Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma.

OBJECTIVES: Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC. METHODS: We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs. RESULTS: Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders. CONCLUSIONS: An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.

Hemoglobin and neutrophil levels stratified according to International Metastatic Renal Cell Carcinoma Database Consortium risk predict the effectiveness of ipilimumab plus nivolumab in patients with advanced metastatic renal cell carcinoma.

OBJECTIVE: To identify biomarkers associated with the effectiveness of ipilimumab plus nivolumab against advanced metastatic renal cell carcinoma. METHODS: We retrospectively analyzed the data of 75 patients treated with ipilimumab plus nivolumab at seven hospitals between August 2018 and April 2021. Prognostic biomarkers were assessed prior to initiating treatment with ipilimumab plus nivolumab. Median overall survival and progression-free survival were examined using the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify predictors of disease progression. The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors most important for predicting disease progression were determined using classification and regression tree analysis. RESULTS: Median overall survival and progression-free survival were longer in the intermediate IMDC risk group than in the poor IMDC risk group (overall: not reached vs. 18.3 months; progression-free: not reached vs. 13.5 months). The multivariate analysis identified poor IMDC risk as a risk factor for disease progression (hazard ratio 2.61, 95% confidence interval: 1.05-6.51). Based on the results of the classification and regression tree analysis, the cohort was divided into non-anemia, anemia + neutro-Low, and anemia + neutro-High groups. Median overall survival and progression-free survival were longer in the non-anemia and anemia + neutro-Low groups than in the anemia + neutro-High group (overall: not reached vs. 29.3 months vs. 4.3 months: progression-free: not reached vs. 29.0 months vs. 3.9 months). CONCLUSION: Hemoglobin and neutrophil levels may represent crucial biomarkers for predicting the effectiveness of ipilimumab plus nivolumab therapy in patients with renal cell carcinoma.

GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma.

INTRODUCTION: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). METHODS: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. RESULTS: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively). CONCLUSION: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

Plasmacytoid Urothelial Carcinoma of the Bladder That Manifests Disseminated Carcinomatosis of the Bone Marrow: A Case Report of Extremely Rapid Progression.

Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare variant of invasive urothelial carcinoma (UC) with aggressive behavior. Despite its prognosis being poorer than that of conventional UC, a median overall survival of approximately 2 years is ensured when it is treated with radical cystectomy (RC), and few patients die within a few months of RC. In this paper, we report the case of a patient with PUC who developed widespread bone metastasis only 6 weeks after RC, which resulted in death within 2 months postoperatively.

Survival Outcome after Reduced-Port Laparoscopic Radical Cystectomy for Bladder Cancer: Long-Term Follow-Up Analysis.

INTRODUCTION: This study had two objectives: (i) to evaluate oncological outcomes in a long-term follow-up of patients with bladder cancer after reduced-port laparoscopic radical cystectomy (RP-LRC) and (ii) to assess the effect of modified Glasgow prognostic scores (mGPS) on patient outcomes. METHODS: Consecutive patients (n = 100) who received RP-LRC between March 2012 and December 2018 at our institution and affiliated hospital were retrospectively reviewed. Preoperative serum albumin and C-reactive protein levels were determined. Patients were grouped based on clinical T stage (≤cT2: n = 75, ≥cT3: n = 25) using pooled cumulative data. Oncological outcomes and mGPS as a prognostic biomarker were analyzed retrospectively. Kaplan-Meier curves displayed recurrence and survival rates. Univariate and multivariate Cox regression analyses evaluated potential prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Patient characteristics between the two groups were statistically similar for preoperative hematological and mGPS status, blood loss level, rate of allogeneic transfusion, and pneumoperitoneum time. After a median follow-up period of 55 months, 40/100 patients experienced disease relapse. RFS and CSS for ≤cT2 were significantly less than for ≥cT3 (p < 0.001, p < 0.05, respectively). Distant metastasis occurred in 30 patients with similar distributions of relapse sites between T-stage cohorts. Median RFS for mGPS 1/2 were 18.9 (95% confidence interval [CI]: 8.8-not assessed [NA]) and 35.0 (95% CI: 8.7-NA) months, respectively, significantly worse than for mGPS 0 (median NA, 95% CI: NA-NA); CSS was similar. Univariate and multivariate analyses revealed ≥cT3 stage, worse clinical N stage, and poor mGPS status were significant prognostic factors for short RFS and CSS. CONCLUSIONS: A large proportion of bladder cancer patients who undergo RP-LRC experience relapse, with ≥cT3 stage, worse clinical N stage or poor mGPS status identified as significant prognostic factors. Our findings may contribute to improved surgical procedures for such patients.

Myocarditis and myasthenia gravis by combined nivolumab and ipilimumab immunotherapy for renal cell carcinoma: A case report of successful management.

Ipilimumab plus nivolumab (Ipi/Nivo) has revolutionized advanced renal cell carcinoma (RCC) treatment. However, it encompassed fatal immune-related adverse events (irAEs). Myocarditis with concomitant myasthenia gravis (MG) has a mortality rate of 50%, and a high dose of methylprednisolone (mPSL) should be administered with careful attention to MG exacerbation. We present the case of a 59-year-old man with progressing lung metastasis of RCC. After one cycle of Ipi/Nivo, he experienced myocarditis and MG, managed by mPSL pulse therapy, plasma exchange, and high-dose intravenous immunoglobulin. We share the therapeutic course, aiming to contribute to the limited literature on rare but aggressive irAEs.

Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model.

BACKGROUND: Cryptorchidism is known to impair spermatogenesis. The blood-testis barrier (BTB) becomes defined in seminiferous tubules around puberty and provides a suitable environment for germ cells. Little is known about the BTB in undescended testes (UDT). OBJECTIVES: To determine the role of BTB during puberty in UDT using a non-surgical cryptorchid rat model. MATERIAL AND METHODS: Unilateral cryptorchid male rats were intraperitoneally injected with non-steroidal antiandrogen during intrauterine development; the testes were harvested at 4, 5, and 6 weeks after birth. Testicular histology, expression levels of the BTB proteins (claudin-11, occludin, zonula occludens-1), and apoptotic cells were evaluated by immunohistochemistry, Western blotting, and TUNEL assay. The functionality of the BTB was investigated by electron microscopy using the lanthanum tracer method. RESULTS: The testicular histology of undescended testes 6 weeks after birth showed maturation arrest at the spermatocyte level. The BTB protein distributions were altered in the UDT, with a noticeable difference in claudin-11(CLDN11) localization from 4 to 5 weeks after birth between control and UDT samples. BTB protein levels were similar. More apoptotic germ cells were detected in the adluminal compartment of tubules in the UDT than in the control testes. Electron microscopy showed that the lanthanum tracer was limited to the BTB of control testes, whereas it penetrated the BTB of UDT. DISCUSSION: Here, loss of normal BTB function and impaired spermatogenesis were observed in UDT during puberty. CLDN11 is a pivotal tight junction protein belonging to the BTB. Tight junctions are considered as essential for normal spermatogenesis, and abnormal CLDN11 organization may cause UDT-associated male infertility. CONCLUSION: CLDN11 disorganization within the BTB may cause spermatogenic impairment, possibly by limiting the BTB function.

Initial treatment outcome and feasibility of low-dose cabazitaxel against docetaxel- and castration-resistant prostate cancer in a Japanese hospital.

Introduction: Cabazitaxel (CBZ) is used worldwide for castration-resistant prostate cancer after docetaxel treatment. In July 2014 the drug was approved in Japan with the same induction dose used for Caucasian patients. In this study, we examined and compared the results of an initial low-dose CBZ treatment in patients admitted to our hospital. Patients and Methods: Between July 2014 and August 2018, sixteen mCRPC patients were enrolled and underwent a low-dose CBZ treatment at our hospital. We compared the results with those of a Japanese metastatic docetaxel- and castration-resistant prostate cancer Phase I study. Results: The median patient age was 77 years (range, 53-84 years). Of the 16 patients, eight (50%) had a lymph node metastasis and 11 (68.8%) had a distant metastasis, 10 of whom had only a bone metastasis. The median dose of CBZ was 30 mg (range, 20-32 mg) and the median number of CBZ cycles was 2.5 (range, 1-18). The PSA level of 9 (56.3%) patients decreased after CBZ treatment, including 4 (25%) who showed a decrease to <50%. The median time interval in which the PSA level decreased was 2 months (range, 1-18 months). The observed adverse events (AE) were neutropenia (31.3%), febrile neutropenia (6.3%), fatigue (43.8%), nausea (18.8%), diarrhea (12.5%), decreased appetite (25%), dysgeusia (6.3%), white blood cell count decrease (43.8%), platelet count decrease (12.3%), and anemia (75%). However, no patient listed an AE as the reason for discontinuing the treatment. Conclusions: Even at a low dose, CBZ could improve the PSA value in patients with CRPC previously treated with docetaxel. Dose reduction and prophylactic administration of sustained G-CSF were also safe treatment options. Further studies involving an introduction period including a modulation of duration and dose are necessary, especially in Japanese patients.

A case of laparoscopic fenestration surgery for pelvic lymphocele occurring after laparoscopic radical prostatectomy.

A 76-year-old Japanese man visited a nearby medical clinic complaining of abdominal distention. He had undergone extraperitoneal laparoscopic prostatectomy at our institution 5 months before the onset of abdominal distention. An imaging study revealed a large cystic lesion, and biochemical examination of a sample obtained via cyst puncture led to a diagnosis of lymphocele. As the lymphocele was resistant to puncture, drainage, and sclerotherapy with minomycin, laparoscopic fenestration was performed. Although the patient developed an adhesive ileus postoperatively, the cyst has not recurred. Fenestration surgery is a feasible option for lymphocele refractory to various conservative therapies.

Skeletal Muscle Mass Reduction Velocity as a Simple Prognostic Indicator for Patients with Metastatic Urothelial Carcinoma Receiving Second-Line Chemotherapy.

BACKGROUND: Patients with metastatic urothelial carcinoma (mUC) have an uncertain prognosis. The aim of the current study was to evaluate the prognostic potential of a skeletal muscle mass reduction index measured by computed tomography (CT) for mUC patients undergoing second-line gemcitabine and docetaxel (GD) chemotherapy. METHODS: We retrospectively reviewed 44 patients with mUC who received second-line GD chemotherapy between 2006 and 2015 in our hospital. Skeletal muscle area (SMA) at the third lumbar vertebra was measured using CT images obtained from medical records, and a skeletal muscle index (SMI) was calculated for each patient as: SMI = SMA / height2. Changes in SMI across timepoints (SMI inclination) were calculated as: SMI inclination = [( SMI/SMI)/duration of the interval between imaging visits]. Patients were then divided into two groups: a "steep" group (SMI inclination < -0.01) and a "gentle" group (SMI inclination ≥ -0.01). Kaplan-Meier curves and multivariate Cox proportional hazards regression models were used to evaluate the relationship between SMI inclination and overall survival (OS). RESULTS: There were no differences in patient characteristics between the two groups with respect to median age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), disease control rate or first-line treatment regimen. OS from the start of second-line GD therapy group was significantly shorter in the "steep" group relative to the "gentle" group. The multivariate analysis revealed that "steep" SMI inclination and presence of anemia were strong predictors of poor prognosis. CONCLUSION: Higher values of SMI inclination, indicating a faster rate of skeletal muscle mass reduction, may serve as a useful predictive marker for OS in mUC patients undergoing second-line GD chemotherapy.

Evaluation of the Dwell-Time and Dose Difference in Intravesical Bacillus Calmette-Guèrin Therapy

Objective: Bacillus Calmette-Guèrin (BCG) intravesical therapy is currently established using a low dose because of the high incidence of side-effects. Moreover, shortening the dwell time of BCG is conducted in some facilities owing to the complications associated with a long dwell time after injection. The method of BCG administration varies in each facility and even with each doctor. We evaluated whether the dwell-time and dose differences in patients who underwent intravesical BCG therapy is related to completion rates, adverse effects, and nonrecurrence rates. Methods: From November 2006 to April 2016, a total of 173 patients who received intravesical BCG therapy after transurethral resection of bladder tumor or transurethral biopsy were evaluated retrospectively. We allocated them into 4 groups based on the dose (40 or 80 mg BCG) and the dwell time (1 or 2 hours). Completion rate, side effects, and nonrecurrence rates were evaluated. Results: No significant improvement in the completion rate or reduction in side-effects was observed in any of the regimens. Although nonrecurrence rates for the 1-hour dwell time tended to be lower than the 2-hour dwell time, the difference was not significant. Conclusion: Our study suggests that reducing the BCG dose or shortening the dwell time does not reduce adverse effects or affect the nonrecurrence rate.

Examination of Diagnostic Accuracy of UroVysion Fluorescence In Situ Hybridization for Bladder Cancer in a Single Community of Japanese Hospital Patients

Objective: UroVysion (Abbott Molecular, Inc., Illinois, USA) is based on multicolor fluorescence in situ hybridization (FISH). It has been used successfully in the USA following its Food and Drug Administration approval in 2001. However, the technology was not approved for use in Japan until 2017. Cystoscopy and urine cytology are the most frequently used examinations to detect bladder cancer in Japan, and there are only a few reports regarding the performance of UroVysion. Therefore, the aim of this study is to examine the diagnostic accuracy of UroVysion FISH in Japanese patients whose tumors are detected by cystoscopy before transurethral resection of bladder tumor (TURBT). Methods: From April 2018 to July 2018, a total of 40 patients who were diagnosed as having bladder tumors by cystoscopy, and therefore underwent TURBT were registered in this study. One day before TURBT, urine cytology and UroVysion FISH were used in order to compare the accuracy with which they could detect bladder carcinoma, as confirmed by pathological results of TURBT. Results: The pathological results of TURBT showed urothelial carcinoma in 33 cases. Urine cytology showed positive results for 0 cases (0%), suspicious results for 10 cases (30.3%), and negative results for 23 cases (69.7%). On the other hand, UroVysion FISH indicated 9 positive cases (27.3%) and 24 negative cases (72.7%). There were 19 cases of urothelial carcinoma (57.6%) that were not detected by either method. Conclusion: We conclude that UroVysion FISH alone is insufficient to detect bladder cancer and that cystoscopy is essential for the optimum detection or follow up of bladder cancer cases in our hospital.

Testicular teratoma demanded in-depth pathological exploration to rule out malignancy: A pediatric case report.

INTRODUCTION: Prepubertal testicular tumors can be both benign and malignant. Although most testicular teratomas are benign, some immature cases include malignant transformation or the mixed type with yolk sac tumor and, occasionally, it is challenging to rule out malignancy. CASE PRESENTATION: We present a case of immature testicular teratoma in a 7-month-old infant, whose alpha-fetoprotein level was sequentially elevated following orchidectomy. Since malignancy could not be ruled out, we performed whole body imaging and in-depth pathological exploration. GLYPICAN3, OCT3/4, and SOX2 staining revealed no evidence of malignancy. The patient was finally diagnosed with benign immature teratoma, and has been free from recurrence for 3 years. CONCLUSION: Here, we describe the case report, as well as all the comprehensive diagnostic tests that we performed in order to rule out the malignant component.

Complete surgical removal of multiple tumor lesions in malignant pheochromocytomas produces a good prognosis.

INTRODUCTION: Malignant pheochromocytomas are rare catecholamine secreting tumors; there is no definitive strategy for the treatment of malignant pheochromocytomas, especially in cases with multiple tumors. CASE PRESENTATION: A 72-year-old woman with diabetic ketoacidosis presented with multiple malignant pheochromocytomas 16 years after undergoing adrenalectomy. After three courses of systemic chemotherapy, there was no change in the size of tumor lesions or serum catecholamine levels; surgical removal of all lesions was carried out. Eighteen months after the operation, the patient has had no recurrences and her diabetes is controlled well by oral medication. CONCLUSION: Our findings indicate that complete surgical resection should be considered, even in patients with multiple malignant pheochromocytomas.

Can lichen sclerosus be diagnosed by preputial appearance or symptoms?

INTRODUCTION: Lichen sclerosus (LS), or balanitis xerotica obliterans, is a chronic, inflammatory disease accompanied by cicatrizing skin conditions resulting in pathologic phimosis. LS can be detected clinically by the whitish appearance of the glans or the foreskin, thickened, nonretractable foreskin, dysuria, and spraying. However, diagnosis is confirmed histopathologically. PURPOSE: The aim of this study was to investigate whether LS can be diagnosed on the basis of clinical manifestation and symptoms. PATIENTS AND METHODS: A retrospective analysis was performed, which included boys referred to our institutions for phimosis evaluation between May 2001 and December 2016. Pediatric urologists clinically diagnosed LS preoperatively. Boys with voiding problems, recurrent balanoposthitis, or who were unresponsive to topical steroid treatment underwent surgical treatment. Patients who underwent religious circumcisions were not included. RESULTS: Three-hundred twenty boys diagnosed with phimosis were identified, and 71 (22%) boys underwent surgery. Fifty-eight boys underwent complete or partial circumcision, and 13 boys underwent a dorsal slit or preputioplasty. Thirty foreskin samples were sent for histopathologic examination. Histopathologic evaluation showed evidence of LS in 13 of 30 (43%) circumcised boys, chronic inflammation in ten (33%), no abnormality in four (13%), dysplasia in two (7%), and acute inflammation in one (3%). In the 22 boys who were clinically diagnosed with LS, 13 patients had histopathologic evidence of LS (59%). Visually, eleven cases had whitish foreskins and 21 cases had thickened nonretractable foreskins, of which there were seven (64%) (P>0.05) and 12 (57%) (P<0.01) cases, respectively. These cases were histopathologically diagnosed with LS. Both whitish and thickened, nonretractable foreskin was observed in eight patients, of which seven (88%) (P<0.01) were also histologically diagnosed with LS. There was no correlation between histopathologic diagnosis and preoperative symptoms such as dysuria, ballooning, spraying, or penile pain (P>0.2). CONCLUSION: It is difficult to reliably distinguish whether a patient has histopathological LS by clinical findings alone.

Unusual Cause of Acute Scrotal Pain-Inflammatory Noncommunicating Hydrocele: A Pediatric Case Report.

The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.

Urothelial carcinoma of the urinary bladder in a 12-year-old girl: A case report with immunohistological analysis and a review of the literature.

Urothelial carcinoma of the bladder in childhood is extremely rare. We report on a 12-year-old girl with urothelial carcinoma of the bladder who presented with gross hematuria. Immunohistochemical staining showed normal levels of cytokeratin 20 expression and decreased levels of Ki67 and p53 expression. Human papillomavirus, which can be a cause of urothelial carcinoma of the bladder, was not detected by polymerase chain reaction. We reviewed the literature focusing on diagnostic tools for urothelial carcinoma of the bladder and determined that abdominal ultrasonography, with an extremely high sensitivity of 98%, could be a useful tool for postoperative follow-up in childhood.

Involvement of the bone morphogenic protein/SMAD signaling pathway in the etiology of congenital anomalies of the kidney and urinary tract accompanied by cryptorchidism.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. METHODS: Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis. Genomic DNA was extracted from peripheral blood, and WES was performed. Disease-specific single nucleotide polymorphisms (SNPs) were determined by comparison with the human genome reference sequence (hg19). Additionally, we searched for SNPs that were common to all three patients, with a particular focus on the coding regions of the target genes. RESULTS: In total, 8710 SNPs were detected. Of the genes harboring these SNPs, 32 associated with renal or testicular development were selected for further analyses. Of these, eight genes (i.e., SMAD4, ITGA8, GRIP1, FREM1, FREM2, TNXB, BMP8B, and SALL1) carried a single amino acid substitution that was common to all three patients. In particular, SNPs in SMAD4 (His290Pro and His291Pro) have not been reported previously in patients with symptomatic CAKUT. Of the candidate genes, four genes (i.e., ITGA8, GRIP1, FREM1, and FREM2) were Fraser syndrome-related genes, encoding proteins that functionally converged on the glial cell-derived neurotrophic factor/RET/bone morphogenic protein (BMP) signaling pathways. As another candidate gene, the protein encoded by BMP8B activates the nuclear translocation of SMAD4, which regulates the expression of genes associated with the differentiation of primordial germ cells or testicular development. Additionally, BMP4, a member of the BMP family, regulates the interaction between metanephric mesenchyme and ureteric buds by suppressing GDNF. CONCLUSIONS: Taken together, our findings suggested that the development of the kidney and urinary tract is intimately linked with that of male reproductive organs via BMP/SMAD signaling pathways.

A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy.

OBJECTIVES: Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. METHODS: We examined 6 patients (median age: 25 years, range: 19-27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8-84 months). RESULTS: Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP)). One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. CONCLUSIONS: Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.