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.

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.

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.

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.

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.

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.

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.

Immune dysregulation in chronic stress: a quantitative and functional assessment of regulatory T cells.

OBJECTIVE: Chronic stress is closely related to immune dysfunction. Immune parameters have been analyzed in many ways in humans and animals under chronic stress. Recently, it has been proved that FoxP3+ regulatory T cells (Tregs) play a key role in immune regulation in vivo. However, it has not yet been elucidated how Tregs respond to chronic stress in vivo. Therefore, in the present study, we investigated the frequency of and functional changes in Tregs from mice under chronic stress. METHODS: Spleen cells were separated from C57/BL6 mice that had been exposed to immobilization stress for 3 weeks. The frequencies of FoxP3+ and CD4+ CD25+ cells were analyzed by flow cytometry. CD4+CD25- cells (effector T cells, Teffs), CD4+CD25+ cells (Tregs) and CD4- cells (antigen-presenting cells, APCs) were separated for the functional assessment of the proliferative activity of Teffs, the suppressive activity of Tregs and the feeder activity of APCs. RESULTS: The results showed that chronic immobilization stress significantly increased the frequencies of CD4+CD25+ and CD4+FoxP3+ cells. Chronic immobilization stress also enhanced the suppressive function of CD4+ CD25+ Tregs. On the other hand, the proliferative activity of Teffs and the feeder activity of APCs were decreased in the mice under chronic immobilization stress. CONCLUSION: Taken together, it is suggested that increased number and function of Tregs may actively contribute to the immune dysfunction in chronic immobilization stress, synergizing with the decreased function of Teffs and APCs.

Prognostic significance of muc4 expression in gallbladder carcinoma.

BACKGROUND: Mucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis. METHODS: The expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining. RESULTS: For gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05). CONCLUSIONS: MUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.

Current status of laparoscopic liver resection in Korea.

Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.

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.

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.

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.

Laparoscopic treatment for intrahepatic duct stones in the era of laparoscopy: laparoscopic intrahepatic duct exploration and laparoscopic hepatectomy.

OBJECTIVE: The aim of this study is to analyze our experiences with laparoscopic surgery for treating intrahepatic duct (IHD) stones and to evaluate its role for the management of IHD stone. SUMMARY BACKGROUND DATA: Until now, laparoscopic surgery for IHD stone has been rarely reported. METHODS: From October 1998 to June 2007, we performed 76 cases of laparoscopic surgery for treating IHD stones [30 laparoscopic IHD explorations (LIHDE) and 46 laparoscopic hepatectomy (LH)]. The choice between LIHDE and LH was based on the severity of the IHD stricture, the presence of parenchymal atrophy, and the impaction of stones, as determined by the preoperative radiologic images or intraoperative choledochoscopy. Retrospective analysis was done on the clinical outcomes of the 76 patients. RESULTS: Conversion to open surgery was needed in 6 patients (7.9%). The mean operation time (LIHDE vs. LH) was 278.4 and 344.3 minutes, respectively. The mean postoperative hospital stay was 14.6 and 12.8 days, respectively. Postoperative complications occurred in 28 patients (36.8%), and all of them responded to the conservative management. There was 1 case of postoperative mortality in the LH group because of sepsis. The overall initial success rate of removing the stones by laparoscopic surgery in our intention-to-treat analysis was 78.9% (60 of 76). The reasons for treatment failure included remnant stones (n = 9), conversion to open surgery (n = 6), and postoperative mortality (n = 1). For the 69 patients who had laparoscopic surgery successfully preformed without mortality, the initial success rate of stone clearance was 87.0% (60 of 69) and the final clearance rate after additional choledochoscopic stone removal was 92.8% (64 of 69). CONCLUSIONS: This study demonstrates that laparoscopic surgery can be an effective option for managing IHD stones and it also suggests the potential role of laparoscopic surgery for treating IHD stones in the era of laparoscopy.

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.

Prognostic significance of CD44s expression in biliary tract cancers.

BACKGROUND: CD44 is an essential surface glycoprotein component of the hyaluronan receptor and is associated with adhesion and metastasis in many solid tumors. There are several isoforms of CD44, including CD44 standard (CD44s) and 10 CD44 variants (CD44v1 to CD44v10). We evaluated the clinical significance of CD44s and CD44v6 in biliary tract cancers. METHODS: Patients who had been diagnosed with primary biliary tract cancers were enrolled onto the study, and tissue specimens were obtained during surgery. Paraffin-embedded tissue sections were evaluated for the presence of CD44s and CD44v6 by immunohistochemical staining. We decided CD44s and CD44v6 expression as overexpression, which shows an intensity grade of >10%. Clinical data of all patients were reviewed. RESULTS: Ninety-five patients (35 men and 60 women; median age, 64 years; range, 37-86 years) were evaluated. The incidence of overexpression (>10%) of CD44s was 49%, and that of CD44v6 was 17%. The median postoperative follow-up duration was 34.3 months, and the median overall survival was 12.2 months. The Cox proportional hazard ratio (HR) test identified CD44s overexpression (0% to 10% vs. 10% to 100%; HR, .420; 95% confidence interval [95% CI], .211-.837; P = .014) and cancer stage as prognostic factors. However, the expression of CD44v6 (0% to 10% vs. 10% to 100%; HR, 1.462; 95% CI, .630-3.393; P = .377) had no prognostic significance for survival. CONCLUSIONS: CD44s overexpression is useful as a marker of a poor prognosis for biliary tract cancer. Aggressive postoperative therapy should be considered for such patients.

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.