Detection of drug-resistant malaria in resource-limited settings: efficient and high-throughput surveillance of artemisinin and partner drug resistance.

OBJECTIVES: Artemisinin-resistant Plasmodium falciparum malaria is currently spreading globally, including in Africa. Artemisinin resistance also leads to resistance to partner drugs used in artemisinin-based combination therapies. Sequencing of kelch13, which is associated with artemisinin resistance, culture-based partner drug susceptibility tests, and ELISA-based growth measurement are conventionally used to monitor resistance; however, their application is challenging in resource-limited settings. METHODS: An experimental package for field studies with minimum human/material requirements was developed. RESULTS: First, qPCR-based SNP assay was applied in artemisinin resistance screening, which can detect mutations within 1 h and facilitate sample selection for subsequent processes. It had 100% sensitivity and specificity compared with DNA sequencing in the detection of the two common artemisinin resistance mutations in Uganda, C469Y and A675V. Moreover, in the partner drug susceptibility test, the cultured samples were dry-preserved on a 96-well filter paper plate and shipped to the central laboratory. Parasite growth was measured by ELISA using redissolved samples. It well reproduced the results of direct ELISA, reducing significant workload in the field (Pearson correlation coefficient: 0.984; 95% CI: 0.975-0.990). CONCLUSIONS: Large-scale and sustainable monitoring is required urgently to track rapidly spreading drug-resistant malaria. In malaria-endemic areas, where research resources are often limited, simplicity and feasibility of the procedure is especially important. Our approach combines a qPCR-based rapid test, which is also applicable to point-of-care diagnosis of artemisinin resistance and centralized analysis of ex vivo culture. The approach could improve efficiency of field experiments and accelerate global drug resistance surveillance.

Latent prostate cancer among Japanese males: a bibliometric study of autopsy reports from 1980-2016.

Prostate cancer is one of the most common malignancies, but a substantial portion remains latent throughout the patients' lifetime. Analysis of temporal change in the latent prostate cancer pool would be beneficial for clinical decision-making, but longitudinal autopsy studies are rare. We conducted a hand-search of the Annual of Pathological Autopsy Cases in Japan from 1980 to 2016 for cases of latent prostate cancer. Of 570 997 males aged 30 or older, latent prostate cancer was detected in 12 562 patients (2.2%). Proportion of detected cases correlated strongly with 'aging rate', the percentage of population aged 65 or older (squared Pearson's correlation coefficient r2 = 0.972, P value <0.0001). Temporal increase in proportion was also seen in each age group as well. This continuous growth reinforces evidence from past Japanese reports on latent prostate cancer. The rapidly rising ageing rate of Japan may forecast further increase in the latent prostate cancer pool moving forward.

Bilateral fumarate hydratase deficient renal cell carcinoma in a patient with hereditary leiomyomatosis and renal cell cancer syndrome.

Introduction: Patients with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome have high risks of uterine and cutaneous leiomyomas and renal cell carcinoma (RCC), which are caused by germline mutation of the fumarate hydratase (FH) gene. RCC lesions are mostly high-grade tumors with a poor prognosis. Case presentation: A 37-year-old man who had previously undergone treatment for a left RCC was referred to our hospital with a diagnosis of right RCC. Robot-assisted partial nephrectomy was performed, and the pathological diagnosis revealed fumarate hydratase (FH)-deficient RCC. The left RCC, which was originally diagnosed as mucinous tubular and spindle cell carcinoma, was reviewed and diagnosed as FH-deficient RCC. The patient's father and uncle both died of RCC, and the father's tumor was also immunohistochemically proven to be FH-deficient RCC. Conclusion: HLRCC-related RCC should be considered in a differential diagnosis of young patients with a family history of RCC.

A case of condyloma acuminatum of the bladder concurrently diagnosed with urothelial carcinoma.

Introduction: Condyloma acuminatum usually occurs in the external genitalia and rarely in the bladder mucosa. Here, we report a case of condyloma acuminatum of the bladder that was detected concurrently with urothelial carcinoma. Case presentation: A 42-year-old man was referred to our urology department with positive urine cytology for urothelial carcinoma. Cystoscopy revealed a broad-base nonpapillary bladder tumor. The patient underwent a transurethral resection of the bladder tumor. Pathological examination revealed urothelial carcinoma, high-grade pT1, and concurrent resection of condyloma acuminatum. DNA was extracted from the paraffin-embedded transurethral resection of the bladder tumor tissue specimens. HPV11 was detected in condylomas by PCR and in situ hybridization, whereas HPV was not detected in urothelial carcinomas. Conclusion: We report a rare case of condyloma acuminatum of the bladder that was concurrently diagnosed with urothelial carcinoma from the same site.

Predictors of renal function deterioration at one year after off-clamp non-renorrhaphy partial nephrectomy.

BACKGROUND: Preservation of renal function is an important goal in renal cell carcinoma-related surgery. Although several case-dependent techniques for renal pedicle clamping and hemostasis have been used, their effects on long-term renal function are controversial. METHODS: The clinical records of 114 patients who underwent off-clamp non-renorrhaphy open partial nephrectomy at our hospital were retrospectively reviewed. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors of eGFR decline 12 months post-surgery and overtime deterioration of renal function were identified using a multivariate regression analysis. RESULTS: The median patient age was 65 years, and the median tumor size was 27 mm. The mean eGFR preservation at 1, 3, and 12 months post-surgery were 90.1%, 89.0%, and 86.9%, respectively. eGFR decline at 1 and 3 months were associated with poor eGFR preservation at 12 months with the odds ratio (95% confidence interval (CI)) of 1.97 and 3.157, respectively. Multivariate regression analyses revealed that tumor size was an independent predictor of eGFR decline at 12 months. Among 65 patients with eGFR preservation over 90% at 1 month post-surgery, eGFR value of 28 patients deteriorated below 90% at 12 months post-surgery compared with preoperative eGFR. Tumor size and eGFR preservation at 1 month were independent predictors of long-term renal function deterioration. CONCLUSION: Tumor size predicted eGFR decline 12 months post-surgery. Only a mild decline in eGFR was observed between 3 and 12 months after open partial nephrectomy. Tumor size and eGFR preservation at 1 month predicted the deterioration of renal function over time.

Trends in surgical treatment for prostate cancer: Analysis of National Database Open Data in Japan.

We conducted a study to clarify the trends in surgical treatments for prostate cancer in Japan between 2014 and 2020 by analyzing the National Database (NDB) Open Data in Japan. Intriguingly, the number of patients over 70 years old who underwent robotic-assisted radical prostatectomy (RARP) nearly doubled from 2015 to 2019, while that in those 69 years old and younger remained almost constant during the same period. The increase in the number of patients over 70 years of age may reflect the fact that RARP can be safely applied to elderly patients. With the new development and spread of surgery-assisting robots, we can foresee a further increase in the number of RARPs performed for elderly patients in the future.

Bladder Preservation After Bilateral Kidney Loss and Bladder Cancer After Renal Transplantation: A Case Report.

Kidney transplantation is now a well-established renal replacement therapy. However, renal transplant recipients are reported to have an increased incidence of cancer. Although the recommended waiting period after each cancerous event in a recipient is indicated in the literature, there is no absolute certainty that cancer will develop even after the recommended waiting period. In this study, we experienced a case of bladder cancer after the recommended waiting period in a patient who had bladder preservation after a right nephrectomy and left nephroureterectomy. A 61-year-old man lost his right kidney due to renal cancer in 2007 and his left kidney to urothelial carcinoma in November 2017. The patient wanted a kidney transplant and bladder preservation at the time of the left nephroureterectomy. The patient's wife offered to donate a kidney. After 2 years of hemodialysis, there was no recurrence or metastasis, and with the approval of the Ethics Committee, the patient received a kidney transplant in January 2020. Although the patient's renal function was good after the transplant, a bladder tumor was found 20 months later and was resected transurethrally. The pathology was nonmuscle invasive bladder cancer. This patient, who had lost both kidneys, was treated with bladder preservation therapy. After subsequent kidney transplantation, he developed bladder cancer. Explaining to the patient the possibility of recurrence after a certain period and the increased risk of cancer, in-depth consultation with the patient is necessary regarding bladder preservation. Regular checkups should be continued after transplantation.

Broad subcutaneous emphysema with airway obstruction during robot-assisted partial nephrectomy: A case report and literature review.

Introduction: Subcutaneous emphysema is a relatively common complication in laparoscopic surgery. However, airway obstruction secondary to subcutaneous emphysema is rare. Case presentation: A 63-year-old woman with a 56-mm left renal tumor underwent a robot-assisted partial nephrectomy. The operative time was 155 min, the insufflation time was 108 min, and the estimated blood loss was 70 mL. The pneumoperitoneum pressure was maintained at 12 mmHg, except at 15 mmHg for 19 min during tumor resection. The end-tidal CO2 was <47 mmHg throughout the procedure. Postoperatively, broad subcutaneous emphysema from the thigh to the eyelid was observed. Computed tomography revealed airway obstruction, and extubation was aborted. On postoperative day 1, emphysema around the trachea and neck improved and the intubation tube was successfully removed. Conclusion: Both laryngeal emphysema and physical compression secondary to emphysema can cause airway obstruction. To reduce gas-related complications, the risk of developing subcutaneous emphysema should be properly assessed during robot-assisted laparoscopic surgery.

Asymptomatic renal granuloma diagnosed 3 years after Bacillus Calmette-Guérin intravesical injection: A case report and a literature review.

Introduction: Intravesical Bacillus Calmette-Guérin immunotherapy is an effective treatment for non-muscle-invasive bladder cancer, which is occasionally associated with side effects and complications. The incidence of significant renal complications after intravesical Bacillus Calmette-Guérin immunotherapy is less than 2%. We report a case of renal granuloma after intravesical Bacillus Calmette-Guérin immunotherapy for bladder cancer, which radiologically resembled a papillary renal cell carcinoma. Case presentation: A 65-year-old man, who had a medical history of urothelial carcinoma and received intravesical Bacillus Calmette-Guérin therapy, was referred to our Urology Department with a right renal tumor. Imaging findings suggested papillary renal cell carcinoma. Robot-assisted partial nephrectomy was performed, and the histopathological examination revealed epithelioid cell granuloma, which were considered to be Bacillus Calmette-Guérin-related renal granuloma. Conclusion: Bacillus Calmette-Guérin-related renal granuloma mimicking papillary renal cell carcinoma have been reported. We should consider the possibility of renal granulomas when encountering image abnormalities for patients treated with intravesical Bacillus Calmette-Guérin therapy.

Advantages of enhanced recovery after surgery program in robot-assisted radical cystectomy.

Radical cystectomy is a gold-standard treatment for muscle-invasive bladder cancer. We recently introduced robot-assisted radical cystectomy (RARC) with perioperative enhanced recovery after surgery (ERAS). The medical records of patients with bladder cancer who underwent open radical cystectomy (ORC) or RARC/ERAS at NTT Medical Center Tokyo were retrospectively reviewed to compare the surgical outcomes, hospital stay, and medical costs between groups. Multidisciplinary full ERAS items were provided for the RARC/ERAS group. The median estimated blood losses in the ORC and RARC/ERAS groups were 650 and 100 mL, and the median operative times were 312 and 445 min, respectively. In addition, the median times to liquid food intake in these groups were 6 and 0 days, the median times to first flatus and first defecation were 2 and 1 day, and 3 and 1.5 days, respectively. The rates of postoperative ileus in the ORC and RARC/ERAS groups were 27.5% and 4.5%, and the median postoperative hospital stays was 26.5 and 12 days, respectively. Medical costs excluding surgery were significantly lower in the RARC/ERAS group. In conclusion, RARC/ERAS represents a safe treatment option for muscle-invasive bladder cancer with decreased perioperative complications and lower medical costs.

A case of cystic mucinous adenocarcinoma of the prostate treated by robot-assisted radical prostatectomy.

A 66-year-old male visited with constipation. Intra-pelvic cystic mass (332 cm3) was found, and PSA was 32.4 ng/ml. Biopsy of the prostate was performed. It wasn't adequate specimen for diagnosis, but the PSA of the fluid was 4791.0 ng/ml. RARP was performed. To make surgical field more visible, fine needle was stuck from the patient's perineum into the cyst intraoperatively. The patient was discharged with nothing complications. It was mucinous adenocarcinoma of the prostate, pT3b, RM1. The patient is now receiving ADT but no recurrence and metastasis are seen to date.

Predictive factors for postoperative renal function after off-clamp, non-renorrhaphy partial nephrectomy.

Background: There is limited information on perioperative renal function during off-clamp, non-renorrhaphy open partial nephrectomy. Therefore, this retrospective study aimed to identify predictive factors of perioperative decline in renal function after off-clamp, non-renorrhaphy open partial nephrectomy. Methods: Clinical records of 138 patients with renal tumors who underwent off-clamp, non-renorrhaphy open partial nephrectomy at our institution were reviewed. Off-clamp, non-renorrhaphy partial nephrectomy was performed using a soft coagulation system. Perioperative estimated glomerular filtration rate (eGFR) preservation was calculated, and predictors were identified using multivariate regression analysis at 5 days, 1 month, and 3 months after surgery. Results: The median operation time was 122 minutes, and the median volume of estimated blood loss was 155 mL. The mean eGFR preservation at 5 days, 1 month, and 3 months after surgery was 95.3%, 91.0%, and 90.7%, respectively. Estimated blood loss was an independent predictor of perioperative decline in eGFR 5 days after surgery [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.96, 0.98; P<0.001]. Preoperative eGFR and estimated blood loss were independent predictors of perioperative decline in eGFR 1 month after surgery (OR: 0.86; 95% CI: 0.77, 0.95; P=0.007 and OR: 0.98; 95% CI: 0.97, 0.99; P<0.001, respectively). Age, preoperative eGFR, and estimated blood loss were independent predictors of perioperative decline in eGFR 3 months after surgery (OR: 0.64; 95% CI: 0.54, 0.81; P<0.001, OR: 0.72; 95% CI: 0.61, 0.85; P<0.001; and OR: 0.98; 95% CI: 0.97, 0.99; P=0.004, respectively). Conclusions: Estimated blood loss during surgery was a predictor of perioperative decline in eGFR within 3 months after off-clamp, non-renorrhaphy open partial nephrectomy. Age was a predictor of perioperative decline in eGFR 3 months after surgery.

Aseptic Cavernosal Abscess: An Unrecognized Feature of Neutrophilic Dermatosis.

A 50-year-old man developed a sterile cavernosal abscess followed by prominent features of necrotizing neutrophilic dermatosis. We conducted a literature review, which revealed that aseptic abscesses in the corpus cavernosum occur in association with neutrophilic dermatosis. Patients with this condition frequently receive unnecessary antibiotic treatment and surgical interventions. Although this condition responds to systemic corticosteroids, the functional prognosis of the penis is poor. Abscess formation may be the initial presentation of neutrophilic dermatoses, and underlying conditions may even be absent. Clinicians need to be aware of this condition to distinguish it from bacterial infection and initiate early disease-specific treatments.

Safety of same-day administration of gemcitabine plus cisplatin chemotherapy for urothelial carcinoma.

The present study aimed to examine the safety of a gemcitabine and cisplatin (GC) combination chemotherapy regimen with short hydration for the treatment of urothelial cancer administered on the same day (same day regimen). Patients with locally advanced or metastatic urothelial cancer received the same-day GC regimen with short hydration every 4 weeks, and their serum creatinine (Cr) level was measured to assess renal function using linear mixed model analysis. A total of 20 patients receiving the same-day regimen exhibited no significant change in their serum Cr level; nor was there any significant change in the serum Cr level between patients who received the same day regimen and those who received the drugs on different days. The present study demonstrated that the same-day regimen was safe for patients with urothelial cancer.

[A CASE OF IgG4-RELATED DISEASE OF THE URETER DIAGNOSED BY TRANSVAGINAL ULTRASOUND-GUIDED BIOPSY].

IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder that systemically causes tissue fibrosis due to infiltration of IgG4-positive plasma cells. Here, we reported a rare case of ureteral IgG4-RD that formed a nodular lesion and diagnosed by trans-vaginal ultrasound-guided needle biopsy.A 72-year-old woman presented with loss of appetite. The patient underwent Computed Tomography (CT), and she was pointed out the thickening of the left side bladder wall. So we performed a transurethral bladder biopsy under lumber anesthesia, but histopathological findings were almost normal. After that, she developed pyelonephritis repeatedly. We performed CT again. A CT revealed a nodular lesion at the end of her left ureter and hydronephrosis. The tumor was gradually getting larger. So we performed placement the ureteral stent for urinary tract obstruction. Left ureteral urine cytology was classIIIa. We performed transvaginal ultrasound needle biopsy for the nodular lesion of the left ureter. Histopathological findings showed infiltration of lymphocytes and fibrosis and infiltration of IgG4 positive plasma cells: the ratio of IgG4/IgG positive cells>0.6, 30>IgG4 positive plasma cells/high power field. The serum IgG and IgG4 levels were also elevated 1,943 and 210 mg/dl. We finally diagnosed IgG4-RD of the ureter and started using steroid for her treatment. One month later, the tumor had reduced after steroid treatment. The ureteral stent was removed. Since then, recurrent ureteral obstruction of the left ureter has not occurred.IgG4-RD of the ureter with nodular type is rare, and the imaging findings are similar to malignant tumors. Accurate diagnosis is very important to rule out malignancy. In our case, transvaginal needle biopsy was helpful to reach final diagnosis.

Metastatic renal cell carcinoma regains sensitivity to tyrosine kinase inhibitor after nivolumab treatment: A case report.

Sequential therapy using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors is the mainstay of treatment for metastatic renal cell carcinoma. Recently, anti-programmed death-1 (PD-1) antibody, a type of immune checkpoint inhibitor, was approved for use against metastatic renal cell carcinoma. In the present report, two cases of TKI-refractory metastatic renal cell carcinoma which regained sensitivity to TKI after immunotherapy with nivolumab were described. In one case, a third challenge with axitinib after nivolumab treatment resulted in tumor shrinkage, although the second challenge with axitinib immediately before nivolumab treatment had no effect. In another case, a second challenge with pazopanib after nivolumab slightly reduced lung metastasis, which was refractory to pazopanib before nivolumab treatment. These cases suggest that nivolumab can influence the response to subsequent TKI treatment.