Search PubMed⌕ Search

Biomedical subjects

C Wittekind

Publications and source records attributed to C Wittekind.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Pancreatic intraepithelial neoplasia in chronic pancreatitis].

Chronic pancreatitis causes destruction of the pancreatic gland which leads to tissue fibrosis and regenerative hyperplasia of the epithelium of pancreatic ducts and ductules. Morphological studies revealed distinct proliferative lesions in the pancreatic ducts and ductules adjacent to infiltrating adenocarcinomas of the pancreas. A stepwise progression from mild to severe dysplasia in these hyperplastic lesions has been reported. These lesions, called Pancreatic Intraepithelial Neoplasia (PanIN), harbour a number of well-characterised genetic alterations. Therefore, PanINs were defined as true clonal neoplastic lesions with minimal to moderate and severe cytological and architectural atypia. Almost all of the genetic alterations that have been identified in pancreatic adenocarcinomas have also been identified in PanIN lesions. The prevalence of genetic changes increases as the degree of cytological atypia and histological dysplasia in the PanIN lesions increases. However, some genetic abnormalities have also been found in chronic pancreatitis and normal pancreas, e. g. K-ras mutations. However, due to intratumorous heterogeneity of the genetic changes, further studies are necessary to search for more specific and homogeneous expressed molecular markers. A better understanding of the molecular genetic changes occurring during neoplastic progression in the pancreas will form the basis for future strategies of early tumour detection and improved therapy.

Adenocarcinoma↗
PubMed2001

[The new WHO classification of liver tumors--what is really new?].

The new WHO (2000) Classification comprises all gastrointestinal tumours including tumours of the liver and intrahepatic bile ducts. The differences between the old edition from 1994 and the new classification will be outlined. A comparison was made with regard to new entities, definitions and tumor subtypes. The eight tumour subgroups of the 1994 classification have been reduced to seven in the 2000 WHO edition, omitting the "unclassified tumors" and changing the group's terms. The 2000 classification shows some minor changes in the ICD-O numbers and in terminology. An important change and hopefully beneficial progress has been achieved by introducing more detailed definitions of epithelial abnormalities, namely liver cell dysplasia and its different subtypes (large cell type dysplasia, small cell type dysplasia, dysplastic nodules low-grade and high-grade). The miscellaneous lesions (former called tumour-like lesions) have been reduced in number. In contrast to the 1994 classification which only contained definitions and short descriptions of macroscopic and microscopic findings as well as only sparse clinical information, the 2000 classification offers much more text with new information on epidemiology, aetiology, clinical features, spread, macroscopy, microscopy, genetic susceptibility, and genetics. Some minor differences between the old and new WHO classification can be recognized. Major changes comprise the extended terminology in precancerous epithelial changes, e.g., liver cell dysplasia and reduction of the amount of text.

Humans↗
PubMed2000

Author reply

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Decreased expression of p27 protein is associated with advanced tumor stage in hepatocellular carcinoma.

Reduced expression of the cyclin-dependent kinase inhibitor p27 has previously been correlated with fatal clinical outcome in some tumors, including gastric, breast, and prostate cancers. For hepatocellular carcinoma, the findings are equivocal. In situ hybridization and immunohistochemistry were performed on a series of 203 curatively (R0) resected hepatocellular carcinomas and in corresponding non-cancerous liver tissue to detect p27. Patients receiving liver transplantation were excluded. The results were correlated with histopathological stage according to the UICC system, Edmondson grade, several other histopathological factors of possible prognostic significance, and finally patient survival. Whereas p27 mRNA was expressed homogeneously in all carcinomas examined, the p27 protein was found in various amounts. The labeling index of p27 protein was significantly lower in advanced stages of the disease (P < 0.001, chi(2) = 28.1). We observed decreased p27 protein in higher pT categories (P < 0.001, chi(2) = 24.7) and in multiple tumor nodules (P < 0.001, chi(2) = 9.3). Multivariate Cox survival analysis identified age, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. We conclude that evaluation of p27 in hepatocellular carcinoma is useful to predict stage of disease and may have clinical significance, e.g., in predicting optimal therapeutic regimes.

Adult↗
PubMed2000

p53 mutation pattern in hepatocellular carcinoma in workers exposed to vinyl chloride.

BACKGROUND: Vinyl chloride (VC) is a known animal and human carcinogen that is associated with liver angiosarcoma and most likely also with hepatocellular carcinoma (HCC) in humans. METHODS: The authors examined the presence of p53 gene mutations in 18 HCC specimens from patients with known exposure to VC (median, 8883 parts per million-years; median duration, 245 months). In all cases, other risk factors for the development of HCC (hepatitis B virus and hepatitis C virus infections, alcohol consumption, and metabolic or autoimmune disorders) were excluded. Three patients had concomitant cirrhosis. The p53 gene was examined by direct sequencing of exons 5-9. RESULTS: Mutations of the p53 gene were found in 11 of 18 HCCs examined. The point mutations detected were comprised of five transversions and five transitions. Five of 11 mutations (codons 175, 245, 248, 273, and 282) occurred at CpG sites. Histopathologic liver alterations (mild sinusoidal dilatation, [portal] fibrosis, and centrilobular siderosis) in tumor surrounding nonneoplastic liver confirmed exposure to VC. CONCLUSIONS: The results of the current study indicated a relation between VC exposure and the development of HCC. The mutation pattern of p53 with a nearly equal rate of incidence of transitions and transversions and a high rate of incidence of mutations at CpG sites may reflect endogenous mechanisms (e.g., deamination of 5-methylcytosine) rather than exogenous carcinogens.

Aged↗
PubMed2000

Photodynamic therapy for advanced bile duct cancer: evidence for improved palliation and extended survival.

Median survival time of nonresectable hilar bile duct cancer is only 4 to 6 months owing to tumor spread in the biliary tree, refractory cholestasis, and sepsis or liver failure. We explored whether local photodynamic therapy of nonresectable bile duct cancer could improve survival. A sample size of 23 patients is required to detect an increase in 6-month survival rate from less than 50% to greater than 70% in a single-arm phase-II trial with a statistical power of 80% (Fleming's single step procedure; alpha = 0.05). Twenty-three consecutive patients (8 women, 15 men; 67 +/- 14 years) with nonresectable bile duct cancer (Bismuth type III n = 2, type IV n = 21) were treated with photodynamic therapy and biliary endoprosthesis. Photofrin (QLT Pharmaceuticals, Vancouver, Canada) (2 mg/kg body weight intravenously) was photoactivated after 1 to 4 days with laser light (630 nm; 242 J/cm(2)) via endoscopic retrograde access. The 6-month survival rate was 91% after diagnosis and 74% after start of photodynamic therapy (30-day mortality rate was 4%) at a median follow-up time of 10.3 months after diagnosis. Causes of death were tumor progression (n = 9) and bacterial infections (n = 4). The median rate of local tumor response was 74%, 54%, 29%, and 67% after the first, second, third, fourth, and fifth photodynamic therapy. Time to progression ranged from 3 to 8 months. All patients, except 1 with diffuse liver metastases, improved in cholestasis, performance, and quality of life. Photodynamic therapy can prevent tumor occlusion of hilar bile ducts. The apparent benefit in survival time should be confirmed in a controlled trial versus palliation by endoprosthesis only.

Adenocarcinoma↗
PubMed2000

Diagnosis and staging of lymph node metastasis.

The process of lymph node metastasis is not completely understood. Although we know some basic molecular mechanisms of metastasis, the exact procedure from the initiation of a primary tumour to overt lymph node metastasis remains obscure. A few morphological features of different primary tumours are known to correlate with the probability of lymph node metastasis, e.g., tumour histology (carcinoma vs. sarcoma), tumour size, T category, poor grade of differentiation and invasion of lymph vessels. Few attempts have been made to use markers of molecular differentiation such as nm23 as an additional indicator of lymph node metastasis. A drawback is the lack of an exact definition of lymph node metastasis or micrometastasis and how to include new findings such as the demonstration of cytokeratin-positive cells in "tumourfree" lymph nodes. Some of these aspects will be discussed within this review and proposals for classifications presented.

Classification↗
PubMed2000

Laparoscopic abdominoperineal resection: early postoperative results of a prospective study involving 116 patients. The Laparoscopic Colorectal Surgery Study Group.

PURPOSE: Although laparoscopic colorectal surgery is attracting ever more attention, its use for curative treatment of colorectal carcinoma in particular continues to be controversial. The present study was an attempt to analyze the results of the perioperative course, oncologic quality, and preliminary long-term results. METHOD: The data considered here were collected within the framework of a prospective, observational study initiated on August 1, 1995, and involving a total of 18 institutions in Germany and Austria. At the end of three years, the results are now being presented selectively, i.e., focusing only on abdominoperineal resection. RESULTS: A total of 116 patients underwent laparoscopic abdominoperineal resections, 98 (84.5 percent) of which were performed with curative intent. The mean operating time was 226 (confidence interval, 140-365) minutes. Seven patients (6 percent) experienced an intraoperative complication, which in more than one-half of the cases was a vascular injury involving the presacral venous plexus; the conversion rate was 3.4 percent. Postoperatively, 40 patients developed 97 complications--including those of a very minor nature--giving an overall morbidity rate of 34.4 percent. Reoperation in six patients (5.2 percent) had to be performed for an afterbleed in one-half of the cases and ileus in the other one-half. Postoperative mortality was a low 1.7 percent. In most of the curative resections, an oncologically radical operation with high transection of the inferior mesenteric artery and a complete dissection of the pelvis down to the floor was performed. The median number of lymph nodes investigated was 11.5, and there was wide fluctuation in the numbers among the individual institutions. Tumor cell dissemination occurred intraoperatively in five patients. In the meantime, 79 patients (81 percent) underwent at least one follow-up examination, the mean follow-up period being 491 days. Seven patients developed a local recurrence, and a further six patients developed distant metastases. For recurrence-free survival rate, the Kaplan-Meier estimation calculated a probability of 71 percent. CONCLUSION: Not all of the reservations about laparoscopic abdominoperineal resection, in particular with regard to resection with curative intent, have yet been eliminated. The present study does, however, show that a laparoscopic approach can in principle meet oncologic requirements of radicality and, with regard to the postoperative course, is associated with considerable benefits to the patient.

Abdomen↗
PubMed2000

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗
PubMed2000

Mutations of p53 tumor suppressor gene, apoptosis, and proliferation in intrahepatic cholangiocellular carcinoma of the liver.

This study was performed to examine the correlation between mutations of the p53 tumor suppressor gene, the occurrence of apoptosis, and proliferation in cholangiocellular carcinoma of the liver. The results obtained were compared with pathohistological stage (according to UICC) and grade and with disease related survival rate. In 41 curatively (R0-) resected intrahepatic cholangiocellular carcinomas, the status of the p53 gene was determined by direct sequencing of exons 4-9 and immunohistochemically. Apoptosis was assessed using the in situ end labeling (ISEL) technique in combination with morphological criteria. Proliferation was analyzed by immunohistochemistry of MIB-1 (Ki-67), Proliferating cell nuclear antigen (PCNA), and silver-stained nucleolar organizer regions (AgNOR). The results obtained were compared with pathohistological stage (according to UICC), grade, several other histopathological factors, and survival rate. Mutations of p53 were detected in 15/41 carcinomas examined (37%). The most common change was a G-->C and C-->T transition, changing the hot spot amino acid determined by exons 4-8. Of these 15 tumors, 14 were also p53-positive by immunohistochemistry. In each carcinoma examined, we could demonstrate MIB-1, PCNA, and AgNOR dots and also apoptotic cells in variable proportions. The proliferation markers showed a significant correlation among themselves. In univariate survival analysis, the extent of the primary tumor, lymph node status, grade, and p53 were significant factors influencing patient survival. Performing multivariate Cox regression survival analysis, however, only the extent of primary tumor and lymph node status had an independent prognostic impact. Apoptosis was not related to patient prognosis or to other parameters examined. In conclusion, these results indicated that p53 could serve as an additional prognostic parameter that could provide auxiliary information for patient outcome. However, tumor stage and lymph node involvement were the strongest prognostic factors. We failed to establish apoptosis or other pathological parameters as factors predicting the prognosis of patients with cholangiocellular carcinoma.

Apoptosis↗
PubMed2000

Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study.

BACKGROUND: Anthranoid laxatives are the most commonly used purgatives in the therapy of acute and chronic constipation. Recent experimental data and a prospective cohort study provide evidence of a possible risk of anthranoid use for the development of colorectal neoplasms. MATERIALS AND METHODS: We performed a prospective case control study at the University of Erlangen to investigate the risk of anthranoid laxative use for the development of colorectal adenomas or carcinomas. A total of 202 patients with newly diagnosed colorectal carcinomas, 114 patients with adenomatous polyps, and 238 patients (controls) with no colorectal neoplasms who had been referred for total colonoscopy were studied. The use of anthranoid preparations was assessed by standardised interview, and endoscopically visible or microscopic melanosis coli was studied by histopathological examination. RESULTS: There was no statistically significant risk of anthranoid use for the development of colorectal adenomas (unadjusted odds ratio 1.0; 95% CI 0.5-1.9) or carcinomas (unadjusted odds ratio 1.0; 95% CI 0.6-1.8). Even after adjustment for the risk factors age, sex, and blood in the stools by logistic regression analysis the odds ratio for adenomas was 0.84 (95% CI 0. 4-1.7) and for carcinomas 0.93 (95% CI 0.5-1.7). Also, there were no differences between the patient and control groups for duration of intake. Macroscopic and high grade microscopic melanosis coli were not significant risk factors for the development of adenomas or carcinomas. CONCLUSION: Neither anthranoid laxative use, even in the long term, nor macroscopic or marked microscopic melanosis coli were associated with any significant risk for the development of colorectal adenoma or carcinoma.

Adenoma↗
PubMed2000

Frequency of p16(INK4A) alterations and K-ras mutations in intrahepatic cholangiocarcinoma of the liver.

BACKGROUND: Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies. AIMS: To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver. METHODS: The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival. RESULTS: Hypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients. CONCLUSION: These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.

Bile Duct Neoplasms↗
PubMed2000

[Current concepts of metastasis classification].

New findings of molecular pathology provide better insight in the process of metastasis. Single findings in few patients are, however, useful in being taken as parameters which signalize the individual risk of a metastasis not detectable by clinical methods. In addition they cannot be used as prognostic factors. On the other hand, there are important data which indicate a prognostic significance of so called isolated tumour cells, which can be detected by cytological or molecular methods. Current and proposed classifications of metastasis reflect the necessity, to better describe the situation of an individual patient to design an optimal therapy. Such more exact classifications will form the basis of a more differentiated therapy and will give more exact data to estimate prognosis.

Humans↗
PubMed2000

[Pathology of liver tumors].

Neoplasms of the liver may arise from any cell type within the liver parenchyma. Hepatocellular carcinoma is by far the most common primary malignant tumour of the liver in adults. Indeed, it is one of the most common tumours in the world with striking geographic differences. These incidence rates can be explained by differences in Hepatitis-Virus carrier rates which they closely reflect. Nearly 10% of malignant liver tumors are represented by cholangiocarcinoma which originates from small intrahepatic bile ducts. Hepatoblastoma accounts for approximately 5% of malignancies in childhood. Most hepatoblastomas fall into epithelial or mixed epithelial and mesenchymal categories. Fetal-type cells and embryonal-type cells represent the epithelial components. Rare primary malignant non-epithelial tumours are angiosarcomas, leiomyosarcomas or fibrosarcomas, arising from vascular or mesenchymal components of the liver respectively. All types of Hodgkin and Non-Hodgkin Lymphomas may secondarily involve the liver. Most primary hepatic lymphomas are of diffuse large B-cell type and are extremely rare.

Adult↗
PubMed2000

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

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

Adult↗
PubMed2000

[Isolated tumor cells in primary malignant liver tumors].

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

Bile Duct Neoplasms↗