Nomogram predicting testicular torsion in Japanese patients with acute scrotal pain using physical examination findings and environmental conditions: Development and prospective external validation.

OBJECTIVES: To develop a prediction tool based on physical findings and environmental conditions without utilizing color Doppler ultrasonography to guide non-urologists and patients' families in determining the testicular torsion possibility among patients with acute scrotal pain. METHODS: Overall, 110 consecutive patients aged ≤30 years with acute scrotal pain at Saitama Medical Center between 2012 and 2014 were retrospectively evaluated. Physical examination results, including scrotal inspection, palpation and gait observation, and environmental conditions at pain onset (time range and ambient temperature) were collected. Multivariate analysis identified significant and independent risk factors for testicular torsion, and a nomogram predicting testicular torsion was constructed. The model underwent prospective validation in an independent set of 123 consecutive patients admitted with acute scrotal pain to our institution between 2015 and 2017. RESULTS: Testicular torsion diagnosis rates were 27% (30/110) and 26% (32/123) in the training and validation cohorts, respectively. Logistic regression analysis showed four risk factors for developing testicular torsion: abnormal testicular position, walking difficulty, midnight to early morning onset and ambient temperature <15°C at pain onset. The constructed nomogram showed that the areas under the receiver operating characteristic curves were 0.92 and 0.84 for the training and validation cohorts, respectively. The calibration plot showed an acceptable fitness between the predicted probability and the observed rate of testicular torsion. CONCLUSIONS: A novel nomogram was developed solely based on physical findings and environmental conditions to predict testicular torsion in Japanese patients with acute scrotal pain.

ALDH1A1 in patient-derived bladder cancer spheroids activates retinoic acid signaling leading to TUBB3 overexpression and tumor progression.

Acquired chemoresistance is a critical issue for advanced bladder cancer patients during long-term treatment. Recent studies reveal that a fraction of tumor cells with enhanced tumor-initiating potential, or cancer stem-like cells (CSCs), may particularly contribute to acquired chemoresistance and recurrence. Thus, CSC characterization will be the first step towards understanding the mechanisms underlying advanced disease. Here we generated long-term patient-derived cancer cells (PDCs) from bladder cancer patient specimens in spheroid culture, which is favorable for CSC enrichment. Pathological features of bladder cancer PDCs and PDC-dependent patient-derived xenografts (PDXs) were basically similar to those of their corresponding patients' specimens. Notably, CSC marker aldehyde dehydrogenase 1A1 (ALDH1A1), a critical enzyme that synthesizes retinoic acid (RA), was abundantly expressed in PDCs. ALDH1A1 inhibitors and shRNAs repressed both PDC proliferation and spheroid formation, whereas all-trans RA could rescue ALDH1A1 shRNA-suppressed spheroid formation. ALDH inhibitor also reduced the in vivo growth of PDC-derived xenografts. ALDH1A1 knockdown study showed that tubulin beta III (TUBB3) was one of the downregulated genes in PDCs. We identified functional RA response elements in TUBB3 promoter, whose transcriptional activities were substantially activated by RA. Clinical survival database reveals that TUBB3 expression may associate with poor prognosis in bladder cancer patients. Moreover, TUBB3 knockdown was sufficient to suppress PDC proliferation and spheroid formation. Taken together, our results indicate that ALDH1A1 and its putative downstream target TUBB3 are overexpressed in bladder cancer, and those molecules could be applied to alternative diagnostic and therapeutic options for advanced disease.

Relevance of concurrent hypercalcemia in ureteric sarcoidosis complicated with bladder urothelial carcinoma: a case report.

BACKGROUND: Sarcoidosis is a multisystem inflammatory disorder and can affect any organ; however, ureteric involvement is extremely rare with only four cases reported in the literature to date, all of which were diagnosed with surgical ureteral resection including a nephroureterectomy. This study reports the first case of ureteric sarcoidosis controlled with medical therapy where a differential diagnosis was performed based on the diagnostic clue of hypercalcemia. A definitive diagnosis was established without surgical resection of the ureter. CASE PRESENTATION: A 60-year-old man presented with anorexia and weight loss. Blood tests showed renal dysfunction and hypercalcemia. Computed tomography revealed left hydronephrosis associated with left lower ureteral wall thickening, which showed high signal intensity on diffusion-weighted magnetic resonance imaging. Similarly, we detected a bladder tumor on cystoscopy, and a 2-cm-long stenosis was revealed by retrograde ureterography; therefore, ureteral cancer was suspected. Meanwhile, considering the clinical implication of hypercalcemia, a differential diagnosis of sarcoidosis was established based on elevated levels of sarcoidosis markers. Fluorodeoxyglucose positron emission tomography showed fluorodeoxyglucose accumulation in the left lower ureter, skin, and muscles, suggestive of ureteric sarcoidosis with systemic sarcoid nodules. For a definitive diagnosis, transurethral resection of the bladder tumor and ureteroscopic biopsy were performed. Histopathological examination revealed ureteric sarcoidosis with bladder urothelial carcinoma. Following an oral administration of prednisolone, hypercalcemia instantly resolved, the renal function immediately improved, and the left ureteral lesion showed complete resolution with no recurrence. CONCLUSIONS: In this case, the co-occurrence of ureteral lesion with bladder tumor evoked a diagnosis of ureteral cancer. However, considering a case of ureteral lesion complicated with hypercalcemia, assessment for differential diagnosis was performed based on the calcium metabolism and sarcoidosis markers. In cases of suspected ureteric sarcoidosis from the assessment, pathological evaluation with ureteroscopic biopsy should be performed to avoid nephroureterectomy.

[HUGE RENAL ANGIOMYOLIPOMA COMPLICATED WITH COMMON ILIAC VEIN THROMBUS BECAUSE OF THE TUMOR PRESSURE].

A 47-year-old woman was transferred to our hospital in June 2014 in hemorrhagic shock due to rupture of a huge right renal angiomyolipoma (AML). Selective right renal arterial embolization performed that same day reversed the shock immediately. Despite the huge abdominal tumor, the patient was discharged 2 weeks later after refusing any further treatment.Two weeks later she noticed the abdominal tumor growing. One month after discharge, she was readmitted due to dyspnea caused by restriction of her breathing by the growing tumor mass. A CT revealed a massive increase in tumor size with internal liquefaction, a thrombus in the left common iliac vein, and a 12 mm aneurysm in the right renal artery. The patient requested removal of the abdominal tumor since her ADL had deteriorated. We decided to perform a right nephrectomy with consideration of the left common iliac vein thrombus and right renal arterial aneurysm.As a precaution against pulmonary embolism in case the left common iliac vein thrombus dislodged, a retrievable inferior vena cava (IVC) filter was inserted before surgery. We were also concerned about possible rupture of the right renal aneurysm, so the right renal artery was embolized before surgery. After these procedures, a right nephrectomy was performed via a transperitoneal approach.The surgery was uneventful. The tumor weighed about 11 kg including 7,000 mL of bloody fluid. The IVC filter was removed the day after surgery, but the thrombus in the left common iliac vein remained, and an anticoagulant was started. Three months later, the thrombus had disappeared, and the anticoagulant was discontinued six months after surgery.According to the treatment guidelines for deep vein thrombosis, anticoagulants are the drugs of choice. IVC filters are seldom used to prevent pulmonary embolism. We initially administered an anticoagulant for the thrombus in the left iliac vein. However, an increase in abdominal tumor size suggested the drug had caused internal rebleeding and it had to be discontinued. Ultimately, we used a temporary retrievable IVC filter during the right nephrectomy with success.There is currently no consensus on when to use an IVC filter. Moreover, very little data exists on the use of an IVC filter during the perioperative period. Therefore, given the risk of potential thromboembolism, although we were able to use it successfully in our surgery, it should not be employed without a thorough benefit-risk assessment.

ASSOCIATION BETWEEN THE RISK OF TESTICULAR TORSION AMONG ACUTE SCROTUM AND AMBIENT TEMPERATURE.

(Objectives) Testicular torsion (TT) is a socially and clinically important urological emergency condition because delayed diagnosis and treatment can lead to testicular loss. Although a possible association between TT and low ambient temperature has been argued, the clinical significance of the association has not been fully elucidated. We retrospectively collected acute scrotum cases and investigated the association between the risk of TT among acute scrotums and ambient temperatures on the day of onset. (Patients and methods) We studied 105 consecutive acute scrotum patients with suspected TT who underwent urgent surgical exploration between October 2004 and October 2014. The patients' age, residential area, time and date of onset, laboratory findings, and operative findings were collected from their medical records. Climate data, including daily mean ambient temperature (DMAT), diurnal temperature change (DTC), humidity, and atmospheric pressure at the time of onset, were obtained from the Japan Meteorological Agency website. The chi-square and Wilcoxon rank sum tests were used to evaluate statistical differences. Logistic regression analysis used to identify significant predictors of TT. (Results) The median age of the patients was 13 years (range, 1-43 years). The affected side was the right/left/bilateral side in 46/58/1 of the patients. Surgical exploration revealed TT in 67 patients. The remaining 38 non-TT patients included 12 with testicular appendage torsions, 12 with epididymal appendage torsions, 9 with epididymitis, 2 with orchitis, 2 with idiopathic hematomas, and 1 with allergic purpura. The median DMATs at the day of onset were 10.8°C (1.8-29.4°C) in the TT patients and 19.4°C (1.9-29.1°C) in the non-TT patients. The incidence of TT among the patients with acute scrotum explored surgically (TT incidence) in days with DMATs <15°C (80%) was significantly higher than that in days with DMATs ≥ 15°C (45%; p<0.001). During days with DMATs ≥15°C, the TT incidence in days with DTCs ≥10°C (62%) was significantly higher than that in days with DTCs <10°C (32%; p=0.037). Multivariate analysis revealed higher age (≥14), low serum C-reactive protein level (<0.5 ng/ml) and low DMAT (<15°C) were significant risk factor for TT in patients with acute scrotum undergoing surgery. (Conclusions) It should be noted that in this study, the onset of acute scrotum during days with low ambient temperatures or large DTCs was associated with a moderate to high possibility of TT.

Female intravesical foreign body penetrating the bladder wall: A rare case of traditional Asian hair stick kanzashi.

A female in her thirties inserted an Asian traditional hair stick, kanzashi, into her urinary bladder for sexual gratification. We need to know that everyday objects can become bladder foreign bodies and how to manage them properly.

Pathological complete response and two-year disease-free survival in a primary gastric choriocarcinoma patient with advanced liver metastases treated with germ cell tumor-based chemotherapy: a case report.

Choriocarcinoma is an early metastasizing and highly invasive tumor and characterized as a high-level human chorionic gonadotropin-secreting tumor. It normally arises in the gestational trophoblast, gonads and much less frequently in the stomach. Primary gastric choriocarcinoma appears to have a poor prognosis; especially with liver metastasis, the survival period is expected to be <1 month. This unfavorable clinical outcome is partly due to the lack of defined chemotherapy against primary gastric choriocarcinoma. We herein report a case of a 68-year-old male primary gastric choriocarcinoma patient with advanced liver metastases in which germ cell tumor-based chemotherapy achieved a pathological complete response and 2-year disease-free survival.

Undifferentiated pleomorphic sarcoma of the retroperitoneum mimicking a cortisol- and catecholamine-secreting adrenal tumor.

Introduction: Retroperitoneal tumors with endocrine abnormalities are suspected to be functional adrenal tumors. Retroperitoneal soft tissue sarcomas are rare tumors, without endocrine potential. Case presentation: A 60-year-old male was referred for a 15 cm mass in the left suprarenal space. His plasma cortisol and catecholamine levels were elevated. He underwent open left adrenalectomy with radical nephrectomy and his endocrinological abnormalities were improved. Pathological findings suggested that it had originated from the retroperitoneal fat tissue, and a diagnosis of undifferentiated pleomorphic sarcoma was made based on the results of immunohistochemical analysis and fluorescence in situ hybridization. Interestingly, neither cortisol nor catecholamine was elevated when, 6 months after surgery, local recurrence developed. Conclusion: This is the first reported case of undifferentiated pleomorphic sarcoma accompanied by high levels of cortisol and catecholamine. We should keep in mind the possibility of tumors like retroperitoneal soft tissue sarcomas inducing endocrine abnormalities.

Rare case of a patient with testicular torsion complicated by acute pneumonia, requiring emergency surgery, during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has been causing delay in patient arrival at hospital and starting surgery. We report a delay in a case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic in Japan. CASE PRESENTATION: A 17-year-old Japanese boy presented to our emergency room with acute left scrotum pain and fever in January 2021. It took 2.5 h to transfer him. Physical examination and color Doppler ultrasonography revealed left testicular torsion. Chest computed tomography indicated acute pneumonia. He successfully underwent surgical detorsion 7.5 h after symptom onset, with COVID-19 preventive measures in place. A negative polymerase chain reaction test result for COVID-19 was revealed after surgery. CONCLUSION: We experienced a rare case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic. Special attention should be paid to preventing infection and surgery delay to avoid testicular loss.

Inhibition of Hsp90 activates osteoclast c-Src signaling and promotes growth of prostate carcinoma cells in bone.

Hsp90 inhibitors are being evaluated extensively in patients with advanced cancers. However, the impact of Hsp90 inhibition on signaling pathways in normal tissues and the effect that this may have on the antitumor activity of these molecularly targeted drugs have not been rigorously examined. Breast and prostate carcinomas are among those cancers that respond to Hsp90 inhibitors in animal xenograft models and in early studies in patients. Because these cancers frequently metastasize to bone, it is important to determine the impact of Hsp90 inhibitors in the bone environment. In the current study, we show that, in contrast to its activity against prostate cancer cells in vitro and its inhibition of s.c. prostate cancer xenografts, the Hsp90 inhibitor 17-AAG stimulates the intraosseous growth of PC-3M prostate carcinoma cells. This activity is mediated not by a direct effect on the tumor but by Hsp90-dependent stimulation of osteoclast maturation. Hsp90 inhibition transiently activates osteoclast Src kinase and promotes Src-dependent Akt activation. Both kinases are key drivers of osteoclast maturation, and three agents that block osteoclastogenesis, the Src inhibitor dasatinib, the bisphosphonate alendronate, and the osteoclast-specific apoptosis-inducer reveromycin A, markedly reduced 17-AAG-stimulated tumor growth in bone. These data emphasize the importance of understanding the complex role played by Hsp90 in regulating signal transduction pathways in normal tissues as well as in cancer cells, and they demonstrate that drug-dependent modulation of the local tumor environment may profoundly affect the antitumor efficacy of Hsp90-directed therapy.

Successful completion of transurethral lithotripsy in a patient with factor XIII deficiency: A case report.

Factor XIII (FXIII) deficiency is a rare inherited coagulopathy. Standard perioperative management in those with FXIII deficiency requiring surgical procedures has not been elucidated. Herein, we report the case of a patient with FXIII deficiency who successfully underwent transurethral lithotripsy. Recombinant FXIII was used effectively in perioperative management and safely without any bleeding complications. This is the first report of a patient with FXIII deficiency in the field of urology.

Cystic partially differentiated nephroblastoma in a 74-year-old patient.

INTRODUCTION: Cystic partially differentiated nephroblastoma is a multilocular cystic variant of Wilms tumor that always presents in children. However, we encountered an elderly patient with cystic partially differentiated nephroblastoma. Therefore, we report it. CASE PRESENTATION: A 74-year-old male presented with a left renal tumor detected with ultrasonography. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a 4 cm multilocular cystic tumor with septa, which suggested multilocular cystic renal cell carcinoma. Therefore, we performed a radical nephrectomy. The definitive diagnosis of cystic partially differentiated nephroblastoma was made with histopathological findings. After the surgical resection, no recurrence has occurred in the past 13 years. CONCLUSION: Cystic partially differentiated nephroblastoma can develop in adults, regardless of age. Furthermore, surgical resection can be used as an established treatment option in adult cystic partially differentiated nephroblastoma cases.

[A CASE REPORT OF VESICAL CALCULUS FORMATION WITH CHROMIC CATGUT AT THE URETEROVESICAL ANASTOMOTIC SITE 28 YEARS AFTER RENAL TRANSPLANTATION].

A 69-year-old man underwent renal transplantation due to chronic renal failure of unknown cause in 1991. Furthermore, in 2012 he again underwent renal transplantation due to renal graft dysfunction with focal segmental glomerulosclerosis. After the second renal transplantation, his renal function has been stable. In 2019, he presented to the urology department with gross hematuria. Cystoscopy revealed a 2 cm vesical calculus at the dome of the bladder near the right lateral wall. Therefore, we performed transurethral lithotripsy using the holumium laser method. The vesical calculus was crushed, revealing a suture at the center, suggesting the suture as the cause. We tried to remove the suture during operation, however, it was impossible. Although the remaining suture posed a risk for calculus development, there has been no recurrence of a calculus for 6 months after the operation. This case reports a vesical calculus at the ureterovesical anastomotic site, wherein the core was an absorbable suture used during the initial renal transplantation. It should be taken into consideration that there is a possibility of anastomotic calculus occurrence with absorbable sutures, even long after renal transplantation.

A novel prognostic model for Japanese patients with newly diagnosed bone-metastatic hormone-naïve prostate cancer.

Objectives: To evaluate the prognosis of newly diagnosed patients with metastatic hormone-naïve prostate cancer (mHNPC) and develop a novel prognostic model based on ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) risk classifications. Patients and methods: We retrospectively analyzed the data of 578 newly diagnosed mHNPC patients initially treated with androgen deprivation therapy. We evaluated three clinical factors, namely, CHAARTED risk classifications (high-volume disease [HVD] vs low-volume disease [LVD]), Gleason scores (GS, 9-10 vs ≤8), and hemoglobin (Hb, ≤13.0 g/dL vs >13.0 g/dL), for their prognostic potential in predicting time to castration-resistant prostate cancer (TTC) and overall survival (OS) of mHNPC patients by multivariate analysis. Moreover, we developed a novel prognostic model that consisted of significant prognostic factors. Results: Of the entire cohort, the median TTC and OS values were 18.3 and 67.5 months, respectively. HVD, GS 9-10, and Hb ≤13.0 g/dL were independent poor prognostic factors for both TTC and OS. We developed a novel prognostic model which could stratify mHNPC patients into four risk groups according to the numbers of poor prognostic factors: group 1, LVD with low-risk (LVD patients without GS 9-10 and Hb ≤13.0 g/dL); group 2, LVD with high-risk (LVD patients with GS 9-10, Hb ≤13.0 g/dL, or both); group 3, HVD with low-risk (HVD patients without GS 9-10 with or without Hb ≤13.0 g/dL); and group 4, HVD with high-risk (HVD patients with GS 9-10 with or without Hb ≤13.0 g/dL). The median TTC and OS of groups 1, 2, 3, and 4 were 124.8, 36.4, 17.9, and 11.2 months, and 117.2, 94.2, 67.9, and 46.2 months, respectively. A significant difference in TCC and OS was found between all groups. Conclusion: We developed a prognostic model for mHNPC patients that consisted of CHAARTED risk classifications, GS, and Hb. Our prognostic model could significantly stratify the prognosis of patients with LVD and HVD into two groups each. This model might be a good reference for shared decision making between patients and physicians on the initial treatment for mHNPC.