Search PubMed⌕ Search

Biomedical subjects

J Klempnauer

Publications and source records attributed to J Klempnauer.

At least 37 records · Page 2Linked to original sources

[Surgical treatment for hilar cholangiocarcinoma (Klatskin's tumor)].

Surgical treatment of hilar bile duct carcinoma remains difficult, which is due to the inadequate possibilities in assessing tumor extent during the preoperative diagnostic procedure as well as intraoperatively. Radical resection with negative histologic margins offers the best chance for long-term survival. The decision regarding the appropriate surgical approach is challenging due to the complexity of tumor localization and neighboring vascular structures. Aggressive resection demands extended liver resection, which is associated with the risk of postoperative liver failure. However, even limited surgery such as hilar resection can be curative and leads to long-term survival in individual cases. The principles of surgical oncology have led to more aggressive procedures, including the combination of liver transplantation and multivisceral resection, and can be performed with calculable morbidity and mortality. Nevertheless, the high risk of tumor recurrence under long-term immunosuppression, the limited availability of donor organs and the excellent results of liver transplantation in non-malignant diseases do not justify this procedure at present. Neoadjuvant radiochemotherapy has failed to demonstrate major benefit. In patients with irresectable tumor or distant metastases palliative measures are aimed at restoring an unobstructed bile flow with endoscopic placement of metal stents. Palliative treatment with additional radio- or photodynamic therapy may be considered in individual cases.

Adult↗

[Angiodysplasia of the colon combined with portal hypertension and recurrent gastrointestinal bleeding].

Angiodysplasia of the colon has been reported as one of the most common sources of lower gastrointestinal bleeding in the elderly whereas it is very rare in younger patients. Apart from this, portal hypertension may also have effects on the colon. There are, however, only a few reports which have investigated the colon in patients with portal hypertension. We report the case of a 16-year-old woman who presented massive bleeding from angiodysplasia of the colon assembled together with portal hypertension due to portal vein thrombosis caused presumably by neonatal umbilical cord infection. In this regard we discuss diagnosis, therapy and prognosis of this disease.

Adolescent↗

Successful outcome of acute graft-versus-host disease in a liver allograft recipient by withdrawal of immunosuppression.

BACKGROUND: Graft-versus-host disease (GVHD) after liver transplantation is uncommon, and the outcome is almost always fatal. Since 1987, about 30 cases have been described, and patient survival is mostly exceptional. METHODS: A 29-year-old man underwent retransplantation due to chronic cholestatic syndrome, 5 years after his first liver transplantation. Indication for the first liver transplantation was acute liver failure caused by exsiccosis. After the second transplantation, the patient had an initially uneventful course, developing thrombocytopenia at day 21 followed by skin rash and septic complications. Diagnosis of acute GVHD was made by using serological techniques for HLA-A and HLA-DRB and subsequently by fluorogenic sequence-specific primed polymerase chain reaction. In addition, donor lymphocytes were marked by immunohistochemical methods via biopsies of the skin. Immunosuppressive therapy was withdrawn to allow the patient's own immune system to eliminate donor cells. RESULTS: By withdrawing the immunosuppressive therapy, clinical and morphological signs of GVHD vanished. The patient is doing well without recurrence 13 months after transplantation. CONCLUSION: Withdrawal of immunosuppressive therapy is a promising approach in the treatment of acute GVHD to allow the patient's immune system to reconstitute itself, reject offending lymphocytes, and avoid lethal septic complications.

Acute Disease↗

[Neuroendocrine tumors of the stomach. Surgery therapy and prognosis].

Gastric carcinoid tumors are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like (ECL) cells of the stomach. A classification system distinguishing three types of gastric carcinoid tumors has been proposed: 1) tumors related to chronic atrophic gastritis, 2) tumors associated with Zollinger-Ellison syndrome, and 3) sporadic lesions. It is apparent that hypergastrinemia-associated gastric carcinoids show a rather benign biological behavior. Normo-gastrinemic sporadic lesions, on the other hand, require an aggressive surgical management. We report seven patients with gastric neuroendocrine tumors ("carcinoids"), who underwent surgical treatment in our department between 1988 and 2000. Surgical therapy included total gastrectomy with D2 lymphadenectomy in two cases with type I tumors and for one patient with type III tumor. One patient with a type II tumor was treated by distal subtotal gastrectomy and another by antrectomy. A local excision was performed on one patient with type I tumor. After a mean follow-up of 8 years, 5 of 7 patients are alive without recurrence.

Adult↗

[Comparison between treatment results for gastric cancer in younger and elderly patients].

INTRODUCTION: While gastric cancer shows an increased incidence in elderly patients, the rate of younger patients affected by this disease represents up to 15 %. Younger patients are frequently diagnosed with advanced tumor stages with a poor prognosis although literature data on this issue are controversial. PATIENTS AND METHODS: 643 patients with primary gastric carcinoma were operated in our institution between March 1986 and December 2000. No neoadjuvant treatment was administered in these patients. We analysed the data of these patients retrospectively. A comparison of the results between patients younger than 40 years (n = 38, median age 37 years) and older than 70 years (n = 182, median age 75 years) was performed. RESULTS: The radical (R0-) resectability rate was rather high for both, younger (78.9 %) and elderly (76.9 %) patients. Postoperative morbidity was higher in elderly than in younger patients (32.9 % vs. 23.2 %; p < 0.05), as well as the postoperative mortality (7.7 % vs. 2.6 %; p < 0.05). Both younger and elderly patients showed advanced (II to IV) tumor stages (76.3 % vs. 73.3 %, n. s.). There was a significant difference between the rate of diffuse carcinomas in young and elderly patients (63.2 % vs. 22.5 %). The 5-years survival rate following R0-resection was significantly higher for younger patients (54.2 % vs. 32.9 %; p = 0.01), differences occurred only after the second postoperative year. CONCLUSIONS: The resectability of gastric carcinoma is not related to the patients age. Due to comorbidity, postoperative morbidity may be increased in elderly patients. Although both younger and elderly patients show advanced tumor stages, diffuse carcinomas are more frequent in younger patients. The short-term prognosis is similar for both age groups, long-term results are better for younger patients. The different life expectancy should be considered when interpreting these results.

Adult↗

Combined pancreas and kidney transplantation in a lean type 2 diabetic patient. Effects on insulin secretion and sensitivity.

BACKGROUND/AIMS: Pancreas transplantation is an established method of treating Type 1 diabetes. It was our aim to test the consequences of pancreas transplantation in a Type 2 diabetic patient by determining insulin secretion and sensitivity before and after surgery. PATIENTS AND METHODS: A female patient with Type 2 diabetes and end-stage nephropathy was treated with combined pancreas and kidney transplantation. Before surgery and at 4 weeks, 6 months and 2 years afterwards, insulin sensitivity was measured using hyperinsulinemic euglycemic clamps and insulin secretion was quantified after oral glucose or intravenous glucagon challenges. RESULTS: The patient was insulin resistant before surgery (glucose infusion 4.6 mg. kg (-1). min (-1), normal range 6.4 +/- 0.5 mg.kg( -1). min (-1). Insulin sensitivity declined further after transplantation (1.4 and 3.0 mg. kg -1. min -1 after 4 weeks and 6 months, respectively), but improved to 5.4 mg. kg (-1). min (-1) after 2 years. Insulin secretion was greatly impaired before surgery. Insulin and C-peptide responses after oral glucose and intravenous glucagon increased into the normal range from 6 months after surgery onwards and oral glucose tolerance remained non-diabetic (IGT). CONCLUSIONS: Insulin resistance is first aggravated after pancreas transplantation, probably due to immunosuppressive treatment including glucocorticoids, but improves on the long term. The initially impaired insulin secretion from the transplant may also be explained by the action of glucocorticoids or by transient and reversible organ damage.

Diabetes Mellitus, Type 2↗

Results of combined gastrectomy and pancreatic resection in patients with advanced primary gastric carcinoma.

BACKGROUND/AIMS: Although the incidence of primary gastric carcinoma is decreasing, the majority of patients in Western countries are still diagnosed with advanced tumor stages. In many cases surgical therapy can be performed only by multivisceral resections including the pancreas. METHODS: Between April 1986 and April 1997, thirty-three patients with primary gastric carcinoma underwent gastric resection and segmental/total pancreatectomy at our institution (21 males, 12 females; median age 57 years). The operative and pathologic findings and clinical course in these patients were analyzed retrospectively. RESULTS: In all patients total gastrectomy with D2 lymphadenectomy was performed. In 26 patients (79%) the pancreatic tail was also resected. Other resections included the pancreatic head in 5 patients (15%) and the whole pancreas in 2 cases (6%). Radical (R0) resections were possible in 73% of all cases (n = 24). 22 patients (67%) had stage-IV disease due to liver/peritoneal metastases (n = 11) or to extensive lymph node metastases (N3, n = 11). Histology showed a predominance of the diffuse type according to Laurén (n = 16, 49%). Intraoperatively suspected tumor infiltration of the pancreas was confirmed by histology only in 39% (n = 13) of the examined resection specimens. Postoperative morbidity was 36% (n = 12) and mortality was 9% (n = 3). Five patients developed pancreatitis or peripancreatic abscess, 2 with a lethal outcome. Overall the median survival was 13 months. Following R0 resection median survival was 17 months. If the pancreas was microscopically not infiltrated, median survival was 23 months. CONCLUSION: Pancreatic invasion in patients with gastric carcinoma is often associated with positive lymph nodes and liver metastases or peritoneal carcinomatosis. Intraoperatively, true pancreas invasion is difficult to differentiate from inflammatory reactions. Postoperative morbidity and mortality are increased by pancreatic resection, mainly due to pancreatitis or peripancreatic abscess. Curative (R0) resection improves prognosis and even long-term survival can be achieved in selected individual cases. Palliative resections can be performed for local complications like bleeding or obstruction refractory to other therapies.

Adult↗

Hemodynamic consequences of porcine kidney xenograft reperfusion in cynomolgus monkeys.

BACKGROUND: After xenograft reperfusion, complement activation may lead to generation of anaphylatoxins and cardiocirculatory instability of the recipient. METHODS: In 13 cynomolgus recipients of either unmodified or human decay accelerating factor transgenic porcine kidneys cardiocirculatory parameters were measured by single indicator transpulmonary thermodilution. RESULTS: After graft reperfusion, recipient cardiac output decreased by 25.4% (P<0.05), intrathoracic blood volume by 22.8% (P<0.05), extravascular lung water increased slightly (P=n.s.). The impairment in cardiac output was neither influenced by the graft's weight or human decay accelerating factor transgenicity. sC3a and sC5b-9 complement levels in the recipient monkeys showed a sharp peak upon reperfusion. CONCLUSIONS: After reperfusion a marked and significant cardiodepression accompanied by relative volume depletion were observed. Analysis of volume status ruled out a mere volume shift as the underlying reason for the observed drop in cardiac output. These data may be relevant for the perioperative management of human recipients of discordant xenografts in the future.

Animals↗

Replacement of calcineurin inhibitors with mycophenolate mofetil in liver-transplant patients with renal dysfunction: a randomised controlled study.

BACKGROUND: Renal dysfunction is a major complication of long-term immunosuppressive therapy with calcineurin inhibitors (CNI) in liver-transplant recipients. We undertook a randomised study to assess the safety and efficacy of CNI withdrawal and replacement by mycophenolate mofetil. METHODS: 28 people who had had renal dysfunction attributable to suspected CNI toxicity after liver transplantation participated in the study. We replaced CNI with mycophenolate mofetil in a stepwise pattern in half the group (study patients); the other half (controls) stayed on CNI immunosuppression. Renal function, blood pressure, uric acid, and blood lipids were measured before and 6 months after study entry. Side-effects of medication and graft function were recorded throughout the study. FINDINGS: At the end of the study, mean (SD) serum creatinine had fallen by 44.4 (48.7) micromol/L in study patients compared with 3.1 (14.3) micromol/L in controls; a mean difference of 41.3 micromol/L (95% CI 12.4-70.2). Moreover, systolic and diastolic blood pressure, and serum uric acid decreased significantly in the study group but not in the control group (mean [95% CI] between group differences 10.8 mm Hg [3.0-18.6], 5.0 mm Hg [0.9-9.2], and 83.1 micromol/L [12.7-153.6], respectively). There were no changes in cholesterol or triglyceride concentrations in either group. Side-effects were reported by eight of the study patients. Three reversible episodes of acute graft rejection occurred in study patients during mycophenolate mofetil monotherapy, whereas none occurred in the control group. INTERPRETATION: Substitution of CNI by mycophenolate mofetil can improve renal function, blood pressure, and uric acid concentration of liver-transplant patients, but there is an increased rejection risk with mycophenolate mofetil monotherapy.

Blood Pressure↗

Differentiation of liver cell adenomas from well-differentiated hepatocellular carcinomas by comparative genomic hybridization.

Liver cell adenomas (LCAs) are rare tumours which may be difficult to differentiate from low-grade hepatocellular carcinomas (HCCs). This study used comparative genomic hybridization (CGH) to look for cytogenetic aberrations which would serve to distinguish between these tumours. For this purpose, ten LCAs and six well-differentiated HCCs were analysed and the results were compared with those reported previously for 15 well-differentiated HCCs. Aberrations were seen in 2/10 LCAs: a gain of chromosome 7p was observed in one and gains of 17q and 20 in a second case. In 6/6 well-differentiated HCCs, up to 13 aberrations were detectable, with a mean of 7.2 aberrations per case in chromosome sites 1q, 4p, 4q, 5p, 5q, 6p, 6q, 7p, 7q, 8p, 8q, 10q, 11p, 13q, 14q, 16p, 16q, 17p, 17q, 20p, 20q, and 21q. Aberrations focused on gains or losses of six chromosome sites, 1q, 4q, 8p, 8q, 16p, and 17p; in all HCC samples, at least two of these sites were affected. None of these aberrations occurred in any of the LCAs analysed. CGH is therefore helpful in distinguishing between LCA and well-differentiated HCC. Detection of one or more of the six most frequent aberrations in HCC supports the diagnosis of carcinoma and makes LCA unlikely.

Adenoma, Liver Cell↗

Guanylin in the human pancreas: a novel luminocrine regulatory pathway of electrolyte secretion via cGMP and CFTR in the ductal system.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a channel and regulator protein that is crucially involved in transepithelial ion transport. In the exocrine pancreas, the CFTR-mediated secretion of an electrolyte-rich fluid is a major but as yet incompletely understood function. We show here that the peptide guanylin is a specific activator of CFTR function in the human pancreas implicating regulation of pancreatic electrolyte secretion. Guanylin and its affiliated signaling and effector proteins including guanylate cyclase C, cGMP-dependent protein kinase II, CFTR, and the epithelial Cl-/HCO3- exchanger, anion exchanger 2, are highly expressed in the human pancreas. Guanylin is localized specifically to the typical centroacinar cells and proximal duct cells which, based on its additional presence in the pancreatic juice, is obviously released luminally into the pancreatic ducts. The guanylin receptor and the respective functional downstream proteins are all confined to the apical membrane of the duct cells implicating an as yet unknown route of luminal regulatory pathway of electrolyte secretion in the ductal system. Functional studies in two different human pancreatic duct cell lines expressing the CFTR Cl- channel that is functionally intact in CAPAN-1 cells but defective (delta F508) in CFPAC-1 cells clearly identify guanylin as a specific regulator of pancreatic CFTR channel function. Whole-cell patch-clamp recordings in CAPAN-1 cells revealed that forskolin induces an increase of Cl- conductance mediated by cAMP. In contrast, guanylin increased Cl- conductance in the same cells via cGMP but not cAMP; the respective membrane current was largely blockable by the sulfonylurea glibenclamide. In CFPAC-1 cells, however, neither guanylin nor forskolin produced a current activation. Based on the present findings we conclude that guanylin is an intrinsic pancreatic regulator of Cl- current activation in pancreatic duct cells via cGMP and CFTR. Remarkably, in the pancreas guanylin may exert its function through an intriguing luminocrine mode via the pancreatic juice.

Cyclic GMP↗