Deep learning analysis for differential diagnosis and risk classification of gastrointestinal tumors.

OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Effectiveness of endoscopic ultrasound-guided tissue acquisition with stereomicroscopic on-site evaluation for preoperative diagnosis of resectable or borderline resectable pancreatic cancer: a prospective study.

Background/Aims: To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC). Methods: Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings. Results: We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively. Conclusions: The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%.

REV7 is involved in outcomes of platinum-based chemotherapy in pancreatic cancer by controlling the DNA damage response.

REV7 is a multifunctional protein implicated in various biological processes, including DNA damage response. REV7 expression in human cancer cells affects their sensitivity to DNA-damaging agents. In the present study, we investigated the significance of REV7 in pancreatic ductal adenocarcinoma (PDAC). REV7 expression was immunohistochemically examined in 92 resected PDAC specimens and 60 endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens of unresectable PDAC treated with platinum-based chemotherapy, and its association with clinicopathologic features was analyzed. Although REV7 expression was not significantly associated with the progression of primary tumors (T-factor and Stage) in either resected or unresectable PDAC, decreased levels of REV7 expression in EUS-FNAB specimens of unresectable PDAC were significantly associated with better outcomes of platinum-based chemotherapy and a favorable prognosis. REV7-deficient PDAC cell lines showed suppressed cell growth and enhanced sensitivity to cisplatin in vitro. Tumor-bearing mice generated using REV7-deficient PDAC cell lines also showed enhanced sensitivity to cisplatin in vivo. RNA sequencing analysis using WT and REV7-deficient PDAC cell lines revealed that REV7 inactivation promoted the downregulation of genes involved in the DNA repair and the upregulation of genes involved in apoptosis. Our results indicate that decreased expression of REV7 is associated with better outcomes of platinum-based chemotherapy in PDAC by suppressing the DNA damage response. It is also suggested that REV7 is a useful biomarker for predicting the outcome of platinum-based chemotherapy and the prognosis of unresectable PDAC and is a potential target for PDAC treatment.

Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells.

OBJECTIVE: The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines. METHODS: Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay. RESULTS: Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines. CONCLUSIONS: Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.

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.

CD109 expression in tumor cells and stroma correlates with progression and prognosis in pancreatic cancer.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

A case of pancreatic neuroendocrine carcinoma with a favorable clinical response to pembrolizumab.

A 76-year-old man with epigastric pain developed 1 month earlier was referred to our department for additional screening and treatment after abdominal ultrasound revealed a mass shadow in the pancreatic head and liver. Blood biochemistry revealed signs of mild jaundice and hepatic dysfunction. Abdominal contrast-computed tomography revealed an irregular hypodense mass with poor enhancement in the pancreatic head and several hypodense nodules in the liver. Endoscopic examination revealed duodenal infiltration signs. The biopsied duodenal mucosa contained atypical cells with high nuclear-to-cytoplasmic ratios; the cells stained positive for CD56, chromogranin, and synaptophysin, and the Ki-67 index was 90%. Accordingly, pancreatic neuroendocrine carcinoma (PanNEC) was diagnosed. Platinum-based chemotherapy (6 courses) and streptozotocin (10 courses) were adopted as the first- and second-line regimens, respectively. However, the patient showed progressive disease (PD). Pembrolizumab was added as a third-line regimen (13 courses) after confirming PanNEC with high microsatellite instability (MSI-high). Despite a temporary partial response (PR), the patient showed PD by the end of the 13 courses and died 1 year and 7 months after diagnosis. Although there is no established PanNEC therapy, those with MSI-high may respond favorably to pembrolizumab. Therefore, we should ascertain the MSI status of any PanNEC in routine practice.

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.

Pancreatic Schwannoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration.

A schwannoma is a tumor originating from Schwann cells. It is occasionally observed in the abdominal viscera in the form of a submucosal tumor derived from the gastric or duodenal muscularis propria. To date, only a few studies have reported on pancreatic schwannomas. Furthermore, very few patients are preoperatively diagnosed with pancreatic schwannoma because of the lack of established imaging characteristics distinguishing this type of schwannoma from other conditions. We herein report the first English publication of pancreatic schwannoma in which surgery was avoided because a pathological diagnosis was made solely on the basis of endoscopic ultrasound-guided fine-needle aspiration findings.

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.

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.

Endoscopic Balloon Dilation for Benign Bilioenteric Stricture: Outcomes and Factors Affecting Recurrence.

BACKGROUND: Balloon dilation (BD) is a simple, effective procedure for postoperative benign bilioenteric strictures (BBESs). Factors associated with BBES recurrence after endoscopic BD have not been studied adequately. This study examined the outcomes and 1-year recurrence factors in patients with BBES who underwent endoscopic BD. METHODS: Patients who underwent endoscopic BD as an initial treatment between April 2008 and March 2017 were retrospectively assessed. The median time to recurrence of BBES (RBBES) and recurrence factors were evaluated. RESULTS: The study group comprised 55 patients (median age 72 years). The rate of RBBES was 52.7% (29/55), and the median time to RBBES was 2.78 years (95% confidence interval [CI] 1.17-4.40). RBBES was observed in 32.7% (18/55) within 1 year after endoscopic BD. The significant factors associated with recurrence within 1 year, revealed by multivariate analysis, were: postoperative bile leak (p = 0.001; hazard ratio [HR] 10.94; 95% CI 2.47-48.39); BBES onset within 6 months, postoperatively (p = 0.013; HR 6.18; 95% CI 1.46-26.21); no intrahepatic stones (p = 0.049; HR 3.05; 95% CI 1.01-9.22); and remaining balloon waist (p = 0.005; HR 5.71; 95% CI 1.69-19.31). The median time to RBBES was significantly shorter in patients with these recurrence factors (0.88 years vs. not reached, p = 0.004). Patients exhibiting at least two recurrence factors were significantly more likely to experience recurrence (p < 0.001). CONCLUSION: Endoscopic BD is effective for BBES, especially for patients with no recurrence factors. Consideration of endoscopic BD and additional treatment may be necessary for patients with recurrence factors.

Stent-induced symptomatic pancreatic duct stricture after endoscopic prophylactic pancreatic duct stent placement for the normal pancreas.

BACKGROUND/OBJECTIVES: Stent-induced pancreatic duct stricture (SI-PDS) is a complication associated with pancreatic stent placement. However, symptomatic SI-PDS associated with prophylactic pancreatic duct stents has not been sufficiently investigated. METHODS: We examined the incidence and characteristics of symptomatic SI-PDS in patients who underwent pancreatic duct stent placement to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) between April 2007 and March 2017. RESULTS: We examined 124 patients with normal pancreases consisting of 75 men and 49 women with a median age of 67.5 years [interquartile range (IQR): 61-74 years]. The median main pancreatic duct (MPD) diameter was 3.3 mm (IQR: 2.6-4.1 mm). The median duration of stent placement was 7 days (IQR: 3-14 days). Spontaneous dislodgment stents were placed in 43.5% of cases (54/124). The diameter of the stent was 5 Fr in 93.5% of cases (116/124) and 7 Fr in 6.5% of cases (8/124). Symptomatic SI-PDS was observed in 2.4% (3/124) of patients overall: 6.5% of patients with an MPD diameter of <3 mm and 0% of patients with an MPD diameter of ≥3 mm. Univariate analysis revealed that an MPD diameter <3 mm was a significant factor for symptomatic SI-PDS (p = 0.048). All cases of symptomatic SI-PDS improved with endoscopic treatment. CONCLUSIONS: Symptomatic SI-PDS occurred in 2.4% of patients who underwent prophylactic pancreatic duct stent placement for normal pancreases. Patients with an MPD diameter of <3 mm may be susceptible to symptomatic SI-PDS.

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.

Pancreatic granular cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration biopsy.

Pancreatic granular cell tumors (GCTs) are rare and making an imaging diagnosis of pancreatic GCT is difficult because it has no definite characteristics on contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging (MRI) owing to varying findings. We report about a 32-year-old woman who presented with an incidental finding of a pancreatic tumor with a past history of excision of a right forearm GCT nodule 12 years ago. CE-CT revealed a 23-mm-sized homogeneous low enhancement tumor in the arterial phase in the pancreatic body. Abdominal MRI revealed a lobulated hypointense mass in T1WI and high signal in DWI. Endoscopic ultrasonography (EUS) revealed that the tumor was oval, hypoechoic with posterior echo enhancement, and had a well-defined border. Although EUS-guided fine needle aspiration revealed benign granular cells of the pancreas, she underwent laparoscopic surgery because the metastatic tumor from the past lesion was not excluded. The pathological finding was benign GCT of the pancreas and it was considered as an original lesion. In the previous reports, most of the resected cases were considered to be pancreatic cancer or neuroendocrine tumor preoperatively. Compared to CE-CT and MRI, EUS imaging and EUS-FNA are more reliable diagnosis tools for pancreatic GCT. Although malignant GCT accounts for approximately 1-2% of all cases, surgical resection or strict follow-up should be considered because it is difficult to predict its biological behavior.

Complications of Long-Term Indwelling Transmural Double Pigtail Stent Placement for Symptomatic Peripancreatic Fluid Collections.

BACKGROUND: Endoscopic transmural drainage is performed for symptomatic peripancreatic fluid collections (PPFCs). Long-term transmural double-pigtail stent (DPS) placement is useful in preventing recurrences. There are few reports on the long-term safety of DPS placement. Thus, this study aimed to examine the complications of long-term indwelling DPS for PPFCs. METHODS: Among 53 patients who underwent endoscopic ultrasound-guided transmural drainage for symptomatic PPFCs between April 2006 and March 2017, those followed up for over one year were included. Complications of long-term indwelling DPS were examined retrospectively. RESULTS: This study enrolled 36 patients [30 men, median age 54 years (range 22-82)]. Walled-off necrosis was present in 22 cases (including 9 disconnected pancreatic duct syndrome cases) and pancreatic pseudocysts, in 14 cases. The median stenting period was 20.9 (range 0.8-142.3) months, and median observation period was 56.2 (range 12.4-147.1) months. Colon perforation due to DPS occurred in 3 cases (8.3%), at 5.8, 17.1, and 33.7 months after indwelling DPS placement; 2 cases developed perforation from the serosal side. In 1 case, the patient was treated surgically, and in 2 cases, the patients underwent endoscopic removal of the stent and showed improvement with conservative treatment. CONCLUSION: Long-term indwelling transmural DPS for symptomatic PPFCs poses a risk of intestinal perforation. Thus, if possible, it may be better to avoid long-term placement.