Prognostic Factors for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Receiving Neoadjuvant FOLFIRINOX.

BACKGROUND/AIMS: There has been growing evidence on the utility of neoadjuvant FOLFIRINOX in borderline resectable (BR) or locally advanced (LA) pancreatic cancer. However, factors predicting survival in these patients remain to be identified, and we aimed to identify these prognostic factors. METHODS: Between January 2013 and April 2017, patients with BR or LA pancreatic cancer who received FOLFIRINOX as their initial treatment were identified. Demographic data and clinical outcomes, including the chemotherapy response, conversion to resection, and survival, were reviewed. RESULTS: A total of 117 patients with BR (n=39) or LA (n=78) pancreatic cancer were included. Of these patients, 29 (24.8%) underwent curative surgery, and R0 resection was achieved in 21 patients (72.4%). The median progression-free survival and overall survival time of all patients were 11.6 and 19.0 months, respectively. In resected patients, the median relapse-free survival and overall survival times were 14.8 and 28.6 months, respectively. In the multivariate Cox model, the lowest level of serum carbohydrate antigen 19-9 (CA 19-9) and resection after FOLFIRINOX were independent factors for improved overall survival. In the subgroup analysis of patients with initial 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images, the maximum standardized uptake value (SUVmax) of the pancreatic mass was also shown as an independent factor for improved overall survival. CONCLUSIONS: In patients with BR or LA pancreatic cancer, FOLFIRINOX is a valuable neoadjuvant treatment that enables curative surgery in approximately one-quarter of patients and significantly improves overall survival. In these patients, the prognosis can be estimated using the lowest level of serum CA 19-9, operative status, and initial FDG-PET SUVmax.

Aspirin for metal stent in malignant distal common bile duct obstruction (AIMS): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Endoscopic retrograde biliary drainage (ERBD) is the treatment of choice for patients with malignant distal common bile duct (CBD) obstruction. Self-expandable metal stents (SEMS), which are commonly used in unresectable cases, have many clinical advantages, including longer stent patency. Although the expected patency of SEMS is around 8 months, it has recently been reported that the duration of SEMS' patency in patients using aspirin is prolonged. Our study, therefore, aims to investigate the effect of aspirin on SEMS' patency. METHODS/DESIGN: This is an investigator-initiated, prospective, multicenter, double-blind, randomized placebo-controlled trial that will be conducted from November 2017 in four tertiary centers in South Korea. We intend to include in our study 184 adult (aged ≥ 20 years) patients with malignant distal CBD obstruction for whom ERBD with SEMS was successfully performed. The patients will be randomly allocated to two groups, which will comprise patients who have either taken 100 mg aspirin or a placebo for 6 months after index ERBD. The primary outcome will be the rate of stent dysfunction, and the secondary outcomes will be the duration of patency, the rate of reintervention, and the occurrence of adverse events. DISCUSSION: The aspirin for metal stents in malignant distal common bile duct obstruction (AIMS) study should determine the efficacy of aspirin in maintaining metal-stent patency in patients with malignant distal CBD obstructive. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03279809. Registered on 5 September 2017.

Lymph node ratio as valuable predictor in pancreatic cancer treated with R0 resection and adjuvant treatment.

BACKGROUND: Lymph-node (LN) metastasis is an important prognostic factor in resected pancreatic cancer. In this study, the prognostic value of American Joint Committee on Cancer (AJCC) 8th edition N stage, lymph-node ratio (LNR), and log odds of positive lymph nodes (LODDS) in resected pancreatic cancer was investigated. METHODS: Between January 2005 and December 2017, there were 351 patients with pancreatic cancer treated with R0 resection and adjuvant therapy at Seoul National University Hospital. Relationships between the three LN parameters and overall survival (OS) and recurrence-free survival (RFS) were evaluated using a log-rank test and Cox proportional hazard regression model. Each multivariate-adjusted LN parameter was internally validated by bootstrap-corrected Harrell's C-index. RESULTS: The mean duration from surgery to adjuvant therapy was 47.6 ± 17.4 days. In total, the median OS and RFS was 31.7 (95% CI, 27.2-37.2) and 15.4 (95% CI, 13.5-17.7) months. The three LN classification systems were significantly correlated with OS and RFS in log-rank tests and multivariate-adjusted models (all p < 0.05). When internally validated, LNR showed the highest discrimination ability in predicting OS and RFS (each C-index = 0.65). LNR also showed the highest C-index in subgroup analysis, classified by adjuvant therapy modality. LNR and the AJCC 8th edition LN classification system were significantly associated with loco-regional recurrence (p = 0.026 and p = 0.027, respectively). CONCLUSIONS: LNR, which showed the best prognostic performance and significant relationship with loco-regional recurrence, can help further stratify the patients and establish an active treatment plan.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients.

BACKGROUND: Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE). METHODS: A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain. RESULTS: A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P < 0.001) were predictive factors for post-procedural abdominal pain. CONCLUSIONS: EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Step-wise endoscopic approach to palliative bilateral biliary drainage for unresectable advanced malignant hilar obstruction.

The ideal type of stent utilized at index endoscopic retrograde cholangiopancreatography (ERCP) in management of malignant hilar obstruction (MHO) remains unclear. We aimed to determine the ideal stent choice in patients with MHO. In this retrospective study, patients with unresectable MHO were separated into the plastic stent (PS) group and the self-expandable metal stent (SEMS) group. The primary outcome was the risk and rate of rescue percutaneous transhepatic biliary drainage (PTBD). The secondary outcomes were the progression-free survival, the overall survival and the PTBD-free period (days). Thirty-six patients in the PS group and 38 patients in the SEMS group were enrolled. The risk for PTBD was higher in SEMS group (HR = 2.205, 95% C.I. 0.977-4.977, P = 0.057). The rate of PTBD was significantly lower in the PS group. (22.2% vs 50.0%, P = 0.017) There were no differences in overall survival and progression-free survival (410 and 269 in the PS group, 395 and 266 in the SEMS group, P = 0.663 and P = 0.757). The PTBD-free period was significantly longer in the PS group. (836.43 vs 586.40, P = 0.039) Although comparable in clinical efficacy, utilization of PS at index ERCP may reduce patient's discomfort by avoiding PTBD and prolonging PTBD-free period in patients with MHO.

Optimal Biliary Drainage for Patients With Biliary Anastomotic Strictures After Right Lobe Living Donor Liver Transplantation.

Right lobe (RL) living donor liver transplantation (LDLT) usually includes 2 bile duct anastomosis sites, namely, the right anterior and the right posterior segmental ducts. This study aimed to evaluate the optimal treatment for biliary strictures following RL LDLT with respect to unilateral or bilateral drainage techniques. From January 2005 to December 2017, 883 patients at Seoul National University Hospital underwent RL LDLT. Of these, 110 patients were enrolled who had 2 duct-to-duct anastomosis sites and who were considered at risk of developing biliary anastomotic strictures. Unilateral or bilateral biliary drainage during the follow-up period was identified by endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD). The clinical success, complication, and 180-day mortality rates were compared between the unilateral and bilateral biliary drainage groups according to the initial ERCP findings. The mean age at the time of LDLT was 54.2 ± 8.2 years. The median time from LDLT to initial biliary anastomotic strictures was 177 (interquartile range, 18-1085) days. At the initial ERCP, unilateral drainage was performed in 55 (50.0%) patients, and bilateral drainage was performed in 11 (10.0%) patients. Of the patients who underwent unilateral drainage, 35 (63.6%) patients required conversion to bilateral drainage during follow-up. Overall, 71 (64.5%) patients required bilateral drainage more than once, whereas only 27 (24.5%) patients reached a resolution with unilateral biliary drainage. In this study, most patients required bilateral biliary drainage more than once during follow-up. An active attempt should be made to drain bilaterally in patients with biliary anastomotic strictures following RL LDLT.

Natural Course and Risk of Cholangiocarcinoma in Patients with Recurrent Pyogenic Cholangitis: A Retrospective Cohort Study.

Background/Aims: Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA. Methods: From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Cox’s proportional hazard regression model. Results: Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023). Conclusions: In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.

A Case of Idiopathic Severe Acute Pancreatitis following Cesarean Section Delivery.

Acute pancreatitis rarely occurs in the postpartum period. Furthermore, there are very few reports of it after cesarean section delivery. A 35-year-old woman presented with dyspnea and abdominal distension on the third day after cesarean section delivery. Under a suspicion of acute pancreatitis, she was initially managed with conservative treatment. However, she developed intra-abdominal fluid collections and gastric bleeding, which were managed with percutaneous drainage, endoscopic hemostasis, and angiographic embolization. She was discharged with good clinical recovery. Postpartum pancreatitis, especially after cesarean section, is rare; however, its management is not different from that for usual pancreatitis.

A Case of Adenomyomatous Hyperplasia of the Distal Common Bile Duct Mimicking Malignant Stricture.

Adenomyomatous hyperplasia is a reactive malformation or non-neoplastic tumor-like lesion frequently observed in the gallbladder, stomach, duodenum and jejunum, but rare in the extrahepatic bile duct. A 42-year-old man with epigastric discomfort had a stricture in the common bile duct on initial CT scans. Initially, it was regarded as a malignant lesion with some evidence, but histopathologic examinations of multiple biopsies obtained by multiple sessions of endoscopic retrograde cholangiopancrea-tography showed no evidence of malignancy. The patient had undergone the pylorus preserving pancreaticoduodenectomy because of the possibility of malignancy; however, the final diagnosis was adenomyomatous hyperplasia. It is important to distinguish a malignancy from benign biliary stricture with endoscopic biopsies. Surgery for suspected biliary malignancy often reveals benign lesions. Therefore, a correct diagnosis is important before deciding upon treatment of bile duct stricture. In conclusion, in younger patients with bile duct stricture where there is no evidence of histologic malignancy despite multiple biopsies, the possibility of benign disease such as adenomyomatous hyperplasia should be considered, to avoid unnecessary radical surgery.