Predictive factors of nivolumab plus ipilimumab treatment efficacy in metastatic renal cell carcinoma patients.

OBJECTIVE: Nivolumab plus ipilimumab is a recommended first-line therapy regimen for metastatic renal cell carcinoma. However, it is not clear which patient characteristics are associated with its effectiveness. METHODS: We retrospectively examined 67 metastatic renal cell carcinoma patients treated with nivolumab plus ipilimumab as a first-line therapy in multiple institutions from September 2018 to August 2022. We analyzed the relationships between survival outcomes and patient-related variables, including paraneoplastic symptoms. We also analyzed the relationships between changes in symptoms and parameters and outcomes. RESULTS: Of the 67 patients, 32 patients had paraneoplastic symptoms. The median progression-free survival was 14.9 months and median overall survival was 43.3 months. The objective response rate was 49.25% (33 patients), including two patients with complete response. Patients with cytoreductive nephrectomy, bone metastasis, high C-reactive protein levels and paraneoplastic symptoms were significantly correlated with short progression-free survival in the univariate analysis. Multivariate analysis of these factors showed that the presence of paraneoplastic symptoms at treatment initiation remained an independent predictor of progression-free survival. Of the 32 patients with paraneoplastic symptoms at treatment initiation, 12 patients had symptomatic improvement and 20 did not. The 1-year progression-free survival rates were significantly longer in improved patients compared with those with no improvement. CONCLUSIONS: Patients without cytoreductive nephrectomy and with bone metastasis, liver metastasis, high C-reactive protein levels and paraneoplastic symptoms were significantly correlated with shorter progression-free survival. The presence of paraneoplastic symptoms was an independent predictor of progression-free survival. Improvement in paraneoplastic symptoms may reflect the treatment efficacy of nivolumab plus ipilimumab.

Primary signet-ring cell carcinoma of the bladder treated with laparoscopic radical cystectomy: a case report.

Primary bladder adenocarcinomas comprise 0.5-2% of all epithelial bladder neoplasms. Of these, primary signet-ring cell carcinoma of the bladder is particularly rare, accounting for 0.24% of all bladder malignancies. This tumor is frequently diagnosed at an advanced stage and has a poor prognosis. No standard treatment has yet been established. We here report a patient in whom laparoscopic cystectomy following neoadjuvant chemotherapy was effective. Our patient was a 69-year-old man who had had microscopic hematuria, undergone transurethral resection of a mass in the bladder, and been diagnosed pathologically with a primary signet-ring cell carcinoma of the bladder. No metastases were detected on computed tomography. The patient was treated with a combination of paclitaxel, cisplatin, and gemcitabine prior to undergoing laparoscopic cystectomy. The histopathological diagnosis on this operative specimen was dysplasia and no metastases were detected in the dissected lymph nodes. Complete remission has now been maintained for 9 years.

Improving Respiratory Muscle Strength and Overall Function in Patients With Cardiovascular Disease Through Rehabilitation Hospitals.

Background: The prevalence of respiratory sarcopenia and its effect on respiratory muscle strength (RMS) in patients with cardiovascular disease (CVD), who are transferred to a convalescent rehabilitation hospital after acute care and require continuous cardiac rehabilitation (CR), is currently unclear. This study aimed to assess changes in RMS, physical function, and activities of daily living (ADL) before and after CR performed in a rehabilitation hospital. Methods: Of 50 consecutive patients transferred to a rehabilitation hospital for ongoing CR, 30 fulfilled the inclusion criteria. Maximal inspiratory and expiratory pressures (MIP and MEP, respectively) were measured at transfer, and patients with decreased RMS were diagnosed with respiratory sarcopenia. RMS, physical function, exercise tolerance, ADL ability, and health-related quality of life (HR-QoL) were measured and compared at transfer and discharge. Results: The prevalence of respiratory sarcopenia at the time of transfer to the rehabilitation hospital was 93.3%. RMS assessments at transfer and discharge demonstrated significant improvements in %MIP (from 46.3±26.1% to 63.6±33.7%) and %MEP (from 44.8±17.3% to 56.6±21.8%). Short physical performance battery, gait speed, handgrip strength, and knee extension muscle strength significantly improved, along with significant prolongation of 6-min walking distance as a measure of exercise tolerance. ADL assessment using the functional independence measure revealed significant improvement, as did HR-QoL assessed according to the five-dimension, five-level, EuroQoL instrument, following CR. Conclusions: Although respiratory sarcopenia was highly prevalent among patients with CVD who required transfer to a rehabilitation hospital after acute care, continuous CR significantly improved RMS, ADL, physical function, and exercise tolerance. These findings support the continued expansion of CR, particularly in dedicated rehabilitation hospitals.

Efficacy and Safety of Brachytherapy for Localized Prostate Cancer in Renal Transplant Recipients.

BACKGROUND: Prostate cancer is common among male renal transplant recipients and can present challenges for medical management and patient survival. It is imperative to have a comprehensive understanding of available treatment options in this population to determine the most effective and safe therapies. Brachytherapy, a safe and effective treatment for localized prostate cancer, has not been sufficiently studied in this patient population. Therefore, this study aimed to evaluate the safety and effectiveness of brachytherapy in treating prostate cancer in renal transplant recipients. METHODS: We retrospectively reviewed our brachytherapy database to identify patients with a previous history of renal transplantation who underwent seed implantation for localized prostate cancer. Long-term prostate-specific antigen control and treatment-related toxicity, including graft dysfunction and urinary and rectal complications, were assessed and compared with published outcomes. Results were analyzed to evaluate the efficacy and safety of seed implantation in this patient population. RESULTS: We identified 2 patients with previous renal transplantation who underwent permanent seed implantation for localized prostate cancer. Follow-ups ranged from 53 to 57 months, and both patients remained free of prostate-specific antigen progression with normal graft function. No acute and late complications occurred. CONCLUSION: Brachytherapy is a safe and effective treatment option for post-renal transplant prostate cancer. Given the paucity of reports on brachytherapy in this population, the findings of this study, despite a small sample size, contribute to the increasing body of evidence supporting the use of brachytherapy in this patient population.

Sarcomatoid renal cell carcinoma with an inferior vena cava tumor thrombus that was completely resected by robot-assisted laparoscopic radical nephrectomy after neoadjuvant therapy nivolumab plus ipilimumab: a case report.

We here present a patient with a sarcomatoid renal cell carcinoma complicated by inferior vena cava tumor thrombus that we treated with nivolumab plus ipilimumab. This resulted in shrinkage of the tumor, enabling complete resection by robot-assisted laparoscopic radical nephrectomy. The patient is still alive with no evidence of recurrence.

Effect of in-patient cardiac rehabilitation at rehabilitation hospital for cardiology patients: two-center trial.

The effectiveness of cardiac rehabilitation (CR) in patients with cardiovascular disease requiring continuous CR from an acute care hospital to a convalescent rehabilitation hospital is unknown. Therefore, we compared the effect of CR in a rehabilitation hospital for patients with cardiovascular disease with that of those who underwent cardiovascular surgery. Sixty-nine consecutive patients were admitted to two rehabilitation hospitals for CR. Patients were classified by primary disease into two groups: patients with cardiovascular disease (cardiology group, 26 patients) and patients who underwent cardiovascular surgery (surgery group, 43 patients). Clinical information, physical function, cognitive function, activities of daily living (ADL), quality of life (QOL), amount of CR, and length of hospital stay were compared between the two groups. Compared with clinical features, age was significantly higher in the cardiology group (P < 0.001), and the preadmission Barthel index was significantly lower in the cardiology group (P = 0.025). Physical function at the time of transfer was significantly lower in the cardiology group than in the surgery group for the short physical performance battery (P < 0.001), gait speed (P = 0.005), and 6-min walking distance (P = 0.042). No significant difference was found in the amount of CR performed or the length of hospital stay, and no interaction effects were observed in improvements in physical function, exercise tolerance, or QOL. In conclusion, in rehabilitation hospitals, patients with cardiovascular disease were older, had lower preadmission ADL, and had lower a physical function at transfer than those who underwent cardiovascular surgery, but CR improved physical function and QOL to the same extent. The results suggest that the recovery of patients with cardiovascular disease may be similar to those who undergo cardiovascular surgery.

Partial penectomy for severe penile ulceration caused by cholesterol crystal embolization.

Introduction: Cholesterol crystal embolism is a rare microembolic disease caused by cholesterol crystals that can present with various symptoms after vascular surgery, catheterization, or anticoagulation therapy. We report a case of penile ulceration caused by cholesterol crystal embolism. Case presentation: A 72-year-old man undergoing maintenance dialysis for end-stage renal failure presented with penile pain and a black glans ulcer. Despite low-density lipoprotein apheresis, he was referred to our hospital because of lack of improvement. Based on his medical history and clinical presentation, including artificial vascular replacement and right toe amputation, cholesterol crystal embolism was suspected and partial penectomy was performed, thus confirming the diagnosis. Penile pain resolved after surgery, and he was discharged on Day 10. Unfortunately, he died after small bowel perforation developed 2 months after surgery. Conclusion: Penile ulcers caused by cholesterol crystal embolism may indicate the severity and progression of disease and typically require surgical intervention.

Influence of Daily Aerobic Exercise Duration on Phase 2 Cardiac Rehabilitation at a Rehabilitation Hospital and Health-Related Quality of Life After Discharge.

Background: Phase 2 in-patient cardiac rehabilitation (CR) at a rehabilitation hospital is now added the medical service fees in Japan and in light of the recent reimbursement for CR, a study needed to be performed to determine exertional exercise on its effectiveness and benefits to patients. We examined the effects of daily aerobic exercise duration on health-related quality of life (HR-QoL) at 6 months after discharge from phase 2 CR. Methods: Of the 54 consecutive cardiovascular disease patients admitted to a rehabilitation hospital after acute care, 43 were considered acceptable candidates for enrollment according to predetermined inclusion and exclusion criteria. Of these, 40 patients completed study requirements, including return of a questionnaire on HR-QoL survey 6 months after discharge. The primary outcome was HR-QoL as evaluated using the EuroQol five-dimension five-level (EQ-5D-5L). Two multiple regression models were constructed to assess the influences of daily aerobic exercise duration (content of rehabilitation) and other clinicodemographic variables assessed during acute care (model 1) or at transfer from acute care to a rehabilitation hospital (model 2). Results: Both model 1, which included age, Barthel index of daily function before hospitalization, and daily aerobic exercise duration in the rehabilitation hospital (R2 = 0.553, P < 0.001), and model 2, which included New York Heart Association functional classification at transfer, Charlson comorbidity index at transfer, and daily aerobic exercise duration (R2 = 0.336, P = 0.002) identified aerobic exercise duration as a significant independent factor influencing HR-QoL at 6 months post-discharge (model 1: P = 0.041; model 2: P = 0.010). Conclusions: Enhanced daily aerobic exercise content during phase 2 in-hospital CR can significantly improve longer-term HR-QoL among cardiovascular disease patients independently of other clinicodemographic factors, including age, activities of daily living before treatment, and baseline condition at rehabilitation onset. These findings, that in the small sample size, support the continued expansion of phase 2 CR at a rehabilitation hospital in Japan.

[Clinical Outcome of Surgical Resection for Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus].

We analyzed 45 patients who were diagnosed with renal cell carcinoma with inferior vena cava tumor thrombus (IVC) and underwent surgical resection at Nagasaki University Hospital during the 17 years from March 2003 to November 2020. The median overall survival (OS) was 68.5, 53.5, 45.7, and 20.4 months, respectively, according to the tumor thrombus level (Lv) of I, II, III and IV, with a median level of (P＝0.025). In multivariate analysis, pathological sarcomatoid changes were associated with risk of tumor recurrence in the postoperative complete remission group, and IVC thrombus level above Lv III was associated with poor prognosis in the postoperative incomplete remission group. On postoperative systemic treatment for the postoperative recurrence group and the incomplete remission group, overall survival was significantly prolonged in cases using immune checkpoint inhibitors. The results of surgical treatment of renal cell carcinoma with IVC tumor embolization were analyzed. Patients who underwent surgical resection and achieved postoperative complete remission had a relatively long prognosis with a median OS of more than 6 years. In contrast, patients with metastases, especially those with postoperative incomplete remission group, had a poor prognosis despite surgical resection, depending on the patient's situation.

Evans syndrome during pembrolizumab therapy for upper urinary tract cancer.

Introduction: Immune checkpoint inhibitors are available for the treatment of advanced urothelial carcinoma; however, serious adverse events occasionally occur. Here, we report a rare case of Evans syndrome attributed to the use of an immune checkpoint inhibitor. Case presentation: A 56-year-old man was diagnosed with left renal pelvic cancer and underwent left laparoscopic radical nephroureterectomy. Eight months postoperatively, computed tomography revealed para-aortic lymph node metastasis. Despite receiving chemotherapy, the disease progressed, and pembrolizumab was initiated. After 26 months of pembrolizumab treatment, the patient developed fever and anemia. Hematologic examination confirmed the diagnosis of Evans syndrome. He was treated with blood transfusions and corticosteroids, and gradual symptom improvement was observed. Conclusion: This report highlights the potential risk of Evans syndrome associated with immune checkpoint inhibitor treatment. Clinicians should be aware of this possibility and consider early intervention with corticosteroids.

Microwave-assisted C-C bond formation of diarylacetylenes and aromatic hydrocarbons on carbon beads under continuous-flow conditions.

The synthesis of polycyclic aromatic compounds generally requires stoichiometric oxidants or homogeneous metal catalysts, however, the risk of contamination of inorganic residues can affect their properties. Here we present a microwave (MW)-assisted platinum on beaded activated carbon (Pt/CB)-catalyzed C-C bond formation of diarylacetylenes and aromatic hydrocarbons under continuous-flow conditions. Various fused aromatic compounds were continuously synthesized via dehydrogenative C(sp2)-C(sp2) and C(sp2)-C(sp3) bond formation with yields of up to 87% without the use of oxidants and bases. An activated, local reaction site on Pt/CB in the flow reaction channel reaching temperatures of more than three hundred degrees Celsius was generated in the catalyst cartridge by selective microwave absorption in CB with an absorption efficiency of > 90%. Mechanistic experiments of the transformation reaction indicated that a constant hydrogen gas supply was essential for activating Pt. This is an ideal reaction with minimal input energy and no waste production.

[A Retrospective Study on the Malignancies after Renal Transplantation].

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.

The Relationship between the Presence of an Earlobe Crease and Overactive Bladder: A Cross-Sectional Case-Controlled Study.

Background and Objectives: To examine the relationship between the presence of earlobe crease (EC) and overactive bladder (OAB). Materials and Methods: The earlobes of the participants were examined macroscopically. ECs were further divided into four groups (grades 0-3) according to severity. Subjective symptoms were assessed using the OAB symptom score (OABSS), and objective findings were assessed using uroflowmetry. The relationship between these findings and the presence or absence and severity of EC was also examined. A score of ≥2 points on OABSS question 3 (urinary urgency), with a total score of ≥3 points, indicated OAB. Results: We analyzed 246 participants, including 120 (48.8%) in the EC group and 126 (51.2%) in the non-EC (N-EC) group. On the OABSS, the EC group scored higher than the N-EC group for all questions and for the total score. The total OABSS of EC grade 3 was the highest of all groups. A total of 115 (95.8%) patients in the EC group (100% in grade 3) and 69 (54.8%) in the N-EC group met the OAB criteria (p < 0.001). The voided volume and maximum flow rate of the EC group were significantly lower than those of the N-EC group (both p < 0.001). The post-void residual urine volume in the EC group was significantly higher than that in the N-EC group (p = 0.029). Multivariate analysis revealed that EC was an independent risk factor for OAB (odds ratio, 8.15; 95% confidence interval, 2.84-24.75; p < 0.001). Conclusions: The presence of an earlobe crease may be a predictive marker for OAB.

Pathological Significance of Kidney and Brain Expressed Protein (KIBRA) in Clear Cell Renal Cell Carcinoma.

BACKGROUND/AIM: Kidney and brain expressed protein (KIBRA), a member of the WW domain-containing protein family, has an important role in tumour growth and progression in various cancers. However, the pathological significance of KIBRA expression in clear cell renal cell carcinoma (ccRCC) tissues is not fully understood. The aim of this study was to clarify the pathological significance and prognostic roles of KIBRA expression in patients with ccRCC. MATERIALS AND METHODS: KIBRA immunoreactivity, proliferation index (PI; with anti-Ki-67 antibody), apoptotic index (AI; using anti-cleaved caspase-3), and large tumour suppressor kinases (LATS-2) were evaluated in 157 ccRCC specimens by immunohistochemistry. Fifty normal kidney tissues were also evaluated as controls. The relationships between KIBRA expression and these cancer-related variables as well as clinicopathological features and survival were analysed. RESULTS: Moderate to strong immunoreactivity of KIBRA was identified in all normal kidney tissues; however, ccRCC cells with strong KIBRA expression was rare. The immunoreactivity score (IRS) of KIBRA was negatively associated with grade, T stage, tumour diameter, and metastasis. Kaplan-Meier survival curves showed that high KIBRA expression was a favourite predictor for overall survival. KIBRA IRS was negatively associated with PI and positively associated with the IRS of LATS-2 by univariate analysis. In addition, multivariate analysis showed that KIBRA was significantly associated with PI. CONCLUSION: KIBRA demonstrated important roles as a tumour suppressor in ccRCC. In addition, its expression was significantly associated with survival in these patients. Several such KIBRA-related functions were speculated to be modulated by cancer cell proliferation and LATS-2.

Initial experience in robot-associated radical nephrectomy with inferior vena cava tumor thrombectomy.

Background: Renal cell carcinoma (RCC) is often locally invasive and may extend from the renal vein into the inferior vena cava (IVC) as a venous tumor thrombus (VTT). Radical nephrectomy with IVC tumor thrombectomy (IVC-TT) via an open approach has been shown to carry high morbidity and mortality. Recently, robot-associated radical nephrectomy (RARN) has been developed with the aim of improving the performance and outcomes of surgery for RCC with IVC-VTT. Methods: We here present four patients who had right RCC with IVC-VTT and underwent RARN with IVC-TT in Nagasaki University Hospital. All four patients had level II IVC-TT and underwent RARN with IVC-TT using a da Vinci Xi surgical system. The procedure comprised performing the Kocher maneuver, exposing the right renal artery in the aortocaval region dorsal to the left renal vein, exposing, mobilizing, and clipping the IVC, clamping and incising the IVC, and removing the kidney with the VTT en bloc. Results: The mean tumor size was 83.1 (range, 50.1-115.2) mm and the mean length of the VTT within the IVC 41.6 (range, 25.3-44.3) mm. The mean console time was 290 (range, 287-367) minutes and the mean blood loss was 200 (range, 175-260) mL and no patient required blood transfusion. Conclusions: Our initial experience of the procedure of RARN with IVC-TT for level II IVC-VTT is that it is safe and has acceptable perioperative outcomes and complications.

Associations among Physician-Patient Communication, Patient Satisfaction, and Clinical Effectiveness of Overactive Bladder Medication: A Survey of Patients with Overactive Bladder.

This cross-sectional survey study evaluated associations between physician−patient communication and patient satisfaction with overactive bladder (OAB) medical care or clinical effectiveness. Japanese patients aged ≥50 years with OAB who had taken OAB medication within 2 years received a web-based survey regarding OAB medical care, physician−patient communication on OAB symptoms and treatment, and OAB symptom score (OABSS) change with treatment. Associations between physician−patient communication and patient satisfaction or OAB medication effectiveness (≥3-point improvement in OABSS) were investigated by multivariate analysis with confounding factors. Stratified analyses were performed based on medication continuation or discontinuation (for reasons except symptom improvement). Of the 1004 respondents included in the analyses, 58.0% continued treatment, and 23.7% discontinued for reasons except symptom improvement. Satisfaction with OAB care was associated with reported effectiveness, medication side effects, physician−patient communication, and whether medication was switched. Medication effectiveness was associated with patient−physician communication, female sex, and not switching medication. Significantly more patients in the continuation group were satisfied and had improvement of ≥3 points in OABSS (p < 0.001 for both). The findings suggest that, in Japan, adequate physician−patient communication contributes significantly to improving clinical effectiveness and satisfaction with medical care in OAB patients as well as treatment continuation.

Impact of Mirabegron Administration on the Blood Pressure and Pulse Rate in Patients with Overactive Bladder.

Background and Objectives: To determine changes in the blood pressure (BP) and pulse rate (PR) before and after the administration of mirabegron in real-world clinical practice for patients with overactive bladder (OAB). Materials and Methods: This study was conducted in patients newly diagnosed with OAB. Before and 12 weeks after mirabegron treatment, we evaluated the effects on BP and PR. An overall examination was conducted, and the patients were divided into two groups according to their age: a young group (<65 years old) and an old group (≥65 years old). Results: A total of 263 patients were enrolled in this study. In the overall and intragroup comparisons, the systolic BP (SBP) did not change significantly after mirabegron administration. However, an increase in SBP of ≥10 mmHg was observed in 53 (20.2%), 4 (7.4%), and 49 (23.4%) in the entire group, young group, and old group, respectively (p = 0.009). Regarding diastolic BP, a significant decrease after the treatment was detected in entire (71.2 ± 11.4 versus 69.8 ± 10.7 mmHg; p = 0.041) and old patients (71.5 ± 10.6 versus 69.5 ± 10.2 mmHg; p = 0.012). There was no significant change in PR in our study population. Further examination using a propensity match score revealed that age was the risk factor for the increase in SBP after mirabegron administration. Conclusions: Mirabegron does not have any adverse effects on BP and PR. However, since some patients in this study had elevated SBP after administration, we suggest regular BP monitoring during mirabegron treatment.

Effects of ß3 Agonists and Anticholinergic Drugs on Defecation in Patients With Overactive Bladder.

BACKGROUND/AIM: In clinical practice, constipation is one of the most frequent adverse events caused by drugs for overactive bladder (OAB). The occurrence of constipation greatly deteriorates the patient's quality of life. The aim of the study was to evaluate and compare the effects of three commonly used ß3 agonists and anticholinergic drugs on the defecation status in patients with OAB. PATIENTS AND METHODS: We retrospectively reviewed the defecation status in patients who received mirabegron, solifenacin, or fesoterodine for OAB. We evaluated changes in the (a) urological parameters using the OAB symptom score (OABSS) and (b) defecation status using the Bristol Stool Form Scale (BSFS) and constipation scoring system (CSS) following 12 weeks of drug administration. RESULTS: We analyzed data from 165 patients (mirabegron=56, fesoterodine=52, and solifenacin=57). The solifenacin group showed a significant decrease in BSFS (from 3.2±1.0 at baseline to 2.3±12 post-treatment) and an increase in hardened stools (p<0.001). Elimination worsened as assessed by almost all items, and the total modified CSS scores worsened significantly from 4.8±2.6 points at baseline to 8.O±4.8 points after 12 weeks of solifenacin treatment (p<0.001). The mirabegron group showed no changes in any of the CSS items. In the fesoterodine group, the CSS scores for "completeness" and "assistance" increased significantly after treatment (p<0.001 and p=0.013, respectively). CONCLUSION: All three drugs were effective for OAB. Mirabegron had almost no effect on constipation; fesoterodine, an anticholinergic drug, also had hardly any effect on defecation.