Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry.

BACKGROUND: To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). PATIENTS AND METHODS: We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. RESULTS: Total 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). CONCLUSION: Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.

Stepwise algorithm using computed tomography and magnetic resonance imaging for differential diagnosis of fat-poor angiomyolipoma in small renal masses: A prospective validation study.

OBJECTIVES: To validate the diagnostic accuracy of a stepwise algorithm to differentiate fat-poor angiomyolipoma (fp-AML) from renal cancer in small renal masses (SRMs). METHODS: We prospectively enrolled 223 patients with solid renal masses <4 cm and no visible fat on unenhanced computed tomography (CT). Patients were assessed using an algorithm that utilized the dynamic CT and MRI findings in a stepwise manner. The diagnostic accuracy of the algorithm was evaluated in patients whose histology was confirmed through surgery or biopsy. The clinical course of the patients was further analyzed. RESULTS: The algorithm classified 151 (68%)/42 (19%)/30 (13%) patients into low/intermediate/high AML probability groups, respectively. Pathological diagnosis was made for 183 patients, including 10 (5.5%) with fp-AML. Of these, 135 (74%)/36 (20%)/12 (6.6%) were classified into the low/intermediate/high AML probability groups, and each group included 1 (0.7%)/3 (8.3%)/6 (50%) fp-AMLs, respectively, leading to the area under the curve for predicting AML of 0.889. Surgery was commonly opted in the low and intermediate AML probability groups (84% and 64%, respectively) for initial management, while surveillance was selected in the high AML probability group (63%). During the 56-month follow-up, 36 (82%) of 44 patients initially surveyed, including 13 of 18 (72%), 6 of 7 (86%), and 17 of 19 (89%) in the low/intermediate/high AML probability groups, respectively, continued surveillance without any progression. CONCLUSIONS: This study confirmed the high diagnostic accuracy for differentiating fp-AMLs. These findings may help in the management of patients with SRMs.

Simple and Practical Method for the Quantitative High-Sensitivity Analysis of N-Nitroso Duloxetine in Duloxetine Drug Products Utilizing LC-MS/MS.

The high-sensitivity analytical method for the determination of N-nitroso duloxetine (NDXT), which can be carcinogenic and harmful in duloxetine drug products, was successfully developed utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tandem mass spectrometric detection at positive electrospray ionization in multiple reaction monitoring (MRM) mode was then employed for the determination of NDXT. The quantitative range for NDXT was found in 0.075-3.75 ng/mL in terms of concentration in the dilution solvent for duloxetine active pharmaceutical ingredient (API) and capsules and 0.075-1.875 ng/mL for duloxetine tablets, and the recovery rates were in the range of 82.5-91.6% for the API, 91.0-113.4% for capsules, and 70.6-109.1% for tablets, respectively. The repeatability was 6.9% with a %RSD of n = 9 for the API, 10.9% with a %RSD of n = 9 for capsules, and 21.6% with a %RSD of n = 9 for tablets, respectively. For reproducibility, the %RSD of the n = 6 measurements between the two sites was 3.5%. The calibration curve of NDXT in the concentration range of 0.075-3.75 ng/mL was carried out, and the correlation coefficient (R) was found to be 1.000. The sample solution was stable for 7 days. The applicability of the determination of the content of NDXT in a variety of duloxetine drug products was demonstrated. This manuscript seeks to aid the risk assessment process of NDXT in duloxetine drug products through providing a fast and reliable quantitative LC-MS/MS analytical method.

Utility of positive core number on MRI-ultrasound fusion targeted biopsy in combination with PI-RADS scores for predicting unexpected extracapsular extension of clinically localized prostate cancer.

OBJECTIVES: To evaluate the utility of magnetic resonance imaging (MRI) and MRI-ultrasound fusion targeted biopsy (TB) for predicting unexpected extracapsular extension (ECE) in clinically localized prostate cancer (CLPC). METHODS: This study enrolled 89 prostate cancer patients with one or more lesions showing a Prostate Imaging-Reporting and Data System (PI-RADS) score ≥3 but without morphological abnormality in the prostatic capsule on pre-biopsy MRI. All patients underwent TB and systematic biopsy followed by radical prostatectomy (RP). Each lesion was examined by 3-core TB, taking cores from each third of the lesion. The preoperative variables predictive of ECE were explored by referring to RP specimens in the lesion-based analysis. RESULTS: Overall, 186 lesions, including 81 (43.5%), 73 (39.2%), and 32 (17.2%) with PI-RADS 3, 4, and 5, respectively, were analyzed. One hundred and twenty-two lesions (65.6%) were diagnosed as cancer on TB, and ECE was identified in 33 (17.7%) on the RP specimens. The positive TB core number was ≤2 in 129 lesions (69.4%) and three in 57 lesions (30.6%). On the multivariate analysis, PI-RADS ≥4 (p = 0.049, odds ratio [OR] = 2.39) and three positive cores on TB (p = 0.005, OR = 3.07) were independent predictors of ECE. Lesions with PI-RADS ≥4 and a positive TB core number of 3 had a significantly higher rate of ECE than those with PI-RADS 3 and a positive TB core number ≤2 (37.5% vs. 7.8%, p < 0.001). CONCLUSIONS: Positive TB core number in combination with PI-RADS scores is helpful to predict unexpected ECE in CLPC.

Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

OBJECTIVE: To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). METHODS: We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. RESULTS: A total of 3,880 patients with a median follow-up of 31 (IQR 9-64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I-III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). CONCLUSION: Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes.

Neoadjuvant Chemoradiotherapy Followed by Radical Cystectomy for Muscle-Invasive Bladder Cancer: Analysis of Efficacy and Safety in 119 Patients.

INTRODUCTION: Cisplatin-based systemic chemotherapy is recommended as neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) before radical cystectomy (RC). However, clinical challenges include the possibility of primary chemoresistance and limited feasibility in patients with renal impairment. This study investigated the efficacy and safety profiles of neoadjuvant chemoradiotherapy (NCRT) followed by RC. MATERIALS AND METHODS: We retrospectively analyzed 119 patients with nonmetastatic MIBC, who were pathologically diagnosed with urothelial carcinoma and underwent NCRT before RC. The pathological response to NCRT was evaluated using RC specimens. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were compared according to pathological responses to NCRT. RESULTS: Of the 119 patients, 111 (93%) underwent RC; ypT0 and downstaging to ≤ypT1 were observed in 42 (38%) and 76 (68%) patients, respectively. In the multivariable analysis, smaller tumor size was independently associated with ypT0. During a median follow-up of 5.2 years, 28 (25%) patients developed recurrence and 22 (20%) died of bladder cancer after RC. The 5-year RFS and CSS rates were 75% and 80%, respectively. The 5-year RFS rates in patients with ypT0, ypTa/is/1, and ≥ypT2 were 87%, 87%, and 46%, respectively. Similarly, patients with ypT0 and ypTa/is/1 had more favorable CSS (90% and 87% at 5 years, respectively) than those with ≥ypT2 (60%, P = .001). None of the patients experienced ≥grade 4 adverse events related to NCRT or ≥grade 4 complications of RC. CONCLUSIONS: This study demonstrated sufficient efficacy and safety profile of NCRT followed by RC. Chemoradiotherapy may be a helpful alternative for neoadjuvant treatment before RC.

Incidence and predictors of intraoperative hypotension during transurethral bladder tumor resection with oral 5-aminolevulinic acid.

OBJECTIVES: To analyze the incidence and risk factors of intraoperative hypotension related to photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) with oral 5-aminolevulinic acid (5-ALA). METHODS: We retrospectively analyzed 487 patients with bladder tumors who underwent PDD-TURBT (n = 184) or conventional TURBT (conv-TURBT) (n = 303) between 2018 and 2021. Intraoperative hypotension was defined as hypotension requiring vasopressors during TURBT, and its incidence was compared between the two groups. Potential risk factors of intraoperative hypotension, including preoperative change in mean arterial pressure (MAP), were further investigated in patients receiving PDD-TURBT. RESULTS: The median age was 72 years, 392 patients (81%) were male, and 203 (42%) had hypertension. TURBT was performed under general and spinal anesthesia in 76 (16%) and 411 (84%) patients, respectively. The incidence of intraoperative hypotension was significantly higher in PDD-TURBT compared to conv-TURBT (43% vs. 17%, respectively). The median change in MAP until the induction of anesthesia was +6.5 mmHg (range: -29.0 to +46.3) in the PDD-TURBT group and +14.7 mmHg (range: -35.3 to +67.7) in the conv-TURBT group, showing a significantly smaller increase in the PDD-TURBT group (p < 0.001). In the multivariable analysis for PDD-TURBT patients, advanced age, general anesthesia, and lower MAP change (<+6.5 mmHg) until anesthesia induction were significantly associated with intraoperative hypotension (p = 0.0104, <0.001, and <0.001, respectively). CONCLUSIONS: Intraoperative hypotension occurred more frequently in patients who underwent PDD-TURBT than in those who underwent conv-TURBT. Using oral 5-ALA decreases preoperative blood pressure elevation and may be responsible for intraoperative hypotension.

Longitudinal deterioration in lower urinary tract symptoms after artificial urinary sphincter implantation in patients with a history of pelvic radiation therapy.

OBJECTIVES: To evaluate longitudinal changes in lower urinary tract symptoms (LUTS) after artificial urinary sphincter (AUS) implantation in patients undergoing radiation therapy (RT) in comparison to those in non-irradiated patients. METHODS: This retrospective study included 20 and 51 patients with and without a history of pelvic RT (RT and non-RT group, respectively) who were treated with primary AUS implantation for post-radical prostatectomy incontinence between 2010 and 2020. Longitudinal changes in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the International Prostate Symptom Score (IPSS), and the Overactive Bladder Symptom Score (OABSS) were calculated with a linear mixed model. RESULTS: In the RT and non-RT group, 18 (90%) and 48 (94%) patients achieved social continence, defined as daily pad use ≤1 at 1 month after activation of AUS, respectively (p = .555). During the mean follow-up of 38 months, ICIQ-SF, IPSS, and OABSS significantly improved after AUS implantation in both the RT and non-RT groups. In the RT group, ICIQ-SF, IPSS, and OABSS subsequently deteriorated with a slope of 0.62/year (p = .010), 0.55/year (p = .025), and 0.30/year (p = .007), respectively. In the non-RT group, no significant longitudinal changes in subsequent IPSS and OABSS were observed, although ICIQ-SF significantly deteriorated (0.43/year, p = .006). Comparing between the groups, the slopes of IPSS and OABSS were significantly greater in the RT group than in the non-RT group (p < .001, and .015, respectively). CONCLUSIONS: Longitudinal deterioration in LUTS that improved immediately after AUS implantation was observed in patients with a history of pelvic RT, but not in patients without a history of pelvic RT.

Incidence, risk factors, and significance of 20% decrease from new baseline estimated glomerular filtration rate after radical and partial nephrectomy within 2 years.

OBJECTIVES: To evaluate the incidence and risk factors of a 20% decrease from new baseline (NB)-estimated glomerular filtration rate (eGFR) within 2 years after radical nephrectomy (RN) and partial nephrectomy (PN) and to examine the difference in the incidence of end-stage renal disease (ESRD) with or without the 20% decrease. METHODS: This retrospective study included 238 patients undergoing RN and 369 undergoing PN for cT1a-cT3a renal cancer. The incidence of a 20% decrease from NB-eGFR within 2 years after RN/PN was examined and its potential risk factors including surgery type were assessed by multivariate logistic regression analysis. The development of ESRD was analyzed as an endpoint and its incidence was compared according to the presence or absence of the 20% decrease from NB-eGFR within 2 years. RESULTS: Overall, the 20% decrease from NB-eGFR within 2 years was observed in 37 patients (6.1%), including 10 (4.2%) and 27 (7.3%) after RN and PN, respectively (p = 0.117). Diabetes mellitus, proteinuria, and perioperative complications were shown to be independent risk factors for the 20% decrease from NB-eGFR, while surgery type was not. During the median follow-up of 65 months, the ESRD-free survival rate at 6 years was 75.5% and 99.6% in patients with and without the 20% decrease from NB-eGFR, respectively (p < 0.001), while no significant difference was observed between patients undergoing RN and PN (98.1% and 98.7%, p = 0.561). CONCLUSIONS: Because the incidence of ESRD after the 20% decrease from NB-eGFR within 2 years was as high as 24.5% at 6 years, these patients should be followed with utmost care.

Preservation of Erectile and Ejaculatory Functions After Tetramodal Bladder-Sparing Therapy Incorporating Consolidative Partial Cystectomy Against Muscle Invasive Bladder Cancer.

OBJECTIVE: To cross-sectionally assess erectile and ejaculatory functions after tetramodal bladder-sparing therapy consisting of transurethral resection, chemoradiotherapy, and consolidative partial cystectomy in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: Among 72 enrolled male patients who underwent tetramodal bladder-sparing therapy from 2006 to 2019, 42 who visited the outpatient clinic from February to October 2020 received questionnaires. Erectile function, ejaculatory function, and quality of life were assessed using the International Index of Erectile Function short form, the Male Sexual Health Questionnaire Ejaculatory Dysfunction short form, and the Functional Assessment of Cancer Therapy. RESULTS: Among the 42 patients, 9 were excluded because of incomplete responses and 33 were eligible for analyses. The median (range) age at survey and the time from treatment completion to responding to the questionnaires was 70 (50-87) years and 4.2 (0.4-14.0) years, respectively. The median International Index of Erectile Function short form-5 score was 11 (5-25), and 3 (9.1%) and 9 (27.3%) patients had no and mild erectile dysfunction, respectively. The Male Sexual Health Questionnaire Ejaculatory Dysfunction short form results showed that 23 (69.7%) patients responded that they could ejaculate. Patients with higher Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores had better erectile function and quality of life than those with lower Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores. CONCLUSION: Preservation of erectile and ejaculatory functions was demonstrated in muscle invasive bladder cancer patients treated with tetramodal bladder-sparing therapy. In addition to lower urinary tract function, preservation of male sexual function, especially ejaculatory function, in bladder-sparing therapy can be an advantage over radical cystectomy.

A case of repeat oligoprogressive castration-resistant prostate cancer treated with pulmonary metastasectomy.

Introduction: Several retrospective studies have demonstrated the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer. However, eligible patients for progressive site-directed therapy in these studies were limited to oligoprogressive castration-resistant prostate cancer with bone or lymph node metastases without visceral metastases, and little is known about the efficacy of progressive site-directed therapy for oligoprogressive castration-resistant prostate cancer with visceral metastases. Case presentation: We report a case with castration-resistant prostate cancer previously treated with enzalutamide and docetaxel, in which only a solitary lung metastasis was identified throughout the course of treatment. The patient underwent thoracoscopic pulmonary metastasectomy with a diagnosis of repeat oligoprogressive castration-resistant prostate cancer. Only androgen deprivation therapy was continued and his prostate-specific antigen levels remained undetectable for 9 months after surgery. Conclusion: Our case suggests that progressive site-directed therapy may be effective for carefully selected repeat OP-CRPC with a lung metastasis.

Surgical outcomes of robot-assisted radical cystectomy in octogenarian or older patients: A Japanese nationwide study.

OBJECTIVE: To evaluate the surgical outcomes of robot-assisted radical cystectomy (RARC) in octogenarian or older patients based on a Japanese nationwide database. METHODS: The diagnosis procedure combination database was used to extract the data on radical cystectomy cases. Surgical outcomes of RARC in octogenarian or older patients (older group) were initially compared to those of patients younger than 80 years (younger group). Then, the surgical outcomes of RARC in the older group were compared to those of open radical cystectomy (ORC) and laparoscopic radical cystectomy (LRC) in the same age group. RESULTS: Between 2018 and 2021, 478 RARC cases in the older group and 2257 RARC cases in the younger group were identified. In the older group, ileal conduit, neobladder, and other urinary diversions were carried out in 352 (73.6%), 22 (4.6%), and 104 (21.8%) patients, respectively. In the older group, when compared with the younger group, the complication rate (24.9%), blood transfusion rate (41.4%), and in-hospital mortality (1.4%) were equivalent, while significantly shorter anesthesia time and longer length of stay were observed in the older group (521.0 ± 140.4 min vs. 595.1 ± 141.71 min, p < 0.01, and 32.9 ± 16.8 days vs. 30.6 ± 17.8 days, p = 0.01, respectively). In the comparison of the surgical outcomes of older patients receiving RARC to those receiving ORC (n = 746) and LRC (n = 375), the RARC group had the lowest complication rate and the shortest length of stay, while the shortest anesthesia time was noted in the ORC group. CONCLUSION: The feasibility of RARC for octogenarian or older patients was demonstrated by the nationwide database study.

Prognostic impact of the radiological infiltrative feature of primary renal tumor in metastatic renal cell carcinoma.

OBJECTIVES: Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model. METHODS: We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma. RESULTS: The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors. CONCLUSIONS: R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model.

Peritoneal closure and the processus vaginalis transection method to prevent inguinal hernia after robot-assisted radical prostatectomy.

OBJECTIVES: Postoperative inguinal hernia (IH) is one of the most common complications of radical prostatectomy (RP) including robot-assisted RP (RARP). However, a procedure to prevent IH after RARP has not been established. We investigated the impact of processus vaginalis transection (PVT) and PVT with peritoneal closure on IH after RARP. METHODS: A retrospective analysis was performed on data from patients who underwent RARP at two tertiary hospitals in Japan, where PVT with subsequent peritoneal closure was introduced after 2014. The incidence of IH for 2 years after RARP was compared among 79 patients without PVT or peritoneal closure, 232 patients with only PVT, and 325 patients with PVT and peritoneal closure. Multivariable Cox proportional hazard models that adjusted for hospital, age, history of abdominal operation, body mass index, operation time, and prostate weight were used. RESULTS: Postoperative IH was observed in seven (8.9%) patients without PVT or peritoneal closure, 34 (15%) patients with only PVT, and nine (2.8%) patients with PVT and peritoneal closure. Compared with patients without PVT or peritoneal closure, the incidence of IH was not different in patients with only PVT (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.34, 2.38) and significantly lower in patients with PVT and peritoneal closure (HR 0.22, 95% CI 0.07, 0.70). CONCLUSION: PVT with peritoneal closure may reduce the risk of postoperative IH after RARP. Future randomized controlled trials are required to confirm these findings.

Prostate and metastasis diffusion volume based on apparent diffusion coefficient as a prognostic factor in Hormone-naïve prostate Cancer.

In this study, to assess the utility of whole-body DWI (WB-DWI) as an imaging biomarker for metastatic hormone-naïve prostate cancer (mHNPC), we evaluated tumor diffusion volume based on apparent diffusion coefficient (ADC) values. WB-DWI results obtained from 62 mHNPC patients were evaluated in this retrospective analysis. The association with castration resistant-free survival (CFS) was evaluated for both prostate and metastatic tumor diffusion volume (pDV and mDV, respectively) based on WB-DWI. The usefulness of pDV and mDV based on ADC values to predict CFS was also examined. During the follow-up period, 22 patients progressed to castration-resistant prostate cancer, and the median CFS was 42.6 months. The median mDV and pDV were 6.7 and 12.6 mL, respectively. mDV was a significant predictor of CFS (hazard ratio [HR]: 2.75; p = 0.022), while pDV was not significant. When DV was divided into groups by ADC values (× 10- 3 mm2/s) of 0.4-1.0 and 1.0-1.8 (× 10- 3 mm2/s), mDV with ADC values (× 10- 3 mm2/s) of 0.4-1.0 (mDV0.4-1.0) showed a more favorable association with CFS compared to total mDV. On multivariate analysis, mDV0.4-1.0 and Gleason grade group had a statistically significant association with CFS (HR: 4.0; p = 0.004, and HR: 3.4; p = 0.006, respectively), while pDV with ADC values (× 10- 3 mm2/s) of 0.4-1.0 did not have a significant association. mDV is useful for predicting CFS in mHNPC patients. mDV may be a better imaging biomarker when based on ADC values.

Defining Tumour Shape Irregularity for Preoperative Risk Stratification of Clinically Localised Renal Cell Carcinoma.

Background: Unexpected adverse pathology is a major concern in surgical management of clinically localised renal cell carcinoma (RCC). Further studies are needed to improve preoperative risk stratification. Objective: To define and classify tumour shape irregularity (TSI) based on preoperative imaging, and to investigate its effect on pathological and oncological outcomes in clinically localised RCC. Design setting and participants: We retrospectively analysed 474 patients with cT1-2N0M0 RCC managed by partial or radical nephrectomy. Preoperative dynamic computed tomography was used to define and classify TSI, graded as 1 (completely elliptical shape), 2 (elliptical shape with minor and focal protrusions), or 3 (nonelliptical shape presenting with major and/or extensive protrusions). Intervention: Partial or radical nephrectomy. Outcome measurements and statistical analysis: A logistic regression analysis evaluated the risk factors for pT3a upstaging and Fuhrman grade 3-4. A Cox proportional hazard analysis assessed preoperative variables for recurrence-free survival (RFS). Results and limitations: The median tumour size was 3.5 cm, and 94 patients (20%) had (R)adius (tumour size as maximal diameter), (E)xophytic/endophytic properties of tumour, (N)earness of tumour deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines (RENAL) score ≥10. TSI was graded as 1, 2, and 3 in 214 (45%), 151 (32%), and 109 (23%) patients, respectively. Higher TSI was significantly associated with a larger tumour size and a higher RENAL score. Overall, pT3a upstaging and Fuhrman grade 3-4 were observed in 45 (9.5%) and 116 patients (31% in 380 clear cell RCC cases), respectively. The incidence of pT3a upstaging and Fuhrman grade 3-4 was significantly higher in patients with higher TSI (0.5%, 8.6%, and 28% for pT3a upstaging and 12%, 33%, and 60% for Fuhrman grade 3-4 in TSI 1, 2, and 3 groups, respectively). In multivariable analyses, higher TSI was independently associated with adverse pathological outcomes. During the median follow-up of 6.0 yr, 49 patients (10%) developed recurrence. Multivariable analyses demonstrated that older age and higher TSI were independent risk factors for worse RFS. The limitations include the retrospective design. Conclusions: TSI may be a useful adjunct in preoperative risk stratification for adverse pathology and recurrence after surgery in clinically localised RCC. Patient summary: Tumour shape irregularity is significantly associated with unfavourable pathological outcomes, that is, locally advanced stage or high-grade cancer, and with a higher recurrence rate after surgery in patients with clinically localised renal cell carcinoma. Preoperative evaluation of the tumour shape may help in patient counselling and treatment decisions.

The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery. METHODS: We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan-Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery). RESULTS: Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0-12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22-258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery. CONCLUSIONS: Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.

Factors associated with liver injury and prognosis in advanced cancer patients treated with immune checkpoint inhibitors.

AIM: The use of immune checkpoint inhibitors (ICIs) has increased remarkably, and immune-related adverse events (irAEs) have also increased. This study aimed to identify factors associated with immune-related liver injury (irLI), and the relationship between the grades of irLI and overall survival (OS) in patients treated with ICIs. METHODS: A total of 571 patients who had been treated for advanced malignancies with ICIs between January 2015 and March 2022 were retrospectively recruited. The presence of liver injury was determined by the aspartate aminotransferase and alanine aminotransferase elevation. The irLI grading was based on Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 50 (8.8%) patients had grade ≥2 irLI and 24 (4.2%) had grade ≥3 irLI. Treatment with anti-cytotoxic T-lymphocyte-associated protein-4 agents and baseline grade 1 aspartate aminotransferase/alanine aminotransferase elevation were independent predictive factors of grade ≥2 irLI. Treatment with anti-cytotoxic T-lymphocyte-associated protein-4 was the only independent predictive factor of grade ≥3 irLI. The median OS for patients who experienced any irAEs was significantly longer than of those without irAEs (hazard ratio 0.503, 95% CI 0.398-0.636, p < 0.001). The median OS in patients with grade ≥2 irLI was significantly longer (HR 0.570, 95% CI 0.387-0.838, p = 0.022). There was no significant difference between the median OS in patients with grade ≥3 irLI and the others (p = 0.11). CONCLUSION: The incidence of irLI was significantly higher in patients treated with anti-cytotoxic T-lymphocyte-associated protein-4 agents. Even in patients with pre-existing grade 1 aspartate aminotransferase/alanine aminotransferase elevation, appropriate follow-up and control of the irLI can improve the prognosis.

Significance of dorsal bladder neck involvement in predicting the progression of non-muscle-invasive bladder cancer.

OBJECTIVES: Accurately predicting of progression is important for patients with non-muscle-invasive bladder cancer (NMIBC). We previously reported that bladder neck involvement (BNI) was significantly associated with progression of NMIBC. In this study, we evaluated the prognostic significance of the detailed BNI location in NMIBC patients. METHODS: We retrospectively reviewed 651 patients diagnosed with primary NMIBC at a single center between 2000 and 2018. Using the detailed BNI location, patients were divided into the following three groups: dorsal BNI (BNId; 4 to 8 o'clock position), ventral BNI (BNIv; 8 to 4 o'clock but not 4 to 8 o'clock position), and non-BNI group. Both time to progression to muscle-invasive disease and distant metastasis was compared among the three groups. A prognostic model was developed and its discriminative ability was evaluated. RESULTS: Dorsal bladder neck involvement and BNIv were observed in 43 (6.6%) and 36 (5.5%) patients, respectively. During a median follow-up of 61 months, 35 (5.4%) patients progressed. The cumulative incidence at 5 years was 12%, 0%, and 5.0% in BNId, BNIv, and non-BNI groups, respectively. On multivariate analysis, BNId was a significant and independent risk factor for progression, tumor stage pT1, and histologic grade G3. One point was assigned to each factor, and patients were classified into four well-stratified prognostic groups based on the total score. CONCLUSION: Dorsal bladder neck involvement was an independent and significant risk factor for progression in primary NMIBC. Our simple and practical prognostic model including BNId is easy to use and may help selecting the optimal treatment and its timing.