[Drug-induced liver injury-significance of pathology]. / Drug-Induced Liver Injury ­ Stellenwert der Pathologie.

Many different medical agents, herbal products, and dietary supplements can induce drug-induced liver injury (DILI) as a clinically relevant complication. DILI, which is direct toxic or idiosyncratic, can have a broad spectrum of clinical appearances from elevation of liver enzymes to acute liver failure. DILI is categorized clinically according to the pattern of serum parameters or pathologically according to the pattern of histomorphology. Histopathological patterns can be described as hepatitic, granulomatous, cholestatic, ductopenic, fibrotic, steatotic, steatohepatitic, and vascular. Correlation to the corresponding drug can be carried out with the corresponding databases (US National Library of Medicine, Liver Tox; www.ncbi.nlm.nih.gov/books/NBK547852/ ). Liver biopsy, in contrast to a clinical/serological diagnostic, has the advantage of an exact resolution with evidence of pathophysiology, activity, regeneration, chronification, and prognosis. Co-occurrence of underlying liver disease can be excluded or confirmed. Histological patterns of DILI are described and illustrated. A diagnostic algorithm for the interpretation of liver biopsies is provided.

Initial experiences with the Hemopatch® as a hemostatic agent in zero-ischemia partial nephrectomy.

PURPOSE: Nephron-sparing surgery (NSS) is the gold standard treatment for resectable renal tumors. In the last decade, laparoscopic partial nephrectomy (LPN) has evolved in technical, surgical and oncological aspects and is an accepted treatment option for local-stage renal tumors. Improvements in not only surgical techniques, but also potent hemostats have encouraged this evolution. Here, we report our initial experiences with a new hemostatic agent, Hemopatch(®) (polyethylene glycol-coated collagen patch, Baxter), in zero-ischemia LPN. METHODS: Seven patients with confirmed renal masses were enrolled and subjected to zero-ischemia LPN. In all cases, Hemopatch(®) was applied to the tumor resection site after suturing of the renal parenchyma. The following clinical data were captured for analysis: staging information, PADUA and RENAL nephrometry scores, operation time, blood loss, complications, pathology and hospitalization length. RESULTS: The median tumor size was 30.0 mm (range 9.5-72). The median PADUA and RENAL nephrometry scores were 6 (range 6-7) and 4 (range 4-6), respectively. All LPNs were performed with the zero-ischemia technique. In six of the seven patients, parenchymal suturing of the resection site was performed. No uncontrolled bleeding was observed. The median operation duration was 139 min (range 103-194), the median blood loss was 325 cc (range 50-700) and the median hospitalization length was 6 days (range 4-7). Hemopatch(®) provided sufficient hemostasis in all cases. No postoperative complications were observed. CONCLUSIONS: Although this study is limited to a small set of initial experiences with Hemopatch(®) in LPN, it proves the feasibility and reliability of this new hemostat. Following further evaluation in prospective randomized comparative studies, Hemopatch(®) might represent a promising tool in NSS.

The lncRNA Fer1L4 is an adverse prognostic parameter in clear-cell renal-cell carcinoma.

PURPOSE: Long non-coding RNAs (lncRNA) are involved in oncogenesis and tumor progression in various tumor entities. At present, little is known about the role in tumor biology of the lncRNA Fer-1 like family member 4 (Fer1L4) in clear-cell renal-cell carcinoma (ccRCC). The aim of this study is to evaluate the expression of Fer1L4 in patients with ccRCC, its association with clinicopathological parameters, and value as prognostic biomarker. MATERIAL AND METHODS: The expression of Fer1L4 was analyzed in the TCGA ccRCC cohort (n = 603; ccRCC n = 522, normal n = 81) and subsequently validated by quantitative real-time PCR in an independent cohort (n = 103, ccRCC n = 69, normal n = 34). Expression profiles were statistically correlated with clinicopathological and survival data. RESULTS: Fer1L4 lncRNA is overexpressed in ccRCC compared to adjacent normal tissues. Increased expression significantly correlates with tumor aggressiveness: high expression levels of Fer1L4 RNA were found in higher grade, higher stage, and metastatic tumors. Furthermore, Fer1L4 overexpression is an independent prognostic factor for overall, cancer-specific, and progression-free survival of patients with ccRCC. CONCLUSION: Fer1L4 expression significantly correlates with aspects of tumor aggressiveness. Based on this impact on tumor progression and its influence as an independent prognostic factor, Fer1L4 appears to exert properties as an oncogene in ccRCC. As a prognostic tissue biomarker, further functional investigations are warranted to investigate Fer1L4 as a potential therapeutic target.

[Pathogenesis of urological complications after radiation therapy]. / Pathogenese urologischer Komplikationen nach Strahlentherapie.

Radiation therapy is a treatment modality that is often used in the uro-oncological setting. The common indication for the radiation therapy in the urological sphere is prostate cancer, whether it is used primarily as a radical approach, or postoperatively as adjuvant or salvage therapy. All urological organs are sensitive to radiation injury with the urinary bladder being the most susceptible with a typical cascade including acute and late changes, arising in the dose-dependent manner. The common indication for radiation therapy in urology is prostate cancer, which collaterally affects the urinary bladder and rarely urethra (especially the bulbo-membranous urethra). Ureteral damage and stricture formation is almost always restricted to the cases of intraoperative therapy and external beam radiation therapy for other urological malignancies (gynecological organs, rectum, retroperitoneal soft tissue tumors) and should not be underestimated. Postradiotherapeutic tissue changes, especially of the prostate, can cause difficulties for pathologists and urologists with regard to diagnosis of prostate cancer recurrence and salvage therapy.

[Molecular biomarkers and prognostic factors for prostate cancer]. / Genetische Marker und Prognosefaktoren beim Prostatakarzinom.

In the era of personalized medicine and precision oncology, innovative genetic biomarkers are of emerging interest to close the diagnostic and prognostic gap that is left by current clinicopathologic risk classifiers. The current review article summarizes evidence regarding prognostic and predictive genetic biomarkers that are currently in widespread clinical use at initial diagnosis as well as following definitive treatment of prostate cancer. We give a brief summary about basic principles of biomarker research studies and present current data for the Progensa PC3 test, TMPRSS2:ERG gene fusion, ConfirmMDx, Prolaris gene panel, OncotypeDX Genomic Prostate score, and Decipher classifier. Evidence regarding those genetic biomarkers has heavily increased recently. However, there is still a lack of large, multicentric and prospective clinical validation studies. Furthermore, comparative studies that investigate the prognostic value of various genetic biomarkers are needed.