Diagnostic performance and safety of endoscopic ultrasound-guided fine-needle aspiration/biopsy for gallbladder lesions.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration and fine-needle biopsy (EUS-FNA/FNB) is not fully established as a pathological sampling tool for gallbladder lesions due to limited evidence. We therefore aimed to clarify the effectiveness and safety of this procedure in a large-population cohort. METHODS: This study retrospectively evaluated the diagnostic yield of EUS-FNA/FNB for accurately differentiating between benign and malignant gallbladder lesions. Puncture targets included the gallbladder mass, lymph node, and liver mass. Adverse events and factors associated with diagnostic accuracy were analyzed as well. RESULTS: In 187 patients with gallbladder lesions undergoing EUS-FNA/FNB, 18 benign lesions and 169 malignant lesions were identified. Overall sampling adequacy was 98% (184/187). The diagnostic accuracy of EUS-FNA/FNB was 97% (182/187), sensitivity was 97% (164/169), and specificity was 100% (18/18). A single postprocedural complication (minor bleeding) was recorded in one patient. In the 169 cases of malignancy, 203 sites were punctured for pathological sampling of the primary mass (n = 94), lymph node (n = 79), and metastatic liver mass (n = 30). No significant difference was found for diagnostic accuracy among the puncture sites (P = 0.70). In cases having specimens obtained from the primary mass, the accuracy of those targeting liver invasion sites was significantly higher than that of other sites (98% vs. 83%, P < 0.01). CONCLUSION: EUS-FNA/FNB demonstrated clinical usefulness and safety for the pathological diagnosis of gallbladder lesions, with high diagnostic yield and a low incidence of adverse events. Targeting the site of liver infiltration may improve the diagnostic rate of EUS-FNA/FNB in the primary mass.

Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses.

BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.

Comprehensive review of undifferentiated carcinoma of the pancreas: from epidemiology to treatment.

Undifferentiated carcinoma (UC) of the pancreas is a rare subtype of pancreatic cancer displaying no definitive direction of differentiation. UC has been reported as a highly aggressive malignant neoplasm, with a median overall survival of <1 year, except for several surgical series. On the other hand, UC tissue sometimes contains non-neoplastic osteoclast-like giant cells (OGCs), and such cases have been reported to have relatively longer survival. Thus, the World Health Organization (WHO) classification histologically distinguishes UC with OGCs (UCOGCs) from UC, and UCs were subclassified into three subtypes: anaplastic UC, sarcomatoid UC and carcinosarcoma. However, still less is known about UC due to its rarity, and such situations lead to further difficulties in treatment for UC. To date, only surgical resection can offer curative treatment for patients with UC, and no clear evidence for chemotherapy exists for them. However, a retrospective cohort study and case reports showed that relatively promising results paclitaxel-containing regimens for treatment of patients with unresectable UC. Furthermore, high programmed cell death protein 1 expression has been reported in sarcomatoid UCs and UCOGCs, and promising responses to anti-programmed death-ligand 1 therapy have been described in case reports of UCOGCs. Recent advances in chemotherapeutic agents and molecular technologies are opening up the possibilities for expanded treatments.

Novel drill dilator facilitates endoscopic ultrasound-guided hepaticogastrostomy.

Tract dilation is one of the most difficult stages of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), especially for beginners. To overcome this problem, we applied a special dedicated dilator. Herein, we retrospectively evaluate the safety and usefulness of a novel drill dilator in EUS-HGS. This single-center retrospective study included 20 consecutive patients who underwent EUS-HGS with a novel drill dilator. The tip is 0.77 mm, and it becomes 7F at 3 cm from tip. The track is dilated to 7F by simple clockwise rotation. The technical success rate of both initial tract dilation and stent placement was 20/20 (100%). No cases required additional dilation such as balloon or electric cautery. In 13/20 cases (65.0%), EUS-HGS was performed by beginner endoscopists. Median time required for dilation was 62.5 s (range, 30-144 s). Median procedure time was 13 min (range, 7-25 min). Early adverse events were two cases of mild fever. There was no bile leakage or bleeding. The novel drill dilator appears to be safe and useful for EUS-HGS. As it is not necessary to press the device strongly, there is no pushback during dilation and the scope position is stable. These characteristics facilitate EUS-HGS even for beginners. This device may enable the further development and increased dissemination of EUS intervention.

Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

Clinical and microbiological features of intratumor abscess with bloodstream infection caused by Plesiomonas shigelloides, Citrobacter freundii, Streptococcus mitis/oralis, Clostridium perfringens, and Candida albicans in a patient with cholangiocarcinoma: A case report.

Plesiomonas shigelloides is a gram-negative facultative anaerobic bacillus, usually found in soil and freshwater, which causes self-limited diarrhea, although reports of bacteremia are rare. Here, we report the first case of an intratumoral abscess with mixed bacteremia caused by P. shigelloides, Citrobacter freundii, Streptococcus mitis/oralis, Clostridium perfringens, and Candida albicans in a patient with recurrent postoperative cholangiocarcinoma. A 77-year-old man with hilar cholangiocarcinoma and hypertension was admitted to our hospital with fever and abdominal pain. He had visited Vietnam for 3 years, 20 years ago. Abdominal computed tomography showed air within the recurrent tumor at the left liver lobectomy resection margin site, which was diagnosed as an intratumor abscess perforating the intestinal tract. P. shigelloides, C. freundii, S. mitis/oralis, C. perfringens, and C. albicans were isolated in blood culture. P. shigelloides was identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and 16S ribosomal RNA (16S rRNA) sequencing. Piperacillin-tazobactam was administered for almost a week, ampicillin-sulbactam and levofloxacin for almost 3 weeks, and antifungal agents for almost 2 weeks, and the patient was discharged thereafter. Although bloodstream infections caused by P. shigelloides in patients with cancer are extremely rare, long-term colonization and the potential for future intra-abdominal infections were implicated.

Current status of artificial intelligence analysis for endoscopic ultrasonography.

Endoscopic ultrasonography (EUS) is an essential diagnostic tool for various types of pancreatic diseases such as pancreatic tumors and chronic pancreatitis; however, EUS imaging has low specificity for the diagnosis of pancreatic diseases. Artificial intelligence (AI) is a mathematical prediction technique that automates learning and recognizes patterns in data. This review describes the details and principles of AI and deep learning algorithms. The term AI does not have any definite definition; almost all AI systems fall under narrow AI, which can handle single or limited tasks. Deep learning is based on neural networks, which is a machine learning technique that is widely used in the medical field. Deep learning involves three phases: data collection and annotation, building the deep learning architecture, and training and ability validation. For medical image diagnosis, image classification, object detection, and semantic segmentation are performed. In EUS, AI is used for detecting anatomical features, differential pancreatic tumors, and cysts. For this, conventional machine learning architectures are used, and deep learning architecture has been used in only two reports. Although the diagnostic abilities in these reports were about 85-95%, these were exploratory research and very few reports have included substantial evidence. AI is increasingly being used for medical image diagnosis due to its high performance and will soon become an essential technique for medical diagnosis.

Usefulness of endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of autoimmune pancreatitis using a 22-gauge Franseen needle: a prospective multicenter study.

BACKGROUND: Detailed histological evaluation is important in the diagnosis of autoimmune pancreatitis (AIP). However, it remains challenging to obtain adequate tissue from the pancreas. Recently, several reports have suggested the usefulness of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using the new "core" needles for acquiring pancreatic tissue. We aimed to investigate the usefulness of EUS-FNB for diagnosing AIP with one such needle, a 22-gauge Franseen needle. METHODS: Patients who met the imaging diagnostic criteria for AIP based on the International Consensus Diagnostic Criteria (ICDC) were enrolled in the study. All patients underwent EUS-FNB with a 22-gauge Franseen needle. Histological findings were evaluated based on the ICDC, and the detection rates of level 1 and level 1 or 2 histology were calculated. RESULTS: 56 patients from 11 different institutions were enrolled in the final analysis (55 suspected to have type 1 AIP and one with type 2 AIP). Lymphoplasmacytic infiltration, obliterative phlebitis, storiform fibrosis, and > 10 IgG4-positive cells per high-power field were detected in 55 (100 %), 24 (43.6 %), 40 (72.7 %), and 36 (65.5 %) of the 55 patients, respectively. The detection rates of level 1 and level 1 or 2 histology for AIP were 58.2 % (95 % confidence interval [CI] 44.1 % - 71.3 %) and 92.7 % (95 %CI 82.4 % - 98.0 %), respectively, which were apparently higher than our historical results (7.9 % [95 %CI 1.7 % - 21.4 %] and 62.2 % [95 %CI 46.5 % - 76.2 %], respectively) using a conventional needle. CONCLUSIONS: EUS-FNB with a 22-gauge Franseen needle demonstrated favorable detection rates which would be clinically beneficial for the histological diagnosis of AIP.

Risk factor analysis for adverse events and stent dysfunction of endoscopic ultrasound-guided choledochoduodenostomy.

BACKGROUND AND AIMS: Although the technique of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is becoming standardized, its safety issues have not been sufficiently investigated. Therefore, we aimed to identify factors associated with adverse events and stent patency in EUS-CDS. METHODS: Consecutive patients who underwent EUS-CDS between September 2003 and July 2017 were included. Technical/clinical success, adverse events and stent dysfunctions were analyzed retrospectively. RESULTS: A total of 151 patients underwent EUS-CDS. In nine patients, procedures were discontinued before puncture. Technical and clinical success rates were 96.5% (137/142) and 98.5% (135/137), respectively. The adverse event rate was 20.4% (29/142). As a risk factor for peritonitis, plastic stents (PS) showed a significantly high odds ratio (OR) compared with covered self-expandable metal stents (CSEMS; OR, 4.31; P = 0.030). CSEMS cases showed a significantly longer patency period than PS cases (329 vs 89 days; HR, 0.35; P < 0.001). As a risk factor for early stent dysfunction (within 14 days), stent direction to the oral side showed a significantly high OR (OR, 43.47; P < 0.001). In cases with oblique-viewing EUS, double penetration of the duodenum occurred at significantly higher frequency than in cases with forward-viewing EUS (7.0 vs 0.0%; P = 0.024). CONCLUSIONS: Plastic stents and stent direction to the oral side were risk factors for peritonitis and early stent dysfunction, respectively. Using covered self-expandable metal stents and changing stent direction to the anal side seemed appropriate to prevent peritonitis and early stent dysfunction.

Features of chronic pancreatitis by endoscopic ultrasound influence the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration of small pancreatic lesions.

BACKGROUND AND AIM: In chronic pancreatitis (CP) patients, diagnosis of small pancreatic lesions by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is challenging. Thus, the aim of the present study was to investigate whether CP influences the diagnostic ability of EUS-FNA for pancreatic lesions ≤10 mm. METHODS: One hundred and seventeen patients who underwent EUS-FNA for pancreatic lesions ≤10 mm in size were enrolled. Patients were classified into two groups based on features of CP observed by EUS (EUS-CP features) in accordance with the Rosemont classification. The CP group was defined as cases consistent with CP or suggestive of CP, and the non-CP group was defined as cases indeterminate for CP or normal. Factors influencing the diagnostic accuracy of EUS-FNA and CP status in pancreatic tumors were also investigated. RESULTS: Diagnostic ability of EUS-FNA (overall cases, non-CP vs CP) had sensitivity (80.4%, 96.7% vs 57.1%; P < 0.001), specificity (100%, 100% vs 100%; P > 0.05), and accuracy (91.5%, 98.6% vs 80.4%; P = 0.001). In multivariate analysis of factors influencing the accuracy of EUS-FNA, CP significantly lowered the accuracy (P = 0.048; odds ratio [OR] = 9.21). Among pancreatic cancer patients, the number of CP patients was significantly higher than the number of patients with benign lesions (P = 0.023). In multivariate analysis, lobularity without honeycombing was more frequently observed in cases of pancreatic cancer (P = 0.018; OR, 12.65). CONCLUSION: Endoscopic ultrasound-guided FNA offers high accuracy for small pancreatic lesions ≤10 mm. However, in cases with CP, the diagnostic ability of EUS-FNA is significantly reduced.

Usefulness of septal thickness measurement on endoscopic ultrasound as a predictor of malignancy of branched-duct and mixed-type intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND AND AIM: Septal thickness (ST) can predict a malignant branch-duct (BD) and mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas, but its cut-off value has not been established. The aim of the present study was to determine the optimal ST cut-off value to predict malignancy using endoscopic ultrasound (EUS). METHODS: We retrospectively identified 200 patients with IPMN, including 132 with BD- and mixed-IPMN, who underwent surgical resection between 1989 and 2017. ST was defined as the septum or lesion wall with the maximum diameter in BD- and mixed-IPMN. The possibility of ST as a malignant predictor was examined, as well as the diagnostic ability of ST combined with mural nodule (MN) height for malignant IPMN. RESULTS: Among the 132 IPMN patients, pathological diagnosis was benign in 81 (61.4%) and malignant in 51 (38.6%). Area under the curve for the diagnosis of malignancy using ST was 0.74 for pathological specimens, 0.70 for EUS and 0.56 for computed tomography. Multivariate analysis showed that the odds ratios for ST ≥2.5 mm and MN height ≥5 mm were 3.51 [95% confidence interval (CI), 1.55-7.97, P = 0.003] and 3.36 (95% CI, 1.52-7.45, P = 0.003), respectively. CONCLUSIONS: Septal thickness was an independent predictive factor similar to MN height for malignant IPMN in a multivariate analysis. The ST on EUS appeared to be the thickness of a fibrotic septum associated with the malignant transformation of IPMN. An ST cut-off value of 2.5 mm might provide an accurate prediction of malignant IPMN.

Comparison of 8- and 10-mm diameter fully covered self-expandable metal stents: A multicenter prospective study in patients with distal malignant biliary obstruction.

OBJECTIVES: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self-expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8- and 10-mm diameter FCSEMS. METHODS: Eighteen tertiary-care centers participated in the study. Patients were allocated to the 8- and 10-mm diameter groups. TRBO, non-inferiority of the 8-mm FCSEMS, overall survival time, frequency and type of adverse events, and non-recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. RESULTS: Median TRBO did not differ significantly between the 8-mm (n = 102) and 10-mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8- to 10-mm groups was 0.90 (80% confidence interval, 0.77-1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8-mm diameter stent was determined to be non-inferior to the 10-mm diameter stent. Survival time, incidence of adverse events and non-RBO rate at the time of death did not differ significantly between the two groups. CONCLUSIONS: Time to RBO with an 8-mm diameter FCSEMS was non-inferior to that with a 10-mm diameter FCSEMS. This finding is important for development of future SEMS.

Efficacy of the 6-mm fully covered self-expandable metal stent during endoscopic ultrasound-guided hepaticogastrostomy as a primary biliary drainage for the cases estimated difficult endoscopic retrograde cholangiopancreatography: A prospective clinical study.

BACKGROUND AND AIM: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is performed as an alternative to the percutaneous or surgical approach. Despite high success rates, the adverse events rate is high. Recently, we used 6-mm fully covered self-expandable metal stents to prevent adverse events and allow easy re-intervention. The purposes were to evaluate the safety, feasibility, and clinical efficacy. METHODS: A prospective study to confirm the safety of EUS-HGS was carried out in six patients, followed by a trial to evaluate the feasibility and efficacy of EUS-HGS in approximately 12 additional patients. We permitted a total of 18 to 20 patients in consideration of possibility such as the deviation after providing informed consent. RESULTS: Twenty patients underwent EUS-HGS. No treatment-related adverse events described in the safety assessment criteria were seen. The technical and clinical success rates were 100% and 95%. The adverse event rate was 15%. Focal cholangitis was seen in two patients and fever in one patient. All cases were treated conservatively. Stent dysfunction was seen in 10 patients. The causes of stent dysfunction were biliary sludge (n = 6) and stent dislocation (n = 4). In nine cases, a new stent was easily inserted. Percutaneous drainage was selected in only one patient because of worsening general condition. CONCLUSIONS: The 6-mm fully covered self-expandable metal stent is safe and effective, especially for avoiding serious adverse events and allowing easy re-intervention. (UMIN000006785).

Usefulness of shear wave elastography as a quantitative diagnosis of chronic pancreatitis.

BACKGROUND AND AIM: Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria is based on subjective judgment. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and noninvasive method for the diagnosis of CP. METHODS: Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into four stages using Rosemont classification and into three stages using Japan Pancreas Society clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM). RESULTS: Pancreatic elastic modulus was significantly positively correlated with Rosemont classification stage (rs  = 0.54), Japan Pancreas Society stage (rs  = 0.41), and the number of EUS features (rs  = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM. CONCLUSIONS: Chronic pancreatitis may be diagnosed noninvasively and objectively using SW-EG without performing EUS.