Her-2/neu expression in testicular cancer--a retrospective analysis in 57 cases.

OBJECTIVES: To evaluate her-2/neu expression in testicular germ cell tumors (GCT). METHODS: In patients with primary GCT her-2/neu expression was analyzed by immunohistochemistry (IHC). Furthermore, gene amplification was analyzed by chromogene in situ hybridization (CISH). For interpretation, the most recent Asco Guidelines were used. RESULTS: The expression patterns were analyzed according to the histologic subtype. Immunohistochemical analysis demonstrated a weak (score 1) to moderate expression (score 2) in 1% of GCT; none of the GCT revealed a score 3 expression profile. By CISH analysis, we did not observe any gene amplification in the 57 GCT. CONCLUSIONS: The analysis of her-2/neu expression in primary testicular cancer is of no therapeutic relevance. However, for the future we will explore the expression of her-2/neu in residual masses after chemotherapy to assess the role of targeted therapy in chemoresistant metastases.

Low frequency of epigenetic events in urothelial tumors in young patients.

PURPOSE: Bladder urothelial cell carcinoma is uncommon in young patients. We recently reported a series of tumors in patients younger than 20 years at diagnosis and performed exhaustive genetic screening for molecular alterations. Few events typical of bladder urothelial cell carcinoma were detected. Since many carcinogenic events occur at the epigenetic rather than the genetic level, we analyzed the same tumors for alterations in DNA hypermethylation. We compared our findings with those in tumors in older patients with similar pathological profiles. MATERIALS AND METHODS: We analyzed 76 bladder urothelial cell carcinomas from 3 groups stratified by age at diagnosis, including less than 19, 20 to 45 and greater than 46 years (median 78), and matched for low grade and nonmuscle invasive stage. We used quantified methyl specific polymerase chain reaction to investigate promoter methylation for 8 tumor suppressor genes implicated in urothelial carcinogenesis. RESULTS: Tumors in the youngest age group had the lowest incidence of global hypermethylation compared to the other tumors with a methyl index of 37.5% vs 62.5% and 50%, respectively (ANOVA p = 0.009). When individual loci were analyzed, younger patients had a significantly lower rate and concentration of methylation at APC, Bcl2, MGMT and E-cadherin promoters than in the older groups (p <0.05). Few differences were present between the 2 older cohorts but the APC and MGMT methylation concentration increased with age. CONCLUSIONS: Urothelial tumors in patients younger than 19 years have a low rate of epigenetic alteration. Tumors in patients older than 20 years have epigenetic profiles similar to those of tumors in patients within the typical bladder urothelial cell carcinoma age range.

Genomic aberrations are rare in urothelial neoplasms of patients 19 years or younger.

Urothelial neoplasms in patients 19 years of age or younger are rare, and the data regarding clinical outcome are conflicting. Molecular data are not available. Urothelial tumours from 14 patients aged 4 to 19 years were analysed, including FGFR3 and TP53 mutation screening, comparative genomic hybridization (CGH), UroVysion FISH analysis, polymerase chain reaction for human papillomavirus (HPV), microsatellite analysis using the NIH consensus panel for detection of microsatellite instability (MSI) and six markers for loss of heterozygosity on chromosome arms 9p, 9q, and 17p and immunohistochemistry for TP53, Ki-67, CK20 and the mismatch repair proteins (MRPs) hMSH2, hMLH1, and hMSH6. Based on the 2004 WHO classification, one urothelial papilloma, seven papillary urothelial neoplasms of low malignant potential (PUNLMPs), five low-grade, and one high-grade papillary urothelial carcinoma were included. No multifocal tumours were found and recurrence was seen in only one patient with a urothelial papilloma. All patients were alive with no evidence of disease at a median follow-up of 3.0 years. We found no mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss, or HPV positivity in any of the patients. Three cases showed chromosome alterations in CGH analyses, urothelial dedifferentiation with CK20 overexpression, or aneuploidy, and one TP53 mutation with TP53 overexpression was found. Urothelial neoplasms in people younger than 20 years are predominantly low grade and are associated with a favourable clinical outcome. Genetic alterations frequently seen in older adults are extremely rare in young patients. Urothelial neoplasms in children and young adults appear to be biologically distinct and lack genetic instability in most cases.

Cytogenetic, oncogenetic, and histopathologic characteristics of colorectal carcinomas with 17p abnormalities.

From a total of 65 colorectal adenocarcinomas studied by cytogenetic methods, 33 were selected for the present study; in addition to other karyotypic anomalies, these 33 showed a loss of the short arm of chromosome 17. This loss was either the result of a deletion or rearrangement, or caused by the loss of a whole chromosome 17. The 17p- tumors were characterized by a high grade of karyotypic abnormality including a high incidence of cases with double minutes. A gain of chromosomes 2, 7, 19, and 20, and the loss of chromosome 18 and the Y-chromosome were the most frequent numerical anomalies associated with 17p-, as were structural changes of chromosomes 1 and 5. The most impressive difference in the pattern of proto-oncogene over-expression between the 17p- tumors and those without this anomaly was the significantly increased frequency of cases with c-erbB over-expression. Some significant, but also loose, associations were found between cytogenetic/oncogenetic and histopathologic or clinical features of these tumors. The patterns of genetic changes in cells of colorectal carcinomas may thus reflect the potential of the future development, rather than the present clinical features, of the respective tumor. Therefore, the character of the change seems to be more prognostic than diagnostic.

[Clinical aspects and assessment of renal oncocytomas]. / Klinik und Wertigkeit renaler Onkozytome.

Oncocytomas represent a special category of renal tumors which can be clearly separated from the renal cell carcinomas by their typical histological presentation as well as by their clinical course. A clear cut preoperative diagnosis based on sonography, CT and angiography, however, is not yet possible. Between 1981 and 1990 16 patients (4 men, 12 women) with a mean age of 65 years underwent a radical tumor nephrectomy, with the histopathological diagnosis of an oncocytic adenoma, whose clinical and pathomorphological parameters were completely evaluated. Oncocytomas are rare, although increasingly found, tumors of the kidney with a benign clinical course. Up to date the treatment for these tumors has been nephrectomy, only rarely extirpation.

Chromosome and oncogene studies in human rectal and colon carcinomas.

Cytogenetic examinations of 48 rectal and 17 colon carcinomas and analyses of proto-oncogene activation on 67 of the former and 8 of the latter tumors were performed. Besides a general considerable heterogeneity of chromosome counts, some chromosomes were found to contribute non-randomly to hypersomies (# 2, 3, 7, 9, 19, 20 and 6) and to hyposomies (# 14, 15, Y, 21, and 18) in this material. Chromosomal markers non-randomly involved breakpoint clusters on 17p11, 13q11, 7p, 1p11, and 1p36 and on the centromeric regions of chromosomes 1, 8, 14, 15 and 21. Cytogenetic equivalents of gene amplification ("double minutes") were present in only rather small cell fractions (less than 20%) of 50% of the studied tumors. Using a cDNA technique and a battery of respective probes, proto-oncogene overexpression was screened for in the tumor samples, but also in 24 samples of inconspicuous mucosae of tumor patients and in two mucosae of healthy individuals. Simultaneous overexpression of several proto-oncogenes was the most characteristic finding in the tumor cells. However several of the mucosa samples obtained from tumor patients also just exhibited clear signals of proto-oncogene overexpression, which were not found in epithelial cells from non-tumor patients.

Solid and cystic pancreatic tumors. Clinical, histochemical, and electron microscopic features in ten cases.

Ten cases of the rare solid and cystic pancreatic tumors are presented. All except one occurred in young women (mean age, 25 +/- 9.2 years). The large neoplasms were evenly distributed across the pancreas; in one case, metastasis occurred; all other cases were free from disease after complete resection. Histologic hallmarks of solid and cystic neoplasms were papillary growth, large intracytoplasmic granules, and immunoreactivity with alpha 1-antitrypsin, alpha 1-antichymotrypsin, phospholipase A2, and neuroendocrine markers (neuron-specific enolase [NSE], synaptophysin). This suggests both endocrine as well as exocrine differentiation.

[Polypoid lesions of the gallbladder]. / Polypoide Läsionen der Gallenblase.

Ultrasound examination of the gallbladder was performed in a prospective study (from 1985 to 1988) of 14,841 consecutive patients. Polypoid changes were found in 224 (129 men, 95 women; mean age 54 [18-88] years), sonographically classified as cholesterol polyps in 212, as polypoid lesions of uncertain benignity in 12. Mean observation time of 92 patients with cholesterol polyps was 9 (3-48) months. In six the polyp diameter increased by up to 5 mm: only two of them were operated upon and the diagnosis was confirmed in both. A total of 21 patients suspected of having cholesterol polyps were operated upon, the diagnosis confirmed in 17, chronic cholecystitis in two and, in one case each, thickened wall-adherent bile or wall-adherent concrements as cause of the ultrasound changes. Six of the 12 patients with polypoid lesions of uncertain benignity were operated upon: two had an adenoma, one each had tissue heterotopy, malignant melanoma metastasis, gall-bladder carcinoma and adenomyomatosis.

Two programmes for examination of regional lymph nodes in colorectal carcinoma with regard to the new pN classification.

The new pN classification for colorectal carcinoma requires not only a statement on absence or presence of regional lymph node metastases but also, if present, a knowledge of the site and number of involved nodes. Subdivision of the fatty tissue with nodes adhering to the tumor resection specimen into two compartments is therefore the first step in pathological examination of lymph nodes. The methods for this as well as the different techniques used in searching for nodes and further histological processing of nodes are presented. We outline a minimal programme for pN classification in which step-wise sequence of examination reduces work load. An extended programme designed to answer special questions regarding lymphatic spread and surgical method is recommended only within the framework of special clinico-pathological studies.

[Induction of urinary bladder urothelial cancers in the rabbit by dibutylnitrosamine with an artificial bladder calculus as cocarcinogen]. / Induktion von Harnblasen-Urothelkarzinomen beim Hasen durch Dibutylnitrosamin mit künstlichem Blasenstein als Co-Karzinogen.

Thirteen rabbits received liquid dibutylnitrosamine (DBN) s.c. at a dosage of 400 mg/kg body weight once a week for a maximum of 16 months to induce transitional cell carcinomas (TCC) of the bladder. In five of these rabbits, 4 months after starting the injection of DBN an artificial stone prepared from a methylmethacrylate 2-component plastic material was implanted into the bladder. Four rabbits developed TCC of the bladder, with latency periods of 15-18 months. These tumors were found in two of the five (40%) rabbits with stones and in two of the eight (25%) rabbits without stones. The stone-bearing animals had more deeply infiltrating tumors, although the tumor induction times were comparable. Within a maximum observation period of 28 months there were no lymphogenous or hematogenous metastases. Another two rabbits showed benign urothelial changes presenting as simple hyperplasia and von Brunn's nests after 4 and 4.5 months, respectively. In two rabbits we found malignant tumors located extravesically, in the lungs and the kidney. The results of our study confirm the feasibility of TCC induction in rabbits by DBN administered s.c. Additional implantation of an artificial bladder stone acting as a co-carcinogen does not lead to a larger number of tumors, but does seem to enhance the degree of TCC induction in the bladder.

[Malignant somatostatinoma of the papilla major and minor]. / Malignes Somatostatinom der Papilla major und minor.

In a 50-year-old man with extrahepatic cholestasis and iron-deficiency anaemia, local operative excision of a 4 cm submucous tumour of the papilla of Vater revealed on histological and immunochemical examination a somatostatinoma. Subsequent duodenopancreatectomy further demonstrated in the surgical specimen a lymph node metastasis and a 5 mm somatostatinoma in the papilla minor. The patient has now been free of symptoms for 12 months on substitution treatment with pancreatic enzymes.

[Manifestation of AIDS in HIV infected homosexual males with lymphadenopathy syndrome]. / Manifestation von AIDS in HIV-infizierten homosexuellen Männern mit Lymphadenopathie-Syndrom (LAS).

26 homosexual men with HIV-infection and lymphadenopathy syndrome were examined between 1982 and 1984 and prospectively observed over a period of 58 months (median, range 53-69 months). 16 (61.5%) developed full blown AIDS within a median period of 41 months (23-63 months). 12 of them died 50 months (median, range 29-67 months) after the first examination. 10 patients showed no symptoms of AIDS after a median observation time of 57 months (54-63 months). A panel of clinical symptoms, signs of concomitant infections, chemical and immunological analyses, including a lymphnode biopsy were correlated to the course of the disease. A decreased proportion of CD4-cells and a lower CD4/CD8 ratio in the lymphnode suspensions at the first examination in patients with disease progression were the only parameter which correlated significantly with the development of AIDS.

Tissue reactions under piezoelectric shockwave application for the fragmentation of biliary calculi.

The tissue reactions that occurred during piezoelectric shockwaves for the fragmentation of biliary calculi were investigated in 10 surgically removed stone containing human gall bladders and in acute (six dogs) and chronic (six dogs) animal experiments. Before and after shockwave (500, 1500 or 3000) in the anaesthetised dogs, computed tomography (CT), magnetic imaging (MRI) and laboratory tests were done; treatment was carried out under continuous ultrasonographic control. Shockwave applications to the human gall bladders resulted in disintegration of the stones with no macroscopically or microscopically detectable tissue changes. In acute animal experiments, small haematomas were observed in all six animals at surfaces, but also inside the liver and gall bladder (max diameter 25 mm). Perforation or intra-abdominal or pleural bleeding did not occur. In chronic experiments, no macroscopic, and only slight microscopic residual lesions (haemosiderin deposits) were seen three weeks after shockwave. In almost all instances, the lesions were detected by CT, MRI, and ultrasonography, while laboratory tests were negative.

[The prognostic value of the new pTNM classification and staging of kidney cancers]. / Die prognostische Aussagekraft der neuen pTNM-Klassifikation und Stadieneinteilung des Nierenkrebses.

In comparison with the former pTNM classification of renal cell carcinoma, the 1987 edition is characterized by a simplification of the classification by inclusion of venous invasion (former separate V classification) into pT and an advantage in estimating prognosis by the new pN classification. The new defined stages are well correlated with survival. On the basis of the presented survival data the criticism of the new TNM/pTNM by the EORTC-GU group can be rejected.

Impalpable testicular tumors diagnosed by scrotal ultrasonography.

Intrascrotal masses can be identified with a high degree of accuracy using scrotal ultrasonography. Ultrasound, however, is useful to identify occult and incidental testicular neoplasms, too. We report 2 cases of impalpable incidental testis germ cell tumors diagnosed by routine scrotal ultrasonography. One of the 2 patients had an incidental sequential second primary testicular germ cell tumor in the palpably normal testis, identified by routine follow-up ultrasound three months after contralateral radical orchiectomy.

Verrucous carcinoma of the esophagus.

The special problems involving the histopathology of verrucous carcinoma of the esophagus are presented on the basis of two patients with this tumor seen at our department. The discussion centers on the question whether a verrucous carcinoma of the esophagus can infiltrate the basal membrane and give rise to metastases.

[7/8th pancreas resection in nesidioblastosis?]. / 7/8 Pankreasresektion bei Nesidioblastose?

UNLABELLED: The extent of pancreatectomy for the treatment of nesidioblastosis is open to dispute. Recurrent hypoglycaemia, insulin-dependent diabetes mellitus, or exocrine insufficiency may result. CASE REPORTS: 1) A female twin presented with hypoglycaemia, insulin response inappropriate for glucose levels, marked leucine sensitivity, low ketones, underwent 7/8 pancreatectomy for multifocal adenomatosis at the age of 13 months. 2) A boy of 7 months of age had a 95% resection including the uncinate process. Focal adenomatosis combined with diffuse nesidioblastosis proved by immunohistological examination. OUTCOME: Both remained asymptomatic and normoglycaemic. DISCUSSION: The prognosis seems to depend on the primary extent of resection.

[News on the surgical pathology of colorectal cancer]. / Neues aus der chirurgischen Pathologie des kolorektalen Karzinoms.

The incidence of regional lymph node metastases in colorectal carcinoma is influenced primarily by depth of invasion, but also by histological grade of malignancy and histologically demonstrable invasion of lymphatics. With regard to the indication for limited treatment of colorectal carcinoma, a differentiation between high risk and low risk tumors is recommended. In 6% of tumors with regional lymph node metastases only micrometastases are observed whose prognostic significance is not yet established. In most cases, lymphatic spread occurs regularly, in conformity with the anatomical situation, skipping of lymph nodes in less than 2% of cases with lymph node metastasis can be observed. The incidence and topography of lymph node metastases are important for the choice of surgical procedures. Because of the observed behaviour in lymphatic spread extended hemicolectomies are recommended for tumors of the transverse colon and the colonic flexures. The surgical treatment of rectal carcinoma should include the systematic node dissection along the inferior mesenteric artery.

Significance of serum phosphohexose isomerase in gastrointestinal cancer at different stages.

The purpose of this study was to reevaluate the significance of serum PHI in gastrointestinal cancer at histopathologically defined stages prior to primary treatment. A total of 248 patients with malignant tumors of the gastrointestinal tract and a collective of 42 patients with noncancerous diseases were studied. The results are compared with those obtained with the established markers tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA). Phosphohexose isomerase (PHI) revealed an overall diagnostic sensitivity of 69%, combined with a specificity of 74%. The corresponding data for TPA were found to be 73 and 47% while for CEA 26 and 95% respectively were determined. Even in the early stages of colorectal and esophageal carcinoma, PHI showed a sensitivity of about 60%. A continuous rise of PHI serum levels, correlating well with the extent of the tumor disease, could be detected. In contrast to TPA and CEA, PHI assay can be carried out with a minimum of laboratory efforts, in a short time and at low costs. These findings suggest that serum PHI assay is a useful aid for screening of gastrointestinal cancer, especially esophageal and gastric carcinoma, and a reliable marker for treatment control and follow-up.