Prediction of pathological up-staging after radical nephroureterectomy in patients with upper tract urothelial carcinoma.

PURPOSE: The diagnostic accuracy of computed tomography urography for upper tract urothelial carcinoma is high; however, difficulties are associated with precisely assessing the T stage. Preoperative tumor staging has an impact on treatment options for upper tract urothelial carcinoma. We herein attempted to identify preoperative factors that predict pathological tumor up-staging, which will facilitate the selection of treatment strategies. MATERIALS AND METHODS: We retrospectively identified 148 patients with upper tract urothelial carcinoma who underwent computed tomography urography preoperatively followed by radical nephroureterectomy without preoperative chemotherapy at our institution between 2000 and 2021. Preoperative factors associated with cT2 or lower to pT3 up-staging were examined using a multivariate logistic regression analysis. RESULTS: Ninety out of 148 patients were diagnosed with cT2 or lower, and 22 (24%) were up-staged to pT3. A multivariate analysis identified a positive voided urine cytology (HR 4.69, p = 0.023) and tumor length ≥ 3 cm (HR 6.33, p = 0.003) as independent predictors of pathological tumor up-staging. CONCLUSIONS: Patients diagnosed with cT2 or lower, but with preoperative positive voided urine cytology and/or tumor diameter ≥ 3 cm need to be considered for treatment as cT3.

Anemia in patients ≥ 75 years with metastatic clear cell renal cell carcinoma: an important poor prognostic factor in the international metastatic renal cell carcinoma database consortium model.

BACKGROUND: Due to an increase in life expectancy, the incidence of metastatic renal cell carcinoma (mRCC) in patients aged ≥75 years has been increasing. In this study we investigated the characteristics before treatment and the outcomes of systemic therapies for patients aged ≥75 years with mRCC and compared the results with those for patients aged < 75 years in order to determine whether differences in age influenced survival. METHODS: A total of 206 consecutive Japanese patients with mRCC, including 47 patients aged ≥75 years, who received systemic therapy were included. Clinical data from medical records were retrieved and analyzed retrospectively. Survival analyses were determined using a Kaplan-Meier method, and analyzed with a log-rank test. RESULTS: Elderly patients categorized as favorable risk group based on the International Metastatic RCC Database Consortium (IMDC) stratification system were significantly lower. Among IMDC risk factors, the rate of anemia was significantly higher in elderly patients. No statistically significant benefit in progression free survival for first and second line treatment was observed, whereas improvements in overall survival as well as cancer specific survival were seen in patients aged < 75 years. CONCLUSIONS: For mRCC patients aged ≥75 years, a higher proportion of base line anemia, which resulted in higher rates of IMDC intermediate/poor risk, would be responsible for shorter OS/CSS. Furthermore, mRCC patients aged ≥75 years tend to receive BSC instead of second line active treatment. Overcoming under-treatment in elderly patients might help to prolong survival in mRCC.

Risk factors for postoperative fever after laparoscopic adrenalectomy focusing on hormones produced: a case control study.

BACKGROUND: Laparoscopic adrenalectomy is widely performed for a number of hormone-producing tumors and postoperative management depends on the hormones produced. In the present study, we conducted a retrospective analysis to clarify the risk factors for postoperative complications, particularly postoperative fever after laparoscopic adrenalectomy. METHODS: We analyzed 406 patients who underwent laparoscopic adrenalectomy at our hospital between 2003 and 2019. Postoperative fever was defined as a fever of 38 °C or higher within 72 h after surgery. We investigated the risk factors for postoperative fever after laparoscopic adrenalectomy. RESULTS: There were 188 males (46%) and 218 females (54%) with a median age of 52 years. Among these patients, tumor pathologies included 188 primary aldosteronism (46%), 75 Cushing syndrome (18%), and 80 pheochromocytoma (20%). Postoperative fever developed in 124 of all patients (31%), 30% of those with primary aldosteronism, 53% of those with pheochromocytoma, and 8% of those with Cushing syndrome. A multivariate logistic regression analysis identified pheochromocytoma and non-Cushing syndrome as independent predictors of postoperative fever. Postoperative fever was observed in 42 out of 80 cases of pheochromocytoma (53%), which was significantly higher than in cases of non-pheochromocytoma (82/326, 25%, p < 0.01). In contrast, postoperative fever developed in 6 out of 75 cases of Cushing syndrome (8%), which was significantly lower than in cases of non-Cushing syndrome (118/331, 35.6%, p < 0.01). CONCLUSION: Since postoperative fever after laparoscopic adrenalectomy is markedly affected by the hormone produced by pheochromocytoma and Cushing syndrome, it is important to carefully consider the need for treatment.

Appropriate definition of non-metastatic castration-resistant prostate cancer (nmCRPC) and optimal timing of androgen receptor signaling inhibitor (ARSI).

BACKGROUND: Defined by rising PSA levels under androgen deprivation therapy (ADT) despite no visible metastases on conventional imaging, non-metastatic castration-resistant prostate cancer (nmCRPC) represents a complex clinical challenge. A significant subset of these patients rapidly develops metastatic disease, negatively impacting survival. We examined the difference in prognosis of nmCRPC patients according to the timing of therapeutic interventions with androgen receptor signaling inhibitor (ARSI). METHODS: We examined 102 nmCRPC patients treated with ARSI. We divided patients according to their PSA levels when ARSI was administered: Cohort A (PSA 0.5-2.0 ng/mL), Cohort B (PSA 2.0-4.0 ng/mL), and Cohort C (PSA > 4.0 ng/mL). Utilizing the Kaplan-Meier method for survival analysis, our analytical starting point was the moment when PSA levels exceeded 0.5 ng/mL post-ADT nadir, ensuring a fair comparison and minimizing lead-time bias. RESULTS: After excluding 5 patients whose PSA nadir after ADT > 0.5 ng/mL, patient distribution across Cohort A, Cohort B, and Cohort C was 32, 24, and 41 patients, respectively. Kaplan-Meier survival analysis highlighted a 2-year metastasis-free survival rate of 97% for Cohort A, 87% for Cohort B, and 73% for Cohort C. A marked statistical difference emerged when comparing Cohort A with Cohorts B and C, with a p-value of 0.043. CONCLUSION: The timely initiation of ARSI is paramount in nmCRPC management. Our findings strongly advocate for consideration of ARSI administration in nmCRPC patients before their PSA levels exceed 2.0 ng/mL. Our results indicated a PSA threshold of 1.0 ng/mL for nmCRPC definition which is more reasonable to administer ARSI without delay.

Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy.

PURPOSE: Prostate-specific antigen (PSA) is thought to be undetectable (< 0.1 ng/mL) after radical prostatectomy (RP), and persistent PSA (≥ 0.1 ng/mL) is considered a failure of curative treatment. MATERIALS AND METHODS: The study population consisted of 135 patients, all of whom underwent RP for localized prostate cancer, and developed persistent PSA. We set the starting point at the timing of RP, and the endpoints were the development of castration-resistant prostate cancer (CRPC) and cancer-specific survival. RESULTS: Salvage radiation therapy (RT) and androgen deprivation therapy (ADT) were performed in 53 (39.3%) and 64 (47.4%) patients, respectively. Eighteen (13.3%) patients didn't receive any salvage treatment. During the median follow-up of 10.1 years, CRPC was observed in 23 patients, and 6 patients died due to prostate cancer. Kaplan-Meier curves demonstrated the 15-year CRPC-free and cancer-specific survivals were 79.5% and 92.7%, respectively. Cox multivariate analysis demonstrated that seminal vesicle invasion (SVI) (p = 0.007) and nadir PSA ≥1.0 ng/mL (p = 0.002) were independent risk factors for CRPC. Salvage RT demonstrated better cancer control (the 10-and 15-year CRPC-free survival was 94.1% and 94.1%) compared to ADT (75.9% and 58.5%, p = 0.017) after 1:1 propensity score matching. CONCLUSIONS: SVI and nadir PSA ≥1.0 ng/mL are independent risk factors for CRPC in patients with persistent PSA after RP. Salvage RT is considered to be the optimal treatment for this condition.

Factors affecting the selection of eligible candidates for focal therapy for prostate cancer.

PURPOSE: Focal therapy (FT) is a treatment modality for prostate cancer that aims to reduce side effects. However, it remains difficult to select eligible candidates. We herein examined eligibility factors for hemi-ablative FT for prostate cancer. METHODS: We identified 412 patients who were diagnosed with unilateral prostate cancer by biopsy and had undergone radical prostatectomy between 2009 and 2018. Among these patients, 111 underwent MRI before biopsy, had 10-20 core biopsies performed, and did not receive other treatments before surgery. Fifty-seven patients with prostate-specific antigen ≥ 15 ng/mL and biopsy Gleason score (GS) ≥ 4 + 3 were excluded. The remaining 54 patients were evaluated. Both lobes of the prostate were scored using Prostate Imaging Reporting and Data System version 2 on MRI. Ineligible patients for FT were defined as those with ≥ 0.5 mL GS6 or GS ≥ 3 + 4 in the biopsy-negative lobe, ≥ pT3, or lymph node involvement. Selected predictors of eligibility for hemi-ablative FT were analyzed. RESULTS: Among our cohort of 54 patients, 29 (53.7%) were eligible for hemi-ablative FT. A multivariate analysis identified a PI-RADS score < 3 in the biopsy-negative lobe (p = 0.016) as an independent predictor of eligibility for FT. Thirteen out of 25 ineligible patients had GS ≥ 3 + 4 tumors in the biopsy-negative lobe, half of whom (6/13) also had a PI-RADS score < 3 in the biopsy-negative lobe. CONCLUSION: The PI-RADS score in the biopsy-negative lobe may be important in the selection of eligible candidates for FT. The findings of this study will help reduce missed significant prostate cancers and improve FT outcomes.

Strategy for PSA progression in patients undergoing salvage radiation for biochemical recurrence after radical prostatectomy.

BACKGROUND: The treatment strategy for prostate-specific antigen (PSA) progression in patients who receive salvage radiation therapy (RT) for biochemical recurrence (BCR) after radical prostatectomy (RP) is salvage androgen deprivation therapy (ADT). However, its optimal timing is highly controversial. METHODS: The study sample consisted of 77 men who underwent RP, received salvage RT against BCR, and underwent salvage ADT for PSA progression. The endpoint of this study was development to castration-resistant prostate cancer (CRPC), from the start of salvage RT. RESULTS: The median follow-up time was 9.5 years, and 20 patients experienced CRPC. The multivariable analysis identified PSA-doubling time (PSA-DT) ≤ 12 months (hazard ratio, 3.5) and seminal vesicle invasion (SVI) (hazard ratio, 4.4) as independent risk factors. We defined the high-risk and low-risk groups as those with one or two risk factors and no risk factors, respectively. In the high-risk group, a significant difference in time to CRPC was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 8) and at > 1.0 ng/mL (n = 27) (10-year non-CRPC rate: 100.0% vs. 46.3%, respectively). In contrast, in the low-risk group, no significant difference in CRPC-free survival was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 14) and at > 1.0 ng/mL (n = 28) (10-year non-CRPC rate: 86.4% vs. 80.8%, respectively). CONCLUSION: In high-risk patients (PSA-DT ≤ 12 months and/or SVI), salvage ADT for PSA progression after salvage RT should be started before the PSA levels exceed 1.0 ng/mL.

Androgen deprivation therapy duration is significantly associated with Testosterone recovery in Japanese patients with prostate cancer.

OBJECTIVE: Due to the fear generated by COVID-19 in Spring 2020, many patients postponed their scheduled outpatient visits. To differentiate those patients with prostate cancer (PCa) whose androgen deprivation therapy (ADT) injection treatment can be postponed, we investigated the characteristics of testosterone (T) recovery in Japanese patients after they received combined ADT and radiation therapy (RT). METHODS: We included 81 patients with PCa treated with ADT and RT at Keio University Hospital from January 2013 to December 2018. T-recovery was defined as the time interval between the last ADT injection and 3-6 months after T-normalization. The Kaplan-Meier method was used to estimate time to T-recovery. Cox proportional hazards models identified T-recovery predictors. RESULTS: The 50% cumulative incidence of T-recovery was 7.0 months for the 6-short-term group (defined as patients having ≤6 months of ADT therapy) versus 13.0 months for the 6-long-term group (>6 months of therapy) (p < 0.001). The incidence was 7.0 months for the 12 short-term-ADT (ST) group versus 18.0 months for the 12 long-term-ADT (LT) group (p < 0.001). Multivariate analysis revealed that a shorter duration of ADT was associated with a shorter time to T-recovery (hazard ratio, 0.253; 95% CI, 0.138-0.465; p < 0.001). No other factors were significant predictors of T-recovery. CONCLUSION: Androgen deprivation therapy duration is significantly associated with T-recovery in Japanese patients with PCa. If a patient undergoes ADT for more than 6 or 12 months, it is possible to postpone their outpatient visits for 13 and 18 months, respectively.

Predictors of urinary function recovery after laparoscopic and robot-assisted radical prostatectomy.

INTRODUCTION: Even in the era of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP), we sometimes encounter patients with severe urinary incontinence after surgery. The aim of the present study was to identify predictors of urinary continence recovery among patients with urinary incontinence immediately after surgery (UIIAS). MATERIALS AND METHODS: We identified 274 patients with clinically localized prostate cancer who underwent LRP and RALP between 2011 and 2018. UIIAS was defined as a urine loss ratio > 0.15 on the first day of urethral catheter removal. Urinary continence recovery was defined as using ≤ 1 pad/day one year after surgery. In the present study, we evaluated factors affecting urinary function recovery one year after surgery among patients with urinary incontinence immediately after LRP and RALP. RESULTS: UIIAS was observed in 191 out of 274 patients (69.7%). A multivariate analysis identified age (<65 years, p = 0.015) as an independent predictor affecting immediate urinary continence. Among 191 incontinent patients, urinary continence one year after surgery improved in 153 (80.1%). A multivariate analysis identified age (<65 years, p = 0.003) and estimated blood loss (≥ 100 mL, p = 0.044) as independent predictors affecting urinary continence recovery one year after surgery. CONCLUSION: The present results suggest that younger patients and patients with higher intraoperative blood loss recover urinary continence one year after surgery even if they are incontinent immediately after surgery.

Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations.

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration-resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single-institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate-specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan-Meier analysis revealed that progression-free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172-34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332-483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross-resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.

Hybridisation chain reaction-based visualisation and screening for lncRNA profiles in clear-cell renal-cell carcinoma.

BACKGROUND: Analysis of long noncoding RNA (lncRNA) localisation at both the tissue and subcellular levels can provide important insights into the cell types that are important for their function. METHODS: By applying new fluorescent in situ hybridisation technique called hybridisation chain reaction (HCR), we achieved a high-throughput lncRNA visualisation and evaluation of clinical samples. RESULTS: Assessing 1728 pairs of 16 lncRNAs and clear-cell renal-cell carcinoma (ccRCC) specimens, three lncRNAs (TUG1, HOTAIR and CDKN2B-AS1) were associated with ccRCC prognosis. Furthermore, we derived a new lncRNA risk group of ccRCC prognosis by combining the expression levels of these three lncRNAs. Examining genomic alterations underlying this classification revealed prominent features of tumours that could serve as potential biomarkers for targeting lncRNAs. We then derived combination of HCR with expansion microscopy and visualised nanoscale-resolution HCR signals in cell nuclei, uncovering intracellular colocalization of three lncRNA (TUG1, HOTAIR and CDKN2B-AS1) signals such as those located intra- or out of the nucleus or nucleolus in cancer cells. CONCLUSION: LncRNAs are expected to be desirable noncoding targets for cancer diagnosis or treatments. HCR involves plural probes consisting of small DNA oligonucleotides, clinically enabling us to detect cancerous lncRNA signals simply and rapidly at a lower cost.

IMAGENE trial: multicenter, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy of niraparib with PD-1 inhibitor in solid cancer patients with homologous recombination repair genes mutation.

BACKGROUND: Previous clinical trials have demonstrated the potential efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis) in patients with cancer involving homologous recombination repair (HRR) gene-mutation. Moreover, HRR gene-mutated cancers are effectively treated with immune checkpoint inhibitors (ICIs) with the increase in tumor mutation burden. We have proposed to conduct a multicenter, single-arm phase II trial (IMAGENE trial) for evaluating the efficacy and safety of niraparib (PARPi) plus programmed cell death-1 inhibitor combination therapy in patients with HRR gene-mutated cancers who are refractory to ICIs therapy using a next generation sequencing-based circulating tumor DNA (ctDNA) and tumor tissue analysis. METHODS: Key eligibility criteria for this trial includes HRR gene-mutated tumor determined by any cancer gene tests; progression after previous ICI treatment; and Eastern Cooperative Oncology Group Performance Status ≤ 1. The primary endpoint is the confirmed objective response rate (ORR) in all patients. The secondary endpoints include the confirmed ORR in patients with HRR gene-mutation of ctDNA using the Caris Assure (CARIS, USA). The target sample size of the IMAGENE trial is 57 patients. Biomarker analyses will be performed in parallel using the Caris Assure, proteome analysis, and T cell repertoire analysis to reveal tumor immunosurveillance in peripheral blood. EXPECTED OUTCOME: Our trial aims to confirm the clinical benefit of PARPi plus ICI combination therapy in ICI-resistant patients. Furthermore, through translational research, our trial will shed light on which patients would benefit from the targeted combination therapy for patients with HRR gene-mutated tumor even after the failure of ICIs. TRIAL REGISTRATION: The IMAGENE trial: jRCT, Clinical trial no.: jRCT2051210120, Registered date: November 9, 2021.

A low subcutaneous fat mass is a risk factor for the development of inguinal hernia after radical prostatectomy.

PURPOSE: Inguinal hernia (IH) after radical prostatectomy (RP) is a complication that impairs quality of life; however, the factors contributing to IH after RP remain unclear. Therefore, we herein attempted to identify the factors responsible for the development of IH after RP. METHODS: We reviewed 622 patients who underwent laparoscopic or robot-assisted laparoscopic RP at our hospital between December 2011 and April 2020. The total fat area and visceral fat area were calculated at the level of the umbilicus using computed tomography, and the subcutaneous fat area (SFA) was calculated by subtracting the visceral fat area from the total fat area. The psoas muscle area was measured at the third lumbar vertebrae level using computed tomography to calculate the psoas muscle mass index, which is used in sarcopenia as an index of muscle mass. We investigated the risk factors for IH after laparoscopic or robot-assisted laparoscopic RP. RESULTS: IH developed in 88 patients (16.7%). Fifty-seven of these patients underwent hernia repair at our hospital, and 56 (98.2%) had indirect hernias. A multivariate analysis identified SFA (odds ratios: 0.383, p < 0.001) as an independent predictor for the development of IH. Two-year IH-free survival rates were 77.3% in the small SFA group (SFA < 123 cm2) and 88.7% in the large SFA group (SFA ≥ 123 cm2) (p < 0.001). CONCLUSION: Subcutaneous fat was associated with the development of IH, particularly indirect IH, after laparoscopic or robot-assisted laparoscopic RP. An indirect IH prevention technique needs to be considered, particularly for patients with less subcutaneous fat.

Characterizing cyclin-dependent kinase 12(CDK12)-altered aggressive prostate cancer: a twelve-case series.

BACKGROUND: Prostate cancer harboring cyclin-dependent kinase 12 (CDK12) abnormalities is a hot topic due to its distinctive clinical features, such as sensitivity to immune checkpoint inhibitors. In the last few years, precision medicine using comprehensive genome sequencing has become familiar, and the era of precision oncology has arrived in the field of prostate cancer. This study aimed to present the demographic characteristics of patients with CDK12 alterations. METHODS: In 12 patients with detected CDK12 alterations in our hospital between 2015 and 2021, we evaluated their genomic features and clinical course. CDK12 allelic status was classified into three groups: monoallelic loss, potentially biallelic loss, and biallelic loss based on the genome analyses. RESULTS: Seven patients already had metastatic cancer at the time of diagnosis, and all 12 patients had Gleason grade ≥ 4. Most cases of biallelic loss or potentially biallelic loss were metastatic cancers at the initial staging, and all these cases were categorized into Gleason grade 5. Two of the 12 patients had BRCA2/RB1 co-loss, and the other two had whole genome duplication. Five patients had a long-term survival of > 6 years, but two patients died within 4 years of diagnosis. CONCLUSION: This is the first Japanese prostate cancer case series with CDK12 alterations. CDK12-altered prostate cancer is a heterogeneous disease, and accumulating cases with detailed information leads to precision oncology.

Predictors of Survival in Favorable Risk Patients with Metastatic Renal Cell Carcinoma Treated with a Single-Agent First-Line Therapy.

INTRODUCTION: The aim of this retrospective study was to elucidate predictors of survival in metastatic renal cell carcinoma (mRCC) patients in an International Metastatic Renal Cell Carcinoma Database Consortium favorable risk group treated with frontline therapy without immune checkpoint inhibitors. METHODS: A total of 238 patients with mRCC were reviewed. Among them, 55 patients in favorable risk group treated with single-agent systemic therapy were retrospectively analyzed. Clinical and pathological data were retrieved and analyzed retrospectively. The prognostic effect of each marker on overall survival (OS) was investigated with univariate and multivariate Cox's proportional hazards regression models. RESULTS: After a median follow-up of 46.2 months after first-line treatment initiation, the median progression-free survival (PFS) was 29.3 months, and the median OS has not been reached. The estimated percentage of patients who were alive at 12 and 24 months were 96.1 and 94.1%, respectively. Multivariate analysis revealed that the long-term duration of first-line treatment (hazard ratio [HR]: 0.972, 95% confidence interval [CI]: 0.944-0.997, p = 0.0299) and the metastases limited to lung (HR: 3.852, 95% CI: 1.080-24.502, p = 0.0361) were independent predictors for longer OS in favorable risk mRCC patients. CONCLUSION: First-line systemic therapy for favorable risk mRCC patients with a single agent resulted in relatively longer PFS and OS. A longer duration of first-line treatment and lung only metastases are correlated with longer OS.

Predictors of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome.

PURPOSE: The postoperative course of renal function remains unclear in Cushing syndrome. We examined changes in renal function after adrenalectomy in patients with Cushing syndrome and attempted to identify predictors of renal impairment. METHODS: The study population comprised 76 patients who underwent adrenalectomy for Cushing and subclinical Cushing syndrome between 2001 and 2018. Renal function and other factors were evaluated pre-operation, at 1 postoperative month, and 1 postoperative year. We defined a ≥10% decrease in the estimated glomerular filtration rate at 1 postoperative year as renal impairment, and predictors associated with this reduction were investigated. The relationship between renal function and steroid replacement after surgery was also examined. RESULTS: Mean pre-operative estimated glomerular filtration rate was 82.2 ml/min/1.73 m2 . While mean estimated glomerular filtration rate was significantly lower at 1 postoperative month than the pre-operative value (71.7 ml/min/1.73 m2 [89.1%], p < 0.001), no significant differences were observed between 1 postoperative year and pre-operation (79.5 ml/min/1.73 m2 [97.6%], p = 0.108). Twenty-six patients (34.2%) developed renal impairment. A multivariate analysis identified a low pre-operative adrenocorticotropic hormone level as an independent predictor of renal impairment (odds ratio 6.30, p = 0.031). Among 43 patients with available records of steroid replacement history, 18 (41.9%) developed renal impairment. The ratio of patients with a reduced steroid replacement dose at 1 postoperative month was significantly lower among patients with renal impairment than those without (22.2% vs. 56.0%, p = 0.027). CONCLUSIONS: The pre-operative adrenocorticotropic hormone level was a predictor of renal function after adrenalectomy in patients with Cushing or subclinical Cushing syndrome.

Profiling the Biological Characteristics and Transitions through Upper Tract Tumor Origin, Bladder Recurrence, and Muscle-Invasive Bladder Progression in Upper Tract Urothelial Carcinoma.

To evaluate biological characteristics and transitions of upper tract urothelial carcinoma (UTUC) through metachronous bladder tumors after radical nephroureterectomy (RNU), we conducted immunohistochemical (IHC) staining of tumor specimens of UTUC tumor origin, non-muscle-invasive bladder cancer (NMIBC) and MIBC progressed after intravesical recurrence (IVR), and bladder primary MIBC. Fibroblast growth factor receptor 3 (FGFR3), p53, cytokeratin 5/6 (CK5/6), and CK20 were stained to examine expression rates. After expression assessment with heatmap clustering, the overexpression of four biomarkers from UTUC origin to metachronous MIBC progression was analyzed with clinicopathological variables. We found that high CK20 and low CK5/6 expression were both observed in UTUC tumor origin and subsequent NMIBC after RNU. By investigating molecular expression in the IVR specimen, we observed that low pT stage bladder recurrence occupied the majority of CK20 high CK5/6 low expression, but would change to CK20 low CK5/6 high expression as it progressed to MIBC. UTUC metachronous MIBC has different characteristics compared with bladder primary MIBC, which comprises favorable biological features such as high FGFR3 expression, and follows favorable prognosis compared to those without FGFR3 expression. The present study demonstrated that the biological characteristics of UTUC tumor origin shifts from luminal to basal-like features with progression to MIBC, but FGFR3 expression taken over from UTUC origin may comprise a favorable entity compared to primary MIBC.

Landscape of prognostic signatures and immunogenomics of the AXL/GAS6 axis in renal cell carcinoma.

BACKGROUND: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. METHODS: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. RESULTS: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. CONCLUSION: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

Grading of Multifocal Prostate Cancer Cases in which the Largest Volume and the Highest Grade Do Not Coincide within One Lesion.

PURPOSE: In general, the index lesion of prostate cancer has the largest tumor volume, the highest Grade Group (GG), and the highest stage (concordant cases). However, these factors sometimes do not coincide within one lesion (discordant cases). In such discordant cases, the largest tumor may not be of biological significance and the secondary tumor may more greatly impact the prognosis. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent radical prostatectomy, and we identified 580 (85.3%) concordant cases and 100 (14.7%) discordant cases. The end point of this study was biochemical recurrence, and median followup was 4.2 years. RESULTS: Among discordant cases in which GGs of the largest tumor and the highest GG tumor differed, the majority (67 patients) had the largest tumor of GG 2, and we set them as the study cohort. On the other hand, we regarded 212 concordant cases with an index tumor of GG 2 as the control cohort. The study cohort comprised 48 (71.6%) patients with a secondary tumor of GG 3 and 19 (28.4%) with a secondary tumor of GG 4/5. Kaplan-Meier curves revealed that the 5-year biochemical recurrence-free survival rates were 76%, and 67%, respectively. The 5-year biochemical recurrence-free survival rate of the control cohort was 91%, which was significantly better than that of the study cohort (p=0.013 and p=0.014, respectively). CONCLUSIONS: Our study suggests that the prognosis of discordant cases is better determined by the secondary cancer lesion with the highest GG instead of the largest lesion.

Risk factors for haemodynamic instability and its prolongation during laparoscopic adrenalectomy for pheochromocytoma.

OBJECTIVE: Pheochromocytoma is a rare neuroendocrine tumour that secretes catecholamines and originates in the adrenal gland. Although surgical resection is the only curative therapy for pheochromocytoma, it is associated with a risk of haemodynamic instability (HDI), such as extremely high blood pressure and/or post tumour removal hypotension and shock. We investigated the risk factors for HDI during pheochromocytoma surgery. DESIGN AND PATIENTS: Eighty-two patients who underwent laparoscopic adrenalectomy for pheochromocytoma between July 2002 and February 2020 were examined. We excluded 3 patients with bilateral disease and 11 without detailed 24 h urinary data. We defined HDI as systolic blood pressure ≥ 200 or <80 mmHg. We investigated the risk factors for HDI during laparoscopic adrenalectomy for pheochromocytoma. RESULTS: There were 29 males and 39 females with a median age of 50.5 years. Tumours were localised on the right adrenal gland in 28 patients and on the left in 40. The median tumour diameter was 37.5 mm and the median pneumoperitoneum time was 93.5 min. Twenty-five out of sixty-eight patients (37%) developed HDI. A multivariate analysis identified diabetes mellitus (DM; odds ratio: 3.834; 95% confidence interval: 1.062-13.83; p = .04) as an independent predictor of HDI. In terms of hormonal data, median 24 h urinary epinephrine levels (p = .04) and metanephrine levels (p = .01) were significantly higher in the HDI group. DM was also considered as a risk factor for prolonged HDI (p = .02). CONCLUSION: Surgeons and anaesthesiologists need to be aware of the risk of HDI and its prolongation during laparoscopic adrenalectomy for pheochromocytoma for DM patients.