PubMed Health⌕ Search

Biomedical subjects

J Lüttges

Publications and source records attributed to J Lüttges.

At least 19 recordsLinked to original sources
PubMed2005

[Intraductal neoplasms of the pancreas: cystic and common].

The most important of the generally rare intraductal tumors of the pancreas is the intraductal papillary-mucinous neoplasm (IPMN). In recent years this tumor type has been described in detail, and it was included in the WHO classification of 1996. IPMNs typically grow for a long time within the ducts, before approximately 50% of them eventually become invasive. Because of this feature the IPMNs are clearly distinct from ductal adenocarcinomas. Currently, IPMNs have advanced to the most commonly resected cystic tumor of the pancreas. Recent studies have shown that IPMNs may be distinguished into different types showing a different biology according to their mucin pattern.

Carcinoma, Pancreatic Ductal↗
PubMed2005

[Solid pseudopapillary neoplasms. Enigmatic entity with female preponderance].

Solid pseudopapillary neoplasms (SPN) of the pancreas represent a special tumor entity, both morphologically and biologically. They form large solitary tumors that occur predominantly in young women. Histologically, they show solid, pseudopapillary, and pseudocystic patterns. The tumor cells are monomorphous and typically express vimentin, neuron-specific enolase, nuclear beta-catenin, and the progesterone receptor. Complete resection cures the tumor in about 90% of the cases. However, because recurrences and even metastases may occur in a small number of cases, SPN are classified as low-grade malignant tumors. Predicting malignancy histologically is not yet possible. The most important differential diagnosis to consider is neuroendocrine tumor of the pancreas. The etiology and pathogenesis of SPN are obscure.

Biomarkers, Tumor↗
PubMed2005

[Spectrum of chronic pancreatitis. On the way to etiological classification].

Chronic pancreatitis is a fibroinflammatory disease that is induced by injuries to the interstitial, ductal, and/or acinar cells. The most important causes are alcohol abuse, gene mutations, autoimmune processes, special anatomic changes, and obstructive duct lesions. The morphologic spectrum of the various types of chronic pancreatitis related to the above causes shows features that increasingly allow an etiological distinction and categorization to be made. A catalog of five criteria is presented for distinguishing chronic pancreatitis from ductal adenocarcinoma of the pancreas.

Alcoholism↗
PubMed2005

[Cystic pancreas tumors and their classification: features old and new].

Cystic tumors and tumor-like lesions of the pancreas are rare, but have attracted a great deal of attention because they are easily recognized with new imaging methods and, in contrast to ductal adenocarcinoma, they can usually be cured surgically. The increasing resection rate in recent years has also increased our knowledge of cystic pancreatic tumors by conspicuously enlarging their morphological spectrum. Known entities have been better characterized (i.e. solid pseudopapillary neoplasm, intraductal papillary mucinous neoplasm) and new ones described (serous oligocystic adenoma, mucinous non-neoplastic cyst, acinar cell cystadenoma and cystic hamartoma). This review discusses the most important cystic tumors and tumor-like lesions, presents a new classification, and summarizes the immunohistochemical differential diagnosis.

Humans↗
PubMed2005

[Pancreatic ductal adenocarcinoma and its precursors].

Pancreatic ductal adenocarcinoma is the most frequent malignant pancreatic tumor. It is one of the tumors that has a particularly poor prognosis. Its morphological characteristics are: preferential localization in the head of the pancreas, ductal-glandular tumor structures combined with marked desmoplasia and CEA and MUC1 positivity. Variants of this carcinoma include adenosquamous carcinomas, undifferentiated pleomorphic carcinomas and mixed ductal-endocrine tumors. With the definition of ductal lesions as pancreatic intraepithelial neoplasia, a progression model for pancreatic ductal carcinoma has been developed and corresponding gene alterations have been detected.

Adenocarcinoma↗
PubMed2005

Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry.

BACKGROUND: Worldwide survival data for ductal adenocarcinoma of the pancreas are the lowest among the 60 most frequent types of organ cancers. Hence published data on long time survivors of this disease are controversial. We performed a nationwide study comprising all Finnish patients diagnosed with pancreatic cancer in the period 1990-1996 who survived for at least five years after diagnosis. METHODS: Data on patients registered as five year survivors of pancreatic cancer were obtained from the Finnish Cancer Registry and Statistics Finland. Slides or paraffin blocks were collected from patients recorded as having histologically proven pancreatic ductal adenocarcinoma (PDAC) and were re-evaluated in a double blind fashion by three pathologists with special expertise in pancreatic pathology. RESULTS: Between 1990 and 1996, the Finnish Cancer Registry recorded 4922 pancreatic cancer patients, 89 of whom survived for at least five years. Reviewing this series of patients revealed 45 (49%) non-PDACs and 18 cases without histological verification. In 26 patients recorded as having histologically proven PDAC, re-evaluation of histological specimens confirmed PDAC in only 10 patients. CONCLUSIONS: This study indicates that (1) the prognosis of PDAC remains poor and (2) careful histopathological review of all patients with pancreatic cancer is mandatory if survival data are to be meaningful.

Carcinoma, Pancreatic Ductal↗
PubMed2004

Cystic neoplasms of the pancreas and tumor-like lesions with cystic features: a review of 418 cases and a classification proposal.

Although cystic neoplasms and lesions of the pancreas are rare, they have attracted a great deal of attention because of their potential curability. Since, in recent years, several new entities have been identified, the relative frequency of the tumors and their classification need to be reevaluated. In a series of 1454 tumorous lesions of the pancreas collected between 1971 and 2003 in our surgical pathology files and consultation files, all cystic pancreatic neoplasms and tumor-like lesions were identified and typed both histologically and immunohistochemically. There were 418 cases (29%) showing cysts with a diameter ranging between 0.5 cm and 27 cm. Most common were solid pseudopapillary neoplasms (21%) and intraductal papillary-mucinous neoplasms (18%). When only the cystic neoplasms and lesions that had been resected in a single institution were considered, intraductal papillary mucinous neoplasms were the most frequent cystic neoplasms, while solid pseudopapillary neoplasms took fifth place behind ductal adenocarcinomas with cystic features, serous cystic neoplasms and mucinous cystic neoplasms. The most frequent cystic tumor-like lesions were pancreatitis-associated pseudocysts. New and rare entities that have recently been identified are mucinous nonneoplastic cysts, acinar cell cystadenomas and cystic hamartomas. Bearing in mind that figures from referral centers such as ours may be biased regarding the relative frequency of lesions, we concluded from our data that intraductal papillary-mucinous neoplasms are the most frequently occurring pancreatic cystic neoplasms, rather than solid pseudopapillary neoplasms. It was possible to classify all cystic lesions encountered in our files or described in the literature in a new system that distinguishes between neoplastic and nonneoplastic lesions, with further subdivisions into epithelial (adenomas, borderline neoplasms and carcinomas) and nonepithelial tumors. This classification is easy to handle and enables a distinction on the basis of clinical behavior and prognosis.

Adolescent↗
PubMed2004

ADAM9 expression in pancreatic cancer is associated with tumour type and is a prognostic factor in ductal adenocarcinoma.

Gene expression profiling revealed ADAM9 to be distinctly overexpressed in pancreatic ductal adenocarcinoma (PDAC). We examined the relevance of ADAM9 expression in PDAC diagnosis and prognosis. A total of 59 infiltrating PDACs, 32 specimens from patients with chronic pancreatitis, 11 endocrine tumours and 24 acinar cell carcinomas were immunohistochemically analysed for ADAM9 expression. Staining for ADAM9 was detected in 58 out of 59 (98.3%) PDACs and in two out of 24 (8.3%) acinar cell carcinomas, but not in endocrine tumours. In the non-neoplastic pancreas, whether normal or chronically inflamed, ADAM9 was expressed in centroacinar and intralobular duct cells, but not in interlobular duct cells and their hyperplastic lesions. Pancreatic ductal adenocarcinomas showing cytoplasmic ADAM9 expression correlated with poor tumour differentiation and also with shorter overall survival than in cases showing only an apical membranous staining pattern (P=0.001). Multivariate analysis identified cytoplasmic ADAM9 expression as an independent marker of shortened survival in a set of 42 curatively (R0) resected PDAC (P<0.05, hazard ratio 2.85, 95% confidence interval: 1.21-6.71). The results show that ADAM9 expression distinguishes PDACs from other solid pancreatic tumours. In addition, cytoplasmic ADAM9 overexpression is associated with poor differentiation and shortened survival. Therefore, ADAM9 overexpression might contribute to the aggressiveness of PDACs.

ADAM Proteins↗
PubMed2003

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001].

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗
PubMed2003

Lichenoid reactions of murine mucosa associated with amalgam.

BACKGROUND: In 97% of all patients with oral lichenoid reactions (OLR) associated with dental amalgam a removal of the fillings leads to a decline of the lesions, as a minimum. OBJECTIVES: The aim of this study was to determine if contact allergic or local toxic effects or both may contribute to OLR using an animal model with mercury-sensitive and non-sensitive rats. METHODS: Twenty Brown Norway rats, which have a genetic predisposition for an autoimmune syndrome after exposure to mercury and 20 Lewis rats, not mercury sensitive, were treated as follows: 10 animals of each group were sensitized with a low dose of mercuric chloride. Half of all animals received local exposure of the right buccal mucosa to amalgam (left: control), the others to amalgam alloy free of mercury. All rats were patch tested with an amalgam series. RESULTS: After 20 days of exposure 96% of all animals showed white mucosal lesions restricted to the contact zone of the alloy on the treated side, but only up to 25% had a positive patch test reaction to amalgam or inorganic mercury (INM). The lesions showed no relation to species, alloy, sensitization or patch test reaction. CONCLUSIONS: While allergic mechanisms may contribute to mucosal contact lesions in Brown Norway rats, this is less probable in Lewis rats. Mercury in general appears to be irrelevant in the development of ORL in this study. If this holds true for humans as well, patch testing with an amalgam series may be helpful in a minor fraction of all patients with OLR.

Animals↗
PubMed2002

The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas.

Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile. To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas. The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.

Adenoma↗
PubMed2001

Allelic loss is often the first hit in the biallelic inactivation of the p53 and DPC4 genes during pancreatic carcinogenesis.

The presumed precursor lesions of pancreatic ductal adenocarcinoma were recently classified according to their increasing grade of dysplasia and were designated as pancreatic intraepithelial neoplasia (PanIN) 1 through 3. In this study, we tested whether molecular genetic alterations can be correlated with this classification and may help to further categorize the various PanIN grades. We determined the frequencies of allelic loss at chromosomal arms 9p, 17p, and 18q in 81 microdissected duct lesions of various PanIN grades, using a combination of whole genome amplification and microsatellite analysis. In addition we examined the p53 and Dpc4 protein expression patterns by immunohistochemical analysis. In PanIN-1, we did not detect allelic losses. In PanIN-2, allelic losses were found in increasing frequency, and were particularly high in those lesions with moderate-grade dysplasia (low grade, 20, 33, and 17%, loss at 9p, 17p, and 18q, respectively; moderate grade, 46, 77, and 58%). PanIN-3 and invasive carcinomas exhibited abundant losses. Abnormal p53 and Dpc4 protein expression was only rarely identified in PanIN-2 lesions, but occurred frequently in PanIN-3 lesions and invasive carcinomas. The combined genetic and protein expression data support a model in which allelic loss is the first hit in the biallelic inactivation of the p53 and DPC4 tumor suppressor genes. In addition, our data indicate that allelic loss analysis may be useful in separating PanIN-2 lesions with low-grade dysplasia from those PanIN-2 lesions with moderate-grade dysplasia, each potentially representing a distinct progression step toward invasive carcinoma.

Alleles↗
PubMed2001

Idiosyncratic drug allergic phenprocoumon-induced hepatitis with subacute liver failure initially misdiagnosed as autoimmune hepatitis.

BACKGROUND: Coumarin anticoagulants are known to cause hepatotoxicity, but only a few cases have been reported. Coumarins are usually administered following cardiovascular surgery and the differential diagnosis is post-transfusion hepatitis. METHODS: We report the case of a 46-year-old woman who presented with jaundice, elevated liver function tests, positive antinuclear and smooth muscle antibodies following prodromal signs of fatigue and nausea. The patient had been treated with phenprocoumon for 5 months in order to prevent thromboembolism after two strokes assumed to be due to an open foramen ovale and an aneurysmatic atrial septum. RESULTS: There was no evidence of viral or other causes of hepatitis. The patient rapidly developed subacute liver failure with encephalopathy and phenprocoumon treatment was stopped. With intensive care support, as well as high-dose prednisolone treatment, she recovered. Owing to positive antinuclear and smooth muscle antibodies, the initial diagnosis 'acute autoimmune hepatitis with liver failure was made. CONCLUSION: The lack of hypergammaglobulinaemia and the rapid recurrence of hepatitis following re-exposure to phenprocoumon led to the final diagnosis of phenprocoumon-induced idiosyncratic drug allergic hepatitis with secondary autoimmune phenomena.

Anti-Inflammatory Agents↗
PubMed2001

Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions.

Proliferative epithelial lesions in the smaller caliber pancreatic ducts and ductules have been the subject of numerous morphologic, clinical, and genetic studies; however, a standard nomenclature and diagnostic criteria for classifying these lesion have not been established. To evaluate the uniformity of existing systems for grading duct lesions in the pancreas, 35 microscopic slides with 35 representative duct lesions were sent to eight expert pathologists from the United States, Canada, and Europe. Kappa values for interobserver agreement could not be calculated initially because more than 70 different diagnostic terms were used by the eight pathologists. In several cases, the diagnoses rendered for a single duct lesion ranged from "hyperplasia," to "metaplasia," to "dysplasia," to "carcinoma in situ." This review therefore demonstrated the need for a standard nomenclature and classification system. Subsequently, during a working group meeting, the pathologists agreed to adopt a single standard system. The terminology pancreatic intraepithelial neoplasia (or PanIN) was selected, and diagnostic criteria for each grade of PanIN were established (http://pathology.jhu.edu/pancreas_panin). This new system was then evaluated by having the eight pathologists rereview the original 35 cases. Only seven different diagnoses were rendered, and kappa values of 0.43, 0.14, and 0.42 were obtained for PanINs 1, 2, and 3 respectively. Cases assigned other diagnoses (e.g., squamous metaplasia) collectively had a kappa value of 0.41. These results show both the potential of the classification system, and also the difficulty of classifying these lesions even with a consistent nomenclature. However, even when there is lack of consensus, having a restricted set of descriptions and terms allows a better understanding of the reasons for disagreement. It is suggested that we adopt and apply this system uniformly, with continued study of its reliability and use, and possibly further refinement. The acceptance of a standard classification system will facilitate the study of pancreatic duct lesions, and will lead ultimately to a better understanding of their biologic importance.

Carcinoma in Situ↗
PubMed2001

The immunohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to mucinous noncystic carcinoma and ductal adenocarcinoma.

Intraductal papillary-mucinous neoplasms of the pancreas seem to comprise various types, whose relationship to ductal adenocarcinoma and mucinous noncystic carcinoma is unclear. We analyzed the mucin immunophenotype and the DPC4/SMAD4 expression in intraductal papillary-mucinous neoplasms, ductal carcinomas, and mucinous noncystic carcinomas to define features that may help to distinguish between different types of intraductal papillary-mucinous neoplasms and to establish their relationship to other neoplasms of the exocrine pancreas. A series of 51 intraductal papillary-mucinous neoplasms, three mucinous noncystic carcinomas (two with an intraductal component), and 35 ductal adenocarcinomas were screened immunohistochemically for their expression of MUC1, MUC2, MUC5, and DPC4/SMAD4. All intraductal papillary-mucinous neoplasms and mucinous noncystic carcinomas were positive for MUC5. Thirty-two intraductal papillary-mucinous neoplasms and three mucinous noncystic carcinomas abundantly expressed MUC2 but no (or only little) MUC1. The remaining intraductal papillary-mucinous neoplasms showed either mainly MUC1 expression or focal MUC1 and MUC2 expression. All ductal carcinomas but one were MUC2 negative and MUC1 and MUC5 positive. DPC4 was not expressed in two intraductal papillary-mucinous neoplasms that showed a tubular invasion pattern. Twelve of 23 ductal adenocarcinomas were DPC4 positive. Intraductal papillary-mucinous neoplasms can be divided into at least three different mucin immunophenotypes. The first and largest group of intraductal papillary-mucinous neoplasms and mucinous noncystic carcinomas is MUC1 negative and MUC2 positive and probably forms one tumor entity. The second group seems to be related to ductal carcinoma because of its MUC1 positivity in the absence or very weak MUC2 staining. The third group shows focal MUC1/MUC2 expression and is characterized by oncocytic histology.

Adenocarcinoma, Mucinous↗
PubMed2001

Update on the pathology and genetics of exocrine pancreatic tumors with ductal phenotype: precursor lesions and new tumor entities.

The majority of pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Pancreatic duct lesions have been discussed as tumor precursors. This review presents a recently adopted standard system for these lesions which distinguishes among three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a distinct step towards invasive carcinoma. Another focus of the review is the advances that have been made in the further immunohistochemical and molecular characterization of special pancreatic neoplasms showing a ductal phenotype, such as undifferentiated carcinoma, mucinous noncystic (colloid) carcinoma, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, medullary carcinoma, and other rare tumors.

Carcinoma in Situ↗
PubMed2001

Expression of the tumor suppressor gene Maspin in human pancreatic cancers.

The tumor suppressor gene maspin, a unique member of the serpin superfamily, inhibits cell motility, invasion, and metastasis in breast and prostate cancers. Maspin is expressed in normal human mammary and prostate epithelial cells but down-regulated during cancer progression. In this study, we analyzed the expression of maspin in various human cancer cells by means of Northern blot and immunohistochemistry. Maspin gene expression proved to be up-regulated in pancreatic cancer. Maspin expression was not detected in any of 6 gastric cancers, 4 melanomas, or 6 of 7 breast cancer cell lines examined. In contrast, 5 of 9 pancreatic cancer cell lines showed maspin expression, although maspin expression was not detected in normal pancreatic tissue. Furthermore, maspin was expressed in 23 of 24 tumor specimens obtained from pancreatic cancer patients as well as all high-grade precancerous lesions (PanIN3 and intraductal carcinoma extension). In contrast, no expression was observed in normal and low-grade precancerous lesions. Our results show that maspin is a new factor associated with pancreatic cancer. In addition, the detection of maspin in pancreatic tumor tissues and its lack of expression in all normal pancreatic tissues suggests that maspin may be a useful marker of primary human pancreatic cancer.

Disease Progression↗