Impact of Nrf2 overexpression on cholangiocarcinoma treatment and clinical prognosis.

PURPOSE: Nrf2 regulates antioxidant protein expression and protects against drug toxicity and oxidative stress, whereas Keap1 controls Nrf2 activity. The Keap1-Nrf2 pathway affects the prognosis of various cancers, however, its effect on cholangiocarcinoma chemoresistance and prognosis remains unclear. This study aimed to determine whether the Keap1-Nrf2 pathway affects chemoresistance and prognosis of distal cholangiocarcinoma. METHODS: We investigated the correlation between Nrf2 and Keap1 expression and clinical characteristics and prognosis in 91 patients with distal cholangiocarcinoma who underwent curative surgery. Immunohistochemical staining was performed on paraffin blocks using primary antibodies against Nrf2 and Keap1. The relationship between Keap1 and Nrf2 protein expression levels, and clinical characteristics and prognosis was examined. RESULTS: Nrf2 expression was not associated with overall survival in patients who did not receive adjuvant chemotherapy (P=0.994). Among patients receiving adjuvant chemotherapy, the Nrf2 low expression group had a significantly longer median overall survival than the Nrf2 high expression group in Kaplan-Meier survival analysis (P=0.019). In multivariate analysis, high expression of Nrf2 was confirmed as an independent poor prognostic factor in the group receiving adjuvant chemotherapy (P=0.041). CONCLUSION: This study suggests that Nrf2 overexpression reduces the efficacy of adjuvant chemotherapy in distal cholangiocarcinoma.

Propensity score matching analysis of perioperative outcomes including quality of life after multi-port vs. single port laparoscopic cholecystectomy: a nationwide prospective multicenter study in Korea.

INTRODUCTION: The usefulness of single-port laparoscopic cholecystectomy (SPLC) as compared to multi-port laparoscopic cholecystectomy (MPLC) remains controversial. Between SPLC and MPLC, we compared outcomes, especially subjective aspects, such as quality of life (QoL). MATERIAL AND METHODS: This multi-center study, involving 20 institutions from 2016 to 2017, enrolled 2507 patients who underwent laparoscopic cholecystectomy. Various perioperative outcomes, pain assessed by the numeric rating scale (NRS) score, and QoL evaluated by the gastrointestinal QoL index (GIQLI) questionnaire, were compared between the two procedures. We generated balanced groups after propensity score matching (PSM) using preoperative factors that influence the decision to perform MPLC or SPLC. RESULTS: MPLC and SPLC were performed in 2176 and 331 patients, respectively. Nine hundred and twelve and 329 patients, respectively, were selected from the two groups by PSM. Operation time was longer and surgical difficulty was lower in SPLC. There were no significant differences in most outcomes, including biliary complications. Significant superiority of SPLC over MPLC was shorter hospitalization, lower NRS score, and favorable GIQLI. CONCLUSIONS: From nationwide prospective data, SPLC showed outcomes comparable to MPLC. In SPLC, morbidity was not high and postoperative QoL was favorable. In the future, more implementations and studies are needed to ensure the safety and feasibility of SPLC.

Multi-biomarker panel prediction model for diagnosis of pancreatic cancer.

BACKGROUND/PURPOSE: The current study aimed to develop a prediction model using a multi-marker panel as a diagnostic screening tool for pancreatic ductal adenocarcinoma. METHODS: Multi-center cohort of 1991 blood samples were collected from January 2011 to September 2019, of which 609 were normal, 145 were other cancer (colorectal, thyroid, and breast cancer), 314 were pancreatic benign disease, and 923 were pancreatic ductal adenocarcinoma. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers: LRG1, TTR, and CA 19-9. Using a logistic regression model on a training data set, the predicted values for pancreatic ductal adenocarcinoma were obtained, and the result was classification into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and three biomarkers. RESULTS: Participants were categorized into four groups as normal (n = 609), other cancer (n = 145), pancreatic benign disease (n = 314), and pancreatic ductal adenocarcinoma (n = 923). The normal, other cancer, and pancreatic benign disease groups were clubbed into the non-pancreatic ductal adenocarcinoma group (n = 1068). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively. CONCLUSIONS: This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing pancreatic ductal adenocarcinoma from normal and benign pancreatic disease states, as well as patients with other cancers.

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.

Fate of Surgical Patients with Small Nonfunctioning Pancreatic Neuroendocrine Tumors: An International Study Using Multi-Institutional Registries.

Several treatment guidelines for sporadic, nonmetastatic nonfunctioning neuroendocrine tumors of the pancreas (NF-pNETs) have recommended resection, however, tumors ≤ 2 cm do not necessarily need surgery. This study aims to establish a surgical treatment plan for NF-pNETs ≤ 2 cm. From 2000 to 2017, 483 patients who underwent resection for NF-pNETs ≤ 2 cm in 18 institutions from Korea and China were enrolled and their medical records were reviewed. The median age was 56 (range 16-80) years. The 10-year overall survival rate (10Y-OS) and recurrence-free survival rate (10Y-RFS) were 89.8 and 93.1%, respectively. In multivariable analysis, tumor size (>1.5 cm; HR 4.28, 95% CI 1.80-10.18, p = 0.001) and nodal metastasis (HR 3.32, 95% CI 1.29-8.50, p = 0.013) were independent adverse prognostic factors for OS. Perineural invasion (HR 4.36, 95% CI 1.48-12.87, p = 0.008) and high Ki-67 index (≥3%; HR 9.06, 95% CI 3.01-27.30, p < 0.001) were independent prognostic factors for poor RFS. NF-pNETs ≤ 2 cm showed unfavorable prognosis after resection when the tumor was larger than 1.5 cm, Ki-67 index ≥ 3%, or nodal metastasis was present. NF-pNET patients with tumors ≤ 1.5 cm can be observed if the preoperative Ki-67 index is under 3%, and if nodal metastasis is not suspected in preoperative radiologic studies. These findings support the clinical use to make decisions about small NF-pNETs.

A retrospective multicentre study on the evaluation of perioperative outcomes of single-port robotic cholecystectomy comparing the Xi and SP versions of the da Vinci robotic surgical system.

BACKGROUND: Single-incision robotic cholecystectomy (SIRC) is widely performed with both the da Vinci Xi system (Xi) and the da Vinci SP system (SP). But there are limited numbers of studies comparing these platforms. METHODS: Patients who underwent SIRC between 2019 and 2020 were enrolled. Patient demographics, intraoperative factors, postoperative complications, postoperative pain were compared using a one-to-one propensity score matching (PSM). RESULTS: Overall, 258 patients underwent SIRC with Xi and 72 with SP. After PSM, there were significant differences between the Xi and SP in operation time at console and numeric rating scale for postoperative pain, but no difference in total operation time and postoperative complications. The SP group showed more estimated blood loss. CONCLUSIONS: Despite the statistical difference, clinical benefit was not significant. Both platforms can be safe and feasible to perform SIRC, but further investigation including the surgeon's workload and ergonomics is needed as a prospective study.

Risk factors of recurrence following common bile duct exploration for choledocholithiasis.

Purpose: The purpose of this study was to investigate the recurrence factors of choledocholithiasis after common bile duct (CBD) exploration. Methods: From January 2000 to December 2018, we retrospectively reviewed 253 patients who underwent CBD exploration surgery. We excluded 100 cases who had residual stone, combined major surgery, or follow-up loss after surgery. Total of 153 patients were included, and we investigated the recurrence factors of choledocholithiasis. Various variables such as patients' demographics, gallstones, preoperative endoscopic treatment, and laboratory data were analyzed to find factors related to recurrent choledocholithiasis. Results: The median follow-up period was 20.6 months (range 4.7-219 months), and 27 patients (17.6%) had experienced recurrent choledocholithiasis. Univariate analysis showed that the following variables were associated with recurrence of choledocholithiasis; preoperative leukocytosis (white blood cell ≥ 11,000/µL), open procedure, T tube insertion, long hospital duration, and long operation time. Logistic regression multivariate analysis identified preoperative leukocytosis (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.21-9.73; p = 0.021), open procedure (OR, 5.54; 95% CI, 4.73-6.35; p = 0.037), and T-tube insertion (OR, 2.82; 95% CI, 1.04-7.65; p = 0.042) as independent predictors of recurrent choledocholithiasis. Conclusion: Because of delayed recurrence of choledocholithiasis, it is recommended to continue follow-up of patients after CBD exploration surgery. Laparoscopic surgery was observed to be associated with a reduction in recurrence. The preoperative leukocytosis and clinical conditions in which open surgery is performed could be associated with recurrence of choledocholithiasis. However, further study is necessary to validate the result.

Long-term patient-reported outcomes following laparoscopic cholecystectomy: A prospective multicenter observational study.

Several studies have reported short-term results for post-cholecystectomy symptoms and quality of life (QoL). However, reports on long-term results are still limited. This study aimed to identify risk factors affecting short- and long-term patient-reported outcome (PRO) following laparoscopic cholecystectomy.From 2016 to 2017, a total of 476 patients from 5 institutions were enrolled. PRO was examined using the Numeric Rating Scale (NRS) pain score and the Gastrointestinal (GI) QoL Index questionnaire at postoperative 1 month and 1 year.Most of patients recovered well at postoperative 1 year compared to postoperative 1 month for the NRS pain score, QoL score, and GI symptoms. A high operative difficulty score (HR 1.740, P = .031) and pathology of acute or complicated cholecystitis (HR 1.524, P = .048) were identified as independent risk factors for high NRS pain scores at postoperative 1 month. Similarly, female sex (HR 1.571, P = .003) at postoperative 1 month and postoperative complications (HR 5.567, P = .001) at postoperative 1 year were independent risk factors for a low QoL. Also, age above 50 (HR 1.842, P = .001), female sex (HR 1.531, P = .006), and preoperative gallbladder drainage (HR 3.086, P = .001) were identified as independent risk factors for GI symptoms at postoperative 1 month.Most patients showed improved long-term PRO measurement in terms of pain, QoL, and GI symptoms. There were no independent risk factors for long-term postoperative pain and GI symptoms. However, postoperative complications were identified to affect QoL adversely at postoperative 1 year. Careful and long-term follow up is thus necessary for patients who experienced postoperative complications.

16S rDNA microbiome composition pattern analysis as a diagnostic biomarker for biliary tract cancer.

BACKGROUND: The aim of this study is to investigate the composition of microbiota in biliary tract cancer patients and healthy adults by metagenome analysis and evaluate its potential values as biomarkers for biliary tract cancer. METHODS: Patients who were diagnosed with biliary tract cancer or benign inflammation were enrolled in this study. The control group consisted of healthy adults who presented with no history of significant medical issues. We isolated bacteria-derived extracellular vesicles in the plasma. The microbiome composition was investigated with 16S rDNA metagenome analysis. We evaluated each microbiome to ensure suitability for the biliary tract cancer prediction model. RESULTS: A total of 155 patients were included in this study: 24 patients with diagnosed biliary tract cancers, 43 diagnosed with cholecystitis or cholangitis, and 88 healthy adults. The microbiome composition pattern of the biliary tract cancer differed from the microbiome composition pattern seen in healthy adult group in beta diversity analysis. The percent composition of microbiota was found to be different from the phylum to genus level. Differences in the composition of the Bifidobacteriaceae and Pseudomonaceae families and Corynebacteriaceae Corynebacterium, Oxalobacteraceae Ralstonia and Comamonadaceae Comamonas species may be used to develop predictive models for biliary tract cancer. CONCLUSION: Biliary tract cancer patients have altered microbiome composition, which represents a promising biomarker to differentiate malignant biliary tract disease from normal control group.

Nutritional risk factors are associated with postoperative complications after pancreaticoduodenectomy.

PURPOSE: The purpose of this study was to investigate whether the indicators of nutritional risk screening tool are associated with postoperative complications following pancreaticoduodenectomy (PD). METHODS: We investigated whether nutritional risk is associated with postoperative complications based on the medical records of 128 patients who underwent PD from 2010. The tool was composed of 6 risk factors: albumin, total lymphocyte count, body mass index, weight loss, dietary intake loss, and nutritional symptoms. The patients were divided into 2 groups: a nutritional risk group and a nonrisk group. The rates of general complications and postoperative pancreatic fistula (POPF) were investigated according to this nutritional status. RESULTS: There were 65 patients who did not have any risk factors. However, 63 patients had one risk factor or more. In the nonrisk group, the overall complication rate and serious complication rate were 30.8% and 15.4%, respectively. If there were one or more risk factors, the overall and serious complication rates were 59.5% and 41.3%, respectively (P = 0.001 and P = 0.001, respectively). The rate of clinically relevant POPF (grade B or C) was 9.2% in the nonrisk group. However, this rate was 23.8% in the NRS risk group (P = 0.029). In multivariate analysis, the NRS risk group was a significant factor of clinically relevant POPF (odds ratio, 9.878; 95% confidence interval, 1.527-63.914; P = 0.016). CONCLUSION: There were statistically significant associations between complications and nutritional indicators. A comprehensive analysis of nutritional parameters will help predict postoperative complications.

Validation of the 8th AJCC Cancer Staging System for Pancreas Neuroendocrine Tumors Using Korean Nationwide Surgery Database.

PURPOSE: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system. MATERIALS AND METHODS: We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included. RESULTS: Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS. CONCLUSION: This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.

Paricalcitol attenuates TGF-ß1-induced phenotype transition of human peritoneal mesothelial cells (HPMCs) via modulation of oxidative stress and NLRP3 inflammasome.

Phenotype transition of mesothelial cells, such as epithelial-to-mesenchymal transition (EMT), is one of the early mechanisms of peritoneal fibrosis, which is mediated by oxidative stress and inflammation. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein oligomer that promotes the maturation of IL-1ß and IL-18. Paricalcitol is reported to exert an anti-inflammatory effect; however, there are no studies as to whether paricalcitol modulates the activation of NLRP3 inflammasome. We investigated the role of NLRP3 inflammasome in peritoneal EMT with an exploration of the effect of paricalcitol on oxidative stress, NLRP3 inflammasome, and EMT of mesothelial cells. TGF-ß1-induced EMT in human peritoneal mesothelial cells (HPMCs) was associated with an up-regulation of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and procaspase-1, with an increased production of IL-1ß and IL-18, which was ameliorated by small interfering (si)NLRP3, siASC, caspase inhibitors, or neutralizing antibodies for IL-1ß and IL-18. TGF-ß1 enhanced reactive oxygen species generation with an increase in NADPH oxidase (NOX) activity and mitochondrial NOX4 production. Paricalcitol alleviated TGF-ß1-induced EMT and the NLRP3 inflammasome, which was associated with a down-regulation of NOX activity by interfering with p47phox and p22phox interaction and mitochondrial NOX4 production in HPMCs. Taken together, paricalcitol ameliorated EMT of HPMCs via modulating an NOX-dependent increase in the activity of NLRP3 inflammasome. Paricalcitol could be a novel approach to protect the peritoneum from the development of EMT and peritoneal fibrosis.-Ko, J., Kang, H.-J., Kim, D.-A., Ryu, E.-S., Yu, M., Lee, H., Lee, H. K., Ryu, H.-M., Park, S.-H., Kim, Y.-L., Kang, D.-H. Paricalcitol attenuates TGF-ß1-induced phenotype transition of human peritoneal mesothelial cells (HPMCs) via modulation of oxidative stress and NLRP3 inflammasome.

Bile duct segmental resection versus pancreatoduodenectomy for middle and distal common bile duct cancer.

PURPOSE: To compare survival outcomes between bile duct segmental resection (BDR) and pancreatoduodenectomy (PD) for the treatment of middle and distal bile duct cancer. METHODS: From 1997 to 2013, a total of 96 patients who underwent curative intent surgery for middle and distal bile duct cancer were identified. The patients were divided into 2 groups based on the type of operation; 20 patients were included in the BDR group and 76 patients were in the PD group. We retrospectively reviewed the clinical outcomes. RESULTS: The number of lymph nodes (LNs) was significantly greater in patients within the PD group compared to the BDR group. The total number of LNs was 6.5 ± 8.2 vs. 11.2 ± 8.2 (P = 0.017) and the number of metastatic LNs was 0.4 ± 0.9 vs. 1.0 ± 1.5 (P = 0.021), respectively. After a median follow-up period of 24 months (range, 4-169 months), the recurrence-free survival of the PD group was superior to that of the BDR group (P = 0.035). In the patients with LN metastases, the patients undergoing PD had significantly better survival than the BDR group (P < 0.001). CONCLUSION: Surgeons should be cautious in deciding to perform BDR for middle and distal common bile duct cancer. PD is recommended if LN metastases are suspected.

The safety and risk factors of major hepatobiliary pancreatic surgery in patients older than 80 years.

PURPOSE: Recently, the number of elderly patients has increased due to a longer life expectancy. Among these elderly patients, more octogenarians will be diagnosed with major hepatobiliary pancreatic (HBP) diseases. Therefore, we need to evaluate the safety and risk factors of major HBP surgery in patients older than 80 years. METHODS: From January 2000 to April 2015, patients who underwent major HBP surgery were identified. The patients were divided into 2 groups according to their age at the time of surgery: Group O (≥80 years) and group Y (<80 years). The patient characteristics and intra- and postoperative outcomes were retrospectively investigated in the 2 groups. RESULTS: The median age was 84 years (range, 80-95 years) in group O and 61 years (range, 27-79 years) in group Y. group O had worse American Society of Anesthesiologists (ASA) physical status (ASA ≥ III: 23% vs. 7%, P = 0.002) and was associated with a higher rate of hypertension and heart problems as comorbidities. There were significant differences in albumin and BUN, favoring group Y. The length of intensive care unit stay was longer in group O, whereas the overall complication and mortality rates did not show statistical difference. But, there was a significant difference in systemic complication of both Clavien-Dindo classification grade ≥II and ≥III as complications were divided into surgical site complication and systemic complication. CONCLUSION: Major HBP surgery can be performed safely in patients older than 80 years if postoperative management is appropriately provided.

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, α-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.

Long-term Outcome of Primary Closure After Laparoscopic Common Bile Duct Exploration Combined With Choledochoscopy.

BACKGROUND: Primary closure after laparoscopic common bile duct exploration (LCBDE) is considered to be a safe alternative to T-tube drainage on the basis of the short-term outcome. However, little published data exist regarding the biliary complications at the long-term follow-up of primary closure versus T-tube drainage following LCBDE. Hence, the aim of this study is to assess the long-term outcome of primary closure after LCBDE. MATERIALS AND METHODS: This is a retrospective study of 142 consecutive patients who underwent LCBDE combined with choledochoscopy for CBD stones. After LCBDE, the choledochotomy was closed by primary closure (group P) in 91 patients (64.1%) and with T-tube drainage (group T) in 51 patients (35.9%). The data on operative outcome and long-term biliary complications were compared between the 2 groups. RESULTS: The mean operation time was significantly shorter in group P than group T (168.9 ± 50.1 min for group P vs. 198.0 ± 59.6 min for group T, P = 0.002). The hospital stay was significantly shorter in group P than in group T (8.59 ± 6.0 d for group P vs. 14.96 ± 5.4 d for group T, P = 0.001). Postoperative bile leak occurred in 2 patients (2.2%) in group P and 1 patient (2.0%) in group T. With a mean follow-up of 48.8 months, the stone recurrence rate in group P and group T were 4.4% and 5.9%, respectively (P = 0.722). During the follow-up period, there was no sign of biliary stricture or other biliary complications in both groups. CONCLUSIONS: The long-term follow-up data on primary closure after LCBDE indicated a low incidence of recurrent stones, and no biliary strictures. Thus, primary closure after LCBDE with choledochoscopy is considered to be a safe and effective alternative to T-tube drainage in terms of long-term outcome.

Does the Difference of Invasiveness between Totally Laparoscopic Distal Gastrectomy and Laparoscopy-Assisted Distal Gastrectomy Lead to a Difference in Early Surgical Outcomes? A Prospective Randomized Trial.

BACKGROUND: Resection and anastomosis in laparoscopic distal gastrectomy can be performed extracorporeally or intracorporeally. Most surgeons have performed laparoscopy-assisted distal gastrectomy (LADG) because of technical difficulties of intracorporeal anastomosis. However, totally laparoscopic distal gastrectomy (TLDG) has recently been attempted and is expected to be feasible and less invasive compared with LADG. In this study, we tried to evaluate the clinical effect of the difference of invasiveness between TLDG and LADG, by way of a randomized prospective trial. METHODS: From February 2011 to September 2013, a total of 110 patients with primary gastric cancer were randomly assigned to either TLDG or LADG. Clinicopathologic features, operative details, postoperative course, and quality of life (QoL) were compared between the two groups. QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and gastric module STO22 at 2 weeks and 3 months after surgery. RESULTS: The two groups were comparable in clinical and pathological characteristics. The proximal resection margin was significantly longer and the length of wound was shorter in the TLDG group. We could not find any significant difference in postoperative inflammatory parameters, postoperative pulmonary function, postoperative recovery, and QoL scores at 2 weeks and 3 months after surgery. There were no significant differences in complication rates. CONCLUSIONS: This study suggests that TLDG is as safe and feasible as LADG in gastric cancer. The parameters used routinely in the clinical field to evaluate early surgical outcomes could not reflect the delicate difference in surgical invasiveness between TLDG and LADG.

Autologous stem cell transplantation for expansion of remnant liver volume with extensive hepatectomy.

BACKGROUND/AIMS: The plasticity of bone marrow stem cells has been confirmed to self-renew and transdifferentiate into hepatocytes. Thus, we performed autologous stem cell transplantation for rapid liver regeneration with extensive hepatectomy in hepatocellular cancer patients. METHODOLOGY: With informed consent, patients aged 20 to 75 who needed large extensive hepatectomy due to hepatocellular carcinoma were randomly divided into three groups: control, mononuclear cells (MNCs), and CD34+ cells, based on infused cell type. After portal vein embolization (PVE), mobilized MNCs or CD34+ cells were returned to the patient via the portal vein on mobilization day without manipulation. Liver volume, liver function, clinical score and Indocyanine green R15 (ICG-R15) were compared before and after PVE. RESULTS: Total bilirubin, albumin, and clinical score showed significant improvement (p < 0.05) 1 week post-infusion, with no significant difference between MNC and CD34+ cell groups. Four patients (control, 1; MNC, 1; CD34+, 2) started at over 18% ICG-R15 but can be overturned after PVE. Daily hepatic volume growth (mL/day) was 2.5 for MNC and 4.9 for CD34+ groups, resulting in significant increase over controls (1.1; p < 0.05). We found no correlation between the number of applied CD34+ cells and daily gains in left lateral lobe volume. CONCLUSIONS: Improvements in liver volume, liver function, clinical score and ICG-R15 suggest that autologous stem cell transplantation is a promising method for liver regeneration.

Immune enhancing effects of Echinacea purpurea root extract by reducing regulatory T cell number and function.

Echinacea purpurea preparations (EPs) have been traditionally used for the treatment of various infections and also for wound healing. Accumulating evidence suggests their immunostimulatory effects. Regulatory T cells (Tregs) are known to play a key role in immune regulation in vivo. However, there have been no reports so far on the effects of EP on the frequency or function of Tregs in vivo. Therefore, in the present study, we investigated the quantitative and functional changes in Tregs by in vivo administration with EP. The frequencies of CD4+FoxP3+ and CD4+CD25+ Tregs in the spleens of BALB/c mice administered with EP for 3 weeks were investigated by flow cytometry. The suppressive function of CD4CD25+ Tregs in association with the proliferative activity of CD4+CD25 effector T cells (Teffs) and the feeder function of CD4 antigen-presenting cells (APCs) were analyzed by carboxyfluorescein succinimidyl ester-dilution assay. The results showed a lowered frequency of CD4+FoxP3+ and CD4+CD25+ Tregs and attenuated suppressive function of CD4+CD25+ Tregs, while the feeder function of APCs was enhanced in the EP-administered mice. On the other hand, the proliferative activity of Teffs was not significantly different in the EP-administered mice. The results suggest that decreased number and function of Tregs, in association with the enhanced feeder function of APCs, may contribute to the enhancement of immune function by EP.

Long-term results of laparoscopic common bile duct exploration by choledochotomy for choledocholithiasis: 15-year experience from a single center.

PURPOSE: The aim of this study is to assess the long-term results of laparoscopic common bile duct exploration (LCBDE) and validate its effectiveness as a primary treatment modality for CBD stone. METHODS: A retrospective review of the medical records of 157 patients who underwent LCBDE from 1997 to 2011 was conducted. All LCBDE were performed by choledochotomy. Clinical demographics, operative outcome, recurrence rate of CBD stones, and long-term bile duct complications were analyzed. The mean follow-up period was 51.9 months. RESULTS: LCBDE was completed in 152 patients (96.8%) and 5 patients (3.2%) had open conversion. The male/female ratio was 78/79 and mean age was 67.3 years. Stone clearance was successful in 149 of 152 patients (98.0%). Nonlethal complications were noted in 11 patients (7.2%), including bile leakage in 6 patients (3.9%). Recurrent CBD stones developed in 9 of 152 patients (5.9%). Preoperative endoscopic sphincterotomy (P = 0.492) and choledochotomy repair type (T-tube drainage vs. primary closure, P = 0.740) were not significantly related to stone recurrence. There were no signs of any type of biliary injury or stricture observed in any of the patients during the follow-up period. CONCLUSION: LCBDE can be performed without increased risk of long-term complications such as bile duct stricture and recurrent CBD stones. LCBDE is a safe and effective treatment option for choledocholithiasis in terms of long-term outcome as well as short-term outcome.