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Biomedical subjects

A Weimann

Publications and source records attributed to A Weimann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation.

PURPOSE: Tumor recurrence is the major limitation of long-term survival after liver transplantation for hepatocellular carcinoma (HCC) or fibrolamellar carcinoma (FLC). Understanding tumor-biologic characteristics is important for selection of patients and for development of adjuvant therapeutic strategies. PATIENTS AND METHODS: The study included 69 patients who underwent potentially curative liver transplantation for HCC/FLC and survived for more than 150 days; minimum follow-up was 33 months. Frequency, localization, and timing of recurrence were analyzed and compared with primary tumor and patient characteristics. RESULTS: Tumor recurrence was observed in 39 patients at 67 locations. Hematogenous spread was the major route of tumor recurrence (87%), and the most frequent sites were the liver (62%), lung (56%), and bone (18%). Parameters associated with recurrence were absence of cirrhosis, tumor size greater than 5 cm, more than five nodules, vascular infiltration, and International Union Against Cancer (UICC) stage IVA. Selective intrahepatic recurrence was found in nine patients (23%); it was associated with highly differentiated tumors, lack of vascular infiltration, and male sex. Recurrence at multiple sites was found predominantly in young patients (< or = 40 years) and for multicentric (> 5) primary tumors. Recurrences were observed within a wide time range after transplantation (43 to 3,204 days; median, 441 days); late recurrences (> 1,000 days, n = 8) were associated with highly differentiated or fibrolamellar tumors and low UICC stages. Surgical treatment was the only therapeutic option associated with prolonged survival after recurrence. CONCLUSION: In transplant recipients, hepatocellular carcinomas vary considerably in their pattern and kinetics of metastases. Tumor cells may persist in a dormant state for long time periods before giving rise to clinical metastases. Surgical treatment of recurrence should be considered whenever possible.

Adult↗
PubMed1999

[Practical aspects of early enteral feeding].

"Gut injury" and a corresponding impaired gut barrier function are thought to have a high impact on the development of multiple organ failure (MOF) in the critically ill. Mucosal lesions and increased intestinal permeability can provoke translocation of bacteria and endotoxins and initiate local and/or systemic immune-inflammatory response, bearing the risk of development of multiple organ failure. Enteral nutrition using the physiological pathway provides the intestinal mucosa with nutrients, which is thought to reduce bacterial translocation and septic complications. Considerable gastric reflux and delayed bowel motility are the principal problems of enteral nutrition. Therefore, in the early postoperative period at least a nasoduodenal or--jejunal feeding tube or feeding jejunostomy is required. The commonly used enteral formulas are well tolerated. So-called "immunonutrition" includes special formulas supplemented with immunemodulating substances like arginine, omega-3-fatty acids, ribonucleic acids and glutamine. Some beneficial effects of immune-enhancing diets have recently been reported for immune response, infectious complication rate, systemic inflammatory response syndrome (SIRS), multiple organ failure (MOF), antibiotic usage and length of hospital stay, especially in patients after trauma or surgery. However, the definite role is still unknown and indications have still to be defined. Enteral feeding should start with small volumes, the amount being gradually increased according to a patient's individual tolerance. Common problems are gastric reflux, diarrhoea and distension, but usage of a suitable formula, a gradual increase or reduction in the amount of enteral feeding and, additionally, parenteral nutrition can help to overcome such complications. Clinical examination of the enterally fed patient should be performed carefully. Standard nutritional monitoring of electrolytes, glucose, triglycerides, cholinesterase, albumin, differential blood count, urine-glucose and nitrogen retention to assess the catabolic state should be performed routinely. Although only little data from randomised trials are available, enteral nutrition has advantages and is cheaper than total parenteral nutrition. In the critically ill, the goal of enteral feeding is not coverage of total caloric requirements, but continuous administration of at least a small amount in order to prevent gut mucosa atrophy. Nutrition is an important aspect in critical care medicine, and enteral feeding should be attempted at least partially.

Critical Care↗
PubMed1998

[Clinical effects of supplemental enteral nutrition solution in severe polytrauma].

Previous studies in critically ill patients have shown the beneficial effects of early enteral nutrition supplemented with arginine, omega-3 fatty acids and nucleotides (Impact) on immunological response, infection rate and length of stay in hospital. No specific data exist for patients with severe multiple injury, who represent a high risk group for systemic inflammatory response syndrome (SIRS), septic complications and multiple organ failure (MOF). In this prospective, randomized, double-blind controlled clinical study on patients after severe trauma (ISS ca. 40) the primary study endpoints were incidence of SIRS and MOF [definitions according to Am Soc Crit Care Med (5) and Goris (23), Sauaia (43)]. Thirty-two patients enrolled in the study, and 29 were eligible for analysis: test (Impact) (n = 16), control (n = 13). Both groups were comparable according to age, body mass index and severity of trauma (PTS-test: 38.8 +/- 12.5, PTS-control: 40.8 +/- 15.5, ISS-test: 39.6 +/- 11.4, ISS-control: 40.5 +/- 9.2). Patients were randomized to receive either Impact (test) or an isonitrogenous isocaloric diet (control). Feeding was started on the 2nd day after trauma via endoscopically placed nasoduodenal or jejunal feeding tubes. The experimental diet was safe and well tolerated. During the 1st week the enteral feeding amount was about 2000 ml without significant difference. Test-fed patients developed SIRS significantly less frequently between day 1 and day 28 (8 vs 13.3; P < 0.05) and especially between day 8 and day 14 (3 vs 6.2; P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16 and 17 and the Sauaia score on days 8, 9, 10 and 11 (P < 0.05; P < 0.01). Mortality rate did not significantly differ (test 2/16, control 4/13), nor did length of ICU or hospital stay. With regard to the acute-phase response, C-reactive protein was significantly lower on day 4 in the test group (test: 131 +/- 67 mg/l, control: 221 +/- 110 mg/l) as was fibrinogen on day 12 (6.6 +/- 1.4 vs 7.5 +/- 1.4 g/l) and day 14 (7.1 +/- 1.3 vs 7.8 +/- 0.8 g/l). No significant difference could be observed for CD4/CD8 ratio, CD45 isotope on activated T-cells and lymphocytic interleukin (II)-2-receptor- and II-6 level. However, HLA-DR antigen presentation on peripheral monocytes was significantly elevated on day 7 in the test group (P < 0.05). According to the results, arginine, omega-3 fatty acids and nucleotides-enriched diet during early enteral feeding leads to reduction of SIRS after severe multiple injury. There is evidence for improvement of post-traumatic immunological response which helps to overcome the immunological depression after trauma.

Adolescent↗
PubMed1998

Perioperative parenteral and enteral nutrition for patients undergoing orthotopic liver transplantation. Results of a questionnaire from 16 European transplant units.

The present clinical experience in perioperative nutrition for patients undergoing orthotopic liver transplantation was evaluated by a questionnaire, answered by 16/21 European transplant units (76.1%). There is agreement, that malnutrition reflects per se the severity of chronic liver disease and should be not considered, in general, to exclude patients from the transplant waiting list. Most centers administer postoperative nutrition without difference to other patients after gastrointestinal major surgery. A combination of parenteral and enteral nutrition is preferred. Experience with preoperative nutritional support and use of new immunomodulating substances is rather limited.

Enteral Nutrition↗
PubMed1998

Arterial chemoembolization before liver transplantation in patients with hepatocellular carcinoma: marked tumor necrosis, but no survival benefit?

BACKGROUND/AIMS: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. METHODS: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44+/-1.15. In addition, six patients of this group received preoperative systemic chemotherapy. RESULTS: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50%) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. CONCLUSION: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

Carcinoma, Hepatocellular↗
PubMed1998

Appraisal of transplantation for malignant tumours of the liver with special reference to early stage hepatocellular carcinoma.

The enthusiasm to treat or even cure patients with unresectable hepatobiliary malignancy by total hepatectomy and liver transplantation has considerably diminished. Nowadays, due to organ-donor shortage, patients have to be selected with predictable likelihood for long-term survival. According to own experience and a review of the literature, liver transplantation may be considered in unresectable early stage hepatocellular and proximal bile duct carcinoma, the uncommon entities fibrolamellar carcinoma, epithelioid haemangioendothelioma and hepatoblastoma as well as in liver metastases from neuroendocrine tumours. At present, advanced stages of hepatocellular and proximal bile duct carcinoma, as well as intrahepatic bile duct carcinoma, haemangiosarcoma and metastases from nonendocrine tumours, should be excluded from transplantation. In order to cure the cancer-bearing disease, liver transplantation might be the ideal treatment for small but still resectable hepatocellular carcinoma with underlying cirrhosis. Our retrospective comparison of survival after resection and transplantation for early stage hepatocellular carcinoma does not reveal a significant difference. Although a tendency has been observed in favour of transplantation, resection of these tumours is still justifiable, not least because of donor organ shortage.

Actuarial Analysis↗
PubMed1998

Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma.

This study investigated the influence of an enteral diet supplemented with arginine, omega-3 fatty acids, and nucleotides (Impact, Sandoz Nutrition, Berne, Switzerland) on the incidence of systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF) in patients after severe trauma. Thirty-two patients with an injury-severity score > 20 were included in this prospective, randomized, double-blind, controlled study. Primary endpoints were the incidence of SIRS and MOF. Secondary endpoints were parameters of acute phase and immune response as well as infection rate, mortality, and hospital stay. For statistical analysis 29 patients (test group n = 16, control n = 13) were eligible. In the test group, significantly fewer SIRS days per patient were found during 28 d. The difference was highly significant between d 8-14 (P < 0.001). MOF score was significantly lower in the test group on d 3 and d 8-11 (P < 0.05). Acute phase parameters showed lower C-reactive protein serum levels (significant on D day 4) and fibrinogen plasma levels (significant on d 12 and 14; P < 0.05). HLA-DR expression on monocytes showed significantly higher fluorescence activity on d 7. No significant difference was found for T-lymphocyte CD4/CD8 ratio, interleukin-2 receptor expression, infection rate, mortality (2/16 vs. 4/13), and hospital stay. The results of the study provide further support for beneficial effects of arginine, omega-3-fatty acids and nucleotide-supplemented enteral diet in critically ill patients.

Acute-Phase Reaction↗
PubMed1998

Modern oral contraceptive use and benign liver tumors: the German Benign Liver Tumor Case-Control Study.

OBJECTIVE: To analyze the association between oral contraceptive use and the risk of benign liver tumors. METHODS: Two parallel case-control studies on hepatocellular adenoma and focal nodular hyperplasia. Collaborative study of 15 German liver centers. Cases defined by histology and compared with population controls. RESULTS: Fifty-one hepatocellular adenoma and 143 focal nodular hyperplasia cases (women) were recruited between 1990 and 1997, and compared to 240 population controls with a recent abdominal imaging test. The frequency age-matched odds ratio was 1.25 (95% confidence interval (CI), 0.37-4.22) and 1.96 (95% CI, 0.85-4.57) for hepatocellular adenoma and focal nodular hyperplasia, respectively. For hepatocellular adenoma, there was neither a significantly increased risk with longer duration of oral contraceptive use, nor an association with time since first or last use. For focal nodular hyperplasia, however, a slightly increased odds ratio was found with longer duration of use and more recent last use. CONCLUSION: There is little evidence for an increased risk for hepatocellular adenoma in women using modern oral contraceptives. If there is a risk not detected by the limited study size, hepatocellular adenoma is an extremely rare, and focal nodular hyperplasia a rare, adverse effect potentially associated with long-term oral contraceptive use and likely to be without public health importance.

Adenoma, Liver Cell↗
PubMed1998

[Diagnosis of liver tumors--when is scintigraphy of value?].

This paper illustrates the importance of utilizing radionuclide techniques to characterize in vivo benign liver masses. Examining the physiologic tumor function cholescintigraphy offers a highly specific pattern for identifying focal nodular hyperplasia (FNH): hypervascularisation, hepatocellular uptake and impaired transport of the bilirubin like tracer documented as trapping in later images. An hemangioma is diagnosed with high probability in case of a positive bloodpoolscintigraphy. But false-positive results have been reported. Therefore, a second unrelated examination, e.g. ultrasound, magnetic resonance imaging or dynamic computerized tomography is necessary to establish this diagnose in a sufficient certainty. If complications due to tumor growth are not expected, both, FNH and hemangioma need no further therapy. High sensitivity is necessary to establish resectability or tumor spread. Scintigraphic techniques are advantageous in scanning completely the whole body. On the other hand, there are limitations as low resolution and anatomical orientation, low specific activity in the tumor and artificial activity near by the tumor. To measure therapy effects and to detect recurrencies especially in borderline-cases positron emission computed tomography (PET)-technology is recommended, because PET offers a specific-parametric evaluation.

Diagnosis, Differential↗
PubMed1998

[Diagnostic and therapeutic strategies in hepatocellular adenoma].

While liver hemangioma and focal nodular hyperplasia are not considered an indication for surgery in asymptomatic patients resection has been recommended for hepatocellular adenoma because of the risk of rupture and malignant transformation. Problems arise from differential diagnosis and the appropriate surgical radicality including the indication for liver transplantation. This retrospective analysis deals with 58 patients who underwent surgery for hepatocellular adenoma: resection of different extension: n = 54, liver transplantation n = 4. In 39.6% of the patients the tumor was an incidental finding. In 62.0% of the character of the lesion was unclear prior to surgery. Tumor rupture and bleeding occurred in 17.2%, malignant transformation in 6.9%. Surgical morbidity was 27.6%, mortality 5.2% with the transplant patients alive for 1.5, 7, 9 and 10 years. Two and five years after resection 2 patients developed hepatocellular carcinoma in the liver remnant. The results confirm the indication for surgery in hepatocellular adenoma. Diagnostic approach for solid liver tumors without serum increase of tumor markers should rule out FNH and hemangioma. In all other patients surgery should be considered whenever possible with the radicality of malignant disease. Liver transplantation can be discussed even in asymptomatic patients with multiple adenoma.

Adenoma, Liver Cell↗
PubMed1998

[The intestine as the central organ in the development of multiple organ failure after severe trauma--pathophysiology and therapeutic approaches].

Multiple organ failure is with an incidence of 10-25% and a mortality of 50-70% the most severe complication after severe trauma. Intestinal ischemia and a corresponding impaired gut barrier function is thought to have a high impact on the development of multiple organ failure after severe trauma. Under normal conditions the intestinal wall is a sufficient barrier against bacteria and their products. Gut ischemia is followed by mucosal lesions, the intestinal permeability is increased. Translocating bacteria and bacterial products (endotoxin, peptidoglykan) can lead to a local and/or systemic immun-inflammatory response, which is made responsible for the development of multiple organ failure. Tonometry as a possibility of monitoring intestinal ischemia as well as a tool to estimate the prognosis of multiple trauma patients is still discussed controversially. Dopexamin, which directly influences intestinal ischemia (goal directed therapy) might be a successful treatment option, however until now no clinical study about beneficial effects of dopexamine in severely injured patients is available. Selective gut decontamination showed no clinical benefits in multiple trauma patients. Early enteral nutrition especially with immunomodulating ingredients ("immunonutrition") decreases posttraumatic complications as well as the incidence of MOF. However a reduction of mortality could not be described in severely injured patients so far.

Bacterial Translocation↗
PubMed1998

[Is modification of systemic inflammatory response syndrome and multiple organ failure by parenteral feeding possible?].

In this prospective, randomized, double-blind controlled clinical study, 29 patients after severe trauma (ISS about 40) were randomized to receive either IMPACT (Test) or an isonitrogenous isocaloric diet (Control). The primary study endopoints were the incidence of SIRS and MOF (definitions according to Bone, Goris and Sauaia). Test-fed patients developed significantly less SIRS between days 1 and 28 (8 vs 13.3, P < 0.05) and especially between days 8 and 14 (3 vs 6.2, P < 0.001). In the control group the Goris score was significantly worse (P < 0.05) on days 3, 4, 6, 7, 10, 11, 16, 17 and the Sauaia score on days 8, 9, 10, 11 (P < 0.05, P < 0.01). According to the results, an arginine, omega-3-fatty acids and nucleotide-enriched diet during early enteral feeding leads to reduction of SIRS and MOF scores after severe multiple injury.

Critical Care↗
PubMed1998

[Volumetry of circumscribed liver changes with 3-D ultrasound in comparison with 3-D computerized tomography].

The accuracy of volume measurement using three-dimensional ultrasound (3D-US) in comparison to three-dimensional computer tomography (3D-CT) was evaluated in 11 patients. The deviation of tumor volumes measured with 3D-US (ellipsoid formula) from 3D-CT was -28% to +9% and for 3D-US (planimetry reconstruction) from 3D-CT was -21% to +9%. These data show that volume measurement using 3D-US provides comparable results to 3D-CT. Clinically, 3D-US could be helpful in the follow-up of patients with non-resectable tumors or in planning liver resections by assessing the volume of liver tissue remaining after resection or by a better visualization of the topography of liver tumors and major hepatic structures.

Follow-Up Studies↗
PubMed1997

Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence.

HIV-1 specifically incorporates the peptidyl prolyl isomerase cyclophilin A (CyPA), the cytosolic receptor for the immunosuppressant cyclosporin A (CsA). HIV-1 replication is inhibited by CsA as well as by nonimmunosuppressive CsA analogues that bind to CyPA and interfere with its virion association. In contrast, the related simian immunodeficiency virus SIVmac, which does not interact with CyPA, is resistant to these compounds. The incorporation of CyPA into HIV-1 virions is mediated by a specific interaction between the active site of the enzyme and the capsid (CA) domain of the HIV-1 Gag polyprotein. We report here that the transfer of HIV-1 CA residues 86-93, which form part of an exposed loop, to the corresponding position in SIVmac resulted in the efficient incorporation of CyPA and conferred an HIV-1-like sensitivity to a nonimmunosuppressive cyclosporin. HIV-1 CA residues 86-90 were also sufficient to transfer the ability to efficiently incorporate CyPA, provided that the length of the CyPA-binding loop was preserved. However, the resulting SIVmac mutant required the presence of cyclosporin for efficient virus replication. The results indicate that the presence or absence of a type II tight turn adjacent to the primary CyPA-binding site determines whether CyPA incorporation enhances or inhibits viral replication. By demonstrating that CyPA-binding-site residues can induce cyclosporin sensitivity in a heterologous context, this study provides direct in vivo evidence that the exposed loop between helices IV and V of HIV-1 CA not merely constitutes a docking site for CyPA but is a functional target of this cellular protein.

Animals↗
PubMed1997

What constitutes long-term survival after surgery for hilar cholangiocarcinoma?

BACKGROUND: Hilar cholangiocarcinomas are rarely considered to be resectable and specific data regarding long-term survival are not available. METHODS: A retrospective single center experience from 1971 and 1995 details long-term survival among 339 patients who underwent surgery for adenocarcinoma of the hepatic duct bifurcation. Tumor removal was accomplished by resection of the bile duct bifurcation either alone (33 patients), in combination with hepatic resection (77 patients), or combined with hepatic and vascular resection (41 patients). Thirty-two patients underwent total hepatectomy and liver transplantation. In 188 patients the tumor was unresectable and palliative internal or external biliary drainage was established. The resectability rate was 49.2% and rose to 54% after inclusion of liver transplantation. The clinicopathologic features of 32 5-year survivors were compared with patients whose survival was less than 5 years. RESULTS: Thirty-two patients survived longer than 5 years after surgical treatment of hilar cholangiocarcinoma; 22 of these patients (69%) were still alive at last follow-up. Twenty-six long-term survivors had primarily undergone resection; 4 received liver transplants. There was 1 long-term survivor beyond 5 years after both exploratory laparotomy and subsequent percutaneous transhepatic drainage, and palliative hepatojejunostomy. Long-term survival after resection was significantly associated with less advanced tumor stages. Lymph node involvement and residual tumor were the primary prognostic factors both in a multivariate analysis after resection and in the cohort of long-term survivors. Nevertheless, long-term survivors were still at a significant risk to die from tumor recurrence. CONCLUSIONS: Radical resection offers the best possibility of prolonged survival with a good quality of life for patients with hilar cholangiocarcinoma.

Bile Duct Neoplasms↗