Differential impact of proton pump inhibitor on survival outcomes of patients with advanced urothelial carcinoma treated with chemotherapy versus pembrolizumab.

OBJECTIVES: We clarified the effect of concomitant proton pump inhibitor use on oncological outcomes in patients with advanced urothelial carcinoma treated either with chemotherapy or immune checkpoint inhibitor. METHODS: We retrospectively reviewed patients with advanced urothelial carcinoma who received paclitaxel-gemcitabine therapy or pembrolizumab after platinum-based chemotherapy. The patients were divided into four groups based on the treatment regimen and the concomitant use of proton pump inhibitor. We compared survival outcomes between the groups and determined which factors predicted overall survival. RESULTS: Among the 60 and 75 patients treated with paclitaxel-gemcitabine and pembrolizumab, 15 and 29 used a concomitant proton pump inhibitor. Progression-free and overall survival was significantly shorter in patients who were administered pembrolizumab with concomitant proton pump inhibitor compared to those without. The use of a concomitant proton pump inhibitor had no effect on survival outcomes in patients who received paclitaxel-gemcitabine therapy. Furthermore, progression-free and overall survival were significantly shorter in patients treated with paclitaxel-gemcitabine therapy compared to those treated with pembrolizumab among patients without concomitant proton pump inhibitor. In contrast, there was no difference in survival outcomes between the two regimens among patients with concomitant proton pump inhibitor. Concomitant proton pump inhibitor use was associated with poor overall survival only in patients treated with pembrolizumab. CONCLUSION: The use of a concomitant proton pump inhibitor use had no impact on oncological outcomes in patients with advanced urothelial carcinoma treated with paclitaxel-gemcitabine therapy, different from those treated with pembrolizumab.

Association Between Body Mass Index and Outcomes in Patients With Urothelial Carcinoma Treated With Pembrolizumab.

BACKGROUND/AIM: We aimed to clarify the association between body mass index (BMI) and clinical outcomes of pembrolizumab treatment for advanced urothelial cancer (UC). PATIENTS AND METHODS: We retrospectively reviewed the records of patients with advanced UC who received pembrolizumab after chemotherapy between March 2018 and December 2021. Patients were divided according to BMI into the non-overweight group (BMI <25 kg/m2) and the overweight group (BMI ≥25 kg/m2). We compared the two groups' tumour response, survival rates, and incidence of immune-related adverse events (irAEs) and investigated the factors predicting survival. RESULTS: Of 84 eligible patients, 63 (75%) and 21 (25%) were in the non-overweight and overweight groups, respectively. Although the objective response rate was higher in the overweight group (55%) than that in the non-overweight group (29%), the difference was not significant. Progression-free survival (PFS) was significantly longer in the overweight group (median 15.2 months) than that in the non-overweight group (median 4.8 months; p=0.01). Overall survival was also longer in the overweight group (median 36.1 months) compared to that in the non-overweight group (13.4 months), but the difference was not significant (p=0.11). Multivariable analysis showed that overweight was significantly associated with favourable PFS. Any and severe (grade 3) irAEs were observed in 15 (24%) and 5 (7.9%) patients in the non-overweight group, respectively, and in 8 (38%) and 2 (9.5%) patients in the overweight group, respectively, but the differences were not significant. CONCLUSION: BMI was associated with oncological outcomes in patients with advanced UC who received pembrolizumab but not with the development of irAEs.

The efficacy of sequential therapy using pazufloxacin followed by oral fluoroquinolones for treatment of pyelonephritis.

The efficacy of sequential therapy of pazufloxacin (PZFX), which is a parenteral fluoroquinolone, followed by oral fluoroquinolones [tosufloxacin tosilate (TFLX) or levofloxacin (LVFX)] for treatment of pyelonephritis, was evaluated. Patients with pyelonephritis who had fever (≥37.5 °C), pyuria (≥10 white blood cells/high-power field), and bacteriuria (≥10(4) colony-forming units/ml) were eligible for this study. PZFX (500 mg) was given intravenously twice a day for at least 3 days. If the patients were clinically improved, TFLX (150 mg) or LVFX (100 mg) was then administered orally three times a day for at least 5 days. Patients underwent clinical and microbiological evaluation at 5-9 days after final drug administration. Clinical and microbiological efficacy could be assessed in 21 of 25 cases enrolled. Both clinical and microbiological efficacy rates were 81.0 % (17/21 cases). In the effective cases, the mean administration time was 4.2 days for PZFX and 6.0 days for oral fluoroquinolones. The mean time to defervescence was 3.4 days for the effective cases. In the four treatment failure cases, three quinolone-resistant Escherichia coli and a quinolone-resistant Enterococcus faecalis were isolated. This sequential therapy seemed to be clinically effective in the treatment of pyelonephritis; however, the prevalence of quinolone-resistant E. coli should be taken into account.

Efficacy of estramustine phosphate according to risk classification of castration-resistant prostate cancer.

Treatment options for patients who progressed to castration-resistant prostate cancer (CRPC) are very limited. The purpose of this study was to assess the efficacy of estramustine phosphate (EMP) in patients with CRPC, grouped according to the risk classification advocated by Armstrong et al. and to identify candidates for EMP treatment. Between March 2003 and July 2010, 82 patients with CRPC were treated with 280 or 560 mg EMP per os daily until disease progression or occurrence of unacceptable adverse events. Prostate-specific antigen (PSA) response and overall survival were evaluated according to risk classification. 52 (67%) patients achieved PSA decline. Rates of PSA decline in the good-, intermediate-, and poor-risk groups were 77, 71, and 25%, respectively, significantly higher in the good- and intermediate-risk groups than the poor-risk group (p=0.03). The median overall survival times in good-, intermediate-, and poor-risk groups were 21, 19, and 9 months, respectively (p=0.005 for good vs intermediate, p=0.001 for intermediate vs poor). When the intermediate-risk group was divided into two subgroups by PSA doubling time (PSADT), men with PSADT≥2 months achieved higher PSA response rate (88%) and longer survival (22 months) than those with PSADT<2 months (53%, 15 months). Patients with good-risk or intermediate-risk with PSA doubling time≥2 months achieved favourable PSA response and survival and may benefit from chemotherapy with EMP.

Single dose 1 g ceftriaxone for urogenital and pharyngeal infection caused by Neisseria gonorrhoeae.

OBJECTIVES: To evaluate the efficacy of 1 g ceftriaxone in the treatment of urethritis, cervicitis and pharyngeal infection caused by Neisseria gonorrhoeae (N. gonorrhoeae) including the oral cephem-resistant strain with chimera penicillin-binding protein 2 (PBP-2) (cefozopran-resistant N. gonorrhoeae, CZRNG). METHODS: From September 2004 to November 2006, 67 patients (27 male and 40 female) who had genital infection and/or pharyngeal infection caused by N. gonorrhoeae were enrolled in this study at five participating centers in Japan. To detect the chimera PBP-2 gene, polymerase chain reaction (PCR) was performed using established primers against the altered penA of CZRNG isolates. All patients received a single 1 g dose of ceftriaxone. Efficacy was evaluated only in those who returned for examination and culture for N. gonorrhoeae between 3 and 14 days after the treatment. RESULTS: CZRNG isolates detected by PCR accounted for 41.7% (20/48) of urogenital infections and 60.0% (15/25) of pharyngeal infections in the treatment efficacy evaluable cases. 37 of 39 CZRNG isolates (94.9%) were multi-drug resistant isolates that had simultaneous resistance to penicillin, tetracycline, and ciprofloxacin. Nineteen patients had N. gonorrhoeae isolates in the urogenital area and pharynx simultaneously. Ceftriaxone treatment eradicated all N. gonorrhoeae isolates from 48 patients with genitourinary infection and 25 patients with pharyngeal infection. CONCLUSIONS: We report for the first time that ceftriaxone is effective in patients with gonococcal urethritis, cervicitis, and pharyngeal infection caused by CZRNG that has chimera PBP-2.

The hypothalamo-pituitary axis responses to lipopolysaccharide-induced endotoxemia in mice lacking inducible nitric oxide synthase.

Nitric oxide (NO) generated by inducible NO synthase (iNOS) may be implicated in the biological responses of the central nervous system to immune stimuli. To elucidate the role of iNOS in the hypothalamo-pituitary axis in responses to endotoxemia, using iNOS knockout (KO) mice, we examined the levels of c-fos, a neural activational marker, and corticotropin-releasing hormone (CRH) gene transcription in the paraventricular nucleus (PVN) and central amygdala (CeAMY) during lipopolysaccharide (LPS)-induced endotoxemia. In addition, the serum adrenocorticotropic hormone (ACTH) levels were also examined during endotoxemia. Following the intraperitoneal administration of LPS (1 mg/kg), the levels of the c-fos gene expression significantly increased in the PVN and the CeAMY regardless of the genotype. However, the disruption of the iNOS gene resulted in a significant decrease in the c-fos gene induction in the PVN in comparison to that observed in control mice. LPS administration caused a significant increase in CRH mRNA levels in the PVN and CeAMY regardless of genotype. However, the LPS-induced upregulation of CRH mRNA was significantly attenuated in the PVN of iNOS KO mice in comparison to that in the control mice. In contrast, no such genotype differences in the neural activity or CRH gene transcription were observed in the CeAMY. The serum ACTH responses to LPS were also significantly blunted in the iNOS KO mice in comparison to the control mice. These results suggest that iNOS-derived NO may therefore play a stimulatory role in the activity of the hypothalamo-pituitary axis during endotoxemia.

[Screening for prostate cancer in Yahata, Kitakyushu].

A remarkable increase has occurred in the incidence of prostate cancer in many countries including Japan. For early detection of prostate cancer, mass screening was initiated in many areas in Japan. We began screening for prostate cancer in 1993 in the Yahata area. Prior to 1996, prostate cancer screening consisted of interview, digital rectal examination, measurement of prostate specific antigen and transrectal ultrasonography. Since 1997, only an interview and PSA measurement has been performed. This screening program is provided free of charge. The men who had abnormal findings on the first screening were advised to visit an urologist for further examination. Over a period of 10 years, we detected prostate cancer in 6 out of 903 men (0.64%). Of those 6 patients, 5 had early localized cancer. In conclusion, we feel it is necessary to increase the number of subjects and visiting rate to an urologist, and to determine the diagnostic strategies including prostate biopsy on the second screening. In addition, the effectiveness of screening should be elucidated.