Clinical Outcomes of Bilateral Stent-in-Stent Placement Using Self-Expandable Metallic Stent for High-Grade Malignant Hilar Biliary Obstruction

PURPOSE: Endoscopic bile duct decompression using bilateral self-expandable metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered a preferred procedure for malignant hilar biliary obstruction (MHBO). However, occlusion thereof occurs frequently. Here, we investigated stent patency duration and risk factors related to stent obstruction with bilateral SIS placement for MHBO at two large centers. MATERIALS AND METHODS: The present study reviewed data on patients with MHBO who underwent endoscopic biliary drainage using the SIS method. Clinical outcomes, including stent patency duration and patient overall survival, were analyzed. Factors associated with stent patency were evaluated using Cox proportional hazards models. RESULTS: Seventy patients with MHBO underwent endoscopic biliary drainage using the SIS method. Median age was 68 years old, and median follow-up duration was 140 days (interquartile range, 57-329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median stent patency duration with the SIS method was 108 days according to Kaplan-Meier curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days. Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as an independent risk factor related to stent patency (p<0.05). CONCLUSION: In endoscopic biliary decompression using SEMS placed with the SIS method, obstructive jaundice was a risk factor for stent patency. The SIS method for high-grade MHBO showed short stent patency.ope

Neoadjuvant and Adjuvant Chemotherapy for Cholangiocarcinoma

Cholangiocarcinoma consists of a heterogeneous group of aggressive and rare malignancies that arise from the bile ducts outside or inside the liver. Although surgical resection remains the only potential curative treatment option for patients with cholangiocarcinoma, curative surgery is only possible in a small number of cases. Furthermore, recurrence rates are high even among patients who undergo surgical resection. Unfortunately, a significant proportion of patients present with locally advanced, unresectable disease. Recently, neoadjuvant chemotherapy has emerged as a promising method to identify patients with poor prognosis, avoiding pathological and non-therapeutic resection, as well as potentially downstaging tumors which cannot be resected initially. This therapeutic strategy has the potential to improve local and distant control, to achieve R0 resection and to prevent distant metastasis. However, few data are currently available supporting neoadjuvant chemotherapy in cholangiocarcinoma and several questions remains unanswered. Adjuvant chemotherapy is administered after surgery to eradicate any remaining cancer cells with the goal of reducing the chances of recurrence. And chemotherapy is also frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear.ope

Gemcitabine plus Nab-paclitaxel as a second-line treatment following FOLFIRINOX failure in advanced pancreatic cancer: a multicenter, single-arm, open-label, phase 2 trial

Background: The aim of this study was to evaluate the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) as second-line chemotherapy following first-line FOLFIRINOX treatment failure in advanced pancreatic cancer. Methods: This was a multicenter, single-arm, open-label, phase 2 trial done at three tertiary centers in South Korea from May 2018 to December 2019. Eligible patients were aged 20 years or older, had histologically confirmed advanced pancreatic ductal adenocarcinoma, and disease progression after receiving first-line FOLFIRINOX. Patients received a second-line GnP regimen as intravenous nab-paclitaxel at a dose of 125 mg/m2 and gemcitabine at a dose of 1000 mg/m2, on days 1, 8, and 15 every 4 weeks until disease progression or unacceptable toxicity. The primary outcome was survival rate at 6 months and the secondary outcomes were median progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events. This study is registered with Clinicaltrials.gov. (NCT03401827). Results: Forty patients were enrolled in the study. The survival rate at 6 months was 72.5% [95% confidence interval (CI), 59.9-87.7], achieving superiority over prespecified assumed 6-month OS rate of 20% for best supportive care only (p < 0.001). The median PFS and OS were 5.8 months (95% CI, 4.3-8.7) and 9.9 months (95% CI, 7.5-12.4), respectively. DCR was 87.5% with six partial responses and 29 stable diseases. Grade 3 or higher treatment-related adverse events occurred in 25 (62.5%) patients with the most common being thrombocytopenia, anemia, neutropenia, peripheral neuropathy, and peripheral edema. Conclusion: GnP demonstrated favorable efficacy with acceptable toxicity in patients with advanced pancreatic ductal adenocarcinoma after FOLFIRINOX failure.ope

Identification of Circulating Serum miRNAs as Novel Biomarkers in Pancreatic Cancer Using a Penalized Algorithm

Pancreatic cancer (PC) is difficult to detect in the early stages; thus, identifying specific and sensitive biomarkers for PC diagnosis is crucial, especially in the case of early-stage tumors. Circulating microRNAs are promising non-invasive biomarkers. Therefore, we aimed to identify non-invasive miRNA biomarkers and build a model for PC diagnosis. For the training model, blood serum samples from 63 PC patients and 63 control subjects were used. We selected 39 miRNA markers using a smoothly clipped absolute deviation-based penalized support vector machine and built a PC diagnosis model. From the double cross-validation, the average test AUC was 0.98. We validated the diagnosis model using independent samples from 25 PC patients and 81 patients with intrahepatic cholangiocarcinoma (ICC) and compared the results with those obtained from the diagnosis using carbohydrate antigen 19-9. For the markers miR-155-5p, miR-4284, miR-346, miR-7145-5p, miR-5100, miR-661, miR-22-3p, miR-4486, let-7b-5p, and miR-4703-5p, we conducted quantitative reverse transcription PCR using samples from 17 independent PC patients, 8 ICC patients, and 8 healthy individuals. Differential expression was observed in samples from PC patients. The diagnosis model based on the identified markers showed high sensitivity and specificity for PC detection and is potentially useful for early PC diagnosis.ope

Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer

Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19- 9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabinebased FL.ope

Systemic Chemotherapy in Advanced Pancreatic Cancer

Pancreatic cancer remains one of the most lethal cancers. These patients often have multiple symptoms, and integrated supportive care is critical in helping them remain well for as long as possible. Fluorouracil-based chemotherapy is known to improve overall survival (OS) by approximately 3 months, compared to the best supportive care alone. A 1997 study comparing gemcitabine and fluorouracil treatment of advanced pancreatic cancer patients showed an improvement in OS of 1 month in patients receiving gemcitabine. Over the next 10 years, multiple randomized studies compared singleagent gemcitabine with combination chemotherapy and showed no effective survival improvement. However, the addition of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, was associated with a significant improvement in OS of approximately 2 weeks. However, adoption of this regimen has not been widespread because of its limited effect and added toxicity. Two clinical trials have recently prolonged OS in advanced pancreatic cancer patients by almost 1 year. The first compared FOLFIRINOX with gemcitabine alone, and was associated with a significant improvement in median survival. The second compared gemcitabine and nabpaclitaxel with gemcitabine alone, and was associated with improvements in OS. At present, these regimens are considered standard treatment for patients with good performance statuses.ope

Healthcare vulnerability disparities in pancreatic cancer treatment and mortality using the Korean National Sample Cohort: a retrospective cohort study

Background: The gap in treatment and health outcomes after diagnosis of pancreatic cancer is a major public health concern. We aimed to investigate the differences in the health outcomes and treatment of pancreatic cancer patients in healthcare vulnerable and non-vulnerable areas. Methods: This retrospective cohort study evaluated data from the Korea National Health Insurance Corporation-National Sample Cohort from 2002 to 2019. The position value for relative comparison index was used to define healthcare vulnerable areas. Cox proportional hazard regression was used to estimate the risk of mortality in pancreatic cancer patients according to healthcare vulnerable areas, and multiple logistic regression was used to estimate the difference in treatment. Results: Among 1,975 patients, 279 (14.1%) and 1,696 (85.9%) lived in the healthcare vulnerable and non-vulnerable areas, respectively. Compared with the non-vulnerable area, pancreatic cancer patients in the vulnerable area had a higher risk of death at 3 months (hazard ratio [HR]: 1.33, 95% confidence interval [CI] = 1.06-1.67) and 6 months (HR: 1.23, 95% CI = 1.03-1.48). In addition, patients with pancreatic cancer in the vulnerable area were less likely to receive treatment than patients in the non-vulnerable area (odds ratio [OR]: 0.70, 95% CI = 0.52-0.94). This trend was further emphasized for chemotherapy (OR: 0.68, 95% CI = 0.48-0.95). Conclusion: Patients with pancreatic cancer belonging to medically disadvantaged areas receive less treatment and have a higher risk of death. This may be a result of the late diagnosis of pancreatic cancer among these patients.ope

The Role of Endoscopy in Diagnosis and Treatment of Ampullary Tumor

Tumors of the major duodenal papilla, also known as ampullary tumor, are rare with an approximate 5% incidence of all gastrointestinal neoplasm. These tumors seem to be detected more frequently with increasing performance of upper endoscopic examination and endoscopic retrograde cholangiopancreatography (ERCP). Adenoma, most common benign disease of ampullary tumor, is very important because of its potential to undergo malignant transformation to ampullary cancer. Especially, endoscopic ultrasound or transpapillary intraductal ultrasonography can provide more detailed and accurate information on the extent of ampullary tumors and proper treatment should be done after diagnosis. Considering perioperative morbidity and mortality of surgical resection, endoscopic papillectomy is regarded as a curative treatment of ampullary adenoma. However, the indication of the procedure is very strict and there are various complications related to the procedure. Therefore, it is important to understand the role of endoscopy in diagnosis and treatment of ampullary tumor. In this review, the diagnostic role of endoscopy for ampullary tumor and the treatment method of endoscopic papillectomy will be discussed.ope

A Hybrid Online and Offline International Conference of the Korean Pancreatobiliary Association in Post-COVID-19 Era

Background/Aim The COVID-19 pandemic has changed the way of traditional conference and meeting. Since social distancing rule was important issue, many conferences across the world were cancelled or postponed indefinitely. In 2020, International Conference of the Korean Pancreatobiliary Association (IC-KPBA) was held as a hybrid online and offline conference. Here, we report the result of a national survey about online and offline medical conference in Korea. Methods The survey was performed for both online and offline participants after IC-KPBA. The contents of survey included their way to access the hybrid online-offline conference and satisfaction with the conference format. Results Total of 78 participants answered the survey and there was no technical problem. Most offline participants were satisfied the prevention measures at conference hall as follows; very satisfied-56%; satisfied-34%. The quality of video and audio were generally satisfactory in both conference hall and virtual conference. ‘Live online lectures’ is the most preferred method of lecture delivery and personal computer with LAN network is preferred to access online conference. Eighty seven percent of offline participants and 91% of online participants answered satisfied and very satisfied, respectively. Conclusions Participants of IC-KPBA 2020 with hybrid online-offline conference showed a high level of satisfaction.ope

Past, Present, and Future of Gastrointestinal Stents: New Endoscopic Ultrasonography-Guided Metal Stents and Future Developments

Innovations in stent technology and technological advances in endoscopic ultrasonography have led to rapid expansion of their use in the field of gastrointestinal diseases. In particular, endoscopic ultrasonography-guided metal stent insertion has been used for the management of pancreatic fluid collection, bile duct drainage, gallbladder decompression, and gastric bypass. Endoscopic ultrasonography-guided drainage of intra-abdominal fluid collections using a plastic or metal stent is well established. Because of the various limitations-such as stent migration, injury and bleeding in the lumen-recently developed, fully covered self-expanding metal stents or lumen-apposing metal stents have been introduced for those fluids management. This article reviews the recent literature on newly developed endoscopic ultrasonography-guided metal stents and the efficacy thereof.ope