Clinical and Technical Guideline for Endoscopic Ultrasound (EUS)-Guided Tissue Acquisition of Pancreatic Solid Tumor: Korean Society of Gastrointestinal Endoscopy (KSGE)

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy (KSGE) appointed a Task Force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in 8 categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice.ope

Mixed neuroendocrine-non-neuroendocrine carcinoma (MiNEN) in gallbladder with liver metastasis of neuroendocrine carcinoma component: a case report

Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder are rare with a lack of established standardized therapeutic strategies. We report a case of gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm with liver metastasis of neuroendocrine carcinoma. A patient who underwent radical cholecystectomy for gallbladder adenocarcinoma was detected with increasing liver mass, and hepatectomy was performed. Pathological report revealed neuroendocrine carcinoma. To find primary origin, pathological review of the old specimen from previous cholecystectomy with a slightly different perspective was conducted, where the neuroendocrine component was positively dyed. In conclusion, though it might be impossible to review every pathological result in cases with ambiguous findings, reviewing the previous specimen can be a useful option in diagnosis. Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2023.ope

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

AIM: To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine (GEM)-refractory unresectable pancreatic cancer (PC). METHODS: This study was a prospective, multicenter, one-arm, open-label, phase II trial. Patients with unresectable PC, who showed disease progression during GEM-based chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin (RIO; irinotecan 120 mg/m2 and oxaliplatin 60 mg/m2), which was set according to the phase I study of FOLFIRINOX. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events were evaluated. Additionally, changes in quality of life (QoL) were assessed using a questionnaire on QoL. RESULTS: Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval (CI): 3.7-7.9] and median OS was 9.0 mo (95%CI: 6.4-11.6). Neutropenia (64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia (16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment (45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548). CONCLUSION: FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.ope

Cancer Cachexia in Pancreatic Cancer Patients: Recent Advances and New Therapeutic Approach

About 80% of all pancreatic cancer patients suffer from a wasting syndrome defined as the cancer cachexia characterized by abnormally low weight, weakness, and loss of skeletal muscle mass, which directly impacts physical activity, quality of life and overall survival. Over the past decades, we have gained new insights into the underlying mechanism of cachexia associated with pancreatic cancer. The aim of this review was to explore recent findings about cancer cachexia pathophysiology and describe the current pharmacologic approach. Pancreatic cancer cachexia is a multifactorial syndrome mediated by mechanical factors, inflammatory cytokines, neuropeptides, hormones and tumor-derived factors. The treatment of cancer cachexia remains controversial but is currently an active area of research. Several new targeted drugs are under investigation, and we hope to open a new prospect in the management of cancer cachexia in the future.ope

췌장신경내분비종양의 내과적 치료

Pancreatic neuroendocrine tumor (PNET) refer to tumors originating from the islet of Langerhans and shows various prognosis based on the presence or absence of symptoms due to hormone secretion, the Ki-67 cell proliferation index, and the histologic grade, and according to the degree of disease progression defined by the tumor-node-metastasis (TNM) stage classification. The purpose of medical treatment for PNET is to control symptoms or inhibit tumor growth. Somatostatin analogues can be administered for the purpose of controlling symptoms caused by the secretion of specific hormones, and are accepted as effective drugs for inhibiting the progression of G1/G2 tumors based on World Health Organization (WHO) classification with a Ki-67 cell proliferation index less than 20%. Among the molecularly targeted agents, everolimus and sunitinib can be considered in patients with WHO G1/G2 PNET showing progression after somatostatin analog therapy. Cytotoxic chemotherapy is generally administered to patients with large tumor volume and rapidly progressing metastatic NET, and etoposide/cisplatin combination therapy has been considered as a standard treatment. For the patient group of Grade 3 PNET (well differentiated) newly classified by the WHO 2017 classification, guidelines for standard treatment have not yet been established. As it has been reported, studies are needed to evaluate the treatment response rate of somatostatin analogues or molecularly targeted therapies for the patient with Grade 3 PNET. It is important to consider a multidisciplinary approach with all possible treatment options including medical treatment, radical resection of primary or metastatic lesions, liver-directed therapies, and peptide receptor radionuclide therapy for the patients with PNET.ope

Clinical and Technical Guideline for Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreatic Solid Tumor: Korean Society of Gastrointestinal Endoscopy

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy appointed a Task Force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice.ope

The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial

Objective: Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices. Methods: Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study. Results: This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.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

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

Comparison of Clinical Performance and Safety between Domestic New Pull-type Triple-lumen Sphincterotome and Conventional Sphincterotome: A Prospective Multicenter Trial

Background/aims: Sphincterotomes are essential for endoscopic sphincterotomy (EST) and can also be used for cannulation in ERCP. A domestic new pull-type sphincterotome (Optimos™, Taewoong, Goyang, Korea) provides acceptable technical feasibility and safety, but there are no comparison results. Thus, this study compared the clinical performance and safety of Optimos™ sphincterotome to a conventional sphincterotome (CleverCut3™, Olympus, Tokyo, Japan) in patients who underwent ERCP. Methods: From April 2021 to July 2021, a randomized prospective comparative study was conducted on 104 consecutive patients who underwent ERCP in three medical centers. The primary endpoint was the clinical performance and safety of sphincterotomes during ERCP. Results: One hundred and four patients were assigned randomly to the Optimos™ group (n=51) or CleverCut3™ group (n=53). All demographic characteristics did not differ between the groups except the BMI. The technical success rate for cannulation, performance of EST, and total procedure time were similar in the two groups. The adverse events did not differ, even though two cases of post-ERCP pancreatitis occurred in CleverCut3™. On the other hand, in questionnaire analysis, CleverCut™ showed a better user's convenience (median [interquartile range] 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.013) and manipulability (median [interquartile range], 4.0 [3.0-4.0] vs. 3.0 [3.0-4.0], p=0.039) than Optimos™, even though the other profiles did not reveal any differences. Conclusions: New domestic pull-type sphincterotome can offer comparable clinical performance and safety profiles to conventional sphincterotome, but it needs refinements to increase the user's convenience and manipulability. Further improvement and innovation will be required to advance domestic medical devices.ope