Management of Small Pancreatic Neuroendocrine Neoplasm

The incidence of small and asymptomatic pancreatic neuroendocrine neoplasms (PNENs) has been increased due to the widespread use of high-resolution imaging techniques and endoscopic procedures in screening programmes. Most of PNENs are indolent neoplasms with slow-growing. However, sometimes, PNENs show local invasion or metastasis with poor prognosis. The management of small, nonfunctioning PNENs remain under debate. The National Comprehensive Cancer Network guidelines recommend observation in selected cases of small PNENs less than 2 cm. Pancreatic surgeons are divided into two factions: “the hawks,” who indicate the high risk of malignancy even in small PNENs and, therefore, the need for an aggressive surgical treatment, and the “the doves,” who accepts the risk of malignancy in some ≤ 2 cm PNENs, advocate that the risk of overtreating many benign ≤ 2 cm PNENs would be much higher. As the pancreatic surgery remains a high-risk operation with a 28–30% morbidity and 1% mortality, the decision for small PNENs is challenging.ope

Usefulness of intraductal RFA in patients with malignant biliary obstruction

Background/aims: Intraductal radiofrequency ablation (ID-RFA) is a novel therapy for unresectable malignant biliary obstructions. ID-RFA for perihilar lesions is associated with a high risk of adverse events. We aimed to evaluate the feasibility and efficacy of temperature-controlled ID-RFA for perihilar malignant biliary obstruction. Methods: Sixteen patients with pathologically proven perihilar cholangiocarcinoma were prospectively enrolled to evaluate the feasibility of hilar ID-RFA. Clinical efficacy and outcomes were subsequently evaluated in a multicenter retrospective cohort. Results: Nine of the 16 patients in the prospective cohort had Bismuth type IV and 7 had type IIIA perihilar cholangiocarcinoma. The median length of stricture was 34.5 mm. The median number of ID-RFA sessions was three, and all sessions were technically and functionally successful without severe adverse events. Clinical outcomes were assessed using a multicenter hilar ID-RFA cohort of 21 patients; the median stent patency and overall survival were 90 days (range: 35-483 days) and 147 days (range: 92-487 days), respectively. An approximate 16-month patency of the bile duct was maintained in one patient who had an intraductal growth pattern. In a comparison of the self-expandable metallic stent (SEMS) and plastic stent (PS) after hilar ID-RFA, no differences in stent patency (89 vs 90.5 days, respectively; P = .912) and adverse events (20.0% vs 10%, respectively; P = .739) were observed. Conclusions: ID-RFA at 7 W for 120 seconds is safe and feasible in patients with advanced perihilar cholangiocarcinoma. After ID-RFA, SEMS and PS placement showed comparable patency and survival rates. Trial registration number: KCT0003223.ope

Intraductal Radiofrequency Ablation for Residual Adenoma after Endoscopic Papillectomy: An Additional Treatment Modality Expected to Be Safe and Effective

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항암제 내성 증가와 연관된 PAUF 단백의 췌장암줄기세포 내 과발현

의과대학/박사Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies. Similar to other tumors, pancreatic cancer stem cells (CSCs) have also been identified, and play an important role in development, maintenance, and metastasis of PDAC. Novel secretory protein of pancreatic adenocarcinoma up-regulated factor (PAUF) has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the association between the functional role of PAUF and pancreatic CSCs. CFPAC-1 cancer spheres were cultured under nonadherent conditions with serum free media. PDAC spheres showed an elevated expression of PAUF protein and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2). The mRNA expression of PAUF was also upregulated in CD44+CD24+ESA+ pancreatic CSCs. Sphere formation and soft agar assays showed diminished number of spheres and colonies by PAUF knockdown (shPAUF) in CFPAC-1 cells. Expression of stemness genes and CSC surface markers (CD133, c-MET and ALDH1) were also lower in shPAUF CFPAC-1 cells than in normal control cells. MTT assay revealed that PAUF silent (siPAUF) CFPAC-1 cells had lower mRNA expression of multidrug resistant protein 5 (MRP5) and ribonucleotide reductase M2 (RRM2) and were more vulnerable to gemcitabine and 5-FU than negative control cells (p<0.05). In conclusion, PAUF is a novel human pancreatic CSC-associated protein that may confer chemoresistance by modulating MRP5 and RRM2. Thus, PAUF may constitute a therapeutic target for overcoming drug-resistant pancreatic CSCs.ope

Long-term Outcomes of Direct Endoscopic Necrosectomy for Complicated or Symptomatic Walled-Off Necrosis: A Korean Multicenter Study

Background/aims: The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods: The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results: Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions: Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.ope

Comparison between three types of needles for endoscopic ultrasound-guided tissue acquisition of pancreatic solid masses: a multicenter observational study

It is debatable which needle has clear superiority of diagnostic performance in endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) of solid pancreatic masses. This study aimed to compare the performance of three needles and determine the variables that affect diagnostic accuracy. From March 2014 to May 2020, 746 patients with solid pancreatic masses who underwent EUS-FNB using three types of needles (Franseen needle, Menghini-tip needle, and Reverse-bevel needle) were retrospectively reviewed. Multivariate analysis using a logistic regression model was used to identify factors related to diagnostic accuracy. There were significant differences between the groups regarding the procurement rate of the histologic and optimal quality cores (Franseen vs. Menghini-tip vs. Reverse-bevel: 98.0% [192/196] vs. 85.8% [97/113] vs. 91.9% [331/360], P < 0.001 and 95.4% [187/196] vs. 65.5% [74/113] vs. 88.3% [318/360], P < 0.001, respectively). The sensitivity and accuracy using histologic samples were 95.03% and 95.92% for Franseen, 82.67% and 88.50% for Menghini-tip, and 82.61% and 85.56% for Reverse-bevel needles, respectively. In direct comparison between the needles using histologic samples, the Franseen needle showed significantly superior accuracy than the Menghini-tip (P = 0.018) and Reverse-bevel needles (P < 0.001). Multivariate analysis indicated that tumor size ≥ 2 cm (odds ratio [OR] 5.36, 95% confidence interval [CI] 3.40–8.47, P < 0.001) and fanning technique (OR 1.70, 95% CI 1.00–2.86, P = 0.047) were significantly associated with an accurate diagnosis. EUS-FNB using the Franseen needle enables the acquisition of a larger and more adequate histologic core tissue and achieves an accurate histological diagnosis when using the fanning technique. © 2023, The Author(s).ope

Annotation-Efficient Deep Learning Model for Pancreatic Cancer Diagnosis and Classification Using CT Images: A Retrospective Diagnostic Study

The aim of this study was to develop a novel deep learning (DL) model without requiring large-annotated training datasets for detecting pancreatic cancer (PC) using computed tomography (CT) images. This retrospective diagnostic study was conducted using CT images collected from 2004 and 2019 from 4287 patients diagnosed with PC. We proposed a self-supervised learning algorithm (pseudo-lesion segmentation (PS)) for PC classification, which was trained with and without PS and validated on randomly divided training and validation sets. We further performed cross-racial external validation using open-access CT images from 361 patients. For internal validation, the accuracy and sensitivity for PC classification were 94.3% (92.8-95.4%) and 92.5% (90.0-94.4%), and 95.7% (94.5-96.7%) and 99.3 (98.4-99.7%) for the convolutional neural network (CNN) and transformer-based DL models (both with PS), respectively. Implementing PS on a small-sized training dataset (randomly sampled 10%) increased accuracy by 20.5% and sensitivity by 37.0%. For external validation, the accuracy and sensitivity were 82.5% (78.3-86.1%) and 81.7% (77.3-85.4%) and 87.8% (84.0-90.8%) and 86.5% (82.3-89.8%) for the CNN and transformer-based DL models (both with PS), respectively. PS self-supervised learning can increase DL-based PC classification performance, reliability, and robustness of the model for unseen, and even small, datasets. The proposed DL model is potentially useful for PC diagnosis.ope

Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus

Pancreatic neuroendocrine neoplasms (pNENs) account for 2-3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived pNEN tissue. To validate the cancer stem cell-like cell characteristics of QGP-1 cells in spheroid culture, in vitro analyses and xenografting were performed. Furthermore, immunohistochemical staining was conducted to verify the overexpression of Prdx2 in pNEN tissue. Prdx2 expression was high at the mRNA and protein levels in QGP-1 cells. Prdx2 was also overexpressed in patient-derived pNEN tissue. Silencing of Prdx2 using siRNA induced overexpression and phosphorylation of ERK and AKT in QGP-1. Cell proliferation was increased by treating QGP-1 cells with siPrdx2, and the IC50 of everolimus increased suggesting resistance to everolimus. Interestingly, QGP-1 spheroid cells, which exhibited cancer stem cell-like features, exhibited lower expression of Prdx2 and mTOR. The results suggest that Prdx2 expression level and its activity may be a potential predictive biomarker for therapeutic response or resistance to everolimus in pNEN.ope

Recent Update of Endoscopic Radiofrequency Ablation for Pancreatobiliary Disease

Despite rapid changes in diagnosis and treatments, pancreatobiliary malignancy has increased in recent years and still has a poor prognosis. Although mainstay of treatment depends on the type of malignancy and the stage, only surgery can be expected to cure, but difficult to apply in all patients. Because most of them are diagnosed at locally advanced or metastatic at presentation, local treatment such radiofrequency ablation (RFA) and photodynamic therapy is emerged as promising therapeutic modality which can directly ablate the malignant tissues in addition to systemic anti-cancer treatment. To date, some studies could support beneficial effects of them, however it has not been confirmed whether RFA is related to favorable treatment outcomes in patient with pancreatobiliary malignancies. Therefore, this review focuses on clinical application and appropriate use of endoscopic retrograde cholangiopancreatography guided intraductal RFA along with their benefits and complications.ope

Multi-Center Study on Gender Difference in Resectability and Pathologic Prognosis of Gallbladder Cancer

Background/Aim In gallbladder cancer (GBC), gender differences in incidence and mortality rates have been reported with geographic variation. However, there is little known about sex-related difference in GBC prognosis. This study compares prognostic factors according to gender for GBC. Methods We searched clinicopathological factors in all stages of 952 GBC patients from seven medical centers in Korea. A total of 927 patients were enrolled and surgery with curative resection was performed in 499 patients. Results Carbohydrate antigen (≥37 U/mL) was a significant prognostic factor in both females and males (odd ratio [OR], 4.30; 95% confidence interval [CI], 3.13-5.89; p2; an independent predictor of poor prognosis via multivariate analysis (OR, 1.03; 95% CI, 1.01-1.05; p=0.005, OR, 1.05; 95% CI, 1.02-1.08; p=0.002). Body mass index (BMI) also showed gender difference, and lower BMI (≤25 kg/m2) was the significant good indicator of multivariate analysis for lymph node metastasis in female patients (OR, 0.42; 95% CI, 0.23-0.77; p=0.005) but, the significant poor indicator of univariate analysis for advanced T-stage in male (OR, 2.79; 95% CI, 1.40-5.54; p=0.003). Conclusions These results suggest that there is a possibility of gender difference in GBC prognosis. Age and high BMI were poor prognostic factors for curative resection for female GBC patients.ope