[T1 bladder cancer: role of documentation for bladder tumor findings and targeted second resection]. / Das T1-Blasenkarzinom : Bedeutung der Dokumentation des Tumorbefundes und der gezielten Nachresektion.

BACKGROUND: For control resection of T1 bladder tumors an exact relocalization of the previously infiltrating tumor spread can be complicated by postreactive alterations, multiple scar tissue or change of surgeons. In this study the results of control transurethral resection of the bladder (TURB) after T1 high grade bladder tumors with the focus on localization and importance of standardized exact documentation were analyzed. PATIENTS AND METHODS: From July to February 2012 a control resection was performed in 167 patients due to a T1 high grade bladder cancer. The rates of residual tumor tissue and localization were investigated with standardized tumor documentation. RESULTS: Out of 167 patients with T1 bladder cancer who underwent a control resection tumor tissue was found in 58.1 % (97 out of 167) and in 85.6 % (83 out of 97) the primary site was affected (41.2 % only at primary site and 44.3 % additionally at other locations). In 11 patients (11.3 %) residual tumor tissue at the initial site was only detected histologically. CONCLUSIONS: Our results indicate that T1 high grade bladder cancers show a relevant rate of residual tumor tissue at control resection which confirms the clinical guidelines of the European Association of Urology (EAU) on mandatory resection. In most cases the primary tumor site is affected. The standardized bladder tumor documetation allows well-directed control resection also in patients with multiple scars and post-TUR alterations, even when performed by a different surgeon.

[Impact of operator experience on TURB of high-grade non-muscle-invasive bladder cancer--analysis of 254 second resections at a university teaching hospital]. / TURB--Welche Bedeutung hat die Erfahrung des Operateurs bei high grade-Tumoren der Harnblase? Analyse von 254 Nachresektionen an einer universitären Ausbildungsklinik.

INTRODUCTION: In departments with urological training of residents, part of the TURB procedures are performed as "teaching surgery". Does resection quality and early recurrence depend on the operator's experience? PATIENTS AND METHODS: From July 2007 to February 2012 254 second resections (TURB) after Ta high-grade and T1 high-grade bladder tumours were performed at our institution. The surgeons were stratified into "junior residents" (first and second year of training), "experienced residents" (3rd-5th year of training), board certified urologists, consultants and chief surgeons. We analysed the risk of recurrence at second resection and characteristics of the initial TURB. RESULTS: 87 patients presented with a Ta high-grade tumour (34.3%) and 167 had a T1 high-grade lesion (67.7%). Most TURBs were performed by "experienced residents" (3rd-5th year) and the chief of department. The recurrence rate at second resection was 52.4%. A significant association with the recurrence rate was shown for the number of initial tumours, size and T-stage. No association was found for the training level of the surgeon. Additionally, there was no different detrusor rate for the surgeons, as a parameter for a correct, muscle-deep TURB. A bias that surgeons in training had more favourable tumours (solitary, less than 3 cm) could be excluded. CONCLUSIONS: In our data detrusor rate and recurrence risk at second resection are independent of the surgeon's experience. The results of "teaching-TURBs" are not inferior compared to TURBs performed by board certified urologists or consultants under the conditions of undisturbed communication and personal supervision.

[T1 high-grade bladder cancer - value of second operation with prognostuic parameters of first operation: analysis of 167 cases]. / T1 high grade-Blasentumor - Wertigkeit der Nachresektion mit prognostischen Parametern der Initialresektion: Analyse von 167 Fällen.

We have evaluated the results of second transurethral resections of the bladder (TURB) after T1 high-grade bladder cancer over a 4.5-year period.From July 2007 to February 2012, 2172 TURB procedures were performed at our institution, of which 1130 were initial resections owing to primary tumour or relapse. Of these, 258 revealed T1 high-grade bladder cancer, and here we investigated tumour characteristics of the initial TURB and results of the second resection.The incidence of T1 high-grade tumours was 22.8% (N=258). Of 167 patients who underwent a second resection, tumour was found in 58.1% (97 of 167). Tumours were mostly multifocal (61.9%) and smaller than 3 cm (69.1%). Histology of the second resection revealed Ta low-grade in 8.4%, Ta high-grade in 16.2%, T1 high-grade in 19.8% and an upstaging to T2 and more in 6.6%. A significant association with the recurrence rate was found for the number of tumours at initial TURB: patients with multiple tumours at initial TURB had a recurrence rate of 69.0% compared with only 46.3% of patients with solitary tumour. For tumour-size and detrusor muscle in specimen a non-significant association was shown.T1 high-grade bladder cancers show a relevant rate of tumour at second TURB which confirms the clinical guidelines of the EAU. A significant association for a tumour-free second TURB in our data was shown for solitary tumours. A non-significant association was shown for tumour-size and when detrusor muscle was present in the specimen. Currently there is no data to determine the best time interval before second resection.

Retroperitoneal tumours: the pathologist's view.

Retroperitoneal lesions/sarcomas are rare. Diagnosis is difficult and needs special methods. Diagnosis and Treatment is an interdisciplinary process. Molecular Diagnostics will become more and more necessary in the future.

Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study.

BACKGROUND: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. PATIENTS AND METHODS: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. RESULTS: Tumors from 312 of 442 patients (71%) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (∼11%). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. CONCLUSION: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN.

[Renal cell carcinomas. Pathomorphologic diagnosis in the light of modern pharmacotherapy]. / Nierenzelltumoren. Pathomorphologische Diagnostik im Lichte moderner Pharmakotherapie.

Renal carcinomas have been classified with increasing accuracy in recent years and new sub-groups have been assigned, which, due to their distinct development pathways, carry varying prognoses and require specific treatment approaches. A range of antibodies are available for their immunohistochemical classification. Identifying a gene defect--mutation, deletion, trisomies and monosomies, oncogene activation--enables the application of targeted therapy, e.g. using antibodies or tyrosine kinase inhibitors in signaling pathways, among others. Renal carcinoma diagnosis by the pathologist is taking on a particularly important role.

[Villous adenoma of the renal pelvis and ureter]. / Villöses Adenom des Nierenbeckens und Ureters.

Villous adenomas of the urinary tract are extremely rare tumours belonging to the adenoepithelial metaplasias. They can be associated with other neoplasias, especially with carcinomas. We describe the case of an 85-year-old female patient suffering from a villous adenoma of the renal pelvis and ureter.

[Choristoma in the vocal fold]. / Choristom des Taschenbandes.

Choristoma in the larynx is rare and related to thyroid or glial tissue. The manifestation of salivary gland tissue in the larynx has not been reported to date. We present the case of an 80 year old male complaining of hoarseness and productive coughing. A left side tumourous swelling was seen in the larynx with intact vocal cord mobility. Using microlaryngoscopy the mass was resected without any intra- or postoperative problems. Histologically, a choristoma-heterotopic salivary gland tissue in the muscle and fat tissue--was found. The mucosa was intact and there were no signs of malignancy. Differential diagnosis of such masses in the larynx include benign lesions as well as specific infections, e.g. tuberculosis, sarcoidosis, amyloidosis and Wegener's granulomatosis. Especially in non-smokers, sarcoma, lymphoma and melanoma should be separated from the frequent squamous cell carcinoma of the laryngeal tissue. In rare cases, heterotopic tissue can mimic a tumourous mass. Intralaryngeal resection is the therapy of choice and should be recommended to the patient.

[Molecular genetic changes in renal cell carcinomas]. / Molekulargenetische Veränderungen in Nierenzellkarzinomen.

Over the last decade several genetic alterations involved in the pathogenesis and progression of renal cell carcinoma have been identified. These findings will have a wide implication for the diagnosis and management of renal cell carcinomas. This review provides a discussion of general principles of tumor development as well as the specific mechanisms underlying renal carcinogenesis.

Low-grade tubular-mucinous renal neoplasms: morphologic, immunohistochemical, and genetic features.

The current classification system of renal tumors is based on morphologic criteria, as supported by genetic findings. We present a group of previously unclassified tumors with similar morphologic and genetic features, suggesting a new entity within renal neoplasms. Seven renal tumors from five patients (ages 31-67 years) were analyzed. All cases were stained with periodic acid-Schiff, Hale's colloidal iron (HCI), and Alcian blue (AB) at pH 2.5/1.0 with and without hyaluronidase (HA) digestion. Immunohistochemical (IHC) stains were performed for CK8, CK18, CK19, vimentin, villin, Tamm-Horsfall protein (THP), renal cell carcinoma marker (RCC), epithelial membrane antigen (EMA), ulex europaeus agglutinin (UEA-1), soy bean agglutinin (SBA), peanut agglutinin (PNA), and MIB-1. Comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies were performed on all cases. All tumors showed circumscribed growth, a tubular growth pattern with focal solid areas, no significant nuclear atypia and absence of necrosis, desmoplasia, or inflammation. Abundant extracellular mucin was present. Immunohistochemistry stains support collecting duct origin (EMA+, PNA+, SBA+/-, CK 8/18/19+, vimentin+/-, UEA-1-, RCC-, villin-, THP-). The proliferative rate was low (<1%). CGH showed multiple consistent chromosomal losses (-1,-4, -6, -8, -9, -13, -14, -15, -22). Clinical outcome was favorable, with recurrences but no known distant metastases or death of disease. These findings are distinct from all previously classified renal neoplasms. Our data suggest the presence of a unique tumor entity within tumors of probable collecting duct origin: tubular-mucinous renal tumors of low malignant potential.

Primary apoptosis as a prognostic index for the classification of metastatic renal cell carcinoma.

PURPOSE: We identified novel biological markers of prognosis in primary histopathological specimens from patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Apoptotic indexes (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling), proliferation rates (Ki-67 antigen), p21 (WAF1/cip1) expression and CD95 (APO-1/Fas) expression were determined in paraffin embedded nephrectomy specimens from 73 patients with histologically confirmed, progressive metastatic disease. Kaplan-Meier survival analysis, log rank statistics and 2-proportional Cox regression analysis were done to identify new risk factors in addition to conventional classification criteria, and demonstrate statistical independence. RESULTS: Multivariate analysis indicated that primary tumor apoptosis (p = 0.0116) and the interval from diagnosis to metastatic disease (p = 0.002) had a high predictive impact on overall survival after initial diagnosis. Patients were assigned to 2 risk groups, namely a poor prognosis group with a median survival of 20 months, defined by apoptosis less than 6% in the primary tumor nephrectomy specimen and a time from initial diagnosis to metastatic disease of less than 6 months, and a good prognosis group with a median survival of 56 months, defined as the absence of 1 or 2 risk factors. CONCLUSIONS: Our findings showed that primary tumor apoptosis is a novel independent predictor in patients with metastatic renal cell carcinoma at initial diagnosis. It leads to a new prognostic index in the pretreatment classification of metastatic renal cell carcinoma.

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines.

This paper describes the production of recombinant Semliki Forest virus encoding murine or human granulocyte-macrophage colony-stimulating factor (GM-CSF) and the capacity of these vectors to transduce murine and human tumor cells ex vivo. High-titer stocks (up to 3 x 10(9) particles/ml) of conditionally infective, replication-defective, recombinant SFV particles were generated using the SFV Helper-2 system. It is shown that the recombinant SFV/GM-CSF virus, as well as recombinant SFV carrying the beta-galactosidase reporter gene, efficiently transduce both murine tumor cell lines as well as primary human renal carcinoma cells. Using ELISA's specific for GM-CSF, levels of GM-CSF production by the cells were determined. Levels of murine GM-CSF (mGM-CSF) produced by SFV/mGM-CSF transduced renal cell cancer cultures were equal to or higher than corresponding levels reported in the literature after transduction of similar renal carcinoma cell cultures using a retroviral vector system. The biological activity of GM-CSF was demonstrated by using cells which are dependent on GM-CSF for growth and by using primary bone marrow cells. All the transduced cell cultures (including the human renal cell carcinoma samples) produced GM-CSF for up to at least 4 days after transduction. The results imply that the recombinant SFV system can be used for rapid and facile preparation of autologous cancer cell vaccines.

Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22-->q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.

Alpha-fetoprotein-producing renal cell carcinoma.

Alpha-fetoprotein (AFP) is recognized as a tumor marker of yolk sac tumors, liver cancer and some other cancers of the digestive organs. Renal cell carcinoma (RCC) producing AFP is a rare entity. A case of AFP-producing RCC with solitary bone metastasis, but without liver involvement, is reported. The stain specific to AFP proved the presence of AFP in the cytoplasms of more cells of the renal tumors. Additionally, the other published cases are reviewed. These cases indicate that mesoderm-originating malignant tumors such as RCCs can produce AFP in some situations. So, AFP is probably more universal than believed, although it is generally a popular and useful tumor marker for hepatocellular carcinomas and yolk sac tumors.