[Intraductal carcinoma of the prostate]. / Intraduktales Karzinom der Prostata.

For many tumor entities, especially in breast cancer, an intraductal carcinoma is generally perceived as a precursor lesion, which precedes the emergence of invasive carcinoma. Therefore, in addition to parameters of the invasive carcinoma, histological parameters of the intraductal component have always played an important role in therapy planning of breast cancer. This is different in prostate cancer and although the term "intraductal carcinoma" has long been propagated by some authors, its routine use remains rare and inconsistent. This is certainly not only due to the far simpler therapy options of prostate cancer, in which focal and organ-preserving therapies still play a subordinate role, but also due to substantial interobserver variation and our inconsistent perception of intraductal carcinomas. This article gives a brief overview of currently available literature on this topic and explains why intraductal carcinoma of the prostate deserves our attention. In contrast to breast cancer, intraductal carcinoma of the prostate usually represents a post-invasive lesion, in which an aggressive tumor exhibits spread into pre-existing ducts; however, in rare cases, intraductal carcinoma may represent a true precursor lesion.

[Mesenchymal gastric tumor--not always GIST]. / Mesenchymaler Magentumor--nicht immer GIST.

The correct histopathological classification of a gastric mesenchymal tumor as a schwannoma is essential because in contrast to gastrointestinal stromal tumors (GIST) it is a definitive benign neoplasm which can be sufficiently treated by in sano (R0) resection. A (partial) gastrectomy is unnecessary. A clear radiological or sonographical differentiation between a schwannoma and GIST is not possible. The histomorphological and immunohistochemical features of this tumor entity are described.

[Combination of Excessive Weight Gain and Interleukin-8: A Possible Predictor of Necrotising Enterocolitis in Neonates?]. / Kann ein Gewichtssprung in Kombination mit einem Anstieg des Interleukin-8 eine nekrotisierende Enterokolitis bei Neonaten vorhersagen?

BACKGROUND: Weight gain before the clinical diagnosis of necrotising enterocolitis (NEC) is described as a predictive factor. HYPOTHESIS: Weight gain of more than 5% one day prior to clinical suspicion plus increase of plasma Iinterleukin-8 (IL-8) are predictive for NEC. METHODS: 48 infants with diagnosis of NEC stage II and III were enrolled in a case-control study. Oral and parenteral nutrition, diuresis and kinetics of weight and of IL-8 were documented. RESULTS: 31 infants with NEC-II and 17 infants with NEC-III were enrolled. Weight gain>5% occurred in 35.3% of NEC-III, in 0% of NEC-II and in 4.2% of the control group. IL-8 increased significantly [NEC-III (6 561.4 pg/mL) vs. NEC-II: (326.7 pg/mL) vs. control group (38.9 pg/mL); p<0.05]. Sensitivity of IL-8 in NEC-II was 87.10% (70.15-96.25) and in NEC-III 100.00% (80.33-100.00). Sensitivity of weight gain was 0.00% (0.00-11.32) in NEC-II and 35.29% (14.30-61.65) in NEC-III. CONCLUSION: Weight gain>5% was found in only 35.3% of the cases with NEC-III. Combination of weight gain and IL-8 did not improve the diagnosis of NEC.

[Cytoreductive surgery and HIPEC for peritoneal malignancies in children]. / Zytoreduktive Chirurgie und HIPEC bei peritoneal-metastasierten Tumoren im Kindesalter.

Peritoneal tumour dissemination represents an advanced tumour stage and survival rates are usually low. In the past, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established in adults leading to increased survival rates in comparison to chemotherapy alone. CRS and HIPEC are indicated in primary peritoneal tumours such as mesothelioma and pseudomyxoma peritonei, and in peritoneal metastases from gastrointestinal and ovarian cancers in adults. The incidence of peritoneal surface malignancies in children seems to be lower than in adults, but the incidence is unknown. Nevertheless, peritoneal carcinomatosis/sarcomatosis may occur in patients suffering from desmoplastic small round cell tumour (DSRCT), soft tissue sarcoma (rhabdomyosarcoma, leiomyosarcoma, GIST or liposarcoma), as well as in patients with gastrointestinal cancers. CRS and HIPEC have been established as a novel treatment option in children suffering from peritoneal carcinomatosis/sarcomatosis in very few centres worldwide. This paper reviews the indications, treatment regimens, and pitfalls of this approach in children.

[Signet ring cell infiltrate in the colon and gastric mucosa]. / Siegelringzellhaltiges Infiltrat in der Kolon- und Magenschleimhaut.

A 49-year-old female patient presented with anemia of unclear origin (hemoglobin level 6 µg/dl). During coloscopy a circular wall edema in the right flexure of the colon was observed and gastroduodenoscopy gave rise to the suspicion of fundic gland polyps (Elster's cysts) of the mucosa. In the lamina propria of the gastric mucosa, infiltration of a poorly differentiated carcinoma with signet ring cell morphology could be histologically identified resulting in the suspected diagnosis of a primary gastric signet ring carcinoma. Using immunohistochemistry it could be shown that the tumor cells expressed cytokeratin 7 (CK7), estrogen receptors and Gata 3 but not CK20 or Cdx2. The diagnosis of metastases of lobular breast cancer in the gastric and colon mucosa could be made.

[Cystic tumor on the porta hepatis]. / Zystischer Tumor an der Leberpforte.

A cystic entity from the porta hepatis of a 64-year-old female patient was sent in for rapid section diagnostics with a clinical suspicion of pancreatic cancer. The rapid section diagnostics revealed aspects of glandular proliferation with mucous-like material in the lumina which led to the suspicion of infiltration of a highly differentiated mucinous adenocarcinoma. However, conventional paraffin-section histology and the immunohistochemical marker profile could not confirm this suspicion but an adenomatoid tumor was diagnosed. In typical locations in the genital area of both genders, this entity is a current differential diagnosis to infiltrations of an adenocarcinoma.

Nephron sparing surgery for synchronous bilateral nephroblastoma involving the renal hilus.

PURPOSE: Bilateral nephroblastoma involving the renal hilus represents a significant surgical challenge. Different operative strategies have been proposed for this condition. We analyzed the outcome of simultaneous bilateral partial nephrectomy for complex stage V nephroblastoma. MATERIALS AND METHODS: We retrospectively analyzed patients with bilateral nephroblastoma involving the renal hilus operated on at our institution between 2002 and 2008. We assessed patient data and surgical and oncologic outcomes. RESULTS: We analyzed data from 5 patients with a median age of 27 months at surgery (range 13 to 58). Two children had additional pulmonary metastases. Patients were treated according to the International Society of Pediatric Oncology 2001/German Society of Pediatric Oncology and Hematology protocol. All children underwent synchronous bilateral nephron sparing surgery (longitudinal partial nephrectomy or enucleation) of the central tumors. Median operating time was 182 minutes (range 129 to 291), with vascular exclusion performed in 4 patients (7 to 25 minutes). Complications consisted of urinary leakage in 2 cases. Postoperative renal function was unimpaired in 4 patients and 1 patient had Wilms tumor/aniridia/genitourinary malformations/retardation syndrome with glomerulopathy. One patient with pulmonary metastases and blastemal histology had multiple pulmonary relapses and died due to pulmonary progressive disease. Four patients are alive without evidence of disease at a median followup of 45 months (range 44 to 73). CONCLUSIONS: Surgery for central stage V nephroblastoma is possible with good functional and oncologic outcomes. The single stage approach is safe, provided that operating and treating physicians have sufficient expertise with such conditions. The ultimate goal is to avoid tumor nephrectomy.

Earthquake recurrence and rupture dynamics of Himalayan Frontal Thrust, India.

The Black Mango fault is a structural discontinuity that transforms motion between two segments of the active Himalayan Frontal Thrust (HFT) in northwestern India. The Black Mango fault displays evidence of two large surface rupture earthquakes during the past 650 years, subsequent to 1294 A.D. and 1423 A.D., and possibly another rupture at about 260 A.D. Displacement during the last two earthquakes was at minimum 4.6 meters and 2.4 to 4.0 meters, respectively, and possibly larger for the 260 A.D. event. Abandoned terraces of the adjacent Markanda River record uplift due to slip on the underlying HFT of 4.8 +/- 0.9 millimeters per year or greater since the mid-Holocene. The uplift rate is equivalent to rates of fault slip and crustal shortening of 9.6(-3.5)(+7.0) millimeters per year and 8.4(-3.6)(+7.3) millimeters per year, respectively, when it is assumed that the HFT dips 30 degrees +/- 10 degrees.

Sonographic diagnosis of an unusual case of multilocular cystic nephroma mimicking polycystic kidney disease.

The following is a report of the unusual case of a multilocular cystic nephroma in an 8-year-old boy who was transferred to our unit with a palpable abdominal tumor. The patient suffered from thoracic pain and night sweating. The laboratory values were normal. Abdominal sonography showed a huge kidney tumor on the right side consisting of numerous small cysts transversed by irregular septa of variable thickness. The cysts had a diameter of 1 -5 mm; larger cysts of more than 1 cm in diameter were not able to be shown. In the center of the tumor a normal renal parenchyma was able to be shown. The tumor arose like a mushroom from the kidney. Color Doppler sonography showed good vascularity of the normal renal parenchyma while the tumor had only a few internal vessels. The tumor was surgically removed. The histologic diagnosis was cystic nephroma. Unusual features of this tumor were the small size of the numerous cysts similar to polycystic kidney disease and the mushroom-like growth of the tumor.

Healing of lymphocytic gastritis after Helicobacter pylori eradication therapy--a randomized, double-blind, placebo-controlled multicentre trial.

BACKGROUND: An association between Helicobacter pylori infection and lymphocytic gastritis has been postulated. AIM: To assess the long-term effect of H. pylori eradication therapy on lymphocytic gastritis in a double-blind, placebo-controlled, multicentre trial. METHODS: Patients with lymphocytic gastritis were randomized to receive either 1-week triple therapy for eradication of H. pylori or omeprazole plus placebo. Endoscopy and histology was performed at baseline and after 3 and 12 months. Patients of the omeprazole/placebo group with persistent lymphocytic gastritis after 12 months received crossover open-label triple therapy. RESULTS: Fifty-one patients were randomized. Intention-to-treat analysis revealed a trend to a higher healing rate of lymphocytic gastritis 3 months after triple therapy compared with omeprazole/placebo (83.3% vs. 57.7%, 95% CI for RR: 0.8-2.8, P = 0.06). After 12 months, the healing rate of lymphocytic gastritis was significantly higher after triple therapy compared with omeprazole/placebo (intention-to-treat 95.8% vs. 53.8%, 95% CI for RR: 1.1-3.5, P = 0.01). All patients (n = 5) who received crossover triple therapy, showed healing of lymphocytic gastritis after further 12 months. CONCLUSION: Our study demonstrates that 1-week triple therapy aiming at eradication of H. pylori leads to a complete and long-lasting resolution of lymphocytic gastritis in the majority of patients.

Specificity of antibodies directed against Env protein of human endogenous retroviruses in patients with germ cell tumors.

We report here that 85% of the patients with germ cell tumors (GCTs) produce antibodies directed against Env protein of human endogenous retroviruses. Individuals that received antitumor treatment showed a decrease with time in their antibody titers. Importantly, of the rare cases of non-GCT individuals with Env-antibodies (n= 15, 0.8%), none produced antibodies directed against the transmembrane domain (TM), whereas all tested Env-positive GCT patients (n= 49) generated such antibodies at high titers. TM is required for Env to be expressed at the cell surface. Thus, anti-TM antibodies constitute highly specific markers for GCT and may hint at a function of Env during tumorigenesis.

Genotypic characterization of prostatic carcinomas: a combined cytogenetic, flow cytometry, and in situ DNA hybridization study.

Cytogenetic studies were performed on 36 biopsies obtained from 26 primary prostatic adenocarcinomas. Following histopathological characterization of control sections, the biopsies were investigated using metaphase cytogenetics, DNA flow cytometry, and fluorescence in situ DNA hybridization. In 12 specimens, no carcinoma was found in control sections by histopathological means. In 24 carcinoma biopsies clonal aberrations were detected in 15 specimens. Tetraploidy as sole aberration was detected in five specimens. Loss of the Y chromosome was seen in eight samples. Only one tumor revealed structural abnormalities. Eight samples were found to be normal (46,XY). Remarkably, nonclonal chromosome aberrations, particularly marked chromosome loss, were frequently detected in prostatic carcinomas and premalignant lesions (prostatic intraepithelial neoplasia). In the series of biopsies investigated by means of cytogenetics and flow cytometry, biopsies with aneuploid DNA content were found to be cytogenetically normal. Conversely, the cytogenetically aberrant clones were found to be of diploid DNA content. Evidence of focal intratumoral heterogeneity was revealed by cytogenetics, flow cytometry, and in situ hybridization.

Stromal expression of c-Ets1 transcription factor correlates with tumor invasion.

The stroma reaction has an important role in tumor growth, invasion, and metastasis. In various invasive human carcinomas, as well as in a mouse model for tumor invasion, transcripts encoding the transcription factor c-Ets1 were detected within stromal fibroblasts, whereas they were absent in epithelial tumor cells. This expression of c-Ets1 was often increased in fibroblasts directly adjacent to neoplastic cells. Endothelial cells of stromal capillaries were also positive for c-Ets1 expression. In contrast, fibroblasts of corresponding noninvasive lesions and of normal tissues were consistently negative. In cultured human fibroblasts stimulated by basic fibroblast growth factor and tumor necrosis factor alpha, the expression of c-Ets1 correlated with the accumulation of transcripts for potential target genes, collagenase-1 and stromelysin-1. The same correlation was observed in some of the invasive carcinomas investigated. These results suggest that c-Ets1 participates in the regulation of tumor invasion in vivo.

The SSX-2 gene, which is involved in the t(X;18) translocation of synovial sarcomas, codes for the human tumor antigen HOM-MEL-40.

Using autologous serum for the serological analysis of recombinantly expressed clones (SEREX) from a cDNA derived from a human melanoma, several new melanoma antigens were identified that are immunogenic in the autologous host. Sequence analysis revealed that one of these antigens, HOM-MEL-40, was coded for by the SSX2 gene, which has recently been described to be involved in the t(X;18) translocation of human synovial sarcomas. Expression analysis performed by Northern blot and RT-PCR demonstrated the presence of HOM-MEL-40 transcripts in a significant proportion of human melanomas (50%), colon cancers (25 %), hepatocarcinomas (30%), and breast carcinoma (20%) but not in normal tissues except for testis. Sequence comparison with transcripts cloned from testis ruled out mutations in the melanoma-derived HOM-MEL-40. Antibodies against HOM-MEL-40 were found in 10 of 89 patients with melanoma, including 3 of 8 patients with HOM-MEL-40-positive tumors, but not in 41 apparently healthy controls. In view of the specific expression pattern and immunogenicity in cancer patients, HOM-MEL-40 holds promise as a target for immune interventions in a considerable population of patients with HOM-MEL-40-positive tumors.

Genetic changes and telomerase activity in human renal cell carcinoma.

Using the sensitive telomeric repeat amplification protocol assay, we detected telomerase activity in 26 of 35 (74.3%) renal cell carcinomas analyzed. Subdivision of the tumors according to telomerase activity did not reveal an obvious association between the presence of telomerase activity and histomorphological stage, grade, tumor size, or DNA ploidy. Furthermore, no association was found between telomerase activity and a distinct chromosomal aberration pattern; namely, loss of genetic material on the short arm of chromosome 3. Telomerase activity was also detected in 6 of 35 (17.1%) normal corresponding renal tissue samples, which seems interesting in light of the supposed biological role of telomerase expression in carcinogenesis. Interestingly, telomerase activity was detected in three of the four (75%) kidneys bearing non-clear cell tumor types, whereas of the 31 kidneys with clear cell carcinomas, telomerase activity was found in only 3 (9.7%) normal tissue samples. In addition, the two renal angiomyolipomas and one of the two analyzed transitional cell carcinomas of the renal pelvis were telomerase negative.

Measurement of Gastric Circumference in Foetuses with Oesophageal Atresia.

Background: The specific recognition of oesophageal atresia (OA) with or without a tracheal fistula in a foetus is a diagnostic challenge for prenatal medicine. The aim of the present work is to analyse the value of the measurement of gastric size in the diagnosis of this significant malformation. Materials and Methods: Altogether, the examinations of 433 pregnancies between the 18.4 and 39.1 weeks of gestation were retrospectively analysed. 59 of these foetuses exhibited an OA. By means of a linear regression analysis with normal foetuses, significant parameters influencing gastric size were examined. Subsequently the gastric sizes were transformed into z values and a comparison was made between OA with and without fistulae with the help of t tests. Results: In the normal foetuses there was a significant association between the gastric circumference and the abdominal circumference (circumference = 6.809 + 0.179 × abdominal circumference, r = 0.686, p < 0.0001). In the normal group the average was 43.0 (standard deviation [SD] 13.7) mm and those in foetuses with and without fistuale were 33.8 (SD 22.7) and 0.9 (SD 3.7) mm. In 34 (57.6 %) foetuses with an OA, the gastric circumference was below the 5th percentile. In detail, there were 13 (34.2 %) foetuses with a fistula and 21 (100 %) without a fistula. The average z values in the normal group and in the groups of OA with fistula and without fistula amounted to 0.0 (SD 1.0), -1.3 (SD 2.2) and -4.5 (SD 1.0). Conclusion: Measurements of the gastric circumference below the 5th percentile should lead to further diagnostic measures, especially when associated with polyhydramnios. Although OA without a fistula is always conspicuous, only about one in three OAs with fistula are associated with a significantly smaller stomach.

Expression of the breast cancer associated gene pS2 and the pancreatic spasmolytic polypeptide gene (hSP) in diffuse type of stomach carcinoma.

Expression of the pancreatic spasmolytic peptide (hSP) gene and pS2 (a gene isolated from oestrogen-induced breast carcinoma cells) were analysed in 36 samples of human stomach carcinoma. 17 tumours were investigated at the RNA level (by northern blots) as well as at the gene product level (by immunochemistry). Since pS2 had been shown to be expressed in normal stomach mucosa its activity in carcinoma samples was expected. Surprisingly, strong pS2 immunoreactivity was noted in the diffuse carcinoma type, whereas the intestinal type displayed weak reactivity. The tumour samples showing strong immunostaining expressed the regular 0.6 kb pS2 RNA band and weak staining was paralleled by aberrant transcripts. Additionally, only in tumour samples with regular pS2 transcription was the typical 0.7 kb hSP RNA band seen; samples with aberrant pS2 bands did not express hSP at all. This is the first demonstration of hSP gene activity in a human tumour.

Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of monoamine transporters in neuroblastoma cell lines: correlations to meta-iodobenzylguanidine (MIBG) uptake and tyrosine hydroxylase gene expression.

Radiolabelled meta-iodobenzylguanidine (MIBG) has been widely used in scintigraphy and targeted radiotherapy in patients with neuroblastoma. Recently, it has been demonstrated that MIBG is incorporated into neuroblastoma cells by the noradrenaline transporter. In vitro experiments on SK-N-SH human neuroblastoma cells performed in the present study showed that uptake of MIBG is inhibited by noradrenaline, more so by dopamine and to a lesser extent, by serotonin, indicating that the respective transporters may also contribute to MIBG uptake. However, neither dopamine nor serotonin transporter gene expression was detected. Noradrenaline transporter gene expression was found in 4 of 6 investigated cell lines, which correlated with specific MIBG uptake. Furthermore, an inverse correlation of noradrenaline transporter and tyrosine hydroxylase gene expression, the key regulatory enzyme of catecholamine synthesis, was observed. These data show that MIBG is specifically incorporated only in neuroblastoma cells in which there is noradrenaline transporter gene expression. Furthermore, the catecholamine status in neuroblastoma cells is regulated by a coordinate expression of the key elements of catecholamine synthesis and reuptake systems.

Ki-ras oncogene and p53 tumour suppressor gene mutations in colorectal carcinomas from the European Saar-Luxembourg region are less frequent than predicted by the classic adenoma-carcinoma sequence model.

Recent investigations of colorectal cancer (CRC) have suggested that the accumulation of specific alterations in cell-growth regulating genes trigger the stage-wise progression to malignancy and that at least some of them could be useful for prognosis. In this study, the frequency, location and type of mutations of the Ki-ras proto-oncogene exons 1-2 and p53 tumour-suppressor gene exons 5-9 were analysed in colorectal carcinomas of 72 patients from the European Saar-Luxembourg region using PCR-SSCP screening and direct sequencing. The incidences of Ki-ras activating and p53 inactivating point mutations in these European samples were much lower (Ki-ras: 5 (6.9%) and p53: 13 (18.1%)) than reported for both genes in American studies (40-50% at least) (P < 1 x 10(-3)). These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.