The Efficacy and Safety of GF101 and Its Antioxidant Effect on In Vitro Fertilization Outcomes: A Double-Blind, Non-Inferiority, Randomized, Controlled Trial with Coenzyme Q10.

(1) Background: Oxidative stress adversely affects fertility by impairing oocyte fertilization potential, primarily due to meiotic segregation errors and cohesion loss. Superoxide dismutase (SOD) and Coenzyme Q10 (CoQ10) are prominent antioxidants known to mitigate oxidative damage. (2) Methods: This study recruited 86 patients undergoing in vitro fertilization (IVF) at a single center for a 12-week, randomized, double-blind, active-comparator-controlled trial. Participants were allocated into two groups: one receiving CoQ10 as an antioxidant (the CoQ10 group) and the other receiving GF Bacillus antioxidative enzyme SOD (the GF101 group). The primary endpoints were changes in serum oxidative markers (SOD and catalase) and IVF outcomes, including clinical pregnancy, miscarriage, and live birth rates. Follicular fluid (FF) SOD and catalase concentrations on the day of retrieval, the metaphase II (MII) oocyte rate, the fertilization rate, and lipid profiles were measured. (3) Results: Initially, 86 patients were enrolled, with 65 completing the protocol (30 in the GF101 group and 34 in the CoQ10 group). There were no significant differences between the GF101 and CoQ10 groups in serum SOD (p = 0.626) and catalase levels (p = 0.061) over 12 weeks. However, within the GF101 group, a significant increase in serum catalase from baseline to 12 weeks was observed (p = 0.004). The non-inferiority analysis for IVF outcomes indicated risk differences in the clinical pregnancy rate, live birth rate, and miscarriage rate of -6.27% (95% CI: -30.77% to 18.22%), -1.18% (95% CI: -25.28% to 22.93%), and -13.49% (95% CI: -41.14% to 14.15%), respectively, demonstrating non-inferiority for the GF101 group. Furthermore, the GF101 group experienced significant reductions in total cholesterol (p = 0.006) and low-density lipoprotein (LDL) levels (p = 0.009) in intra-group comparisons, with both groups exhibiting comparable safe profiles. (4) Conclusions: GF101 may be non-inferior to CoQ10 in treating infertility in women and potentially offers additional benefits for women with dyslipidemia.

Clinical outcome of surgical resection for multifocal T2-T3 hepatocellular carcinoma up to 3 nodules: a comparative analysis with a single nodule.

BACKGROUND/AIMS: Although the Barcelona Clinic Liver Cancer staging system seems to underestimate the impact of curative-intent surgical resection for multifocal hepatocellular carcinoma (HCC), recent studies have indicated favorable results for the surgical resection of multiple HCC. This study aimed to assess clinical outcomes and feasibility of surgical resection for multifocal HCC with up to three nodules compared with single tumor cases. METHODS: Patients who underwent surgical resection for HCC with up to three nodules between 2009 and 2020 were included, and those with the American Joint Committee on Cancer (AJCC) 8th edition, T1 and T4 stages were excluded to reduce differences in disease distribution and severity. Finally, 81 and 52 patients were included in the single and multiple treatment groups, respectively. Short- and long-term outcomes including recurrence-free survival (RFS) and overall survival (OS), were evaluated. RESULTS: All patients were classified as Child-Pugh class A. RFS and OS were not significantly different between the two groups (P=0.176 and P=0.966, respectively). Multivariate analysis revealed that transfusion and intrahepatic metastasis were significantly associated with recurrence (P=0.046 and P=0.005, respectively). Additionally, intrahepatic metastasis was significantly associated with OS (hazard ratio, 1.989; 95% confidence interval, 1.040-3.802; P=0.038). CONCLUSIONS: Since there was no significant difference in survival between the single and multiple groups among patients with AJCC 8th stage T2 and T3, surgical resection with curative intent could be considered with acceptable long-term survival for selected patients with multiple HCC of up to three nodules.

A single-center experience of over 300 cases of single-incision robotic cholecystectomy comparing the da Vinci SP with the Si/Xi systems.

Minimally invasive surgery is usually more beneficial than open surgeries in various fields of surgery. With the newly developed Single-Port (SP) robotic surgical system, even single-site surgery has become easier to access. We compared single-incision robotic cholecystectomy between the Si/Xi and SP systems. This retrospective single-center study enrolled patients who underwent single-incision robotic cholecystectomy between July 2014 and July 2021. The clinical outcomes of the da Vinci Si/Xi and SP systems were compared. In total, 334 patients underwent single-incision robotic cholecystectomy (118 Si/Xi vs. 216 SP). The SP group had more chronic or acute cholecystitis than the Si/Xi group did. There was more bile spillage in the Si/Xi group during the surgery. The total operative and docking times were significantly shorter in the SP group. There was no difference in the postoperative outcomes. The SP system is safe and feasible regarding comparable postoperative complication rates and is more convenient regarding docking and techniques.

A dual-center study of predictive factors for sperm retrieval through microdissection testicular sperm extraction and intracytoplasmic sperm injection outcomes in men with non-mosaic Klinefelter syndrome.

PURPOSE: This study evaluated the predictors of sperm retrieval (SR) in non-mosaic Klinefelter syndrome (KS) patients undergoing microsurgical testicular sperm extraction (mTESE). The cutoff values of the predictors of SR and overall pregnancy rates after intracytoplasmic sperm injection (ICSI) were analyzed for the positive SR (PSR) cases. MATERIALS AND METHODS: The study was a dual-center retrospective study. Overall 118 patients with KS underwent mTESE between January 2011 and July 2021. Clinicopathological factors including comorbidities, endocrine profiles, and testicular volumes were analyzed. RESULTS: A total of 58 patients showed PSR (49.2%) and 60 patients (50.8%) had negative SR (NSR). The mean overall age of the patients was 32.5 years. The NSR patients had a significantly greater prevalence of obesity, diabetes mellitus, and cerebrovascular disease. The PSR group had a significantly higher left testis mean volume (p=0.039). The differences between the two study groups regarding follicular-stimulating hormone, luteinizing hormone, and testosterone variations at 1 and 3 months after mTESE were insignificant. Preoperative mean neutrophil-to-lymphocyte ratio was significantly greater in the NSR group (p=0.011), but the platelet-to-lymphocyte ratio showed no significant difference between the two study groups. A live child birth was achieved in 53.4% of the PSR patients. Multivariate logistic analysis showed that total testicular volume >3.93 mL, left testis volume >1.79 mL, and neutrophil-to-lymphocyte ratio ≤1.82 were significantly associated with PSR. CONCLUSIONS: mTESE-ICSI is a feasible method for KS patients to have a child, and total testicular volume, left testis volume, and neutrophil-to-lymphocyte ratio might be predictors of successful SR.

The Prevalence of Sexually Transmitted Infections and Sociosexual Behaviors in the South Korean Military Before and During the COVID-19 Pandemic.

INTRODUCTION: This study evaluated the epidemiological factors of sexually transmitted infections (STIs) among South Korean troops including the prevalence, therapeutic methods, and sexual risk behaviors. MATERIAL AND METHODS: The medical records of the STIs diagnosed troops at the Armed Forces Capital Hospital (AFCH) for 36 months (between January 2018 and December 2020) were retrospectively reviewed. The data collection for the study began after obtaining research approvals from the institutional ethics committee of AFCH. The patients were classified into two subgroups, pre-coronavirus disease 2019 (COVID-19) and COVID-19 groups. The clinical parameters of the patients including STI-related symptoms and underlying diseases were analyzed. The sociosexual conduct of the two study groups was evaluated and compared by using a survey questionnaire. RESULTS: Overall, 138 STI patients with mean age of 21.2 years were included (pre-COVID-19: 106 patients/COVID-19: 32 patients). 32.6% of the patients received college education before the military service. Regarding previous history of STIs, 24 patients (17.4%) had previous experience of STIs, which occurred before participation in the current study. Initial urine analysis results showed that 95 (68.8%) and 79 patients (57.2%) showed pyuria and bacteriuria, respectively. Neisseria gonorrhoeae (29.7%) was the most commonly identified pathogen. Each pathogen was treated with the therapies recommended by the current treatment guidelines, and no patient showed any recurrence of the disease during follow-up. Both pre-COVID-19 (91.5%) and COVID-19 (93.8%) groups showed high rates of binge drinking during off-duty. The pre-COVID-19 group had a greater number of patients (21.7%) having multiple sex partners (during the past 12 months) than the COVID-19 group (15.6%). The COVID-19 group had 18.8% of the troops involved in sexual activity even after the onset of STI-related clinical symptoms, whereas the rate was significantly higher than 2.8% of the pre-COVID-19 group (P = .001). The COVID-19 groups showed a significantly higher number of patients (four patients, 12.5%) experiencing suicidal ideation than the pre-COVID-19 group (two patients, 1.9%) (P = .010). Both groups showed <40% of condom use rates at the last sexual intercourse. CONCLUSION: The soldiers with STIs showed high rates of binge alcohol consumption, while the rates of engaging in safe sex by using condoms are markedly low. Although the COVID-19 group was under influence of social distancing and military base lockdown, the soldiers' sociosexual conduct was not significantly different in the pre-COVID-19 group. The importance of education on alcohol misuse and safe sexual relationships should be taken more seriously within the military.

Should we be reluctant to perform pancreatectomy in patients with chronic liver disease? A single center 10-year experience.

PURPOSE: Many studies have shown extra-hepatic surgery in patients with chronic liver disease (CLD) with or without portal hypertension can result in complications. The aim of this study was to analyze the results of major pancreatectomy in patients with CLD including cirrhosis and to evaluate their efficacy and safety. METHODS: We retrospectively reviewed 319 patients undergoing open pancreatoduodenectomy (PD) or distal pancreatectomy (DP) in our center. Those who received PD and DP in patients without CLD were classified into groups A and D, and those with CLD into groups B and C, respectively. Group B and C were subdivided into groups 1 and 2 according to the presence of portal hypertension. RESULTS: Forty-three patients (13.5%) had CLD. Of the 221 patients who received PD, 25 had CLD. Of the 98 patients who received DP, 18 (Group C) had CLD. In the PD group, patients with portal hypertension (group B1) had longer operative time. However, the transfusion rate and complication rate were not significantly different from other groups. There was no mortality in patients with CLD without portal hypertension (group B2) and the complication and mortality rate was comparable to patients with normal liver function (group A). In the DP group, the transfusion rate, complication rate and mortality rate were significantly higher in patients with portal hypertension (group C1). CONCLUSIONS: Acceptable outcomes were obtainable following pancreatic surgery in cirrhotic, non-portal hypertensive patients with surgical outcomes equivalent to non-cirrhotic patients.AbbreviationsCLDchronic liver diseasePDpancreaticoduodenectomyDPdistal pancreatectomy.

Left liver graft in adult-to-adult living donor liver transplantation with an optimal portal flow modulation strategy to overcome the small-for-size syndrome - A retrospective cohort study.

BACKGROUND: Adult-to-adult living donor liver transplantation (LDLT) is a notable type of liver transplantation. Several centers prefer the right liver graft (RLG) over the left liver graft (LLG) for better recovery of recipients. We compared the outcomes of donors and recipients between LDLT using LLGs and RLGs. MATERIALS AND METHODS: The study cohort comprised of 25 patients in the LLG group and 93 in the RLG group. When both hemiliver grafts met the selection criteria, an LLG was preferred. When portal flow (≥300 ml/min/100gLW) and hepatic venous pressure gradient (≥10 mmHg) were increased, intraoperative splenic artery ligation was performed for portal modulation. Postoperatively, somatostatin was administered when small-for-size syndrome (SFSS) was highly suspected. RESULTS: The graft-to-recipient weight ratio was lower in the LLG group than in the RLG group. There was no significant complication above Clavien-Dindo grade IIIA in donors. Regarding recipient outcomes, SFSS occurred in four (16.0%) patients in the LLG group and three (3.2%) in the RLG group (P = 0.036). Splenic artery ligation was frequently performed in the LLG group than the RLG group (5 [20.0%] vs. 12 [12.9%], P = 0.035) and 5 patients received intravenous continuous somatostatin for 7 (5-12) days. SFSS-related hospital mortality did not occur. There was no significant difference in the short-term and long-term outcomes between the groups. CONCLUSION: This study demonstrates the comparable outcomes of donors and recipients between the LLG and RLG groups although with a higher risk of SFSS that needs high experience to avoid severe complications and graft loss. We expect LLG to be used more actively in adult-to-adult LDLT with portal flow modulation strategies to overcome fatal SFSS.

Prevalence and clinical significance of pancreatic cystic lesions in immunosuppressed patients following solid organ transplantation.

Background: Pancreatic cystic lesions (PCLs) are occasionally found in solid organ transplant (SOT) recipients. In such recipients, the risk of cancer is increased due to immunosuppressive therapy. This study investigated the prevalence of PCLs and described their clinical course in immunosuppressed patients following SOT. Methods: The presence of PCLs in a retrospective cohort of 805 consecutive SOT recipients from 2009 to 2019 was examined. The characteristics of PCLs were compared using initial and follow-up imaging, where available. These results were compared to an age- and sex-matched immunocompetent control group monitored for at least 12 months. Results: PCLs were present in 15 of 805 SOT patients (seven liver and eight kidney transplantations). The median diameter of the largest lesion was 20 mm (range, 0.2-60 mm) and 60% of lesions were benign. During follow-up imaging, the cyst size remained stable in 46.7%, increased in 13.3%, and decreased in 40.0% of the SOT group. Significantly more of the SOT patients showed PCL size reductions (P=0.007). Among SOT patients diagnosed with intraductal papillary mucinous neoplasms (6/15), worrisome features were noted in one patient at the time of cyst diagnosis. Differences in the development of worrisome features between the study and control groups were not statistically significant. Conclusions: The malignant transformation of PCLs in SOT recipients is rare and most such PCLs can be managed conservatively. The presence of a PCL should therefore not affect transplant eligibility.

Artificial intelligence for predicting survival following deceased donor liver transplantation: Retrospective multi-center study.

BACKGROUND: Previous studies have indicated that the model for end-stage liver disease (MELD) score may fail to predict post-transplantation patient survival. Similarly, other scores (donor MELD score, balance of risk score) that have been developed to predict transplant outcomes have not gained widespread use. These scores are typically derived using linear statistical models. This study aimed to compare the performance of traditional statistical models with machine learning approaches for predicting survival following liver transplantation. MATERIALS AND METHODS: Data were obtained from 785 deceased donor liver transplant recipients enrolled in the Korean Organ Transplant Registry (2014-2019). Five machine learning methods (random forest, artificial neural networks, decision tree, naïve Bayes, and support vector machine) and four traditional statistical models (Cox regression, MELD score, donor MELD score and balance of risk score) were compared to predict survival. RESULTS: Among the machine learning methods, the random forest yielded the highest area under the receiver operating characteristic curve (AUC-ROC) values (1-month = 0.80; 3-month = 0.85; and 12-month = 0.81) for predicting survival. The AUC-ROC values of the Cox regression analysis were 0.75, 0.86, and 0.77 for 1-month, 3-month, and 12-month post-transplant survival, respectively. However, the AUC-ROC values of the MELD, donor MELD, and balance of risk scores were all below 0.70. Based on the variable importance of the random forest analysis in this study, the major predictors associated with survival were cold ischemia time, donor ICU stay, recipient weight, recipient BMI, recipient age, recipient INR, and recipient albumin level. As with the Cox regression analysis, donor ICU stay, donor bilirubin level, BAR score, and recipient albumin levels were also important factors associated with post-transplant survival in the RF model. The coefficients of these variables were also statistically significant in the Cox model (p < 0.05). The SHAP ranges for selected predictors for the 12-month survival were (-0.02,0.10) for recipient albumin, (-0.05,0.07) for donor bilirubin and (-0.02,0.25) for recipient height. Surprisingly, although not statistically significant in the Cox model, recipient weight, recipient BMI, recipient age, or recipient INR were important factors in our random forest model for predicting post-transplantation survival. CONCLUSION: Machine learning algorithms such as the random forest were superior to conventional Cox regression and previously reported survival scores for predicting 1-month, 3-month, and 12-month survival following liver transplantation. Therefore, artificial intelligence may have significant potential in aiding clinical decision-making during liver transplantation, including matching donors and recipients.

Comparison of oncologic outcomes between open and laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma using data from the KOTUS-BP national database: overcoming selection bias and the necessity of definite indications.

BACKGROUND: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

Right posterior bile duct stricture after central bisectionectomy or anterior sectionectomy.

PURPOSE: Before performing anterior sectionectomy (AS) or central bisectionectomy (CBS), the anatomy of the right posterior bile duct (RPBD) must be cautiously assessed owing to the many variations of the RPBD and its variations could be related to bile duct injury. METHODS: Clinical data of patients who underwent AS or CBS from 2009 to 2018 were reviewed. The bile duct anatomy according to Okubo's criteria and the right bile duct (RBD) length were evaluated using MRI, and we performed a risk factor analysis of the RPBD stricture (RPBDS). RESULTS: A total of 68 patients were included. Type A bile ducts were the most common (n = 36, 52.9%). Five (7.2%) patients had RPBDS requiring intervention. RPBDS only occurred in patients with a type A bile duct and a type A portal vein undergoing surgery using the Glissonian sheath approach. Moreover, when the RBD length was > 12 mm, the sensitivity and specificity were 0.8 and 0.889, respectively. In multivariate analysis, RBD length of > 12 mm was significant. CONCLUSION: A careful review of RPBD anatomy especially in patient with long RBD and caution when using the anterior Glissonian sheath approach might be helpful to prevent RPBDS during AS or CBS.

Single-port robot plus one port (SP + 1) distal pancreatectomy using the new da Vinci SP system.

PURPOSE: Single-incision laparoscopic distal pancreatectomy has not been widely applied due to technical challenges and increased operative risks. The newly released da Vinci SP system has been introduced to overcome these limitations and offer improvements for established robotic single-site procedures. We report our experience of robotic single port plus one port distal pancreatectomy using the da Vinci SP system. METHODS: We performed robotic distal pancreatectomy in three patients using the da Vinci SP surgical system with one additional port used for applying the energy device and stapling. Technical and clinical feasibility were examined. RESULTS: The mean age and body mass index were 70.7 years and 27.8 kg/m2, respectively. The mean operation time was 215 min. The estimated blood loss was less than 500 mL. All patients underwent combined splenectomy. The postoperative course of all patients was uneventful. CONCLUSION: Robotic distal pancreatectomy using the da Vinci SP system is safe and feasible, with acceptable perioperative outcomes.

Efficacy and Safety of Hepatitis B Virus Vaccination Following Hepatitis B Immunoglobulin Withdrawal After Liver Transplantation.

BACKGROUND: Hepatitis B immunoglobulin (HBIG) and oral nucleoside/nucleotide analogs have been the mainstay of hepatitis B virus (HBV) prophylaxis after liver transplantation. However, long-term HBIG administration could have disadvantages, such as an increase in medical costs and the development of mutant HBV strains. This study aimed to investigate the safety and efficacy of HBV vaccination after the withdrawal of HBIG after liver transplantation. METHODS: This prospective open-label single-arm observational clinical trial enrolled 41 patients who underwent liver transplantation between 2010 and 2016 because of a condition related to chronic HBV infection. At the time of enrollment, all patients had taken entecavir and discontinued HBIG administration. When hepatitis B surface antibody titer was undetectable after the withdrawal of HBIG, a recombinant HBV vaccine was injected intramuscularly at month 0, 1, and 6. RESULTS: After excluding 5 patients who dropped out and 2 patients who had a persistent hepatitis B surface antibody titer, 9 (26.5%) of 34 patients had a positive vaccination response. The median hepatitis B surface antibody titer at seroconversion was 86 (12-1000) IU/L, and those at the end of follow-up were 216 (30-1000) IU/L. No patients experienced HBV recurrence during the study period. Sex (female, odds ratio 32.91 [1.83-592.54], P = .018) and the dosing interval of HBIG before withdrawal (≥90 days, 16.21 [1.21-217.31], P = .035) were independent contributing factors for positive response to the vaccination. CONCLUSION: HBV vaccination still deserves consideration as active immunoprophylaxis after liver transplantation because it could provide added immunity to nucleoside/nucleotide analogs monotherapy with excellent cost-effectiveness.

Usefulness of artificial intelligence for predicting recurrence following surgery for pancreatic cancer: Retrospective cohort study.

BACKGROUND: or Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of mortality in the world with the overall 5-year survival rate of 6%. The survival of patients with PDAC is closely related to recurrence and therefore it is necessary to identify the risk factors for recurrence. This study uses artificial intelligence approaches and multi-center registry data to analyze the recurrence of pancreatic cancer after surgery and its major determinants. METHODS: Data came from 4846 patients enrolled in a multi-center registry system, the Korea Tumor Registry System (KOTUS). The random forest and the Cox proportional-hazards model (the Cox model) were applied and compared for the prediction of disease-free survival. Variable importance, the contribution of a variable for the performance of the model, was used for identifying major predictors of disease-free survival after surgery. The C-Index was introduced as a criterion for validating the models trained. RESULTS: Based on variable importance from the random forest, major predictors of disease-free survival after surgery were tumor size (0.00310), tumor grade (0.00211), TNM stage (0.00211), T stage (0.00146) and lymphovascular invasion (0.00125). The coefficients of these variables were statistically significant in the Cox model (p < 0.05). The C-Index averages of the random forest and the Cox model were 0.6805 and 0.7738, respectively. CONCLUSIONS: This is the first artificial-intelligence study with multi-center registry data to predict disease-free survival after the surgery of pancreatic cancer. The findings of this methodological study demonstrate that artificial intelligence can provide a valuable decision-support system for treating patients undergoing surgery for pancreatic cancer. However, at present, further studies are needed to demonstrate the actual benefit of applying machine learning algorithms in clinical practice.

The Prognosis and Oncological Predictor of Urachal Carcinoma of the Bladder: A Large Scale Multicenter Cohort Study Analyzed 203 Patients With Long Term Follow-Up.

AIM: This study evaluated the prognosis and survival predictors for bladder urachal carcinoma (UC), based on large scale multicenter cohort with long term follow-up database. METHODS: A total 203 patients with bladder UC treated at 19 hospitals were enrolled. Clinical parameters on carcinoma presentation, diagnosis, and therapeutic methods were reviewed for the primary cancer and for all subsequent recurrences. The stage of UC was stratified by Mayo and Sheldon pathological staging system. Oncological outcomes and the possible clinicopathological parameters associated with survival outcomes were investigated. RESULTS: The mean age of the patients was 54.2 years. Among the total of 203 patients, stages I, II, III, and IV (Mayo stage) were 48 (23.8%), 108 (53.5%), 23 (11.4%), and 23 (11.4%), respectively. Gross hematuria and bladder irritation symptoms were the two most common initial symptoms. The mean follow-up period was 65 months, and 5-year overall survival rates (OS), cancer-specific survival rates (CSS), and recurrence-free survival rates (RFS) were 88.3, 83.1, and 63.9%, respectively. For the patients with Mayo stage ≥III, OS, CSS, and RFS were significantly decreased to 38.0, 35.2, and 28.4%, respectively. The higher pathological stage (Mayo stage ≥III, Sheldon stage ≥IIIc), positive surgical margin (PSM), and positive lymphovascular invasion (PLM) were independent predictors of shorter OS, CSS, and RFS. CONCLUSION: The pathological stage, PSM, and PLM were significantly associated with the survival of UC patients, emphasizing an importance of the complete surgical resection of tumor lesion.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP).

Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions: The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Successful Treatment of Sinusoidal Obstructive Syndrome with Deceased-Donor Liver Transplant Following Hematopoietic Stem Cell Transplant.

Sinusoidal obstructive syndrome, also known as venoocclusive disease, is a potentially life-threatening complication of hematopoietic stem cell transplant. The conditioning regimens given before hematopoietic stem cell transplant result in the production of toxic metabolites that trigger the activation, damage, and inflammation of the endothelial cells that line the sinusoids. Although liver transplant has been performed for treatment of sinusoidal obstructive syndrome, reports by various liver transplant centers worldwide have been limited and disappointing. We report our experience of successfully treating a patient with sinusoidal obstructive syndrome with deceased donor liver transplant. A 34-year-old male patient was referred to our department due to refractory ascites and jaundice within 1 month after receiving peripheral blood stem cell transplant for acute lymphocytic leukemia. He was diagnosed with biopsy-proven sinusoidal obstructive syndrome. Despite therapy with defibrotide, his condition continued to deteriorate, which included development of intractable pleural effusion, ascites, and progressive renal failure. After undergoing deceased donor liver transplant, the patient's serum bilirubin levels and prothrombin time began to decrease. The histology of the excised liver was compatible with hepatic sinusoidal obstructive syndrome. After being treated for pneumonia, pulmonary edema, and cytomegalovirus viremia, the patient was discharged 2 months after transplant. At 18 months after liver transplant, although he was treated for fungal pneumonia and is being considered for kidney transplant due to unsuccessful weaning from renal replacement therapy, the patient has shown stable liver function and no signs of either graft-versus-host disease or a relapse of acute lymphocytic leukemia. In conclusion, although severe sinusoidal obstructive syndrome in the setting of stem cell transplant has a poor prognosis, we suggest that deceased donor liver transplant should be considered in the treatment of select patients with life-threatening liver dysfunction after hematopoietic stem cell transplant.

The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria.

BACKGROUND: Ureaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP). METHODS: This study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months. RESULTS: Forty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH. CONCLUSIONS: UP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.

Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review.

Prostate cancer (PCa) has a vast clinical spectrum from the hormone-sensitive setting to castration-resistant metastatic disease. Thus, chemotherapy regimens and the administration of androgen receptor axis-targeted (ARAT) agents for advanced PCa have shown limited therapeutic efficacy. Scientific advances in the field of molecular medicine and technological developments over the last decade have paved the path for immunotherapy to become an essential clinical modality for the treatment of patients with metastatic PCa. However, several immunotherapeutic agents have shown poor outcomes in patients with advanced disease, possibly due to the low PCa mutational burden. Adoptive cellular approaches utilizing chimeric antigen receptor T cells (CAR-T) targeting cancer-specific antigens would be a solution for circumventing the immune tolerance mechanisms. The immunotherapeutic regimen of CAR-T cell therapy has shown potential in the eradication of hematologic malignancies, and current clinical objectives maintain the equivalent efficacy in the treatment of solid tumors, including PCa. This review will explore the current modalities of CAR-T therapy in the disease spectrum of PCa while describing key limitations of this immunotherapeutic approach and discuss future directions in the application of immunotherapy for the treatment of metastatic PCa and patients with advanced disease.

Feasibility and early toxicity of focal or partial brachytherapy in prostate cancer patients.

PURPOSE: The aim of this study was to compare short-term oncologic outcomes and toxicity of focal or partial low-dose-rate brachytherapy (focal/partial LDR-BT) with whole gland low-dose-rate brachytherapy (whole LDR-BT) in localized prostate cancer patients. MATERIAL AND METHODS: Medical records of eligible patients who underwent focal/partial LDR-BT and whole LDR-BT between 2015 and 2017 at our institution were reviewed retrospectively. Clinical characteristics and pathologic outcomes were compared between focal/partial LDR-BT group and whole LDR-BT group. Biochemical recurrence-free survival was analyzed using Kaplan-Meier method and difference between two groups was assessed with log-rank test. Genitourinary and rectal toxicity were also evaluated between the two groups. RESULTS: Of the 60 patients analyzed, 30 focal/partial LDR-BT patients and 30 whole LDR-BT brachytherapy patients were included. Relative to the whole LDR-BT group, the focal/partial LDR-BT group had significantly higher initial PSA level (p = 0.002), smaller number of implanted seeds (p < 0.001), and shorter follow-up duration (p < 0.001). There was no significant difference between the two groups with regard to prostate volume, biopsy Gleason score, and risk group stratification. The 3-year biochemical recurrence-free survival estimates for focal/partial LDR-BT group and whole LDR-BT group were 91.8% and 89.6%, respectively, which was not significantly different (p = 0.554). Genitourinary symptoms were significantly worse in whole LDR-BT group than in focal/partial LDR-BT group. The incidence of rectal toxicity was similar between two groups. CONCLUSIONS: Our findings indicate that the focal/partial LDR-BT is comparable to the whole LDR-BT with respect to short-term biochemical recurrence and toxicities.