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H Witzigmann

Publications and source records attributed to H Witzigmann.

At least 19 recordsLinked to original sources
PubMed2007

Sirolimus improves early microcirculation, but impairs regeneration after pancreatic ischemia-reperfusion injury.

Ischemia and reperfusion injury remains a relevant problem in clinical pancreas transplantation. We investigated the effect of sirolimus (SRL) in a rodent model of 90-min warm pancreatic ischemia. Four groups were studied: (1) sham surgery and vehicle; (2) sham surgery and SRL; (3) warm ischemia and vehicle; (4) warm ischemia and SRL. SRL (1.5 mg/kg/day) and vehicle were administered intraperitoneally for 3 days prior to surgery until the animals were killed. Microcirculation was assessed immediately after reperfusion by means of intravital fluorescence microscopy. Histopathological injury, apoptosis, proliferation and biochemical parameters were analyzed at 2 h, 1 day and 5 days after surgery. Ninety minutes after ischemia, intravital microscopy revealed an improved functional capillary density (p < 0.05) and reduction of adherent leucocytes (p < 0.01) and platelets (p < 0.05) in the SRL-treated group compared to the vehicle-treated controls. In contrast, on day 5 after ischemia, the pancreatic tissue of SRL-treated animals showed a higher grade of histological injury (p < 0.05) and higher rate of apoptotic cells (p < 0.05) than the vehicle controls. In summary, our data indicate that administration of SRL improves microcirculation at a very early stage, but results in an impairment of the recovery phase after pancreatic ischemia-reperfusion injury.

Animals↗
PubMed2005

[Current diagnostics and therapy for carcinomas of the biliary tree and gallbladder].

Carcinoma of the biliary tree are rare tumours of the gastrointestinal tract with a rising incidence during the last years. Biliary neoplasms are classified into intra- and extrahepatic cholangiocarcinoma (Klatskin tumour, middle and distal extrahepatic tumours), gallbladder cancer, and ampullary carcinoma. Transformation of normal into malignant bile duct tissue requires a chain of consecutive gene mutations, similar to the adenoma-dysplasia-carcinoma-sequence in colon cancer. Abdominal ultrasound, combined non-invasive magnetic resonance cholangiography/tomography (MRC/MRT), and facultatively endoscopic retrograde cholangiography (ERC) for unclear diagnosis, represent the gold standard for primary diagnosis. For ampullary carcinoma, endosonography and endoscopic biopsy are the diagnostic tools of choice. Cure is attainable only by formal curative radical surgical resection. Increasing surgical radicality within the last years enabled clearly improved 5-year survival rates. In contrast, there has been no clinical benefit for adjuvant and neoadjuvant therapies. For palliation, bile duct stenting and photodynamic therapy are established methods. Radio- and chemotherapy should be reserved for clinical studies. New therapeutic approaches include brachytherapy, the use of modern chemotherapeutics, COX-2- and tyrosine kinase-receptor-inhibitors.

Algorithms↗
PubMed2005

Are endoscopic antireflux therapies cost-effective compared with laparoscopic fundoplication?

BACKGROUND AND STUDY AIMS: A number of endoscopic antireflux therapies (EATs) have emerged as potential nonmedical treatment options for patients with gastroesophageal reflux disease (GERD). Concerns about clinical efficacy and costs have given rise to debate about their role in GERD management. The costs of laparoscopic fundoplication (LF) were compared with the costs of EAT when used in a sequential strategy that reserves the option of LF for EAT failure. METHODS: A simple mathematical criterion of direct medical costs was applied. Published articles concerning EAT were reviewed to assess its effectiveness, durability and costs, in order to estimate the parameters of the model. The costs of EAT and LF were evaluated from the perspective of a German third-party payer. Only direct medical costs were considered. RESULTS: Assuming that EAT has no impact on potential LF later on, the outcome of both strategies (LF, or EAT first with LF in case of failure of EAT) is identical and preference is a simple question of costs. The sequential strategy in nonmedical GERD treatment would be preferable if the long-term relief rate with EAT exceeds the ratio of the cost of EAT to the cost of LF. Long-term success rates of EAT do not exceed 0.65. At current prices EAT is clearly not cost-effective in Germany. CONCLUSION: Our simple criterion indicates that EAT would only be cost-effective and beneficial in a sequential strategy if the costs of EAT were to be decreased to around 30 % of current retail prices. However, long-term studies and randomized controlled trials are necessary to finally determine the role of EAT in GERD treatment, and the preference may change in either direction.

Cost-Benefit Analysis↗
PubMed2003

Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma.

BACKGROUND: The Raf/MEK/ERK (mitogen activated protein kinase-MAPK) signal transduction cascade is an important mediator of a number of cellular fates, including growth, proliferation, and survival. The BRAF gene, one of the human isoforms of RAF, is activated by oncogenic Ras, leading to cooperative effects in cells responding to growth factor signals. AIMS: The aim of this study was to elucidate a possible function of BRAF in liver tumours. METHODS: Mutations of BRAF and KRAS were evaluated in 25 hepatocellular carcinomas (HCC) and in 69 cholangiocarcinomas (CC) by direct DNA sequencing analyses after microdissection. The presence of active intermediates of the MAPK pathway was assessed immunohistochemically. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Activating BRAF missense mutations were identified in 15/69 CC (22%) and in one case of tumour surrounding liver. KRAS mutations were found in 31 of 69 (45%) CC examined and in two cases of tumour surrounding non-neoplastic liver tissue. In HCC, neither BRAF nor KRAS mutations were detected. All 31 CC with KRAS mutations had an intact BRAF gene. We failed to observe a correlation between BRAF or KRAS mutations and histopathological factors or prognosis of patients. CONCLUSIONS: Our data indicate that BRAF gene mutations are a relatively common event in CC but not in HCC. Disruption of the Raf/MEK/ERK (MAPK) kinase pathway, either by RAS or BRAF mutation, was detected in approximately 62% of all CC and is therefore one of the most frequent defects in cholangiocellular carcinogenesis.

Base Sequence↗
PubMed2002

[Recurrent lower gastro-intestinal bleeding in a 38-year-old patient].

HISTORY AND CLINICAL FINDINGS: A 38-year-old patient with a history of recurrent gastrointestinal bleeding for more than 15 years was transferred for the treatment of a new onset of hematochezia and anemia. His general condition was clearly reduced. EXAMINATIONS: Laboratory results showed a distinct microcytic hypochromic anemia; ferrum, ferritin, albumin, and protein were also diminished. Colonoscopy and transrectal ultrasound uncovered large hemangiomatous structures in the rectum. Digital substraction angiography of the bilateral internal iliac artery, superior and inferior mesenteric arteries including its branches showed a perirectal polypoid tumour with a discrete angiomatous structural shadow in the capillary phase. MRI of the pelvis revealed angiomatous blood vessels in the whole pararectal space and to a minor extension in the gluteal muscles. DIAGNOSIS, TREATMENT AND COURSE: The diagnosis of cavernous hemangioma of the rectum was made and a distal mesorectal resection of the rectum including a coloanal anastomosis and double-running ileostomy was performed. 3 months later the ileostomy was reversed. There was no further bleeding and the rectal continence was normal. CONCLUSION: In case of unclear recurrent lower gastrointestinal bleeding, with onset in the early childhood and impressive rectal varices, one has to think about the rare diagnosis of cavernous hemangioma.

Adult↗
PubMed2002

Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients.

Adenocarcinoma↗
PubMed2002

INK4a-ARF alterations in liver cell adenoma.

BACKGROUND: The INK4a-ARF (CDKN2A) locus on chromosome 9p21 encodes two tumour suppressor proteins, p16(INK4a) and p14(ARF), whose functions are inactivated in many human cancers. AIMS: To evaluate p14(ARF) and p16(INK4a) alterations in liver cell adenoma. METHODS: After microdissection, DNA from 25 liver cell adenomas and corresponding normal liver tissue were analysed for INK4-ARF inactivation by DNA sequence analysis, methylation specific polymerase chain reaction, restriction enzyme related-polymerase chain reaction (RE-PCR), mRNA expression, microsatellite analysis, and immunohistochemistry. In addition, microdeletion of p14(ARF) and p16(INK4a) were assessed by differential PCR. RESULTS: Methylation of p14(ARF) was found in 3/25 cases (12%) and alterations in p16(INK4a) occurred in 6/25 liver cell adenomas (24%) which correlated with loss of mRNA transcription. We failed to detect microdeletions or specific mutations of both exons. p16(INK4a) methylation appeared in the context of an unmethylated p14(ARF) promoter in six cases. In normal liver tissue, p14(ARF) or p16(INK4a) alterations were not observed. CONCLUSIONS: Our data suggest that p14(ARF) methylation occurs independently of p16(INK4a) alterations in liver cell adenomas. Furthermore, methylation of p14(ARF) and p16(INK4a) may be a result of cell cycle deregulation and does not seem to be a prerequisite of malignancy.

Adenoma, Liver Cell↗