Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem-immunoreceptor tyrosine-based activation motif.

Bladder cancer is one of the most common cancers among men worldwide. Although multiple genomic mutations and epigenetic alterations have been identified, an efficacious molecularly targeted therapy has yet to be established. Therefore, a novel approach is anticipated. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that is highly expressed in various cancers. In this study, we evaluated bladder cancer patient samples and found that GPNMB protein abundance is associated with high-grade tumors, and both univariate and multivariate analyses showed that GPNMB is a prognostic factor. Furthermore, the prognosis of patients with high GPNMB levels was significantly poorer in those with nonmuscle invasive bladder cancer (NMIBC) than in those with muscle invasive bladder cancer (MIBC). We then demonstrated that knockdown of GPNMB in MIBC cell lines with high GPNMB inhibits cellular migration and invasion, whereas overexpression of GPNMB further enhances cellular migration and invasion in MIBC cell lines with originally low GPNMB. Therefore, we propose that GPNMB is one of multiple driver molecules in the acquisition of cellular migratory and invasive potential in bladder cancers. Moreover, we revealed that the tyrosine residue in the hemi-immunoreceptor tyrosine-based activation motif (hemITAM) is required for GPNMB-induced cellular motility.

The prognostic impact of treatment centralization in patients with testicular germ cell tumors: analysis of hospital-based cancer registry data in Japan.

BACKGROUND: To identify the prognostic impact of treatment centralization in patients with testicular germ cell tumors (TGCT). METHODS: We used a hospital-based cancer registry data in Japan to extract seminoma and non-seminoma cases that were diagnosed in 2013, histologically confirmed, and received the first course of treatment. To compare the 5-years overall survival (OS) rates of patients stratified by institutional care volume, we performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) method to adjust patient backgrounds. RESULTS: A total of 1767 TGCT patients were identified. The 5-years OS rates for stage II and III TGCT patients treated at low-volume institutions (< 7 cases) were significantly worse than high-volume institutions (≥ 7 cases) (91.2% vs. 83.4%, p = 0.012). Histological stratification revealed that 5-year OS rates for stage II and III seminoma patients in the low-volume group were significantly worse than the high-volume group (93.5% vs. 84.5%, p = 0.041). Multivariate OS analysis using an IPTW-matched cohort showed that institutional care volume was an independent prognostic factor (hazard ratio 2.13 [95% confidence interval: 1.23-3.71], p = 0.0072). CONCLUSION: Our results indicate that stage II and III TGCT patients experience lower survival rates at low-volume institutions and would benefit from treatment centralization.

Differences of Bone Mineral Density by Characteristics of Sports in Amenorrheic Athletes.

Hypothalamic amenorrhea leads to a hypoestrogenic state, causing decreased bone mineral density (BMD), while strong impact loading on bone has been shown to increase BMD. The purpose of this study is to compare BMD in female athletes based on menstrual status and their sports/events by impact loading characteristics. BMD at the lumbar spine was measured by dual-energy X-ray absorptiometry and hormone level. The subjects were classified into four groups and BMD and hormone levels were compared among the four groups, which were divided into amenorrheic athletes (AAs) and eumenorrheic athletes (EAs). This study recruited 410 female athletes (164 in the AAs and 246 in the EAs), 55 athletes in non-impact sports, 123 in low-impact sports, 141 in multidirectional sports, and 91 in high-impact sports. In the AAs group, BMD Z-score was lowest in low-impact sports (Z-score: -1.53 [-1.76, -1.30]), and was highest in high-impact sports (Z-score: 0.02 [-0.34, 0.38]). In multidirectional and high-impact sports, BMD Z-score in the AAs group did not show results lower than the average for non-athletes. When screening female athletes for low BMD, it is important to evaluate the risk of low BMD based on the impact loading characteristics of their sports/events, in addition to the menstrual state.

Enfortumab vedotin prolongs overall survival in metastatic urothelial carcinoma following pembrolizumab therapy in real-world data.

OBJECTIVE: In December 2021, enfortumab vedotin (EV), an antibody-drug conjugate directed against nectin-4, was approved in Japan as a new treatment after platinum-containing chemotherapy and PD-1/PD-L1 inhibitors. This study evaluated, using real-world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). MATERIALS AND METHODS: Fifty-five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non-EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. RESULTS: The median (range) follow-up period after pembrolizumab discontinuation was 6.3 (0.7-31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non-EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non-EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non-EV group; hazard ratio 0.26; 95% confidence interval 0.16-0.41; p < 0.001) was an independent prognostic factor for OS. CONCLUSION: EV prolonged OS in mUC following pembrolizumab therapy in real-world data.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

Oncological outcomes of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer: A nationwide multi-institutional study.

OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Development and validation of a survival nomogram and calculator for male patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate and/or enzalutamide.

BACKGROUND: Despite the widespread availability of medication choices for metastatic castration-resistant prostate cancer (mCRPC), biomarkers to predict the efficacy of each mCRPC treatment have not yet been established. This study developed a prognostic nomogram and a calculator to predict the prognosis of patients with mCRPC who received abiraterone acetate (ABI) and/or enzalutamide (ENZ). METHODS: In total, 568 patients with mCRPC who underwent ABI and/or ENZ between 2012 and 2017 were enrolled. A prognostic nomogram based on the risk factors was developed using the Cox proportional hazards regression model and clinically important factors. The discriminatory ability of the nomogram was assessed according to the concordance index (C-index). A 5-fold cross-validation was repeated 2000 times to estimate the C-index, and the means of the estimated C-index for the training and validation sets were determined. A calculator based on this nomogram was then developed. RESULTS: The median overall survival (OS) was 24.7 months. Multivariate analysis showed that the time to CRPC, pre-chemotherapy, baseline prostate-specific antigen, baseline alkaline phosphatase, and baseline lactate dehydrogenase levels were independent risk factors for OS (hazard ratio [HR]: 0.521, 1.681, 1.439, 1.827, and 12.123, p = 0.001, 0.001, < 0.001, 0.019, and < 0.001, respectively). The C-index was 0.72 in the training cohort and 0.71 in the validation cohort. CONCLUSIONS: We developed a nomogram and calculator to predict OS in Japanese patients with mCRPC who received ABI and/or ENZ. Reproducible prognostic prediction calculators for mCRPC will facilitate greater accessibility for clinical use.

Improved survival of poor-risk non-seminomatous germ cell tumor patients: real-world data from a single institute in Japan.

OBJECTIVES: The International Germ Cell Cancer Collaborative Group Update Consortium showed the improved survival of patients with a non-seminomatous germ cell tumor. We updated the survival data of the non-seminomatous germ cell tumor patients treated at our hospital. PATIENTS AND METHODS: We analyzed the outcomes of 138 patients treated in 1981-2018. We compared the survival of the patients treated in the early (1981-99) and later (2000-18) periods and determined the groups' progression-free survival and overall survival using the Kaplan-Meier method. We used a web-based application of the International Germ Cell Cancer Collaborative Group Update model to calculate each patient's predicted 3-year progression-free survival. RESULTS: The 5-year progression-free survival rates of the good, intermediate and poor prognosis groups were 91, 83 and 64%, and their 5-year overall survival rates were 97, 89 and 82%, respectively. There were no significant differences in the progression-free survival or overall survival of the good and intermediate prognosis groups by treatment year. The 5-year progression-free survival of the poor prognosis group was almost identical in both treatment year (60 and 65%, respectively). By contrast, the 5-year overall survival in the later period (85%) was higher than that in the early period (70%). The median-predicted 3-year progression-free survival rates of the good, intermediate and poor prognosis groups were 92, 83 and 51% (P < 0.01), respectively. The concordance index for the good, intermediate and poor prognosis groups were 0.56, 0.79 and 0.67, respectively. CONCLUSION: The survival of our poor prognosis non-seminomatous germ cell tumor patients improved over time. The 5-year overall survival of patients treated in 2000-18 reached 85%.

Plasma circulating tumor DNA profiling in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Molecular analysis of tumor tissues has been extensively analyzed in germ cell tumors. However, genetic analysis of plasma circulating tumor DNA has been limited. Our objective was to analyze genetic alterations in circulating tumor DNA as well as its impact on prognosis in patients with chemo-refractory germ cell tumors. METHODS: We included 13 patients with chemo-refractory germ cell tumors who relapsed after second-line or higher previous chemotherapy and performed targeted sequencing of plasma cell-free DNA using an AVENIO Expanded kit. RESULTS: Tumor-specific genetic alterations were identified in all patients. The most frequently mutated gene was TP53 (53.4%), followed by PTEN (23.1%), GNAS (15.4%) and MTOR (15.4%). Moreover, EGFR amplification (38.5%) and MET amplification (15.4%) were also identified. We defined two or more single nucleotide variants detected in plasma cell-free DNA as circulating tumor DNA-positive. Kaplan-Meier analysis revealed that overall survival was significantly shorter in circulating tumor DNA-positive patients than circulating tumor DNA negative-patients (median overall survival 3.13 vs. 8.73 months; p = 0.042). CONCLUSION: Analysis of plasma circulating tumor DNA could detect genetic alterations in patients with chemo-refractory GCT. Moreover, detectable circulating tumor DNA in plasma was associated with poor prognosis in those patients. These results suggest that liquid biopsy using analysis of plasma circulating tumor DNA may be clinically useful for germ cell tumor patients.

[Two Cases of Femoral Nerve Palsy after Pelvic Surgery].

Postoperative femoral nerve palsy (FNP) is a rare complication associated with urologic surgery. Inappropriate use of retractors, use of lithotomy position, and prolonged surgery that lead to the femoral nerve compression have been reported as risk factors for FNP. Here, we report two cases of FNP after pelvic surgery. Case 1: A 47-year-old woman underwent ureterocystoneostomy for a giant ureterocele. On the first postoperative day, she developed muscle weakness and paresthesia in the left lower leg. An orthopedic surgeon diagnosed her with FNP associated with the surgery. Case 2: An 82-year-old woman underwent radical cystectomy for invasive bladder cancer. On the second postoperative day, she developed extension deficit in the left lower leg and was diagnosed with an iatrogenic FNP. Although this complication is infrequent, at onset, it leads to difficulty in walking and gait disturbance in the patient. As a result, it greatly reduces the patient's postoperative quality of life. Therefore, preventive measures should be taken to reduce the risk of this postsurgical nerve injury, such as appropriate placement of retractors and proper patient positioning during the operation.

Immune-related adverse events in urothelial cancer patients: Adjustment for immortal time bias.

To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC.

A high serum dehydroepiandrosterone concentration is a predictor of candidates for active surveillance in men with serum prostate-specific antigen < 10 ng/mL.

BACKGROUND: There is no consensus on the role of serum dehydroepiandrosterone (DHEA) concentrations in the detection of prostate cancer. This study examined the effectiveness of serum DHEA in predicting candidate patients for active surveillance (AS) prior to prostate biopsy. METHODS: A systematic prostate needle biopsy was performed in 203 men with serum PSA levels of < 10 ng/mL to detect prostate cancer. Serum DHEA concentrations were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) just before biopsy. Patient's age, serum prostate-specific antigen (PSA) levels, prostate volume, and serum DHEA concentrations were compared with pathological findings in multivariate analyses. RESULTS: The median patient's age, PSA, serum DHEA concentration and prostate volume were 68 years, 5.5 ng/mL, 1654.7 pg/mL, and 31.2 mL, respectively. In a multivariate analysis, low PSA values, high serum DHEA concentrations, and large prostate volume were significant predictors of the patients with benign prostatic hyperplasia (BPH) or prostate cancer with a Gleason score of ≤ 3 + 4 who are candidate for AS. The DHEA cut-off point for predicting BPH or prostate cancer with a Gleason score of ≤ 3 + 4 was 2188 pg/mL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 33.7%, 96.0%, 98.4%, and 16.9%, respectively. CONCLUSION: The study indicated that higher serum DHEA concentrations prior to prostate biopsy might predict the patients with BPH or prostate cancer with a Gleason score ≤ 3 + 4 who are candidate for AS, in men with PSA of < 10 ng/mL.

Administration of radium-223 and the prognosis in Japanese bone metastatic castration-resistant prostate cancer patients: A large database study.

BACKGROUND: The ALSYMPCA trial revealed radium-223 (Ra-223) to be a life-prolonging agent for bone metastatic castration-resistant prostate cancer (CRPC). However, only 2.8% of enrolled patients in that clinical trial were Asian, and no Japanese patients were enrolled. Several retrospective studies have been published concerning Japanese bone metastatic CRPC patients receiving Ra-223. However, no study has yet reported the correlation between Ra-223 induction and the survival in Japanese bone metastatic CRPC patients. This study investigated the effect of Ra-223 as a life-prolonging agent in a large Japanese healthcare fee database. METHODS: A total of around 410 000 prostate cancer patients were extracted from this database, and 25 934 were diagnosed with CRPC. In these patients, the age, date of the CRPC diagnosis, date of Ra-223 induction, and prognosis were analyzed. RESULTS: A total of 1628 patients received Ra-223, and 6693 patients were diagnosed with bone metastasis CRPC, with the remaining 17 613 patients diagnosed with CRPC without bone metastasis. The patients who completed six courses of Ra-223 showed a significantly more favorable overall and cancer-specific survival than those who received ≤5 courses (p < 0.0001 and p < 0.0001, respectively). For time from CRPC diagnosis date to death, the Ra-223 induction group showed a significantly more favorable prognosis with regard to both the overall and cancer-specific survival than the bone metastatic CRPC patients without Ra-223 (p < 0.0001 and p < 0.0001, respectively). CONCLUSIONS: Bone metastatic CRPC patients who received Ra-223 showed a significantly better prognosis than bone metastatic CPRC patients who did not receive Ra-223.

Phase II trial of nivolumab monotherapy and biomarker screening in patients with chemo-refractory germ cell tumors.

OBJECTIVES: Germ cell tumors are highly susceptible to chemotherapy; however, there is a lack of established treatments for consistently relapsing germ cell tumor. Therefore, in this phase II study, we evaluated the efficacy and safety of nivolumab for relapsed germ cell tumor. METHODS: Seventeen adult patients (median age 34 years) with refractory primary germ cell tumor after second-line or higher chemotherapy were enrolled. Nivolumab was administered over 30 min at 240 mg/body every 2 weeks until disease progression or intolerable adverse event occurrence. The primary endpoint was the overall response rate. RESULT: We performed a biomarker analysis of programmed death ligand-1 expression and genomic sequencing. Tumor histology revealed nonseminoma and seminoma in 14 and three patients, respectively. Patients were pretreated with a median of three chemotherapy lines, and three patients received high-dose chemotherapy. The median number of nivolumab doses was 3 (range 2-46). One patient showed a partial response and three showed stable disease. Responses were durable in one patient with a partial response and one patient with stable disease (median 90 and 68 weeks, respectively). Nivolumab was well-tolerated, with only two Grade 3 adverse events observed. Programmed death ligand-1 expression was not associated with objective responses. Genomic sequencing revealed a high tumor mutation burden in a patient with a durable partial response. While a small subset of chemorefractory germ cell tumors may respond to nivolumab, programmed death ligand-1 is unreliable to measure response. CONCLUSIONS: Tumor mutation burden is a potential biomarker for future testing of germ cell tumor response.

Clinicopathological features of adrenal malignancies: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: To identify the clinicopathological features of adrenal malignancies and analyze the prognoses of patients with adrenal cortical carcinoma (ACC) and malignant pheochromocytoma (MPCC). PATIENTS AND METHODS: We used a hospital-based cancer registry data in Japan to extract cases of adrenal malignancies that were histologically confirmed, diagnosed, and initially treated from 2012-2015. For survival analysis, we used data from the 2008-2009 cohort to estimate 5-year overall survival (OS) by the Kaplan-Meier method. RESULTS: A total of 989 adrenal malignancies were identified in the 2012-2015 cohort. The most common histologies were ACC (26.4%), diffuse large B-cell lymphoma (DLBCL; 25.4%), neuroblastoma (22.2%), and MPCC (11.9%). While most ACC and MPCC patients were in their 60s, DLBCL patients accounted for 61.5% of adrenal malignancies in the over-70 cohort. Among ACC patients with clinical staging data, 46.3% of patients were stage IV. Although surgery was a chief strategy for all stages, younger patients tended to receive combination therapy, including surgery and chemotherapy or hormone therapy. In the 2008-2009 cohort, the 5-year OS rates of ACC (n = 49) and MPCC (n = 23) patients were 56.2% and 86.4% while ACC patients without surgery had 1- and 2-year OS rates of 25.0% and 12.5%. CONCLUSION: In Japan, DLBCL accounted for the majority of adrenal malignancies in older patients. Despite advanced staging, ACC patients were mainly treated with surgery and their prognosis was not satisfactory. Such epidemiological data may be useful in considering initial management strategies.

[Adrenocortical Oncocytic Tumor : A Report of Two Cases].

Adrenocortical oncocytic tumors are rare. As the Weiss criteria overestimate the malignancy of oncocytic tumor due to histological hallmarks, the Lin-Weiss-Bisceglia system (LWB system) is required for an accurate diagnosis of the malignant potential of an oncocytic tumor. We report two cases diagnosed as an oncocytic tumor with uncertain malignant potential (borderline) and an oncocytic tumor (benign) based on the LWB system, both of which were diagnosed as malignant based on the Weiss criteria. Case 1 : A man in his 20s was referred to our hospital for treatment of a left adrenal tumor. A non-functional pheochromocytoma or adrenal cancer was suspected. He underwent surgical resection of the left adrenal tumor and left kidney. The specimen was positive for 3 of the 9 Weiss criteria, but met one minor criterion in the LWB system. He was diagnosed with an oncocytic tumor with uncertain malignant potential (borderline). Case 2 : A woman in her 40s was referred to our hospital for treatment of a left adrenal tumor. Under the possibility of adrenal cancer, she underwent surgical resection of the left adrenal tumor. The specimen was positive for 3 of the 9 Weiss criteria, but the specimen met no criteria in the LWB system. She was diagnosed with an oncocytic tumor (benign). There has been no recurrence of the oncocytic tumor as of 2 years of follow-up in the two patients.

A novel prediction model for the completion of six cycles of radium-223 treatment and survival in patients with metastatic castration-resistant prostate cancer.

PURPOSE: We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. METHODS: We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. RESULTS: We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. CONCLUSION: Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.

Dural sac shrinkage signs on magnetic resonance imaging at the thoracic level in spontaneous intracranial hypotension-its clinical significance.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is secondary to a cerebrospinal fluid leak at the spinal level without obvious causative events. Several signs on brain and cervical spine magnetic resonance (MR) imaging (MRI) have been associated with SIH but can be equivocal or negative. This retrospective study sought to identify characteristic SIH signs on thoracic spinal MRI. METHODS: Cranial and spinal MR images of 27 consecutive patients with classic SIH symptoms, who eventually received epidural autologous blood patches (EBPs), were analyzed. RESULTS: The most prevalent findings on T2-weighted MRI at the thoracic level were anterior shift of the spinal cord (96.3%) and dorsal dura mater (81.5%), probably caused by dural sac shrinkage. These dural sac shrinkage signs (DSSS) were frequently accompanied by cerebrospinal fluid collection in the posterior epidural space (77.8%) and a prominent epidural venous plexus (77.8%). These findings disappeared in all six patients who underwent post-EBP spinal MRI. Dural enhancement and brain sagging were minimum or absent on the cranial MR images of seven patients, although DSSS were obvious in these seven patients. For 23 patients with SIH and 28 healthy volunteers, a diagnostic test using thoracic MRI was performed by 13 experts to validate the usefulness of DSSS. The median sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of the DSSS were high (range, 0.913-0.931). CONCLUSIONS: Detection of DSSS on thoracic MRI facilitates an SIH diagnosis without the use of invasive imaging modalities. The DSSS were positive even in patients in whom classic cranial MRI signs for SIH were equivocal or minimal.