Stereomicroscopic on-site evaluation in endoscopic ultrasound-guided tissue acquisition of upper gastrointestinal subepithelial lesions.

BACKGROUND/AIMS: In stereomicroscopic sample isolation processing, the cutoff value (≥4 mm) of stereomicroscopically visible white cores indicates high diagnostic sensitivity. We aimed to evaluate endoscopic ultrasound-guided tissue acquisition (EUS-TA) using a simplified stereomicroscopic on-site evaluation of upper gastrointestinal subepithelial lesions (SELs). METHODS: In this multicenter prospective trial, we performed EUS-TA using a 22-gauge Franseen needle in 34 participants with SELs derived from the upper gastrointestinal muscularis propria, requiring pathological diagnosis. The presence of stereomicroscopically visible white core (SVWC) in each specimen was assessed using stereomicroscopic on-site evaluation. The primary outcome was EUS-TA's diagnostic sensitivity with stereomicroscopic on-site evaluation based on the SVWC cutoff value (≥4 mm) for malignant upper gastrointestinal SELs. RESULTS: The total number of punctures was 68; 61 specimens (89.7%) contained stereomicroscopically visible white cores ≥4 mm in size. The final diagnoses were gastrointestinal stromal tumor, leiomyoma, and schwannoma in 76.5%, 14.7%, and 8.8% of the cases, respectively. The sensitivity of EUS-TA with stereomicroscopic on-site evaluation based on the SVWC cutoff value for malignant SELs was 100%. The per-lesion accuracy of histological diagnosis reached the highest level (100%) at the second puncture. CONCLUSION: Stereomicroscopic on-site evaluation showed high diagnostic sensitivity and could be a new method for diagnosing upper gastrointestinal SELs using EUS-TA.

New image-processing technology for endoscopic ultrasound-guided fine-needle aspiration biopsy specimen evaluation in patients with pancreatic cancer.

Objectives: We evaluated the usefulness of a newly developed system with which the total amount of whitish cores in endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) samples is automatically calculated (automated multiband imaging system [AMUS]). Methods: From 30 prospectively enrolled patients suspected of having pancreatic cancer, four EUS-FNAB specimens per patient were obtained. Following AMUS calculations, two specimens were prepared after stereomicroscopy-guided manual division into whitish and reddish sections (isolation group), and the other two were prepared without such division (no-isolation group). The relation of the AMUS results pertaining to the length of the manually measured whitish cores (stereo-microscopically visible white core [SVWC]) and the sample suitability for pathologic evaluation were analyzed. Results: Histological diagnostic accuracy was 90%; median SVWC length, 14 mm; and median area of whitish core calculated using the AMUS, 13 mm2. The SVWC length correlated with whitish core amount (ρ = 0.83, p < 0.01) and adequacy score (ρ = 0.50, p < 0.01). The whitish core amount correlated with the adequacy score (ρ = 0.40, p < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.84 (p < 0.01; cutoff ≥ 8 mm2, sensitivity 92.5%). Subgroup analysis (isolation vs. no-isolation group) revealed no significant between-group differences in the median histological adequacy (p = 0.27) or tumor cell content ratio (p = 0.28). The median scores for degree of blood contamination were significantly lower in the isolation group than in the no-isolation group (p < 0.01). Conclusion: AMUS is a simple on-site verification procedure for determining the appropriate sampling tissue quantity for high diagnostic accuracy.

Usefulness of the automated multiband imaging system for EUS-FNA biopsy specimen evaluation in patients with upper gastrointestinal subepithelial lesions.

Background and Objectives: Sample isolation processing by stereomicroscopy (SIPS) was recently introduced as an alternative to rapid on-site cytologic evaluation and showed high accuracy for use in pathologic diagnoses. SIPS is a useful, but slightly complicated procedure; therefore, a new, more straightforward method for the objective estimation of the core tissue amount required during the sampling is desirable. We evaluated the usefulness of the automated multiband imaging system (AMUS) for calculating whitish core amounts in EUS-FNA biopsy (EUS-FNAB) samples from patients with subepithelial lesions (SELs). Methods: Four EUS-FNAB specimens per patient were obtained from 20 patients with upper gastrointestinal SELs. The correlation between the whitish core amount calculated by AMUS, length of the manually measured whitish cores (stereomicroscopically visible white core [SVWC]), and sample suitability for pathologic evaluation were analyzed. Results: We identified 13 patients with gastrointestinal stromal tumors, five with leiomyomas, one with a schwannoma, and one with an ectopic pancreas. The histological diagnostic accuracy was 100%, median SVWC length was 9 mm, and median whitish core area, calculated using AMUS, was 10 mm2. SVWC length correlated with whitish core amount (ρ = 0.81, P < 0.01) and adequacy score (ρ = 0.54, P < 0.01). Whitish core amount correlated with adequacy score (ρ = 0.54, P < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.83 (P < 0.01; cutoff ≥4 mm2, sensitivity 98.4%). Conclusions: AMUS, a simple on-site verification instrument, is an alternative to SIPS for determining the appropriate SEL tissue sampling quantity with high diagnostic accuracy.

Multicenter prospective study of the efficacy of stereomicroscopic on-site evaluation in endoscopic ultrasound-guided tissue acquisition in patients with pancreatic cancer.

OBJECTIVE: In sample isolation processing by stereomicroscopy (SIPS), a technique used to assess the quality of specimens collected during endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA), the cutoff value of stereomicroscopically visible white core (SVWC) (≥11 mm) indicates high diagnostic sensitivity. However, the procedure of SIPS is complicated and time-consuming. Therefore, we devised the stereomicroscopic on-site evaluation (SOSE), a new rapid assessment method that is simpler than SIPS and only determines if the SVWC cutoff value is attained. We aimed to examine the usefulness of SOSE in a multicenter, prospective setting. METHODS: Seventy patients from multiple institutions with solid pancreatic masses suspected to be pancreatic cancer were included. EUS-TA was performed using a 22-gauge Franseen needle. SVWCs were measured on-site using stereomicroscopy. The primary outcome was the sensitivity of SVWC cutoff value in EUS-TA with SOSE. RESULTS: The total number of punctures was 214 and SOSE was performed on 150 punctures. The SVWC cutoff value collection rate was 100% per lesion, with 80% in the first pass, 79% in the second pass, and 78% per puncture in all passes. The median time taken to determine the SVWC cutoff value for SOSE was 47 s. The sensitivity of the SVWC cutoff value was 93.2% for histology and 96.6% for cytology + histology. The per-lesion accuracy of pathological diagnosis reached the highest level (98.6%) at the second puncture. CONCLUSIONS: SOSE showed high diagnostic sensitivity and may be a new rapid assessment method for the diagnosis of malignant pancreatic cancer using EUS-TA.

Histopathological comparison of aspiration and biopsy needles in endoscopic ultrasound-guided tissue acquisition in patients with subepithelial lesions.

BACKGROUND: Information on whether a fine-needle biopsy (FNB) needle can improve histopathological specimen quality or the amount of core tissue collected in the diagnosis of subepithelial lesions (SELs) remains insufficient. In this study, we aimed to compare the procedure outcomes and adequacy of histopathological specimens of fine-needle aspiration (FNA) and FNB needles in endoscopic ultrasound-guided tissue acquisition (EUS-TA) using sample isolation processing by stereomicroscopy (SIPS) in patients with SELs. METHODS: We performed a retrospective comparison of SEL cases registered in two previously conducted prospective studies. Of 61 cases, we identified 56 cases of SELs that involved the muscularis propria layer. Of these, 27 patients who underwent EUS-TA using a 22-gauge FNA needle between July 2016 and December 2017, and 29 patients who underwent the procedure using a 22-gauge FNB needle between March 2018 and January 2019 were included in the FNA and FNB group, respectively. RESULTS: Patient background characteristics did not differ between the groups. The technical success rate was 100% in both groups. The median adequacy score was significantly higher in the FNB group than in the FNA group (P < .01). The histological diagnosis showed no significant difference in the accuracy rate between the groups. CONCLUSIONS: In EUS-TA using the SIPS procedure to target SELs derived from the muscularis propria layer, FNB needles collect more core tissues and significantly improve histopathological specimen quality compared with FNA needles. When combined with SIPS, a high tissue diagnosis rate may be obtained regardless of the type of puncture needle used.

Nafamostat Mesylate is Not Effective in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with complications such as post-ERCP pancreatitis (PEP). Protease inhibitors, including nafamostat mesylate (NM), have been evaluated for prophylaxis against PEP. AIM: We describe the first multicenter randomized controlled trial assessing the prophylactic efficacy of NM against PEP. METHODS: In this multicenter prospective study, we aimed to enroll 800 patients aged ≥ 20 years with a planned ERCP between December 2012 and March 2019. The primary outcome was the incidence and severity of PEP in patients who did not receive NM (non-NM) versus those who did (NM; 20 mg). Secondary outcomes included the incidence of PEP by NM initiation (pre- and post-ERCP), risk factors for PEP, and NM-related adverse events. RESULTS: Only 441 of the planned 800 patients were enrolled (non-NM: n = 149; NM: n = 292 [pre-ERCP NM: n = 144; post-ERCP NM: n = 148]). Patient characteristics were balanced at baseline with no significant differences between groups. PEP occurred in 40/441 (9%) patients (non-NM: n = 15 [10%]; NM: n = 25 [9%]), including 17 (12%) and eight (8%) in the pre-ERCP and post-ERCP NM groups, respectively. In the NM group, the incidence of PEP was lower in the low-risk group than in the high-risk group. Pancreatic injection and double-guidewire technique were independent risk factors for PEP. NM-related adverse events of hyperkalemia occurred in two (0.7%) patients. CONCLUSIONS: We found no evidence for the prophylactic effect of NM against PEP, regardless of the timing of administration; however, further studies are needed.

The First Case of Metastatic Pancreatic Leiomyosarcoma Derived from the Urinary Bladder Diagnosed Using an Endoscopic Ultrasound-guided Fine-needle Biopsy.

We herein report the first case of metastatic pancreatic leiomyosarcoma derived from the urinary bladder diagnosed by an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) in a 65-year-old woman. The patient had undergone total cystectomy for bladder leiomyosarcoma. Four years thereafter, a nodule was observed in her left lung on chest computed tomography. Suspecting primary lung cancer, pulmonologists at our hospital recommended a thoracoscopic lung biopsy, which the patient refused. Five years post-cystectomy, fluorodeoxyglucose positron emission tomography revealed enlargement of the left lung nodule and a new mass in the pancreatic head. She was referred to our department for the pathological diagnosis of a pancreatic head mass by an EUS-FNB. The EUS-FNB yielded adequate pancreatic tissue for an immunohistochemical analysis. A diagnosis of metastatic pancreatic lesion originating from the urinary bladder was made. In atypical pancreatic tumors, the utilization of an EUS-FNB and immunohistochemical analysis can help establish an accurate diagnosis.

Diagnostic efficacy of white core cutoff lengths obtained by EUS-guided fine-needle biopsy using a novel 22G franseen biopsy needle and sample isolation processing by stereomicroscopy for subepithelial lesions.

OBJECTIVES: The aim of this study is to estimate the cutoff length for stereomicroscopically visible white core (SVWC) required for the pathological diagnosis of subepithelial lesions (SELs) from samples obtained using a novel 22-G Franseen biopsy needle and determine the sensitivity using the SVWC cutoff length. PATIENTS AND METHODS: Thirty patients with SELs requiring pathological diagnoses were included. EUS-guided fine-needle biopsies (EUS-FNBs) were performed using a novel 22G Franseen biopsy needle. SVWC cutoff lengths were measured using sample isolation processing by stereomicroscopy (SIPS). The utility of the calculated SVWC cutoff lengths was measured. RESULTS: The procedural success and SVWC sampling rates were both 100%. The median SVWC length was 14.5 mm. Pathological examinations identified 16 patients with gastrointestinal stromal tumors, 7 with schwannomas, 6 with leiomyomas, and 1 with an ectopic pancreas. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing malignancy using EUS-FNB were all 100%. The final diagnostic accuracy was 100%. Regarding the final diagnosis, based on the receiver operating characteristic curves calculated using the SVWC length, the area under the curve was 0.958 (95% confidence interval: 0.897-1.020, P < 0.001) and the cutoff length was 4 mm. The sensitivity of the new SVWC cutoff length was 98.7%. CONCLUSIONS: Diagnostic results of EUS-FNBs using a novel 22-G Franseen biopsy needle were significantly better with SVWC cutoff lengths ≥4 mm. Performing the SIPS procedure with a cutoff value of 4 mm as an index may be especially useful for successful pathological diagnosis of SELs at institutions where rapid on-site evaluation cannot be performed.

On-site stereomicroscope quality evaluations to estimate white core cutoff lengths using EUS-FNA biopsy sampling with 22-gauge needles.

BACKGROUND AND AIMS: Although rapid on-site cytologic evaluation (ROSE) during EUS-guided FNA biopsy (EUS-FNAB) sampling may improve accuracy of pathologic analyses, cytopathologists are not widely available. We calculated the cutoff lengths required for accurate pathologic diagnoses from stereomicroscopically visible white cores (SVWCs) sampled using 22-gauge needles. METHODS: Overall, 118 patients with mediastinal or upper abdominal solid masses requiring pathologic diagnoses were included. EUS-FNAB sampling was performed using 22-gauge needles. SVWCs were isolated and measured using stereomicroscopy, and the utility of calculated cutoff lengths in diagnosis was investigated. RESULTS: The procedure success and SVWC sampling rates were both 100%, and the median SVWC length was 10 mm. Pathologic examination identified 75, 31, and 12 patients with pancreatic neoplasms (PNs), subepithelial lesions (SELs), and other lesions, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing malignancy using EUS-FNAB sampling were 93.1%, 100%, 100%, 69.6%, and 94%, respectively. The final diagnostic accuracy in the entire cohort, PNs, and SELs was 92.4%, 90.7%, and 93.5%, respectively. Receiver operating characteristic curves demonstrated the overall SVWC cutoff length to be 11 mm (11 mm for PNs, 3.5 mm for SELs). The overall sensitivity according to SVWC cutoff length was 91.4% (87.6% for PNs, 98.8% for SELs). Compared with cutoff length, multivariate analysis confirmed SVWC length to be a stronger independent factor for tissue diagnosis in both groups. CONCLUSIONS: Diagnosis improved significantly with SVWC cutoff lengths ≥11 mm. This may be a useful index for endoscopists, particularly where ROSE is unavailable. (Clinical trial registration number: UMIN000023013.).

Usefulness of serum lipase for early diagnosis of post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is new onset acute pancreatitis after ERCP. This complication is sometimes fatal. As such, PEP should be diagnosed early so that therapeutic interventions can be carried out. Serum lipase (s-Lip) is useful for diagnosing acute pancreatitis. However, its usefulness for diagnosing PEP has not been sufficiently investigated. AIM: This study aimed to retrospectively examine the usefulness of s-Lip for the early diagnosis of PEP. METHODS: We retrospectively examined 4192 patients who underwent ERCP at our two hospitals over the last 5 years. The primary outcomes were a comparison of the areas under the receiver operating characteristic (ROC) curves (AUCs) of s-Lip and serum amylase (s-Amy), s-Lip and s-Amy cutoff values based on the presence or absence of PEP in the early stage after ERCP via ROC curves, and the diagnostic properties [sensitivities, specificities, positive predictive values (PPV), and negative predictive value (NPV)] of these cutoff values for PEP diagnosis. RESULTS: Based on the eligibility and exclusion criteria, 804 cases were registered. Over the entire course, PEP occurred in 78 patients (9.7%). It occurred in the early stage after ERCP in 40 patients (51.3%) and in the late stage after ERCP in 38 patients (48.7%). The AUCs were 0.908 for s-Lip [95% confidence interval (CI): 0.880-0.940, P < 0.001] and 0.880 for s-Amy (95%CI: 0.846-0.915, P < 0.001), indicating both are useful for early diagnosis. By comparing the AUCs, s-Lip was found to be significantly more useful for the early diagnosis of PEP than s-Amy (P = 0.023). The optimal cutoff values calculated from the ROC curves were 342 U/L for s-Lip (sensitivity, 0.859; specificity, 0.867; PPV, 0.405; NPV, 0.981) and 171 U/L for s-Amy (sensitivity, 0.859; specificity, 0.763; PPV, 0.277; NPV, 0.979). CONCLUSION: S-Lip was significantly more useful for the early diagnosis of PEP. Measuring s-Lip after ERCP could help diagnose PEP earlier; hence, therapeutic interventions can be provided earlier.

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy.

BACKGROUND/OBJECTIVES: A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount. METHODS: We conducted the first-ever examination of the feasibility of analyzing BRCAness using multiplex ligation-dependent probe amplification (MLPA). Formalin-fixed paraffin-embedded (FFPE) tissue samples obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) from 20 patients with the highest pancreatic carcinoma cell counts in tissue samples out of 40 consecutive PDAC patients who underwent EUS-FNAB at our hospital were analyzed by MLPA for BRCAness. RESULTS: We were able to accurately analyze BRCAness in 75% of the 20 cases of PDAC using FFPE tissue obtained by EUS-FNAB. BRCAness was observed in one of the 20 cases. CONCLUSIONS: In PDAC, analyzing BRCAness by MLPA using FFPE tissue obtained by EUS-FNAB offers the remarkable benefit of yielding results in a short period of time and at a low cost. In addition, this method of BRCAness analysis may prove to be a feasible and effective approach for performing precision medicine.

Transpapillary Biliary Cannulation is Difficult in Cases with Large Oral Protrusion of the Duodenal Papilla.

BACKGROUND: Biliary cannulation failure is a major problem during endoscopic retrograde cholangiopancreatography. It remains unclear how duodenal papilla morphology affects biliary cannulation. Therefore, we proposed a new classification system for the duodenal papilla based on oral protrusion pattern (ratio of the length of the oral protrusion to the transverse diameter of the papilla) and papilla pattern. AIMS: To retrospectively compare biliary cannulation results with regard to classification and operator experience. METHODS: We analyzed 589 naïve major duodenal papillae. Our classification system comprised oral protrusion pattern, classified as small (Protrusion-S), regular (Protrusion-R), or large (Protrusion-L), and the papilla pattern, classified as annular (Papilla-A), unstructured (Papilla-U), longitudinal (Papilla-LO), isolated (Papilla-I), or gyrus (Papilla-G). Intra-evaluator concordance and the results of biliary cannulation were analyzed. RESULTS: The following oral protrusion pattern classifications were observed: Protrusion-S, 11.7%; Protrusion-R, 77.9%; and Protrusion-L, 10.4%. The following papilla patterns were observed: Papilla-A, 67.1%; Papilla-U, 7.0%; Papilla-LO, 7.5%; Papilla-I, 1.2%; Papilla-G, 15.6%; and unclassified, 1.7%. Intra-evaluator concordance value (Fleiss kappa) was 0.788 for oral protrusion pattern and 0.750 for papilla pattern. A logistic regression analysis of cannulations performed by an experienced endoscopist identified Protrusion-L as a significant risk factor for difficult cannulation (odds ratio 2.956; 95% confidence interval 1.115-7.84; p = 0.029). Multivariate analysis confirmed Protrusion-L as an independent risk factor for difficult biliary cannulation (odds ratio 3.772; 95% confidence interval 1.359-10.464; p = 0.011). CONCLUSIONS: We propose a new general classification system for the duodenal papilla. Protrusion-L is a significant risk factor for difficult biliary duct cannulation.

Randomized controlled exploratory study comparing the usefulness of two types of metallic stents with different axial forces for the management of duodenal obstruction caused by pancreatobiliary cancer.

BACKGROUND: Very few studies have examined effectiveness of duodenal stent placement (DSP) for duodenal obstruction (DO) caused specifically by pancreatobiliary cancer. We compared two types of stents with different axial forces (AF) for DO with pancreatobiliary cancer. METHODS: The patients were randomly assigned to two stent groups with different AF (high AF stent, WallFlex™: W-group or low AF stent, Niti-S™: N-group). The primary endpoint was improvement in the Gastric Outlet Obstruction Scoring System (GOOSS) score. This study was registered at UMIN000009061. RESULTS: The GOOSS scores significantly improved in both W-group (0.9 before vs. 2.7 after; P = 0.002) and N-group (1.0 before vs. 2.5 after; P = 0.001). The change in the GOOSS score after DSP did not differ significantly between the groups (P = 0.482). The median time to recurrent DO (RDO) was significantly shorter in W-group than in N-group (89 days vs. 421 days; P = 0.025). The incidence of RDO was significantly higher in W-group than in N-group (64% vs. 24%; P = 0.027). Stent kinking occurred only in W-group. CONCLUSIONS: The GOOSS scores significantly improved after DSP, but effectiveness did not differ significantly between groups. The use of stents with high AF was related to short-term stent patency, but did not influence survival time.

First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia.

To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.

A resected perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed using endoscopic ultrasound-guided fine-needle aspiration.

Primary perivascular epithelioid cell tumors (PEComas) of the pancreas are extremely rare. We herein report our experience with a patient who had a primary PEComa of the pancreas that was diagnosed by the preoperative histopathological examination of a biopsy specimen obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The patient was a 43-year-old woman whose chief complaint was abdominal pain. Imaging studies revealed a pancreatic tumor. Gastrointestinal stromal tumor (GIST), solid pseudopapillary tumor and neuroendocrine tumor were considered in the differential diagnosis. A histopathological examination of a specimen of the tumor obtained using EUS-FNA showed spindle-shaped tumor cells with enlarged nuclei and eosinophilic cytoplasm. The tumor cells proliferated in a sheet-like fashion and stained positive for the melanoma-associated antigen HMB-45. A PEComa was thus diagnosed. If an adequate tumor specimen can be obtained using EUS-FNA, immunostaining may facilitate the diagnosis of extremely rare diseases and therefore assist in deciding the treatment policy.