Decision regret after prostate biopsy for prostate cancer diagnosis: a Korean multicenter cohort study.

BACKGROUND: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa. METHODS: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up. RESULTS: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related. CONCLUSIONS: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful.

Nuclear Localization of Yes-Associated Protein Is Associated With Tumor Progression in Cutaneous Melanoma.

Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to YapS127A transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapS127AB16F1 (P = .003) and YapS127AB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapS127AB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapS127AB16F, P < .001; YapS127AB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.

Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups. RESULTS: No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% vs. 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% vs. 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups. CONCLUSIONS: ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.

Diffraction-engineered holography: Beyond the depth representation limit of holographic displays.

Holography is one of the most prominent approaches to realize true-to-life reconstructions of objects. However, owing to the limited resolution of spatial light modulators compared to static holograms, reconstructed objects exhibit various coherent properties, such as content-dependent defocus blur and interference-induced noise. The coherent properties severely distort depth perception, the core of holographic displays to realize 3D scenes beyond 2D displays. Here, we propose a hologram that imitates defocus blur of incoherent light by engineering diffracted pattern of coherent light with adopting multi-plane holography, thereby offering real world-like defocus blur and photorealistic reconstruction. The proposed hologram is synthesized by optimizing a wave field to reconstruct numerous varifocal images after propagating the corresponding focal distances where the varifocal images are rendered using a physically-based renderer. Moreover, to reduce the computational costs associated with rendering and optimizing, we also demonstrate a network-based synthetic method that requires only an RGB-D image.

Prognostic nutritional index as a prognostic factor for renal cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Prognostic nutritional index (PNI) is a simple parameter which reflects patient's nutritional and inflammatory status and reported as a prognostic factor for renal cell carcinoma (RCC). Studies were included from database inception until February 2, 2022. The aim of this study is to evaluate prognostic value of PNI by meta-analysis of the diagnostic test accuracy in RCC. METHODS AND FINDINGS: Studies were retrieved from PubMed, Cochrane, and EMBASE databases and assessed sensitivity, specificity, summary receiver operating characteristic curve (SROC) and area under curve (AUC). Totally, we identified 11 studies with a total of 7,296 patients were included to evaluate the prognostic value of PNI in RCC finally. They indicated a pooled sensitivity of 0.733 (95% CI, 0.651-0.802), specificity of 0.615 (95% CI, 0.528-0.695), diagnostic odds ratio (DOR) of 4.382 (95% CI, 3.148-6.101) and AUC of 0.72 (95% CI, 0.68-0.76). Heterogeneity was significant and univariate meta-regression revealed that metastasis and cut-off value of PNI might be the potential source of heterogeneity. Multivariate meta-regression analysis also demonstrated that metastasis might be the source of heterogeneity. CONCLUSIONS: PNI demonstrated a good diagnostic accuracy as a prognostic factor for RCC and especially in case of metastatic RCC.

Liver-Directed Concurrent Chemoradiotherapy versus Sorafenib in Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis.

This study aimed to investigate the efficacy of liver-directed concurrent chemoradiotherapy (LD-CCRT) compared with sorafenib in patients with liver-confined locally advanced hepatocellular carcinoma (HCC) presenting portal vein tumor thrombosis (PVTT). This single institute retrospective cohort study included patients treated with sorafenib or LD-CCRT between 2005 and 2016. Patients with extrahepatic disease and those without PVTT were excluded, leaving 28 and 448 patients in the sorafenib and LD-CCRT groups, respectively. Propensity score matching was performed to balance the differences in clinical features between the two groups. At baseline, the sorafenib group presented higher incidences of unfavorable clinical features, including type III-IV PVTT (53.6% vs. 30.6%, p = 0.048) and bilateral disease extent (64.3% vs. 31.5%, p = 0.001), than the LD-CCRT group. A total of 27 patients from the sorafenib group and 52 patients from the LD-CCRT group were matched. At a median follow-up of 73 months, the median overall survival (OS) was 4.3 and 9.8 months in the sorafenib and LD-CCRT groups, respectively (p = 0.002). Patients with PVTT type II and higher benefited more from LD-CCRT in terms of OS. The Cox proportional hazard model showed that LD-CCRT was a significant prognostic factor for OS. One patient from the sorafenib group and seven patients from the LD-CCRT group underwent curative surgical treatment. Patients who underwent surgical treatment had significantly longer OS. In conclusion, LD-CCRT showed superior survival outcomes to sorafenib in HCC patients with PVTT. LD-CCRT needs further consideration for its substantial local tumor control that can enable curative surgical treatment in selected patients.

Albumin-to-Alkaline Phosphatase Ratio as a Novel Prognostic Factor in Patients Undergoing Nephrectomy for Non-Metastatic Renal Cell Carcinoma: Propensity Score Matching Analysis.

INTRODUCTION: To evaluate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) on recurrence and survival in patients with non-metastatic renal cell carcinoma (RCC) treated with radical or partial nephrectomy. PATIENTS AND METHODS: Between June 1994 and December 2018, 491 patients with RCC who underwent radical or partial nephrectomy at 2 institutions were enrolled in this study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) analyses were performed to distinguish the differences in postoperative recurrence and survival between patients stratified by an optimal cut-off value of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors after propensity score weighting. RESULTS: Of the total 491 patients, 51 patients (10.4%) developed local recurrence or distant metastasis and 26 patients (5.3%) died of disease during the follow-up period. Patients with AAPR<0.41 had significantly lower rates of RFS and CSS than those of patients with AAPR≥0.41 in multivariate analysis (P < .001 and P = .027, respectively). After propensity scroe matching analyses, this difference was still remained for RFS (P < .001). However, AAPR was not an independent prognostic factor for CSS but the value was almost pregnant (HR = 2.674; 95%CI = 0.872-8.203; P = .086). CONCLUSION: AAPR can serve as a novel and useful tool to refine prognosis in patients with non-metastatic RCC treated with partial or radical nephrectomy. These findings suggest that AAPR could be a promising prognostic factor for prediction of recurrence and survival in patients with non-metastatic RCC who undergo nephrectomy.

Diagnostic Utility of Somatostatin Receptor 2A Immunohistochemistry for Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excessive fibroblast growth factor 23 (FGF23) secretion. FGF23 immunohistochemistry (IHC) is proposed as a useful adjunctive marker to confirm TIO diagnosis. However, it often stains focally, limiting its diagnostic utility. OBJECTIVE: This work aimed to compare the diagnostic performance between somatostatin receptor 2A (SSTR2A) and FGF23 IHC for TIO. METHODS: We retrospectively reviewed TIO-diagnosed patients in Severance Hospital between July 2006 and May 2020. Histologic evaluation was performed using histoscore (H score) (expression area proportion score [0-2] × intensity score [1-3], [total, 0-6]). FGF23 and SSTR2A IHC were performed using unstained slides from 18 localized TIO patients and 9 and 15 non-TIO controls with bone and soft-tissue tumors, respectively. SSTR2A positivity was defined as cytoplasmic, membranous, or Golgi staining in more than 1% of tumor cells, and negativity as nonspecific nuclear staining. FGF23 positivity was defined as cytoplasmic expression in more than 1% of the tumor area and negativity as nonspecific nuclear staining. RESULTS: Suspicious lesions were successfully detected in 14 of 15 patients who underwent 68Ga-DOTATOC scans. Diffuse cytoplasmic SSTR2A expression was identified in all TIO patients and focal weak nuclear staining in 12 of 15 controls. FGF23 cytoplasmic expression was identified in 11 of 18 TIO patients and diffuse nuclear staining in 9 of 9 controls. The H score was higher in SSTR2A than in FGF23 IHC (median [interquartile range]: 6 [6-6] vs 1 [0-2], P < .001). CONCLUSION: SSTR2A IHC with H-score quantification might be a more sensitive, adjunctive diagnostic tool than FGF23 IHC for TIO diagnosis.

Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides.

The International Society for Cutaneous Lymphoma (ISCL) proposes a diagnostic algorithm for early mycosis fungoides (MF) that includes clinical, histological, immunophenotypical, and molecular criteria. Here, we analyzed the immunologic markers and features of T-cell clonality in 38 early MF cases and 22 non-MF cases to validate the ISCL algorithm. We found that CD5 and CD7 expression differed significantly between early MF and non-MF cases, with epidermal discordance of CD7 expression more frequently identified in early MF. Notably, increasing the cut-off value for CD7 expression from 10% to 22.5% improved its sensitivity. Furthermore, TCR-γ and ß chain rearrangements were more frequently detected in early MF than in non-MF cases. Based on these findings, we propose CD5 and CD7 deficiency as mandatory immunopathologic criteria and PCR-based testing for TCR-γ and ß chains as required molecular/biologic criteria to improve the efficiency of early MF diagnosis using the ISCL algorithm.

Practice Patterns of Korean Urologists Regarding Positive Surgical Margins after Radical Prostatectomy: a Survey and Narrative Review.

BACKGROUND: There is no clear consensus on the optimal treatment with curative intent for patients with positive surgical margins (PSMs) following radical prostatectomy (RP). The aim of this study was to investigate the perceptions and treatment patterns of Korean urologists regarding the resection margin after RP. METHODS: A preliminary questionnaire was prepared by analyzing various studies on resection margins after RP. Eight experienced urologists finalized the 10-item questionnaire. In July 2019, the final questionnaire was delivered via e-mail to 105 urologists in Korea who specialize in urinary cancers. RESULTS: We received replies from 91 of the 105 urologists (86.7%) in our sample population. Among them, 41 respondents (45.1%) had performed more than 300 RPs and 22 (24.2%) had completed 500 or more RPs. In the question about whether they usually performed an additional biopsy beyond the main specimen, to get information about surgical margin invasion during surgery, the main opinion was that if no residual cancer was suspected, it was not performed (74.7%). For PSMs, the Gleason score of the positive site (49.5%) was judged to be a more important prognostic factor than the margin location (18.7%), multifocality (14.3%), or margin length (17.6%). In cases with PSMs after surgery, the prevailing opinion on follow-up was to measure and monitor prostate-specific antigen (PSA) levels rather than to begin immediate treatment (68.1%). Many respondents said that they considered postoperative radiologic examinations when PSA was elevated (72.2%), rather than regularly (24.4%). When patients had PSMs without extracapsular extension (pT2R1) or a negative surgical margin with extracapsular extension (pT3aR0), the response 'does not make a difference in treatment policy' prevailed at 65.9%. Even in patients at high risk of PSMs on preoperative radiologic screening, 84.6% of the respondents said that they did not perform neoadjuvant androgen deprivation therapy. Most respondents (75.8%) indicated that they avoided nerve-sparing RP in cases with a high risk of PSMs, but 25.7% said that they had tried nerve-sparing surgery. Additional analyses showed that urologists who had performed 300 or more prostatectomies tended to attempt more nerve-sparing procedures in patients with a high risk of PSMs than less experienced surgeons (36.6% vs. 14.0%; P = 0.012). CONCLUSION: The most common response was to monitor PSA levels without recommending any additional treatment when PSMs were found after RP. Through this questionnaire, we found that the perceptions and treatment patterns of Korean urologists differed considerably according to RP resection margin status. Refined research and standard practice guidelines are needed.

Antioxidant and Anti-Inflammatory Effect and Probiotic Properties of Lactic Acid Bacteria Isolated from Canine and Feline Feces.

Oxidative stress is a phenomenon caused by an imbalance between the production of reactive oxygen species and antioxidant defenses. It plays an important role in numerous disease states, including chronic kidney disease, neurological disorders, cardiovascular diseases, diabetes, and cancer. Lactic acid bacteria (LAB) are known to have prominent antioxidant properties. Therefore, this study aimed to measure the antioxidant activity and anti-inflammatory potential of LAB isolated from animals for the efficient use of probiotics with host specificity. Antioxidant activity measurements of sixteen strains revealed that ABTS radical scavenging activities ranged from 26.3 to 57.4%, and DPPH free radical scavenging activities ranged from 4.7 to 13.5%. Based on the antioxidant activity assessment, five strains (Enterococcus faecium MG9003(YH9003), Enterococcus faecium MG9007(YH9007), Lactobacillus reuteri MG9012(YH9012), Lactobacillus fermentum MG9014(YH9014), and Pediococcus pentosaceus MG9015(YH9015)) were selected with the consideration of fermentation productivity (>1 × 109 CFU/g). The selected strains exhibited nitric oxide inhibition and inhibited inducible nitric oxide synthase and cyclooxygenase expression. Furthermore, probiotic properties, including intestinal adhesion and stability, were identified. Our results show that the selected animal-derived strains can be effective probiotic candidates for potential effects on animal hosts.

Chondroradionecrosis of the trachea after definitive radiotherapy for cervical esophageal cancer: A case report.

Chondroradionecrosis (CRN) is an infrequent phenomenon after definitive RT. The clinical manifestation is usually difficult to distinguish from that of tumor recurrence; however, clinicians should be aware of the possibility of CRN.

Prognostic nutritional index and prognosis in renal cell carcinoma: A systematic review and meta-analysis.

PURPOSE: To perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC). MATERIALS AND METHODS: Eligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). RESULTS: In total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I2 = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I2 = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle-Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757). CONCLUSION: This meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC.

The presence of prostate-specific antigen checked more than 1 year before diagnostic biopsy is an independent prognostic factor in patients undergoing radical prostatectomy.

PURPOSE: In large scale prospective studies, prostate-specific antigen (PSA)-screening not only decreased prostate cancer mortality, but also reduced biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP). We investigated the independent effect of the presence of PSA checked more than 1 year before diagnostic biopsy on the prognosis of patients undergoing RP in a real world setting without PSA-screening. MATERIALS AND METHODS: We reviewed the database of patients undergoing RP at Ajou University Hospital from March 1999 to May 2018. Clinicopathological features assessed were age, presence of lower urinary tract symptoms at presentation, presence of PSA checked over 1 year before biopsy, presence of PSA checked within 4 to 1 years of biopsy, last pre-biopsy PSA (pPSA), biopsy grade group (bGG), cT, cN, percentage of positive biopsy cores (PPBC), pathological GG (pGG), pT, pN, surgical margin, and index tumor diameter. The primary endpoint was BCR-free survival (BCRFS). RESULTS: Of 598 patients enrolled, 211 experienced BCR at the mean follow-up of 64±37 months. The 5-year and 10-year BCRFS were 62.8% and 53.9%, respectively. In multivariate analyses including clinical variables only, pPSA, bGG, cT, PPBC, and PSA within 4 to 1 years of biopsy independently affected BCRFS. In multivariate analyses including pathological variables only, pPSA, pGG, pT, pN, PSA checked over 1 year before biopsy and PSA checked within 4 to 1 years of biopsy independently affected BCRFS. CONCLUSIONS: Patients who has checked PSA at least once beyond 1 year before diagnosis of prostate cancer show better BCRFS regardless of other factors.

Cell membrane and nuclear expression of programmed death ligand-1 in prostate needle biopsy tissue in prostate cancer patients undergoing primary radiation therapy.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression in cancer is often associated with cancer aggressiveness and responsiveness to treatment with PD-1 pathway inhibitors. We conducted a systematic study on the expression of membranous PD-L1 (mPD-L1) and nuclear PD-1-L1 (nPD-L1) in prostate needle biopsy specimens of prostate cancer patients who underwent primary radiotherapy and analyzed the association between PD-L1 expression and clinicopathological characteristics and prognosis of patients. METHOD: A total of 971 cancer-containing prostate needle biopsy cores from 172 patients were immunohistochemically stained with anti-PD-L1 antibody. The association of PD-L1 expression with Gleason score and tumor volume percentage was evaluated for each biopsy core. Total of 171 patients were divided according to mPD-L1 or nPD-L1 expression, and clinicopathological characteristics were compared between the positive and negative groups. The prognostic significance of mPD-L1, nPD-L1 and common prognostic factors were analyzed in terms of biochemical recurrence. RESULT: Total of 15% and 46% of biopsy cores were stained positive for mPD-L1 and nPD-L1, respectively. There was a positive correlation between Gleason score and mPD-L1 and a negative correlation between Gleason score and nPD-L1. Between mPD-L1 and nPD-L1, there was no significant correlation. There was intraindividual heterogeneity in PD-L1 expression among different Gleason scores. For mPD-L1, only pretreatment PSA was significantly higher in the positive group than in the negative, but not Gleason score and T stage. For nPD-L1, Gleason score and T stage were significantly higher in the positive group than in the negative. Both mPD-L1 and nPD-L1 expression were not predictive of BCR-free survival in univariate and multivariate analyses. CONCLUSIONS: Our results suggest that PD-1 pathway inhibitor may be a potential therapeutic option in high risk prostate cancer patients as early as neoadjuvant setting. The novel discovery of PD-L1 expression in the nucleus of PC should be subjected to further research.

TERT promoter mutations in penile squamous cell carcinoma: high frequency in non-HPV-related type and association with favorable clinicopathologic features.

PURPOSE: Penile carcinoma is a rare malignant neoplasm with a largely unknown molecular pathogenesis. Telomerase reverse transcriptase promoter (TERT-p) mutations have been detected in several types of human malignancies. The aim of this study was to investigate the presence of TERT-p mutations in penile squamous cell carcinomas (SCCs) and their associations with clinicopathologic features. METHODS: In this retrospective study, Sanger sequencing was performed to detect TERT-p mutations in formalin-fixed paraffin-embedded tissue samples from 37 patients with penile SCC, 16 patients with cutaneous SCC, and 4 patients with non-neoplastic penile/skin tissue. The expression of p16INK4a and Ki-67 was investigated via immunohistochemistry. Associations of TERT-p mutation with clinicopathological factors, immunohistochemical results, and clinical outcome were statistically analyzed. RESULTS: Recurrent TERT-p mutations were identified in 18 out of 37 (48.6%) penile SCCs, including all 3 carcinoma in situ cases. TERT-p mutations were significantly more frequent in non-human papilloma virus (HPV)-related penile SCC types than in non-HPV-related penile SCC based on both histologic classification and p16INK4a immunoreactivity. Furthermore, TERT-p mutation was associated with a low histologic grade, low mitotic count, absence of necrosis, low Ki-67/MIB-1 labeling index, and absence of lymph node or distant metastasis. CONCLUSION: Our study shows TERT-p mutations are the most frequent somatic mutations in penile SCC. In addition, TERT-p mutations are far more frequent in non-HPV-related penile SCC than in HPV-related penile SCC, indicating TERT-p mutations may have a role in tumorigenesis distinct from HPV-related penile SCC.

A Case Report of Cholangiocarcinoma Arising from a Biliary Adenofibroma: Radiologic Findings and Review of Literature.

Biliary adenofibromas are rare biliary epithelial tumors that are classified as benign. Nevertheless, some cases have been reported to show malignant transformations. The radiologic findings of biliary adenofibromas and their malignant transformation are not well-established because of their rarity. We present a case of a cholangiocarcinoma arising from a biliary adenofibroma assessed using ultrasonography, CT, and MRI. The differential diagnoses include other hepatic tumors.

Isolation and Characterization of Effective Bacteria That Reduce Ammonia Emission from Livestock Manure.

Ammonia from livestock manure reacts with chemical components discharged from various emission sources to produce airborne particulate matter. This study aimed to investigate a novel effective microbial agent to suppress ammonia gas emitted from manure. Both isolated L12I and 12III strains, identified as Pediococcus acidilactici (PA), were selected for their superior activity in assays performed with the evaluation criteria such as acid production, ammonia decomposition, and urease inhibition, which are key factors influencing ammonia excretion. The survivability of PA strains was confirmed by an increase in DNA abundance in the manure. PA strains lowered the pH of manure and suppressed the growth of hyper-ammonia-producing bacteria (HAB) possessing urease activity. The L12I and 12III treatment groups showed 23.58% and 38.00% emission reductions, respectively. Especially, the 12III strain was proven to be the more effective strain for reducing ammonia gas emission, with the best ability to reduce pH and inhibit HAB. The strains could have an additive effect in improving the manure quality as a nitrogen fertilizer by preserving the total nitrogen and urea content. These results suggest that PA strains can be used as unprecedented microbial agents to improve manure-derived environmental pollution and improve fertilizer quality.

External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival.

PURPOSE: Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. MATERIALS AND METHODS: The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)-free survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS: Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. CONCLUSION: The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.