Impact of non-obese metabolic dysfunction-associated fatty liver disease on risk factors for the recurrence of esophageal squamous cell carcinoma treated with endoscopic submucosal dissection: A multicenter study.

AIM: Metabolic dysfunction is a risk factor for esophageal squamous cell carcinoma (ESCC). We investigated the impact of the recently proposed metabolic dysfunction-associated fatty liver disease (MAFLD) and its subtypes on ESCC recurrence after endoscopic treatment. METHODS: This multicenter observational cohort study enrolled consecutive patients newly diagnosed with ESCC after endoscopic treatment. Patients were classified into MAFLD or non-MAFLD groups. The MAFLD group was further classified into non-obese and obese MAFLD groups with a body mass index cutoff value of 25 kg/m2 . The impact of MAFLD on the recurrence of ESCC was evaluated using a decision tree algorithm and random forest analysis. RESULTS: A total of 147 patients (average age 69 years; male : female, 127:20; observational period, 2.4 years) were enrolled. The 1-, 3-, and 5-year recurrence rates were 2.0%, 21.1%, and 33.7%, respectively. Independent risk factors for the recurrence of ESCC were MAFLD (HR 2.2812; 95% confidence interval 1.0497-4.9571; p = 0.0373), drinking status, and smoking status. Metabolic dysfunction-associated fatty liver disease was identified as the second most important classifier for recurrence, followed by drinking status. The cumulative incidence of ESCC recurrence was higher in the MAFLD group than in the non-MAFLD group. In a subanalysis, the cumulative incidence of recurrence was significantly higher in the non-obese than in the obese MAFLD group among abstainers/non-drinkers. Directed acyclic graphs revealed that MAFLD directly contributes to ESCC recurrence. CONCLUSIONS: MAFLD was independently and directly associated with ESCC recurrence after endoscopic treatment; a high recurrence rate was observed in patients with non-obese MAFLD. Metabolic dysfunction-associated fatty liver disease may identify patients at high risk for ESCC recurrence.

Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer.

AIM: The incidence of Helicobacter pylori-negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD. METHODS: This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision-tree algorithm and random forest analysis. RESULTS: Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451-16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32). CONCLUSIONS: Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer.

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27-0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58-1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

A Significant Increase in the Serum Carbohydrate Antigen 19-9 Level Accompanied by Acute Cholecystitis and Choledocholithiasis: A Case Report and Review of the Literature.

An 80-year-old man with jaundice and fatigue was referred to our hospital. A laboratory examination revealed increased levels of hepatobiliary enzymes, and CA19-9 levels increased to 29,512 U/mL. Based on the findings of imaging examination and laboratory data, the patient was diagnosed with acute cholecystitis and choledocholithiasis. The possibility of malignancy could not be ruled out because of the high levels of CA19-9. Antibiotic administration was commenced, and the common bile duct stone was endoscopically removed. One month after treatment, the CA19-9 level decreased to within the normal range. One year after treatment, imaging examinations did not reveal any malignancy.

KRAS Mutation Analysis Using Cell-free DNA of Pancreatic Cancer.

BACKGROUND/AIM: Detection of pancreatic cancer using small samples of the pancreas obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) remains a challenge. The purpose of this study was to investigate whether the detection of KRAS mutations in cell-free DNA (cfDNA) extracted from supernatants of liquid-based fixed cytology (LBC) specimens obtained using EUS-FNA in solid pancreatic cancer can be an auxiliary test for differential diagnosis. The purpose of this study was to investigate whether the detection of KRAS mutations in cell-free DNA (cfDNA) extracted from supernatants of liquid-based fixed cytology (LBC) specimens obtained using EUS-FNA in solid pancreatic cancer can be an auxiliary test for differential diagnosis. PATIENTS AND METHODS: This was a single-institution cohort study that included 50 patients with pancreatic lesions. cfDNA was isolated from the supernatant of fixed LBC samples, and KRAS mutation status was compared between cfDNA samples and FFPE small fragment tissues. RESULTS: Of the 50 cfDNA samples, 84% (42/50) were valid. KRAS mutations were detected in 57.1% (24/42) of the 42 valid samples. The sensitivity, specificity, and accuracy of KRAS mutation detection using cfDNA samples in the pancreatic lesions were 63.2% (24/38), 100.0% (4/4), and 66.7% (28/42), respectively. KRAS mutation status between FFPE small tissues and cfDNA samples were comparable. CONCLUSION: Gene mutation analysis using cfDNA from the supernatant of fixed LBC samples is an effective ancillary diagnostic tool for pancreatic cancer.

Lymph node metastatic status could predict the prognosis of intracholecystic papillary neoplasm of gallbladder.

Intracholecystic papillary neoplasm (ICPN) is a non-invasive epithelial tumor that presents as a grossly identifiable mass arising in the mucosa and protruding into the lumen. ICPN is associated with invasive carcinoma. There are few studies on the clinicopathological features of ICPN, including that with invasive carcinoma. We evaluated the clinicopathological characteristics of 42 ICPNs and 41 conventional gallbladder adenocarcinomas (cGBAs). Subserosa or deeper (≥ss) invasion was significantly lower in ICPN (61.9%) than that in cGBA (90.2%) (P = 0.004). Cox regression analysis revealed that lymph node metastasis (hazard ratio [HR] [95% confidence interval (CI)]: 2.610 [1.131, 6.024], P = 0.025) and positive margin (HR [95% CI]: 5.143 [2.113, 12.516], P < 0.001), but not ≥ss invasion (HR [95% CI]: 1.541 [0.479, 4.959], P = 0.469), were independent prognostic factors. In addition, there was a significant interaction between histological type and lymph node metastasis (HR [95% CI]: 0.191 [0.042, 0.983], P = 0.033). In cGBA, the presence or absence of lymph node metastasis did not affect prognosis; however, ICPN without lymph node metastasis had better prognosis. Therefore, the histological classification of ICPN and cGBA and the pathological evaluation of lymph node metastasis in ICPN are crucial for determining prognosis.

Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study.

BACKGROUND: Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have few treatment options. It is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine + nab-PTX (GnP) or FOLFIRINOX. METHODS: This analysis was conducted as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with metastatic pancreatic cancer. Excluding censored cases, 156 and 77 patients, respectively, received second-line chemotherapy (CTx) and best supportive care (BSC). Using prognostic factors for post-discontinuation survivals (PDSs) at the first-line determination in multivariate analysis, we developed a scoring system to demonstrate the benefit of second-line CTx. RESULTS: The second-line CTx group had a median PDS of 5.2 months, whereas the BSC group had a median PDS of 2.7 months (hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01). According to the Cox regression model, serum albumin levels below 3.5 g/dL, and CA19-9 levels above 1000 U/mL were independent prognostic factors (p < 0.01). Serum albumin (≥ and < 3.5 g/dL allotted to scores 0 and 1) and CA19-9 (< and ≥ 1000 U/mL allotted to scores 0 and 1) at first-line determination were used to develop the scoring system. The PDSs of patients with scores of 0 and 1 were significantly better than those of the BSC group; however, there was no significant difference between the PDSs of patients with score 2 and the BSC group. CONCLUSION: The survival advantage of second-line CTx, was observed in patients with scores of 0 and 1 but not in those with score 2.

Prognostic Factors for Distal Bile Duct Carcinoma After Surgery.

BACKGROUND: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma. METHODS: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses. RESULTS: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance. CONCLUSION: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

Predictive and Prognostic Value of SUOX Expression in Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Sulphite oxidase (SUOX) is a metalloenzyme that catalyses ATP synthesis via oxidative phosphorylation in the mitochondria. Although SUOX has been reported to affect the invasiveness and differentiation of cancer cells, its clinicopathological significance in pancreatic adenocarcinoma (PDAC) remains unclear. In this study, we investigated the utility of SUOX expression as a prognostic factor in PDAC. PATIENTS AND METHODS: This study included 56 patients with PDAC who underwent pancreatic resection at the Kurume University Hospital between 2014 and 2018. SUOX immunohistochemistry was evaluated using tissue microarray specimens from patients. Patients were classified into a high SUOX expression group (≥10% of cells stained) or a low SUOX expression group (<10% of cells stained), and the associations of SUOX with clinicopathological characteristics and survival were analysed. Statistical analysis was performed using Cox regression analysis, the Kaplan-Meier method, and log-rank test. RESULTS: SUOX was expressed in the cytoplasm of normal pancreatic ductal epithelium, pancreatic acinar cells, and islets of Langerhans. Although we did not find any significant correlation between SUOX expression and clinicopathological factors, SUOX was identified as an independent prognostic factor based on univariate and multivariate analyses. Pathological stage was also an independent prognostic factor. The high SUOX expression group showed a significantly poorer prognosis than the low SUOX expression group (p=0.018). CONCLUSION: SUOX-mediated mitochondrial metabolism in PDAC may be a factor influencing prognosis and SUOX may be a potential novel prognostic biomarker.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

SUOX and GLUT1 are biomarkers for the prognosis in large duct type intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignant disease and has a poor prognosis, but few biomarkers have been found. SUOX is an important factor in energy metabolism and a poor prognostic factor in other malignancies. In this study, we aimed to clarify the relationship between SUOX and GLUT expression in large duct type iCCA and the mechanism of mitochondrial energy metabolism in iCCA. We evaluated SUOX and GLUT1 expression in 96 large duct type iCCA cases and proportion score (PS) was used to evaluate the expression; receiver operating characteristic (ROC) curves of both SUOX and GLUT1 expression were generated, and the Kaplan-Meier method and Cox regression analysis were used to estimate overall survival. Of the 96 iCCA cases, 73 (76.0%) showed low SUOX expression and 66 (68.8%) showed high GLUT1 expression. The 5-year survival rate of iCCA with low SUOX expression was significantly shorter than that of iCCA with high SUOX expression (p = 0.001). In contrast, the 5-year survival rate of iCCA with high GLUT1 expression was significantly shorter than that of iCCA with low GLUT1 expression (p = 0.005). According to Spearman's correlation, there was no correlation between SUOX and GLUT1. Conversely, the combination of low SUOX and high GLUT1 expression was the most common in 51 of 96 cases (53.1%), and the overall survival was significantly shorter than that of patients with other combinations. Furthermore, SUOX was shown to be an independent prognostic factor together with GLUT1, suggesting that SUOX in combination with GLUT1 can predict the prognosis of large duct type iCCA.

Vascular/perivascular inflammation in IgG4-related disease.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is characterized by the infiltration of IgG4-positive plasma cells and fibrosclerotic inflammation in multiple organs. Although vascular complications are present in some patients with IgG4-RD, vascular and/or perivascular inflammatory activity compared to control subjects remains unknown. This study sought to investigate vascular/perivascular inflammation in IgG4-RD patients compared to control subjects using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography (FDG-PET/CT). METHODS: We examined 37 consecutive patients diagnosed as IgG4-RD (29 males, mean age of 64.3 ± 8.3 years old), who underwent FDG-PET/CT. Thirty-seven age- and gender-matched subjects without IgG4-RD were employed as controls. Vascular/perivascular inflammation was quantified by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). RESULTS: All IgG4-RD patients presented with multiple region involvements. Twelve (32.4%) of the IgG4-RD patients had vascular complications, all of which appeared in the abdominal aorta. IgG4-RD patients had significantly higher TBR values in the descending aorta, abdominal aorta, and common iliac artery than control subjects. Also, IgG4-RD patients with vascular complication exhibited higher TBR values in the infra-renal aorta and common iliac artery than those without vascular complication. CONCLUSIONS: We found that vascular FDG activity is significantly elevated in IgG4-RD patients regardless of vascular complication than control subjects. FDG-PET/CT is a useful modality for assessing vascular/perivascular inflammation, which may contribute vascular complication in IgG4-RD patients.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Fully covered metal stents vs plastic stents for preoperative biliary drainage in patients with resectable pancreatic cancer without neoadjuvant chemotherapy: A multicenter, prospective, randomized controlled trial.

BACKGROUND/PURPOSE: Whether a fully covered self-expanding metal stent (FCSEMS) or plastic stent (PS) is preferable for preoperative biliary drainage in patients with resectable pancreatic cancer (RPC) is controversial. This study aimed to evaluate the safety and efficacy of drainage with FCSEMS for obstructive jaundice caused by RPC without neoadjuvant chemotherapy. METHODS: Seventy patients with RPC who required preoperative biliary drainage were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was endoscopic re-intervention rate during the waiting period for surgery. Secondary endpoints were drainage procedure time, drainage-related adverse events (AE), waiting period for surgery, operative time, intraoperative blood loss, surgery-related AE, and postoperative hospital stay. RESULTS: Thirty-nine patients underwent surgery. None required re-intervention in the FCSEMS group, whereas five PS patients underwent re-intervention (P = .023). The FCSEMS group had significantly more intraoperative blood loss (P = .0068) and AE (P = .011) than the PS group. Postoperative hospital stay was significantly longer in the FCSEMS group (P = .016). CONCLUSIONS: Fully covered self-expanding metal stent had a lower rate of endoscopic re-intervention during the waiting period for surgery than PS, but showed more intraoperative blood loss, higher incidence of surgery-related AE, and longer postoperative hospital stays.

Diagnostic Categories and Key Features for Pathological Diagnosis of Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy Samples of Pancreatic Lesions: A Consensus Study.

OBJECTIVES: This study aimed to establish a reliable and reproducible categorized diagnostic classification system with identification of key features to achieve accurate pathological diagnosis of endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) samples of pancreatic lesions. METHODS: Twelve pathologists examined virtual whole-slide images of EUS-FNAB samples obtained from 80 patients according to proposed diagnostic categories and key features for diagnosis. Fleiss κ was used to assess the concordance. RESULTS: A hierarchical diagnostic system consisting of the following 6 diagnostic categories was proposed: inadequate, nonneoplasm, indeterminate, ductal carcinoma, nonductal neoplasm, and unclassified neoplasm. Adopting these categories, the average κ value of participants was 0.677 (substantial agreement). Among these categories, ductal carcinoma and nonductal neoplasm showed high κ values of 0.866 and 0.837, respectively, which indicated the almost perfect agreement. Key features identified for diagnosing ductal carcinoma were necrosis in low-power appearance; structural atypia/abnormalities recognized by irregular glandular contours, including cribriform and nonuniform shapes; cellular atypia, including enlarged nuclei, irregular nuclear contours, and foamy gland changes; and haphazard glandular arrangement and stromal desmoplasia. CONCLUSIONS: The proposed hierarchical diagnostic classification system was proved to be useful for achieving reliable and reproducible diagnosis of EUS-FNAB specimens of pancreatic lesions based on evaluated histological features.

A Prospective Multicenter Study of "Inside Stents" for Biliary Stricture: Multicenter Evolving Inside Stent Registry (MEISteR).

BACKGROUND: Endoscopic biliary stent placement is the standard of care for biliary strictures, but stents across the papilla are prone to duodenobiliary reflux, which can cause stent occlusion. Preliminary studies of "inside stents" placed above the papilla showed encouraging outcomes, but prospective data with a large cohort were not reported. METHODS: This was a prospective multicenter registry of commercially available inside stents for benign and malignant biliary strictures. Primary endpoint was recurrent biliary obstruction (RBO). Secondary endpoints were technical success of stent placement and removal, adverse events, and stricture resolution. RESULTS: A total of 209 inside stents were placed in 132 (51 benign and 81 malignant) cases with biliary strictures in 10 Japanese centers. During the follow-up period of 8.4 months, RBO was observed in 19% of benign strictures. The RBO rate was 49% in malignant strictures, with the median time to RBO of 4.7 months. Technical success rates of stent placement and removal were both 100%. The adverse event rate was 8%. CONCLUSION: This prospective multicenter study demonstrated that inside stents above the papilla were feasible in malignant and benign biliary strictures, but a randomized controlled trial is warranted to confirm its superiority to conventional stents across the papilla.

A phase II study of gemcitabine plus nab-paclitaxel as first-line therapy for locally advanced pancreatic cancer.

ABSTRACT: Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety.We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable.The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.

A deep learning model to detect pancreatic ductal adenocarcinoma on endoscopic ultrasound-guided fine-needle biopsy.

Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.