Impact of Tumor Grade Distribution on Genetic Alterations in Clear Cell Renal Cell Carcinoma and Prostate Cancer.

BACKGROUND/AIM: A genomic analysis based on next-generation sequencing is important for deciding cancer treatment strategies. Cancer tissue sometimes displays intratumor heterogeneity and a pathologic specimen may contain more than two tumor grades. Although tumor grades are very important for the cancer prognosis, the impact of higher tumor grade distribution in a specimen used for a genomic analysis is unknown. PATIENTS AND METHODS: We retrospectively analyzed the data of 61 clear cell carcinoma and 46 prostate cancer patients that were diagnosed between December 2018 and August 2022 using the GeneRead Human Comprehensive Cancer Panel or SureSelect PrePool custom Tier2. Genome annotation and curation were performed using the GenomeJack software. RESULTS: Tumor mutation burden (TMB) was increased in proportion to the higher tumor grade distribution in grade 2 clear cell renal cell carcinoma (ccRCC). In PC, Grade Group 3/4 specimens that included an increased distribution of Gleason pattern 4 had more frequent gene mutations. CONCLUSION: Our results suggest the importance of selecting the maximum distribution of higher tumor grade areas to obtain results on the precise gene alterations for genomics-focused treatments.

Postoperative infectious complications in patients undergoing holmium laser enucleation of the prostate: Risk factors and microbiological analysis.

OBJECTIVES: To examine the incidence of postoperative bacteriuria and febrile complications, and to investigate bacterial strains in the urine of patients undergoing holmium laser enucleation of the prostate. METHODS: We retrospectively analyzed 190 evaluable patients treated with holmium laser enucleation of the prostate at the Gifu University Hospital, Gifu, Japan, between September 2005 and May 2014. All patients presented with lower urinary tract symptoms as a result of benign prostatic hyperplasia. We also evaluated the causative bacteria and compared the findings with the results of preoperative urine cultures. We analyzed the relationship between the emergence of postoperative febrile complications, antibiotic prophylaxis, patient background and surgical procedure. RESULTS: The frequency of bacterial isolation in preoperative and postoperative urine cultures was 41% and 23%, respectively. Preoperatively, Enterococcus faecalis was the most frequently cultured bacteria, second was methicillin-resistant Staphylococcus epidermidis, and third was Escherichia coli. Postoperatively, Enterococcus faecalis was still the most frequently cultured bacteria, whereas the second was Escherichia coli. Risk factors for postoperative bacteriuria were evaluated. Multivariate analysis showed that the rate of postoperative bacteriuria in patients who had taken dutasteride preoperatively was significantly lower than that in the other patients. Risk factors for febrile complications could not be identified. CONCLUSIONS: The use of perioperative prophylactic antibacterial agents for holmium laser enucleation of the prostate keeps the rate of postoperative infectious complications low. Dutasteride treatment administered before surgery might reduce the risk of postoperative bacteriuria.

[Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

Selection of Mycoplasma genitalium strains harbouring macrolide resistance-associated 23S rRNA mutations by treatment with a single 1 g dose of azithromycin.

OBJECTIVE: A single 1 g dose regimen of azithromycin has been recommended for the treatment of Mycoplasma genitalium infections. The authors evaluated whether this regimen could select M genitalium strains with macrolide resistance after treatment for M genitalium-positive non-gonococcal urethritis. METHODS: In seven men with non-gonococcal urethritis, who were infected with M genitalium without macrolide resistance-associated mutations but experienced microbiological azithromycin treatment failure, M genitalium DNAs in their post-treatment urine specimens were examined for mutations in the 23S rRNA gene and the ribosomal protein genes of L4 and L22. To assess the relatedness of M genitalium strains before and after treatment, their DNAs in pretreatment and post-treatment urine were genotyped by analysing short tandem repeats of an AGT/AAT unit in the MG309 gene and single nucleotide polymorphisms in the MG191 gene. RESULTS: In four of seven patients, M genitalium in post-treatment urine had an A-to-G transition at nucleotide position 2071 or 2072, corresponding to 2058 or 2059 in the 23S rRNA gene of Escherichia coli. In one of the four strains, Pro81Ser in the ribosomal protein L4 accompanied the mutation in the 23S rRNA gene. The genotyping of M genitalium DNAs suggested that these four post-treatment strains were selected from the respective closely related or identical pretreatment strains without macrolide resistance-associated mutations by the treatment. CONCLUSIONS: The single 1 g dose treatment of azithromycin could select M genitalium strains harbouring macrolide resistance-associated mutations. For M genitalium, this regimen might increase the risk of macrolide resistance selection after treatment.

[Case of urachal cancer treated by neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin)].

A 52-year-old woman was referred to our hospital for treatment of urachal cancer. She complained of supurapubic dull pain and gross hematuria. Computed tomography and magnetic resonance imaging showed a non-papillary sessile tumor, which was located on the dome of the bladder and invaded the small intestine. The tumor was diagnosed as Sheldon's stage IIIC urachal cancer. After three courses of neoadjuvant chemotherapy with FOLFOX4 (oxaliplatin, 5-FU and leukovolin), the tumor was reduced from 7 x 6 cm to 5.5 x 5 cm in size. Consequently, the patient underwent an en-bloc resection of the urachal tumor with the dome of the bladder and the parts of the ileum invaded by the tumor. One course of adjuvant chemotherapy (FOLFOX4) was performed. Surgical specimen revealed histologically well differentiated squamous carcinoma and invasion to the propria of the ileum. The surgical margins were negative for the cancer. For 1.5 years after the surgery, no local recurrence or distant metastasis has been observed.

Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval.

The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC(90)). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC(90)s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC(90)s of 0.06, 0.125, 0.25, and 0.5 microg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC(90)s of < or =0.125 microg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC(90) of cefixime for the 61 isolates tested was 0.125 microg/ml. All strains with MICs of < or =0.06 microg/ml were eradicated, whereas 8 of 16 strains with MICs of > or =0.125 microg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC(90)s of > or =0.125 microg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.