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Biomedical subjects

H Witzigmann

Publications and source records attributed to H Witzigmann.

At least 37 records · Page 2Linked to original sources

[Surgery for complications of chronic pancreatitis].

At least 50 % of all patients with chronic pancreatitis require surgical treatment in the course of their disease. Indications for surgery are intractable pain, intra- and extrapancreatic complications and the suspicion of a carcinoma. The basic principles of surgery are resection and drainage. The choice of the surgical procedure depends on the morphological expression and the localization of the pathological changes. Regarding resections in the head-area, previous studies demonstrated uniformly the superiority of the duodenum-preserving pancreas head resection (DPPHR) compared to the Kausch-Whipple operation with and without maintenance of the pylorus. Drainage procedures (pain recurrence in 20-40 % in the long-term course) and left pancreatic resections (de-novo diabetes mellitus in up to 45 %) should be considered critically. Between May 1994 and November 2000 117 patients underwent surgical therapy for complications of chronic pancreatitis at our institution. Resections were performed in 68 % of the patients and drainage procedures in 20 %. There was no mortality. Over the years the proportion of the DPPHR increased in comparison to the Kausch-Whipple procedure and the number of the drainage operations decreased continuously. The DPPHR was significantly superior to the Kausch-Whipple procedure with regard to the glucose metabolism and the quality-of-life. In the spectrum of surgical procedures in chronic pancreatitis, the DPPHR represents a modern, organ-preserving procedure for patients with complications in the pancreas head.

Adolescent↗

Importance of microcirculatory disturbances in the pathogenesis of pancreatitis.

Pancreatic microvascular control is a complex physiological process which is incompletely understood. Blood flow in the pancreas is altered by a large number of endogenous and exogenous factors in the context of acute and chronic pancreatitis. The frequency of progression from acute pancreatitis to a chronic form is a controversial question. In acute pancreatitis reductions in blood flow and alterations of microvascular integrity resulting in impaired tissue oxygenation play an important part in the progression and possibly the initiation of the disease. Endothelin and nitric oxide are believed to be two of the most effective vasoactive mediators. The beneficial effect of therapeutic strategies affecting vasoactive mediators is confirmed in experimental studies. Chronic disease is associated with decreased pancreatic blood flow and histological changes in the vasculature in both patients and animal models. Further studies are needed to clarify whether ischemia in chronic pancreatitis is more important in perpetuating the disease or as primary cause of the inflammatory processes.

Acute Disease↗

Pharmacological regulation of postischemic sinusoidal diameters in rats--a new approach for reducing hepatic ischemia/reperfusion injury.

UNLABELLED: Ischemia leads to profound endothelin-related constriction of the hepatic microcirculation with resulting disturbances in blood and oxygen supply. The aim of the study was to modulate hepatic microvascular diameters by blocking endothelin receptors with bosentan, and also to find the best possible vessel width (as produced by bosentan) for minimizing ischemia/reperfusion injury. METHODS: In an in vivo rat model hepatic ischemia was induced for 30 minutes by crossclamping the hepatoduodenal ligament. The endothelin receptor antagonist (ERA) bosentan was administered before ischemia in stepwise dosages of 0.1, 1.0 and 10 mg/kg bw i.v. and 10 mg/kg bw intraportally (i.p.). Vasoactive effect was assessed by in vivo microscopy. The influence on hepatic oxygen supply and hepatocellular function was evaluated by measuring local tissue pO(2) and AST levels. RESULTS: Because of ischemia sinusoidal diameters were reduced to 76.3 +/- 7.4% compared with values found in sham-operated animals. After administration of 0.1 mg/kg ERA (bosentan) the sinusoids remained constricted (89.7 +/- 9.9%). Blocking endothelin receptors with 1 mg/kg bosentan avoided sinusoidal constriction (99.0 +/- 8.8%, p<0.05) and led to the most effective reduction of AST level peak after 6 h of reperfusion (244.0 +/- 34.2 U/l vs 422.9 +/- 163.3 U/l in untreated ischemia). 10 mg/kg i.v. caused an increase in sinusoidal diameter to 109.1 +/- 6.4% and 10 mg/kg intraportally to 136.8 +/- 19.3% and even an increase in AST levels (618.9 +/- 209.3 U/l). Hepatic ischemia led to a significant decrease of local tissue pO(2) after reperfusion (9.4 +/- 1.2 mm Hg; p<0.05 vs sham: 16.8 +/- 1.8 mm Hg). The greatest improvement in postischemic oxygen supply was found in the 1.0 mg/kg group (12.9 +/- 1.0 mm Hg; p< 0.05 vs ischemia). Venular diameter changed almost to the same extent as sinusoidal diameter. Perfusion rate was significantly increased and sticking of leukocytes in sinusoids and venules was reduced after doses of 1 and 10 mg/kg bw bosentan i.v. (p<0.05). IMPLICATIONS: In this model we were able to regulate the diameters of sinusoids and postsinusoidal venules incrementally. We conclude that the avoidance of constriction, without excessive vasodilatation gives increased perfusion rates with improved hepatic oxygen supply and hepatocellular function.

Animals↗

[Treatment concept of adenomas of Vater's ampulla].

INTRODUCTION: The most common benign ampullary tumors are adenomas (80%). They are considered as premalignant lesions with a transformation rate to carcinoma of up to 30%. METHODS: From 1 January 1997 to 28 February 1999 we treated 11 patients with adenoma of the ampulla of Vater. An ampullectomy was performed in 10 cases. One poor-risk patient could not be operated on. RESULTS: No operative mortality occurred. In two patients a pT1 adenocarcinoma was diagnosed postoperatively. One of the two patients with a high-risk carcinoma underwent a second operation, a Whipple pancreatoduodenectomy. Nine of 10 patients had no recurrence with a median follow-up of 12 months. CONCLUSION: One patient died of glioblastoma. We would therefore recommend ampullectomy as the first-line treatment for benign tumors of the ampulla of Vater. In low-risk pT1 carcinoma (G1/G2, L0) and R0 resection, local excision is acceptable. In high-risk pT1 carcinoma (G3 and/or L1) Whipple pancreatoduodenectomy is mandatory.

Adenocarcinoma↗

Diagnosis and monitoring of acute cytomegalovirus infection in peripheral blood of transplant recipients by nested reverse transcriptase polymerase chain reaction (RT-PCR).

The aim of this novel diagnostic approach is to monitor cytomegalovirus (CMV) infection in immunocompromised transplant recipients using early, sensitive, and specific predictors before and during antiviral therapy. The peripheral blood cells of 20 patients after transplantation (9 liver, 7 kidney, 4 simultaneous kidney-pancreas) were studied for an early diagnosis of acute infection. The mRNA and DNA of human CMV immediate-early antigen (IEA) were detected by nested-polymerase chain reaction (PCR) assay. Results of nested PCR were compared with the immunological detection of antigen pp65 and serological diagnosis of CMV infection. All data were correlated with clinical symptoms like leukopenia, thrombopenia, pneumonia, and allograft-rejection reaction. Of 20 transplant recipients, 12 were infected by CMV, and 9 suffered from a CMV-related disease. CMV mRNA were detected simultaneously with antigen pp65 and CMV DNA in all patients with symptomatic infection. Additionally, CMV mRNA was found over a longer period after ganciclovir treatment of infected recipients. Nested reverse transcriptase (RT)-PCR for CMV-IEA mRNA allows a sensitive and specific diagnosis of an acute CMV infection. CMV mRNA was found to be a good marker of acute viremia and could be a useful tool for CMV monitoring over the whole period of disease management, even during antiviral therapy.

Cytomegalovirus↗

A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma.

BACKGROUND: Pegylated liposomal doxorubicin has an enhanced efficacy and reduced toxicity compared with free doxorubicin. The efficacy and toxicity of pegylated liposomal doxorubicin was investigated in patients with hepatocellular carcinoma. PATIENTS AND METHODS: Patients with histologically confirmed, locally advanced or metastatic hepatocellular carcinoma and a Karnofsky index > 60% were included in this prospective single-arm study. Exclusion criteria were liver cirrhosis stage Child-Pugh C, previous chemotherapy, or chemoembolization. Pegylated liposomal doxorubicin was given in a dose of 30 mg/m2 every three weeks until progression of disease. After inclusion of five patients the dose could be escalated to 40 mg/m2 in absence of toxicity grade 3 and 4. RESULTS: Sixteen patients were evaluable for response. No objective response was achieved. The median survival time was 140 days (95% confidence interval: 126-154 days). Treatment toxicities grade > or = 3 comprised increased liver enzymes in patients with preexisting grade 1 or 2 elevation (n = 6), hematologic toxicity (n = 5), and hypersensitivity (n = 2). CONCLUSIONS: Pegylated liposomal doxorubicin is not effective for treatment of advanced hepatocellular carcinoma. The favorable toxicity profile was confirmed even in patients with underlying liver disease.

Adult↗

Decrease of CA 19-9 during chemotherapy with gemcitabine predicts survival time in patients with advanced pancreatic cancer.

Chemotherapy with gemcitabine has been shown to be an effective regimen in advanced or metastatic pancreatic cancer with improvement of both quality of life and survival time. The response of the tumour marker CA 19-9 to chemotherapy with gemcitabine was studied in order to find out whether it is related to survival time of patients. Forty-three consecutive patients (median age 61 years, range 39-76 years; 20 males, 23 females) suffering from histologically proven locally advanced or metastatic pancreatic adenocarcinoma and a baseline Karnofsky-index > or = 60 were treated with gemcitabine in a dose of 1,000 mg/m(-2) weekly x 7 followed by 1 week of rest during the first cycle and thereafter 1,000 mg/m(-2) weekly x 3 followed by 1 week of rest until progression. In 36 of 43 patients serial measurements of CA 19-9 could be performed. Patients with a decrease of > 20% of the baseline CA 19-9 level after 8 weeks of treatment (n = 25) had a significantly better median survival than patients with a rise or a decrease < or = 20% (n = 11) (268 vs 110 days; P < 0.001). The response of CA 19-9 was the strongest independent predictor of survival (P < 0.001) in the multivariate analysis. In conclusion, a decrease of CA 19-9 > 20% during the first weeks of chemotherapy with gemcitabine is associated with a better survival of patients with locally advanced or metastatic pancreatic cancer. Serial measurements of CA 19-9 are useful to decide whether further chemotherapy after the first weeks of treatment is indicated.

Adult↗

[Prognostic significance of proliferation markers in hepatocellular carcinoma (HCC)].

BACKGROUND: The prognosis of patients with curatively resectable hepatocellular carcinoma depends mainly on anatomic extent of the tumour and on the general condition of the patient. Given the growing evidence that proliferation indices may be of prognostic significance in hepatocellular carcinomas, identification and quantitation of proliferative capacity may be of prognostic importance. METHODS: We have compared four different methods to assess proliferation in a series of 193 curatively (R0-) resected hepatocellular carcinomas: Mitotic count, immunohistochemical assessment of the MIB-1- (Ki-67-), Antigen Proliferating Cell Nuclear Antigen (PCNA) and silverstained nucleolar organiser regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), Edmondson Grade and with survival rate. RESULTS: In each carcinoma, we could demonstrate mitotic figures, MIB-1, PCNA and AgNOR dots in variable proportions. Significant statistical correlations were seen between Mitotic Index, the rate of nuclear positivity for MIB-1 and PCNA and the number of AgNOR dots. In univariate survival analysis tumour stage and Edmondson Grade, Mitotic Index, MIB-1 and PCNA Index and mean AgNOR-number were significant patients' survival influencing factors. Performing multivariate Cox survival analysis, Mitotic Index, concomitant cirrhosis, Edmondson Grade and patient age were the only significant independent prognostic factors. CONCLUSION: These results indicated that Mitotic Index is an additional prognostic parameter which could provide auxiliary information for patients' outcome.

Adult↗

[Isolated tumor cells in primary malignant liver tumors].

The failure to reduce the mortality of patients with malignant liver tumors (hepatocellular carcinoma, cholangiocarcinoma) is probably a result of the early dissemination of cancer cells to secondary sites, which is usually missed by conventional diagnostic procedures used for tumor staging. Recent developments in the field of molecular biology enable us to detect tumor cells at a submicroscopic level. Therefore, over the past 10 years, sensitive assays have been developed to detect individual carcinoma cells disseminated to regional lymph nodes or distant organs. In contrast to colorectal and also breast cancer where disseminated tumor cells may be of additional prognostic value, few data exist for hepatocellular carcinomas. Until now, no relevant studies have been reported for cholangiocarcinoma. Alpha-fetoprotein and also albumin mRNA have been used for the detection of circulating micrometastatic tumor foci of hepatocellular carcinoma (HCC); however, the interpretation of the results has been equivocal. If hepatocyte-specific mRNAs are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells. The literature about the incidence of "micrometastases" and specificity of different assays for hepatocellular carcinomas varies tremendously. This clearly indicates the need for uniformity in protocols. For hepatocellular carcinoma, mRNA for alpha-fetoprotein and albumin is not a specific marker of circulating micrometastases, but may serve for treatment monitoring. Nevertheless, PCR-based techniques are a powerful tool in the therapeutical monitoring of hepatocellular carcinoma and will find their way into the daily practice of diagnostic histopathologists in the near future.

Bile Duct Neoplasms↗

[Hepatocellular carcinoma: resection versus transplantation].

For decision of adequate surgical therapy and comparison of results differentiation of hepatocellular carcinomas (HCC) in cirrhotic and noncirrhotic livers is important. Liver resection is the treatment of choice for HCC in noncirrhotic liver. Between 4/94 and 8/99 we treated 54 patients with hepatocellular carcinoma (HCC) by subtotal hepatic resection (n = 40) and orthotopic liver transplantation (n = 14). Overall 1- and 3-year survival rates of the resection group were 45 and 25% (median follow up: 3.5 years). One-year survival in the transplantation group was 72% (median follow up: 2.2 years). In patients with HCC in cirrhosis in UICC stage I to III the optimal therapy is a controversial issue. In these patients the results after liver resection are poor due to high operative mortality and recurrence (3-year recurrence-free survival: 30%). Regarding the literature, liver transplantation is the treatment of choice in small (< 3-5 cm, < or = 2 tumors) HCCs arising in cirrhosis with better outcome compared to resection. The data in the literature report 3-year-survival rates after liver transplantation of 60-80%. However, consequent patient selection is necessary for this treatment modality. Due to the limited donor resources liver transplantation is rarely justified in advanced tumors.

Carcinoma, Hepatocellular↗

[Vulvar involvement as a rare extra-intestinal manifestation of Crohn disease].

BACKGROUND: Crohn's disease may involve all parts of the gastrointestinal tract. Extraintestinal manifestations with and without continuity to the intestine are described. The most common complications are the involvement of bone (articulations), liver and eyes. Crohn's disease of the vulva is rare and only a few cases have been reported in the literature. CASE REPORT: The 45-year-old woman has a 15-year history of a marked chronic-inflammatory bowel disease. The diagnosis of Crohn's disease was never confirmed histologically. In 1984, she developed a painful vulvar swelling and erythema. A fungal infection was suspected and she was treated with topical antimycotic medication, but there wasn't any improvement. In July 1995, biopsies of the vulva showed a granulomatous inflammation consistent with Crohn's disease. Oral metronidazol therapy (20 mg/kg/day) was started. After 2 months, the erythema had healed completely but the vulvar swelling remained. CONCLUSIONS: The treatment of this extraintestinal manifestation is very difficult. Systemic or topical application of steroids is without response in most cases. Surgical excision showed good results in a few cases. A long-term treatment with oral metronidazol 20 mg/kg/day could be a chance for healing without adverse effects.

Administration, Oral↗

[Intra-abdominal abscess].

In more than 80% of cases, intra-abdominal abscesses derive from an intra-abdominal organ, and in most cases they develop after operative procedures. Regarding anatomy, intra-abdominal abscesses can be divided into intra-peritoneal and visceral abscesses and those located in the anterior retroperitoneal space. Despite improvements in ultrasonography, CT is still the most effective method in diagnosis and therapy. Percutaneous ultrasound or CT-guided drainage is a therapy characterized by low procedural morbidity and is successful in 80% of cases if strict criteria are met. Complicated abscesses and those cases in which the underlying disease has to be treated require surgical intervention. Most liver abscesses are treated interventionally; in abscesses of the pancreas or spleen and in Crohn's disease, surgery is necessary. The combination with sufficient antibiotic drug therapy is very important. Specific infectious diseases appearing as intra-abdominal conglomerates (tuberculosis, actinomycosis, amebiasis) lead to a delay in diagnostics because of their scarcity and are characterized by special patho-anatomical, diagnostic and therapeutic features. The crucial thing is to take a specific infection into consideration.

Abdominal Abscess↗

Exogenous L-arginine protects liver microcirculation from ischemia reperfusion injury.

UNLABELLED: Hepatic ischemia followed by reperfusion evokes an imbalance between the vasoregulatory compounds endothelin and nitric oxide (NO) followed by constriction of the vascular bed, leading to microcirculatory disturbances and reduced blood flow, thereby causing hypoxia and liver damage. The aim of this study was to protect the liver microcirculation by maintaining this delicate balance. MATERIAL AND METHODS: In an in vivo ischemia/reperfusion model with portal decompression by a splenocaval shunt, hepatic ischemia was induced for 30 min by Pringle's maneuver. The effect of the NO donor L-arginine (400 mg/kg b.w. i.v.) was assessed by in vivo microscopy. Microhemodynamic studies, including the sinusoidal perfusion rate, diameters of hepatic sinusoids and postsinusoidal venules, leukocyte endothelium interactions and leukocyte velocity were performed. Microcirculatory data were compared with local tissue pO2 and serum transaminase levels. RESULTS: After ischemia the diameters of sinusoids and postsinusoidal venules were significantly reduced to 76+/-7 and 86+/-10% respectively in the nontreatment group, but dilated to 102+/-3 and 105+/-7% in the group treated with L-arginine (p < 0.001). The percentage of permanently adherent leukocytes in sinusoids and venules was increased by ischemia, but L-arginine reversed this increase (p < 0.001). Perfusion rate was improved to 90+/-2 compared with 83+/-5% in the untreated group (p < 0.01). Systemic arterial blood pressure was not affected by administration of the NO donor. The postischemic increase in serum transaminase levels was diminished in the treatment group (ASAT: p < 0.05). Local postischemic hepatic tissue pO2 was significantly decreased to 45% of basal values after 30 min and to 55% after 60 min of reperfusion (p < 0.05). Administration of L-arginine results in a significant increase in local tissue pO2 to 86 and 106% of basal values respectively (p < 0.05). CONCLUSION: These data indicate that L-arginine improves hepatic microcirculation after warm ischemia by increasing sinusoidal perfusion rate and by diminishing leukocyte endothelium interactions. Maintained integrity of microcirculation is associated with sufficient oxygen supply and improved hepatocellular function.

Animals↗

[Role of endothelin-nitrogen monoxide equilibrium in ischemia/reperfusion damage of the liver].

Elevated levels of endothelin (ET) are measured during ischemia and reperfusion, but no adequate increase of nitric oxide (NO) can be observed. Thus, the balance of both substances, which occurs under physiological conditions and regulates microcirculatory vessel widths, is disturbed. This leads to microcirculatory damages. As well ET receptor blocking using a mixed ET receptor antagonist as increase of NO production after L-arginine treatment influenced this pathomechanism. The preischemic sinusoidal diameters were maintained and leukocyte endothelial interactions reduced. Concomitantly, sinusoidal perfusion rate and local hepatic tissue pO2 were increased. Because of significant reduced hepatocellular damage in both therapy groups both therapeutical ways might exert beneficial effects to attenuate ischemia/reperfusion induced microvascular and tissue injury.

Animals↗

[Laparoscopic implantation of catheters for continuous ambulatory peritoneal dialysis].

Continuous ambulatory peritoneal dialysis (CAPD) has become an established procedure and is an equal alternative to haemodialysis (HD) in the management of terminal renal failure. Nevertheless CAPD still plays a minor role compared with HD (10% of all dialyses). CAPD offers advantages in quality of live but is still associated with a significant number of complications. The improvement of surgical technique and development of new peritoneal dialysis catheters (PDK) improved the results of peritoneal dialysis. 3 methods for implantation of PDK are used: the open surgical technique, the blind percutaneous procedure and the laparoscopic method. The latter technique is currently an accepted practice. 10 patients were treated by the laparoscopic method. Additionally to the PDK-tunnel of the abdominal wall we used 2 trocars (1 x 5 mm, 1 x 12 mm). Advantages of this technique are avoiding of perforating lesions, possibility for further operations and a safe implantation of the PDK. Peritoneal dialysis was started 7 days after operation with initially low dialysate volumes. The observed incidence of complications and removed catheters are comparable to the reports in the literature.

Catheters, Indwelling↗

[Effect of forced organ cooling on microperfusion of donor livers].

UNLABELLED: With regard to the factors of graft damage the role of rapid cooling during cold in situ perfusion should not be underestimated. The aim of this study was to analyse the effect of rapid cooling on microperfusion of rat livers in an in vitro model. MATERIAL AND METHODS: During harvest of 14 rat livers the organs' core temperature was monitored. Two groups were formed: (1) cold UW perfusion. (2) cold UW perfusion under additional graft cooling by iced water. Thereafter, isolated livers were perfused (4 degrees C. 1 h, 5 mmHg) monitoring the portocaval resistance, and liver enzyme release and pH levels in the perfusate. Finally, portal angiography of each liver was performed. RESULTS: Rapid in situ cooling resulted in a decrease of the plateau temperature of the organ by 6.5 degrees C (p < 0.01). The pH slope in the perfusate and the enzyme release were diminished obviously, but not significantly. On the other hand, the portocaval resistance was increased by more than 20% (p < 0.05). Portal angiographies assessed by a special score expressed a marked deterioration of microperfusion in peripheral and subcapsular regions. CONCLUSIONS: This study shows that rapid cooling results in worsened microperfusion of liver grafts. The effect of rapid cooling on function and histomorphology of transplanted livers should be analysed in further investigations.

Animals↗

[Therapy and follow-up of injuries after laparoscopic operations].

From May 1993 to September 1997 we treated 22 patients with complications after laparoscopic surgery. We report on 18 patients after laparoscopic cholecystectomy, three patients after diagnostic laparoscopy and one after TAPP. Two patients died (hepatic failure and without any possibility of definitive therapy) and the injuries of the other 20 patients were repaired.

Biliary Fistula↗