Prognostic value of various nutritional risk markers in patients hospitalized for the treatment of genitourinary cancer: A retrospective study.

BACKGROUND & AIMS: Because malnutrition adversely affects the prognosis of patients with cancer, accurate nutritional status assessment is important. Therefore, this study aimed to verify the prognostic value of various nutritional assessment tools and compare their predictability. METHODS: We retrospectively enrolled 200 patients hospitalized for genitourinary cancer between April 2018 and December 2021. Four nutritional risk markers, namely, Subjective Global Assessment (SGA) score, Mini-Nutritional Assessment-Short Form (MNA-SF) score, Controlling Nutritional Status (CONUT) score, and Geriatric Nutritional Risk Index (GNRI), were measured at admission. The endpoint was all-cause mortality. RESULTS: SGA, MNA-SF, CONUT, and GNRI values were all independent predictors of all-cause mortality (hazard ratio [HR] = 7.72, 95% confidence interval [CI]: 1.75-34.1, P = 0.007; HR = 0.83, 95% CI: 0.75-0.93, P = 0.001; HR = 1.29, 95% CI: 1.16-1.43, P < 0.001; and HR = 0.95, 95% CI: 0.93-0.98, P < 0.001, respectively) even after adjustment for age, sex, cancer stage, and surgery or medication. However, in the model discrimination analysis, the net reclassification improvement of the CONUT model (vs. SGA: 0.420, P = 0.006 and vs. MNA-SF: 0.57, P < 0.001) and GNRI model (vs. SGA: 0.59, P < 0.001 and vs. MNA-SF: 0.671, P < 0.001) were significantly improved compared to the SGA and MNA-SF models, respectively. The combination of CONUT and GNRI models also had the highest predictability (C-index = 0.892). CONCLUSIONS: Objective nutritional assessment tools were superior to subjective nutritional tools in predicting all-cause mortality in inpatients with genitourinary cancer. Measurement of both the CONUT score and GNRI might contribute to a more accurate prediction.

The Efficacy and Safety of Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Combination Therapy for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Real-World Cohort Study.

We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We enrolled 51 patients to receive ICI+TKI therapy for mRCC at 9 Japanese institutions. The overall survival (OS) of the patients treated with ICI+TKI was the primary endpoint., and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Furthermore, we analyzed the clinical prognostic and predictive factors in patients with mRCC treated with ICI+TKI therapy. Seven months was the median follow-up period. The OS rates at 6, 12, and 18 months were 93.1, 82.5, and 68.8%, respectively. The median PFS for patients who received ICI+TKI was 19.0 months, ORR was 68.6%, and DCR was 88.2%. ICI+TKI-related adverse events occurred in 43 patients (84.3%) with any grade and in 22 patients (43.1%) with grade ≥3. Treatment selection with poor prognostic factors may be prudent, even though ICI+TKI is an efficacious and safe first-line treatment in patients with mRCC.

CALN1 hypomethylation as a biomarker for high-risk bladder cancer.

BACKGROUND: DNA methylation in cancer is considered a diagnostic and predictive biomarker. We investigated the usefulness of the methylation status of CALN1 as a biomarker for bladder cancer using methylation-sensitive restriction enzyme (MSRE)-quantitative polymerase chain reaction (qPCR). METHODS: Eighty-two bladder cancer fresh samples were collected via transurethral resection of bladder tumors. Genomic DNA was extracted from the samples, and MSRE-qPCR was performed to determine the CALN1 methylation percentage. Reverse transcription-qPCR was performed to assess the correlation between CALN1 methylation and mRNA expression. The association between CALN1 methylation percentage and clinicopathological variables of all cases and intravesical recurrence of non-muscle-invasive bladder cancer (non-MIBC) cases were analyzed. RESULTS: Of the 82 patients, nine had MIBC and 71 had non-MIBC who had not undergone total cystectomy. The median CALN1 methylation percentage was 79.5% (interquartile range: 51.1-92.6%). The CALN1 methylation percentage had a negative relationship with CALN1 mRNA expression (Spearman's ρ = - 0.563 and P = 0.012). Hypomethylation of CALN1 was associated with advanced tumor stage (P = 0.0007) and histologically high grade (P = 0.018). Furthermore, multivariate analysis revealed that CALN1 hypomethylation was an independent risk factor for intravesical recurrence in non-MIBC patients (hazard ratio 3.83, 95% confidence interval; 1.14-13.0, P = 0.031). CONCLUSION: Our findings suggest that CALN1 methylation percentage could be a useful molecular biomarker for bladder cancer.

Effectiveness and Safety of Molecular-Targeted Therapy after Nivolumab Plus Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

This study aimed to evaluate the effectiveness and safety of molecular-targeted therapies (MTTs) after the discontinuation of nivolumab and ipilimumab (NIVO+IPI) combination therapy in patients who had been diagnosed with advanced/metastatic renal cell carcinoma as real-world outcomes. We enrolled patients treated with MTTs following initial therapy with NIVO+IPI at nine institutions in Japan. We evaluated the objective response rate (ORR) as the primary endpoint and disease control rate (DCR), best overall response, and oncological outcomes (overall survival (OS) and progression-free survival (PFS)) as the secondary endpoints. We also evaluated factors predictive of disease progression after the administration of MTTs. Patients were followed up for a median of 8 months. The ORR was 44.8%, and the DCR was 72.4%. The median OS and PFS of MTTs after NIVO+IPI were 18 months and 8 months, respectively. A total of 31% of patients experienced grade 3/4 MTT-related adverse events. The median PFS in patients with bone metastases was significantly shorter than that in those without bone metastases (4 vs. 12 months, p = 0.012). MTTs may be a useful secondary treatment option after the discontinuation of NIVO+IPI.

Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma after Discontinuing Pembrolizumab as a Second-Line Treatment: A Retrospective Multicenter Real-World Cohort Study.

The treatment options are currently limited, and the oncological outcomes remain unclear, for patients with metastatic urothelial carcinoma (mUC) with or without third-line systemic therapy. We aimed to evaluate the oncological outcomes in real-world daily clinical practice after platinum-based chemotherapy followed by pembrolizumab for mUC. This retrospective, multicenter cohort study included patients with mUC who received second-line pembrolizumab in Japan. The patients were divided into the treatment group (those who received third-line treatment) and the BSC group (those who did not receive other treatments). The primary endpoint of this study was to evaluate the oncological outcomes. Of 126 patients enrolled in this study, 40 received third-line therapy. The median follow-up period was 8.0 months. The median overall survival (OS) times were nine months in the BSC group and 17 months in the treatment group (p < 0.001). The median progression-free survival (PFS) times were 4 months in the BSC group and 14 months in the treatment group (p < 0.001). In the multivariate analysis, performance status and liver metastasis were significantly associated with OS. Third-line therapy may have clinical potential advantages for improving the oncological outcomes in patients with mUC.

Clinical Lymph Node Involvement as a Predictor for Cancer-Specific Survival in Patients with Penile Squamous Cell Cancer.

We aimed to identify prognostic predictive factors of patients with penile squamous cell carcinoma (PSCC). This retrospective study reviewed the clinical and pathological data of patients with PSCC at 10 institutions in Japan between January 2008 and December 2019. The primary endpoint was cancer-specific survival (CSS). We also identified useful predictive factors for CSS in patients with PSCC. In total, 64 patients with PSCC were enrolled. At the end of the follow-up period, 15 patients (23.4%) died owing to PSCC and six (9.4%) died owing to other causes. The 2- and 3-year CSS rates were 78.9% and 76.6%, respectively. Using the Kaplan−Meier method, the Eastern Cooperative Oncology Group performance status 0, serum albumin levels ≥4.2 g/dL, hemoglobin levels ≥13.2 g/dL, C-reactive protein levels <0.21 mg/dL, clinical T stage ≤2, clinically negative lymph node (LN) status, and tumor size <30 mm were associated with a significantly better CSS. In the multivariate analysis, the clinically positive LN status was a significant predictive factor for CSS in patients with PSCC. Further prospective large-scale and long-term studies are required to validate our findings.

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma.

We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.

Prognostic Value of the Controlling Nutritional Status (CONUT) Score in Patients at Dialysis Initiation.

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD), and affects their prognosis. The Controlling Nutritional Status (CONUT) score is a nutritional screening tool calculated using only blood test data. This study aimed to investigate the prognostic value of CONUT score in patients just initiating dialysis. A total of 311 CKD patients who stably initiated dialysis were enrolled. Only 27 (8.7%) patients were classified as having normal nutritional status. The CONUT score was also independently correlated with elevated C-reactive protein levels (ß = 0.485, p < 0.0001). During the median follow-up of 37 months, 100 patients (32.2%) died. The CONUT score was an independent predictor of all-cause mortality (adjusted hazard ratio 1.13, 95% confidence interval 1.04−1.22, p < 0.0024). As model discrimination, the addition of the CONUT score to a prediction model based on established risk factors significantly improved net reclassification improvement (0.285, p = 0.028) and integrated discrimination improvement (0.025, p = 0.023). The CONUT score might be a simplified surrogate marker of the PEW with clinical utility and could predict all-cause mortality, in addition to improving the predictability in CKD patients just initiating dialysis. The CONUT score also could predict infectious-disease mortality.

Robot-Assisted Radical Prostatectomy for Potential Cancer Control in Patients with Metastatic Prostate Cancer.

Recently, cytoreductive prostatectomy for metastatic prostate cancer (mPCa) has been associated with improved oncological outcomes. This study was aimed at evaluating whether robot-assisted radical prostatectomy (RARP) as a form of cytoreductive prostatectomy can improve oncological outcomes in patients with mPCa. We conducted a retrospective study of twelve patients with mPCa who had undergone neoadjuvant therapy followed by RARP. The endpoints were biochemical recurrence-free survival, treatment-free survival, and de novo metastasis-free survival. At the end of the follow-up period, none of the enrolled patients had died from PCa. The 1- and 2-year biochemical recurrence-free survival rates were 83.3% and 66.7%, respectively, and treatment-free survival rates were 75.0% and 56.3%, respectively. One patient developed de novo bone metastases 6.4 months postoperatively, and castration-resistant prostate cancer 8.9 months postoperatively. After RARP, the median duration of recovery of urinary continence was 5.2 months. One patient had severe incontinence (>2 pads/day) 24 months postoperatively. RARP may be a treatment option in patients with mPCa who have achieved a serum prostate-specific antigen level < 0.2 ng/mL, and present without new lesions on imaging.

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab.

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes.

Efficacy and Safety of Nivolumab and Ipilimumab for Advanced or Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Cohort Study.

We conducted a multicenter, retrospective study to evaluate the efficacy and safety of combination nivolumab plus ipilimumab (NIVO+IPI) in 35 patients with advanced or metastatic renal cell carcinoma (mRCC). In this study, we focused on patients who received NIVO+IPI and were stratified into intermediate- or poor-risk disease according to the International Metastatic Renal Cell Carcinoma Database Consortium model at five institutions in Japan. The primary endpoint was overall survival (OS). Secondary endpoints were disease control rate (DCR), best overall response (BOR), objective response rate (ORR), and progression-free survival (PFS). In addition, we evaluated the role of inflammatory cell ratios, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), as predictive biomarkers in patients with mRCC. The median follow-up period was 1 year, and the 1-year OS rate was 95.8%. The ORR and DCR were 34.3% and 80.0%, respectively. According to BOR, four patients (11.4%) achieved complete response. According to NLR stratification, the 1-year PFS rates were 82.6% and 23.7% when the NLR was ≤4.6 and >4.6, respectively (p = 0.04). Based on PLR stratification, the 1-year PFS rates were 81.7% and 34.3% when the PLR was ≤188.1 and >188.1, respectively (p = 0.033). Although 71.4% of the patients experienced treatment-related adverse events (TRAEs) with NIVO+IPI, only four patients discontinued NIVO+IPI due to grade 3/4 TRAEs. Patients treated with NIVO+IPI as a first-line therapy for advanced or mRCC achieved relatively better oncological outcomes. Therefore, NIVO+IPI may have potential advantages and may lead to a treatment effect compared to those receiving targeted therapies. In addition, PLR >188.1 may be a useful predictive marker for mRCC patients who received NIVO+IPI.

A case of temporary metastatic pulmonary calcification in a patient with hyperparathyroidism on peritoneal dialysis.

INTRODUCTION: Ectopic calcification is associated with secondary hyperparathyroidism (HPT) in patients with end-stage renal failure (ESRD). Metastatic pulmonary calcification (MPC) is another rare type of ectopic calcification, and there are a few reports on MPC in dialysis patients. CASE PRESENTATION: We report the case of a 52-year-old woman admitted with general fatigue and appetite loss, who was on peritoneal dialysis (PD) for 7 years. Although she was initially suspected of having secondary HPT due to ESRD, we finally diagnosed ectopic HPT that was caused by a cystic mass behind her thyroid gland overlapping with secondary HPT. We carefully observed her under conservative therapy because she refused surgery. On admission, she was diagnosed as having MPC because she had ground-glass-like opacification in her lung fields on high-resolution computed tomography scan, which was caused by a parathyroid tumor complicated by secondary HPT associated with ESRD. After she began intravenous injection of etelcalcetide hydrochloride, serum calcium, and intact parathyroid hormone (iPTH), values were adjusted, and the opacification disappeared. CONCLUSION: In a patient on PD, this is the first case of MPC that developed due to acute hypercalcemia, hyperphosphatemia, and dehydration and in which the ectopic pulmonary calcification clearly decreased with optimization of iPTH.

Impact on survival of urgent dialysis initiation in patients with end-stage renal disease: a case-control study.

BACKGROUND: Outcomes of patients with end-stage renal disease at urgent dialysis initiation are varied, but evidence of their long-term prognosis is limited. We aimed to characterize patients undergoing urgent dialysis initiation and analyse its effect on survival outcome. METHODS: We retrospectively identified 208 patients who began haemodialysis from 1 January 2012 to 31 December 2018 at our hospital. In this observational case-control study, the case group comprised patients starting urgent dialysis, and the control group comprised patients starting planned dialysis. We analysed laboratory data, sex, age, smoking history, comorbidities and presence of vascular access and nephrology care that potentially affected the outcome. Data were analysed with Kaplan-Meier curves of early and late period (3 years after dialysis initiation) survival and log-rank tests and with Cox regression analysis. RESULTS: Median age (range) at dialysis initiation was 73 (28-90) years, with 50 (24%) patients in the urgent initiation group. Five (10%) patients in this group had vascular access at dialysis initiation, whereas 21 (42%) had not received adequate pre-dialysis nephrology care. The estimated median overall survival rates of the urgent group and planned initiation group were 42 months and not reached, respectively (P = 0.0011). Multivariable analysis found urgent dialysis initiation to be an independent risk factor for survival (HR 2.36; 95% CI 1.36-4.00; P = 0.02). Survival was not significantly different between the groups for patients who continued chronic dialysis for > 3 years from dialysis initiation (P = 0.1339). CONCLUSION: The prognosis of patients starting dialysis in an urgent condition was poor compared with those who started planned dialysis.

[A Study on the Number of Cycles of First-Line Chemotherapy for Advanced Urothelial Carcinoma].

The first line chemotherapy for advanced urothelial carcinoma is combination chemotherapy based on platinum. The optimal number of cycles for first line chemotherapy has not been defined yet. While cumulative toxicity of cisplatin can be a problem, the approval of pembrolizumab has changed the aspect of secondary treatment. We investigated 39 patients who were diagnosed with advanced urothelial carcinoma and treated with platinum-based chemotherapy between August 2009 and October 2018 in our hospital. We evaluated the correlation between number of cycles of first line chemotherapy and the survival rate of patients with advanced urothelial carcinoma. The primary tumor site was found in the bladder in 22 patients and in the upper urinary tract in 17 patients. Thirty one patients received cisplatin and 8 received carboplatin. Twelve patients received 2 or less cycles, 16 received 3 to 5 cycles and 11 received 6 or more cycles. The median overall survival in those populations was 5 months, 18 months, and 20 months, respectively. Patients who received 2 or less cycles showed significantly lower response rates to chemotherapy and the overall survival worsened. There was no significant difference in overall survival between patients who received 3 to 5 cycles and those who received more than 6 cycles. These results suggested that it may be excessive to continue the first line chemotherapy for more than 6 cycles.

Retroperitoneal lipogranuloma mimicking recurrence of renal cell carcinoma after laparoscopic partial nephrectomy.

Lipogranuloma is a rare inflammatory reactive process often reported to occur in the dermis and subcutis in the cosmetic surgery field.1 It very rarely occurs in the retroperitoneum. We present a case of retroperitoneal lipogranuloma mimicking metastases of renal cell carcinoma (RCC) after laparoscopic partial nephrectomy. A 63-year-old man who underwent laparoscopic left partial nephrectomy for RCC one year earlier had developed a left retroperitoneal tumor during postoperative surveillance. The tumor looked identical to an implant or recurrence of RCC on contrast-enhanced computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/CT. We resected the tumor, and pathology showed a lipogranuloma.

[A Case of Adult Mature Teratoma Located in Retroperitoneum].

A 35-year-old man wasreferred to our hospital for treatment of a right adrenal tumor detected by ultrasonography during a physical check-up. Contrast-enhanced abdominal computed tomography revealed a poorly enhanced 74 mm tumor situated adjacent to the upper pole of the right kidney. The tumor consisted of fat with peripheral calcification. Magnetic resonance imaging also revealed a right retroperitoneal tumor with fatty contents and well-circumscribed capsule. The endocrine examination revealed the tumor as non-functioning. These findings were suggestive of a right adrenal myelolipoma. We performed laparoscopic right adrenalectomy because of its large size and malignant potency. The pathological examination revealed the retroperitoneal tumor asa mature teratoma existing apart from the adrenal gland. Primary retroperitoneal teratomasare relatively rare. Herein, we report thiscas e of adult mature teratoma occurring in the retroperitoneum.

[Three Patients with Acute Myocardial Infarction Associated with Targeted Therapy of Sorafenib for Metastatic Renal Cell Carcinoma : Case Report].

Sorafenib is a tyrosine kinase inhibitor (TKI) of the vascular endothelial growth factor receptor (VEGFR) used for advanced renal cell carcinoma. Treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal cell carcinoma. However, in spite of its therapeutic efficacy, sorafenib causes a wide range of adverse events. Cardiovascular adverse events have been observed when sorafenib was used with targeted agents. Although these adverse events like hypertension, reduced left ventricular ejection fraction, cardiac ischemia or infarction were manageable with standard medical therapies in most cases, some had a poor clinical outcome. We report three cases of acute myocardial infarction associated with sorafenib in patients with metastatic renal cell carcinoma.

Prospective evaluation of the safety of transrectal ultrasound-guided transperineal prostate biopsy based on adverse events.

BACKGROUND: Although transperineal (TP) prostate biopsy is growing in popularity, its safety has not been evaluated based on extensive studies. We prospectively assessed the adverse events associated with transrectal ultrasound (TRUS)-guided TP 16-core prostate biopsy at a single institution. PATIENTS AND METHODS: We enrolled 2,086 males who underwent first-time TRUS-guided TP prostate biopsy under lumbar spinal anesthesia at Chiba Cancer Center between 2009 and 2013. Eight adverse events were assessed prospectively using a purpose-designed questionnaire. The prevalence and duration of all adverse events were evaluated. We performed subgroup analyses for hematuria and urinary retention in relation to clinical factors. RESULTS: Questionnaires were collected from 1,663 cases (79.7 %). The cancer detection rate was 53.5 % in all patients. The prevalence and duration of complications were as follows: hematuria, 73.4 % and 4.51 ± 2.88 days; perineal bleeding, 7.1 % and 2.20 ± 2.24 days; hematospermia 14.4 %; dysuria, 15.7 % and 3.12 ± 2.71 days; urinary tract pain, 49.5 % and 2.43 ± 2.08 days; perineal pain, 35.5 % and 3.53 ± 2.59 days; fever ≥37 °C, 1.7 % and 1.79 ± 1.72 days; and headache, 22.1 % and 3.40 ± 2.10 days. Seventeen patients (1.1 %) required indwelling urethral catheterization for grade 2 urinary retention. Pre-biopsy International Prostate Symptom Score (p = 0.014) was an independent related factor for hematuria. Prostate volume (p = 0.001) was an independent related factor for grade 2 urinary retention. CONCLUSIONS: TRUS-guided TP prostate biopsy under lumbar spinal anesthesia can be performed safely with only minor adverse events.

ALK Gene Translocation in Inflammatory Myofibroblastic Tumor of the Urinary Bladder: A Case Report.

A 26-year-old woman with gross hematuria was seen in a previous hospital. Magnetic resonance imaging (MRI) showed a tumor at the dome of the urinary bladder with invasion outside of the bladder wall. The patient underwent transurethral resection of the bladder tumor (TUR-BT). From the result of the pathological examination, the tumor was suggested to be carcinosarcoma of the bladder. The patient was then referred to our hospital for treatment. We performed radical cystectomy and ileal conduit diversion. Pathological examination of the excised specimen revealed an inflammatory myofibroblastic tumor as the basis for immunostaining of anaplastic lymphoma kinase (ALK).