metastasis of the liver, appearing 7 months postoperatively, was treated by intraparenchymatous laser coagulation; a local recurrence, appearing 19 months postoperatively, led to another tumor resection. The main symptom was a palpable intraabdominal mass in this case. In the third case, a malignant schwannoma of the abdominal wall was resected in fragments in another clinic. Six months later a local recurrence with infiltration of the liver appeared in spite of postoperative radiation and was resected en bloc. Early peritoneal sarcomatosis was apparent at that time. Postoperative chemotherapy did not prevent quick progression of the tumor. The patient died 18 months after the first operation. The clinical presentation, differential diagnosis and operative strategy for benign and malignant intraabdominal schwannomas are discussed.

Abdominal Neoplasms↗
PubMed1997

p53 hot-spot mutational analysis in advanced Western gallbladder carcinoma.

In gallbladder carcinoma, studies on the prime target of genetic alterations and gene therapy in human gallbladder malignancies, the p53 tumor suppressor gene, have been focusing on this gene's immunohistochemical detection. From November 1991 to October 1993, seven patients suffering from gallbladder carcinoma underwent surgical resection. Cancerous and normal liver tissues were obtained immediately after surgery, snap-frozen in liquid nitrogen, and stored at -80 degrees C for immunohistochemistry and DNA isolation. Exons 5, 6, 7, and 8 of the p53 gene were completely sequenced following polymerase chain reaction (PCR) amplification of a 1574-bp fragment. Missense mutations were detected in the cancerous tissues of two patients: one transition each on codons 134 (Phe-->Leu) and 146 (Trp-->Arg). Immunohistochemical p53 staining was positive in the latter patient only. This is the first report on sequence analysis and mutagenesis of the p53 gene in Caucasian patients with gallbladder cancer. Both mutations were transitions and seem to represent a rather rare event. The possible impact of p53 mutagenesis on gallbladder tumorigenesis requires evaluation in larger studies.

Adenocarcinoma↗
PubMed1997

Female sex hormone receptor status in advanced hepatocellular carcinoma and outcome after surgical resection.

BACKGROUND: There is a limited amount of data regarding the estrogen receptor (ER) and progesterone receptor (PgR) status of hepatocellular carcinomas (HGCs), and the relationship between receptor status and clinicopathologic features of tumors has not been reported. METHODS: Between April 1992 and December 1993, cancerous tissues for cytosolic preparation and receptor quantification in a monoclonal solid-phase enzyme immunoassay were obtained from 28 patients undergoing resection, three patients with total hepatectomy and subsequent liver transplantation, and two patients suffering from nonresectable HCC. RESULTS: ER and PgR were detected in the HCCs of 13 (39%) and 6 patients (18%), respectively. A lower age was observed among the female patients whose receptor status was negative for ER or PgR or both, as compared with the respective receptor-positive groups. No significant differences with respect to tumor stage and grading could be observed. There was one perioperative death (3%). In patients undergoing curative resection, 1-year survival in the ER(+) group was significantly lower than in the ER(-) group (40% versus 79%, p < 0.05). The 2-year survival rates in the ER(+) and ER(-) groups were 40% and 71%, respectively. A comparable trend did not become evident for PgR(+) and PgR(-) patients. CONCLUSIONS: Our data suggest a negative effect of an ER(+) tumor on patient survival after curative resection of advanced HCC.

Aged↗