Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. Materials and Methods: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. Results: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. Conclusion Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Background and Objectives: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). Methods: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). Results: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. Conclusion Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

PURPOSE: Laparoscopic major liver resection (major LLR) remains a challenging procedure because of the technical difficulty. Several significant technical innovations have been applied in our center since 2012. They include routine application of bipolar electrocautery, initiation of temporary increase of intra-abdominal pressure during bleeding events from veins to balance the central venous pressure, and use of temporary inflow control of the Glissonean pedicle. This study evaluated the impact of these technique modifications in patients with major LLR. METHODS: Between January 2004 and February 2015, a total of 606 patients underwent LLR at Samsung Medical Center in Seoul, Korea. Major LLR was employed in 233 cases. All major LLR procedures were anatomical resections performed with a totally laparoscopic approach. We compared surgical parameters of right hepatectomy (RH), left hepatectomy (LH), and right posterior sectionectomy (RPS) before and after 2012. RESULTS: Open conversion rates of RH and LH and estimated blood loss in RPS significantly decreased after 2012. The postoperative complication rate of major LLR was 12.7% and was similar before and after 2012. Bile leakage was the most common complication (3.2%). CONCLUSION: The modifications of surgical techniques resulted in good outcomes for laparoscopic major LLR. We recommend routine application of these techniques to improve outcomes, especially in patients requiring major liver resection.
Bile ; Central Venous Pressure ; Electrocoagulation ; Hemorrhage ; Hepatectomy ; Humans ; Korea ; Laparoscopy ; Learning Curve ; Liver* ; Minimally Invasive Surgical Procedures ; Postoperative Complications ; Seoul ; Veins

PURPOSE: Percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) has some limitations such as poor sonic window and injury to adjacent organs. The laparoscopic approach has been suggested as an alternative option. The aim of this study was to show the safety and efficacy of laparoscopic RFA for single, small (≤3 cm), and primary or recurrent HCC that is not suitable for percutaneous RFA or surgical resection. METHODS: We reviewed the cases of 37 patients (32 men and 5 women, mean age 61 ± 8.1 years) who underwent laparoscopic RFA for single, small HCC (≤3 cm) that was unsuitable for percutaneous RFA or surgical resection. RESULTS: The technical success rate was 94.6% and 34 patients (95%) had no complications. There were no conversions to open RFA and no operative mortality. The primary effectiveness rate 1 month after the procedure was 100%. The overall recurrence rates at 3, 6, 12, and 24 months after the laparoscopic RFA were 8.1%, 14.4%, 25%, and 35.7%, respectively. The local tumor progression rate was 4.2% at 6 months and 8.7% at 9 months. CONCLUSION: Laparoscopic RFA is a safe and effective treatment for HCC cases that are unsuitable for percutaneous RFA.
Carcinoma, Hepatocellular* ; Catheter Ablation* ; Female ; Humans ; Laparoscopy ; Male ; Mortality ; Neoplasm Recurrence, Local ; Recurrence

BACKGROUND: As aging occurs, the skin develops more wrinkles and pigmentation, becomes drier, and loses its elasticity. In previous reports, light-emitting diode (LED) phototherapy was proven to stimulate collagen synthesis and accelerate fibroblast-myofibroblast transformation, which has a composite rejuvenation effect. OBJECTIVE: To evaluate the effectiveness and safety of LED phototherapy with 592 nm yellow light for photoaged skin. METHODS: Forty patients with photoaged skin (Korean photographic scale; grade 4approximately7) were enrolled and treated with an LED device producing 592+/-10 nm yellow light for 5 minutes twice a week for 4 weeks. The skin changes were assessed at 0, 2, 4, and 8 weeks by clinical photographs and the Cutometer(R) & Mexameter(R) (MPA 580, Courage+Khazaka Electronic GmbH, Koln, Germany). Measurements were made on the cheek, periorbital area, nasolabial fold, and glabella. RESULTS: At the final visit at 8 weeks, the Cutometer(R) parameters R4 and R6 decreased significantly compared to before treatment, from 0.118 to 0.099 for the periorbital (p=0.017) and 0.517 to 0.425 for the nasolabial fold (p=0.003). The average melanin index decreased significantly, from 133.65 to 124.55 (p<0.005). Fine improvement of wrinkles was shown grossly by reviewing follow-up clinical photographs. No adverse reactions occurred. LED phototherapy with 592+/-10 nm wavelength can be effective and safe in the treatment of photoaged skin. CONCLUSION: The findings suggest the LED with 592 nm yellow light might be an adjuvant therapeutic tool for photoaged skin.
Aging ; Cheek ; Collagen ; Elasticity ; Follow-Up Studies ; Humans ; Melanins ; Nasolabial Fold ; Phototherapy ; Pigmentation ; Rejuvenation ; Skin*

PURPOSE: Generic substitution of brand-name medications can lead to significant cost savings and is an accepted medical practice. This study evaluated clinical and safety outcomes among liver transplant recipients whose mycophenolate mofetil (MMF) was converted from the brand-name formulation (Cellcept) to a generic formulation (My-rept). METHODS: Clinical data from multiple centers were prospectively collected for determination of complications, safety, and quality of life after in 154 clinically stable, adult liver transplant recipients whose MMF was converted to a generic formulation between April 2010 and September 2012. This protocol was approved by Institutional Review Boards of all involved sites. RESULTS: In eight patients (5.19%), nine instances of drug-related complications occurred after medication conversion. Half of these complications were gastrointestinal disorders (n = 4), and most (7 of 9) were mild. No significant differences were noted in mean pre- and postconversion gastrointestinal symptoms via a rating system (8.9 vs. 10.4) or gastrointestinal quality-of-life index scores (125.6 vs. 123.1). More than 90% of patients reported a status of "about the same" when questioned about the brand-name and generic formulation using the Patient Overall Treatment Effect and Investigator Overall Treatment Effect measures. The incidence of serious adverse events was 5.8%. Acute rejection occurred in two patients, with no graft loss or death. CONCLUSION: Clinical experience as well as research data showed that generic MMF was comparable in efficacy to the brand-name drug. Given the lack of adverse events and the safety findings, conversion from brand-name MMF to generic MMF should be encouraged.
Adult ; Cost Savings ; Drug Substitution ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Generic ; Ethics Committees, Research ; Humans ; Incidence ; Liver* ; Prospective Studies ; Quality of Life ; Research Personnel ; Transplantation* ; Transplants

Despite a remarkable increase of deceased donors, organ shortage is the main hurdle of organ transplantation in Korea. Therefore, liver transplantation priority is a major issue of liver allocation. We confront a situation that needs to change in order to achieve more adequate and objective allocation of the system. We considered the MELD system as an alternative to the CTP score and Status system. For application of the MELD system, comparison between two systems is required; and a national-based retrospective review of liver transplantation candidates (waiting list) was conducted as a multi-center collaborative study. Eleven transplant centers participated in this national study. From 2009 to 2012, 2,702 waiting lists were enrolled. After mean 349+/-412 days follow-up, 967 patients (35.8%) of liver transplantation, 750 patients (27.8%) of drop-out/mortality, and 719 patients (26.6%) on waiting were identified. In analysis of patient mortality during waiting time, status system showed significant difference of waiting mortality by status at registration. However, differences of waiting mortality by MELD system were more prominent and discriminate. In comparisons by MELD score in exclusive Status 2A waiting patients, there was a significant difference of waiting mortality by MELD score. This means that the MELD system is a good predictor of short-term survival after listing compared with status system with CTP score. Korean national-based retrospective study showed the superiority of the MELD system in prediction of short-term mortality and usefulness as a determinant for allocation priority.
Cytidine Triphosphate ; Emergencies* ; End Stage Liver Disease ; Follow-Up Studies ; Humans ; Korea ; Liver Transplantation* ; Liver* ; Mortality ; Organ Transplantation ; Resource Allocation ; Retrospective Studies ; Survival Analysis* ; Tissue Donors* ; Transplants ; Waiting Lists