Next-generation sequencing of adrenocortical carcinoma reveals new routes to targeted therapies.

AIMS: Adrenocortical carcinoma (ACC) carries a poor prognosis and current systemic cytotoxic therapies result in only modest improvement in overall survival. In this retrospective study, we performed a comprehensive genomic profiling of 29 consecutive ACC samples to identify potential targets of therapy not currently searched for in routine clinical practice. METHODS: DNA from 29 ACC was sequenced to high, uniform coverage (Illumina HiSeq) and analysed for genomic alterations (GAs). RESULTS: At least one GA was found in 22 (76%) ACC (mean 2.6 alterations per ACC). The most frequent GAs were in TP53 (34%), NF1 (14%), CDKN2A (14%), MEN1 (14%), CTNNB1 (10%) and ATM (10%). APC, CCND2, CDK4, DAXX, DNMT3A, KDM5C, LRP1B, MSH2 and RB1 were each altered in two cases (7%) and EGFR, ERBB4, KRAS, MDM2, NRAS, PDGFRB, PIK3CA, PTEN and PTCH1 were each altered in a single case (3%). In 17 (59%) of ACC, at least one GA was associated with an available therapeutic or a mechanism-based clinical trial. CONCLUSIONS: Next-generation sequencing can discover targets of therapy for relapsed and metastatic ACC and shows promise to improve outcomes for this aggressive form of cancer.

Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer.

AIMS: Small cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ∼5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice. METHODS: DNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations. RESULTS: A total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1­10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions in RICTOR (10%), KIT (7%), PIK3CA (6%), EGFR (5%), PTEN (5%), KRAS (5%), MCL1 (4%), FGFR1 (4%), BRCA2, (4%), TSC1 (3%), NF1 (3%), EPHA3 (3%) and CCND1. The most common non-actionable genomic alterations were alterations in TP53 (86% of SCLC cases), RB1 (54%) and MLL2 (17%). CONCLUSIONS: Greater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease.

[Complications and limitations of transurethral prostatic resection: retrospective study of 366 patients]. / Complicanze e limiti della resezione prostatica transuretrale: studio retrospettivo su 366 pazienti.

In present paper we report our experience on 366 patients underwent to transurethral resection of prostate from January 1988 to January 1990. All patients were controlled by uroflowmetry and retrograde plus minctional urethrography, with evaluation of the possible immediate and latest complications. Among the latest complications, the most representative had been urethral stricture, occurred in 24 patients (6.5%) according with international literature. We considered also various iatrogenics factors (operator experience, endoscopic time, catheter section, catheter permanence time, use of lubricator, presence of catheter before TURp, preventive Otis urethrotomy). From our study rises out that the most important risk factors are: a) catheter permanence time; b) TURp without preventive Otis urethrotomy.

[Neoadjuvant chemotherapy of locally advanced tumors of the bladder: preliminary experience]. / Chemioterapia neoadiuvante nei tumori vescicali localmente avanzati: esperienza iniziale.

From february 1988 to march 1989, 6 patients with locally advanced bladder cancer (T3b-T4, N0-N1, M0) were treated with 4 courses of neoadjuvant MP chemotherapy (methotrexate 300 mg/mq. + cisplatinum 100 mg/mq). In two patients chemotherapy was stopped because minimal or no response after two courses. Partial response (RP) was achieved in three patients (50%). Two patients died 2 and 5 month later. One patients developed metastases at 11 month. The remaining three cases showed NED at 3, 4 and 15 months of follow-up. In the same period 4 patients with metastatic bladder tumor were treated with M-VAC chemotherapy according to Yagoda before the cystectomy. M-VAC obtained a complete response in one case, and PR in 3 cases. All the metastases showed evidence of objective tumor regression. Reduction of bone pain was observed in one case. One patient died 15 months later with bone massive involvement. Another patient developed invasive tumor at 13 months. Two patients were disease-free at 3 and 5 months, respectively. Toxicity was more frequent in patient treated with M-VAC than with MP chemotherapy. M-VAC, we believe, represents a reliable neoadjuvant treatment of advanced metastatic bladder cancer.

[The Wolf piezolith 2300: lights and shadows]. / Piezolith 2300 Wolf: luci ed ombre.

Extracorporeal piezoceramic Wolf lithotripter was developed in West Germany by Ziegler and Associates in collaboration with Wolf GmbH. Piezolith 2300 has no cumbersome water tube and it was constructed as a mobile unit. It requires no patient irradiation, a special room adaptation, a electrodes replacement or any auxiliary staff. From February 1988 up to May 1989 a total of 230 stones in 218 patients, 18 to 79 years old, was treated with Piezolith 2300, in our Center. Ultrasound localization failed in 7 more cases of ureteral stones. Treatment resulted quite painless. Auxiliary measures before EPL, were performed in 12 cases, only (5%). 15 pts were managed with combined procedures: ESWL + EPL, PCNL + EPL, surgery + EPL. The mean of SW was 3000 (800-6500) for each piezoelectric session. In 27 pts (12%), 4 or more EPL sessions were performed. A successful disintegration was achieved in 210 cases (90.2%). Out of 20 unsuccessful cases, 15 were managed by Dornier HM3 mod lithotripter and 4 by ULL. Post EPL ancillary procedures were required in 4 pts (1.8%). No major complications were observed in our series. At the 30-days follow-up, 57.3% of the patients were stone free. At preliminary 3-month follow-up in 120 pts the rate of the entire success raised to 75%. We think, according to others authors, that EPL is the treatment of first choice in 70% of reno-ureteral stones.

Ceftriaxone in chemoprophylaxis and therapy of urinary tract infections.

We analysed eight prospective randomized trials describing the use of ceftriaxone (Rocephin) in short-term prophylaxis in patients undergoing urologic surgery. The results of these trials show that chemoprophylaxis with ceftriaxone is effective. In the therapy of postoperative infections in urologic surgery the single daily dose of ceftriaxone represents a considerable advantage both regarding patients' compliance and clinical convenience. From March 1987 to January 1988, 25 patients with postoperative infections after urologic surgery were treated with ceftriaxone 1 g i.m. once daily. Quick resolution of signs and symptoms of infection occurred in all cases.