Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Clinical significance of serum-derived exosomal PD-L1 expression in patients with advanced pancreatic cancer.

BACKGROUND: Interactions between the programmed cell death receptor 1 (PD-1) and its ligand (PD-L1) lead to immune evasion in various tumors and are associated with poor prognosis in patients with pancreatic cancer; however, the roles of PD-L1-containing exosomes in pancreatic cancer is poorly understood. Here, we investigated the correlation between circulating exosomal PD-L1 (exoPD-L1) and PD-L1 expression in tumor tissue, and survival outcomes in patients with advanced PDAC. METHODS: Exosomes were derived from pre-treatment serum samples isolated using ExoQuick kit from 77 patients with advanced pancreatic cancer. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immunosorbent assay, and matched tumor tissues PD-L1 expression were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with receiver operating characteristic curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival (OS), and hazard ratio was estimated using a stratified Cox regression model. RESULTS: The median exoPD-L1 serum concentration was 0.16 pg/mg, with undetected levels in seven patients. ExoPD-L1 levels were significantly higher in patients with systemic disease than in those with locally advanced disease (p = 0.023). There was a significantly higher proportion of elevated exoPD-L1 levels in patients with positive PD-L1 expression compared to patients with negative PD-L1 expression (p = 0.001). Patients were classified into groups with low and high exoPD-L1 levels using ROC curve-derived cutoffs (0.165 pg/mg; area under the curve, 0.617; p = 0.078). At a median follow-up of 8.39 months, the median OS was 13.2 (95% CI, 8.17-18.3) and 6.36 months (95% CI, 3.27-9.45) in the low and high exoPD-L1 groups, respectively (HR = 0.61; 95% CI, 0.35-1.04; p = 0.059). ExoPD-L1 levels did not affect the proportion of CD8+CD69+ effector cytotoxic T cells in either of the groups (p = 0.166). CONCLUSIONS: The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Collectively, higher serum exoPD-L1 levels in patients with advanced pancreatic cancer suggested worse survival outcomes and may have clinical implications.

The role of natural killer cell activity as a milestone in oncologic outcome after curative resection of pancreatic adenocarcinoma.

BACKGROUND: The objective of this study was to investigate differences in oncologic outcomes of patients with pancreas cancer according to natural killer cell activity (NKA). METHODS: A total of 118 patients who underwent curative resection for primary pancreas cancer in two hospitals were analyzed. NKA change pattern was analyzed. Difference in disease-free survival or overall survival was investigated by dividing subjects into two groups based on a normal NKA value for each period. RESULTS: NKA value decreased after surgery compared to the value measured at admission. It recovered to normal levels at 5 weeks postoperatively. The low NKA (less than 250 pg/mL) group at admission, 5 weeks postoperatively, and before 1st chemotherapy had significantly poorer disease-free survival than the normal NKA group. In multivariate analysis, NKA values less than 250 pg/mL at admission (odds ratio = 2.267, p = 0.023) and N 1 or N2 category (odds ratio = 2.478, p = 0.023) were significant factors associated with recurrence after curative resection. CONCLUSIONS: NKA in patients with pancreatic cancer demonstrated noticeable changes after surgery. Immunologically predisposed patients with a low NKA value had a high risk of early recurrence and a poor prognosis, although pancreatic cancer was surgically removed.

Effects of extremely low-pressure pneumoperitoneum on postoperative recovery after single site robot-assisted cholecystectomy: a randomized controlled trial.

PURPOSE: A robotic platform has enabled extremely low-pressure pneumoperitoneum (ELPP, 4 mmHg) to reduce surgical insults to human physiology during a minimally invasive surgery. The objective of this study was to investigate the effect of ELPP in single-site robotic cholecystectomy (SSRC) on postoperative pain, shoulder pain, and physiological changes during surgery compared to a standard pressure pneumoperitoneum (SPP, 12-14 mmHg). METHODS: A total of 182 patients who underwent an elective cholecystectomy were randomized into an ELPP SSRC group (n = 91) and an SPP SSRC group (n = 91). Postoperative pain was assessed at 6, 12, 24, and 48 h after surgery. The number of patients complaining of shoulder pain was observed. Intraoperative changes of ventilatory parameters were also measured. RESULTS: Postoperative pain scores (p = 0.038, p < 0.001, p < 0.001, and p = 0.015 at 6, 12, 24, and 48 h after surgery, respectively) and the number of patients with shoulder pain (p <0.001) were significantly lower in the ELPP SSRC group than in the SPP SSRC group. Intraoperative changes in peak inspiratory pressure (p < 0.001), plateau pressure (p < 0.001), EtCO2 (p < 0.001), and lung compliance (p < 0.001) were also less in the ELPP SSRC group. CONCLUSION: The ELPP during robotic cholecystectomy could significantly relieve postoperative pain and shoulder pain. In addition, the ELPP can reduce changes in lung compliance during surgery and the demand for postoperative analgesics, thereby improving the quality of life of patients during early stages of postoperative rehabilitation.

What we should consider to facilitate recovery of the hematological profile in all patients after pancreaticoduodenectomy: the role of preoperative intravenous iron treatment.

BACKGROUND: In pancreaticoduodenectomy (PD), the duodenum and upper jejunum responsible for iron absorption are removed, which can lead to massive hemorrhage during surgery and cause iron deficiency anemia after PD. The aim of this study was to evaluate overall changes in hematologic profiles of patients who underwent pancreaticoduodenectomy. Effect of preoperative intravenous iron treatment on recovery of anemia after surgery was also investigated. METHODS: From March 2021 to December 2021, patients who underwent curative PD at our institution due to periampullary lesions were enrolled. They were divided into two groups according to whether or not iron was administered before surgery. In the IV iron group, all patients had been routinely administered with 1000 mg of ferric carboxymaltose intravenously once about 3-7 days before the operation day. Contrarily, patients in the control group did not receive intravenous iron before PD. Changes in hematological profile were measured preoperatively and at 5, 14, and 30 days postoperatively. Clinical results of the two groups were compared and analyzed. Additionally, a subgroup analysis was performed for selected non-anemic patients who had preoperative hemoglobin level of 12.0 g/dl or higher to compare changes in hematologic profiles between the two groups. RESULTS: Thirty patients of the IV iron group and 34 patients of the control group were analyzed. Although no difference was observed in postoperative complications or mortality, hemoglobin and iron levels were recovered significantly faster at two weeks postoperatively in the IV iron group than in the control group. Iron levels were significantly higher in the IV iron group throughout the postoperative period. In subgroup analysis conducted for non-anemic patients, hemoglobin levels were recovered significantly faster and maintained higher in the IV iron group throughout the postoperative period, although baseline levels of hemoglobin were similar between the two groups. In addition, the length of intensive care unit stay was significantly shorter in the IV iron group than in the control group. CONCLUSIONS: Preoperative intravenous iron treatment might be effective in facilitating recovery of hematologic profiles of patients during the recovery period after PD regardless of the presence of preoperative anemia, thus preventing postoperative iron deficiency anemia.

Palliative laparoscopic Roux-en-Y choledochojejunostomy as a feasible treatment option for malignant distal biliary obstruction.

PURPOSES: The advantages of surgical bypass for patients with distal biliary obstruction caused by advanced periampullary cancer include a low risk of recurrent biliary obstruction; however, the highly invasive nature of the operation limits its use. Herein, we present the clinical findings of patients who underwent laparoscopic Roux-en-Y choledochojejunostomy (LRYCJ) compared with those who underwent endoscopic stent insertion. METHODS: We reviewed, retrospectively, the palliative care outcomes for malignant bile duct obstruction according to the type of intervention: LRYCJ vs. endoscopic stenting. After initial intervention, the factors predisposing to recurrent biliary obstruction (RBO) were identified via multiple regression analysis. RESULTS: The final analysis included 28 patients treated with LRYCJ (22.4%) and 97 patients who underwent endoscopic stent insertion (77.6%). The two groups did not differ in the incidence of early or late complications and mortality; however, the LRYCJ group had a lower incidence of RBO (4 patients, 14.3% vs. 73 patients, 75.3%; p < 0.001). As a predisposing factor for RBO, endoscopic stenting was the only highly significant predictor (OR 16.956, CI 5.140-55.935, p < 0.001). CONCLUSIONS: LRYCJ represents an attractive option for palliation of malignant distal biliary obstruction, with improved biliary-tract patency and less need for subsequent interventions such as additional stenting.

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.

Clinical significance of skeletal muscle density and sarcopenia in patients with pancreatic cancer undergoing first-line chemotherapy: a retrospective observational study.

BACKGROUND: To investigate the clinical impact of sarcopenia and skeletal muscle density (SMD) among patients with metastatic pancreatic adenocarcinoma who underwent palliative first line gemcitabine-based chemotherapy. METHODS: A total of 330 patients treated with first line gemcitabine-based chemotherapy between January 2010 and March 2017 were included. CT scans before chemotherapy and after 8±2 weeks were evaluated. The L3 skeletal muscle index (SMI) was used to detect sarcopenia and calculated as the total area of the L3 skeletal muscle divided by the height-squared (cm2/m2). SMD was quantified as the mean muscle radiation attenuation of the muscle cross-sectional area across the L3 vertebral body level and was assessed between - 29 and + 150 Hounsfield units. RESULTS: A SMI to SMD comparison revealed a positive correlation (R2 = 0.058, P < 0.001). Compared with high SMD, the risks of low SMI were 1.516 (95% confidence interval [CI]: 1.164-1.973) among patients with low SMD. Kaplan-Meier analysis showed that the low SMD was related to poor overall survival (OS, median, 6.1 versus [vs.] 7.9 months, P = 0.010). Multivariate analysis using Cox regression showed that low SMI (hazard ratio [HR]: 1.35, 95% CI: 1.03-1.78, P = 0.032) and low SMD (HR: 1.45, 95% CI: 1.09-1.93, P = 0.011) were poor prognostic factors for OS, respectively. Co-presence of low SMI and low SMD had more powerful prognostic implication for OS (HR: 1.58, 95% CI: 1.12-2.23, P = 0.010). Grade 3 or higher toxicity of chemotherapy was more frequently observed in patients who have a low SMI (43% vs. 59%, P = 0.019) and low SMD (44% vs. 60%, P = 0.023). OS was not related to SMD status among patients who were chemotherapy responders (complete or partial responses). However, among non-responders (stable or progressive disease), low SMD groups had significantly poorer OS in comparison with high SMD groups (median, 5.6 vs 7.4 months, P = 0.006). CONCLUSIONS: Sarcopenia and SMD status can be considered a prognostic factor in patients with metastatic pancreatic adenocarcinoma who received palliative first line gemcitabine-based chemotherapy. Severe chemotherapy toxicity occurred in the sarcopenia and low SMD groups. Our data suggest that a comprehensive assessment of skeletal muscle parameters may be more useful prognostic factors.

Nanoliposomal irinotecan plus fluorouracil and folinic acid as a second-line treatment option in patients with metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: According to the NAPOLI-1 trial, nanoliposomal irinotecan (nal-IRI) plus fluorouracil/folinic acid (5-FU/LV) showed improved overall survival compared to fluorouracil alone for patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapy. In that trial, Asian patients had frequent dose modification due to haematological toxicity. There has been limited information on the clinical benefits and toxicity of this regimen in real-world settings. In this study, we assessed real-world experience of nal-IRI plus 5-FU/LV in patients with advanced pancreatic cancer after gemcitabine failure. METHODS: We conducted a single institution, retrospective analysis of response, survival and safety in patients who had been treated with nal-IRI with 5-FU/LV. Patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy received nal-IRI (80 mg/m2) with 5-FU/LV every 2 weeks. Kaplan-Meier analysis was performed to obtain median progression free survival and median overall survival. The hazard ratio and 95% confidence interval (CI) were estimated using a stratified Cox regression model. A multivariate Cox proportional hazards regression model was used to identify the effects of clinical factors. RESULTS: Fifty-one patients received nal-IRI plus 5-FU/LV between January 2015 and December 2020. The median age was 67 years, and males were 58.8%. A total of 40 (78.4%) and 11 (21.6%) patients had received one and two lines of prior chemotherapy before enrollment, respectively. Median progression-free survival was 2.8 months (95% CI 1.8-3.7) and median overall survival was 7.0 months (95% CI 6.0-7.9). Chemotherapy doses were reduced or delayed in 33 (64.7%) patients during the first 6 weeks and median relative dose intensity was 0.87. Thirty-six (70.6%) patients experienced grade 3 or 4 adverse events, most commonly neutropenia (58.8%). Most non-haematologic adverse events were under grade 2. Since the start of first-line chemotherapy, median overall survival was 16.3 months (95% CI 14.1-18.4). CONCLUSIONS: Nal-IRI plus 5-FU/LV seems to be effective, with manageable toxicities, following gemcitabine-based treatment in patients with metastatic pancreatic ductal adenocarcinoma. Nal-IRI plus 5-FU/LV following gemcitabine with nab-paclitaxel is a feasible sequential treatment option in patients with metastatic pancreatic cancer. TRIAL REGISTRATION: Retrospectively registered.

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.

The chronological change of indications and outcomes for single-incision laparoscopic cholecystectomy: a Korean multicenter study.

BACKGROUND: Although single-incision laparoscopic cholecystectomy (SILC) is a common procedure, the change in its surgical indications and perioperative outcomes has not been analyzed. METHODS: We collected the clinical data of patients who underwent pure SILC in 9 centers between 2009 and 2018 and compared the perioperative outcomes. RESULTS: In this period, 6497 patients underwent SILC. Of these, 2583 were for gallbladder (GB) stone (39.7%), 774 were for GB polyp (11.9%), 994 were for chronic cholecystitis (15.3%), and 1492 were for acute cholecystitis (AC) (23%). 162 patients (2.5%) experienced complication, including 20 patients (0.2%) suffering from biliary leakage. The number of patients who underwent SILC for AC increased over time (p = 0.028), leading to an accumulation of experience (27.4 vs 23.7%, p = 0.002). The patients in late period were more likely to have undergone a previous laparotomy (29.5 vs 20.2%, p = 0.006), and to have a shorter operation time (47.0 vs 58.8 min, p < 0.001). Male (odds ratio [OR]; 1.673, 95% confidence interval [CI] 1.090-2.569, p = 0.019) and moderate or severe acute cholecystitis (OR; 2.602, 95% CI 1.677-4.037, p < 0.001) were independent predictive factors for gallbladder perforation during surgery, and open conversion (OR; 5.793, 95% CI 3.130-10.721, p < 0.001) and pathologically proven acute cholecystitis or empyema (OR; 4.107, 95% CI 2.461-6.854, p < 0.001) were related with intraoperative gallbladder perforation CONCLUSION: SILC has expanded indication in late period. In this period, the patients had shorter operation times and a similar rate of severe complications, despite there being more numerous patients with AC.

Radical antegrade modular pancreatosplenectomy (RAMPS) versus conventional distal pancreatectomy for left-sided pancreatic cancer: findings of a multicenter, retrospective, propensity score matching study.

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported to achieve high rates of a negative margin and resected metastatic lymph nodes. However, many studies have used historical controls and the results remain controversial. We conducted this study to compare the surgical and long-term outcomes of RAMPS vs. conventional distal pancreatectomy (DP). METHODS: The subjects of this multicenter retrospective study were 106 patients who underwent curative resection for left-sided pancreatic cancer between 2012 and 2017. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier estimates. RESULTS: The RAMPS group had more advanced T (T3/T4) and N stages (N1/N2) and a larger tumor size than the conventional group (T stage, p = 0.04; N stage, p = 0.02; tumor size, p = 0.04). The RAMPS group had more harvested metastatic lymph nodes (p = 0.02). After propensity-score matching, 37 patients from each group were included in the final analysis. There was no significant difference in RFS (p = 0.463) or OS (p = 0.383) between the groups. Multivariate analyses revealed the completion of chemotherapy to be an independent factor for RFS and OS (both p < 0.001). CONCLUSIONS: There was no difference in the RFS or OS between RAMPS and conventional DP in this series. RAMPS may be an option for R0 resection of advanced tumors; however, postoperative chemotherapy has a greater influence than the surgical procedure on the prognosis of patients with pancreatic cancer.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Bile cholesterol and viscosity, the keys to discriminating adenomatous polyps from cholesterol polyps by a novel predictive scoring model.

BACKGROUND: Adenomatous gallbladder polyps, premalignant lesions of the gallbladder, have fatal outcomes, whereas cholesterol polyps have benign features. Herein, we proposed a novel, predictive scoring model of adenomatous polyps to distinguish them from cholesterol polyps, by analyzing bile components and bile viscosity. METHODS: Patients with gallbladder polyp pathologically confirmed after cholecystectomies were analyzed. After dividing patients into two groups (adenomatous or cholesterol polyps), the clinicopathologic profiles and bile nature, including components and viscosity were compared and a predictive scoring model for adenomatous polyps was assessed. RESULTS: Eleven adenomatous polyps and 96 cholesterol polyps were analyzed. The variables significantly associated with adenomatous polyps were age > 55 years (OR = 23.550, p = 0.020), bile viscosity< 7.5 s- 1 (OR = 22.539, p = 0.012), and bile cholesterol< 414.5 mg/dl (OR = 10.004, p = 0.023) and the points for each variable in the predictive scoring model were allocated as 3, 3, and 2, respectively. Final scores ranged from 0 to 8 points and the best performance of model at a cutoff of ≥6 points had 90.9% of sensitivity and 80.2% of specificity. CONCLUSIONS: Bile viscosity and bile cholesterol accompanied by age were revealed as significant predictors of adenomatous polyps, distinguishing them from cholesterol polyps of gallbladder. It can be the cornerstone for creating accurate guidelines for preoperatively determining treatment strategies of gallbladder polyps.

Clinical outcomes of primary aldosteronism based on lateralization index and contralateral suppression index after adrenal venous sampling in real-world practice: a retrospective cohort study.

BACKGROUND: We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice. METHODS: We retrospectively reviewed 48 patients who had resistant hypertension (HTN) or hypokalemia with a biochemical diagnosis of primary aldosteronism and who underwent AVS from January 2009 to June 2017 at a tertiary referral hospital. Selection index (SI), lateralization index (LI), and contralateral suppression index (CSI) were calculated based on AVS results and the final clinical outcomes were evaluated. RESULTS: The catheterization of both adrenal veins was successful in 43 of 48 (89.6%) patients. The lateralization based only on LI was performed in 23 out of 43 (53.5%) patients. When CSI and LI were combined in decision making, the concordance between adrenal computed tomography scan and AVS for unilateral lesion improved from 59.3% (19/32) to 75.0% (24/32). CSI also correlated well with unilateral adrenal disease in the catheterization failure group. The final outcomes of HTN were better in the contralateral suppression group. CONCLUSION: CSI combined with LI could be a supplementary diagnostic tool in patients with non-lateralization or catheterization failure and predict the clinical outcomes of HTN in patients with primary aldosteronism.

Celiac plexus block with botulinum toxin in severe chronic pancreatitis-A case report.

WHAT IS KNOWN AND OBJECTIVE: The botulinum toxin (BoNT) has been widely used for various conditions associated with pain. CASE DESCRIPTION: Here, we report a case where celiac plexus block (CPB) with BoNT relieved intractable chronic pancreatic pain without complications. CPB was performed at the L1 level under fluoroscopic guidance, and 50 IU BoNT was injected on each side. After 15 weeks, pain was decreased to 0/10 on a visual analogue scale, without opioids or tramadol. WHAT IS NEW AND CONCLUSION: Our case demonstrates the efficacy of CPB with BoNT in intractable pain due to severe chronic pancreatitis.

A Novel Way of Preventing Postoperative Pancreatic Fistula by Directly Injecting Profibrogenic Materials into the Pancreatic Parenchyma.

This paper aims to validate if intrapancreatic injection of penicillin G can enhance hardness and suture holding capacity (SHC) of the pancreas through prompting the fibrosis process. Soft pancreatic texture is constantly mentioned as one of the most contributory predictors of postoperative pancreatic fistula (POPF). Soft pancreas has poor SHC and higher incidence of parenchymal tearing, frequently leading to POPF. From a library of 114 antibiotic compounds, we identified that penicillin G substantially enhanced pancreatic hardness and SHC in experimental mice. Specifically, we injected penicillin G directly into the pancreas. On determined dates, we measured the pancreatic hardness and SHC, respectively, and performed molecular and histological examinations for estimation of the degree of fibrosis. The intrapancreatic injection of penicillin G activated human pancreatic stellate cells (HPSCs) to produce various fibrotic materials such as transforming growth factor-ß1 (TGF-ß1) and metalloproteinases-2. The pancreatic hardness and SHC were increased to the maximum at the second day after injection and then it gradually subsided demonstrating its reversibility. Pretreatment of mice with SB431542, an inhibitor of the TGF-ß1 receptor, before injecting penicillin G intrapancreatically, significantly abrogated the increase of both pancreatic hardness and SHC caused by penicillin G. This suggested that penicillin G promotes pancreatic fibrosis through the TGF-ß1 signaling pathway. Intrapancreatic injection of penicillin G promotes pancreatic hardness and SHC by enhancing pancreatic fibrosis. We thus think that penicillin G could be utilized to prevent and minimize POPF, after validating its actual effectiveness and safety by further studies.

Efficacy and safety of a novel topical agent for gallstone dissolution: 2-methoxy-6-methylpyridine.

BACKGROUND: Although methyl-tertiary butyl ether (MTBE) is the only clinical topical agent for gallstone dissolution, its use is limited by its side effects mostly arising from a relatively low boiling point (55 °C). In this study, we developed the gallstone-dissolving compound containing an aromatic moiety, named 2-methoxy-6-methylpyridine (MMP) with higher boiling point (156 °C), and compared its effectiveness and toxicities with MTBE. METHODS: The dissolubility of MTBE and MMP in vitro was determined by placing human gallstones in glass containers with either solvent and, then, measuring their dry weights. Their dissolubility in vivo was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after directly injecting each solvent into the gallbladder in hamster models with cholesterol and pigmented gallstones. RESULTS: In the in vitro dissolution test, MMP demonstrated statistically higher dissolubility than did MTBE for cholesterol and pigmented gallstones (88.2% vs. 65.7%, 50.8% vs. 29.0%, respectively; P < 0.05). In the in vivo experiments, MMP exhibited 59.0% and 54.3% dissolubility for cholesterol and pigmented gallstones, respectively, which were significantly higher than those of MTBE (50.0% and 32.0%, respectively; P < 0.05). The immunohistochemical stains of gallbladder specimens obtained from the MMP-treated hamsters demonstrated that MMP did not significantly increase the expression of cleaved caspase 9 or significantly decrease the expression of proliferation cell nuclear antigen. CONCLUSIONS: This study demonstrated that MMP has better potential than does MTBE in dissolving gallstones, especially pigmented gallstones, while resulting in lesser toxicities.

Clinical Course of Hepatic Artery Thrombosis After Living Donor Liver Transplantation Using the Right Lobe.

Hepatic artery thrombosis (HAT) can result in biliary tree necrosis and graft loss, necessitating retransplantation. The most effective treatment approach is still controversial. This study was performed to review the outcomes of HAT after living donor liver transplantation (LDLT) and to clarify the feasibility of different strategies. From May 1996 to August 2017, LDLT using the right lobe was performed in 827 adult patients in our center. Our technique of hepatic artery (HA) reconstruction is end-to-end anastomosis under a microscope (10×). Diagnosis of HAT was performed using Doppler sonography and computed tomography (CT) angiography. HAT was initially treated with surgical or endovascular procedure, and retransplantation was considered according to the graft condition. Among the 827 cases of LDLT using the right lobe, HAT occurred in 16 (1.9%) cases within 1 month after transplantation. Within the first week, 7 of these HAT cases (43.8%) occurred (early HAT), while the remaining 9 cases (56.2%) occurred between the first week and 1 month (late HAT). The incidence of graft failure was high in early HAT (42.9%), and the frequency of biliary complications was high in late HAT (77.8%). The success rate of HA recanalization was 62.5% (10/16): 100% (5/5) after reoperation and 45.5% (5/11) after the endovascular procedure. Of the patients in whom treatment failed in late HAT (n = 5), 4 underwent neovascularization during observation. A total of 5 patients underwent graft failure, and 3 of these patients underwent repeat liver transplantation (LT). Mortality occurred in 3 patients, including 1 in the surgical group and 2 in the endovascular group. In conclusion, early diagnosis and aggressive treatment of HAT are necessary to avoid graft failure, and the choice of treatment depends on various factors. Although further studies are required, early HAT requires preparation for graft failure, while late HAT requires treatment for biliary complications.

Perioperative outcomes of laparoscopic pancreaticoduodenectomy for benign and borderline malignant periampullary disease compared to open pancreaticoduodenectomy.

PURPOSE: The objective of this study was to compare perioperative outcomes between laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for benign and borderline malignant periampullary diseases. METHODS: Of 107 pancreaticoduodenectomy cases for non-malignant diseases from March 1993 to July 2017, 76 patients underwent OPD and 31 patients received LPD. To adjust for baseline differences and selection bias, operative outcomes and complications were compared after propensity score matching (PSM). RESULTS: After 1:1 PSM, well-matched 31 patients in each group were evaluated. As a result, significant differences were observed between two groups in some aspects: mean operative time (LPD 426.8 ± 98.58 vs. OPD 355.03 ± 100.0 min, p = 0.031), estimated blood loss (LPD 477.42 ± 374.80 vs. OPD 800.00 ± 531.35 ml, p = 0.008), and postoperative hospital stay (LPD 14.74 ± 5.40 vs. OPD 23.81 ± 11.63 days, p < 0.001). The average visual analogue scores for pain observed from patients in LPD group on postoperative day (POD) 1 (4.23 ± 1.83 vs. 5.55 ± 2.50, p = 0.021) and POD 3 (3.32 ± 1.66 vs. 5.26 ± 2.76, p = 0.002) were significantly less than those from patients in OPD group, as well. There were no significant differences between groups about major complications including the rate of postoperative pancreatic fistula. CONCLUSIONS: LPD is a safe procedure and provides less postoperative pain and the shortening length of hospitalization. LPD may serve the feasible alternative approach for benign and borderline malignant periampullary disease.