Cushing's syndrome in pregnancy in which laparoscopic adrenalectomy was safely performed by a retroperitoneal approach.

Introduction: Laparoscopic adrenalectomy is the standard treatment for adrenal tumors caused by Cushing's syndrome. However, few pregnant women have undergone adrenalectomy because of the risk of general anesthesia and surgery. Case presentation: A 28-year-old woman presented with gradually worsening Cushing's signs at around 12 weeks of pregnancy. Magnetic resonance imaging displayed a 38-mm left adrenal tumor, which was the cause of the adrenal Cushing's syndrome. Metyrapone was started, which increased androgen levels. Since the management of Cushing's syndrome by medication alone is challenging, unilateral laparoscopic adrenalectomy by a retroperitoneal approach was performed at 23 weeks of the pregnancy. No perioperative complications were noted. Conclusion: Adrenalectomy is considered safe in pregnant women with Cushing's syndrome. Laparoscopic adrenalectomy by retroperitoneal approach should be chosen and performed between 14 and 30 weeks of pregnancy to prevent mother and fetal complications.

Tumor localization by Prostate Imaging and Reporting and Data System (PI-RADS) version 2.1 predicts prognosis of prostate cancer after radical prostatectomy.

An improved reading agreement rate has been reported in version 2.1 (v2.1) of the Prostate Imaging and Reporting and Data System (PI-RADS) compared with earlier versions. To determine the predictive efficacy of bi-parametric MRI (bp-MRI) for biochemical recurrence (BCR), our study assessed PI-RADS v2.1 score and tumor location in Japanese prostate cancer patients who underwent radical prostatectomy. Retrospective analysis was performed on the clinical data of 299 patients who underwent radical prostatectomy at Chiba University Hospital between 2006 and 2018. The median prostate-specific antigen (PSA) level before surgery was 7.6 ng/mL. Preoperative PI-RADS v2.1 categories were 1-2, 3, 4, and 5 in 35, 56, 138, and 70 patients, respectively. Tumor location on preoperative MRI was 107 in the transition zone (TZ) and 192 in the peripheral zone (PZ). BCR-free survival was significantly shorter in the PZ group (p = 0.001). In the total prostatectomy specimens, preoperative PI-RADS category 5, radiological tumor location, pathological seminal vesicle invasion, and Grade Group ≥ 3 were independent prognostic factors of BCR. These four risk factors have significant potential to stratify patients and predict prognosis. Radiological tumor location and PI-RADS v2.1 category using bp-MRI may enable prediction of BCR following radical prostatectomy.

Machine-learning predicts time-series prognosis factors in metastatic prostate cancer patients treated with androgen deprivation therapy.

Machine learning technology is expected to support diagnosis and prognosis prediction in medicine. We used machine learning to construct a new prognostic prediction model for prostate cancer patients based on longitudinal data obtained from age at diagnosis, peripheral blood and urine tests of 340 prostate cancer patients. Random survival forest (RSF) and survival tree were used for machine learning. In the time-series prognostic prediction model for metastatic prostate cancer patients, the RSF model showed better prediction accuracy than the conventional Cox proportional hazards model for almost all time periods of progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). Based on the RSF model, we created a clinically applicable prognostic prediction model using survival trees for OS and CSS by combining the values of lactate dehydrogenase (LDH) before starting treatment and alkaline phosphatase (ALP) at 120 days after treatment. Machine learning provides useful information for predicting the prognosis of metastatic prostate cancer prior to treatment intervention by considering the nonlinear and combined impacts of multiple features. The addition of data after the start of treatment would allow for more precise prognostic risk assessment of patients and would be beneficial for subsequent treatment selection.

Tumor Location and a Tumor Volume over 2.8 cc Predict the Prognosis for Japanese Localized Prostate Cancer.

(1) Objective: Our study investigated the prognostic value of tumor volume and location in prostate cancer patients who received radical prostatectomy (RP). (2) Methods: The prognostic significance of tumor volume and location, together with other clinical factors, was studied using 557 patients who received RP. (3) Results: The receiver operating characteristic (ROC) curve identified the optimal cutoff value of tumor volume as 2.8 cc for predicting biochemical recurrence (BCR). Cox regression analysis revealed that a tumor in the posterior area (p = 0.031), peripheral zone (p = 0.0472), and tumor volume ≥ 2.8 cc (p < 0.0001) were predictive factors in univariate analysis. After multivariate analysis, tumor volume ≥ 2.8 cc (p = 0.0225) was an independent predictive factor for BCR. Among them, a novel risk model was established using tumor volume and location in the posterior area and peripheral zone. The progression-free survival (PFS) of patients who met the three criteria (unfavorable group) was significantly worse than other groups (p ≤ 0.001). Furthermore, multivariate analysis showed that the unfavorable risk was an independent prognostic factor for BCR. The prognostic significance of our risk model was observed in low- to intermediate-risk patients, although it was not observed in high-risk patients. (4) Conclusion: Tumor volume (≥2.8 cc) and localization (posterior/peripheral zone) may be a novel prognostic factor in patients undergoing RP.

A clinical investigation of recurrence and lost follow-up after renal cell carcinoma surgery: a single-center, long-term, large cohort, retrospective study.

BACKGROUND: Late recurrence of renal cell carcinoma (RCC) is observed in some postoperative patients. In addition, some of these patients are lost to long-term postoperative follow-up. We reviewed the treatment results and prognosis of postoperative patients with RCC at Chiba University Hospital, with the aim of clarifying the proportion and background of patients lost to follow-up. METHODS: This retrospective study included 1176 RCC patients who underwent radical or/and partial nephrectomy. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and lost follow-up free survival (LFFS) were evaluated and the risk factors for LFFS identified. RESULTS: The median RFS for stage II and II cases was 188.3 and 104.0 months, respectively. Even in stage I, recurrence was observed in about 20% of patients 20 years after surgery. The Kaplan-Meier curve for LFFS showed a linear descent over time, with 50% of patients lost to follow-up within 25 years. Older age (≥ 62 years), histological type (clear cell RCC), and no recurrence were significant risk factors for lost follow-up. CONCLUSIONS: Long-term follow-up is necessary after RCC surgery because late recurrence cases are not uncommon. We believe that lifelong follow-up with imaging studies is recommended for postoperative RCC patients. Early detection of recurrence in postoperative patients is a very important issue, and it may be worthwhile for improving the prognosis of postoperative patients to focus on patients lost to follow-up who may have been overlooked.

Successful treatment of metastatic bladder cancer by gemcitabine-cisplatin re-challenge after pembrolizumab.

INTRODUCTION: The advent of pembrolizumab has contributed to improved treatment outcomes for metastatic urothelial carcinoma, but the outcomes of treatments after second-line treatment have not been established. CASE PRESENTATION: A 72-year-old man was referred to our hospital with gross hematuria and diagnosed with suspicion of bladder cancer cT1N0M0. Transurethral resection of the bladder tumor was performed, but local recurrence and multiple lung metastases appeared 5 months after surgery. Although gemcitabine-cisplatin was performed as first-line chemotherapy, the local lesion increased, and pembrolizumab was used as a second-line treatment. Pembrolizumab was also ineffective; however, re-challenge with gemcitabine-cisplatin as third-line treatment produced a good therapeutic effect. CONCLUSION: We report a successful case in which gemcitabine-cisplatin re-challenge after pembrolizumab therapy was effective in metastatic bladder cancer. Re-administration of chemotherapy after immune checkpoint inhibitors may be a broadly effective treatment option.

Adrenalectomy in Japanese patients with subclinical Cushing syndrome: 1-mg dexamethasone suppression test to predict the surgical benefit.

OBJECTIVES: To investigate whether the result of the 1-mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. METHODS: This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1-mg dexamethasone suppression test. RESULTS: Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0 µg/dL after the 1-mg dexamethasone suppression test. CONCLUSIONS: The result of the 1-mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision-making for the treatment of subclinical Cushing syndrome.

Relationship between post-void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma.

OBJECTIVES: To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. METHODS: The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. RESULTS: The median follow-up period for all patients was 44 months. The presence of residual urine (P = 0.0164) and pyuria (P = 0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P = 0.0002) and intermediate-risk groups (P = 0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P = 0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guérin treatment. CONCLUSIONS: Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.

Detection of Nonpalpable Tiny Axillary Lymph Nodes Surrounded by Adipose Tissue Using a Near-Infrared Camera.

Background: It is not always possible to detect nonpalpable small lymph nodes (LNs) surrounded by adipose tissue under the wavelength of visible light. A newly developed near-infrared camera with InGaAs element was able to capture photographs using light at >1000-nm wavelength, at which the difference in absorbance between water and lipids is large. This study investigated the ability to detect nonvisible small LNs using light at 1300-nm wavelength. Methods and Results: Following retrieval of LNs through axillary LN dissection from 20 patients with breast cancer, residual specimens were simultaneously photographed using light at 970-, 1070-, 1200-, 1300-, 1450-, and 1600-nm wavelengths. A total of 45 specimens were observed pathologically at the selected portions in which the 1300-nm light was absorbed (high absorbance group [HA group], n = 25) and those in which the 970-nm light was absorbed instead (low absorbance group [LA group], n = 20). All specimens categorized in the HA group detected the LNs, whereas none of those categorized in the LA group detected an LN. The sensitivity and specificity in the identification of an LN were 1.0. The LNs detected using this camera were significantly smaller than those detected by surgeons (3.00 ± 2.93 mm vs. 5.90 ± 3.91 mm, p < 0.01). Discussion: The light at 1300-nm wavelength was absorbed by axillary LNs. This camera detected LNs that were undetectable by surgeons. This novel technology may be applied to lymphatic microsurgery and contribute to the development of a minimally invasive LN dissection method.

Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma.

L-type amino acid transporter 1 (LAT1) plays a role in transporting essential amino acids including leucine, which regulates the mTOR signaling pathway. Here, we studied the expression profile and functional role of LAT1 in bladder cancer. Furthermore, the pharmacological activity of JPH203, a specific inhibitor of LAT1, was studied in bladder cancer. LAT1 expression in bladder cancer cells was higher than that in normal cells. SiLAT1 and JPH203 suppressed cell proliferative and migratory and invasive abilities in bladder cancer cells. JPH203 inhibited leucine uptake by > 90%. RNA-seq analysis identified insulin-like growth factor-binding protein-5 (IGFBP-5) as a downstream target of JPH203. JPH203 inhibited phosphorylation of MAPK / Erk, AKT, p70S6K and 4EBP-1. Multivariate analysis revealed that high LAT1 expression was found as an independent prognostic factor for overall survival (HR3.46 P = 0.0204). Patients with high LAT1 and IGFBP-5 expression had significantly shorter overall survival periods than those with low expression (P = 0.0005). High LAT1 was related to the high Grade, pathological T stage, LDH, and NLR. Collectively, LAT1 significantly contributed to bladder cancer progression. Targeting LAT1 by JPH203 may represent a novel therapeutic option in bladder cancer treatment.

Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer.

Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied. The relationships between progression-free survival (PFS), overall survival (OS), and clinical factors were studied by Cox proportional hazard and Kaplan-Meier models. In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, p = 0.0032) remained an independent prognostic factor for PFS. In the Enza group, TST ≥ 13 ng/dL (median) was found to be a significant prognostic factor (HR 0.28, p = 0.0044), while, in the Abi group, TST ≥ 12 ng/dL (median) was not significant (HR 0.40, p = 0.0891). TST showed significant correlation with PFS periods (r = 0. 32, p = 0.0067), whereas, for OS, TST ≥ 13 ng/dL (median) showed no significant difference in the Abi and Enza groups overall. According to Kaplan-Meier analysis, a longer PFS at first-line therapy showed a favorable prognosis in the Enza group (p = 0.0429), while no difference was observed in the Abi group (p = 0.6051). The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients.

Biparametric Prostate Imaging Reporting and Data System version2 and International Society of Urological Pathology Grade Predict Biochemical Recurrence after Radical Prostatectomy.

BACKGROUND: We retrospectively assessed the clinical significance of the Prostate Imaging Reporting and Data System (PI-RADS), version 2, criteria based on biparametric magnetic resonance imaging (bp-MRI), together with the International Society of Urological Pathology (ISUP) grade, for predicting biochemical recurrence (BCR) after radical prostatectomy. MATERIALS AND METHODS: The data from 126 patients who had undergone radical prostatectomy were retrospectively analyzed. The prognostic significance of the PI-RADS v2 score based on bp-MRI was assessed with other clinical factors, including the ISUP grade. We defined a positive PI-RADS and ISUP score as ≥ 4 and ≥ 3, respectively. Statistical analysis was performed using Cox proportional hazard models, logistic regression analysis, and the Kaplan-Meier method. RESULTS: The median age and median prostate-specific antigen level were 66 years and 7.96 ng/mL, respectively. The number of positive PI-RADS scores was 106 (84.1%) and the number of positive ISUP grade scores was 71 (56.3%). PI-RADS ≥ 4 (P = .0031) and ISUP ≥ 3 (P = .070) were the 2 independent prognostic factors predictive of BCR. A positive PI-RADS score was related to tumor volume (P = .014), and a positive ISUP score was related to prostate-specific antigen level (P = .043), extraprostatic extension (P = .029), and Gleason upgrading (P < .0001). After stratifying patients into risk groups according to PI-RADS and ISUP positivity, the poor-risk group (PI-RADS and ISUP grade positive) showed significantly worse BCR-free survival compared with that of the favorable- and intermediate-risk groups (P < .0001), with a median survival difference of 21 months. CONCLUSION: Biparametric PI-RADS v2 and ISUP grade criteria predicted for BCR after radical prostatectomy. PI-RADS v2 combined with the ISUP grade might be helpful in choosing the treatment modality of patients with localized prostate cancer.

Apparent diffusion coefficient value for estimating clinicohistological factors in bladder cancer including infiltration style and lymphatic invasion.

OBJECTIVE: To evaluate a role of apparent diffusion coefficient (ADC) values measured from diffusion-weighted imaging we investigated its association with clinicopathological tumor characteristics of bladder cancer. MATERIALS AND METHODS: Diffusion-weighted MRI at 1.5 Tesla using b-values of 0, 1000 s/mm(2) was taken before transurethral resection by 114 bladder urothelial tumor patients. ADC value was measured and its relationship with pathological factors including T stage, tumor grade, infiltration style (INF) and lymphatic invasion (ly) was analyzed. RESULTS: Median ADC value was significantly lower in Grade 3 than in Grade 1 (P < 0.001) or in Grade 2 (P = 0.002), in INFb than in INFa (P = 0.004), in INFc than in INFa (P < 0.001), in ly1 than in ly0 (P < 0.001) and lower in T2≦ than in T1≧ (P < 0.001), respectively. Receiver operating curve demonstrated the accuracy of detecting muscle invasive bladder cancer or ly+ by using area under curve (AUC), showing 0.758 and 0.748. CONCLUSION: ADC value is likely to serve as a useful biomarker showing clinicopathological characterictics of bladder cancer.

[An infected renal cyst communicating with the urinary tract: a case report].

A 36-year-old man presented with fever and right backache. Abdominal computed tomographic scan revealed a right renal cyst, with a maximum diameter of 12 cm, and surrounded by a hyperdense area of perirenal fat tissue. The cyst appeared to be infected. Accordingly, we performed a percutaneous puncture of this cyst, and drained the fluid. The brown and cloudy fluid gradually became clear, the fluid volume increased a few days after the drainage. A communication between the infected cyst and urinary tract was suspected ; retrograde pyelography confirmed the presence of fistulas. The urine was drained, ＞ 600 ml per day, for four weeks. Surgical resection of the cyst wall and closure of the fistulas were performed as an additional treatment. A year after the open surgical procedure, the renal cyst did not recur, and his renal function has been normal.

[Clinical impact of peripheral lymphocyte counts for metastatic urothelial carcinoma patients treated with chemotherapy].

Pre-chemotherapeutic factors to assess the prognosis of patients with advanced urothelial carcinoma have not yet been completely established. The immune response of the host to the tumor is lymphocyte dependent. However, the effect of lymphocytes on chemotherapy prognosis is unknown. In this study, we investigated the correlation between pre-chemotherapeutic lymphocyte counts and the clinical characteristics of urothelial carcinoma and determined the effectiveness of lymphocytes as a prognostic predictor for metastatic urothelial carcinoma treated with chemotherapy. Between April 2003 and March 2011, data from 34 patients with unresectable or metastatic urothelial carcinoma were retrospectively subjected to multivariate regression analysis to determine the patient characteristics with independent prognostic significance for survival. The median patient age was 71 ; 21 patients were male and 13 female. The number of primary tumors in the pelvis, ureter, and bladder were four, six, and 24, respectively. Seventeen patients underwent prior curative resections, and visceral metastases at chemotherapy were detected in 14 patients. The median lymphocyte count at chemotherapy was 1,292/ml. Cancer-specific survival was significantly lower in patients with lymphocyte counts ＜1,000/ml than in patients with lymphocyte counts ≥1,000/µl (p＝0. 001). During multivariate analysis, visceral metastasis and lymphocyte counts were independent factors for predicting poor prognosis. In addition, lymphocyte counts of ＜1, 000/ml or positive visceral metastases also affected survival. This information may be useful for identifying patients who are likely to benefit from chemotherapy.

[Treatment outcome of intrarenal Bacillus Calmette-Guerin therapy for carcinoma in situ of the upper urinary tract].

We investigated the long-term efficacy and safety of intrarenal bacillus Calmette-Guerin (BCG) therapy for carcinoma in situ (CIS) of the upper urinary tract. We retrospectively reviewed the medical records of 9 patients who underwent BCG perfusion therapy for CIS of the upper urinary tract from January 2005 to December 2011 at our institute. All patients were treated by retrograde catheterization using a 6 Fr double- J ureteric stent. BCG at half the dose (40.5 mg or 40 mg) in 40ml saline was instilled into the bladder weekly for 6 or 8 weeks as one course. The mean follow-up period was 32.7 months (range 4-75 months). In all patients (100%), cytology became negative after one course of BCG perfusion and 8 patients (88. 9%) remained disease-free for a median follow-up of 35.1 months. Among these 9 patients, 1 patient showed recurrence after 6 months of the first BCG therapy. The patient received a second course of BCG therapy, but the patient developed invasive tumor and distant metastases. Two patients could not continue the treatment due to pyelonephritis. In conclusion, although longer follow up and further experience with treatment for CIS of the upper urinary tract are required, this treatment is considered to be effective and safe.

Spinal nephroblastoma in a miniature Dachshund.

A 2-year-old castrated miniature Dachshund dog was presented to the Rakuno Gakuen Veterinary Teaching Hospital for diagnosis of progressive hindlimb paresis and ataxia. There was no thoracolumbar intervertebral disk hernia and magnetic resonance imaging revealed an intramedullary spinal cord lesion at the ninth and tenth thoracic vertebrae. Following surgical excision of the neoplasm, there was minor amelioration of neurological signs, but forelimb function was not recovered. The extracted tumor was histopathlogically diagnosed as spinal nephroblastoma.