Comparison of Cabozantinib and Axitinib as Second-line Therapy After Nivolumab Plus Ipilimumab in Patients With Metastatic Clear Cell Renal Cell Carcinoma: A Comparative Analysis of Retrospective Real-world Data.

BACKGROUND: To date, no studies have compared the treatment outcomes of second-line therapies in patients with metastatic clear cell renal cell carcinoma (ccRCC). This study retrospectively evaluated the efficacy of cabozantinib and axitinib as second-line treatments in patients with metastatic ccRCC who previously received immune-oncology combination therapy. PATIENTS AND METHODS: Patients with metastatic ccRCC treated with cabozantinib and axitinib as second-line therapy after nivolumab-ipilimumab treatment were identified among 243 patients with RCC treated between August 1, 2018 and January 31, 2022 at 34 institutions belonging to the Japanese Urological Oncology Group. Patients were assessed for treatment outcomes, including progression-free survival (PFS), overall survival, objective response rate (ORR), and incidence rate of treatment-related adverse events (AEs). RESULTS: Forty-eight patients treated with cabozantinib and 60 treated with axitinib as second-line therapy after nivolumab-ipilimumab treatment for metastatic ccRCC were identified. The median PFS (95% confidence interval) was 11.0 months (9.0-16.0) with cabozantinib and 9.5 months (6.0-13.0) with axitinib. The ORRs were 37.5% (cabozantinib) and 38.3% (axitinib). The rates of any-grade AEs and grade ≥3 AEs were 79.2% (cabozantinib) versus 63.3% (axitinib; P = .091) and 35.4% (cabozantinib) versus 23.3% (axitinib; P = .202), respectively. In the poor-risk group, PFS was longer in the cabozantinib group than in the axitinib group (P = .033). CONCLUSION: The efficacy and safety of cabozantinib and axitinib were comparable. In the poor-risk group, cabozantinib was more effective than axitinib. These findings provide valuable insights into the selection of second-line treatment options after nivolumab-ipilimumab treatment in patients with metastatic ccRCC.

Clinical characteristics and survival outcomes of elderly patients with de novo metastatic germ cell tumors.

OBJECTIVES: To determine the outcomes for elderly patients with de novo metastatic germ cell tumors and the influence of patient age on adherence to standard chemotherapy. METHODS: A total of 150 patients who were initially diagnosed with metastatic germ cell tumors and treated at our institution between 2007 and 2021 were included. Patients were classified according to three age groups: aged <40, 40-49, and ≥50 years. Clinicopathological features, adherence to standard first-line chemotherapy, overall survival, and disease-free survival were compared between these groups. We also analyzed the outcomes of patients who received low-intensity induction chemotherapy due to adverse events and/or comorbidities. RESULTS: There was no significant difference in any of the survival outcomes and in the rate of adherence to standard first-line chemotherapy between the three age groups, although elderly patients with intermediate/poor prognosis group tended to receive less-intense chemotherapies. The rate of febrile neutropenia as a chemotherapy-related adverse event was significantly higher in patients aged ≥50 years. No statistical significance in survival outcomes was detected between the group of patients who received relatively low-intensity induction chemotherapy and those who received adequately intensive planned chemotherapy. CONCLUSIONS: The adherence rate of standard fist-line chemotherapy of elderly patients is almost comparable to that of younger patients, although some adverse events should be carefully managed. Even elderly patients with metastatic germ cell tumors can aim for equivalently good survival outcome like younger populations, with effort to adhere to standard chemotherapy.

Significant reduction in burden of metastatic disease by intermittent docetaxel therapy in a patient with castration-resistant prostate cancer.

Intermittent docetaxel therapy (IDT) is rarely used nowadays as a treatment option for men with metastatic castration-resistant prostate cancer (mCRPC) because of the widespread availability of androgen receptor axis-targeted therapy, which is less toxic. Therefore, there is limited information available on whether IDT has a clinical benefit in the treatment of men with mCRPC. This report describes the case of a 66-year-old man with a diagnosis of cT2N1M0 prostate cancer who underwent neoadjuvant combined androgen blockade and whole-pelvis radiation therapy. However, the tumor had progressed to mCRPC with metastasis to the bladder and a left pelvic lymph node within 2 years. Docetaxel had been administered as first-line chemotherapy, and the patient achieved a complete response in terms of the bladder metastasis. Docetaxel was stopped after 15 cycles. When a durable response had been maintained for more than 2 years, during which only androgen deprivation therapy was administered, the patient was switched to observation only. However, his prostate-specific antigen level gradually increased. Abiraterone was started as second-line therapy, during which there was a rapid increase in the PSA level. Computed tomography revealed further enlargement of the left pelvic lymph node, bladder metastasis, metastasis to the left common iliac lymph nodes, and several disseminated nodules around the bladder. Docetaxel was reintroduced as IDT for third-line therapy, and a complete response was achieved for all metastases, with the exception of the metastasis in the left pelvic lymph node. Thus far, the patient has survived for more than 7 years after starting docetaxel as first-line therapy for mCRPC. IDT is potentially useful in a subgroup of patients with mCRPC and could achieve long-term survival. Comprehensive genomic profiling may help physicians to select patients with mCRPC who are more likely to benefit from docetaxel than other systemic therapy.

Prognostic impact of histological discordance between transurethral resection and radical cystectomy.

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

The clinical significance of perioperative inflammatory index as a prognostic factor for patients with retroperitoneal soft tissue sarcoma.

BACKGROUND: The prognostic factors of retroperitoneal soft tissue sarcoma (STS) have been explored but not yet certain. This study evaluated the prognostic impact of various preoperative clinical parameters and inflammatory indices in primary STS, with a particular focus on the transition of inflammatory index before and after tumor resection in de-differentiated liposarcoma (DD-LPS). METHODS: The clinical data of 113 patients with primary retroperitoneal STS receiving tumor resection were reviewed. Six variables (neutrophils, platelets, C-reactive protein (CRP), lymphocytes, albumin, and hemoglobin) in the blood samples were measured and nine inflammatory indices (neutrophil-lymphocyte ratio (NLR), CRP-lymphocyte ratio (CLR), platelet-lymphocyte ratio (PLR), neutrophil-albumin ratio (NAR), CRP-albumin ratio (CAR), platelet-albumin ratio (PAR), HALP (hemoglobin, albumin, lymphocyte and platelet), prognostic nutrition index (PNI), and modified Glasgow Prognostic Score (mGPS)) were calculated. The prognostic value of the indices was analyzed by univariate and multivariate analyses. RESULTS: Elevated NLR, CLR, PLR, NAR, CAR, PAR, and mGPS were associated with a worse overall survival (p = 0.0124, 0.0011, 0.049, 0.0047, 0.0085, 0.0332, and 0.0086, respectively) in univariate analysis. Multivariate analysis showed that elevated CLR and DD-LPS were associated with poor overall survival (p = 0.0267 and 0.0218, respectively) in all retroperitoneal STS. In DD-LPD, patients with preoperative high CLR, whose postoperative CLR was normalized, demonstrated a favorable survival rate similar to those with preoperative low CLR. CONCLUSIONS: Elevated CLR before surgery as well as DD-LPS were poor prognostic markers for overall survival in primary retroperitoneal STS. Perioperative CLR normalization may be related to a favorable prognosis in DD-LPS.

Isostearyl Mixed Anhydrides for the Preparation of N-Methylated Peptides Using C-Terminally Unprotected N-Methylamino Acids.

Sustainable and efficient manufacturing methods for N-methylated peptides remain underexplored despite growing interest in therapeutic N-methylated peptides within the pharmaceutical industry. A methodology for the coupling of C-terminally unprotected N-methylamino acids mediated by an isostearic acid halide (ISTAX) and silylating reagent has been developed. This approach allows for the coupling of a wide variety of amino acids and peptides in high yields under mild conditions without the need for a C-terminal deprotection step in the process of C-terminal elongation. These advantages make this a useful synthetic method for the production of peptide therapeutics and diagnostics containing N-methylamino acids.

[Rupture of Adrenal Artery Aneurysm : A Case Report].

A 45-year-old man with severe left flank pain was brought by ambulance to our hospital early in the morning. On arrival, his circulation dynamics were stable. His urinalysis results were normal, and ultrasonography showed no hydronephrosis. Abdominal dynamic computed tomography (CT) showed a huge retroperitoneal hematoma suspected of hemorrhage from a left adrenal artery aneurysm. After 3 hours of absolute bed rest, the patient experienced episodes of anemia, decreased blood pressure and increased pulse. Recheck of CT showed bleeding into the peritoneal cavity. Therefore, the patient was immediately treated with transcatheter arterial embolization.

[Treatment outcome of laparoscopic radical cystectomy at a single institution].

OBJECTIVE: The standard care for invasive bladder cancer is radical cystectomy with urinary diversion, but laparoscopic radical cystectomy (LRC) is still being evaluated. We describe our initial experience of laparoscopic radical cystectomy compared to open radical cystectomy (ORC). PATIENTS AND METHODS: From January 2000 to June 2012, 84 patients underwent radical cystectomy by ORC (n = 54) or LRC (n = 30). Treatment outcomes including surgical and oncological outcomes between LRC and ORC were compared. We also assessed learning curve during LRC as to blood loss, operating time and complication rate. RESULTS: The patients' characteristics were similar in LRC and ORC groups except for ASA score. Importantly, Operating time during LRC was longer but complication rate of LRC was lower than that of ORC (586 min vs 424 min and 40% vs 69%, respectively). In addition, pathological stage or outcomes were similar in both groups and there were no significant difference between LRC and ORC groups in terms of overall and recurrence free survival rate. As for learning curve of LRC, operating time and blood loss tended to decrease with increased experience. CONCLUSION: These results indicate that LRC could be performed safely with decreased complication rate and similar oncological outcomes compared to ORC.

Safety and efficacy of ureteroscopy after obstructive pyelonephritis treatment.

OBJECTIVES: An obstructed, infected kidney combined with ureteral stones can be lethal, and requires urgent drainage and complete stone removal. However, the optimal method of stone removal, and its safety and efficacy have yet to be conclusively established. The aim of this study was to determine the safety and efficacy of carrying out ureteroscopy after kidney drainage for septic patients with obstructing stones. METHODS: From January 2004 to September 2011, 88 patients underwent stone removal by either ureteroscopy (n = 48) or extracorporeal shock wave lithotripsy (n = 40) after drainage of obstructive pyelonephritis. Patients' characteristics were analyzed, and treatment outcomes between the ureteroscopy and extracorporeal shock wave lithotripsy groups were compared. The outcomes of ureteroscopy carried out during the same period between patients with preoperative obstructive pyelonephritis and those without were also compared. RESULTS: Obstructed, infected kidneys were decompressed with retrograde ureteral stenting, except for two and three cases treated with nephrostomy in the ureteroscopy and extracorporeal shock wave lithotripsy groups, respectively. The severity of preoperative pyelonephritis was similar in both groups. Importantly, the success rate was 67.5% for extracorporeal shock wave lithotripsy and 98% for ureteroscopy (P < 0.001). Likewise, the retreatment and auxiliary procedure rates were significantly greater in the extracorporeal shock wave lithotripsy group than in the ureteroscopy group (90% vs 0% and 32.5% vs 2%, respectively). Furthermore, patients treated by ureteroscopy with or without preoperative pyelonephritis had similar stone-free and ureteroscopy complication rates (97% vs 93%, and 10% vs 12%). CONCLUSIONS: Ureteroscopy after drainage of an obstructed infected kidney can be a safe and effective option, as it seems to not be associated with an increased risk of complications.

[Retrospective analysis of the long-term indwelling ureteral stent].

An indwelling ureteral stent is commonly used for relief of ureteral obstruction. However, few reports have documented the frequency of febrile urinary tract infection and changes in renal function in patients with long-term ureteral stent placement. Here we report our experience with patients who had undergone long-term placement of ureteral stents. Between January 2005 and March 2011, we performed exchange of ureteral stents in 25 patients for more than one year. The mean serum creatinine level at the baseline, after stent placement, and 1 year later was 2.10, 1.24, and 1.39 mg/dl, respectively. In 14 of the patients, 39 episodes of febrile urinary tract infection occurred. Among a total of 1,055 stent exchanges, 39 episodes (3.7%) of stent encrustation occurred. Two patients in whom stents had been forgotten suffered septic shock. The serum creatinine level following a long placement period did not change significantly, and of the patients whose hydronephrosis remained after stent placement, the risk of febrile urinary tract infection rises. Our results suggest that ureteral stents could be indwelt for a fairly long period of time without major complications as long as they were carefully followed up and regularly exchanged.

[Outcome analysis of the urethral stent (Memotherm®)].

A number of patients with benign prostatic hyperplasia can not undergo surgical therapy because of advanced age, concomitant diseases, and other reasons. Since 1980, various types of urethral stents have been used for high-risk patients with benign prostatic hyperplasia. We report our experience with the use of urethral stents (Memotherm®). Between July 2002 and December 2010, we implanted urethral stents in 36 patients. The average follow-up period was 24.0 months. After stent implantation, 34 of the 36 patients were able to micturate. The average residual urine volume was 24.7 ml (0-250 ml), and the maximal urinary flow rate was 10.7 ml/s (3-24 ml/s). One stent had to be removed due to bladder tamponade, and one had to be exchanged due to dislocation. In 2 patients, a stone formed at the bladder end of the stent, and one of these patients underwent transurethral lithotripsy. Our results suggest that therapy with the Memotherm® urethral stent is a good option for patients suffering from urinary retention due to benign prostatic hyperplasia.

[A case of renal arteriovenous fistula complicated with pyelonephritis].

We report a case of renal arteriovenous fistula, which was found during treatment for pyelonephritis. A 61-year-old woman was referred to our hospital because of lumbar backache and infectious fever. The computed tomographic scan showed right hydronephrosis and perinephritis. We treated her conservatively for pyelonephritis, but 5 days later, the contrast-enhanced computed tomographic scan showed retroperitoneal hemorrhage. Renal angiography demonstrated an arteriovenous fistula in the central portion of the right kidney. Superselective transcatheter arterial embolization of the AVF was performed. Hemostasis was possible by embolization. She has not had any recurrence of renal arteriovenous fistula. To our knowledge, this is the 5th report of a rupture in the retroperitoneum of an arteriovenous fistula, and renal arteriovenous fistula with the pyelonephritis is very rare.