Clinical Utility of Whole-Genome Analysis as One-for-All Test for Breast Cancer: A Case Series.

Introduction: Breast cancer exhibits vast genomic diversity, leading to varied clinical manifestations. Integrating molecular subtyping with in-depth genomic profiling is pivotal for informed treatment choices and prognostic insights. Whole-genome clinical analysis provides a holistic view of genome-wide variations, capturing structural changes and affirming tumor suppressor gene loss of heterozygosity. Case Presentation: Here we detail four unique breast cancer cases from Seoul St. Mary's Hospital, highlighting the actionable benefits and clinical value of whole-genome sequencing (WGS). As an all-in-one test, WGS demonstrates significant clinical utility in these cases, including: (1) detecting homologous recombination deficiency with underlying somatic causal variants (case 1), (2) distinguishing double primary cancer from metastasis (case 2), (3) uncovering microsatellite instability (case 3), and (4) identifying rare germline pathogenic variants in TP53 gene (case 4). Our observations underscore the enhanced clinical relevance of WGS-based testing beyond pinpointing a few driver mutations in conventional targeted panel sequencing platforms. Conclusion: With genomic advancements and decreasing sequencing costs, WGS stands out as a transformative tool in oncology, paving the way for personalized treatment plans rooted in individual genetic blueprints.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Strategies to Improve Smoking Cessation for Participants in Lung Cancer Screening Program: Analysis of Factors Associated with Smoking Cessation in Korean Lung Cancer Screening Project (K-LUCAS).

PURPOSE: Smoking cessation intervention is one of the key components of successful lung cancer screening program. We investigated the effectiveness and related factors of smoking cessation services provided to the participants in a population-based lung cancer screening trial. MATERIALS AND METHODS: The Korean Lung Cancer Screening Project (K-LUCAS) is a nationwide, multi-center lung cancer screening trial that evaluates the feasibility of implementing population-based lung cancer screening. All 5,144 current smokers who participated in the K-LUCAS received a mandatory smoking cessation counseling. Changes in smoking status were followed up using a telephone survey in 6 months after lung cancer screening participation. The lung cancer screening's impact on smoking cessation is analyzed by variations in the smoking cessation interventions provided in screening units. RESULTS: Among 4,136 survey responders, participant's motivation to quit smoking increased by 9.4% on average after lung cancer screening. After 6 months from the initial screening, 24.3% of participants stopped smoking, and 10.6% of participants had not smoked continuously for at least 6 months after screening. Over 80% of quitters stated that participation in lung cancer screening motivated them to quit smoking. Low-cost public smoking cessation program combined with lung cancer screening increased the abstinence rates. The smokers were three times more likely to quit smoking when the smoking cessation counseling was provided simultaneously with low-dose computed tomography screening results than when provided separately. CONCLUSION: A mandatory smoking cessation intervention integrated with screening result counselling by a physician after participation in lung cancer screening could be effective for increasing smoking cessation attempts.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance. METHODS: Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival. RESULTS: Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. CONCLUSIONS: We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Versatile Post-synthetic Modifications of Helical ß-Peptide Foldamers Derived from a Thioether-Containing Cyclic ß-Amino Acid.

We introduce a novel cyclic ß-amino acid, trans-(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of ß-peptide hexamers containing ATTC using various techniques, including X-ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC-containing foldamers can adopt 12-helical conformations similar to their isosteres and offer the possibility of fine-tuning their properties via post-synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post-synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic ß-amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.

Analysis of genomic and immune intratumor heterogeneity in linitis plastica via multiregional exome and T-cell receptor sequencing.

The molecular landscape and the intratumor heterogeneity (ITH) architecture of gastric linitis plastica (LP) are poorly understood. We performed whole-exome sequencing (WES) and T-cell receptor (TCR) sequencing on 40 tumor regions from four LP patients. The landscape and ITH at the genomic and immunological levels in LP tumors were compared with multiple cancers that have previously been reported. The lymphocyte infiltration was further assessed by immunohistochemistry (IHC) in LP tumors. In total, we identified 6339 non-silent mutations from multi-samples, with a median tumor mutation burden (TMB) of 3.30 mutations per Mb, comparable to gastric adenocarcinoma from the Cancer Genome Atlas (TCGA) cohort (P = 0.53). An extremely high level of genomic ITH was observed, with only 12.42%, 5.37%, 5.35%, and 30.67% of mutations detectable across 10 regions within the same tumors of each patient, respectively. TCR sequencing revealed that TCR clonality was substantially lower in LP than in multi-cancers. IHC using antibodies against CD4, CD8, and PD-L1 demonstrated scant T-cell infiltration in the four LP tumors. Furthermore, profound TCR ITH was observed in all LP tumors, with no T-cell clones shared across tumor regions in any of the patients, while over 94% of T-cell clones were restricted to individual tumor regions. The Morisita overlap index (MOI) ranged from 0.21 to 0.66 among multi-regions within the same tumors, significantly lower than that of lung cancer (P = 0.002). Our results show that LP harbored extremely high genomic and TCR ITH and suppressed T-cell infiltration, suggesting a potential contribution to the frequent recurrence and poor therapeutic response of this adenocarcinoma.

Immunogenomic profiling of lung adenocarcinoma reveals poorly differentiated tumors are associated with an immunogenic tumor microenvironment.

OBJECTIVES: Pathologists have routinely observed distinct histologic patterns of growth in early-stage lung adenocarcinoma (LUAD), which have been suggested to be associated with prognosis. Herein, we investigated the relationship between LUAD patterns of growth, as defined by the updated international association for the study of lung cancer (IASLC) grading criteria, and differences in the tumor immune microenvironment to identify predictors of response to immunotherapy. METHODS: 174 resected stage I-III LUAD tumors were classified by histologic pattern of growth (i.e. solid, micropapillary, acinar, papillary, and lepidic) and then grouped as well differentiated, moderately differentiated, and poorly differentiated. Comprehensive multiplatform analysis including whole exome sequencing, gene expression profiling, immunohistochemistry, CIBERSORT, and T-cell receptor sequencing was performed and groups were compared for differences in genomic drivers, immune cell infiltrate, clonality, and survival. Finally, multivariate analysis was performed adjusting for pathologic stage and smoking status. RESULTS: Poorly differentiated tumors demonstrated a strong association with smoking relative to moderately differentiated or well differentiated tumors. However, unlike in prior reports, poorly differentiated tumors were not associated with a worse survival after curative-intent resection. Genomic analysis revealed that poorly differentiated tumors are associated with high tumor mutation burden but showed no association with oncogenic drivers. Immune analyses revealed that poorly differentiated tumors are associated with increased T-cell clonality, expression of PD-L1, and infiltration by cytotoxic CD8 T-cells, activated CD4 T-cells, and pro-inflammatory (M1) macrophages. Finally, multivariate analysis controlling for stage and smoking status confirmed independence of immune differences between IASLC grade groups. CONCLUSIONS: Poorly differentiated tumors, as defined by the updated IASLC grading criteria, are associated with a distinct immunogenic tumor microenvironment that predicts for therapeutic response to immune agents, including checkpoint inhibitors, and should be included in the clinical trial design of immunotherapy studies in early-stage lung adenocarcinoma.

Prediction of the composition of urinary stones using deep learning.

PURPOSE: This study aimed to predict the composition of urolithiasis using deep learning from urinary stone images. MATERIALS AND METHODS: We classified 1,332 stones into 31 classes according to the stone composition. The top 4 classes with a frequency of 110 or more (class 1: calcium oxalate monohydrate [COM] 100%, class 2: COM 80%+struvite 20%, class 3: COM 60%+calcium oxalate dihydrate [COD] 40%, class 4: uric acid 100%) were selected. With the 965 stone images of the top 4 classes, we used the seven convolutional neural networks (CNN) to classify urinary stones and compared their classification performances. RESULTS: Among the seven models, Xception_Ir0.001 showed the highest accuracy, precision, and recall and was selected as the CNN model to predict the stone composition. The sensitivity and specificity for the 4 classes by Xception_Ir0.001 were as follows: class 1 (94.24%, 91.73%), class 2 (85.42%, 96.14%), class 3 (86.86%, 99.59%), and class 4 (94.96%, 98.82%). The sensitivity and specificity of the individual components of the stones were as follows. COM (98.82%, 94.96%), COD (86.86%, 99.64%), struvite (85.42%, 95.59%), and uric acid (94.96%, 98.82%). The area under the curves for class 1, 2, 3, and 4 were 0.98, 0.97, 1.00, and 1.00, respectively. CONCLUSIONS: This study showed the feasibility of deep learning for the diagnostic ability to assess urinary stone composition from images. It can be an alternative tool for conventional stone analysis and provide decision support to urologists, improving the effectiveness of diagnosis and treatment.

Organometallic hotspot engineering for ultrasensitive EC-SERS detection of pathogenic bacteria-derived DNAs.

The sensitivity and limit-of-detection (LOD) of the traditional surface-enhanced Raman spectroscopy (SERS) platform suffer from the requirement of precise positioning of small analytes, including DNAs and bacteria, into narrow hotspots. In this study, a novel SERS sensor was developed using electrochemical deposition onto metal nanopillars (ECOMPs) combined with complementary DNAs (cDNAs) for the detection of pathogenic bacteria. Applying a redox potential to AuCl4- ions actively engineered the organometallic hotspots based on the cDNAs in a short time (<10 min) and simultaneously produced SERS signals. Because of the influence of potential-driven morphological properties on the SERS efficiency in the cDNA domains and the resonant coupling of internal fields with the fields confined between adjacent ECOMPs-cDNAs, the optimum growth time was determined to be 5 min. The EC-SERS detection and discrimination of Enterococcus faecium and Staphylococcus aureus were successfully carried out because of the DNA complementarity. Compared with plasmonic metal nanopillars (MPs)-cDNAs, the enhancement factor of the ECOMPs-cDNAs was estimated to be ∼2.0 × 103. A quantitative investigation revealed that a highly linear progression in the target DNA concentration range (0.05-100 nM) and a LOD of ∼0.035 nM were achieved. The specificity of the ECOMPs-cDNAs was validated by cross-hybridization. The platform was also used to assay human whole blood containing 0.1 nM bacterial DNAs. The proposed strategy provides the potential for highly sensitive SERS-based multiplex DNA detection in clinical diagnostics.

Comparative oncological outcomes after radical prostatectomy or external beam radiation therapy plus androgen deprivation therapy in men with clinical T3b prostate cancer.

OBJECTIVE: To compare oncological outcomes in men with clinical T3b prostate cancer who underwent radical prostatectomy or a combination of radiation therapy plus androgen deprivation therapy. METHODS: Men with clinical T3b prostate cancer who underwent radical prostatectomy or radiation therapy plus androgen deprivation therapy between 2007 and 2014 were evaluated. All patients were relatively healthy, with Eastern Cooperative Oncology Group performance status of 0 or 1 without nodal or distant metastasis. Cancer-specific survival was analyzed. Age, Charlson Comorbidity Index, biopsy Gleason score and pretreatment prostate-specific antigen were adjusted by propensity score matching. The Cox proportional hazards model was used to assess factors prognostic of cancer-specific survival. RESULTS: Of the 152 patients with clinical T3b prostate cancer, 45 underwent radical prostatectomy, and 107 underwent radiation therapy plus androgen deprivation therapy between 2007 and 2014. The mean cancer-specific survival was significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (P = 0.029). Age, Charlson Comorbidity Index and pretreatment prostate-specific antigen were significantly higher in the radiation therapy plus androgen deprivation therapy group. In the propensity score matched population of 24 patients each, the median cancer-specific survival remained significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (not reached vs 112.93 ± 11.94 months, P = 0.026). Multivariate analysis showed that undergoing radiation therapy plus androgen deprivation therapy was the only significant poor prognostic factor for cancer-specific survival (hazard ratio 6.694, 95% confidence interval 1.642-27.592, P = 0.008). CONCLUSION: Cancer-specific survival was significantly longer in men with clinical T3b prostate cancer who underwent radical prostatectomy than radiation therapy plus androgen deprivation therapy, suggesting that radical prostatectomy can be a better treatment option for the initial definitive treatment for these patients.

Clinical features and oncological outcomes of primary female urethral cancer.

PURPOSE: Investigation of the clinical features and treatment outcomes of primary female urethral cancer (FUC) at a single institution. MATERIALS AND METHODS: We retrospectively reviewed 32 FUC patients during 1997-2017. We investigated preoperative risk factors predicting overall (overall survival [OS]) and recurrence-free survival (RFS) and reviewed clinical features, treatment modality, and oncologic outcomes according to pathology. The median follow-up duration and age was 56 months (range: 4-229) and 61 years (range: 15-82), respectively. RESULTS: The median OS and RFS were 70 and 16 months, respectively. A total of 19 (59.4%) patients received systemic chemotherapy, including 14 (43.8%) who received radiation therapy. Further, 22 patients (68.8%) underwent surgery. On univariate analysis, >T2, N+, and tumor size ≥3 cm were associated with poorer OS. There were 15 cases of distant metastasis and five local recurrences. Outcomes were poorest in adenocarcinoma (AC), moderate in clear cell carcinoma and transitional cell carcinoma, and best in squamous cell carcinoma (SCC). CONCLUSION: Female urethral lesions should be carefully examined to exclude FUC. Distal urethral SCC was responsive to surgical excision, but proximal urethral AC had poor oncological outcome even after extensive treatment. Due to the heterogeneity and poor prognosis of FUC, multimodal treatment is mandatory.

Impact of preoperative chemotherapy on pathologic nodal status in muscle-invasive bladder cancer: optimal lymphadenectomy in the preoperative chemotherapy era.

PURPOSE: To investigate the impact of preoperative chemotherapy (pCTX) on pathologic nodal (pN) status and evaluate the optimal lymphadenectomy method according to clinical nodal (cN) status in patients with muscle-invasive bladder cancer who received pCTX. MATERIALS AND METHODS: We retrospectively reviewed 449 patients with muscle-invasive bladder cancer who underwent radical cystectomy. Among them, 139 (31.0%) received pCTX. We analyzed overall survival among three groups (cN-pCTX-, cN-pCTX+, and cN+pCTX+); the impact of lymphadenectomy extent according to the history of pCTX in cN- patients (n = 393); and the pN status which includes number of positive lymph nodes, and lymph node density in cN- patients who underwent extended lymphadenectomy (n = 222). RESULTS: Overall survival was significantly dependent on cN status, and pCTX had no survival advantage although it decreased the percentage of pN+ patients and the number of positive lymph nodes in cN- patients. Lymph node density showed a significant prognostic effect on overall survival in Cox regression analysis both in cN- and cN+ patients. In cN- patients, there was no significant survival difference according to lymphadenectomy extent regardless of receiving pCTX. CONCLUSIONS: pCTX can control micrometastases but not overt metastases, despite decreasing the number of positive lymph nodes in patients with muscle-invasive bladder cancer. Although extended lymphadenectomy is a reasonable diagnostic strategy in the pCTX era, standard dissection is as therapeutic as extended dissection in patients with cN- disease.

Biopsy-detected Gleason grade 5 tumor is an additional prognostic factor in metastatic hormone-sensitive prostate cancer.

PURPOSE: A Gleason score ≥ 8, metastatic tumor burden, and visceral metastasis are known prognostic factors for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, however, these indicators have not been fully validated internationally. We aimed in this present study to further analyze the factors that influence the prognosis of mHSPC. METHODS: In this retrospective study, we identified 201 patients with newly diagnosed mHSPC between 2008 and 2014 and collected their clinical information. Cox proportional hazard regression models were used to identify prognostic factors in mHSPC. RESULTS: The mean age of the patients at presentation was 70 years (interquartile range (IQR), 64-76 years). The prostate-specific antigen level was 141 ng/mL (IQR, 58.8-464.5 ng/mL). Of the 201 study patients, 191 (94.5%) and 131 (65.2%) cases had a biopsy Gleason score ≥ 8 and grade 5, respectively. More than 4 metastases were detected in 134 patients. Castration-resistant prostate cancer (CRPC) was evident in 160 cases after a mean follow-up period of 46.6 months. By multivariable analysis, a Gleason grade of 5 and bone metastasis lesion count ≥ 4 were found to be significantly associated with CRPC-free survival (hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.01-2.07) and (HR 2.02; 95% CI 1.39-2.92) and overall survival (HR 1.67 95%; CI 1.16-2.42) and (HR 1.67 95%; CI 1.16-2.41). CONCLUSIONS: Bone metastases ≥ 4 and a Gleason grade 5 are independent prognostic factors for CRPC-free and overall survival in mHSPC. A Gleason grade 5 is therefore a new prognostic indicator in mHSPC.

The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics.

Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.

Cold and heterogeneous T cell repertoire is associated with copy number aberrations and loss of immune genes in small-cell lung cancer.

Small-cell lung cancer (SCLC) is speculated to harbor complex genomic intratumor heterogeneity (ITH) associated with high recurrence rate and suboptimal response to immunotherapy. Here, using multi-region whole exome/T cell receptor (TCR) sequencing as well as immunohistochemistry, we reveal a rather homogeneous mutational landscape but extremely cold and heterogeneous TCR repertoire in limited-stage SCLC tumors (LS-SCLCs). Compared to localized non-small cell lung cancers, LS-SCLCs have similar predicted neoantigen burden and genomic ITH, but significantly colder and more heterogeneous TCR repertoire associated with higher chromosomal copy number aberration (CNA) burden. Furthermore, copy number loss of IFN-γ pathway genes is frequently observed and positively correlates with CNA burden. Higher mutational burden, higher T cell infiltration and positive PD-L1 expression are associated with longer overall survival (OS), while higher CNA burden is associated with shorter OS in patients with LS-SCLC.

Impact of positive surgical margin on biochemical recurrence in localized prostate cancer.

BACKGROUND: We analyzed the relationship between biochemical recurrence (BCR) and the status of positive surgical margin (PSM) in patients with pT3a prostate cancer (PCa). MATERIALS AND METHODS: Patients (n = 150) who underwent radical prostatectomy for pT3a PCa without nodal/distant metastasis were retrospectively reviewed between 2010 and 2013. The data regarding the status of PSM including the number, length, and margin Gleason score were collected. The predictors of BCR were analyzed using Cox regression hazard models. BCR-free survival was compared between the patients with negative surgical margin (NSM) and with PSM using Kaplan-Meier curves and log-rank tests. RESULTS: PSM was noted in 74 patients (49.3%). Seventy-six patients (50.7%) had NSM and 38 patients (25.3%) had single PSM. Twenty patients (13.3%) had two PSMs and 16 patients (10.7%) had ≥3 PSMs. In total patients, the multivariate analysis demonstrated that a pathological Gleason score of ≥8 was significantly associated with BCR [hazard ratio (HR), 2.173; 95% confidence interval (CI), 1.244-3.797; P = 0.038]. In patients with PSM, the number of PSM more than two was significantly associated with BCR (HR, 2.723; 95% CI, 1.256-5.902; P = 0.011). PSM length of ≥3 mm was also a significant predictive factor (HR, 1.024; 95% CI, 0.994-1.055, P = 0.042). Patients with the highest margin Gleason score of ≥4 had poorer BCR-free survival than those with that of 3/no surgical margin. CONCLUSIONS: Number (more than one), length (≥3 mm), and higher margin Gleason score (≥4) of PSM were significantly associated with an increased likelihood of BCR in patients with pT3a PCa.

The curative effect of androgen deprivation therapy alone is insufficient in high-risk prostate cancer.

ABSTRACT: To compare the outcomes of patients with high-risk prostate cancer treated by primary radical prostatectomy (RP) and primary androgen deprivation therapy (ADT).The study included patients with high-risk or very high-risk prostate cancer. Patients treated with definitive radiation therapy and those with clinical N1 and M1 disease were excluded. The RP group was divided into sub-cohorts of patients treated with ADT and those who received ADT after biochemical recurrence post-RP. Cancer-specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.The study analyzed 859 patients divided into the RP group (n = 654) and ADT group (n = 205). Castration-resistant prostate cancer was detected in 23 (3.5%) patients in the RP group and 43 (21.0%) patients in the ADT group. Mortality cases included 63 (9.6%) patients in the RP group and 91 (44.4%) patients in the ADT group. CSS (P = .0002) and OS (P < .0001) were significantly higher in the RP group than in the ADT group. In the sub-cohort, CSS did not differ significantly between the RP and ADT groups, whereas OS was significantly higher in the RP group than in the ADT group (P < .0001). In the multivariate analysis, primary ADT increased CSS (hazard ratio, 2.068; P = .0498) and OS (hazard ratio, 3.218; P < .0001) compared with RP.In clinically localized high-risk prostate cancer patients, primary RP was associated with better CSS and OS than primary ADT. Comprehensive counseling in this cohort of patients will help the selection of treatment.

Hybrid ileal pouch with concomitant anti-refluxing and refluxing ureteroileal anastomosis.

PURPOSE: We report our preliminary experience of using a hybrid ileal pouch, assessing oncologic outcomes, complications, voiding, and renal function. METHODS: The study included 25 patients with bladder cancer treated with radical cystectomy with a hybrid ileal pouch with concomitant anti-refluxing and refluxing anastomosis, performed by a single surgeon. The patients were divided into two groups (first and last cases) according to the surgery date. Postoperative complications, separate renal function by renal scan, voiding function by uroflowmetry with residual urine, and oncologic outcomes were assessed. RESULTS: The surgery duration was shorter in the last cases than the first cases. The voiding volume increased with time. There were 23 cases of grade 3 complication in 12 patients and one case of grade 4 complication (sepsis). In the first cases, ureterovesical stenosis occurred in five cases, whereas in the last cases, there were no cases of stenosis. In separate renal function, there was no difference between the left and right side or between the first and last cases. CONCLUSIONS: The hybrid ileal pouch showed acceptable oncologic and functional outcomes and complications; therefore, it can be used according to the appropriate surgical situation with a relatively short bowel segment during neobladder construction.

Feasibility of implementing a national lung cancer screening program: Interim results from the Korean Lung Cancer Screening Project (K-LUCAS).

BACKGROUND: Lung cancer screening conducted in high-risk group using low-dose computer tomography (LDCT) has been reported as an effective method to reduce lung cancer mortality in two large randomized-control trials. However, the effectiveness is uncertain when lung cancer screening is expanded to a nationwide population-based program. METHODS: The Korean Lung Cancer Screening Project (K-LUCAS) is a single-arm cohort study that was conducted from February 2017 to evaluate the feasibility of implementing an organized national lung cancer screening program in Korea. High-risk population aged 55-74 years with more than a 30-pack-year smoking history was recruited. Smoking history was obtained from administering questionnaires at national health screening programs or public smoking cessation programs which are already established programs in Korea. The screening results were reported using the Lung Imaging Reporting and Data System (Lung-RADS), suggested by the American College of Radiology. K-LUCAS was performed by a network-based diagnosis supporting system using a computer-aided detection (CAD) program to maintain screening quality. Current smokers were provided with mandatory smoking counseling. RESULTS: Among 71,829 participants aged 50 years or older in the national health screening program, 5,975 (8.3%) were eligible for lung cancer screening. Among them, 1,062 (17.8%) refused to participate in K-LUCAS. Additionally, 779 participants were recruited in the smoking cessation program. Thus, a total of 5,692 eligible high-risk participants were recruited in this study. Among them, 865 (15.2%) had positive screening results, which requires a further examination; 529 (9.3%) had Lung-RADS category 3 (indeterminate), and 336 (5.9%) had category 4 (suspicious of lung cancer); 42 (0.7%) had confirmed lung cancer. Approximately 66.7% had early-stage lung cancer: 24 (57.1%), stage I and 4 (9.5%), stage II. Six (1.1%) patients developed complications at the time of diagnosis, including one death. The anxiety level related to cancer screening was low. Participation in screening encouraged motivation to quit smoking. CONCLUSIONS: K-LUCAS provided promising evidence supporting the implementation of a national lung cancer screening program to detect early stage lung cancer and promote smoking cessation for participants in Asian population.

Efficacy and tolerability of metallic stent in patients with malignant prostatic obstruction secondary to prostatic cancer.

OBJECTIVE: To evaluate the efficacy and tolerability of a self-expandable covered metallic stent in patients with malignant prostatic obstruction secondary to prostate cancer (PC). METHODS: We reviewed 22 cases of insertion of self-expandable covered metallic stents with barbs. Data were collected about PC status. Uroflowmetry variables, residual urine volume, International Prostate Symptom Score (IPSS), quality of life (QOL), and duration from stent insertion to removal were surveyed. These clinical parameters were compared before and after stent insertion. RESULTS: The patients with PC showed a mean age of 75.5 ± 6.5 years and mean 5.1 ± 1.9 Charlson comorbidity index. The average flow rate (2.4 ± 1.9 vs 5.9 ± 2.4 mL/s, P = .005), peak flow rate (6.9 ± 6.2 vs 14.1 ± 5.5 mL/s, P = .003), flow time (54.6 ± 29.1 vs 23.6 ± 13.7 s, P = .002), residual urine volume (178.7 ± 195.5 vs 7.0 ± 7.1 mL, P = .004), IPSS (26.2 ± 8.1 vs 8.0 ± 6.5 points, P = .001), and QOL (4.7 ± 1.3 vs 2.4 ± 2.1 points, P = .030) improved between before and after stent insertion, respectively. Pain was the most common complication, but 60% of the patients were managed without any intervention. There were hematuria, urinary retention, urinary frequency, obstruction, and urinary incontinence. However, there was no urinary tract infection due to the stent. The median time to stent removal was 5.7 months. CONCLUSIONS: The stent was maintained for about 6 months with improved objective and subjective outcomes. The patients with PC, who had a poor comorbidity index and advanced PC status showed a tolerable maintenance period. Self-expandable covered metallic stents can be used for PC patients with a short life expectancy and unsuitability for general anesthesia.