Successful embolization of subcutaneous mesenteric varices within an ileal conduit in a patient with liver cirrhosis.

Introduction: Venous hemorrhage from ectopic varices is potentially fatal. This report describes a rare case in which bleeding from mesenteric varices in an ileal conduit was treated successfully by embolization therapy. Case presentation: The patient was an 82-year-old man who had previously undergone total pelvic exenteration for colon cancer with creation of an ileal conduit for urinary diversion. He subsequently developed liver cirrhosis and underwent partial hepatectomy for hepatocellular carcinoma. 9 years after his colon surgery, he was admitted with gross hematuria. Computed tomography revealed subcutaneous mesenteric varices in the ileal conduit and hemorrhage as a result of rupture of the varices. The bleeding continued despite repeated manual compression but was eventually stopped by embolization therapy. Conclusion: Embolization therapy may be helpful for hemostasis in the event of intractable bleeding from mesenteric varices in an ileal conduit.

Predictive models of long-term survival outcomes following radical cystectomy.

BACKGROUND: Identifying the likelihood of life-threatening recurrence after radical cystectomy by reliable and user-friendly predictive models remains an unmet need in the clinical management of invasive bladder cancer. METHODS: A total of 204 consecutive patients undergoing open radical cystectomy (ORC) for bladder cancer were retrospectively enrolled between May 2005 and August 2020. Clinicopathological and peri-ORC therapeutic data were extracted from clinical records. We explored predictive factors that significantly affected the primary endpoint of overall survival (OS) and secondary endpoints of cancer-specific survival (CSS) and recurrence-free survival (RFS). RESULTS: During a median follow-up of 3.9 years, 42 (20.6%) and 10 (4.9%) patients died due to bladder cancer and other causes, respectively. Five-year RFS, CSS, and OS were 66.5%, 77.6%, and 75.4%, respectively. Pathological T and N categories and lymphovascular invasion (LVI) significantly affected RFS by Cox regression analysis. Accordingly, clinical T and pathological N categories and LVI significantly affected CSS. Clinical T and pathological N categories, LVI, age, and ORC tumor grade significantly affected OS. Based on the assessment score for each independent risk factor, we developed the Gunma University Oncology Study Group (GUOSG) score, which predicts RFS, CSS, and OS. The GUOSG score classified four groups for RFS, three for CSS, and five for OS, with statistically significant distribution for nearly all comparisons. CONCLUSIONS: The GUOSG model is helpful to show individualized prognosis and functions as a risk-stratified historical cohort for assessing the lifelong efficacy of new salvage treatment regimens.

Retroperitoneal urothelial carcinoma arising after bladder diverticulectomy: a case report.

BACKGROUND: Urothelial carcinoma arises from the inner urothelial membrane of the renal pelvis, ureter, and bladder and often causes macrohematuria. Here, we report a rare case in which the patient developed non-symptomatic urothelial carcinoma anatomically outside the bladder wall 17 years after bladder diverticulectomy. CASE PRESENTATION: An 82-year-old male patient previously underwent gastrectomy for stomach cancer and partial hepatectomy for intrahepatic cholangiocarcinoma. Follow-up computed tomography revealed a tumor in the retroperitoneal space, where a bladder diverticulum was removed 17 years earlier. Multiparametric magnetic resonance imaging suggested that the tumor was malignant with rectal invasion. Subsequent computed tomography-guided percutaneous biopsy revealed that the tumor was urothelial carcinoma. The patient underwent two courses of neoadjuvant chemotherapy followed by pelvic exenteration with pelvic lymph node dissection. He is currently receiving adjuvant therapy with an immune checkpoint inhibitor and has had no recurrence for 3 months. CONCLUSIONS: Multiparametric magnetic resonance imaging is a helpful tool for predicting both tumor malignancy and invasion before a pathologically confirmed diagnosis. Although this case is rare, urologists should be aware of the occurrence of urothelial carcinoma after bladder diverticulectomy in cases of incomplete resection of the diverticulum.

The utility of the [-2]pro-prostate-specific antigen level as a prognostic marker in patients with castration-resistant prostate cancer treated with enzalutamide.

BACKGROUND: The prostate health index (phi) derived using [-2]pro-prostate-specific antigen (p2PSA), a precursor of PSA, has been shown to predict cancer in the gray zone. However, the utility of p2PSA in predicting outcomes for castration-resistant prostate cancer (CRPC) patients remains unknown. Therefore, in this study, we aimed to evaluate the usefulness of p2PSA in predicting the efficacy and prognosis of enzalutamide treatment in CRPC patients. METHODS: We conducted a prospective study of CRPC patients treated with enzalutamide at our institution, measuring p2PSA levels in 98 pre-treatment serum samples. All patients were divided into two groups based on the median values of each parameter. The PSA progression-free survival (PSA-PFS) and overall survival (OS) were compared using the Kaplan-Meier method. This study was approved by the Institutional Review Board of Gunma University Hospital (IRB No. 2021-092, 1983). RESULTS: The median PSA level before enzalutamide treatment was 25.59 ng/mL, the median p2PSA level was 208.75 pg/mL, and the median phi was 187.95. PSA, p2PSA, and phi were not all predictors of PSA-PFS. However, the OS was significantly better in the low-value groups (log-rank p-values of PSA, p2PSA, and phi were 0.024, 0.034, and 0.018, respectively). In the docetaxel (DOC)-naive group (n = 58), PSA was not a predictor of OS, but p2PSA and phi were significantly associated with better OS in the low group. This relationship was not observed in the DOC-treated group. CONCLUSIONS: Our study elucidates the usefulness of p2PSA in predicting outcomes for CRPC patients treated with enzalutamide. It suggests that p2PSA and phi may be prognostic markers after enzalutamide administration in CRPC patients.

Two cases of CRPC with BRCA mutation treated by olaparib after favorable response to cisplatin.

Introduction: Several prostate cancers carry homologous recombination repair mutations that respond to olaparib. Because of the mechanism, the efficacy of platinum-based therapy can be used to predict the efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors such as olaparib. Case presentation: We experienced two neuroendocrine prostate cancer patients who achieved a response duration of more than 1 year with platinum-based therapy. Case 1 had a BRCA2 mutation in the germline and case 2 had a BRCA2 mutation in a somatic chromosome only. Both patients responded well to olaparib. Conclusion: Cisplatin and olaparib may overlap in response due to their medicinal action. It may be useful to consider genetic testing in some CRPC patients who have responded to cisplatin.

Fibroblast growth factor receptor inhibitor erdafitinib promotes Mcl-1 degradation and synergistically induces apoptosis with Bcl-xL/Bcl-2 inhibitor in urothelial cancer cells.

Metastatic urothelial cancer is a lethal disease. Although recent advances in immunotherapies and targeted therapy against fibroblast growth factor receptor (FGFR)2/3 mutation (erdafitinib) have improved patient survival, there is still a critical need for novel therapeutic strategies for patients who do not benefit from these treatments. Evasion of apoptosis through amplifying anti-apoptotic Bcl-2 family proteins (Mcl-1, Bcl-xL, Bcl-2) is one mechanism responsible for treatment resistance in urothelial cancers, suggesting that targeting anti-apoptotic proteins may be a possible therapeutic strategy for urothelial cancers. Here, we showed that erdafitinib increased Mcl-1 degradation mainly through previously unknown mechanisms and synergized with a BH3 mimetic drug targeting Bcl-xL/Bcl-2 to induce apoptosis in FGFR wild-type urothelial cancer cells. Strikingly, clinical sequencing data showed amplification of MCL1 or BCL2L1 (encoding Bcl-xL) in subsets of FGFR mutation-negative bladder cancer tissues. In conclusion, these findings suggest that exploiting apoptosis pathways may be a promising treatment strategy for patients with FGFR wild-type metastatic urothelial cancer with Mcl-1 or Bcl-xL overexpression.

[Malignant Central Nervous System Lymphoma after Radical Total Cystectomy : A Diagnostic Challenge].

We report a case of primary central nervous system lymphoma (PCNSL) in an 81-year-old man who had undergone radical cystectomy with an ileal conduit urostomy due to a diagnosis of muscle-invasive bladder cancer. The postoperative diagnosis was invasive urothelial carcinoma (pT2bN1M0, stage IV). Gemcitabine-cisplatin therapy was provided as adjuvant chemotherapy, and there was no recurrence during follow-up. Four years after surgery, he visited the emergency department because of weakness of the lower extremities and stuttering. He was found to have a parietal lobe mass on magnetic resonance imaging (MRI) and hospitalized with suspicion of brain metastasis. Despite examination by a neurosurgeon, it was not possible to make a clinical diagnosis, and the patient gradually deteriorated and died 21 days later. The pathology results were diagnostic of PCNSL.

Long-term longitudinal changes in baseline PSA distribution and estimated prevalence of prostate cancer in male Japanese participants of population-based PSA screening.

Japan has experienced a drastic increase in the incidence of prostate cancer (PC). To assess changes in the risk for PC, we investigated baseline prostate specific antigen (PSA) levels in first-time screened men, across a 25-year period. In total, 72,654 men, aged 50-79, underwent first-time PSA screening in Gunma prefecture between 1992 and 2016. Changes in the distribution of PSA levels were investigated, including the percentage of men with a PSA above cut-off values and linear regression analyses comparing log10 PSA with age. The 'ultimate incidence' of PC and clinically significant PC (CSPC) were estimated using the PC risk calculator. Changes in the age-standardized incidence rate (AIR) during this period were analyzed. The calculated coefficients of linear regression for age versus log10 PSA fluctuated during the 25-year period, but no trend was observed. In addition, the percentage of men with a PSA above cut-off values varied in each 5-year period, with no specific trend. The 'risk calculator (RC)-based AIR' of PC and CSPC were stable between 1992 and 2016. Therefore, the baseline risk for developing PC has remained unchanged in the past 25 years, in Japan. The drastic increase in the incidence of PC, beginning around 2000, may be primarily due to increased PSA screening in the country.

Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

OBJECTIVES: To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. METHODS: The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. RESULTS: The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. CONCLUSIONS: Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance.

[A Case of Primary Renal Malignant Lymphoma Initially Managed as Severe Pyelonephritis in a Patient Undergoing Hemodialysis].

A 75-year-old male undergoing hemodialysis because of diabetic nephropathy was referred to our hospital complaining of high fever and swelling of the left kidney. Our initial clinical diagnosis was severe pyelonephritis. He was initially treated with intravenous antibiotics and his clinical symptoms subsequently improved but only temporarily. The high fever soon recurred, accompanied by progressive thrombocytopenia. His general condition deteriorated despite conservative treatment. He then underwent nephrectomy of the left kidney. However, the thrombocytopenia persisted and his general condition did not improve. The pathological diagnosis was malignant lymphoma (non-Hodgkin's lymphoma, diffuse large B-cell type). He received chemotherapy, but his status rapidly deteriorated and he died 1.5 months after the operation. Primary renal malignant lymphoma is very rare, because the kidney lacks lymphatic tissue.

Comprehensive assessment for novel prostate cancer markers in the prostate-specific antigen era: focusing on Asians and Asian countries.

We reviewed the current evidence for three novel prostate tumor markers (PCA3, TMPRSS2:ERG and proPSA) that have been recently reported predominantly in Western countries. We focus our attention on Asian men in both clinical and basic research studies. There have been no reports on the clinical usefulness of these three markers for Asians living in Western countries. In Asian countries, evidence for the clinical usefulness of PCA3 and proPSA-related indices including Prostate Health Index is being accumulated, mainly in Japan. The process for how a novel marker is approved in the clinical setting is also discussed.

Next-generation prostate-specific antigen test: precursor form of prostate-specific antigen.

An urgent need exists to develop a more sophisticated screening system in order to improve diagnostic accuracy of clinically significant cancer and also to reduce the drawbacks of prostate-specific antigen (PSA) screening including overdetection and overtreatment. The most promising next-generation PSA test, which can improve the management of prostate cancer, may be proenzyme PSA (proPSA) or precursor PSA (pPSA). proPSA has pro-leader peptide sequences of seven or less amino acids and previous studies demonstrated that [-2]proPSA, which contains only a 2-amino-acid propeptide leader, could be more useful not only to distinguish between men with and without cancer, but also between tumors with aggressive features with performance exceeding other classical PSA-related indices including ratio of free PSA to total PSA (%f-PSA) and PSA density. Recently, it was demonstrated that baseline [-2]proPSA-related indices were independent factors to predict pathological reclassification at one year or several years after entering active surveillance. Furthermore, a retrospective study suggested that [-2]proPSA might be a useful predictive marker for future developing clinically manifested prostate cancer as well as aggressive tumors. ProPSA-related indices may have the potential for developing a more ideal risk classification for men at risk for prostate cancer, with a screening system maintaining the sensitivity of detecting clinically significant prostate cancer while saving cost, individualized treatment strategies, and follow-up procedures of active surveillance or active treatments. At a minimum, proPSA will be one of the most important new markers on the prostate cancer management in the near future.