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Biomedical subjects

M Klimpfinger

Publications and source records attributed to M Klimpfinger.

At least 19 recordsLinked to original sources
PubMed2004

Inherent growth advantage of (pre)malignant hepatocytes associated with nuclear translocation of pro-transforming growth factor alpha.

The pro-peptide of transforming growth factor alpha (proTGFalpha) was recently found in hepatocyte nuclei preparing for DNA replication, which suggests a role of nuclear proTGFalpha for mitogenic signalling. This study investigates whether the nuclear occurrence of the pro-peptide is involved in the altered growth regulation of (pre)malignant hepatocytes. In human hepatocarcinogenesis, the incidence of proTGFalpha-positive and replicating nuclei gradually increased from normal liver, to dysplastic nodules, to hepatocellular carcinoma. ProTGFalpha-positive nuclei almost always were in DNA synthesis. Also, in rat hepatocarcinogenesis, proTGFalpha-positive nuclei occurred in (pre)malignant hepatocytes at significantly higher incidences than in unaltered hepatocytes. For functional studies unaltered (GSTp(-)) and premalignant (GSTp(+)) rat hepatocytes were isolated by collagenase perfusion and cultivated. Again, DNA synthesis occurred almost exclusively in proTGFalpha-positive nuclei. GSTp(+) hepatocytes showed an approximately 3-fold higher frequency of proTGFalpha-positive nuclei and DNA replication than GSTp(-) cells. Treatment of cultures with the mitogen cyproterone acetate (CPA) elevated the incidence of proTGFalpha-positive nuclei and DNA synthesis in parallel. Conversely, transforming growth factor beta1 (TGFbeta1) lowered both. These effects of CPA and TGFbeta1 were significantly more pronounced in GSTp(+) than in GSTp(-) hepatocytes. In conclusion, nuclear translocation of proTGFalpha increases in the course of hepatocarcinogenesis and appears to be involved in the inherent growth advantage of (pre)malignant hepatocytes.

Animals↗
PubMed2004

Prognostic relevance of tumour-associated macrophages and von Willebrand factor-positive microvessels in colorectal cancer.

Tumour-associated macrophages (TAM) are involved in tumour angiogenesis and anti-tumour immune response. In colorectal cancer (CRC), an association of high microvascular density (MVD) and unfavourable prognosis has been reported by some investigators. However, heterogeneous patient groups were studied. We, therefore, analysed the correlation between TAM and MVD and the prognostic relevance of MVD, TAM and T lymphocyte infiltration for long-term survival in a homogeneous group of 70 patients with moderately differentiated cancers of the International Union Against Cancer (UICC) stages II and III, who did not receive chemotherapy. MVD was evaluated using immunohistochemistry with antibodies against CD34 and von Willebrand factor (vWF). TAM and T lymphocytes were visualised with antibodies against CD68 and CD3, respectively. Statistical analysis did not reveal a significant correlation between TAM and T lymphocyte numbers and MVD. Multivariate analysis of immunohistochemical data from all CRC patients and the subgroup of patients with UICC stage-II CRC identified TAM- and vWF-positive microvessel numbers as prognostically relevant markers. Low numbers of TAM- and high numbers of vWF-positive microvessels were associated with an unfavourable prognosis. In conclusion, TAM- and vWF-positive microvessel numbers may serve as independent prognostic markers for patients with UICC stage-II and -III CRC and may help to identify patients with an unfavourable prognosis.

Aged↗
PubMed2003

The pathological assessment of mesorectal excision: implications for further treatment and quality management.

BACKGROUND AND AIMS: Most clinical practice guidelines today recommend total mesorectal excision (TME) for carcinoma of the middle and lower rectal thirds and partial mesorectal excision (PME) for the upper rectal third. However, these procedures may not always fulfill the oncological requirements. The pathological examination of resected rectal carcinomas should always include a visual assessment of the mesorectal excision to ensure oncological adequacy and appropriate quality. The clinical practice guideline of the German Cancer Society recommends reporting of the distal extent of mesorectal excision (total or partial without coning) and the excision in an inviolate fascial envelope. PATIENTS AND METHODS: Reporting schemas of assessment and documentation for daily use and for studies are presented. RESULTS: Careful macroscopic evaluation of the resection specimen should be standardized. This may be supplemented by stain marking after postoperative filling the inferior mesenteric or superior rectal artery with ink or methylene blue solution. Photodocumentation is highly desirable. The pathological assessment of adequacy of mesorectal excision should be taken into account in selection for adjuvant radiotherapy. Objective macro- and microscopic assessment of mesorectal excision by pathologists is essential for quality management throughout patient care and in clinical trials.

Carcinoma↗
PubMed2002

[Pericarditis as the initial manifestation of retroperitoneal fibrosis--a case report].

HISTORY AND CLINICAL FINDINGS: A 70-year-old patient with invasive ductal breast cancer underwent conserving surgery of the right breast and right axillary dissection as well as postoperative irradiation therapy. Five months later, she presented with dyspnoea and progressive weakness. INVESTIGATIONS: Clinically, the patient showed anasarca and petechial hemorrhages, laboratory tests revealed thrombopenia, hepatic dysfunction, radiologic investigations showed enlargement of the liver and spleen, effusions of the pleura and pericardium, and ascite. Echocardiography showed pericardial effusion without cardiac tamponade. TREATMENT AND COURSE: Despite supportive therapy the patient's performance status deteriorated significantly, the diagnosis of the underlying disease could not be established, the patient died with the clinical signs of cardiovascular failure. Autopsy revealed progressive retroperitoneal fibrosis with systemic involvement of pleura, pericardium, epicardium, myocardium, lungs, and kidneys and pericarditis. Retrospectively clinical symptoms were interpreted as right heart insufficiency due to pericardial effusion. CONCLUSION: This case report reminds of occurrence of manyfold clinic manifestations of retroperitoneal fibrosis in dependence of particular organic involvement and that retroperitoneal fibrosis represents a differential diagnosis.

Aged↗
PubMed2001

Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer.

The tumour-suppressor protein p53 has recently been shown to belong to a family that includes two structurally related proteins, p63 and p73. This study investigated the status of p53 and its two homologues in multiple simultaneous gastric carcinomas. Expression and mutation of p53, p73 and p63 including the two major isotypes TAp63 and black triangleNp63, were examined by direct DNA-sequencing, in situ hybridization, western blotting and immunohistochemistry in 68 gastric carcinomas of 32 patients. The results obtained were correlated with pathohistological stage (according to UICC(16)) and several other histopathological factors and finally with patient survival. p53 mutations were detected in 23/68 carcinomas (34%) from 18 patients with a discordant mutation pattern. Independently of p53 mutation status, p73 transcripts and protein expression were found in 33/68 carcinomas from 24 patients. p63 positivity was found in 21 patients; 25 out of 68 tumours expressed p63. The number of cells containing p63 and their distribution depend on the degree of tumour differentiation. High grade carcinomas of the diffuse type exhibited a significantly higher p63 expression. In intestinal metaplasia and atrophic gastritis, an increase of TAp63 and black triangleNp63 staining was also observed. Specific mutations of p73 or p63 causing amino acid substitutions were not identified. Neither p53, p73 nor p63 were related to prognosis. p73 and p63 have rarely been found to be mutated in gastric carcinomas, but both proteins were expressed in only a subset of tumours. The status of these p53 homologues was discordant in all patients with multiple simultaneous gastric carcinomas. The increased expression of p63 (TAp63 and black triangleNp63) in less well differentiated gastric carcinomas may indicate that p63 can act to promote neoplastic growth in the gastric epithelium.

DNA Mutational Analysis↗
PubMed2000

Long-term prognosis for colon cancer related to consistent radical surgery: multivariate analysis of clinical, surgical, and pathologic variables.

Despite the improvement in its prognosis in most Western countries, death from colon cancer is still a major problem. In a prospectively planned observation study, a large patient collective from a single institution in Austria was analyzed in terms of the surgical approach and factors influencing survival. A total of 696 patients with colonic carcinomas were admitted to our surgical department between January 1, 1984 and December 31, 1997. Radical surgery for localized tumors was consistently performed, including wide resection margins and complete removal of the regional lymph drainage zones. Clinical, histopathologic, and therapy-related factors were examined for their influence on long-term survival by means of univariate and multivariate analysis. The overall tumor resection rate was 99.3% (691/696); complete tumor removal (R0) was possible for 84.8% (590/696) of all patients. The overall postoperative hospital mortality rate was 3.2% (22/696), and it was 13% (7/556) for potentially curative resections. Five- and ten-year tumor-specific survival rates for stage I to III R0 resections were 83.8% and 78.8%, respectively. Adjuvant chemotherapy reduced tumor recurrence for stage III patients by 52.4%. The depth of tumor infiltration, lymph node status, and adjuvant chemotherapy were found to have an independent influence on survival as identified by the Cox models. In conclusion, a consistent radical surgical approach for potentially curative resected colonic cancer patients had survival rates that surpassed those of most published series without sacrificing low complication rates. In addition, adjuvant chemotherapy for stage III substantially improved survival.

Adult↗
PubMed2000

The Vienna classification of gastrointestinal epithelial neoplasia.

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.

Adenoma↗
PubMed1999

[Hypersensitivity vasculitis causing an acute abdomen].

The members of a family of four persons suffered acute gastroenteritis after eating a meal consisting of chicken. While three of them recovered rapidly, the 18-year old son developed an acute abdomen which had to be treated surgically and led to a complicated stay at the intensive care unit. Intraoperatively, a mild insignificantly inflamed appendix and an obscure segmental inflammatory process of the small bowel with local peritonitis were seen; this required an appendectomy and a peritoneal lavage. The development of bacterial peritonitis with multiple organ dysfunction required several surgical revisions with an open abdominal toilet treatment. Histological examination of the resected appendix specimen showed a severe primary fibrinoid necrotizing vasculitis with epitheloid-granulomatous reaction. Diseases such as Panenteritis nodosa, Wegener's disease and Churg-Strauss's syndrome were excluded by negative serology. By a process of exclusion, a hypersensitivity vasculitis was diagnosed and treated successfully with a high-dose cortisone regime.

Abdomen, Acute↗
PubMed1999

Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution.

Recent molecular studies have suggested that hyperplastic duct lesions of the pancreas are potential precursors of pancreatic ductal carcinoma. This study examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancreases from 140 patients were screened for the presence of mucinous cell hypertrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyperplasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples were analyzed for K-ras codon 12 mutations by polymerase chain reaction amplification of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 showed duct lesions. The lesions were evenly distributed throughout the pancreas. They were more common beyond the age of 40. MHT was present in 68%, DPH in 36%, ADH in 40%, and SQM in 36% of the cases. K-ras mutations were found in 19 samples from 15 out of 79 pancreases (18%), including all types of duct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positive specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/metaplastic duct changes of the pancreas increase with age, but their distribution pattern in the pancreas differs from that of ductal carcinomas.

Adolescent↗
PubMed1999

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Adult↗
PubMed1999

Long-term results of radical surgery for rectal cancer: multivariate analysis of prognostic factors influencing survival and local recurrence.

AIMS: To evaluate consistent radical surgery performed over a 13-year period for rectal cancer in terms of local tumour control and long-term survival. METHODS: Radical surgical procedure principally using total mesorectal excision (TME) for middle and lower rectal tumours, high ligation of the inferior mesenteric artery and sphincter-saving resections (SSR) whenever possible, has been performed prospectively since January 1984. RESULTS: Tumour resection was possible in 98.8% (636/644), potentially curative resections (UICC/AJCC R0 resection) in 85.7% (552/644) and sphincter preservation in 71.7% (462/644). Five- and 10-year observed survival rates, surgical mortality not excluded, for all patients were 49.2% and 37.4%. Tumour-adjusted 5- and 10-year survival rates were 60.5% and 55.3%. For curatively operated patients (UICC/AJCC R0) 5- and 10-year observed survival rates were 56.3% and 42.6% and tumour-adjusted survival rates were 68.6% and 62.7%. The 5- and 10-year local recurrence rates for R0 resected patients were 12.0% and 12.6%. Post-operative hospital mortality was 3.1%. CONCLUSIONS: Multivariate analysis using Cox's model identified increasing pT category and pN category, old age and low tumour location as detrimental factors having independent influence on survival. For local tumour failure only pT and pN category as well as adjuvant radiation therapy were identified in the Cox model as having an independent detrimental influence.

Adult↗
PubMed1999

Primary biliary cystadenocarcinoma perforating the duodenum and left intrahepatic biliary tree--mimicking a hydatid cyst.

We report the case of a 76-year-old woman with biliary cystadenocarcinoma perforating the left biliary tree and exhibiting intra-tumoral gas bubbles resulting from invasion of the duodenum. The clinical history included subfebrile temperatures of 3 months duration, and pains associated with an abdominal mass in the right upper quadrant. Blood tests showed leucocytosis, and radiological studies revealed the features of a partially calcified septated tumor with nodular components combined with multiple gas-fluid levels, mimicking an infected hydatid cyst. Intraoperative ultrasonography, cholangiography and frozen section histology were necessary to prove the malignant nature of this cystic tumor. Provided that complete resection with strict adherence to oncological precepts is possible, the prognosis of cystadenocarcinoma is better than in hepatocellular or cholangiocellular carcinoma.

Aged↗
PubMed1998

Multivariate karyometric approach in differential diagnosis of follicular thyroid neoplasms. A study of 31 cases.

A retrospective analysis of 19 follicular adenomas, 12 minimally invasive follicular carcinomas and 3 widely invasive follicular carcinomas of the thyroid was performed on 5-microm-thick Feulgen-stained paraffin sections by means of a semiautomatic system for picture analysis. The major aim was to assess the potential of multiparameter karyometry for separation of the first two tumour types. Sixteen planimetric and densitometric features were defined in each case on 200-300 randomly selected nuclei and processed by a number of uni- and multivariate statistical methods. Despite predominantly significant ANOVA results a substantial overlap between tumour groups limited the practical usefulness of any karyometric feature alone. Factor and cluster analyses indicated independence of planimetric and densitometric parameters from each other, which was of crucial importance in finding an optimal subset of variables for discriminant analysis. The classification rule derived from the latter procedure was checked by the "jack-knife" method, by classification of 3 widely invasive cancers and by hierarchical tumour clustering. Sensitivity and specificity of the model for detection of malignancy were 100% and 94.7%, respectively. A multivariate karyometric approach, when applied correctly, can be a useful tool for differentiation between follicular adenomas and minimally invasive follicular carcinomas of the thyroid.

Adenocarcinoma, Follicular↗
PubMed1997

Experience with a high speed biopsy gun in breast cancer diagnosis.

Pre-operative determination of histology and receptor status is important in optimizing the management of breast cancer. The purpose of our study was to evaluate the high speed biopsy gun in 109 patients with palpable breast tumours. High speed biopsies were performed using the system BIP High Speed Multi 22 with 16-gauge-needles at a speed of 30 m/s. All biopsies could be used for frozen sections and for determination of receptor status. In 81 patients (74.3%) malignant breast tumours were diagnosed, and three patients (2.8%) had highly suspicious lesions. The oestrogen receptor status was negative in 32%, progesterone receptor status negative in 41%. In one patient (0.9%) a high grade non-Hodgkin's lymphoma of B-cell-type was diagnosed. In 21.1% benign tumours were found. In one patient a malignant tumour was missed at biopsy (0.9% false-negative). It was concluded that high speed biopsy is a reliable and simple method for preoperative sampling of breast lesions.

Biopsy, Needle↗
PubMed1997

Multiple simultaneous gastric carcinomas.

A total of 1664 patients with gastric cancer were examined to evaluate the rate of multiple synchronous primary tumours. In cases of multiple synchronous cancer (MSC), the tumours were analysed immunohistochemically for their expression pattern of p53, c-erbB2, ras, E-cadherin and proliferative activity. Multiple synchronous gastric carcinomas (MSCs) were observed in 61 out of 1664 patients (3.7%), with a total of 134 carcinomas. In our series, early carcinoma was observed more frequently in MSC than in solitary cancers. The comparison of tumour stage in MSC and solitary tumours revealed that multiple early gastric cancers were significantly more often of type I (protruded type) and IIa (superficial elevated type) than solitary early cancer. Multiple advanced carcinomas were more often of a lower pT category than solitary advanced gastric cancer. Performing immunohistochemistry for p53, c-erbB2 and ras in 134 tumours with MSCs, we observed positivity rates of 33%, 59% and 87% respectively. In 43 patients, the multiple tumours in each individual patient demonstrated an identical status of p53 and c-erbB2, and in 42 patients a similar pattern of E-cadherin expression was observed. The proliferative index, determined by proliferating cell nuclear antigen (PCNA) immunolabelling, did not differ significantly between the MSC in each patient. Ras immunostaining was detected in 53 out of 61 patients, but also in metaplasia and regenerative hyperplasia in the specimens. In survival analysis, no difference was observed between patients with solitary or multiple early or advanced carcinomas. Our results suggest that in at least a high proportion of patients with gastric cancer multiple primary tumours arise from precancerous conditions leading to similar genetic alterations.

Aged↗