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Biomedical subjects

J Klempnauer

Publications and source records attributed to J Klempnauer.

At least 55 records · Page 3Linked to original sources

Early gastric cancer--excellent prognosis after curative resection in 87 patients irrespective of submucosal infiltration, lymph-node metastases or tumor size.

BACKGROUND AND AIMS: Despite a decreasing incidence of primary gastric carcinoma over the last decade, the incidence of early gastric cancer has remained unchanged. Some aspects of the surgical treatment (e.g., extent of resection, lymphadenectomy) are still controversially discussed in the literature. PATIENTS/METHODS: Between May 1986 and July 1999, 87 patients were operated upon due to primary early gastric adenocarcinoma. All patients data were analyzed retrospectively. RESULTS: Of 626 patients with primary gastric carcinoma, 87 (13.9%) had an early carcinoma (54 men, 33 women; median age 61 years). In all patients, curative (R0-) gastrectomy could be performed, total in 62 patients (71.4%) and subtotal in 25 patients (28.6%). Postoperative morbidity was 23% and mortality 4.5%. Mucosal tumors were found in 34 (39.1%) and submucosal in 53 (60.9%) patients. Multicentricity was present in eight cases (9.1%). Twelve patients (13.8%) had lymph-node metastases. The 5-year survival rate was 88.8%. The submucosal infiltration, the lymph-node infiltration, the histological type, and the tumor size had no statistically significant impact on prognosis. CONCLUSION: Radical resection of early gastric cancer cured most of the patients, irrespective of lymph-node metastases or tumor size. Multicentricity, increasing incidence of proximal cancers, and low mortality suggest that total gastrectomy may be indicated. Patients with early gastric cancer may benefit from D2-lymphadenectomy, but this has to be assessed in further randomized studies, in particular for those with small mucosal tumors.

Adenocarcinoma↗

Quantification of alpha 1-fetoprotein mRNA in peripheral blood and bone marrow: a tool for perioperative evaluation of patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Quantification of alpha 1-fetoprotein (AFP) mRNA in the blood using reverse transcriptase polymerase chain reaction (RT-PCR) could be a useful tool in monitoring the dynamics of minimal residual disease in patients with hepatocellular carcinoma (HCC). Since all available assays do not take into account the efficiency of cell separation, RNA extraction and reverse transcription, a competitive RT-PCR assay for quantification of AFP mRNA in relation to the housekeeping gene glyceraldehyde phosphate dehydrogenase (GAPDH) was established. PATIENTS AND METHODS: Peripheral blood of 22 patients and bone marrow aspirates of 11 patients with hepatocellular carcinoma was monitored perioperatively. Eighteen patients with other hepatic tumours or non-malignant hepatic diseases and 26 healthy blood donors served as controls. Messenger RNA contents were calculated relative to the content of GAPDH mRNA as an indicator of total cell count. RESULTS: Among HCC patients, 6 of 22 (26%) were positive for AFP mRNA before operation with values ranging from 2 ag/100 fg to 36 ag/100 fg GAPDH mRNA (mean 14). Among bone marrow samples, AFP mRNA was detectable in 5 of 11 (45%) cases, with 4 ag/100 fg to 23 ag/100 fg GAPDH (mean 9). However, AFP mRNA was also detectable in 3 of 18 (17%) control patients and in 2 of 26 (8%) healthy blood donors. Perioperative findings were highly variable. CONCLUSION: AFP mRNA is not a specific marker for circulating malignant hepatocytes. Whether definition of a cut-off level or the use of a multimarker-PCR will provide more useful data remains to be established.

Adult↗

Lamivudine and low-dose hepatitis B immune globulin for prophylaxis of hepatitis B reinfection after liver transplantation possible role of mutations in the YMDD motif prior to transplantation as a risk factor for reinfection.

BACKGROUND/AIMS: Reinfection with hepatitis B virus (HBV) after liver transplantation (OLT) is associated with an unfavourable clinical course. Lamivudine/hepatitis B immune globulin (HBIG) combination treatment reduces reinfection rates. However, it is unclear at what time point lamivudine should be started and which HBIG doses are sufficient. METHODS: Twenty-one patients receiving combination treatment were studied. Lamivudine was started up to 16.5 months before OLT and continued thereafter. HBIG was started intraoperatively and continued according to anti-HBs-titers. Median follow-up after OLT was 20 months. RESULTS: Eleven patients received lamivudine pretreatment for >2 (median 6) months due to initial HBV-DNA-positivity (median 749 pg/ml). After initial lamivudine response HBV-DNA increased in two of them to concentrations above 10 pg/ml prior to OLT. Both had developed mutations in the YMDD motif and suffered from HBV reinfection 13 and 75 days postoperatively. Individual HBIG consumption was highly variable (range 787-4,766 lU/month). Twenty-two percent of anti-HBs titers measured before HBIG administration were below 100 IU/l. CONCLUSIONS: Combined reinfection prophylaxis with lamivudine and HBIG is effective in patients with controlled viral replication at the time of OLT. However, pretransplantation lamivudine resistance is a risk factor for reinfection. Low dose HBIG maintenance therapy individualized according to anti-HBs-titers appears to be tenable.

Adolescent↗

Diagnostic impact of fluorescence in situ hybridization in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma.

Histopathological differentiation between hepatocellular adenoma and well differentiated hepatocellular carcinoma (HCC) may be a difficult task in small biopsies and occasionally in resected tumor specimens. Whether the analysis of chromosome aberrations can contribute to a more precise discrimination has not been analyzed systematically up to now. Therefore, fluorescence in situ hybridization was applied to 28 cases of adenoma and well differentiated carcinoma, using centromeric probes for chromosomes 1, 6, 7, 8, and X. None of 14 adenomas revealed an aberrant count in the analyses performed. By contrast, 13/14 carcinomas demonstrated aberrations for 2-5 chromosomes/case. Chromosome 1 was aberrant in 8/12 cases informative for this probe (67%), chromosomes 6 and 7 were aberrant in 9/14 cases (64%), chromosome 8 was aberrant in 11/14 cases (79%), and chromosome X in 7/14 cases (50%). Taking results for chromosomes 1 and 8 together, 13/14 HCC revealed aberrations for at least one of these chromosomes. Probes for 6, 7, and X revealed no additional aberrant cases.Thus, FISH for chromosomes 1 and 8, extended by probes for chromosomes 6, 7 and X, represents a promising approach toward a more accurate differentiation between hepatocellular adenoma and carcinoma.

Adenoma, Liver Cell↗

[Chronic cholecystitis simulating gallbladder tumor with liver abscess. Case report].

We report on a 58 year-old male who presented with nausea, a painful tumor palpable in the upper right epigastrium, moderate fever without leukocytosis. Both ultrasonic scan and subsequent computerized tomography lead to the primary diagnosis of a malignant tumor of the gall bladder infiltrating the liver and inducing an intrahepatic abscess formation in segments 4b and 3. The patient was scheduled for emergency operation, i.e. abscess drainage, cholezystectomy, and hemihepatectomy. However, at operation a purulent chronic cholezystitis was found without involvement of the liver itself. Consequently, a cholezystectomy was necessary and performed. Histological examination of the gall bladder revealed no signs of malignancy. The patient had an uneventful recovery and was discharged on post-operative day seven. This case report shows the difficulties in the differential diagnosis of inflammable processes and malignancies, which affect the gall bladder and adhering structures. A chronic inflammable process can mimic solid tumors. Despite cost-effective diagnostic tools the correct diagnosis was finally found by surgery.

Cholecystectomy↗

Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications.

Adult↗

Tracheal reconstruction under tension: an experimental study in sheep.

AIMS: Invasion of the trachea by thyroid cancer is a difficult problem. Circumferential resection and end-to-end reconstruction is the treatment of choice. The objective of our study was to investigate the effect of tension on tracheal healing and stenosis formation, and to ascertain the maximum tolerable tension. METHODS: Tracheal resections of 3, 6 and 9 cm with end-to-end anastomosis were performed on 25 sheep. The intraoperative force required for approximation of the tracheal stumps was measured. Luminal stenosis was determined with the aid of computerized planimetry 1, 2, 4, 8 and 24 weeks post-operatively. RESULTS: A gradual increase of the stenosis rate occurred with increasing tension on the anastomosis. Acceptable results were achieved in the majority of cases without release techniques or tension suture. CONCLUSIONS: Tracheal anastomosis under tension does not always lead to disruption or separation of the anastomosis. With the additional use of release manoeuvres and tension sutures, tracheal anastomosis under tension are possible without severe stenosis. The additional use of temporary stenting needs to be elucidated.

Anastomosis, Surgical↗

[Multiorgan resection in combination with intraoperative, hyperthermic chemotherapy in recurrent fibrolamellar hepatocellular carcinoma. An individual therapeutic concept for a 21-year-old patient].

The fibrolamellar karzinoma of the liver (FLC) as an uncommon variant of the hepatocellular karzinoma (HCC) is an indolent growing tumor. In its prior manifestation the FLC occurs at the adolescence and young adult stage. Early stage diagnosis and aggressive surgical treatment achieve better long-term results than usual resection of the HCC. Usually the FLC is, caused by its inconspicuous clinical appearance, diagnosed at a stage too advanced for effective surgical treatment. Especially the young patient's age and the remaining therapeutic options for palliative or curative treatment postulate a difficult decision for the surgeon. When a subtotal hepatectomy cannot be performed, total hepatectomy with liver transplantation is a valuable option. Palliative treatment protocols include systemic chemotherapy, ethanol instillation and chemoembolisation. We report the case of a 21-year-old male patient who presented with a recurrent intrahepatic FLC, peritoneal karzinomatosis confined to the right lower abdomen including gastric, splenic, diaphragmatic and colon transversum metastasis 14 months after primary surgery. We selected this patient as a reasonable candidate for an extended resection in trying to offer the optimal therapeutic modality. Thus we performed a right hemihepatectomy, near complete resection of the right diaphragm, total gastrectomy with lymphadenectomy including en bloc resection of spleen, colon transversum, omentum majus and peritonectomy of the paravesical region. Furthermore hyperthermic intraperitoneal chemotherapy was carried out the next day. The patient's postoperative course remained uncomplicated with fast recovery. Presently, 6 months after surgery, the patient has no evidence of recurrence.

Adult↗

[Surgical therapy of cystic echinococcosis of the liver].

This study analyses the results of a surgical deroofing technique that was used for the treatment of cystic echinococcosis of the liver in our institution during the last 18 years. The deroofing technique was used on 106 of 132 patients from January 1981 to December 1998. Other operative techniques (pericystectomy, hemihepatectomy) were performed on 26 patients. In 12 cases (9%) the operative procedure was completed by interventions at the extrahepatic bile ducts. 99 patients (75%) showed one or two cysts, and the remaining 33 patients (25%) had three or more cysts in the liver. 18 (14%) patients had to be reoperated on account of complications: in 5 cases a postoperative hemorrhage, in 11 cases a bile duct leakage and in 2 cases an intraabdominal abscess had to be treated operatively. The follow-up of 74 patients (81%) revealed recurrent disease in 14 (19%) cases. Surgical deroofing of cystic echinococcosis of the liver is easy to perform and in contrast to other minor surgical interventions universally applicable. The recurrence rate and the rate of postoperative complications are comparable to other minor surgical techniques. Therefore in our view this procedure represents the therapy of choice.

Adolescent↗

Surgical removal of a distinct subcutaneous metastasis of multilocular hepatocellular carcinoma 2 months after initial percutaneous ethanol injection therapy.

Subcutaneous tumor seeding after percutaneous ethanol injection therapy (PEI) for hepatocellular carcinoma is a rarely seen complication. It is reported due to needle track seeding during PEI after a distance of 6-46 months. Metastatic tumor spread is described subcutaneously, to the chest wall, abdominal wall and diaphragm. We report the case of a 76-year-old patient with chronic hepatitis B infection and cirrhosis which let to a multilocular hepatocellular carcinoma who underwent PEI. This patient developed 2 months after primary PEI a subcutaneous tumor formation confined to the right lower chest wall. Surgical tumor resection was performed. The histopathological evaluation confirmed subcutaneous seeding of the preknown hepatocellular carcinoma with a maximum of 30 mm in diameter. As a risk of PEI subcutaneous metastasis of the primary tumor should be considered even in early stage of therapy and close follow-up of the patient during treatment is required. Surgical tumor resection to ensure the curative intention of PEI is advisable.

Aged↗

Recovery of pancreatic beta cells in response to long-term normoglycemia after pancreas or islet transplantation in severely streptozotocin diabetic adult rats.

In the well-established, high-dose streptozotocin diabetic rat model, it is unknown whether normoglycemia after pancreas or islet transplantation may induce the expression of the glucose recognition structures and stimulate the replication of the few surviving pancreatic beta cells. Therefore, the endocrine pancreatic tissue was examined immunocytochemically in streptozotocin-treated major histocompatibility complex congenic Lewis rats at 10 and 100 days after transplantation of whole pancreata or isolated islets implanted under the kidney capsule. In the diabetic state the pancreatic beta cells displayed a weak immunostaining for insulin and glucokinase together with a lack of GLUT2 glucose transporter immunoreactivity in the plasma membrane. Ten days after transplantation, the surviving beta cells had regained their normal immunostaining for insulin and for the glucose recognition structures glucokinase and the A single high dose of streptozotocin causes severe experimental insulin-dependent diabetes mellitus in adult rats due to a selective destruction of the pancreatic beta cells in the islets of Langerhans. At doses between 50 and 60 mg/kg of body weight, only very few beta cells survive in the pancreas (1-3). The diabetic state is irreversible and insulin-dependent, thus representing an experimental animal model for type I diabetes (2). Because of the prevailing hyperglycemia, even the few residual beta cells in the pancreas do not function properly and therefore cannot contribute even to a basal supply of insulin to the organism (4). Pancreatic beta cells can function properly in a diabetic organism apparently only after restitution of normoglycemia (5). GLUT2 glucose transporter. One hundred days after transplantation, both of whole pancreas or isolated islets, the number of surviving beta cells in islets of the pancreata of the recipient animals had increased by two- to threefold. The regenerated beta cells were surrounded by a rim of other endocrine cells. The increase in the number of beta cells was not accompanied by signs of neogenesis from ductal structures in the pancreata. The authors' observations support the concept that strict long-term maintenance of normoglycemia through adequate supply of insulin from endocrine grafts is the ideal prerequisite for beta-cell recovery and restitution of the glucose recognition structures, as well as replication of beta cells in pancreata with end-stage diabetic beta-cell destruction after high-dose streptozotocin treatment.

Animals↗

[Peritoneal carcinosis in appendiceal carcinoma--at what price can the prognosis be improved?].

BACKGROUND AND AIM: Many patients with appendix carcinoma develop peritoneal carcinomatosis with poor prognosis. The purpose of this study was to look for results of multimodality treatment in these patients. PATIENTS AND METHODS: Data of 13 patients (11 men, 2 women, median age 58 years) with proven peritoneal carcinomatosis from appendiceal carcinoma, operated between 07/1995 and 10/1998 were analysed retrospectively with special regard to extent of resection, postoperative morbidity and mortality, survival. RESULTS: A macroscopically complete cytoreduction could be achieved in all patients by multivisceral resection with peritonectomy. Intraoperatively, after resection, an open, hyperthermic intraperitoneal chemotherapy with Cisplatin was performed. Morbidity and 90-days-mortality were 62% and 15%, respectively. After a median follow-up of 36 months all patients survived the therapy (excepting two postoperative deaths). CONCLUSIONS: In selected patients with advanced appendix carcinoma and peritoneal carcinomatosis prognosis can be improved by peritonectomy with intraperitoneal hyperthermic chemotherapy. This results in high mortality and morbidity.

Adenocarcinoma↗

Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil.

BACKGROUND: Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. PATIENTS: In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. METHODS: In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine +/-SD (micromol/L) was 201+/-77 at entry and 153+/-65 after 3 months (P<0.001). (3) Improvement occurred in 11 of 15 patients with creatinine elevation > or =12 months and in 6 of 6 patients with creatinine elevation < or =6 months. (4) One patient developed transient liver dysfunction and a second required retransplantation for progressive cholestasis but without signs of rejection. CONCLUSIONS: In patients who undergo liver transplantation, substitution of CNI by MMF leads to improvement of acute as well as chronic renal dysfunction in most cases. Side effects of MMF may be limiting in some patients, and the immunological consequences remain to be studied.

Adult↗

Transplantation of H-2Kb-transgenic adrenocortical cells in the mouse having undergone an adrenalectomy: functional and morphological aspects.

BACKGROUND: A new model of cellular adrenocortical transplantation after bilateral adrenalectomy in the mouse was established. This model was used to study the effects of the expression of the transgenic MHC class I molecule H-2K(b) (Kb) on graft survival and morphologic features, corticosterone secretion, and the possibility of tolerance induction in the recipient. METHOD: A single cell suspension of purified adrenocortical cells was grafted under the kidney capsule of B10.Br (H-2k) mice having adrenalectomies. Syngeneic, fully MHC-mismatched, and MHC class I-incompatible Kb-transgenic mice served as donor strains. To analyze graft function, urinary excretion and serum levels of corticosterone were monitored over 100 days. Tolerance induction in the graft recipients of Kb-transgenic and third party skin grafts was tested on day 50 after adrenocortical transplantation. Histological sections of the adrenocortical grafts were obtained on day 100. RESULTS: Recipients of syngeneic and Kb-transgenic grafts displayed pretransplant corticosterone levels on days 20, 50, and 100 and ACTH-stimulated serum corticosterone levels similar to those of controls on day 100 after adrenocortical transplantation. In contrast, in recipients of fully MHC-mismatched grafts, corticosterone excretion was significantly reduced. In this group, 4 of 7 mice did not survive. Syngeneic skin grafts survived indefinitely in recipients of syngeneic and Kb-transgenic adrenocortical grafts, whereas Kb-transgenic and fully MHC-mismatched skin grafts were acutely rejected. Tissue sections of the adrenocortical grafts revealed vascularized cell conglomerates in syngeneic and Kb-transgenic grafts without infiltrations of mononuclear cells. Furthermore, a differentiation similar to adrenocortical organization was partly found. CONCLUSION: In conclusion, a model of cellular adrenocortical transplantation was established. The results show that syngeneic transplantation resulted in physiological corticosterone levels early after transplantation, whereas fully MHC-incompatible grafts were rejected. Recipients of Kb-transgenic grafts showed unimpaired adrenocortical function, but did not tolerize toward Kb-transgenic skin grafts. Possible mechanisms include a local immunomodulatory effect of glucocorticoids secreted by the graft and a low immunogenicity of the relatively small numbers of transplanted cells.

Adrenal Cortex↗

Influence of cold ischemia time, pretransplant anti-porcine antibodies, and donor/recipient size matching on hyperacute graft rejection after discordant porcine to cynomolgus kidney transplantation.

Organs transplanted between phylogenetically disparate species, such as from the pig into the primate, are subject to hyperacute rejection (HAR). This form of xenograft rejection is mediated by preformed natural antibodies and is believed to occur invariably in discordant xenografts thus leading to rapid destruction and complete thrombosis of the graft. Recent data, however, have shown that in the porcine to cynomolgus monkey setting, HAR is not inevitably seen after porcine kidney transplantation. The influence of preoperative antiporcine antibody levels in the recipient, cold ischemia time, and donor organ weight on the onset of HAR was investigated by using unmodified large white pigs (aged 3-12 weeks) as organ donors and adult cynomolgus monkeys (aged 1.5-3.5 years) as recipients. Porcine kidney xenotransplantation was performed in either a non-life-supporting model (n=7) or in a life-supporting model (n=8). In both models, no correlation was found between cold ischemia time and HAR. When preoperative anti-porcine antibody levels were investigated, a significant increase in incidence of HAR was observed in animals with elevated anti-porcine IgM (P<0.05) but not IgG levels (P=NS). Interestingly, although 5 of 12 grafts with an organ weight of less than 50 g underwent HAR, none of three grafts with a donor organ weight of more than 70 g showed signs of HAR. In addition, all three larger grafts showed intraoperative and postoperative urine production, although only in 1 (48 g) of the 12 grafts weighing less than 50 g primary graft function was observed. In one animal, a second porcine kidney (23 g) was successfully transplanted (without HAR) immediately after HAR and subsequent removal of a first porcine kidney (20 g). These results indicate that in the porcine to cynomolgus monkey setting anti-porcine IgM rather than IgG anti-porcine antibody levels seem to be of predominant importance for the induction of HAR. By increasing the donor organ size and weight the frequency of the onset of HAR can be at least reduced. This is most likely due to immunoabsorption of the recipients preformed antibodies in the porcine kidney without lethal damage for the graft.

Acute Disease↗