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Peyronie’s disease is an acquired condition characterized by penile deformities caused by fibrosis of the penile tunica albuginea, leading to symptoms such as penile pain, erectile dysfunction, and other associated issues. Despite extensive research, the pathophysiology of this condition remains poorly understood, and standardized diagnostic and treatment protocols are lacking. While clinical guidelines from several professional societies exist, they do not consistently account for factors such as patient ethnicity, geography, and socioeconomic status. Thus, the Korean Society for Sexual Medicine and Andrology (KSSMA) aimed to develop recommendations tailored to clinical practice in Korea. These recommendations summarize the latest evidence, including clinical practice guidelines from various international professional societies, and represent the consensus opinion of an expert group within the KSSMA. They encompass all aspects of Peyronie’s disease, including the definition, diagnosis, non-surgical interventions, and surgical treatment options.

Abstract Endoscopic middle meatal antrostomy (MMA) is commonly used for maxillary sinus (MS) fungal ball removal. For challenging cases involving anterior or inferior recess, an additional inferior meatal approach (IMA) might be needed. We analyzed the differences in MS dimensions on CT scans according to the surgical approach to suggest preoperative variables that could facilitate an additional IMA. CT scans of 281 adult patients who underwent ESS for the MS fungal ball (139 MMA, 62 MMA & IMA) were evaluated for comparative analysis of 8 MS measurements based on the surgical approach. Complete removal was achieved in all cases. Age and sex didn't differ significantly (p > 0.05). The maximum distances between the anterior–posterior walls, the inferior ostium border to the lateral recess, and the ostium to the inferior wall of the MS were statistically greater in the MMA & IMA group compared to the MMA group (p = 0.003, p = 0.005, and p = 0.010, respectively), especially among females. This study underscores the clinical importance of specific measurements—anterior to posterior wall, medial wall to lateral recess, and ostium to inferior wall of the maxillary sinus—for guiding optimal surgical approaches in MS lesions.

Abstract Introduction The EVEREST II study previously reported that intravitreally administered ranibizumab (IVR) combined with photodynamic therapy (PDT) achieved superior visual gain and polypoidal lesion closure compared to IVR alone in patients with polypoidal choroidal vasculopathy (PCV). This follow-up study reports the long-term outcomes 6 years after initiation of the EVEREST II study. Methods This is a non-interventional cohort study of 90 patients with PCV from 16 international trial sites who originally completed the EVEREST II study. The long-term outcomes were assessed during a recall visit at about 6 years from commencement of EVEREST II. Results The monotherapy and combination groups contained 41 and 49 participants, respectively. The change in best-corrected visual acuity (BCVA) from baseline to year 6 was not different between the monotherapy and combination groups; − 7.4 ± 23.0 versus − 6.1 ± 22.4 letters, respectively. The combination group had greater central subfield thickness (CST) reduction compared to the monotherapy group at year 6 (− 179.9 vs − 74.2 µm, p = 0.011). Fewer eyes had subretinal fluid (SRF)/intraretinal fluid (IRF) in the combination versus monotherapy group at year 6 (35.4% vs 57.5%, p = 0.032). Factors associated with BCVA at year 6 include BCVA (year 2), CST (year 2), presence of SRF/IRF at year 2, and number of anti-VEGF treatments (years 2–6). Factors associated with presence of SRF/IRF at year 6 include combination arm (OR 0.45, p = 0.033), BCVA (year 2) (OR 1.53, p = 0.046), and presence of SRF/IRF (year 2) (OR 2.59, p = 0.042). Conclusion At 6 years following the EVEREST II study, one-third of participants still maintained good vision. As most participants continued to require treatment after exiting the initial trial, ongoing monitoring and re-treatment regardless of polypoidal lesion status are necessary in PCV. Trial Registration ClinicalTrials.gov identifier, NCT01846273.

Irreparable massive rotator cuff tears can significantly impact daily life; and these types of tears can be difficult to repair completely, especially in younger patients who are more active and have higher functional requirements. Since its introduction by Mihata and the colleagues, superior capsular reconstruction (SCR) has gained popularity in the treatment of irreparable massive rotator cuff tears and has shown promising short-term results. A variety of studies have focused on the clinical and biomechanical outcomes of this procedure. This article reviews the biomechanics, indications for the surgical procedure, graft options, surgical technique, and rehabilitation from SCR.

Abstract Background Programmed death‐ligand 1 (PD‐L1) is an important screening biomarker to select patients with gastric cancer (GC) for optimized treatment, including immune checkpoint inhibitors (ICI). Methods In this single‐institution retrospective cohort study, patients with metastatic GC with available PD‐L1 results between October 2019 and September 2021 were identified by reviewing their electronic medical records. Genomic data were obtained from the Samsung Medical Center Clinical Sequencing Platform. Results Among the 399 patients, 276 (69%) had a PD‐L1 combined positive score (CPS) ≥1, 155 (39%) had a CPS between 1 and 5, and 121 (30%) had a CPS ≥5. Of the 121 patients with CPS ≥5, 28 (23%) had a known etiology for “inflamed tumor,” with Epstein–Barr virus (EBV) positivity (N = 11) or high tumor mutational burden (TMB) (N = 17), which included microsatellite instability (MSI) (N = 9). PD‐L1 CPS ≥5 was observed in 11/11 (100%) patients with EBV positivity, 9/12 (75%) patients with MSI, and 17/33 (52%) patients with high TMB. For the 108 patients who received ICI therapy, CPS ≥5 was the only predictor significantly associated with survival in multivariable analyses, including TMB, MSI, or EBV. Objective response rate (ORR) was 49% in patients with CPS ≥5, 30% in patients with 1 ≤ CPS

Abstract Background Neurogenic differentiation factor 1 (NEUROD1) is frequently overexpressed in small‐cell lung cancer (SCLC). NEUROD1 plays an important role in promoting malignant behavior and survival. Methods In this study, we evaluated the association between putative functional polymorphisms in 45 NEUROD1 target genes and chemotherapy response and survival outcomes in 261 patients with SCLC. Among the 100 single nucleotide polymorphisms (SNPs) studied, two were significantly associated with both chemotherapy response and overall survival (OS) of patients with SCLC. Results The SNP rs3806915C>A in semaphorin 6A (SEMA6A) gene was significantly associated with better chemotherapy response and OS (p = 0.04 and p = 0.04, respectively). The SNP rs11265375C>T in nescient helix–loop helix 1 (NHLH1) gene was also associated with better chemotherapy response and OS (p = 0.04 and p = 0.02, respectively). Luciferase assay showed a significantly higher promoter activity of SEMA6A with the rs3806915 A allele than C allele in H446 lung cancer cells (p = 4 × 10−6). The promoter activity of NHLH1 showed a significantly higher with the rs11265375 T allele than C allele (p = 0.001). Conclusion These results suggest that SEMA6A rs3806915C>A and NHLH1 rs11265375C>T polymorphisms affect the promoter activity and expression of the genes, which may affect the survival outcome of patients with SCLC.

Abstract Background In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric cancer. Patients and Methods Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm. Results Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow‐up of 12.6 months (range, 0.1–29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67–1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65–1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand‐foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2–1.7). Conclusion The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first‐line treatment of metastatic gastric cancer.

Background : : Acute complications within 100 days after allogeneic hematopoietic stem cell transplantation (HSCT) can increase immediate mortality as well as the risk of chronic complications and morbidity. A comprehensive review collecting systemic complications following transplantation would be important in pediatric patients. Methods : : We report a retrospective study of pediatric patients who underwent allogeneic HSCT during the 11 years (2009-2020), and their acute complications after transplantation within 100 days. A total 227 pediatric patients' (90 females, 137 males) data were collected. Results : : Among the patients, 62.6% (N=142) suffered from acute graft-versus-host disease, and 118 (52.0%) patients had an acute infection. Pulmonary complications occurred in 52 (22.9%) patients followed by hepatic sinusoidal obstruction syndrome in 30 (18.1%) patients. In the study, 19 died within the first 100 days after HSCT (8.4%), and the 5-year overall survival rate of the patients was 65.4%. Conclusion : : This study widens the understanding of acute toxicities of pediatric HSCT. A significant number of children still have experienced a variety of acute infectious or non-infectious complications after allogeneic HSCT that contribute to morbidity and mortality. Therefore, continuous efforts are needed to reduce them.

Purpose: Several studies have shown that zinc has a significant influence on erectile function. However, no studies evaluating the cellular distribution of free zinc in penile erectile tissue have been performed. Therefore, this study aimed to test whether free zinc is present in penile tissue and whether it may be involved in the electrical stimulation (ES)-induced penile erection. Materials and Methods: The subjects for this study were 26 young (8-week-old) male C57BL/6J mice. After the cavernous nerve was exposed through a midline stomach incision, 14 mice received ES of the cavernous nerve (ES group), whereas 12 mice did not (control group). Intracavernous pressure (ICP) (consisting of 10 V at a duration of 1 min, frequency of 12 Hz and a pulse width of 1 m/s) was recorded during ES. Immediately after ICP was recorded, penile tissues were harvested for histological and biochemical analysis, including analysis of zinc transporter 3 (ZnT3) and intracellular free zinc levels. Results: The expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in penile tissue was significantly greater in the ES group than in the control group (p=0.036 and 0.016, respectively). And then, ZnT3 and intracellular free zinc were present in the penile tissue of both groups. However, ZnT3 immunofluorescence in the ES group was more intense in the dorsal nerve bundle (22% increase, p=0.032). The ES group also showed higher intensity N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) fluorescence signals indicative of intracellular free zinc level in the penile tissue compared to the control group (49% increase in dorsal nerve bundle, p=0.001; 50% increase in corpus cavernosum, p=0.001). Conclusions: The results of the study supported the expression and distribution of free zinc in penile tissue and increased levels after penile erection. Therefore, this study provides anatomical evidence for the potential role of free zinc in penile erection.

Background: To aid in oncology drug development, we investigated MET proto-oncogene receptor tyrosine kinase gene aberrations in 2,239 oncology patients who underwent next-generation sequencing (NGS) in clinical practice.Materials and methods: From November 2019 to January 2021, 2,239 patientswith advanced solid tumors who visited oncology clinics underwent NGS. The NGS panel included >500 comprehensive NGS tests using archival tissue specimens. Programmed death-ligand 1(PD-L1) 22C3 assay results and clinical records regarding initial chemotherapy were available for 1,137 (50.8%) and 1,761 (78.7%) patients, respectively for overall survival (OS) analysis.Results: The 2,239 patients represented 37 types of cancer. The NGS panel included >500 genes, microsatellite instability status, tumor mutational burden, and fusions. The most common cancer types were colorectal (N = 702), gastric (N = 481), and sarcoma (N = 180). MET aberrations were detected in 212 patients. All MET-amplified tumors had microsatellite stable status, and 8 had a high tumor mutational burden. Of 46 patients with MET-amplified cancers, 8 had MET-positive protein expression by immunohistochemistry (2+ and 3+). MET fusion was detected in 10 patients. Partner genes of MET fusion included ST7, TFEC, LRRD1, CFTR, CAV1, PCM1, HLA-DRB1, and CAPZA2. In survival analysis, patients with amplification of MET gene fusion had shorter OS and progression-free survival (PFS) than those without. Thus, MET aberration was determined to be a factor of response to chemotherapy.Conclusion: Approximately 2.1% and 0.4% of patients with advanced solid tumors demonstrated MET gene amplification and fusion, respectively, and displayed a worse response to chemotherapy and significantly shorter OS and PFS than those without MET gene amplification or fusion.

This study examines attenuated risk responses among individuals who do not adhere to preventive COVID-19 measures (e.g., antimaskers). Guided by the Social Amplification of Risk Model, a survey (N = 373) of nonabiding populations showed that news media use was positively associated with risk perceptions, information seeking and sharing, and preventive measure adoption. By contrast, negative emotions to COVID-19 and perceived knowledge hindered preventive measure adoption from increased information seeking and sharing. Theoretical and practical implications are discussed.

Background Targeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination.Methods This phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15–28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients.Results Among 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p

Abstract Survival analyses for malignancies, including renal cell carcinoma (RCC), have primarily been conducted using the Cox proportional hazards (CPH) model. We compared the random survival forest (RSF) and DeepSurv models with the CPH model to predict recurrence-free survival (RFS) and cancer-specific survival (CSS) in non-metastatic clear cell RCC (nm-cRCC) patients. Our cohort included 2139 nm-cRCC patients who underwent curative-intent surgery at six Korean institutions between 2000 and 2014. The data of two largest hospitals’ patients were assigned into the training and validation dataset, and the data of the remaining hospitals were assigned into the external validation dataset. The performance of the RSF and DeepSurv models was compared with that of CPH using Harrel’s C-index. During the follow-up, recurrence and cancer-specific deaths were recorded in 190 (12.7%) and 108 (7.0%) patients, respectively, in the training-dataset. Harrel’s C-indices for RFS in the test-dataset were 0.794, 0.789, and 0.802 for CPH, RSF, and DeepSurv, respectively. Harrel’s C-indices for CSS in the test-dataset were 0.831, 0.790, and 0.834 for CPH, RSF, and DeepSurv, respectively. In predicting RFS and CSS in nm-cRCC patients, the performance of DeepSurv was superior to that of CPH and RSF. In no distant time, deep learning-based survival predictions may be useful in RCC patients.

Abstract Background Gastric cancer (GC) is a heterogenous disease consisted of several subtypes with distinct molecular traits. The clinical implication of molecular classification has been limited especially in association with treatment efficacy of ramucirumab or various targeted agents. Methods We conducted a prospective non-randomized phase II single-arm trial of ramucirumab plus paclitaxel as second-line chemotherapy in 62 patients with metastatic GC who failed to respond to first-line fluoropyrimidine plus platinum treatment. For integrative molecular characterization, all patients underwent pre-ramucirumab treatment tissue biopsy for whole-exome/whole-transcriptome sequencing to categorize patients based on molecular subtypes. We also systematically performed integrative analysis, combining genomic, transcriptomic, and clinical features, to identify potential molecular predictors of sensitivity and resistance to ramucirumab treatment. Results Sixty-two patients were enrolled in this study between May 2016 and October 2017. Survival follow-up in all patients was completed as of the date of cut-off on January 2, 2019. No patient attained complete response (CR), while 22 patients achieved confirmed partial response (PR), resulting in a response rate (RR) of 35.5% (95% CI, 23.6–47.4). According to TCGA molecular classification, there were 30 GS, 18 CIN, 3 EBV, and 0 MSI tumors. The RR was 33% in GS (10/30), 33% in CIN (6/18), and 100% in EBV-positive GC patients with significant statistical difference for EBV(+) against EBV(−) tumors (P = 0.016; chi-squared test). Moreover, responsive patients were marked by activation of angiogenesis, VEGF, and TCR-associated pathways, while non-responder patients demonstrated enrichments of sonic hedgehog signaling pathway and metabolism activity. Integrative multi-layer data analysis further identified molecular determinants, including EBV status, and somatic mutation in GNAQ to ramucirumab activity. Conclusions Prospective molecular characterization identified a subset of GC patients with distinct clinical response to ramucirumab therapy, and our results demonstrate the feasibility of personalized therapeutic opportunities in gastric cancer. Trial registration The study was registered on ClinicalTrial.gov ( NCT02628951 ) on June 12, 2015.

Background Endoscopic forehead lift effectively corrects brow ptosis, and is less invasive and has fewer complications than classic forehead lift. Therefore, endoscopic procedures are often used instead of making a coronal incision. However, very few studies have investigated changes in the height of the hairline and documented exact values regarding the extent of forehead elongation after these procedures. Therefore, we conducted this study to determine the degree to which the height of the forehead changes after endoscopic forehead lift. Methods Patients’ medical records were retrospectively analyzed and measurements of clinical photography were made to investigate changes in the height of the forehead after the procedure. Subjects were divided into an experimental group (n=33) and an age-matched control group (n=33) for analysis; the experimental group comprised those who underwent endoscopic forehead lift from January 2015 to March 2018, and the control group comprised those who underwent upper blepharoplasty without forehead rejuvenation from July 2009 to September 2017. Results The changes between the preoperative and postoperative height of the forehead in the experimental group were not statistically significant (right, P=0.163; left, P=0.256; midline, P=0.545). However, the changes in the height of the forehead in the control group were statistically significant on the right side (P=0.026) and left side (P=0.028), but not at the midline (P=0.244). Conclusions We investigated the extent of forehead elongation that occurred in cases of endoscopic forehead lift and verified that significant forehead height changes did not occur after endoscopic forehead lift.

Abstract Background The prevalence of allergic rhinitis (AR), an environment- and lifestyle-dependent condition, has been constantly increasing in Korea. Although the environment and lifestyle of the Korean people have recently undergone rapid changes, corresponding changes in the characteristics of AR patients have not been well documented. Therefore, we aimed to outline the changes in allergens and clinical manifestations of AR in Korean patients from the 1990s and 2010s. Methods We reviewed 1447 and 3388 AR patients who visited the same tertiary hospital in the 1990s and 2010s, respectively. All patients were diagnosed with AR based on the presence of characteristic symptoms, positive skin prick test results, and answered a symptom questionnaire at the time of visit. We compared differences in the allergens and results of the symptom questionnaire between the two sets of patients. Results When compared with the 1990s, the rate of sensitization to house dust mites, cockroaches, Aspergillus, Alternaria, and tree pollen significantly increased and that to cat fur significantly decreased in patients from the 2010s (all P

Abstract Background Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. Methods To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. Results We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. Conclusions Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Objective:Among the various risk factors associated with contrast-induced acute kidney injury (CI-AKI), the importance of osmolality and viscosity is emerging among the characteristics of contrast media (CM) itself. High osmolality CM (HOCM) is deprecated and low osmotic pressure (LOCM) and iso-osmotic pressure (IOCM) are mainly used in clinical situations where the results of studies on their effect on the development of CI-AKI are contradictory. We evaluated the association between the type of CM and the risk of CI-AKI.Materials and MethodsA retrospective observational cohort study to analyze the effect of the type of CM on the development of CI-AKI. Using propensity score (PS) matching, 2,263 LOCM and IOCM groups were paired for analysis from 5,267 patients and fulfilled the inclusion criteria among 12,742 patients who underwent CAG between 1 January 2007, and 31 December 2016. LOCM included iopromide and iopamidol, IOCM was iodixanol. CI-AKI, which was the primary endpoint, was defined based on the Kidney Disease Improving Global Outcomes criteria within 48 h after exposure to the CM. A multivariable logistic regression analysis was used in the unmatched and matched cohorts, respectively. In addition, a stratified model on clinically important variables, including a high Mehran score (≥ 6), was also used in the matched cohort.ResultsLOCM users showed an increased incidence of CI-AKI (11.7% vs. 9.3%; p = 0.006), but it lost statistical significance after PS matching (9.9% vs. 9.5%, p = 0.725). In multivariable analyses, the adjusted odds ratio for CI-AKI in the LOCM group were 1.059 [95% confidence interval (CI) = 0.875–1.282; p = 0.555] in unmatched cohort and 0.987 (95% CI = 0.803–1.214; p = 0.901) in matched cohort. These results were also consistent with the high-risk (high Mehran score) group.ConclusionsAlthough the role of CM types in the development of CI-AKI has been debated, our observation shows that the selection between LOCM and IOCM during CAG has no influence on the incidence of CI-AKI.

BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.

Abstract Background We sought to describe corneal epithelial changes after using epidermal (EGFR) or fibroblast growth factor receptor (FGFR) inhibitors as chemotherapy and to clarify incidence and prognosis. Materials Retrospective chart review. Results Among 6871 patients and 17 EGFR or FGFR inhibitors, 1161 patients (16.9%) referred for ophthalmologic examination. In total, 1145 patients had disease-related or unrelated ocular complications. Among 16 patients with treatment-related ocular complications, three patients had treatment-related radiation retinopathy and one patient showed treatment-related corneal ulcer. Finally the authors identified that, in 12 patients, three EGFR inhibitors and two FGFR inhibitors caused corneal epithelial lesions. Vandetanib, Osimertinib, and ABT-414 caused vortex keratopathy in nine patients, while ASP-5878 and FPA-144 caused epithelial changes resembling corneal dysmaturation in three patients. The mean interval until symptoms appeared was 246 days with vandetanib, 196 days with osimertinib, 30 days with ABT-414, 55 days with ASP-5878, and 70 days with FPA-144. The mean of the lowest logarithm of minimal angle of resolution visual acuity results of the right and left eyes after chemotherapy were 0.338 and 0.413. The incidence rates of epithelial changes were 15.79% with vandetanib, 0.5% with osimertinib, 100% with ABT-414, 50.0% with ASP-5878, and 18.2% with FPA-144. After excluding deceased patients and those who were lost to follow-up or still undergoing treatment, we confirmed the reversibility of corneal lesions after the discontinuation of each agent. Seven patients showed full recovery of their vision and corneal epithelium, while three achieved a partial level of recovery. Although patients diagnosed with glioblastoma used prophylactic topical steroids before and during ABT-414 therapy, all developed vortex keratopathy. Conclusions EGFR and FGFR inhibitors are chemotherapy agents that could make corneal epithelial changes. Contrary to the low probability of ocular complication with old EGFR drugs, recently introduced EGFR and FGFR agents showed a high incidence of ocular complication with severe vision distortion. Doctors should forewarn patients planning chemotherapy with these agents that decreased visual acuity could develop due to corneal epithelial changes and also reassure them that the condition could be improved after the end of treatment without the use of steroid eye drops. Trial registration This study was approved by the institutional review board (IRB) of Samsung Medical Center (IRB no. 2019–04-027) and was conducted according to the principles expressed in the Declaration of Helsinki.

Purpose Immune checkpoint blockades (ICB) have been successful in gastric cancer (GC). However, the majority of unselected patients with GC fail to respond to ICB. It is crucial to identify precise biomarkers to predict response to ICB. Methods Gene expression profiling of formalin-fixed and paraffin-embedded GC tissues from 25 patients treated with ICB (pembrolizumab) targeting programmed cell death protein 1 (PD-1) was performed using NanoString (NanoString Technologies). For development of a gene signature to predict response to ICB, differential gene expression analysis with linear regression modeling was performed with area under the curve packages in R. Results From the analysis, 10 genes were differentially expressed between patients with response and no response to ICB (P< 0.01). To identify a biomarker predicting response to ICB, four genes were selected based on |log2(foldchange)|≥ 1. After calculating the IMmunotherapy Against GastrIc Cancer (IMAGiC) score, patients were divided into two groups: to be responder and to be non-responder, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. The IMAGiC score was significantly associated with RECIST groups (P= 0.0057), Epstein-Barr virus (P= 0.048), and tumor mutational load (P= 0.023); however, was not significantly correlated with microsatellite instability status (P = 0.14) and programmed death ligand 1 (PD-L1) expression (P= 0.095). To reproduce IMAGiC with different technology, we retested the results with a quantitative real-time polymerase chain reaction (qRT-PCR) method, and the precision of reproduction of 87.5%. In validation cohort with 17 samples from the ongoing trial with nivolumab, the precision of IMAGiC qRT-PCR was 100%. Conclusion Our identified gene signatures and proposed IMAGiC model for predicting response to pembrolizumab in patients with GC showed validity.

Next-generation sequencing (NGS)-based cancer panel tests are actively being applied in the clinic for precision oncology. Given the importance of NGS panel tests in the palliative clinical setting, it is critical to understand success rates, factors responsible for test failures, and the incidence of clinically meaningful genetic alterations. We performed NGS cancer panel test with tumors from the stomach (n = 234), colorectum (n = 196), and rare tumors (n = 105) from 535 recurrent or metastatic cancer patients for 1 year. Sequencing was successful in 483 (95.3%) archival tumor samples to find single nucleotide variant (SNV), copy number alteration (CNA), and fusion. NGS testing was unsuccessful in 52 (9.7%) specimens due to inadequate tissue (n = 28), low tumor volume (n = 19), and poor quality of nucleic acid (n = 5). According to the Tier system, variants were classified as Tier IA, 0.8%; IIC, 10.3%; IID, 2.0%; III, 66.7% for gastric: Tier IA, 3.6%; IIC, 11.6% for colorectal: Tier IA, 1.6%; IIC, 13.5%; IID, 0.5%; III, 70.8% for melanoma, and Tier IA, 9.1%; IIC, 1.8%; IID, 1.0%; III, 66.4% for GIST. In total, 30.8% of 483 sequenced cases harbored clinically meaningful variants. In Tier IA, KRAS and ERBB2 were the most commonly altered genes. Interestingly, we identified CD274 (PD-L1) amplification, PTPN11 (SHP2) SNV, TPM3-NTRK1 fusion, and FGFR3-TACC3 fusion as a rare (90% of archival tissue samples, and 30.8% of them harbored clinically meaningful variants.

Abstract Anti-EGFR antibodies are effective in therapies for late-stage colorectal cancer (CRC); however, many tumours are unresponsive or develop resistance. We performed genomic analysis of intrinsic and acquired resistance to anti-EGFR therapy in prospectively collected tumour samples from 25 CRC patients receiving cetuximab (an EGFR inhibitor). Of 25 CRC patients, 13 displayed intrinsic resistance to cetuximab; 12 were intrinsically sensitive. We obtained six re-biopsy samples at acquired resistance from the intrinsically sensitive patients. NCOA4–RET and LMNA–NTRK1 fusions and NRG1 and GNAS amplifications were found in intrinsic-resistant patients. In cetuximab-sensitive patients, we found KRAS K117N and A146T mutations in addition to BRAF V600E, AKT1 E17K, PIK3CA E542K, and FGFR1 or ERBB2 amplifications. The comparison between baseline and acquired-resistant tumours revealed an extreme shift in variant allele frequency of somatic variants, suggesting that cetuximab exposure dramatically selected for rare resistant subclones that were initially undetectable. There was also an increase in epithelial-to-mesenchymal transition at acquired resistance, with a reduction in the immune infiltrate. Furthermore, characterization of an acquired-resistant, patient-derived cell line showed that PI3K/mTOR inhibition could rescue cetuximab resistance. Thus, we uncovered novel genomic alterations that elucidate the mechanisms of sensitivity and resistance to anti-EGFR therapy in metastatic CRC patients.

Post-micturition dribble (PMD) is the involuntary loss of urine immediately after urination. It is classified as a post-micturition symptom and is more common in males. Traditionally, PMD has been considered to be part of the aging process, to have a low prevalence, and to be less bothersome than other lower urinary tract symptoms (LUTS). However, recent evidence suggests that PMD is not less common and does not elicit less discomfort compared with other LUTS in males. Also, PMD seems to commonly overlap with other LUTS and to be associated with erectile dysfunction. Although the etiology of PMD is not fully understood, a weakness or failure of the pelvic floor muscles is considered to be the most important factor. Although bulbar urethral massage and pelvic floor exercises are known to be effective in treating PMD, pharmacologic treatment has not yet been introduced. Recently, the possibility of treating PMD with phosphodiesterase-5 inhibitor has been suggested.

MET amplification is a frequently observed genomic aberration in solid tumors. We conducted a phase I trial to evaluate dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) for the combination therapy. The following dose levels were tested in this single-arm phase I study: docetaxel as an intravenous infusion over 1 hour at 60 mg/m2 once every 3 weeks of a 21-day schedule plus savolitinib (level 1, 200 mg qd; level 2, 400 mg qd; level 3, 600 mg qd; level 4800 mg qd). In total, there were 17 patients enrolled on to this study [7 gastric cancer (GC) patients, 5 melanoma patients, 3 sarcoma patients, and 2 rectal cancer patients]. Most of the patients (14 of 17) were heavily pretreated (≥third line or greater lines of treatment). For the first 3 cohorts (200 mg savolitinib + docetaxel 60 mg/m2, 400 mg savolitinib + docetaxel 60 mg/m2, 600 mg savolitinib + docetaxel 60 mg/m2), there were no DLTs. In the fourth dose cohort (800 mg savolitinib + docetaxel 60 mg/m2), one DLT occurred with generalized edema grade 3 that required intensive management. One GC patient with both MET overexpression (3+) and MET amplification (MET/CEP7 ratio, 7.3) achieved a durable partial response for 297 days, and another MET-amplified GC patient (MET/CEP7 ratio, 7.6) achieved stable disease for 86 days. Due to the higher incidence of G4 neutropenia in cohort 4 (800 mg), we recommend savolitinib 600 mg qd in combination with docetaxel 60 mg/m2 as the RP2D for phase II trial. The combination therapy demonstrated a very promising antitumor activity with durable responses in MET amplified GC patients.

Purpose The Adjuvant chemoRadioTherapy In Stomach Tumors 2 (ARTIST 2) trial was conducted to compare the efficacy between adjuvant chemotherapy regimens and chemoradiotherapy in D2-resected, node-positive, stage 2 or 3 gastric cancer. Methods In this prospective, multicenter, phase IIItrial, we randomly assigned patients to three treatment arms: patients who receive adjuvant S-1 for 1 year, S-1 plus oxaliplatin (SOX) for 6 months, or SOX plus chemoradiotherapy (SOXRT). Herein, we report the safety outcomes of patients who received adjuvant chemotherapy or chemoradiotherapy. Results Among a total of 514 patients registered between February 2013 and December 2017, 499 patients who either completed or discontinued the assigned study treatments were included in the present analysis. Allthe three treatment arms were generally well-tolerated, with the overall treatment completion rate of 94% (96% in S-1, 93% in SOX, and 92% in SOXRT). The median delivered dose of radiotherapy in the SOXRT arm was 4,500 cGy (range, 0 to 4,500 cGy). The most frequently observed adverse events were fatigue (29%) in S-1 arm and peripheral neuropathy in the SOX and SOXRT arms (59% and 50%,respectively). Conclusion Our preliminary data confirm that there are no significant safety concerns in ARTIST 2 trial (ClinicalTrials.gov, NCT0176146). According to the Independent Data Monitoring Committee, patient accrual is underway.

BackgroundWe explored the combined effects of sarcopenia (SAR) and radiotherapy (RT) on outcomes in patients with advanced gastric cancer (AGC) treated with immune-checkpoint blockade (ICB).MethodsAmong 185 patients with AGC treated with ICB, we defined SAR as skeletal muscle index

Background: Immune checkpoint inhibitors (ICIs) have become established as a new therapeutic paradigm in various solid cancers. Predictive biomarkers to ICIs have not yet been fully established. Tumor mutational burden (TMB) has been considered as a useful marker to indicate patients who benefit from ICIs. Methods: We performed next-generation sequencing, including TMB analysis, as a routine clinical practice in 501 patients with advanced gastrointestinal (GI), genitourinary (GU), or rare cancers. The TruSight ™ Oncology 500 assay from Illumina was used as a cancer panel. Results: In total, 11.6% (58/501) were identified with tumors with high TMB and MSI-high status was confirmed in seven out of 501 cases (1.4%). High TMB was observed in 11.6% of patients with various solid tumors, including: GU cancers (36.0%, 9/25), colorectal cancer (15.2%, 23/151), biliary tract cancer (14.6%, 7/48), melanoma (14.3%, 3/21), gastric cancer (11.2%, 13/116), hepatocellular carcinoma (8.3%, 1/12), other GI tract cancers (4.5%, 1/22), and sarcoma (1.7%, 1/60). The objective response rate (ORR) to ICIs was 75% (nine out of 12) in solid tumor patients with high TMB and 25% (30 out of 40) in those with non-high TMB. Patients with high TMB had better ORR to ICIs than those with non-high TMB ( p = 0.004). Univariate analysis revealed that the status of PD-L1 expression and of TMB (high versus non-high) had significant association in response to ICIs. However, in multivariate analysis, the status of TMB (high versus non-high) was only significantly related to the response to ICIs ( p = 0.036). Conclusion: In the present study, we analyzed the TMB using a cancer panel for various solid tumor patients in routine clinical practice and also demonstrated the usefulness of TMB to predict the efficacy for ICIs.

The purpose of the present study was to investigate the clinical significance of preoperative hematological parameters in patients with advanced stomach cancer, and to explore who might benefit from adjuvant concurrent chemoradiotherapy (CCRT) compared to chemotherapy alone. Among 1032 patients with node-positive stomach cancer who had a confirmed diagnosis after complete D2 resection, and who received adjuvant chemotherapy alone or CCRT, a total of 692 patients was selected using propensity score matching. Among absolute neutrophil count, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, AMC was the most relevant prognostic factor for overall survival and recurrence-free survival (hazard ratio (HR) 1.674, 95% confidence interval (CI) 1.180–2.376; HR 1.908, 95% CI 1.650–2.695, respectively). In a subgroup with a high ALC, patients treated with adjuvant CCRT had a favorable recurrence-free survival (HR 0.620, 95% CI 0.393–0.980) compared to those treated with chemotherapy alone. Further study is needed to confirm our findings and to develop tailored adjuvant treatment.

Regorafenib (Stivarga, BAY 73-4506; Bayer Pharma AG, Berlin, Germany) is a novel oral multikinase inhibitor that blocks the activity of several protein kinases. However, few guidelines exist for novel biomarkers to select patients who will likely benefit from regorafenib treatment. Metastatic colorectal cancer (mCRC) patients treated with regorafenib were evaluated in this study. Tumor tissues of these patients were subjected to next-generation sequencing-based cancer panel tests. The relationship between molecular profiling and efficacy of regorafenib was analyzed. Among the 76 mCRC patients, the median age was 58 years (range 22–79 years), and 73.7% received regorafenib as a third-line therapy. The primary tumor locations were the right side ( n = 15, 19.8%) and the left side ( n = 61, 80.2%). Most patients (97.4%) had received prior anti-angiogenetic agents, and a prior anti-Epidermal Growth Factor Receptor (EGFR) agent had been administered to 32.9%. Of these 76 patients, 65 were evaluated to determine the efficacy of treatment. We observed zero complete responses, seven confirmed partial responses (PR 9.2%), 26 stable disease states (34.2%), and 32 disease progressions (42.1%). The overall confirmed response rate and the disease control rate were 9.2% and 43.4%, respectively. Genomic analysis revealed that APC mutations were significant in patients who demonstrated a tumor response to regorafenib ( p

Background: YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo . This is a first-in-human trial of this antibody. Materials and Methods: YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were studied. HGF, MET, PD-L1, and ERK expression was evaluated for 9 of 17 patients of the expansion cohort (20 mg/kg). Results: In 39 patients enrolled, no dose-limiting toxicity was observed at 0.3 mg/kg, and the most commonly detected toxicity was generalized edema ( n = 7, 18.9%) followed by pruritis and nausea ( n = 5, 13.5%, each), fatigue, anemia, and decreased appetite ( n = 4, 10.8%, each). No patient discontinued treatment because of adverse events. YYB101 showed dose-proportional pharmacokinetics up to 30 mg/kg. Partial response in 1 (2.5%) and stable disease in 17 (43.5%) were observed. HGF, MET, PD-L1, and ERK proteins were not significant predictors for treatment response. However, serum HGF level was significantly lowered in responders upon drug administration. RNA sequencing revealed a mesenchymal signature in two long-term responders. Conclusion: YYB101 showed favorable safety and efficacy in patients with refractory solid tumors. Based on this phase I trial, a phase II study on the YYB101 + irinotecan combination in refractory metastatic colorectal cancer patients is planned. Conclusion: ClinicalTrials.gov Identifier: NCT02499224

Objective: Panel-based sequencing is widely used to measure tumor mutational burden (TMB) in clinical trials and is ready to enter routine diagnostics. However, cut-off points to distinguish “TMB-high” from “TMB-low” tumors are not consistent and the clinical implications of TMB in predicting responses to immune checkpoint blockade (ICB) in gastric cancer are not clearly defined. We aimed to assess whether TMB is associated with the response to immunotherapy and to examine its relation with other biomarkers of immunotherapy response in advanced gastric cancer.Design: In total, 63 patients with advanced gastric cancer treated with ICB were included in the study. Panel-based TMB in gastric tumor samples, treatment responses to ICB, clinicopathological data, and time to progression were retrospectively analyzed. Microsatellite instability (MSI) status, Epstein–Barr virus (EBV) positivity, and programmed death-ligand 1 (PD-L1) combined positive score (CPS) were also analyzed.Results: TMB ranged from 0 to 446 mutations/megabase (mt/mb) and was significantly associated with MSI (P < 0.001), PD-L1 CPS (P = 0.022), response to ICB (P = 0.04), chemotherapy (P = 0.02) and older patient age (≥65 years; P = 0.0014). The cut-off point of 14.31 mt/mb determined by log-rank statistics for progression-free survival divided the tumors into eight (12.7%) TMB-high and 55 (87.3%) TMB-low tumors. The median TMB of the chemo-refractory group was significantly higher (8.43 mt/mb) compared to that of chemo-naïve group (3.42 mt/mb) (P = 0.02). Patients with TMB-high tumors showed prolonged progression-free survival in univariate [HR, 0.32; 95% confidence interval (CI), 0.12–0.90] and multivariate (HR, 0.21; 95% CI, 0.07–0.69) analyses. In area under the receiver operating curve (AUC) analysis of TMB, PD-L1, EBV, MSI, and their combination, the AUC value was the highest for EBV (0.97), followed by MSI (0.96), PD-L1 (0.81), the combination (0.78), and TMB (0.56).Conclusion: In addition to EBV, MSI, and PD-L1 CPS, TMB could be used as a predictive biomarker in patients with advanced gastric cancer treated with ICB and may aid clinical decision making.

Abstract Background Triptolide induces apoptosis and DNA damage followed by inhibition of DNA repair associated gene expression. However, there is the limited data for biomarker to predict the benefit to triptolide in various cancers including pancreatic cancer. Methods We investigated the anti tumor efficacy of triptolide in various pancreatic cancer cell lines (Capan-1, Capan-2, SNU-213, SNU-410, HPAFII, and Hs766T) and patient derived cells (PDCs) from metastatic pancreatic cancer patients. Results In vitro cell viability assay for triptolide in 6 PC cell lines, the IC50 was 0.01 uM, 0.02 uM, 0.0096 uM for triptolide in Capan-1, Capan-2 and SNU-213. However, the growth of tumor cells was not significantly reduced by triptolide in Hs766T, SNU-410 and HPAFII. The distinct difference of gene expression was also observed between Capan-1, Capan-2 and SNU-213 and Hs766T, SNU-410 and HPAFII. In analysis of pathway using gene expression profiles, the integrin mediated RAS signaling pathway was associated with the sensitivity of the triptolide in PC cell lines. Immunoblot assay showed that Chk2 phosphorylation after triptolide was distinctively observed in SNU-213 sensitive to triptolide but, not in SNU-410 insensitive to triptolide. This finding in immunoblot assay was also reproduced in PDCs originated from pancreatic cancer patients. Conclusions Our findings might be helpful to completely capture the subset of patients who may benefit to tripolide (minnelide). More robust biomarkers such as KRAS mutation and Chk2 phosphorylation and careful clinical trial design using triptolide (minnelide) are warranted.

Purpose: Lower urinary tract symptoms (LUTS) are correlated with erectile dysfunction (ED), but research on whether post-micturition dribble (PMD) is related to ED is limited. We assessed the correlation between PMD and ED in middle-aged and older Korean men with LUTS. Materials and Methods: In our prospective, cross-sectional, observational, multicenter study, we enrolled 205 men (age >40 years) with LUTS. LUTS and ED were assessed using the International Prostate Symptom Score (IPSS) and International Index of Erectile Function-5 (IIEF-5), respectively. PMD was assessed using the Hallym PostMicturition Dribble Questionnaire, Question 1, and the PMD volume was calculated in a paper test. Age, prostate volume, serum prostate-specific antigen, maximum urinary flow rate, and postvoid residual urine were also evaluated. Results: There were significant differences in the total and voiding IPSS between men with and without ED (p=0.042 and 0.043, respectively). The Hallym PostMicturition Dribble Questionnaire 1 score was inversely well correlated with the IIEF-5 score (r=-0.388, p

The prognosis and treatment of gastric cancer is complicated by heterogeneity. Here, the authors reveal two molecular subtypes, the mesenchymal subtype associated with poor survival and chemoresistance, and the epithelial phenotype associated with better survival and sensitivity to chemotherapy.

BACKGROUND: Biliary tract cancers (BTCs) are known to have a dismal prognosis. A number of chemokines play important roles in the progress of BTCs. However, the serum levels of chemokines in BTCs have not yet been explored. METHODS: The sera of healthy donors (n = 8) and patients with BTCs who were enrolled in second line sunitinib trials (n = 27) were collected. The concentrations of three kinds of chemokines (CXCL5, CXCL8 and CXCL12) were measured using ELISA assay. The median concentrations of chemokines were compared between healthy donors and BTC patients and the role of chemokines as a prognostic biomarker was examined. RESULTS: BTC patients generally had higher serum levels of CXCL5 and CXCL12 compared to healthy donors. Patients with cholangiocarcinoma showed significantly higher levels of serum CXCL12 than patients with gallbladder cancer. In survival analysis, only CXCL12 level showed a prognostic impact on overall survival (median OS: 6.9 vs. 0.9 months in low CXCL12 vs. high CXCL12, respectively; P = .008). High CXCL5 levels were also correlated with poor survival without statistical insignificance (median OS: 6.2 vs. 2.0 months in low CXCL5 vs. high CXCL5, respectively; P = .070). CONCLUSIONS: There was a significant difference in OS according to the level of CXCL12, suggesting that serum CXCL12 levels may be a useful surrogate marker for clinical outcome in advanced BTCs.

Purpose Addition of molecular markers to the American Joint Committee on Cancer (AJCC) staging system would allow further refinements in predicting recurrence and help individualize treatment decisions. We aimed to validate the Gastric Cancer Prognostic Score (GCPS) in an independent cohort using an easy and cost effective quantitative real-time polymerase chain reaction (qRT-PCR) assay. Methods We performed qRT-PCR using 48 samples from our previous study and expanded to 128 independent patients. The GCPS was recalculated using Cox regression estimates and the performance of cutoff values for GCPS was reassessed. Results The qRT-PCR results showed a similar pattern to nanostring data by scale function data comparison. Using a new cutoff value, GCPS stratified 95 stage IB–III patients who received adjuvant chemotherapy into 74 high-risk patients and 21 low-risk patients with significantly different recurrence-free survival (P< 0.0001). The survival difference remained significant (P= 0.028) in 27 patients who did not receive adjuvant chemotherapy. Among stage I and II patients who were treated with surgery only, one AJCC stage IIA patient was defined as low-risk and showed long-term survival. Nine of 12 high-risk patients showed recurrence less than 67 months after operation. Conclusion We reproduced the GCPS with an easily applicable qRT-PCR assay and successfully predicted recurrence in patients with gastric cancer.

There is no safe and effective standard method for glans penis augmentation. Furthermore, there has been scant research on glans penis augmentation due to a poor understanding of glans anatomy, technical difficulty, and a lack of suitable substances for augmentation. Cross-linked dextran gel is a newly developed filler for soft-tissue augmentation. We evaluated the efficacy and safety of using a novel technique to inject cross-linked dextran gel for glans penis augmentation during a 24-week follow-up study. This prospective, single-arm, multicenter study enrolled twenty healthy adult men who underwent glans penis augmentation between June and August 2013. Cross-linked dextran gel was injected into the glans penis using a simple and easy technique. The sizes of the glans penis and individual satisfaction were assessed. Any adverse event was also reported. A total of 18 individuals were analyzed; two of them were lost to follow-up. The mean procedure time and injected volume were about 30 min and 6.6 ± 0.9 ml, respectively. The mean surface areas of the glans at baseline and 24 weeks were 20.0 ± 3.5 cm2 and 33.6 ± 5.4 cm2 , respectively, representing a mean increase of 68.7% ± 14.0% (P < 0.001). Sixteen individuals (88.9%) were satisfied with the outcomes, and none were dissatisfied. There were no serious adverse events during the study. Cross-linked dextran gel injection for glans penis augmentation was easy and showed a significant augmentative effect on the glans penis, good durability, and was well tolerated without serious adverse events. Therefore, cross-linked dextran gel injection may be an effective, new technique for glans penis augmentation.

In preclinical cancer models, fibroblast growth factor receptor (FGFR) gene aberration has been known to be associated with increased tumor cell proliferation and survival in several cancer types. Oncogenic fusions consisting of FGFR3 and transforming acid coiled coil 3 (TACC3) had been identified as potential therapeutic target. We report on a gastric cancer patient with liver metastases who harbored FGFR3-TACC3 fusion which is extremely rare in gastrointestinal cancer. Herein, we report a case presentation with literature review of FGFR3-TACC3 fusion.

Purpose Neurotropic tropomyosin receptor kinase (NTRK) fusions have been identified in a variety of cancers, and tyrosine kinase inhibitors targeting the tropomyosin receptor kinase (TRK) receptor are currently in clinical trials. However, no reports are available on the effects of NTRK gene amplification. Methods Samples from patients enrolled in the sequencing program were analyzed using a next-generation sequencing (NGS) cancer panel. For cases in which NTRK amplification (defined as ≥ 4.0 copies) was identified, panTRK immunohistochemical (IHC) staining of tissue microarrays was performed. Results A total of 1,250 tumor specimens collected between February 2014 and January 2016 were analyzed using the NGS cancer panel. NTRK amplification was detected in 28 cases of various types of cancer. Among 27 cases, only four were positive for pan-TRK IHC. These four cases were melanoma, sarcoma, lung cancer, and gastric cancer. We found that 2.2% of cancer patients showed NTRK amplification using NGS cancer panel and NTRK amplification resulted in protein overexpression in 14.8% of these patients. Conclusion Patients with NTRK amplification and increased TRK protein expression may be considered for inclusion in clinical trials for NTRK inhibitors.

BACKGROUND: FGFR2 amplification is associated with aggressive gastric cancer (GC), and targeted drugs have been developed for treatment of GC. We evaluated the antitumor activity of an FGFR inhibitor in FGFR2-amplified GC patients with peritoneal carcinomatosis. METHODS: Two GC patients with FGFR2 amplification confirmed by fluorescence in situ hybridization showed peritoneal seeding and malignant ascites. We used the patient-derived xenograft model; patient-derived cells (PDCs) from malignant ascites were used to assess FGFR2 expression and its downstream pathway using immunofluorescence analysis and immunoblot assay in vitro. Apoptosis and cell cycle arrest after treatment of FGFR inhibitor were analyzed by Annexin V-FITC assay and cell cycle analysis. RESULTS: FGFR2 amplification was verified in both PDC lines. AZD4547 as an FGFR inhibitor decreased proliferation of PDCs, and the IC50 value was estimated to be 250 nM in PDC#1 and 210 nM in PDC#2. FGFR inhibitor also significantly decreased levels of phosphorylated FGFR2 and downstream signaling molecules in FGFR2-amplified PDC lines. In cell cycle analysis, apoptosis was significantly increased in AZD4547-treated cells compared with nontreated cells. The proportion of cells in the sub-G1 stage was significantly higher in AZD4547-treated PDCs than in control cells. CONCLUSION: Our findings suggest that FGFR2 amplification is a relevant therapeutic target in GC with peritoneal carcinomatosis.

Background/Aims: To date, the best therapeutic modality for gastric adenoma, especially low-grade adenoma, has not been established. The aim of this study was to assess the usefulness of argon plasma coagulation (APC) in treating gastric adenoma compared with endoscopic submucosal dissection (ESD). Methods: We included 210 patients with gastric adenoma, who underwent treatment with either APC (97 patients) or ESD (113 patients). The clinical and pathologic characteristics, mean duration of hospital stay, complications, and recurrence rates between the two groups were compared. Results: The mean adenoma size was 0.9 cm and 1.1 cm in the APC group and ESD group, respectively (p

Tumor heterogeneity greatly limits personalized treatment of cancer. Patient-derived tumor cell (PDC) models precisely recapitulate the molecular properties and biology of the disease, making them effective preclinical tools for assessing anti-cancer drug activities. Accurate estimation of tumor purity is essential for performing high-throughput drug screening (HTS). In the present study, we measured and predicted the tumor population index in PDC models for two-drug combinational strategies using HTS system. Gastric cancer cell-lines and PDCs were subjected to multi-color immunofluorescence analysis against EpCAM and vimentin to evaluate the tumor cell index based on EpCAM expression levels. We generated a tumor purity prediction model using five different gastric cancer cell-lines (AGS, KATO-III, MKN-45, NCI-N87, SNU-216) with fluorescence intensity-based techniques. Afterwards, stage IV gastric cancer PDC models were evaluated using a micropillar/microwell chip-based HTS system. HER2/CCNE1-amplified PDCs were considerably resistant to an HER2 inhibitor, while combinational treatment consisting of an HER2 inhibitor with anti-WEE1 compound substantially suppressed tumor cellular growth. Moreover, PDCs with BRCA1/2 mutations were synergistically sensitive to HER2 and PARP inhibition therapy. Finally, somatic mutations in TP53 and CDKN2A with MYC amplification rendered PDCs susceptible to the drug combination of WEE1 and HER2. Collectively, our systematic method of high-throughput drug sensitivity screening is an integral pre-clinical platform for evaluating potential two-drug combinational approaches for personalized treatment of cancer.