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ObjectivesTo determine risk factors influencing the incidence of parastomal hernia (PH) associated with ileal conduit (IC).MethodsA total of 194 Japanese patients who underwent IC diversion followed by regular postoperative radiographic follow-up from 2005 through 2016 were enrolled. The diagnosis of PH was determined by computed tomography (CT) for patients with and without related symptoms. The cumulative incidence of PH was assessed by the Kaplan–Meier method. The log-rank test and a multivariate Cox proportional hazards model were used to evaluate risk factors associated with the incidence of PH.ResultsPH was observed in 20 patients (10.3%) after a median follow-up of 25.5 months. Of the 20 patients, three were symptomatic. The cumulative incidences were 3.6%, 10.1% and 15.1% at 1, 2 and 5 years after operation, respectively. The median body mass index (BMI) was 23.1 kg/m2 (IQR 20.4–24.6). The BMI and diameter of the passage through the rectus abdominis muscle for the IC (DPRAM) were significant predictors for PH (p = 0.04 and p < 0.001, respectively). In proportional hazards regression analysis, DPRAM ≥ 2.4 cm was the only independent risk factor for developing PH (HR 10.94, 95% CI 3.66–32.64).ConclusionsThe incidence of PH in the current Japanese series was relatively low. Even in the population with low BMI, higher BMI might have an impact on incidence of PH. Moreover, DPRAM was also significantly associated with the incidence, suggesting that the operative procedure for creation of the passage is critical for future development of PH.

Neutrophil-to-lymphocyte ratio (NLR) was reported to be associated with prognosis of urothelial cancer (UC) patients receiving systemic chemotherapy or immunotherapy. However, it has not been elucidated how preceding first-line chemotherapy affects NLR and subsequent second-line pembrolizumab treatment. This multicenter study analyzed 458 patients with metastatic UC who received first-line chemotherapy and second-line pembrolizumab with regard to pre-chemotherapy and pre-pembrolizumab NLR in association with the efficacy of chemotherapy and pembrolizumab treatment. NLR was increased in 47% while decreased in 53% of patients before and after first-line chemotherapy. High pre-chemotherapy NLR (≥ 3) was significantly associated with unfavorable overall (OS, P = 0.0001) and progression-free (P < 0.0001) survivals after first-line chemotherapy. However, pre-chemotherapy NLR showed only modest influence on radiological response and survival after second-line pembrolizumab treatment, whereas pre-pembrolizumab NLR showed higher association. NLR decrease was associated with partial response or greater objective response by first-line chemotherapy, while NLR increase was associated with higher patient age. In conclusion, immediate pre-chemotherapy and pre-pembrolizumab NLR was significantly associated with efficacy of the following treatment, respectively. However, even patients with high pre-chemotherapy NLR achieved favorable OS if they had their NLR reduced by chemotherapy, whereas those with high pre-chemotherapy NLR yielded unfavorable OS if they had their NLR remained high after chemotherapy, suggesting that chemotherapy may have differential effect on the efficacy of subsequent pembrolizumab treatment in UC patients.

Background: To clarify the timing of treatment initiation for non-metastatic castration-resistant prostate cancer (nmCRPC), we investigated the impact of baseline prostate-specific antigen (PSA) at treatment initiation on outcomes, the stability of PSADT estimation at low PSA levels, and the prognostic significance of PSADT. Methods: We retrospectively analyzed 129 consecutive nmCRPC patients between 2000 and 2023. All patients were divided by PSADT ≤ 10 months (n = 109) or >10 months (n = 20). PSA progression-free survival (PSA-PFS) and metastasis-free survival (MFS) were assessed by the Kaplan–Meier method, with predictive factors analyzed using Cox proportional hazards modeling. PSA-PFS was further compared across baseline PSA subgroups (<3, 3–5, 5–10, >10 ng/mL) in the PSADT ≤ 10 months cohort. Results: Patients with PSADT ≤ 10 months had worse MFS than patients with PSADT > 10 months (4-year: 71.9% vs. 100%; p = 0.021). In the PSADT ≤ 10 months group, novel androgen receptor pathway inhibitor (ARPI) treatment significantly improved PSA-PFS compared to those who did not (median: 44.0 vs. 16.6 months; p < 0.001). In multivariate analysis, prior definitive local therapy (Hazard Ratio [HR] 0.409, p < 0.001), ARPIs as first-line treatment (HR 0.421, p < 0.001) and lower baseline PSA at treatment initiation (HR 0.961, p = 0.004) were significantly predictive factors for PSA-PFS. PSADT estimation remained accurate when calculated from PSA nadir values ≥0.5 ng/mL. Conclusions: In patients with nmCRPC with PSADT ≤ 10 months, early initiation of ARPIs at lower PSA levels was associated with improved PSA-PFS. PSADT stabilized at PSA levels of >0.5 ng/mL. These findings support earlier ARPI initiation to optimize outcomes in high-risk nmCRPC.

Purpose To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). Methods We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. Results One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P  < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P  < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P  = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P  < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P  = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P  < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P  < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. Conclusions We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

Introduction Pyoderma gangrenosum is a rare dermatological disease associated with underlying inflammatory conditions. Case presentation A 59‐year‐old man was diagnosed with right renal cancer cT1aN0M0 and laparoscopic right radical nephrectomy was performed. Five days after surgery, he had a high‐grade fever, surgical site flare, and severe pain. At first, we diagnosed surgical site infection and wound dehiscence. Despite treatment for infection, his general condition and dermatological symptoms did not improve. Thereafter, a dermatologist advised us to perform a skin biopsy and blood culture examinations. Finally, the man was diagnosed with pyoderma gangrenosum according to the pathology of the skin biopsy and negative blood culture. After both intravenous administration of predonisolone and a topical corticosteroid, the high‐grade fever and dermatological symptoms improved greatly. Conclusion Although pyoderma gangrenosum is a rare disease, we should bear in mind the disease since the treatment strategy is completely different from that for surgical site infection.

BackgroundThere is no useful predictive marker for reclassification on active surveillance. Thus, we aimed to investigate thresholds of [−2] proPSA (p2PSA)-related parameters to predict reclassification of the first-year protocol biopsy (1-year PBx) and evaluate the influence of clinical decision-making.MethodsThis was an observational, prospective cohort study conducted at 19 Japanese institutes. The inclusion criteria included clinical stage T1c/T2, prostate-specific antigen (PSA) levels ≤10 ng/mL, PSA density <0.2 ng/ml/cc, one or two positive biopsy cores, and Gleason score (GS) ≤6 (GS ≦7 for patients aged ≥70 years) at diagnostic biopsy. All participants were required to receive a blood-sampling test on a protocol visit at inclusion and at the 1-year PBx. PSA and PSA isoforms (free PSA, p2PSA) were measured, and parameters (%free PSA, %p2PSA, phi) were calculated. Multivariable logistic regression models were used to predict the reclassification risk. To assess the predictive power and thresholds for reclassification, we plotted Receiver Operating Characteristic (ROC) curves. Decision curve analysis (DCA) was used to evaluate the variables that yielded a net clinical benefit.ResultsA total of 135 patients were included, and 36 patients were reclassified on the 1-year PBx. Multivariate analyses showed that %p2PSA and phi at inclusion and p2PSA, %p2PSA, and phi before the 1-year PBx were significant predictors of reclassification at the 1-year PBx. The ROC analysis showed an optimal cutoff point, sensitivity, and specificity of %p2PSA and phi before the 1-year PBx of 1.64, 86%, 49% and 35.92, 89%, 47%, respectively. The DCA showed that phi before the 1-year PBx had the highest net benefit. The study limitation was its single-arm observational design.Conclusions%p2PSA and phi before the 1-year PBx had a good prediction power. phi is the most useful indicator for clinical decision-making on active surveillance.Trial registrationThis study is registered atthe Japan Trial Register with ID UMIN000009876 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011573).

Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumor-initiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade ( P =0.014), pathological N stage ( P =0.005) and ALDH1 expression ( P =0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively ( P <0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

Background Neuroendocrine (NE) cells may have an impact on the development and initial growth of benign prostatic hyperplasia (BPH) according to previous human studies. Methods To explore the relationship of NE cells and BPH development, we compared the density of NE cells and also prostatic weight in spontaneously hypertensive rats (SHR), which develop by aging, and Wistar-Kyoto rats (WKY) as control. The total weights of the epithelium and stroma in the ventral lobes of 8-, 12, 16-, 28- and 56-week-old SHR and WKY were calculated using Image J software. NE cells in the ventral prostatic ducts (VPd) were quantified using immunohistochemical staining for serotonin. Results Although there was no significant difference in the estimated total weight of the epithelium and stroma in the ventral lobes adjusted by body weight (ES weight) between the two groups at 8, 12 and 16 weeks of age, ES weight was significantly greater in the SHR group than in the WKT group at 28 and 56 weeks. The density of NE cells in the VPd decreased with aging in the WKY group, whereas it was sustained until 16 weeks and then decreased with aging in the SHR group. The difference in the density between the two groups was most marked at 16 weeks of age. Conclusion In the natural history of BPH, NE cells may play an important role in the initial development of BPH because sustained density of NE cells in the VPd precedes the development of prostatic hyperplasia.

There is no standard second‐line chemotherapy treatment for recurrent or metastatic urothelial cancer (MUC). The purpose of this phase II study was to evaluate the efficacy and toxicity of the three‐drug combination of paclitaxel, ifosfamide, and nedaplatin (TIN). Patients with MUC were eligible after treatment failure with methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcitabine and cisplatin. Doses for TIN therapy were paclitaxel 175 mg/m2 on day 1, ifosfamide 1500 mg/m2 on days 1–3, and nedaplatin 70 mg/m2 on day 1, every 4 weeks. Tumor response, the primary efficacy parameter, was assessed according to unidimensional measurements (Response Evaluation Criteria in Solid Tumors criteria, version 1.0). Secondary efficacy parameters were overall survival (OS) and progression‐free survival (PFS). Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria, version 3.0. A total of 45 patients (13 females and 32 males) with MUC were evaluable for response and toxicity. The overall response rate was 40.0%. Median PFS time was 4.0 months (95% confidence interval [CI], 4.6–11.6). Median OS time was 8.9 months (95% CI, 10.5–18.9). Grade 3 or 4 hematologic adverse events were neutropenia (95.6%), anemia (15.6%), and thrombocytopenia (17.8%). The most common grade 3 or 4 non‐hematologic adverse events were anorexia (4.4%) and elevated aspartate transaminase/alanine transaminase (2.2%). No toxic death was observed. The main limitation of this study is that only 10 patients (22.2%) who were previously treated with gemcitabine and cisplatin were included. In conclusion, TIN as second‐line treatment for MUC is an active regimen with a manageable toxicity profile. (Cancer Sci 2011; 102: 1171–1175)

Background To best employ radium‐223 dichloride (Ra‐223) for patients with castration‐resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone‐predominant status in patients treated with Ra‐223. Methods We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra‐223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra‐223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression‐free survival (PFS). Results During the median follow‐up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13‐1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04‐2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02‐2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11‐2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra‐223 treatment. This was associated with non‐bone metastasis progression, especially visceral metastasis, and overall survival. Conclusions Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone‐predominant metastasis type to benefit from Ra‐223. We developed the risk assessment based on the types of dynamic changes of bone metastasis before the use of radium‐223 dichloride (Ra‐223). This risk assessment can be used to maximize the clinical benefits of Ra‐223 treatment for bone‐predominant metastasis.