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.

Entecavir versus tenofovir on the recurrence of hepatitis B-related HCC after liver transplantation: A multicenter observational study.

Considerable controversy exists regarding the superiority of tenofovir disoproxil fumarate (TDF) over entecavir (ETV) for reducing the risk of HCC. This study aimed to compare outcomes of ETV versus TDF after liver transplantation (LT) in patients with HBV-related HCC. We performed a multicenter observational study using data from the Korean Organ Transplantation Registry. A total of 845 patients who underwent LT for HBV-related HCC were divided into 2 groups according to oral nucleos(t)ide analogue used for HBV prophylaxis post-LT: ETV group (n = 393) and TDF group (n = 452). HCC recurrence and overall death were compared in naïve and propensity score (PS)-weighted populations, and the likelihood of these outcomes according to the use of ETV or TDF were analyzed with various Cox models. At 1, 3, and 5 years, the ETV and TDF groups had similar HCC recurrence-free survival (90.7%, 85.6%, and 84.1% vs. 90.9%, 84.6%, and 84.2%, respectively, p = 0.98) and overall survival (98.4%, 94.7%, and 93.5% vs. 99.3%, 95.8%, and 94.9%, respectively, p = 0.48). The propensity score-weighted population showed similar results. In Cox models involving covariates adjustment, propensity score-weighting, competing risk regression, and time-dependent covariates adjustment, both groups showed a similar risk of HCC recurrence and overall death. In subgroup analyses stratified according to HCC burden (Milan criteria, Up-to-7 criteria, French alpha-fetoprotein risk score), pretransplantation locoregional therapy, and salvage LT, neither ETV nor TDF was superior. In conclusion, ETV and TDF showed mutual noninferiority for HCC outcomes when used for HBV prophylaxis after LT.

Surgical Outcomes of Laparoscopic versus Open Hepatectomy for Left Hepatocellular Carcinoma: Propensity Score Analyses Using Retrospective Japanese and Korean Individual Patient Data.

Introduction: This study aimed to compare the prognostic impact of laparoscopic left hepatectomy (LLH) with that of open left hepatectomy (OLH) on patient survival after resection of left hepatocellular carcinoma (HCC). Methods: Among the 953 patients who received initial treatment for primary HCC that was resectable by either LLH or OLH from 2013 to 2017 in Japan and Korea, 146 patients underwent LLH and 807 underwent OLH. The inverse probability of treatment weighting approach based on propensity scoring was used to address the potential selection bias inherent in the recurrence and survival outcomes between the LLH and OLH groups. Results: The occurrence rate of postoperative complications and hepatic decompensation was significantly lower in the LLH group than in the OLH group. Recurrence-free survival (RFS) was better in the LLH group than in the OLH group (hazard ratio, 1.33; 95% confidence interval, 1.03-1.71; p = 0.029), whereas overall survival (OS) was not significantly different. Subgroup analyses of RFS and OS revealed an almost consistent trend in favor of LLH over OLH. In patients with tumor sizes of ≥4.0 cm or those with single tumors, both RFS and OS were significantly better in the LLH group than in the OLH group. Conclusions: LLH decreases the risk of tumor recurrence and improves OS in patients with primary HCC located in the left liver.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Treatment strategies of drain after complicated laparoscopic cholecystectomy for acute cholecystitis.

Acute cholecystitis (AC) is the most common biliary tract disease, and laparoscopic cholecystectomy (LC) is recognized as the treatment of choice. The present study in this issue compared the surgical outcomes, particularly the occurrence of postoperative surgical site infections (SSIs) in patients with and without drain placement following complicated LC for AC. It showed that late drain removal demonstrated significantly worse surgical outcomes than no drain placement and early drain removal for overall complications, postoperative hospital stay, and SSIs. Drain placement is not routinely recommended, even after complicated LC for AC. When placing a drain, early drain removal is recommended for postoperative outcomes such as SSIs.

Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month.

Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06−3.53) and infection (HR = 1.44, 95% CI 1.12−1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients' renal functional reserve.

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.

p21-activated kinase 4 inhibition protects against liver ischemia/reperfusion injury: Role of nuclear factor erythroid 2-related factor 2 phosphorylation.

BACKGROUND AND AIMS: p21-activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. APPROACH AND RESULTS: Hepatocyte- and myeloid-specific Pak4 knockout (KO) mice and their littermate controls were subjected to a partial hepatic I/R (HIR) injury. We manipulated the catalytic activity of PAK4, either through genetic engineering (gene knockout, overexpression of wild-type [WT] or dominant-negative kinase) or pharmacological inhibitor, coupled with a readout of nuclear factor erythroid 2-related factor 2 (Nrf2) activity, to test the potential function of PAK4 on HIR injury. PAK4 expression was markedly up-regulated in liver during HIR injury in mice and humans. Deletion of PAK4 in hepatocytes, but not in myeloid cells, ameliorated liver damages, as demonstrated in the decrease in hepatocellular necrosis and inflammatory responses. Conversely, the forced expression of WT PAK4 aggravated the pathological changes. PAK4 directly phosphorylated Nrf2 at T369, and it led to its nuclear export and proteasomal degradation, all of which impaired antioxidant responses in hepatocytes. Nrf2 silencing in liver abolished the protective effects of PAK4 deficiency. A PAK4 inhibitor protected mice from HIR injury. CONCLUSIONS: PAK4 phosphorylates Nrf2 and suppresses its transcriptional activity. Genetic or pharmacological suppression of PAK4 alleviates HIR injury. Thus, PAK4 inhibition may represent a promising intervention against I/R-induced liver injury.

IL4Rα and IL13Rα1 Are Involved in the Development of Human Gallbladder Cancer.

BACKGROUND: Gallbladder cancer is commonly associated with inflammation, which indicates that inflammation-related cytokines and cytokine receptors are related to the progression of gallbladder cancers. Interleukin 4 (IL4) is a well-known cytokine that promotes the differentiation of naive helper T cells (Th0) to T helper type 2 cells (Th2). IL13 is a cytokine that is secreted by Th2 cells. IL4 and IL13 are closely related in immune responses. However, the role of IL4Rα and IL13Rα1 signaling pathway has not been fully understood in the development of gallbladder cancer. METHODS: In human gallbladder carcinomas, the expression of IL4Rα and IL13Rα1 were evaluated with immunohistochemical staining in tissue microarray tissue sections. After knockdown of IL4Rα or IL13Rα1, cell assays to measure the proliferation and apoptosis and Western blotting analysis were conducted in SNU308 human gallbladder cancer cells. Since Janus kinases2 (JAK2) was considered as one of the down-stream kinases under IL4Rα and IL13Rα1 complex, the same kinds of experiments were performed in SNU308 cells treated with AZD1480, Janus-associated kinases2 (JAK2) inhibitor, to demonstrate the cytotoxic effect of AZD1480 in SNU308 cells. RESULTS: Immunohistochemical expression of IL4Rα was significantly associated with the expression of IL13Rα1 in human carcinoma tissue. In univariate analysis, nuclear expression of IL4Rα, cytoplasmic expression of IL4Rα, nuclear expression of IL13Rα1, and cytoplasmic expression of IL13Rα1 were significantly associated with shorter overall survival and shorter relapse-free survival. Multivariate analysis revealed nuclear expression of IL4Rα as an independent poor prognostic indicator of overall survival and relapse-free survival. Then, we found that knockdown of IL4Rα or IL13Rα1 decreased viability and induced apoptosis in SNU308 cells via activation of FOXO3 and similarly, AZD1480 decreased viability and induced apoptosis in SNU308 cells with dose dependent manner. CONCLUSIONS: Taken together, our results suggest that IL4Rα and IL13Rα1 might be involved in the development of human gallbladder cancer cells and IL4Rα and IL13Rα1 complex/JAK2 signaling pathway could be efficient therapeutic targets for gallbladder cancer treatment.

Korean Surgical Practice Guideline for Pancreatic Cancer 2022: A summary of evidence-based surgical approaches

Pancreatic cancer is the eighth most common cancer and the fifth most common cause of cancer-related deaths in Korea. Despite the increasing incidence and high mortality rate of pancreatic cancer, there are no appropriate surgical practice guidelines for the current domestic medical situation. To enable standardization of management and facilitate improvements in surgical outcome, a total of 10 pancreatic surgical experts who are members of Korean Association of Hepato-Biliary-Pancreatic Surgery have developed new recommendations that integrate the most up-to-date, evidence-based research findings and expert opinions. This is an English version of the Korean Surgical Practice Guideline for Pancreatic Cancer 2022. This guideline includes 13 surgical questions and 15 statements. Due to the lack of high-level evidence, strong recommendation is almost impossible. However, we believe that this guideline will help surgeons understand the current status of evidence and suggest what to investigate further to establish more solid recommendations in the future.

Identification of key genes and carcinogenic pathways in hepatitis B virus-associated hepatocellular carcinoma through bioinformatics analysis.

BACKGROUNDS/AIMS: Mechanisms for the development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected patients remain unclear. The aim of the present study was to identify genes and pathways involved in the development of HBV-associated HCC. METHODS: The GSE121248 gene dataset, which included 70 HCCs and 37 adjacent liver tissues, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in HCCs and adjacent liver tissues were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were then performed. RESULTS: Of 134 DEGs identified, 34 were up-regulated and 100 were down-regulated in HCCs. The 34 up-regulated DEGs were mainly involved in nuclear division, organelle fission, spindle and midbody formation, histone kinase activity, and p53 signaling pathway, whereas the 100 down-regulated DEGs were involved in steroid and hormone metabolism, collagen-coated extracellular matrix, oxidoreductase activity, and activity on paired donors, including incorporation or reduction of molecular oxygen, monooxygenase activity, and retinol metabolism. Analyses of protein-protein interaction networks with a high degree of connectivity identified significant modules containing 14 hub genes, including ANLN, ASPM, BUB1B, CCNB1, CDK1, CDKN3, ECT2, HMMR, NEK2, PBK, PRC1, RACGAP1, RRM2, and TOP2A, which were mainly associated with nuclear division, organelle fission, spindle formation, protein serine/threonine kinase activity, p53 signaling pathway, and cell cycle. CONCLUSIONS: This study identified key genes and carcinogenic pathways that play essential roles in the development of HBV-associated HCC. This may provide important information for the development of diagnostic and therapeutic targets for HCC.

Delayed pseudoaneurysm formation of the carotid artery following the oral cavity injury in a child: A case report.

BACKGROUND: An impalement injury of the oral cavity is a common traumatic injury in children. In most cases, it is not accompanied by sequelae, but if foreign body residues are not found due to a minor injury, they may result in inflammatory responses and delayed vascular injuries in the surrounding tissues. Without early diagnosis and appropriate initial management, residual foreign bodies can cause serious complications and even mortality in some cases. CASE SUMMARY: A 9-year-old boy suffered an intra-oral injury by a wooden chopstick, and the patient was discharged from the hospital after receiving conservative treatment for the injury. However, the patient was readmitted to the hospital due to intra-oral bleeding, and since neck hematoma and right internal carotid artery pseudoaneurysm formation were detected on computed tomography, emergency surgery was performed. A remnant fragment of a wooden chopstick was found during the operation, and a delayed rupture of the internal carotid artery caused by the foreign body was also found. CONCLUSION: The failure of early detection and diagnosis of a residual foreign body may result in delayed vascular rupture.

Laparoscopic lumbar artery ligation of type II endoleaks following endovascular aneurysm repair: A case report.

INTRODUCTION: Although the clinical significance of type II endoleaks remain controversial, management strategies continue to expand. The laparoscopic approach is a minimally invasive method for persistent type II endoleak repair after endovascular aneurysm repair. PATIENT CONCERNS: A 70 - year - old male patient with a history of endovascular aneurysm repair with left internal iliac artery embolization presented with persistent type II endoleak from the lumbar arteries 2 years ago. The aneurysm sac size had increased more than 10 mm during follow up period. DIAGNOSIS: Persistent type II endoleak after endovascular aneurysm repair. INTERVENTIONS: Transarterial embolization was attempted and failed. A minimally invasive laparoscopic lumbar artery ligation was then utilized. OUTCOMES: The patient was discharged without any complications after surgery. Follow-up computed tomography angiography has shown the complete disappearance of the type II endoleaks. CONCLUSIONS: Laparoscopic lumbar artery ligation may be a safe and effective alternative treatment for type II endoleaks, especially in high resource settings.

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.

A comparative study of postoperative outcomes between minimally invasive living donor hepatectomy and open living donor hepatectomy: The Korean organ transplantation registry.

BACKGROUND: This study evaluated the safety and effectiveness of minimally invasive living donor hepatectomy in comparison with the open procedure, using Korean Organ Transplantation Registry data. METHODS: We reviewed the prospectively collected data of all 1,694 living liver donors (1,071 men, 623 women) who underwent donor hepatectomy between April 2014 and December 2017. The donors were grouped on the basis of procedure type to the minimally invasive procedure group (n = 304) or to the open procedure group (n = 1,390) and analyzed the relationships between clinical data and complications. RESULTS: No donors died after the procedure. The overall complication rates after operation in the minimally invasive procedure group and the open procedure group were 6.2% and 3.5%, respectively. Biliary complications were the most frequent events in both groups (minimally invasive procedure group, 2.4%; open procedure group, 1.6%). The majority of complications occurred within 7 days after surgery in both groups. The duration of hospitalization was shorter in the minimally invasive procedure group than in the open procedure group (9.04 ± 3.78 days versus 10.29 ± 4.01 days; P < .05). CONCLUSION: Based on its similar outcomes in our study, minimally invasive donor hepatectomy cannot be an alternative option compared with the open procedure method. To overcome this, we need to ensure better surgical safety, such as lower complication rate and shorter duration of hospitalization.

Comparison of Oncologic Outcomes between Transduodenal Ampullectomy and Pancreatoduodenectomy in Ampulla of Vater Cancer: Korean Multicenter Study.

This study used multicenter data to compare the oncological safety of transduodenal ampullectomy (TDA) with that of pylorus-preserving pancreatoduodenectomy (PPPD) in early ampulla of Vater (AoV) cancer. Data for patients who underwent surgical resection for AoV cancer (pTis-T2 stage) from January 2000 to September 2019 were collected from 15 institutions. The clinicopathologic characteristics and survival outcomes were compared between the PPPD and TDA groups. A total of 486 patients were enrolled (PPPD, 418; TDA, 68). The oncologic behavior in the PPPD group was more aggressive than that in the TDA group at all T stages: larger tumor size (p = 0.034), advanced T stage (p < 0.001), aggressive cell differentiation (p < 0.001), and more lymphovascular invasion (p = 0.002). Five-year disease-free survival (DFS) and overall survival (OS) did not differ between the two groups when considering all T stages or only the Tis+T1 group. Among T1 patients, PPPD produced significantly better DFS (PPPD vs. TDA, 84.8% vs. 66.6%, p = 0.040) and superior OS (PPPD vs. TDA, 89.1% vs. 68.0%, p = 0.056) than TDA. Lymph node dissection (LND) in the TDA group did not affect DFS or OS (TDA + LND vs. TDA-only, DFS, p = 0.784; OS, p = 0.870). In conclusion, PPPD should be the standard procedure for early AoV cancer.

Comparison of Compressed Sensing and Gradient and Spin-Echo in Breath-Hold 3D MR Cholangiopancreatography: Qualitative and Quantitative Analysis.

While magnetic resonance cholangiopancreatography (MRCP) is routinely used, compressed sensing MRCP (CS-MRCP) and gradient and spin-echo MRCP (GRASE-MRCP) with breath-holding (BH) may allow sufficient image quality with shorter acquisition times. This study qualitatively and quantitatively compared BH-CS-MRCP and BH-GRASE-MRCP and evaluated their clinical effectiveness. Data from 59 consecutive patients who underwent both BH-CS-MRCP and BH-GRASE-MRCP were qualitatively analyzed using a five-point Likert-type scale. The signal-to-noise ratio (SNR) of the common bile duct (CBD), contrast-to-noise ratio (CNR) of the CBD and liver, and contrast ratio between periductal tissue and the CBD were measured. Paired t-test, Wilcoxon signed-rank test, and McNemar's test were used for statistical analysis. No significant differences were found in overall image quality or duct visualization of the CBD, right and left 1st level intrahepatic duct (IHD), cystic duct, and proximal pancreatic duct (PD). BH-CS-MRCP demonstrated higher background suppression and better visualization of right (p = 0.004) and left 2nd level IHD (p < 0.001), mid PD (p = 0.003), and distal PD (p = 0.041). Image quality degradation was less with BH-GRASE-MRCP than BH-CS-MRCP (p = 0.025). Of 24 patients with communication between a cyst and the PD, 21 (87.5%) and 15 patients (62.5%) demonstrated such communication on BH-CS-MRCP and BH-GRASE-MRCP, respectively. SNR, contrast ratio, and CNR of BH-CS-MRCP were higher than BH-GRASE-MRCP (p < 0.001). Both BH-CS-MRCP and BH-GRASE-MRCP are useful imaging methods with sufficient image quality. Each method has advantages, such as better visualization of small ducts with BH-CS-MRCP and greater time saving with BH-GRASE-MRCP. These differences allow diverse choices for visualization of the pancreaticobiliary tree in clinical practice.

Is cholecystectomy safe in extremely elderly patients?

Gallstone disease is the most common global indication for abdominal surgery. Especially acute cholecystitis in the elderly is frequently encountered due to an increasingly elderly population. Although cholecystectomy is the gold standard treatment for acute cholecystitis, the surgical management in the elderly presents specific challenges due to associated comorbidities, the severity of their presenting disease, and a greater likelihood of suffering postoperative complications and prolonged hospital stay. Further effort to provide firm evidence to clarify the safety and feasibility of cholecystectomy for acute cholecystitis in extremely elderly patients such as octogenarians and even nonagenarians.

ERRγ suppression by Sirt6 alleviates cholestatic liver injury and fibrosis.

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) stimulates bile acid production; however, the role and the regulatory mechanism of ERRγ in cholestatic liver disease are largely unknown. This study identifies that Sirt6 is a deacetylase of ERRγ and suggests a potentially novel mechanism by which Sirt6 activation alleviates cholestatic liver damage and fibrosis through regulating ERRγ. We observed that hepatic expression of Sirt6 is repressed, whereas hepatic expression of ERRγ is upregulated in murine cholestasis models. Hepatocyte-specific Sirt6-KO mice were more severely injured after a bile duct ligation (BDL) than WT mice, and adenoviral reexpression of Sirt6 reversed liver damage and fibrosis as demonstrated by biochemical and histological analyses. Mechanistically, Sirt6 deacetylated ERRγ, thereby destabilizing ERRγ and inhibiting its transcriptional activity. Elimination of hepatic ERRγ using Ad-shERRγ abolished the deleterious effects of Sirt6 deficiency, whereas ERRγ overexpression aggravated cholestatic liver injury. Administration of a Sirt6 deacetylase activator prevented BDL-induced liver damage and fibrosis. In patients with cholestasis, Sirt6 expression was decreased, whereas total ERRγ and acetylated ERRγ levels were increased, confirming negative regulation of ERRγ by Sirt6. Thus, Sirt6 activation represents a potentially novel therapeutic strategy for treating cholestatic liver injury.

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.