Cancer Antigen 125 Expression Enhances the Gemcitabine/Cisplatin-Resistant Tumor Microenvironment in Bladder Cancer.

Cancer antigen 125 (CA125) is one of the mucin family proteins and is a serum tumor marker for various tumors, such as ovarian cancer, endometrial cancer, pancreatic cancer, and bladder cancer. CA125 is used to distinguish between benign and malignant tumors, monitor the response to chemotherapy, and detect relapse after initial treatment. Recently, CA125 was reported to be involved in chemoresistance through the physical characteristics of mucin or by modifying the immune tumor-microenvironment. However, the relationship between CA125 expression and chemoresistance in bladder cancer is still unclear. In this study, the clinicopathologic features of bladder cancer with CA125 expression and the status of the tumor-microenvironment related to gemcitabine/cisplatin resistance were investigated using publicly available data sets (Cancer Genome Atlas Expression, GSE169455 data set) from the cBioPortal website, the National Center for Biotechnology Information website, and an in-house case collection of bladder cancer. The cases with CA125 expression had poorer disease-free and overall survival rates than those without CA125 expression. A mucinous area surrounding cancer cells was frequently detected in cases with CA125 expression (81%; 13/16 cases). CA125 expression was also related to the immunosuppressive tumor-microenvironment through the infiltration of immunosuppressive immune cells, such as regulatory T cells and M2 macrophages. These results suggest that the status of tumor-microenvironment associated with CA125 is involved in gemcitabine/cisplatin resistance in bladder cancer.

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.

Prevalence of Lynch syndrome among patients with upper urinary tract carcinoma in a Japanese hospital-based population.

BACKGROUND: The prevalence of Lynch syndrome and the use of universal tumor screening to identify Lynch syndrome among unselected patients with upper urinary tract urothelial carcinoma, which is associated with Lynch syndrome, have not been closely investigated yet. METHODS: A total of 166 tumors from 164 upper urinary tract urothelial carcinoma patients were tested for microsatellite instability and expression of mismatch repair proteins (MLH1, MHS2, MSH6 and PMS2) by immunohistochemistry. Genetic testing was performed for patients suspected of having Lynch syndrome. Clinicopathological factors, including familial and personal cancer history associated with mismatch repair deficiency, were evaluated. RESULTS: The frequency of high-level microsatellite instability and loss of at least one mismatch repair protein was 2.4% (4/164); the microsatellite instability and immunohistochemistry results showed complete concordance. Of these four patients, three were genetically proven to have Lynch syndrome, while the remaining one was highly suggestive for Lynch syndrome based on their personal cancer history. Univariate analysis showed that age<70 years (P = 0.04), ureter as the tumor location (P = 0.052), previous history/synchronous diagnosis of colorectal cancer (P < 0.01) and fulfillment of the criteria per the revised Bethesda guideline (P < 0.01) tended to be or were significantly associated with high-level microsatellite instability/mismatch repair loss. CONCLUSIONS: The prevalence of Lynch syndrome among unselected upper urinary tract urothelial carcinoma patients was at least 1.8% in our study population. The screening efficacies of the microsatellite instability test and immunohistochemistry appear equivalent. Universal tumor screening may be a valid approach; however, selective screening methods that consider factors associated with mismatch repair loss/high-level microsatellite instability tumors require further investigation.

[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.

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.

Spermatic cord metastasis from colon cancer: report of a case.

We herein report an extremely rare case of a solitary metastasis to the spermatic cord from colon cancer. A 71-year-old man who had undergone a right hemicolectomy for stage II cecal cancer 12 months prior, and who had not received adjuvant chemotherapy, was found to have a mass in the right groin region. Computed tomography (CT) revealed that the right spermatic cord was involved in a heterogeneously enhanced mass that measured 37 mm in diameter. A right high orchiectomy was performed. Histological examination of the resected tumor revealed well-differentiated adenocarcinoma compatible with a metastasis from colon cancer. The patient has been doing well, without recurrence, for 15 months postoperatively. To our knowledge, this is the 9th case of a solitary metastasis to the spermatic cord from colon cancer to be reported in the Japanese literature. The survival data of the collected cases suggest that resection of the solitary metastasis to the spermatic cord from colon cancer improves the patient prognosis.

[Case of far-advanced retroperitoneal extra-gonadal germ cell tumor responding to intensive treatment including multi-drug chemotherapy with peripheral blood stem cell transplantation and residual tumor removal].

A 37-year-old man with the chief complaints of lumbago and fever is presented. Laboratory data showed the extreme elevation of alfa feto-protein (AFP), human chorionic gonadotropin (hCG) and lactate dehydorgenase (LDH). Computed tomography (CT) scan revealed a huge retroperitoneal tumor with multiple pulmonary nodules as well as left supraclavicular and left axillary lymph nodes enlargement. Although he was suspected the testicular tumor with metastasis, he had no testicular abnormalities including tumor and microlithiasis. Therefore, he was diagnosed as a retroperitoneal extra-gonadal germ cell tumor, which had poor prognosis because of multiple metastasis and the tremendous increase of hCG. Although he was treated with three cycles of bleomycin, etoposide, and cisplatin (BEP), he achieved partial response and no normalization of tumor markers. After three cycles of BEP, he was treated with four cycles of paclitaxel and ifosfamide plus cisplatin (TIP) immediately. During chemotherapy, he was treated with his peripheral blood stem cell transplantation (PBSCT) as well. After the completion of two regimens' chemotherapies, all his tumor markers returned to be normal. However, retroperitoneal tumor, left supraclavicular and axillary lymphnodes still remained. He underwent three operations including retroperitoneal lymphnode dissection with nephrectomy, left supraclavicular and axillary lymphnodes removal, respectively. All specimens had no viable cells, histologically, The patient has been quite well and free of disease for 24 months. It is concluded that even if far-advanced germ cell tumor is discovered, a more promising prognosis could be expected with intensive and aggressive treatment such as our case.

Parsing apical oxalate exchange in Caco-2BBe1 monolayers: siRNA knockdown of SLC26A6 reveals the role and properties of PAT-1.

The purpose of this investigation was to quantitate the contribution of the anion exchanger PAT-1 (putative anion transporter-1), encoded by SLC26A6, to oxalate transport in a model intestinal epithelium and to discern some characteristics of this exchanger expressed in its native environment. Control (Con) Caco-2 BBe1 monolayers, 6-8 days postseeding, were compared with those transfected with a small interfering RNA targeted to SLC26A6 (A6KD). Radiotracer and Ussing chamber techniques were used to determine the transepithelial unidirectional fluxes of Ox(2-), Cl(-), and SO(4)(2-) whereas fluorometric/BCECF measurements of intracellular pH were used to assess HCO(3)(-) exchange. PAT-1 was functionally targeted to the apical membrane, and SLC26A6 knockdown reduced PAT-1 protein (>60%) and mRNA (>75%) expression in A6KD. No net flux of Ox(2-), Cl(-), or SO(4)(2-) was detected in Con or A6KD monolayers, yet the unidirectional fluxes in A6KD were reduced 50, 35, and 15%, respectively. Cl(-)-dependent HCO(3)(-) efflux from A6KD was reduced 50% compared with Con. The difference between Con and A6KD properties represents that mediated solely by PAT-1, and by this approach we found that PAT-1-mediated oxalate influx and efflux are inhibited equally by mucosal DIDS (EC(50) approximately 5 microM) and that mucosal Cl(-) inhibits oxalate uptake with an EC(50) < 20 mM. Transepithelial Cl(-) gradients supported large, DIDS-sensitive net absorptive or secretory fluxes of oxalate in a direction opposite that of the imposed Cl(-) gradient. The overall symmetry of PAT-1-mediated oxalate exchange suggests that vectorial oxalate transport observed in vivo is principally dependent on the magnitude and direction of counterion gradients.

Retroperitoneal Cystic Nodal Metastasis of Renal Cell Carcinoma.

Cystic nodal metastasis of renal cell carcinoma is very rare. The pathogenesis of cystic nodal metastasis is thought to involve obstruction of a lymphoid vessel draining the kidney by tumor cells and retrograde metastasis from the primary site to the lymph node along the lymphatic vessels. In this study, a surgical case of small renal cell carcinoma with retroperitoneal cystic nodal metastasis is reported.

Foreign-body granuloma mimicking post-chemotherapy residual seminoma: A case of true-negative findings using diffusion-weighted whole-body magnetic resonance imaging with background suppression.

Diffusion-weighted whole-body magnetic resonance imaging with background suppression (DWIBS) is increasingly used in cancer imaging. However, little is known about its usefulness in the management of metastatic seminoma, in which evaluation of the viability of postchemotherapy residual nodules is pivotal. To date, 2-18fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) has been recommended for post-chemotherapeutic assessment. We describe a case of metastatic seminoma in a 27-year-old man in which the viability of post-chemotherapy residual nodules tested false-positive on FDG-PET, but true-negative on DWIBS. DWIBS may be a good alternative technique to evaluate post-chemotherapy seminoma, although further studies are required to determine its usefulness.

[A pediatric case diagnosed as urachal cyst and vesicoureteral reflux by urinary tract infection: a case report].

A one-month-old girl was refereed to our department because of urinary tract infection. Ultrasonography showed grade III left hydronephrosis and cystic mass at the dome of the urinary bladder. Voiding cystourethrography revealed grade 4 vesicoureteral reflux associated with Hutch's diverticulum. In addition, magnetic resonance imaging revealed multiple cysts at the dome of the urinary bladder. The vesicoureteral reflux was repaired and the urachal cyst removed.

[A case of grade fever acute disseminated encephalomyelitis exhibiting urinary retention and high grade fever].

Acute disseminated encephalomyelitis is an acute inflammatory demyelinating disorder of the cenrtral nervous system and patients usually present with signs of meningitis, depressed levels of consciousness, disorientation and/or motor or sensory deficits, depending on the affected sites. We present an unusual case of acute disseminated encephalomyelitis with the chief complaint of high-grade fever and urinary retention instead of any signs of neurological disturbances. This is the 10th report of this kind of presentation in Japan.

[Prevalence of hydronephrosis and vesicoureteral reflux in pediatric urinary tract infection].

We studied 108 children diagnosed with urinary tract infection (UTI) to determine the frequency of hydronephrosis and vesicoureteral reflux (VUR). Fifty-two children (48.1%) had hydronephrosis (pyeloureteral junction obstruction: 27.8%) and 43 children (39.8%) had VUR (primary VUR: 36.1%). A renal scar was seen in 25.8% of the VUR cases. We recognized again that children with a history of UTI need to be examined promptly and thoroughly.

[A case of hypospadias with a dicentric Y chromosome].

An infant was referred to our department with complaint of abnormality of the external genitalia. Hypospadias and right inguinal hernia were detected and left testis was palpable, but right testis was not palpable. Chromosomal examination revealed 45, X/46, X, idic (Y) (q11.2). On ultrasonographic examination, uterus and ovary were not recognized. At one year of age, we performed operation of right inguinal hernia and right cryptorchism. During operation right spermatic cord and epididymis were detected, but right testis was not detected. At two years of age, urethroplasty was performed. After the operation closure of hypospadias fistulas was performed. Now the patient does not have fistulas and has good clinical progress.

Nuclear expression of Y box binding-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.

The development and acquisition of multiple drug resistance in cancer cells remain a major obstacle in the treatment of bladder cancer. Nuclear translocation of Y box binding-1 (YB-1), which is a member of a family of DNA-binding proteins that contain a cold shock domain, plays a significant role in the acquisition of drug resistance by upregulating expression of the multidrug resistance-1 (MDR-1) gene product, p-glycoprotein. The tumor suppressor protein p53 is thought to be essential for nuclear translocation of YB-1. We hypothesized that nuclear translocation of YB-1 might be associated with drug resistance of bladder cancer with an abnormality of the TP53 gene that results in a mutated p53 protein. To test this hypothesis, we analyzed the association of YB-1 with drug resistance of TP53-mutated bladder cancer, including immunohistochemical analysis of YB-1, p-glycoprotein and p53 in vivo as well as the function of YB-1 nuclear translocation and regulation of its translocation by p53 in vitro. Additionally, we examined the association between the nuclear translocation of YB-1 and gemcitabine, a major anticancer-drug for bladder cancer, in cancer cell lines. Nuclear expression of YB-1 was correlated with the expression of p-glycoprotein and p53 in bladder cancer cases (p<0.05). In vitro, both introduction of TP53 and gemcitabine induced nuclear translocation of YB-1. These data indicate that YB-1 translocates to the nucleus coordinately with p53 expression and is involved in gemcitabine resistance in bladder cancer. Nuclear expression of YB-1 is important for resistance to chemotherapy including gemcitabine in TP53-mutated bladder cancer.