Ampullary Neuroendocrine Neoplasm: Clinicopathological Characteristics and Novel Endoscopic Entity.

BACKGROUND: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN. METHODS: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN). RESULTS: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of 4 cases of neuroendocrine tumor Grade 1 (NET G1), 1 NET G2 (Grade 2), and 5 neuroendocrine carcinomas (NECs). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 (<10 mm) with endoscopic papillectomy and large NET G1 with pancreaticoduodenectomy. There were no cases of recurrence after resection. All ampullary NECs presented with the characteristic endoscopic finding of a "crater sign" similar to deep-mining ulcers seen in gastric malignant lymphoma. Four cases underwent surgical resection, and 1 case was unresectable. Two patients who underwent multidisciplinary treatment were maintained without recurrence for over 2 years. CONCLUSIONS: Endoscopic findings showed identifiable distinctions between ampullary NETs and NECs.

Risks and benefits of pancreaticoduodenectomy in patients aged 80 years and over.

PURPOSE: The frequency of pancreaticoduodenectomy is increasing in oldest old patients owing to population aging. We aimed to clarify the clinical significance of pancreaticoduodenectomy in patients aged ≥ 80 years with multiple underlying diseases. METHODS: A total of 649 consecutive patients who underwent pancreaticoduodenectomy from April 2010 to March 2021 in our institute were divided into two groups according to their age: ≥ 80 years (51) and ≤ 79 years (598). We compared mortality and morbidity between the groups. The age-related prognosis was analyzed in 302 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma treatment. RESULTS: There were no significant differences in morbidity (Clavien-Dindo classification grade III or higher; P = 0.1300), mortality (P = 0.0786), or postoperative hospital stay (P = 0.5763) between the groups. Patients aged ≥ 80 years, who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, had shorter overall survival than those aged ≤ 79 years (median survival time, 16.7 months vs. 32.7 months; P = 0.0206). However, the overall survival of patients aged ≥ 80 years who received perioperative chemotherapy was comparable to that of patients aged ≤ 79 years (P = 0.9795). In the multivariate analysis, the absence of perioperative chemotherapy was identified as an independent prognostic factor, while age ≥ 80 years was not. Perioperative chemotherapy was the sole independent prognostic factor in patients aged ≥ 80 years who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. CONCLUSIONS: Pancreaticoduodenectomy is safe for patients aged ≥ 80 years. The survival benefits of pancreaticoduodenectomy for patients with pancreatic ductal adenocarcinoma aged ≥ 80 years might be limited to those who can receive perioperative chemotherapy.

Circulating CD8+CD122+ T cells as a prognostic indicator of pancreatic cancer.

PURPOSE: The distribution of tissue infiltrating lymphocytes has been shown to affect the prognosis of patients with pancreatic cancer in some previous studies. However, the role of peripheral lymphocytes in pancreatic cancer remains debated. The purpose of this study was to analyze the peripheral subtypes of T lymphocytes, and establish their association with the prognosis of patients with pancreatic cancer. METHODS: Blood and tissue samples were collected from patients with metastatic pancreatic cancer (n = 54), resectable pancreatic cancer (n = 12), and benign pancreatic cysts (n = 52) between April 2019 and January 2022 and analyzed. RESULTS: Patients with metastatic pancreatic cancer had a larger proportion of both tumor-suppressive and tumor-promoting cells than those with benign pancreatic cysts. In addition, the proportion of peripheral CD4+ T cells positively correlated with the survival of patients with metastatic pancreatic cancer, and the proportion of peripheral CD8+CD122+ T cells was associated with early mortality (< 90 days). After chemotherapy, CD8+CD122+ T cells decreased in patients who had a partial response or stable disease. Moreover, by analyzing resected specimens, we first proved that the existence of CD8+CD122+ T cells in a tumor microenvironment (TME) depends on their proportion in peripheral blood. CONCLUSION: Circulating CD8+CD122+ T cells can be a prognostic indicator in patients with pancreatic cancer.

Phase I/II study of streptozocin monotherapy in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: This phase I/II study was conducted to evaluate the efficacy, safety and pharmacokinetics of streptozocin (STZ) in Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: Twenty-two patients received up to 4 cycles of intravenous STZ at either 500 mg/m2 once daily for 5 consecutive days every 6 weeks (daily regimen) or at 1000-1500 mg/m2 once weekly for 6 weeks (weekly regimen). Tumor response was evaluated using the modified RECIST criteria ver. 1.1, and adverse events were assessed by grade according to the National Cancer Institute CTCAE (ver. 4.0). RESULTS: Fourteen (63.6%) patients completed the study protocol. No patients had complete response; partial response in 2 (9.1%), stable disease in 17 (77.3%), non-complete response/non-progressive disease in 2 (9.1%) and only 1 (4.5%) had non-evaluable disease. Excluding the latter, the response rate in the daily and weekly regimens was 6.7% (1/15) and 16.7% (1/6), respectively, with an overall response rate of 9.5% (2/21). However, the best overall response in each patient showed that the disease control rate was 100%.Adverse events occurred in all 22 patients, including 17 grade 3 adverse events in 11 patients; however, no grade 4 or 5 adverse events were reported. Prophylactic hydration and antiemetic treatment reduced the severity and incidence of nephrotoxicity, nausea and vomiting. Plasma STZ concentrations decreased rapidly after termination of infusion, with a half-life of 32-40 min. Neither repeated administration nor dose increases affected pharmacokinetic parameters. CONCLUSIONS: STZ may be a useful option for Japanese patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumors.

Feasibility and Efficacy of Endoscopic Ultrasound-Guided Hepaticogastrostomy Without Dilation: A Propensity Score Matching Analysis.

BACKGROUND: Recently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) procedures have been gradually established; nonetheless, some adverse events (AEs) have been reported. Dilation procedures using a non-cautery or cautery device increase the incidence of AEs in EUS-HGS. AIMS: We evaluated EUS-HGS procedures without dilation and the factors associated with dilation. METHODS: We enrolled 79 patients who underwent EUS-HGS between July 2015 and March 2021 at two centers, 72 of whom had technical success (72/79, 91%). During the EUS-HGS procedures, we defined patients without dilation procedures as the dilation (-) group. We divided the patients into two groups: the dilation (+) (35 patients) and dilation (-) (37 patients) groups. We performed a propensity score matching analysis to adjust for confounding bias between the two groups. Multivariable logistic regression analysis was conducted to identify factors associated with dilation. RESULTS: There was no difference in clinical success rate between the dilation (+) and dilation (-) groups (91% vs. 95%, P = 0.545). The AE rate (P = 0.013) and long procedure time (P = 0.017) were significantly higher in the dilation (+) group than in the dilation (-) group before and after propensity score matching. Factors associated with dilation were plastic stent placement (odds ratio [OR], 6.96; 95% confidence interval [CI], 1.68-28.7; P = 0.007) and puncture angle of ≤ 90° (OR, 44.6; 95% CI, 5.1-390; P < 0.001). CONCLUSIONS: A dilation procedure in EUS-HGS may not always be necessary. However, patients with an angle of ≤ 90° between the needle and intrahepatic biliary tract or plastic stent deployment require dilation procedures.

A clinical analysis on functioning pancreatic neuroendocrine tumors (focusing on VIPomas): a single-center experience.

VIPomas are generally rare functioning pancreatic neuroendocrine tumors (PanNETs) that cause watery diarrhea, hypokalemia, and achlorhydria. Due to their extreme rarity, the clinicopathological features and outcomes of VIPomas have not been well reported. This study aimed to determine the diagnostic and therapeutic characteristics and prognosis of VIPomas and to compare them with other PanNETs at a Japanese reference hospital. Medical records of 293 patients with PanNETs were collected. Patient and tumor characteristics and outcomes were retrospectively reviewed. This cohort had only 1.4% (four patients) of patients with VIPomas, and three of these patients changed from non-functioning (NF-) PanNETs during their disease course. Recurrences of hormonal symptoms were observed in all patients despite the initial controls, and all of them died from their disease, more specifically mainly from hormonal symptoms. Compared to the other PanNETs, VIPomas were all located at the pancreatic tail, were larger, and had a higher Ki-67 index and more metastasis. The median survival time was significantly shorter for patients with VIPoma than for those with NF-PanNET (5.9 vs. 26.7 years, p < 0.0001), insulinoma (21.8 years, p < 0.0001), and gastrinoma (12.3 years, p = 0.0325). This study presents the possibility of shifting from non-symptomatic to symptomatic VIPomas as they grow or of transforming from NF-PanNETs to VIPomas. VIPomas should be considered in patients with relatively large NF-PanNETs, especially those located in the pancreatic tail, when diarrhea is continuously observed. As hormonal symptoms are an important cause of death in VIPomas, long-term symptomatic control, which is relatively difficult, is of great significance.

Discriminant equation using mucosally expressed cytokines and transcription factor for making definite diagnosis of inflammatory bowel disease unclassified.

BACKGROUND: The pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC. METHODS: A total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis. RESULTS: Through discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively. CONCLUSIONS: The discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC.

Natural history and clinical outcomes of pancreatic neuroendocrine neoplasms based on the WHO 2017 classification; a single-center experience of 30 years.

BACKGROUND/OBJECTIVES: This single-center study aimed to evaluate treatment outcomes and long-term prognosis of patients with pancreatic neuroendocrine neoplasms (PanNENs) based on the World Health Organization (WHO) 2017 classification. METHODS: We enrolled 245 patients with PanNENs treated at Kyushu University Hospital between January 1987 and March 2018. PanNENs were categorized according to the WHO 2017 classification or further subdivisions of Ki-67 index. Clinicopathological features, median survival time (MST), and prognostic factors were retrospectively analyzed. RESULTS: The number of PanNENs, especially non-functioning PanNENs, has increased over the last decade. The mean MST of all patients was 202 months; which was longest in patients with NET G1 (n = 145, MST = 261 months) relative to NET G2 (n = 72, 132 months), NET G3 (n = 3, 34 months) and NEC G3 (n = 17, 9 months). Prognosis in patients with surgery as the first-line treatment was significantly better than in those with drug therapy. However, 26% of patients who underwent curative resection developed recurrence after a median time of 28.7 months. In unresectable PanNENs (n = 97), the MST and 5-year survival rate were 78 months and 55.8%, respectively. Poor differentiation, Ki-67 index of >10% and presence of liver metastasis were significant unfavorable predictors. Response to first-line therapy (stable disease/partial response) and three or more treatment regimens were significant favorable predictors for unresectable PanNENs according to multivariate analyses (p < 0.01). CONCLUSIONS: We demonstrated the utility of the WHO 2017 classification for PanNENs in the real clinical setting. For better prognosis in PanNENs, the use of three or more regimens should be considered.

[Fulminant type 1 diabetes mellitus following acute pancreatitis and hypoglycemia with sequential imaging of the pancreas using computed tomography: a case report].

We herein report a rare case of fulminant type 1 diabetes mellitus (FT1DM) following acute pancreatitis and hypoglycemia, in which the pancreas was evaluated by serial computed tomography (CT). A 30-year-old male presented to a local hospital with a two-day history of abdominal pain and was diagnosed with acute pancreatitis based on elevated serum amylase and peripancreatic fluid collection on CT images. The patient developed sudden hypoglycemia (plasma glucose, 45mg/dL;serum C-peptide, 3.4ng/mL) the next day and hyperglycemia (plasma glucose, 250-480mg/dL) on admission day four. CT revealed a low attenuation area extending from the pancreatic head to the pancreatic tail. On admission day eight, he was referred to our hospital and diagnosed with FT1DM after he developed ketoacidosis immediately after hospitalization, with a plasma glucose level of 442mg/dL, hemoglobin A1c concentration of 5.7% and undetectable urinary C-peptide with a serum C-peptide level of 0.1ng/mL before and after intravenous glucagon loading. CT imaging revealed dramatic improvement at the time, and no pancreatic islets were detected in the pancreatic biopsy specimens.

PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist.

There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic ß cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas.

A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats.

BACKGROUND: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti-fibrotic effect on the lungs, heart, and kidneys that is partly associated with the induction of hepatocyte growth factor (HGF). This study examined the anti-fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. METHODS: CP was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301-treated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28, we evaluated the histopathological CP score and mRNA expressions of HGF, cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and pancreas, respectively. The cytokine and collagen expressions of monocytes and PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by BrdU assay. RESULTS: Histopathological CP scores in vivo improved in the ONO-1301-treated group compared to the DBTC-treated group, particularly inflammatory cell infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased significantly after ONO-1301 administration, whereas IL-1ß, TNF-α, TGF-ß, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone. However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or collagen expression of PSCs. CONCLUSIONS: ONO-1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by ONO-1301 itself.

Large area of walled-off pancreatic necrosis successfully treated by endoscopic necrosectomy using a grasping-type scissors forceps.

Endoscopic necrosectomy (EN) for walled-off pancreatic necrosis (WOPN) is less invasive than surgical treatment and has become the first choice for pancreatic abscess. EN is usually carried out with several devices including snares, baskets, and grasping forceps. Occasionally, we have encountered cases in which EN has not been satisfactorily carried out, and there is pressure for further innovation in EN. Here, we describe a case of a large area of WOPN that was successfully treated by EN with endoscopic submucosal dissection and associated techniques, which facilitated removal of necrotic tissues. A 60-year-old man was referred to our hospital for WOPN as a complication of necrotizing pancreatitis. As a result of his complicating conditions including ischemic heart disease, uncontrollable arrhythmia, chronic renal failure, and persistent pleural effusion, he was deemed a poor surgical candidate. Although EN with conventional devices was carried out for five sessions, we could not remove the dense and massive necrotic tissues. At the sixth EN session, the Clutch Cutter device (Fujifilm, Tokyo, Japan) was used to remove the necrotic tissues, without major complications. This is believed to be the first report of EN using the Clutch Cutter for successful treatment of WOPN.

ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells.

The clinical course of chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) have an important role in the pathogenesis of alcoholic CP. Chemokines recruit inflammatory cells, resulting in chronic pancreatic inflammation. Although serum levels of fractalkine (CX3CL1) are significantly elevated in patients with alcoholic CP, the mechanism of this elevation remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 to 20 weeks were used as rodent models of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats. The effects of cytokines, PAMPs, and ethanol and its metabolites on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release and activated extracellular signal-regulated kinase (ERK), MMP-9, and ADAM17. CX3CL1 release was suppressed by specific inhibitors of ERK, MMP, and ADAM, and ERK was associated with CX3CL1 transcription. Ethanol and phorbol myristate acetate synergistically increased CX3CL1 release. Real-time PCR and western blotting confirmed the synergistic activation of ERK and ADAM17. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. In conclusion, we demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs at least in part through activation of ERK mitogen-activated protein kinase and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP.

Incidence and appropriate management of drug-induced interstitial lung disease in Japanese patients with unresectable pancreatic cancer: A multicenter retrospective study.

AIM: Drug-induced interstitial lung disease (DI-ILD) is a serious adverse event during chemotherapy. This study aimed to obtain real-world data of the incidence, clinical characteristics, predictive factors, and prognosis of patients with pancreatic cancer who developed DI-ILD. METHODS: In patients with locally advanced or metastatic pancreatic cancer who underwent standard chemotherapy at our hospital and its participating facilities between April 2014 and March 2019, the clinical features, occurrence rate and clinical course of DI-ILD, and prognosis were retrospectively evaluated. RESULTS: Altogether, 390 patients were finally enrolled. DI-ILD occurred in 24 cases (6.2%). The median period from diagnosis of pancreatic cancer to the onset of DI-ILD was 2.2 months (.6-13.3 months). The rate of DI-ILD onset according to each regimen was 5.8% of gemcitabine (GEM) plus albumin-bound paclitaxel therapy (18/308), 3.8% of GEM (4/106), and 2.3% of FOLFIRINOX (2/88). The incidence of DI-ILD in GEM-based regimens was significantly higher than that in non-GEM-based regimens (p < .01). The median overall survival (OS) of the patients with and without DI-ILD after propensity score matching was 11.5 months and 11.4 months (p = .99), respectively. After the resolution of DI-ILD, no statistical significance in the median OS of the patients with and without subsequent treatment (11.0 vs. 6.8 months, p = .18) was observed. CONCLUSION: DI-ILD is not a rare adverse event in the current standard chemotherapy for pancreatic cancer in Japan. With appropriate management of DI-ILD, the prognosis of patients with DI-ILD can be equivalent to that of patients without DI-ILD.

Machine learning-based model for prediction and feature analysis of recurrence in pancreatic neuroendocrine tumors G1/G2.

BACKGROUND: Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors. Although the prognosis of resected PanNENs is generally considered to be good, a relatively high recurrence rate has been reported. Given the scarcity of large-scale reports about PanNEN recurrence due to their rarity, we aimed to identify the predictors for recurrence in patients with resected PanNENs to improve prognosis. METHODS: We established a multicenter database of 573 patients with PanNENs, who underwent resection between January 1987 and July 2020 at 22 Japanese centers, mainly in the Kyushu region. We evaluated the clinical characteristics of 371 patients with localized non-functioning pancreatic neuroendocrine tumors (G1/G2). We also constructed a machine learning-based prediction model to analyze the important features to determine recurrence. RESULTS: Fifty-two patients experienced recurrence (14.0%) during the follow-up period, with the median time of recurrence being 33.7 months. The random survival forest (RSF) model showed better predictive performance than the Cox proportional hazards regression model in terms of the Harrell's C-index (0.841 vs. 0.820). The Ki-67 index, residual tumor, WHO grade, tumor size, and lymph node metastasis were the top five predictors in the RSF model; tumor size above 20 mm was the watershed with increased recurrence probability, whereas the 5-year disease-free survival rate decreased linearly as the Ki-67 index increased. CONCLUSIONS: Our study revealed the characteristics of resected PanNENs in real-world clinical practice. Machine learning techniques can be powerful analytical tools that provide new insights into the relationship between the Ki-67 index or tumor size and recurrence.

The feasibility of percutaneous transhepatic gallbladder aspiration for acute cholecystitis after self-expandable metallic stent placement for malignant biliary obstruction: a 10-year retrospective analysis in a single center.

BACKGROUND/AIMS: Patients with acute cholecystitis (AC) after metallic stent (MS) placement for malignant biliary obstruction (MBO) have a high surgical risk. We performed percutaneous transhepatic gallbladder aspiration (PTGBA) as the first treatment for AC. We aimed to identify the risk factors for AC after MS placement and the poor response factors of PTGBA. METHODS: We enrolled 401 patients who underwent MS placement for MBO between April 2011 and March 2020. The incidence of AC was 10.7%. Of these 43 patients, 37 underwent PTGBA as the first treatment. The patients' responses to PTGBA were divided into good and poor response groups. RESULTS: There were 20 patients in good response group and 17 patients in poor response group. Risk factors for cholecystitis after MS placement included cystic duct obstruction (p<0.001) and covered MS (p<0.001). Cystic duct obstruction (p=0.003) and uncovered MS (p=0.011) demonstrated significantly poor responses to PTGBA. Cystic duct obstruction is a risk factor for cholecystitis and poor response factor for PTGBA, whereas covered MS is a risk factor for cholecystitis and an uncovered MS is a poor response factor of PTGBA for cholecystitis. CONCLUSION: The onset and poor response factors of AC after MS placement were different between covered and uncovered MS. PTGBA can be a viable option for AC after MS placement, especially in patients with covered MS.