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H P Dienes

Publications and source records attributed to H P Dienes.

At least 19 recordsLinked to original sources

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer.

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.

Aged↗

[Morphology of drug induced liver damage].

Hepatotoxicity is a significant complication of therapeutic drug use. As ist can imitate nearly all hepatopathies, the diagnosis of drug-induced liver disease is difficult. Most often, it is a diagnosis of exclusion. The following morphological changes are known, dependent on the target cell type: acute and chronic hepatitis, granuloma formation, and fatty liver disease, cholestatic type acute and chronic liver damage with or without inflammation,or mixed forms of liver injury. Portal or perisinusoidal fibrosis can occur following each type of liver damage. Vascular changes or neoplasms are rare. Drug induced liver injuries are more likely induced by type B damage, which is not expected and cannot be reproduced in animal testing. Type A damage, which is known from toxicity assays, is less likely. A specific therapeutic regime is not available. Therefore, early recognition and cessation of the use of the drug is necessary.

Acute Disease↗

[Malignant lymphomas of the liver: new diagnostic algorithms].

Primary hepatic lymphomas represent rare neoplasms, which are partly observed in association with chronic viral hepatitis, immunosuppression and autoimmune diseases. In contrast, secondary hepatic lymphomas are much more frequent and represent disseminated disease. Lymphomas involving the liver include, with decreasing frequency, diffuse large B-cell lymphoma, small lymphocytic lymphoma, Hodgkin's lymphoma, peripheral T-cell lymphoma, follicular lymphoma and extranodal marginal zone B-cell lymphoma. Many B-cell lymphomas in the liver reveal a characteristic infiltration pattern allowing a rapid and cost-effective diagnosis based on focused immunohistochemical analyses. In contrast, most T-cell lymphomas show a more diverse morphology, which is sometimes difficult to differentiate from a reactive condition. Therefore, additional molecular analyses are frequently necessary. The differential diagnosis includes hepatitis and inflammatory bile duct diseases, undifferentiated carcinoma, inflammatory myofibroblastic tumor as well as histiocytic and dendritic cell neoplasms.

Algorithms↗

[Primary cholangiocarcinoma in a case of Caroli's disease: case report and literature review].

Caroli's disease is a liver disease with segmental cystic dilatation of the intrahepatic bile ducts. It belongs to the group of congenital ductal plate malformations. With an incidence of only 0.05% of all liver cases in the Liver Registry of the University of Cologne, it is a very rare disorder. Caroli's disease is usually combined with cholangitis and bile duct stones. Control of these infections and maintenance of biliary drainage are the main therapeutic aims. The development of intra epithelial neoplasia and invasive carcinoma are rare complications. We report a case of Caroli's disease with the development of cholangiocarcinoma and review the literature.

Bile Duct Neoplasms↗

[Diagnosis and differential diagnosis of hepatocellular carcinoma].

The incidence of hepatocellular carcinoma (HCC) will continue to increase for the next decade due to a latency of about 30 years due to cirrhosis caused by chronic hepatitis C. The diagnosis of an underlying cirrhosis is of diagnostic importance. According to WHO guidelines, HCC encompasses the following: trabecular, pseudoglandular, acinar, compact, scirrhous and fibrolamellar subtypes. Cytological appearance includes hepatocellular pleomorphic, clear cell and sarcomatous subtypes. Tumor cells in hepatocellular carcinoma may display intracytoplasmic inclusions that are helpful for establishing the diagnosis. Differential diagnosis has to be considered for such hepatic tumors as adenoma and precancerous lesions such as dysplastic nodules or mesenchymal tumors. Metastases in the liver may be difficult to differentiate, especially for primary tumors from the gastrointestinal tract which may be similar to glandular or scirrhous type of HCC. The existence of underlying cirrhosis is helpful for the diagnosis and an ample spectrum of antibodies against liver antigens and adenocarcinomas are commercially available to confirm the correct diagnosis.

Carcinoma, Hepatocellular↗

[Primary infection with Epstein-Barr virus in a 77-year-old patient with B symptoms and hepatitis -- a case report].

Epstein-Barr virus (EBV) infection has a prevalence of 90 % and is - depending on the immune status of the host - associated with a broad spectrum of clinical manifestations. By presenting a case report we would like to demonstrate an unusual clinical course of a primary infection with EBV in an elderly patient. A 77-year-old patient was admitted to hospital in reduced health condition because of a persisting bronchopulmonary infection with B symptoms. The patient had already been treated with antibiotics. Because of elevated liver enzymes, a liver biopsy was performed. Histopathology revealed moderate acute hepatitis with cholangitis und endothelialitis, pointing to an EBV-induced hepatitis. Serological examinations confirmed the diagnosis, revealing a primary infection with positive EBV VCA IgM and IgG. EBV PCR of the liver tissue was positive, viral genome could be demonstrated within lymphocytes. A short period later the patient was discharged to reconvalescence. This case report demonstrates an unusual primary infection with EBV at the age of 77 with atypical clinical symptoms and hepatitis. The relevance of EBV in the differential diagnosis of atypical infectious diseases with hepatitis of unknown aetiology is strengthened on taking data reports from the literature into consideration.

Aged↗

Induction of early murine cytomegalovirus infection by different reporter gene-associated recombinant viruses.

Murine cytomegalovirus (MCMV) has provided useful models for acute, chronic and latent CMV infection because of its similarities in structure and biology with human CMV. We report the induction of acute MCMV hepatitis with different bacterial artificial chromosome (BAC)-cloned virus constructs [MCMV-SEAP which includes the gene for secreted alkaline phosphatase (SEAP) under Rous sarcoma virus (RSV)-promoter control, MCMV-GFP which includes the gene for enhanced green fluorescent protein (eGFP) under HCMV-ie promoter control, MCMV-HBs includes the gene for hepatitis B surface antigen (HBsAg) under simian virus (SV)40-promoter control and the DeltaMC95.21 virus in which the m152 gene was deleted and substituted by the reporter gene lacZ] in order to elucidate the histopathological changes together with different reporter-gene products in the liver tissue and the effect of the deletion of a certain gene. All the virus constructs induced a similar mild acute hepatitis which had its climax from days 3 to 5 post-infection in immunocompetent mice. In situ, the reporter-gene products beta-galactosidase and secreted alkaline phosphatase could be visualized in relation to the inflammatory changes. The composition of the invading cell populations did not change even in the absence of the m152 gene. Additionally discrete inflammatory changes were seen in kidney and serosa while the other organs were not involved. This model helps us understand the immunological and histopathological mechanisms of the CMV-induced hepatitis, which plays an important role especially in the immunocompromised patient. The morphological changes can be analysed while the respective reporter gene product is expressed by the virus construct.

Acute Disease↗

Lewis(y) antigen (CD174) and apoptosis in gastric and colorectal carcinomas: correlations with clinical and prognostic parameters.

Lewis(y) (Le(y)), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Le(y) expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Le(y) and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Le(y) reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Le(y) expression compared to other tumor types. In colorectal cancers, Le(y) was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Le(y) antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.

Adenocarcinoma↗

Rapid immunohistochemical detection of tumor cells in gastric carcinoma.

The detection of single tumor cells or tumor cell clusters represents an important issue in intraoperative frozen section analysis. For example, surgical margins may be evaluated in order to minimize the number of additional operations. Furthermore, intraoperative diagnosis of lymph node micrometastasis (LNM) may help to define the area of appropriate lymph node dissection. In addition to haematoxylin and eosin (H&E)-stained sections, immunohistochemical detection of single tumor cells or cell clusters may be helpful in this context. The aim of this study was to evaluate the clinical significance, reliability and sensitivity of intraoperative rapid immunostaining of frozen sections. Therefore, we compared the results of rapid immunohistochemical staining of frozen sections and paraffin sections applying the EnVision and Histofine(R) detection systems. In a prospective immunohistochemical study, paraffin and frozen sections of 20 gastric cancer specimens were analyzed. Paraffin as well as frozen sections were stained immunohistochemically applying the EnVision and Histofine detection systems. As primary antibodies, AE1/AE3 (anti-cytokeratin), EMA (anti-MUC1) and B lymphocyte marker anti-CD20 were applied. The rapid immunostaining procedure was able to be completed within 10-13 min. Rapid immunohistochemical staining of frozen and paraffin sections of the same tumors resulted in comparable immunoreactivity. The rapid EnVision and Histofine procedures allowed immunostaining of frozen sections in less than 13 min. These methods can represent useful additional tools in routine surgical pathology and research, enabling a more accurate frozen section diagnosis compared to staining with H&E alone. Intraoperative rapid immunostaining can be a simple and useful technique to detect LNM.

Adenocarcinoma↗

[Recurrent aseptic osteonecrosis in Crohn's disease - extraintestinal manifestation or steroid related complication?].

HISTORY: A 57-year-old woman complained about increasing pain and weakness in her hips and legs. 7 months earlier active (Crohn's) ileocolitis had been diagnosed. She had received several bouts of steroids and had been in clinical remission for 12 weeks under a dosage of 40 mg/d prednisone. INVESTIGATIONS: Clinical examination, laboratory work up, x-rays and MRI of the pelvis, bone scan, neurologic examination and muscle biopsy showed unspecific results. THERAPY AN COURSE: Steroides were tapered and replaced by weekly intramuscular methotrexate 20 mg which resulted in long lasting clinical remission. Pain and weakness persisted. 6 months later MRI revealed osteonecrosis of both femoral heads. 4 1/2 years after the initial diagnosis of Crohn's disease the patient complained about pain in her lower legs without evidence of osteonecrosis in MRI. Another 2 years later avascular osteonecrosis was diagnosed by tibial bone biopsy. Now MRI verified patchy osteonecrosis of the tibiae. Further osteonecrosis of the left foot were diagnosed by MRI ten years after initial diagnosis of Crohn's disease in the now 67-year-old patient. She is still in remission on weekly intramuscular 15 mg methotrexate. CONCLUSION: The long interval between steroid treatment and recurrent avascular bone necrosis as well as the unusual pattern of bone involvement indicate that osteonecrosis is an extraintestinal manifestation of Crohn's disease. More reports and comparative studies are necessary to give more evidence that avascular osteonecrosis is an extraintestinal manifestation of inflammatory bowel disease.

Anti-Inflammatory Agents↗

[Adenocarcinoid of the appendix vermiformis].

Adenocarcinoids are rare tumors with histological features of both carcinoid tumor and adenocarcinoma. They show a more aggressive biological behaviour than conventional carcinoids. We report a case of a 64-years-old female patient with a diffuse infiltration of the appendicular wall by an adenocarcinoid. Due to the positive surgical margin and the tumor expansion a hemicolectomy was performed. There are no precise criteria to direct the operative choice between appendectomy and hemicolectomy. It is thought that appendectomy is sufficient in case of small tumors in the tip of the appendix. Patients with diffuse appendicular involvement require a more aggressive surgical therapy.

Adenocarcinoma↗

[Clear cell tumor of the lung].

Clear cell tumors of the lung are rare tumors composed of epithelioid HMB45 positive tumor cells. It has been proposed that clear cell tumors generate from perivascular epithelioid cells which are also found in renal angiomyolipoma. Due to its morphologic epithelioid features with clear cytoplasm the distinction from either primary or metastatic clear cell carcinoma is difficult. Usually clinical investigations do not lead to the final diagnosis so that only subsequent histological examination and immunophenotyping can establish the correct tumor classification. We describe the case of a 52 year old woman who underwent exploratory thoracotomy because of a lung mass in the right lower lobe. In frozen sections a solid trabecular tumor was diagnosed, paraffin histology and immunohistochemistry revealed a clear cell tumor of the lung. The difficulty of the correct diagnosis of the clear cell tumor of the lung in frozen sections is discussed as well as the differential diagnosis.

Adenocarcinoma, Clear Cell↗

[Liver metastases: incidence and histogenesis].

Metastases are the most common malignant tumors of the liver. In the files of the Institute of Pathology of the University of Cologne 12,161 liver tissue cases are registered. Of them, 1,357 cases (11.2%) showed tumors or tumor like masses. Liver metastases of solid tumors were the largest group of the neoplasias with 611 cases (5.0%) followed by hepatocellular carcinoma (380 cases; 3.1%). Other entities were rare and include cholangiolar carcinoma (0.5%), vascular tumors (0.4%), lymphomas (0.4%), focal nodular hyperplasias (0.36%) and liver cell adenomas (0.23%). Adenocarcinomaa are the largest group of metastases with 400 cases (65.5%). 48.2% of this group were metastases of colorectal cancer, 13.5% of pancreatic cancer, 13% of breast cancer, 6.2% of gastric cancer, 4.5% of lung cancer and 3.7% of esophageal cancer. Neuroendocrine carcinomas are the second largest group with 16% of liver filiae. Other entities were rarely found. Metastases in cirrhotic livers are seldom. The gross findings, the histology, the differential diagnosis including immunohistochemistry and the value of the liver biopsy is discussed.

Adenocarcinoma↗

Quantitative c-erbB-2 but not c-erbB-1 mRNA expression is a promising marker to predict minor histopathologic response to neoadjuvant radiochemotherapy in oesophageal cancer.

We examined the potential of quantitative epidermal growth factor receptor (EGFR, synonym: c-erbB-1) and c-erbB-2 (synonym: HER2/neu) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy), followed by radical surgical resection, in patients with oesophageal cancer. Tissue samples were collected by endoscopic biopsy prior to treatment. RNA was isolated from biopsies and quantitative real-time reverse transcriptase-polymerase chain reaction assays were performed to determine c-erbB-1 and c-erbB-2 mRNA expression. Relative expression (tumour/paired normal tissue ratio standardised for beta-actin) was calculated for EGFR and c-erbB-2 mRNA. Expression levels were correlated with the objective histopathologic response in resected specimens. Histomorphologic regression was defined as major response when resected specimens contained less than 10% of residual vital tumour cells, or in case a pathologically complete response was achieved. Expression of c-erbB-1 mRNA was not associated with the degree of histomorphological response. In contrast, the relative expression levels of c-erbB-2 mRNA >1 were not associated with major histopathologic responses (sensitivity 41.6%, specificity 100%), and 10 out of 36 (28%) patients could be unequivocally identified, whose tumours did not respond well to the delivered neoadjuvant radiochemotherapy (P<0.01). Quantitative expression levels of c-erbB-2, but not c-erbB-1 mRNA, in pretreatment biopsies appear to predict minor histopathologic response to our neoadjuvant radiochemotherapy protocol. This test could be used to prevent expensive, non effective and potentially harmful therapies in approximately one-fourth of our patients, and leads to a more individualised type of combined modality treatment.

Adult↗

[HPV-associated tonsillar cancer. An update].

The major risk factors for head and neck squamous cell carcinomas (HNSCC) are considered to be tobacco and alcohol. A link between oncogenic types of the human papilloma virus (HPV) and the risk of HNSCC has been suggested in the literature. However, the causal link is now becoming more firmly established on the basis of recent analyses. About 20% of all HNSCC and more than 50% of tonsillar cancers contain HR-HPV. The causal role of HPV-infection in carcinogenesis and the molecular mechanisms involved could thus far be best elucidated in the case of cervical carcinomas. New insights and increasing evidence for the analogy of HPV-positive HNSCC with cervical cancer are discussed. The definition of HPV-positive HNSCC has become more important due to the implications for risk factors and prognosis.

Alcohol Drinking↗

[Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation].

Following surgical resection locally advanced oesophageal carcinomas exhibit a bad prognosis and therefore neoadjuvant therapeutic strategies were developed. Because success of therapy is associated with the extent of tumor regression in this context, the introduction of objective histopathological criteria seems to be very important. This study included 67 patients with oesophageal carcinomas (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil-containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24 cases adenocarcinomas were diagnosed. After completion of therapy, a surgical resection and a histopathological examination of the tissue specimens were performed. The extent of tumor regression was histologically evaluated and therapy-induced alterations were graded semiquantitatively. Thereby, a significantly favorable prognosis was observed in the group of patients that showed a regression of carcinomas of 90% or more. Additionally, the extent of a resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates correlated with the grade of regression. These results underline the importance of an exact examination and histomorphological evaluation of the response for the assessment of survival probability after neoadjuvant radiochemotherapy of oesophageal carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗