Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet-Uro 19BEYOND study.

BACKGROUND: Nivolumab and cabozantinib are currently approved agents in metastatic renal cell carcinoma (mRCC) but there are no data available for patients progressing to both treatments. The aim of this study was to compare active therapeutic options and best supportive care (BSC) after progression to nivolumab and cabozantinib in mRCC. METHODS: In this retrospective study, we selected 50 patients from eight Italian centers. The primary endpoint of the study was the overall survival (OS) of patients on active treatment versus BSC. Secondary endpoints were the progression-free survival (PFS) and objective response rate (ORR). The efficacy of active therapy was also investigated. RESULTS: After progression to both nivolumab and cabozantinib, 57.1% of patients were given active treatment (mainly everolimus and sorafenib) while 42.9% received BSC. The median OS was 13 months (95% CI: 4-NR) in actively treated patients and 3 months (95% CI: 2-4) in BSC patients (p = 0.001). Patients treated with sorafenib had better disease control than those treated with everolimus (stable disease: 71.4% vs. 16.7%, progression disease: 14.3% vs. 58.3%; p = 0.03), with no significant differences in PFS (5 and 3 months, 95% CI: 1-6 vs. 2-5; p = 0.6) and OS (12 and 4 months, 95% CI: 3-NR vs. 2-NR; p = 0.2). CONCLUSION: After treatment with both nivolumab and cabozantinib, the choice of a safe active systemic therapy offered better outcomes than BSC.

Prognostic Role of Mismatch Repair Status, Histotype and High-Risk Pathologic Features in Stage II Small Bowel Adenocarcinomas.

BACKGROUND: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer. PATIENTS AND METHODS: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability. RESULTS: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status. CONCLUSIONS: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Asymptomatic bacteriuria treatment is associated with a higher prevalence of antibiotic resistant strains in women with urinary tract infections.

BACKGROUND: Women suffering from recurrent urinary tract infections (rUTIs) are routinely treated for asymptomatic bacteriuria (AB), but the consequences of this procedure on antibiotic resistance are not fully known. The aim of this study was to evaluate the impact of AB treatment on antibiotic resistance among women with rUTIs. METHODS: The study population consisted of 2 groups of women who had previously been enrolled in a randomized clinical trial: group A was not treated, and group B was treated. All women were scheduled for follow-up visits every 6 months, or more frequently if symptoms arose. Microbiological evaluation was performed only in symptomatic women. All women were followed up for a mean of 38.8 months to analyze data from urine cultures and antibiograms. RESULTS: The previous study population consisted of 673 women, but 123 did not attend the entire follow-up period. For the final analysis, 257 of the remaining 550 patients were assigned to group A, and 293 to group B. At the end of follow-up, the difference in recurrence rates was statistically significant (P < .001): 97 (37.7%) in group A versus 204 (69.6%) in group B. Isolated Escherichia coli from group B showed higher resistance to amoxicillin-clavulanic acid (P = .03), trimethoprim-sulfamethoxazole (P = .01), and ciprofloxacin (P = .03) than that from group A. CONCLUSIONS: This study shows that AB treatment is associated with a higher occurrence of antibiotic-resistant bacteria, indicating that AB treatment in women with rUTIs is potentially dangerous.

Surgical treatment of chagasic megacolon with Duhamel-Habr-Gama technique modulated by frozen-section examination.

BACKGROUND: Migration from Latin American countries has increased the number of cases of chagasic megacolon in Western countries. Megacolon is a late complication of Chagas disease, resulting from irreversible destruction of the intramural intestinal nervous system with extensive loss of neurons, ganglionitis, and myositis at the sites of the myenteric and submucosal plexuses. Several surgical procedures involving partial or total resection of the dilated colon have been proposed for treating chagasic megacolon, but intra-operative evaluation of neuronal degeneration in the residual colon has not been commonly done. METHODS: Case report and literature review. CASE REPORT: We describe a case of chagasic megacolon treated successfully with a modified Habr-Gama technique, with the intra-operative examination of frozen sections of the residual segments of the colon for the presence of neurons. CONCLUSIONS: The recurrence of constipation after surgical treatment can result from the progression of chagasic neuronal degeneration in the preserved colon, and may be preventable by intra-operative evaluation of whether signs of neuronal degeneration or inflammation are absent in the anastomosed colonic tract.

Solidago, orthosiphon, birch and cranberry extracts can decrease microbial colonization and biofilm development in indwelling urinary catheter: a microbiologic and ultrastructural pilot study.

PURPOSE: Plants extracts are used in urology to manage urinary tract infections. We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon, birch and cranberry extracts (CISTIMEV PLUS(®)) in reducing microbial colonization and biofilm development in patients with indwelling urinary catheters. METHODS: All consecutive outpatients attending our department between January and June 2010 for the substitution of indwelling catheters were considered for this single-blinded, randomized and controlled pilot study to test superiority of the preventative management (CISTIMEV PLUS(®), 1 tablet daily for 30 days) in respect to no treatment. A sample size of 10-40 participants per group was considered adequate. All patients underwent urine culture the same day of the catheter substitution and were then randomized into test group (n = 48) and control group (n = 35). Ultrastructural analysis was also performed. After 30 days, the catheter was replaced and the analysis repeated. The primary outcome was the rate of positive urinary culture at the end of the entire study period. RESULTS: Ten patients abandoned the study. At 30 days, according to per-protocol analysis, the groups statistically differed regarding the rate of positive urine cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI -51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and Enterococcus faecalis. CONCLUSIONS: The use of solidago, orthosiphon, birch and cranberry extracts resulted in a significant reduction of microbial colonization in patients with indwelling urinary catheters. Larger clinical trials are needed to demonstrate that the effects here reported are sufficient to reduce symptomatic catheter-associated urinary tract infections.

[Medical research through historical resources. Talking objects: a case of a parasitic perineal monstrosity]. / La ricerca medica attraverso la ricerca storica: mostri e mostruosità. Di una mostruosità parassitaria felicemente risolta con operazione chirurgica.

A case of a parasitic perineal monstrosity from the collection of the Pathology Museum of the University of Florence, is described on the basis of the original medical records and illustrations. The surgeon Giorgio Pellizzari (1814-1894) first reported this extraordinary case of sacrococcygeal teratoma containing a rudimentary inferior limb. Reader of Descriptive Anatomy, Pellizzari was a well-known Anatomy Dissector and Curator of the Physiological Museum of the Regio Arcispedale di Santa Maria Nuova in Florence. This report underlines the importance of studying the archive material in order to thoroughly comprehend a single museum talking object. This handling of matters will help to turn anatomical collections into a unique teaching toolfor modern medical practice and a noteworthy documentation of scientific, artistic and historical value. Through analysis of the original catalogue and investigation by means of modern scientific techniques, discovering the story behind the object becomes afeasible challenge.

Semen quality in patients with Chlamydia trachomatis genital infection treated concurrently with prulifloxacin and a phytotherapeutic agent.

Chronic prostatitis (CP) due to Chlamydia trachomatis (Ct) infection has a significant impact on young male fertility, and eradication of Ct infection after antibiotic therapy does not always result in recovery of semen quality. The study aim was to evaluate the effects on fertility parameters of L-arginine, L-carnitine, acetyl-L-carnitine, and ginseng extracts (FERTIMEV) associated with prulifloxacin in patients affected by CP and oligoasthenoteratozoospermia due to Ct infection. Two hundred and six patients with proven Ct genital infection and oligoasthenoteratozoospermia were enrolled in a prospective, randomized, and controlled study. Prulifloxacin (600 mg) was administered daily for 14 days, and patients were divided into 2 groups: group A: antibiotic therapy alone; and group B: antibiotic therapy and additional therapy with FERTIMEV (1 vial daily for 6 months). Microbiological and semen parameter analyses were performed both at enrollment and after 6 months. National Institutes of Health Chronic Prostatitis Symptom Index and International Prostatic Symptom Score questionnaires were applied. Of the 206 patients, 109 were assigned to group A and 97 to group B. At the enrollment time, no differences were reported with regard to clinical, instrumental, and laboratory data. Six months after treatment, statistically significant differences were demonstrated between both groups in terms of sperm concentration (21.3 ± 13.2 millions/mL vs 11.5 ± 13.2 millions/mL) (Cohen's d = 0.61) (P < .001, df = 2, F = 62.10) and percentage of motile sperm (42.4% ± 5.2% vs 29.3% ± 11.0%) (Cohen's d = 1.52) (P < .001, df = 2, F = 91.48). In this study treatment with FERTIMEV together with prulifloxacin improved semen parameters in patients with Ct genital infection and oligoasthenoteratozoospermia compared to treatment with prulifloxacin therapy alone.

Prognostic role of cell apoptotic rate in prostate cancer: outcome of a long-time follow-up study.

The tumour apoptotic pattern is described as a good predictor of outcome in patients with prostate cancer (PCa). So far no authors have evaluated the role of apoptotic characteristics in patients who have undergone radical prostatectomy (RRP) alone. The aim of the present study is to estimate the prognostic role of the apoptotic index (AI) in a group of patients with prostatic adenocarcinoma subjected to RRP with no adjuvant therapy. Fifty patients underwent RRP according to standardised techniques and the surgical specimens were analysed histologically. In order to evaluate the AI and correlate these results with the follow-up data, we used a standardised apoptotic regulatory terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine-triphosphate-biotin nick end-labelling technique (Becton Dickinson Immunocytometry Systems, San Jose, CA, USA). The mean follow-up period was 66 months. Significant correlations were found between the AI and pathological features, such as stage (p<0.001) and grade (p<0.001). Out of 50 patients, 13 (26%) had biochemical recurrence and clinical disease progression, with an AI of 1.93 (range, 0.76-5.22), while 37 patients (74%) who did not report any disease progression, had an AI of 0.58 (range, 0.1-3.12). Furthermore, the AI significantly correlated with status at the end of follow-up (r=0.75, p=0.002), these data being confirmed by Kaplan-Meier curve analysis (p<0.001). On multivariate analysis, the AI proved to be an independent prognostic factor of progression-free probability (p<0.001). Our results highlight the utility of AI analysis in assessing the probability risk of clinical progression in PCa patients who are treated with RRP.