Hyun Jik Lee, Chang Min Cho, Jun Heo, Min Kyu Jung, Tae Nyeun Kim, Kook Hyun Kim, Hyunsoo Kim, Kwang Bum Cho, Ho Gak Kim, Jimin Han, Dong Wook Lee, and Yoon Suk Lee. Gut and Liver 2020;14:257-64. https://doi.org/10.5009/gnl18537

There is limited data on miRNA expression in pancreatic neuroendocrine tumors (PanNETs). In this study, we aimed to identify miRNAs that could be potential prognostic biomarkers of PanNETs in patients who underwent curative surgery. For miRNA target screening, 2 primary PanNETs and corresponding liver metastases were screened for miRNA expression by the NanoString nCounter analysis. Candidate miRNAs were selected by ≥2-fold difference of expression between metastatic versus primary tumor. For miRNA target validation, quantitative real-time PCR was performed for candidate miRNAs on 37 PanNETs and matched nonneoplastic pancreata, and the miRNA levels were correlated with the clinicopathological features and patient survival data. Eight miRNAs (miRNA-27b, -122, -142–5p, -196a, -223, -590–5p, -630, and -944) were selected as candidate miRNAs. Only miR-196a level was significantly associated with stage, and mitotic count. When PanNETs were stratified into high (n = 10) and low (n = 27) miRNA-196a expression groups, miRNA-196a-high PanNETs were significantly associated with advanced pathologic T stage (50.0% vs 7.4%), N stage (50.0% vs 3.7%), higher mitotic counts (60.0% vs 3.7%), and higher Ki-67-labeling indices (60.0% vs 22.2%). In addition, high miRNA-196a expression was significantly associated with decreased overall survival (P = 0.046) and disease-free survival (P < 0.001) during a median follow-up of 37.9 months with the hazard ratio for recurrence of 16.267 (95% confidence interval = 1.732–153.789; P = 0.015). MiRNA-196a level may be a promising prognostic marker of recurrence in resected PanNETs, although further experimental investigation would be required.

The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.

Yoon Suk Lee, Chang Min Cho, Kwang Bum Cho, Jun Heo, Min Kyu Jung, Sung Bum Kim, Kook Hyun Kim, Tae Nyeun Kim, Dong Wook Lee, Jimin Han, Ho Gak Kim, Daejin Kim, and Hyunsoo Kim. Gut and Liver 2021;15:459-65. https://doi.org/10.5009/gnl19304

Background/Aims: There is no standard consensus on a strategy in the second-line setting for gemcitabine-refractory advanced pancreatic cancer. This study evaluated the activity and tolerability of oxaliplatin, irinotecan, 5-fluorouracil and leucovorin (FOLFIRINOX) as a second-line therapy in advanced pancreatic adenocarcinoma pretreated with a gemcitabine-based regimen. Methods: A retrospective survey was carried out on 18 patients with advanced pancreatic cancer who had been on gemcitabine-based chemotherapy and were then treated with FOLFIRINOX as a second-line therapy. Results: One patient (5.6%) had a confirmed complete response, 4 (22.2%) had confirmed partial responses and 5 (27.8%) had stable disease, resulting in a rate of disease control of 55.6% (95% CI, 33.3-77.8%). The median progression-free survival and median survival were 2.8 months and 8.4 months, respectively. Seven patients (38.9%) experienced grade 3-4 neutropenia. Grade 3 or 4 nonhematologic adverse events included nausea (38.9%) and vomiting (16.7%). Conclusions: These results suggest the modest clinical activity regarding efficacy and the acceptable toxicity profile with the FOLFIRINOX regimen as a second-line treatment.

There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy). We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011. Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively). TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.