Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

PURPOSE: Hepatic resection is considered as the optimal treatment for intrahepatic cholangiocarcinoma (IHCC); however, the survival rate after resection is low and the analysis of long-term (≥10 years) survivors is rare. This study aims to analyze the clinicopathological factors affecting the long-term survival of patients with IHCC. METHODS: Between January 2003 and December 2012, a single-institution cohort of 429 patients who underwent hepatic resection for IHCC were reviewed retrospectively. Surgical results, recurrence, and survival rates were investigated, and multivariate analyses were performed to identify prognostic factors. RESULTS: The overall 1- , 3- , 5- and 10-year survival rates of patients were 76.5%, 44.1%, 33.3%, and 25.1%, respectively. Multivariate analysis showed that the serum CA 19-9 level (≥38 U/mL) (P < 0.001), lymph node (LN) metastasis (P = 0.001), and lymphovascular invasion (LVI) (P = 0.012) were independent factors associated with overall survival. In particular, CA 19-9 level and histologic type were determined to be independent factors affecting survival for more than 10 years. CONCLUSION CA 19-9 (≥38 U/mL), LN metastasis, and LVI were identified as independent risk factors for survival after resection of IHCC. CA 19-9 (<38 U/mL) and histologic type were independent factors predicting survival for more than 10 years.

Purpose: Ampulla of Vater (AoV) carcinoma has a relatively good prognosis. The 5-year recurrence rate for AoV is still around 40%–50% however, and most recurrences occur in the early period. The aim of this study was to identify predictors of an early recurrence in AoV patients following a curative resection. Methods: The clinicopathological data for 501 consecutive patients that underwent a resection for AoV in our institute between January 2000 and December 2015 were retrospectively reviewed. The characteristics of any recurrences and early recurrence patients were analyzed accordingly. Early recurrence was defined as occurring within one year of resection. Results: There were 170 diagnosed recurrences in our study population, 57.1% of whom were men, with a mean age of 60.1 years (range, 30–94 years). Almost all of the study patients underwent a pancreaticoduodenectomy, and 9% underwent minimally invasive surgery. Of the 170 recurrent cases, 107 were diagnosed with an early recurrence and had 1-, 3-, and 5-year overall survival rates of 77.7%, 18.4%, 10.5%, respectively. The factors that significantly influenced early recurrences, determined by multivariate analysis, lymphovascular invasion (LVI), lymph node ratio (LNR), and poor differentiation were found to be independent determinants of a recurrence within 1 year. Conclusion An early recurrence in AoV patients is ultimately lethal even though this cancer has a good prognosis. LVI, LNR, and poor differentiation are powerful predictors of an early recurrence in AoV. Hence, intensive surveillance and new therapeutic strategies should be considered for AoV patients with these predictors following a curative resection.

PURPOSE: Transduodenal ampullectomy (TDA) has been reported in a limited number of cases and in a small number of case series. The aim of this study was to analyze perioperative and long-term oncological outcomes of patients with ampullary tumors who underwent TDA in a single large-volume center. METHODS: Through a retrospective review of data from 2004 to 2016, we identified 26 patients who underwent TDA at Asan Medical Center. RESULTS: Eleven of 26 patients underwent TDA for T1 and carcinoma in situ (high-grade dysplasia) cancer; these patients are still alive without recurrence. A major in-hospital complication (3.8%) occurred in 1 case, but there was no case of 90-day mortality. In addition, none of the patients was diagnosed as having newly developed diabetes mellitus after TDA. No significant differences were found between open and laparoscopic-TDA in terms of operation time, painkiller use, and hospital stay. CONCLUSION: TDA is a feasible and effective surgical procedure for the treatment of selected patients with ampullary tumors. It is an alternative treatment option in cases of ampullary tumors not amenable to endoscopic papillectomy or pancreaticoduodenectomy.
Ampulla of Vater ; Carcinoma in Situ ; Chungcheongnam-do ; Diabetes Mellitus ; Humans ; Length of Stay ; Mortality ; Pancreaticoduodenectomy ; Recurrence ; Retrospective Studies

PURPOSE: Despite the great advances in laparoscopic techniques, most active general surgeons do not apply laparoscopic surgery in the treatment of duodenal ulcer perforation when facing a real-life emergency. Therefore, our study was designed to evaluate the feasibility of laparoscopic surgery in duodenal ulcer perforation, and provide a step-by-step protocol with tips and recommendations for less experienced surgeons. MATERIALS AND METHODS: Between March, 2011 and May, 2012, 21 patients presenting with duodenal ulcer perforation underwent laparoscopic primary repair with omentopexy. There were no contraindications to perform laparoscopic surgery, and the choice of primary repair was decided according to the size of the perforation. The procedure for laparoscopic primary repair with omentopexy consisted of peritoneal lavage, primary suture, and omentopexy using a knot pusher. RESULTS: During the operation, no conversion to open surgery or intra-operative events occurred. The median operation time was 45.0 minutes (20~80 minutes). Median day of commencement of a soft diet was day 6 (4~17 days). After surgery, the median hospital stay was 8.0 days (5~27 days). Postoperative complications occurred in one patient, which included a minor leakage. This complication was resolved by conservative management. CONCLUSIONS: Although our study was carried out on a small number of patients at a single institution, we conclude that laparoscopic primary repair can be an effective surgical method in the treatment of duodenal ulcer perforation. We believe that the detailed explanation of our procedure will help beginners to perform laparoscopic primary repair more easily.
Conversion to Open Surgery ; Diet ; Duodenal Ulcer ; Emergencies ; Humans ; Laparoscopy ; Length of Stay ; Peritoneal Lavage ; Postoperative Complications ; Sutures

PURPOSE: Despite the great advances in laparoscopic techniques, most active general surgeons do not apply laparoscopic surgery in the treatment of duodenal ulcer perforation when facing a real-life emergency. Therefore, our study was designed to evaluate the feasibility of laparoscopic surgery in duodenal ulcer perforation, and provide a step-by-step protocol with tips and recommendations for less experienced surgeons. MATERIALS AND METHODS: Between March, 2011 and May, 2012, 21 patients presenting with duodenal ulcer perforation underwent laparoscopic primary repair with omentopexy. There were no contraindications to perform laparoscopic surgery, and the choice of primary repair was decided according to the size of the perforation. The procedure for laparoscopic primary repair with omentopexy consisted of peritoneal lavage, primary suture, and omentopexy using a knot pusher. RESULTS: During the operation, no conversion to open surgery or intra-operative events occurred. The median operation time was 45.0 minutes (20~80 minutes). Median day of commencement of a soft diet was day 6 (4~17 days). After surgery, the median hospital stay was 8.0 days (5~27 days). Postoperative complications occurred in one patient, which included a minor leakage. This complication was resolved by conservative management. CONCLUSIONS: Although our study was carried out on a small number of patients at a single institution, we conclude that laparoscopic primary repair can be an effective surgical method in the treatment of duodenal ulcer perforation. We believe that the detailed explanation of our procedure will help beginners to perform laparoscopic primary repair more easily.
Conversion to Open Surgery ; Diet ; Duodenal Ulcer ; Emergencies ; Humans ; Laparoscopy ; Length of Stay ; Peritoneal Lavage ; Postoperative Complications ; Sutures