Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis.

BACKGROUND: Immune-related adverse events (irAEs) in patients treated with immune check inhibitors are associated with favourable response rate and survivals in multiple cancers, including renal cell carcinoma (RCC). The aim of this study was to investigate how irAEs were associated with improved survivals in advanced RCC patients treated with nivolumab plus ipilimumab. MATERIALS AND METHODS: This retrospective study included patients who received nivolumab plus ipilimumab at six centres, institutions, or hospitals between September 2018 and February 2022. We assessed associations of the development and the number of irAEs with overall survival (OS) and progression-free survival (PFS). To eliminate immortal time bias, landmark analysis and a Cox model with time-dependent variables were used. RESULTS: This study included 129 patients with a median follow-up of 12.3 months. The 2-year OS and PFS rates were 55% and 42%, respectively. Ninety six patients experienced irAEs. The development of irAEs was positively associated with OS and PFS rates (hazard ratio [HR] 0.328, 95% confidence interval [CI] 0.165-0.648, p = 0.001; HR 0.334, 95% CI 0.151-0.737, p = 0.007). Patients who experienced multiple irAEs had longer OS (HR 0.507, 95% CI 0.235-1.097, p = 0.085 or HR 0.245, 95% CI 0.110-0.544, p < 0.001) and PFS (HR 0.572, 95% CI 0.316-1.036, p = 0.085 or HR 0.267, 95% CI 0.113-0.628, p = 0.002) compared with those who experienced single or zero irAE. CONCLUSIONS: Developing irAEs, particularly multiple irAEs, is associated with favourable survivals in advanced RCC patients treated with nivolumab plus ipilimumab.

Clinical outcomes of nivolumab plus ipilimumab in patients with metastatic non-clear cell renal cell carcinoma: Real-world data from a Japanese multicenter retrospective study.

OBJECTIVES: Although nivolumab plus ipilimumab has become a standard treatment regimen for metastatic clear cell renal cell carcinoma (ccRCC), its efficacy in non-clear cell carcinoma (nccRCC) has not been fully examined. In the current study, we evaluated the clinical outcomes of nivolumab plus ipilimumab in nccRCC compared with ccRCC. METHODS: We retrospectively analyzed 22 patients with metastatic and/or locally advanced unresectable nccRCC who received nivolumab plus ipilimumab as a first-line therapy and compared them with 107 patients with ccRCC. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity were compared between the nccRCC and ccRCC groups. RESULTS: The histology of nccRCC included eight papillary, six unclassified, three chromophobe, two collecting duct carcinoma, and three other subtypes. Best objective response in nccRCC patients included three complete responses and five partial responses, resulting in an ORR of 36%, while that in ccRCC patients was 50% (p = 0.22). With a median follow-up of 11.9 months, OS was significantly shorter in patients with nccRCC than in those with ccRCC (median 20.8 months vs. not reached, p = 0.04), while there was no significant difference in PFS (median 6.3 vs. 10.8 months, p = 0.21). Treatment-related adverse events occurred in 14 (64%) nccRCC patients and 81 (76%) ccRCC patients. CONCLUSIONS: Combination treatment with nivolumab and ipilimumab demonstrated modest clinical efficacy in patients with nccRCC compared with patients with ccRCC, suggesting it could be a therapeutic option for metastatic nccRCC patients.

[A Case of Left Renal Cell Carcinoma with Renal Arteriovenous Fistula and Multiple Vascular Malformation Undergoing Nephrectomy].

A 69-year-old woman was referred to our hospital for the treatment of a left renal tumor found by computed tomography (CT) during examination for microscopic hematuria. Contrast-enhanced CT showed a 5 cm tumor in the inferior pole of the left kidney. Left renal cell carcinoma (RCC) (cT1bN0M0) was suspected. In addition, the left renal and gonadal veins were dilated and enhanced in an arterial phase; renal arteriovenous fistula (RAVF) was suspected. Moreover, there were multiple focal arterial dilatations, suggesting the presence of multiple vascular malformation. Hereditary aortic disease, including vascular Ehlers-Danlos syndrome (vEDS), was a concern. In general, surgery is not recommended for patients with vEDS, due to vascular fragility. As such, a panel analysis of genes for hereditary aortic diseases, including vEDS, was performed; no pathogenic variants in candidate genes including COL3A1 were identified. After detailed discussions with the patient, she underwent a left nephrectomy, following transcatheter arterial embolization (TAE) of the left renal artery. We prepared a balloon catheter for aortic occlusion as a preventative measure for massive bleeding; this was not the case, as only a small amount of intraoperative bleeding occurred. Thus, the nephrectomy was performed successfully without using the balloon catheter. The patient recovered uneventfully and was discharged on day 8. Pathological examination showed clear-cell RCC (pT1a) and a RAVF near the tumor. Herein we report this case of left RCC with RAVF and multiple arterial malformation, which was successfully managed by evaluating preoperative risks with a genetic test, followed by TAE of the renal artery and open nephrectomy.

Hypereosinophilia is a predictive biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma.

BACKGROUND: This study aimed to evaluate whether hypereosinophilia is a clinical biomarker of immune checkpoint inhibitor-induced hypopituitarism in patients with renal cell carcinoma treated with nivolumab plus ipilimumab. METHODS: This was a retrospective cohort study conducted at Jichi Medical University Saitama Medical Center between January 2018 and December 2020. In total, 12 patients with renal cell carcinoma who presented with immune checkpoint inhibitor-induced hypopituitarism were enrolled in this study. The clinical parameters and symptoms at baseline, last visit, and onset of hypopituitarism were analyzed. RESULTS: The median period from the initial treatment with immune checkpoint inhibitors to the onset of hypopituitarism was 82.5 (range: 56-196) days. Most patients developed hypopituitarism within 6 months. One patient presented with hypophysitis and 11 patients presented with isolated adrenocorticotropic hormone deficiency. The major symptoms noted at onset were fatigue (66.7%) and loss of appetite (41.7%). None of the patients had symptoms during the last visit. However, four developed hypereosinophilia. Eosinophil fraction (%) and eosinophil count (/µL) increased during the last visit and at the onset of hypopituitarism, respectively. The serum sodium and plasma glucose levels were similar. CONCLUSIONS: The eosinophil count increased before the onset of hypopituitarism. Thus, hypereosinophilia can be an early predictor of hypopituitarism.

Combination of biparametric magnetic resonance imaging with prostate-specific antigen density to stratify the risk of significant prostate cancer: Initial biopsy and long-term follow-up results.

OBJECTIVES: To assess whether the combination of biparametric magnetic resonance imaging with prostate-specific antigen density can properly stratify the risk of significant prostate cancer in patients undergoing prostate biopsies and how this approach affects the detection of prostate cancer during follow-up in patients who do not undergo prostate biopsy. METHODS: In total, 411 biopsy-naïve patients who had elevated prostate-specific antigen levels and then underwent biparametric magnetic resonance imaging for suspicious prostate cancer were analyzed: 203 patients underwent prostate biopsies, whereas 208 patients did not. Significant prostate cancer detection rates stratified by the combination of Prostate Imaging Reporting and Data System score and prostate-specific antigen density were assessed in patients who underwent prostate biopsies. The cumulative incidence of prostate cancer detection during the follow-up was assessed in patients who omitted biopsy. RESULTS: The negative predictive value for significant prostate cancer was 89% for Prostate Imaging Reporting and Data System scores 1-3, which increased to 97% when prostate-specific antigen density <0.15 ng/ml/cm3 was combined. Among patients who did not undergo biopsy, patients with Prostate Imaging Reporting and Data System scores 1-3 plus prostate-specific antigen density <0.15 ng/ml/cm3 included significantly less cases in which significant prostate cancer was detected during the follow-up, compared with the others (3.2% versus 17% at 36 months). CONCLUSIONS: Restriction of prostate biopsies to patients with Prostate Imaging Reporting and Data System scores 4-5 or prostate-specific antigen density ≥0.15 ng/ml/cm3 proved to be the good biopsy strategy, effectively balancing risks and benefits.

Prostate-specific antigen level, biopsy grade group, and tumor-capsular contact length on magnetic resonance imaging are independently associated with an extraprostatic extension.

OBJECTIVE: To define the clinicopathological and radiological factors independently associated with the existence of an extraprostatic extension in radical prostatectomy specimens. METHODS: A total of 202 patients who underwent robotic prostatectomy following biparametric magnetic resonance imaging were assessed. We evaluated the clinicopathological and magnetic resonance imaging variables. We performed receiver-operating characteristic curve analyses to identify factors associated with extraprostatic extension. We engaged in multivariate analysis to identify factors independently associated with such extension. RESULTS: Extraprostatic extensions were apparent in the final prostatectomy specimens of 62 patients (31%). The areas under the curves of the prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were 0.76, 0.71, and 0.70, respectively, in receiver-operating characteristic analysis when used to predict extraprostatic extension; thus, higher than the areas under the curves of the other variables (0.61-0.68). The prostate-specific antigen level (odds ratio 1.090, p = 0.004), the biopsy grade group (odds ratios 2.678 and 6.358, p = 0.017 and p < 0.001 for grade group 3-4 and 5), and the tumor-capsular contact length (odds ratio 1.079, p = 0.001) were independently associated with extraprostatic extension. When the three factors were combined, the area under the receiver-operator characteristic curve increased to 0.79. CONCLUSIONS: The prostate-specific antigen level, the biopsy grade group, and the tumor-capsular contact length on magnetic resonance imaging were independently associated with extracapsular extension.

[A Case of Metachronous Occurrence of Interstitial Pneumonitis and Hypophysitis Following Nivolumab Plus Ipilimumab for Metastatic Renal Cell Carcinoma].

A 71-year-old man presented with neck pain. He was diagnosed with renal cell carcinoma of the left kidney with lung and bone metastases. After laparoscopic left nephrectomy, nivolumab plus ipilimumab was introduced as a first-line therapy for intermediate risk metastatic renal cell carcinoma based on the IMDC risk classification. After four cycles of nivolumab plus ipilimumab, he experienced dyspnea and was diagnosed with interstitial pneumonitis. Corticosteroid therapy was initiated, after which the symptoms of interstitial pneumonitis subsided. Corticosteroid therapy was tapered and discontinued after two months of treatment. The patient experienced fatigue at one week after the discontinuation of corticosteroid therapy and was diagnosed with isolated ACTH deficiency due to hypophysitis. He recovered after hydrocortisone treatment. This case involved two different immune-related adverse events (irAE), interstitial pneumonitis and hypophysitis, that occurred asynchronously following nivolumab plus ipilimumab therapy. It is important to observe the patient's condition carefully whether additional irAEs arise when corticosteroid therapy is tapered or discontinued.

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction.

Partial or complete obstruction of the urinary tract is a common and challenging urological condition caused by a variety of conditions, including ureteral calculi, ureteral pelvic junction obstruction, ureteral stricture, and malignant ureteral obstruction. The condition, which may develop in patients of any age, induces tubular and interstitial injury followed by inflammatory cell infiltration and interstitial fibrosis, eventually impairing renal function. The serum creatinine level is commonly used to evaluate global renal function but is not sensitive to early changes in the glomerular filtration rate and unilateral renal damage. Biomarkers of acute kidney injury are useful for the early detection and monitoring of kidney injury induced by upper urinary tract obstruction. These markers include levels of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1, kidney injury molecule 1, N-acetyl-b-D-glucosaminidase, and vanin-1 in the urine and serum NGAL and cystatin C concentrations. This review summarizes the pathophysiology of kidney injury caused by upper urinary tract obstruction, the roles played by emerging biomarkers of obstructive nephropathy, the mechanisms involved, and the clinical utility and limitations of the biomarkers.

A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study.

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-ß-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

Early urinary biomarkers of renal tubular damage by a high-salt intake independent of blood pressure in normotensive rats.

Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high-salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high-salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt-loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin-1, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (Kim-1) were measured. At 17 weeks of age, 8% salt-loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N-acetyl-ß-D-glucosaminidase (NAG), or Kim-1 during the study period among the groups, urinary vanin-1 and NGAL significantly increased in 8% salt-loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin-1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high-salt intake.

Cancer detection rate of prebiopsy MRI with subsequent systematic and targeted biopsy are superior to non-targeting systematic biopsy without MRI in biopsy naïve patients: a retrospective cohort study.

BACKGROUND: To determine whether prebiopsy multiparametric magnetic resonance imaging (mpMRI) with subsequent systematic plus targeted biopsies for suspicious lesions improve prostate cancer detection compared with standard non-targeting systematic biopsies without mpMRI in biopsy-naïve patients. METHODS: Patients who underwent their first prostate biopsy due to suspicion of prostate cancer were analyzed retrospectively to compare the biopsy outcomes between patients who received prebiopsy mpMRI (215 patients) and those who did not (281 patients). mpMRI was performed to determine pre-biopsy likelihood of the presence of prostate cancer using a three-point scale (1 = low level of suspicion, 2 = equivocal, and 3 = high level of suspicion). Systematic biopsies were performed in both groups. Targeted biopsies were added for a high level of suspicious lesions on mpMRI. All biopsies were performed by transperineal biopsy technique. After biopsy, Prostate Imaging Reporting and Data System ver. 2 (PIRADS-2) scoring was performed to describe the mpMRI findings and predictive value of PIRADS-2 was evaluated. RESULTS: The detection rate of total and clinically significant prostate cancer was significantly higher in patients who received prebiopsy mpMRI than in those who did not (55.3 and 46.0% vs. 42.0 and 35.2%, respectively; p = 0.004 and p = 0.016). The clinically insignificant prostate cancer detection rate was similar between the two groups (9.3% vs. 6.8%; p = 0.32). Of 86 patients who underwent systematic plus targeted biopsy in the MRI cohort and were diagnosed with prostate cancer, seven patients were detected by addition of targeted biopsy whereas 29 patients were missed by targeted biopsy but detected by systematic biopsy. There was a correlation between the PIRADS-2 and prostate cancer detection rate, and a receiver-operator curve analysis yielded an area under the curve of 0.801 (p <  0.0001). CONCLUSIONS: Prebiopsy mpMRI with subsequent systematic plus targeted biopsies for suspicious lesions can yield a higher cancer detection rate than non-targeting systematic biopsies. PIRADS-2 scoring is useful for predicting the biopsy outcome.

Combination of prostate imaging reporting and data system (PI-RADS) score and prostate-specific antigen (PSA) density predicts biopsy outcome in prostate biopsy naïve patients.

OBJECTIVE: To assess the value of the Prostate Imaging Reporting and Data System (PI-RADS) scoring system, for prostate multi-parametric magnetic resonance imaging (mpMRI) to detect prostate cancer, and classical parameters, such as prostate-specific antigen (PSA) level, prostate volume and PSA density, for predicting biopsy outcome in biopsy naïve patients who have suspected prostate cancer. PATIENTS AND METHODS: Patients who underwent mpMRI at our hospital, and who had their first prostate biopsy between July 2010 and April 2014, were analysed retrospectively. The prostate biopsies were taken transperineally under transrectal ultrasonography guidance. In all, 14 cores were biopsied as a systematic biopsy in all patients. Two cognitive fusion-targeted biopsy cores were added for each lesion in patients who had suspicious or equivocal lesions on mpMRI. The PI-RADS scoring system version 2.0 (PI-RADS v2) was used to describe the MRI findings. Univariate and multivariate analyses were performed to determine significant predictors of prostate cancer and clinically significant prostate cancer. RESULTS: In all, 288 patients were analysed. The median patient age, PSA level, prostate volume and PSA density were 69 years, 7.5 ng/mL, 28.7 mL, and 0.26 ng/mL/mL, respectively. The biopsy results were benign, clinically insignificant, and clinically significant prostate cancer in 129 (45%), 18 (6%) and 141 (49%) patients, respectively. The multivariate analysis revealed that PI-RADS v2 score and PSA density were independent predictors for prostate cancer and clinically significant prostate cancer. When PI-RADS v2 score and PSA density were combined, a PI-RADS v2 score of ≥4 and PSA density ≥0.15 ng/mL/mL, or PI-RADS v2 score of 3 and PSA density of ≥0.30 ng/mL/mL, was associated with the highest clinically significant prostate cancer detection rates (76-97%) on the first biopsy. Of the patients in this group with negative biopsy results, 22% were subsequently diagnosed as prostate cancer. In contrast, a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL yielded no clinically significant prostate cancer and no additional detection of prostate cancer on further biopsies. CONCLUSIONS: A combination of PI-RADS v2 score and PSA density can help in the decision-making process before prostate biopsy and in the follow-up strategy in biopsy naïve patients. Patients with a PI-RADS v2 score of ≤3 and PSA density of <0.15 ng/mL/mL may avoid unnecessary biopsies.

Risks and complications of transurethral resection of bladder tumors in patients receiving antiplatelet and/or anticoagulant therapy: a retrospective cohort study.

BACKGROUND: Information on the safety of transurethral resection of bladder tumors (TURBT) in patients receiving anti-thromboembolic drugs is currently lacking. This study aimed to evaluate the clinical safety of TURBT in patients receiving anti-thromboembolic agents compared with patients not taking these agents and patients who interrupted their use perioperatively. METHODS: We retrospectively analyzed data for patients who underwent TURBT at Jichi Medical University Saitama Medical Center from September 2013 to August 2016.Patients who underwent surgery while receiving antiplatelet and/or anticoagulant drugs were allocated to the continuation group, those who interrupted these drugs comprised the interruption group, and those who did not use these agents were designated as the control group. We compared the patient characteristics, hemoglobin levels, and complications among the three groups. RESULTS: A total of 174 patients were analyzed including 19, 18, and 137 in the continuation, interruption, and control groups, respectively. There were no significant differences in patient and tumor characteristics, apart from age, among the three groups. Decreases in hemoglobin levels were similar in the continuation, interruption, and control groups (-0.50 g/dl, -0.40 g/dl, and -0.50 g/dl, respectively).Significantly more patients in the continuation group experienced clot retention compared with the control group (21% vs 5%, p = 0.03). Large tumor size tended to be a risk factor for clot retention in the continuation group (p = 0.07). No patient in the continuation or interruption group required blood transfusion, compared with two patients (1%) in the control group. No patients in any of the groups experienced cardiovascular events during their hospital stay or required rehospitalization for hematuria after discharge. CONCLUSIONS: TURBT can be performed safely in patients who continue to take antiplatelet and/or anticoagulant agents, without increasing the risks of severe hemorrhage and blood transfusion. However, the risk of postoperative clot retention may be increased in these patients.

Transperineal ultrasound-guided prostate biopsy is safe even when patients are on combination antiplatelet and/or anticoagulation therapy.

BACKGROUND: To assess whether hemorrhagic complications associated with transperineal prostate biopsy increased in patients on antiplatelet and/or anticoagulant therapy. METHODS: In total, 598 consecutive patients underwent transperineal prostate biopsy. The medication group comprised patients who took anti-thromboembolic agents, and the control group comprised those who did not take these agents. No anti-thromboembolic agent was stopped before, during, or after prostate biopsy in the medication group. Complications developing in both groups were compared and classified using the modified Clavien classification system. Subgroup analyses to compare complications in patients taking single antiplatelet, single anticoagulant, and dual antiplatelet and/or anticoagulant agents, and multivariate analyses to predict bleeding risk were also performed. RESULTS: Of the 598 eligible patients, 149 comprised the medication group and 449 comprised the control group. Hematuria (Grade I) developed in 88 (59.1%) and 236 (52.5%) patients in the medication and control group, respectively (p = 0.18). Clot retention (Grade I) was more frequently observed in the medication group than the controls (2.0% versus 0.2%, respectively, p < 0.05). Hospitalization was more frequently prolonged in the medication than the control group (4.0% versus 0.4% of patients, respectively). No complication of Grade III or higher developed in either group. Hematuria was more frequent in patients taking a single anticoagulant (p = 0.007) or two anti-thromboembolic agents (p = 0.04) compared with those taking a single antiplatelet agent. Other complications were generally similar among the groups. In the multivariate analysis, taking more than two anti-thromboembolic agents was the only significant risk factor for bleeding events. CONCLUSION: No severe complication developed after the transperineal biopsies in either group, although minor bleeding was somewhat more frequent in the medication group. It may not be necessary to discontinue anticoagulant and/or antiplatelet agents when transperineal prostate biopsy is contemplated.

Influence of genetic polymorphisms of multidrug and toxin extrusion protein 1 on its mRNA expression in peripheral blood cells.

This study aimed to determine the effect of multidrug and toxin extrusion protein 1 (MATE1) genetic variants on its transcript expression in peripheral blood cells. Consistent with previous in vitro findings, MATE1 mRNA levels were significantly higher in subjects carrying rs2453579, but not rs2252281, compared to those without either of these promoter variants. In addition, the mRNA levels did not differ between subjects with both variants and those with neither allele. Thus, this study reveals that the influence of MATE1 genetic variants on its mRNA expression can be detected in vivo using peripheral blood.

Heavy hematuria requiring cystectomy in a patient with hemophilia A: a case report and literature review.

BACKGROUND: Hemophilia A is an X-linked recessive disorder caused by a deficiency in factor VIII. Hemophilia A affects 1 in 5,000-10,000 males. Hematuria is frequent in hemophilia. Hematuria in hemophilia is generally considered benign and manageable with conservative therapy; however, severe hematuria requiring surgical therapy has rarely been reported. CASE PRESENTATION: A 60-year-old male with hemophilia A presented with persistent gross hematuria of unknown cause. He was treated with recombinant factor VIII products, followed by several conservative therapies as follows: clot evacuation by vesicoclysis, continuous bladder irrigation with normal saline, and intravesical instillation of aluminum hydroxide/magnesium hydroxide (Maalox); however, these failed to resolve the hemorrhaging. The patient was offered and consented to cystectomy with an ileal conduit. Intraoperative clotting was normal with the infusion of adequate recombinant factor VIII products and transfusion of fresh-frozen plasma, and the procedure was performed safely. After surgery, the patient had blood in his stool several times. No bleeding site was demonstrated in the colon by colonoscopy and (99m)Technetium-human serum albumin-diethylenetriaminepenta-acetic acid scintigraphy demonstrated that the extravasation of radioactive isotope was detected at the anal side of terminal ileum but not at the oral side. These findings were suspected to be bleeding from the ileoileal anastomosis. However, the bleeding was managed with recombinant factor VIII products. CONCLUSIONS: Cystectomy in hemophilia may be safe, if monitored appropriately. Urinary diversion using the intestine may be avoided because anastomotic hemorrhage may become a problem.

[SMALL CELL CARCINOMA OF THE PROSTATE: A CASE REPORT OF RELATIVE LONG-TERM SURVIVAL].

Small cell carcinoma of the prostate (SCCP) is rare, and no standard treatment regimen has yet been established. The overall prognosis remains poor. We experienced a case who obtained relative long-term survival with two types of chemotherapy treatments. A 69-year-old man underwent combined androgen blockade (CAB) with a diagnosis of prostate adenocarcinoma (Gleason score = 5 + 3) that was staged T3bN1M1b (initial PSA = 352 ng/ml). Twenty-five months after hormonal therapy, the level of serum PSA had elapsed remain low, however, FDG-PET/CT revealed high value at the lymph node of para-aortic and pelvic lesion. The levels of serum NSE and Pro-GRP elevated, and a prostate re-biopsy revealed a small cell carcinoma. Therefore, he was treated with 12-cycles of combination chemotherapy consisting of etoposide and carboplatin. Then, disease has progressed, so he was changed to second line chemotherapy with amrubicin. He underwent 12-cycles chemotherapy with amrubicin, but he died of cancer 39 months after the initial treatment of SCCP.

Temsirolimus induces surfactant lipid accumulation and lung inflammation in mice.

Interstitial lung disease (ILD) is a well-known adverse effect of mammalian target of rapamycin (mTOR) inhibitors. However, it remains unknown how lung toxicities are induced by mTOR inhibitors. Here, we constructed a mouse model of mTOR inhibitor-induced ILD using temsirolimus and examined the pathogenesis of the disease. Male ICR mice were treated with an intraperitoneal injection of different doses of temsirolimus (3 or 30 mg·kg(-1)·wk(-1)) or vehicle. Temsirolimus treatment increased capillary-alveolar permeability and induced neutrophil infiltration and fibrinous exudate into the alveolar space, indicating alveolar epithelial and/or endothelial injury. It also induced macrophage depletion and the accumulation of excessive surfactant phospholipids and cholesterols. Alveolar macrophage depletion is thought to cause surfactant lipid accumulation. To further examine whether temsirolimus has cytotoxic and/or cytostatic effects on alveolar macrophages and alveolar epithelial cells, we performed in vitro experiments. Temsirolimus inhibited cell proliferation and viability in both alveolar macrophage and alveolar epithelial cells. Temsirolimus treatment caused some signs of pulmonary inflammation, including upregulated expression of several proinflammatory cytokines in both bronchoalveolar lavage cells and lung homogenates, and an increase in lymphocytes in the bronchoalveolar lavage fluid. These findings indicate that temsirolimus has the potential to induce alveolar epithelial injury and to deplete alveolar macrophages followed by surfactant lipid accumulation, resulting in pulmonary inflammation. This is the first study to focus on the pathogenesis of mTOR inhibitor-induced ILD using an animal model.

Retrotrigonal Layer Dissection from a Posterior Approach Enables Bladder Neck Preservation in Robot-Assisted Radical Prostatectomy.

BACKGROUND: We developed a novel surgical technique: dissection of the retrotrigonal layer from a posterior approach in robot-assisted radical prostatectomy (RARP). This approach enables earlier access to the posterior space during bladder neck dissection and helps preserve the bladder neck. We evaluated the safety and efficacy of this technique in terms of bladder neck preservation Methods: We retrospectively reviewed 238 consecutive patients who underwent RARP using this technique from August 2021 to September 2023. Key metrics included the success rate of accessing the posterior space prior to bladder neck opening during the dissection and the rate of bladder neck preservation. In addition, oncological and surgical safety, as well as continence recovery, were assessed. RESULTS: The median age and prostate-specific antigen level were 72 (65-75) years and 7.35 (5.40-11.5) ng/mL, respectively. In 153 (64%) patients, the posterior space was successfully accessed before bladder neck opening, with the success rate increasing from 56% in the series' first half to 72% in the second half (p = 0.015). The bladder neck was preserved in 120 (53%) patients, and this rate increased from 39% in the first half to 63% in the second half (p = 0.0004). Positive surgical margins at the junction between the prostate and bladder were observed in 10 cases (4%). Bladder neck preservation correlated with early continence recovery (hazard ratio 1.37 [95% confidence interval 1.03-1.83], p = 0.030). The grade 3 complication associated with this technique occurred in one case (0.5%). CONCLUSION: Retrotrigonal layer dissection from a posterior approach in RARP enhances the safety and ease of bladder neck dissection and aids in its preservation, potentially leading to improved continence recovery.

A novel anterior approach that involves Retzius space development between the umbilical ligaments is associated with a lower incidence of postoperative inguinal hernia in robotic radical prostatectomy.

Background: To facilitate robotic radical prostatectomy (RP), we developed a novel anterior approach that utilizes a peritoneal incision between the umbilical ligaments to develop the Retzius space without contacting the internal inguinal rings, followed by closure of this space prior to prostatectomy and vesicourethral anastomosis. This approach could decrease the incidence of postoperative inguinal hernia (IH), similar to a Retzius-sparing RP (RS-RP). We compared the incidence of IH following this novel approach with that following conventional anterior RP and RS-RP. Methods: We retrospectively reviewed 532 patients who underwent robotic RP from September 2017 to August 2022. We compared the incidence of IH following novel anterior RP (n = 153) to that following conventional anterior RP (n = 284) and RS-RP (n = 95). We also assessed the independent factors associated with postoperative IH using Cox hazard models. Results: The 12- and 24-month cumulative incidences of postoperative IH following novel anterior RP were 1.3% and 1.3%, significantly lower than those associated with conventional anterior RP (8.0% and 12.6%, p = 0.009) but not significantly different from those following RS-RP (1.1% and 2.1%, p = 0.782). In multivariate analysis, use of the novel anterior RP approach, RS-RP, and body mass index were independent factors negatively associated with the occurrence of postoperative IH. Conclusions: This novel anterior approach involves developing the Retzius space between the umbilical ligaments and closure of this space following prostatectomy and vesicourethral anastomosis. It can decrease the incidence of IH compared to the conventional anterior approach. Prospective comparative studies are necessary to confirm the benefits of this approach.