Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Comparison of Survival Outcomes between Radical Antegrade Modular Pancreatosplenectomy and Conventional Distal Pancreatosplenectomy for Pancreatic Body and Tail Cancer: Korean Multicenter Propensity Score Match Analysis.

(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

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.

Imaging Findings of an Intraluminal Duodenal Diverticulum Associated with Adult Duodeno-Duodenal Intussusception and Recurrent Pancreatitis: A Case Report.

Intraluminal duodenal diverticulum (IDD) is a rare congenital abnormality, consisting of a sac-like mucosal lesion in the duodenum. Cases of IDD can present with gastrointestinal bleeding, duodenal obstruction, or pancreatitis. Here, we report a rare case of a 25-year-old female presenting with IDD complicated by duodeno-duodenal intussusception and recurrent pancreatitis. The diagnosis was based on findings from radiologic examinations (CT and MRI), upper gastrointestinal series (barium swallow), and gastroduodenofiberscopy. Laparoscopic excision of the presumed duodenal duplication was performed. The subsequent histopathologic evaluation of the excised sac revealed normal mucosa on both sides, but the absence of a proper muscle layer confirmed the diagnosis of IDD. Radiologic detection of a saccular structure in the second portion of the duodenum can indicate IDD with duodeno-duodenal intussusception as the lead point.

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

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

Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

BACKGROUND: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. METHODS: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. RESULTS: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. CONCLUSION: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized 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.

Risk Factors for Recurrence in Pancreatic Neuroendocrine Tumor and Size as a Surrogate in Determining the Treatment Strategy: A Korean Nationwide Study.

INTRODUCTION: The prognostic factors of pancreatic neuroendocrine tumor (PNET) are unclear, and the treatment guidelines are insufficient. This study aimed to suggest a treatment algorithm for PNET based on risk factors for recurrence in a large cohort. METHODS: Data of 918 patients who underwent curative intent surgery for PNET were collected from 14 tertiary centers. Risk factors for recurrence and survival analyses were performed. RESULTS: The 5-year disease-free survival (DFS) rate was 86.5%. Risk factors for recurrence included margin status (R1, hazard ratio [HR] 2.438; R2, HR 3.721), 2010 WHO grade (G2, HR 3.864; G3, HR 7.352), and N category (N1, HR 2.273). A size of 2 cm was significant in the univariate analysis (HR 8.511) but not in the multivariate analysis (p = 0.407). Tumor size was not a risk factor for recurrence, but strongly reflected 2010 WHO grade and lymph node (LN) status. Tumors ≤2 cm had lower 2010 WHO grade, less LN metastasis (p < 0.001), and significantly longer 5-year DFS (77.9 vs. 98.2%, p < 0.001) than tumors >2 cm. The clinicopathologic features of tumors <1 and 1-2 cm were similar. However, the LN metastasis rate was 10.3% in 1-2-cm sized tumors and recurrence occurred in 3.0%. Tumors <1 cm in size did not have any LN metastasis or recurrence. DISCUSSION/CONCLUSION: Radical surgery is needed in suspected LN metastasis or G3 PNET or tumors >2 cm. Surveillance for <1-cm PNETs should be sufficient. Tumors sized 1-2 cm require limited surgery with LN resection, but should be converted to radical surgery in cases of doubtful margins or LN metastasis.

National survey of Korean hepatobiliary-pancreatic surgeons on attitudes about the enhanced recovery after surgery protocol.

BACKGROUNDS/AIMS: The purpose of this study was to investigate attitudes regarding the Enhanced Recovery After Surgery (ERAS) protocol of hepato-biliary-pancreatic (HBP) surgeons in Korea and the extent to which they use the protocol for perioperative management. METHODS: An online survey was conducted among members of the Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS) for eight weeks beginning on August 2019. The questionnaire, which was written in Korean, was based on the latest ERAS guidelines. Total responses were collected from 127 surgeons. RESULTS: Of the 127 total respondents, the largest proportion (44.9%) were working in Seoul. In terms of established in-hospital clinical pathways (CP), 19.7% of the participating surgeons had and followed a CP in pancreaticoduodenectomy (PD) and 21.3% in hepatectomy. Regarding the ERAS protocol for each surgery, four items (18.2%) regarding PD and seven items (35.0%) related to hepatectomy were followed by more than 50% of respondents. CONCLUSIONS: ERAS guidelines are one of the consensuses for better recovery in perioperative management of patients undergoing major surgeries and encompass the overall process of patient recovery including patient education, pain control, physiologic balance, and perioperative nutrition. A novel project is needed to successfully implement an evidence-based enhanced recovery strategy.

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.

Oral health and gastrointestinal cancer: A nationwide cohort study.

AIMS: Poor oral hygiene is closely associated with bacteraemia and systemic inflammation, which are known mediators of cancer development. We investigated the relationship between oral hygiene indicators and the risk of gastrointestinal cancer in a nationwide population-based cohort. MATERIALS AND METHODS: This study was conducted on data from 150,774 subjects from the Korean National Health Screening Cohort. The occurrence of gastrointestinal cancer was analysed according to the presence of periodontal disease and oral hygiene indicators: frequency of toothbrushing, dental visits for any reason, professional dental cleanings and number of missing teeth. Gastrointestinal cancer was defined using International Statistical Classification of Diseases-10 codes C15-C26. RESULTS: During a median 11.6 years of follow-up, the estimated 10-year event rate for gastrointestinal cancer was 6.76%. In a multivariable analysis, after adjusting for age, sex, income level, regular exercise, alcohol consumption, smoking status, body mass index, history of comorbidities, systolic blood pressure and laboratory findings, frequent toothbrushing (≥3/day) was significantly associated with a reduced risk for gastrointestinal cancer (hazard ratio: 0.91, 95% confidence interval (0.86-0.96), p < .001, p for trend < .001). CONCLUSIONS: Good oral hygiene behaviour, especially frequent toothbrushing, could be associated with a lower risk of gastrointestinal cancer.

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.

Safety and Feasibility of Robotic Reduced-Port Distal Pancreatectomy: a Multicenter Experience of a Novel Technique.

BACKGROUND: A reduced-port approach including single-site surgery has been used for distal pancreatectomy. However, triangulation is difficult in reduced-port laparoscopic distal pancreatectomy, and instrument crowding, and collision may occur, so this approach has not been widely used. Recently, an innovative technique for distal pancreatectomy using a robotic single-site surgical system was introduced. Herein, we evaluate the safety and feasibility of this technique. METHODS: Twenty-seven patients with a pancreatic tail mass underwent robotic single-site plus one-port distal pancreatectomy at six centers. We collected clinicopathologic data and evaluated the short-term perioperative outcomes of robotic single-site plus one-port distal pancreatectomy. RESULTS: We evaluated 26 patients who underwent robotic single-site plus one-port distal pancreatectomy excluding one patient who needed more ports because of fatty abdomen. The mean age and body mass index were 47.3 years (range 21-74) and 22.6 kg/m2 (range 15.8-28.8), respectively. The most common pathologic diagnosis was solid papillary neoplasm followed by a neuroendocrine tumor. The mean operating time was 201 min. The mean length of hospital stay after surgery was 7 days (range 4-10). The rate of spleen preservation was 34.6% (9/26). Six patients had postoperative pancreatic fistula (POPF) grade A, and no patients had POPF grade B or C. Only one patient had class II morbidity. CONCLUSION: Robotic single-site plus one-port distal pancreatectomy is safe and feasible in terms of short-term outcomes. This technique could be performed in select cases to expand the surgical boundaries of the robotic single-site platform. Further studies are needed with more cases to investigate long-term outcomes.

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.

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.

Extended versus peripancreatic lymph node dissection for the treatment of left-sided pancreatic cancer.

PURPOSE: The pathways of lymphatic metastases differ according to the tumor location in pancreatic cancer patients. However, it is unclear whether extended lymph node dissection (LND) is essential for all left-sided pancreatic cancer. The aim of this study is to evaluate the survival outcomes according to the extent of LND and tumor location in patients with left-sided pancreatic cancer. METHODS: January 2005 to December 2013, we retrospectively identified 107 patients who underwent curative intent surgery for left-sided pancreatic cancer. The left-sided pancreatic cancer was defined as a tumor located in pancreatic body or tail. The extent of LND was divided into 2 groups: extended LND and peripancreatic LND. The extended LND group included celiac and superior mesenteric LNs. RESULTS: We included 107 patients with left-sided pancreatic cancer; 59 patients with pancreatic body cancer and 48 patients with pancreatic tail cancer. The median follow-up period was 17 months (range, 3-110 months). Fifty patients with pancreatic body cancer and 30 patients with pancreatic tail cancer underwent extended LND. In patients with pancreatic body cancer, extended LND was associated with improved disease-free survival (DFS) (P = 0.010) and overall survival (P = 0.014). However, extended LND was not associated with DFS in patients with pancreatic tail cancer. CONCLUSION: Extended LND could improve survival in patients with pancreatic body cancer. However, extended LND had no survival benefit for the treatment of pancreatic tail cancer.

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.