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.

Efficacy of endoscopic ultrasound-guided tissue acquisition using stereo-microscopic on-site evaluation for possible comprehensive genome profile in patients with advanced pancreatic cancer.

BACKGROUND AND AIM: Stereomicroscopic on-site evaluation (SOSE) is a rapid evaluation method for endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a high diagnostic sensitivity when the stereomicroscopically visible white core (SVWC) cut-off value (≥ 11 mm) is met. We prospectively examined the association between SVWCs and the adequacy of tissue specimens, assuming subsequent comprehensive genome profiling (CGP). METHODS: This study included 66 consecutive patients with suspected unresectable pancreatic cancer who underwent EUS-TA. The primary endpoint was the frequency of combined samples with ≥ 20% tumor cell content that met over twice the SVWC (T-SVWC) cut-off value, achieved through multiple punctures. The secondary endpoints were the number of punctures, the percentage of SVWC cut-off values, adverse events, the positive diagnosis rate, and the tissue section area. RESULTS: The median number of EUS-TA punctures for suspected unresectable pancreatic cancer was 3 (range, 3-4); SVWC and T-SVWC cut-off values were obtained in 171/206 specimens and 65/66 patients, respectively. There were no EUS-TA-related adverse events. The positive diagnosis rate of EUS-TA was 95.5%. Among the 63 patients meeting the T-SVWC cut-off value in pathological diagnoses, the median tumor cell content was 40% (range, 5-80%), with 57 patients having tumor cell content ≥ 20%. The median tissue section area was 15 (range, 3-40) mm2. CONCLUSIONS: When performing EUS-TA for unresectable pancreatic cancer with the intention of subsequent CGP, obtaining a high tumor cell content (≥ 20%) by assessing the T-SVWC cut-off value via SOSE may serve as a novel indicator for on-site estimation of CGP suitability for EUS-TA specimens.

Endoscopic Ultrasound-Guided Tissue Acquisition Using Fork-Tip Needle for Subepithelial Lesions: A Single-Center Validation Study.

BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.

Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106.

OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.

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.

Endoscopic re-intervention after stent-in-stent versus side-by-side bilateral self-expandable metallic stent deployment.

BACKGROUND AND AIM: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is widely performed; however, re-intervention after recurrent biliary obstruction (RBO) is often challenging. We compared stent-in-stent (SIS) and side-by-side (SBS) SEMS placement for MHBO considering re-intervention for RBO. METHODS: One hundred five consecutive patients with MHBO who underwent endoscopic bilateral SEMS placement in our hospital and its affiliated institutions were enrolled in this study; 75 patients underwent partial SIS deployment between December 2005 and December 2012; and 30 underwent SBS deployment between January 2013 and March 2019. Initial treatments and re-interventions in each group were retrospectively evaluated. RESULTS: Technical success rate (92% vs 100%, P = 0.179), procedure duration (46 vs 35 min, P = 0.382), functional success rate (97.1% vs 100%, P = 1.00), complication rate (24.6% vs 20.0%, P = 0.797), time to RBO (260 vs 312 days; Gray test, P = 0.815), and rate of RBO (59.4% vs 70.0%, P = 0.371) were not significantly different between the SIS and SBS groups. However, bilateral re-stenting with plastic stents through SEMS was successful in 63.4% of patients in the SIS group compared with 100% of patients in the SBS group (P = 0.0013). Median time to RBO upon first re-stenting with a plastic stent was 75 days (range, 11-195 days). CONCLUSIONS: Endoscopic re-stenting after RBO was significantly more successful in the SBS group than in the SIS group. SBS method is suitable for MHBO considering revisionary stent placement.

Risk Factors for Perforation During Endoscopic Papillary Large Balloon Dilation and Bile Duct Stone Removal.

BACKGROUND: Stone removal using endoscopic papillary large balloon dilation (EPLBD) is extremely effective. However, limited research exists regarding the risk factors for perforation of the duodenal papilla and bile duct, which may be fatal. AIMS: We aimed to investigate the risk factors for perforation during EPLBD + stone removal. METHODS: We included patients who underwent EPLBD + stone removal at four medical facilities between January 2008 and December 2018. We retrospectively analyzed the risk factors for perforation and their relationship between overdilation and adverse events. Overdilation was defined as a ratio of the balloon diameter to the diameter of the bile duct that exceeded 100%. The diameter of the distal bile duct was measured using the diameter of the intrapancreatic bile duct at a point 10 mm toward the liver from the narrow distal segment on a cholangiogram. RESULTS: We included 310 patients (177 males; median age: 79 years [range: 46-102 years]). Perforation occurred in five patients (1.6%). Multivariate analysis indicated that no surrounding-pancreas (half or less of the circumference of the intrapancreatic bile duct was surrounded by the pancreatic parenchyma) was a significant risk factor (perforation rate: 8.3%, p = 0.011, odds ratio: 12.7 [95% confidence interval: 1.8-90.5]). No significant difference was found between the overdilation and non-overdilation groups regarding the occurrence of pancreatitis, bleeding, and cholangitis. Perforation rate in patients with no surrounding pancreas + overdilation was 16.7% (2/12). Patients with perforation underwent conservative therapy, which improved their conditions. CONCLUSIONS: EPLBD + stone removal should be avoided in patients with no surrounding pancreas. Overdilation is not a risk factor for adverse procedural events; however, it should be limited in patients with surrounding pancreas.

Factors for unsuccessful endoscopic hemostasis in patients with severe peptic ulcer bleeding.

OBJECTIVES: Although the first approach for peptic ulcer bleeding is endoscopic hemostasis, quick determination of a hemostatic strategy is important in patients with vitals indicating shock. However, the unsuccessful factors for endoscopic treatment have yet to be sufficiently examined. We aimed to investigate the factors for unsuccessful endoscopic hemostasis in severe peptic ulcer bleeding. MATERIALS AND METHODS: Unsuccessful factors were retrospectively investigated in 150 eligible patients who underwent endoscopic hemostasis for shock-presenting peptic ulcer bleeding at our critical care center between April 2007 and March 2021. RESULTS: There were 123 and 27 cases of successful and unsuccessful endoscopic hemostasis, respectively. Causative diseases included gastric ulcer bleeding in 124 patients (82.7%) and duodenal ulcer bleeding in 26 patients (17.3%). Shock index (SI) (1.46 vs. 1.60) (p = .013), exposed blood vessel diameter (1.4 mm vs. 3.1 mm) (p < .001) identified on contrast-enhanced computed tomography (CE-CT), duodenal ulcer bleeding (p = .012), and Forrest classification Ia (p = .004) were extracted as independent factors for unsuccessful endoscopic hemostasis. In receiving operating curve analysis, when the cut-off value for the SI was set at 1.53, the sensitivity and specificity were 70.4% and 63.4%, respectively. When the cut-off value for the exposed blood vessel diameter was set at 1.9 mm, these were 88.9% and 83.7%, respectively. CONCLUSIONS: When these factors (SI ≥ 1.53, exposed blood vessel diameter ≥1.9 mm identified on CE-CT, duodenal ulcer bleeding, and Forrest Ia) are present in patients with severe peptic ulcer bleeding, non-endoscopic hemostasis, such as interventional radiology (IVR) and surgery, should be considered.

A prospective multicenter study of endoscopic ultrasound-guided fine needle biopsy using a 22-gauge Franseen needle for pancreatic solid lesions.

BACKGROUND AND AIM: While encouraging data of endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) using a 22-gauge Franseen needle have been reported, large-scale data of per pass and quantitative analyses are still lacking. METHODS: This was a multicenter prospective study of EUS-FNB using the 22-gauge Franseen needle for a pancreatic solid lesion. Cytological and histological analyses per pass were evaluated and semi-quantitative analyses were performed on core tissue and blood contamination. Primary end-point was diagnostic accuracy per session. Prognostic factors were analyzed for diagnostic accuracy, sensitivity, core tissue, and blood contamination. RESULTS: A total of 629 passes were performed in 244 cases at 14 centers between 2018 and 2019. The median tumor size was 29 mm, and the puncture was transduodenal in 43%. The median pass number was 2. Diagnostic accuracy per session, at a first pass, and per pass were 93%, 90%, and 88%. In 198 cases with pancreatic cancer, diagnostic sensitivity per session, at a first pass, and per pass were 94%, 89%, and 89%. The rates of core tissue score of 4 and blood contamination score of 3 were 50% and 47%. The adverse event rate was 1.6%. In the multivariate analysis, tumor size ≤20 mm (odds ratio [OR] of 0.46, P = 0.03), transduodenal puncture (OR of 0.53, P = 0.04), and suction (OR of 0.16, P = 0.01) were associated with lower diagnostic accuracy. CONCLUSIONS: The EUS-FNB using the 22-gauge Franseen needle for pancreatic solid lesions showed high per pass and overall diagnostic accuracy.

Fibroblast growth factor receptor 2 (FGFR2) fusions in Japanese patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Fibroblast growth factor receptor gene alterations have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer that has a poor prognosis. This study evaluated the frequency of fibroblast growth factor receptor 2 fusions in clinical specimens from Japanese patients with iCCA. METHODS: This study enrolled 116 patients who had histologically or cytologically confirmed adenocarcinoma and been diagnosed as relapsing after resection or with unresectable intrahepatic cholangiocarcinoma. We evaluated the frequency of fibroblast growth factor receptor 2 fusions-positive cells in their specimens using break-apart fluorescent in situ hybridization 'for 114 patients who met the study protocol'. RESULTS: Of a total of 114 cases, six (5.3%) were identified as fibroblast growth factor receptor 2 fusions-positive with a high frequency (87% or more) of fibroblast growth factor receptor 2 fusions-positive tumour cells whereas the remainder, with the exception of three cases with indeterminate results, were identified as fibroblast growth factor receptor 2 fusions-negative. The patients' baseline characteristics as well as their objective response rates, disease control rates, times to progression, and times to treatment failure with previous or ongoing first-line chemotherapy did not have any obvious relationship to the proportion of fibroblast growth factor receptor 2 fusions-positive case. CONCLUSIONS: Further detailed elucidation of fibroblast growth factor receptor 2 fusion status is expected to contribute to the development of promising therapeutic options for patients suffering from recurrent or unresectable intrahepatic cholangiocarcinoma.

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.

Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN).

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) involves adenoma (IPMA), a precancerous lesion, cancer (IPMC) including high-grade dysplasia (HGD), and invasive carcinoma (IC). DNA markers of IPMN are required for detection of invasive disease, and cysteine dioxygenase 1 (CDO1) gene promoter hypermethylation is a potential candidate. However, it has never been investigated in the context of IPMN. PATIENTS AND METHODS: A total of 107 IPMN tumor tissues, including 41 IPMC and 66 IPMA, were studied. CDO1 promoter methylation was quantified using TaqMan quantitative methylation-specific polymerase chain reaction (qMSP) in patients with IPMN and other pancreatic cystic disorders after pancreatectomy. RESULTS: The methylation values (TaqMeth Vs) of CDO1 increased when noncancerous pancreas tissues were compared with IPMA and HGD (p < 0.0001). Among IPMC, the TaqMeth Vs in IC were not significantly higher than in HGD. The TaqMeth Vs of the solid tumors were higher than those of the cystic tumors (p = 0.0016), which were in turn higher than the corresponding noncancerous tissues (p < 0.0001). Prognostic analysis revealed that high TaqMeth Vs (≥ 14.1) resulted in a poorer prognosis than low TaqMeth Vs (< 14.1) (p < 0.0001). In other pancreatic cystic diseases, only malignant mucinous cystic neoplasm showed DNA hypermethylation of its promoter. A pilot study in pancreatic juice confirmed methylation in all IPMN samples but not in benign pancreatic diseases (p = 0.0277). CONCLUSIONS: CDO1 promoter hypermethylation is extremely specific to IPMN and may accumulate with IPMN tumor progression during the adenoma-carcinoma sequence. It might be a promising candidate as a diagnostic marker of pancreatic cystic diseases.

Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer.

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation-specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound-fine needle aspiration (EUS-FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS-FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS-FNA cytology.

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.

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.).

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.

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.

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.

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer.

BACKGROUND: The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) in elderly Japanese patients with pancreatic cancer remain unclear. Therefore, we prospectively investigated the tolerability and efficacy of nab-PTX + GEM in Japanese patients aged ≥ 75 years with non-curatively resectable pancreatic cancer. METHODS: We treated eligible patients (n = 27) with nab-PTX + GEM until disease progression, appearance of adverse events, or withdrawal of consent. The primary endpoints included adverse events as well as dosing- and survival-related parameters. RESULTS: The rates of 2-cycle completion were 48.1% for nab-PTX and 55.6% for GEM; the relative dose intensities for the 7th (median) treatment cycle were 65.1% and 74.1%, respectively, whereas the dose-reduction rates were 81.5% and 48.1%, respectively. Grade 3 or higher hemotoxicity was observed in 14 of 27 subjects (51.9%); moreover, 22% experienced grade ≥ 3 peripheral nerve disorder and 1 patient (3.7%) died owing to chemotherapy-related interstitial pneumonia. The disease control rate was 92.6% (25/27), while the median progression-free and overall survival times were 7 and 10.3 months, respectively. CONCLUSION: The nab-PTX + GEM regimen is as efficacious in elderly patients who meet certain criteria as it is in previously reported non-elderly patients. The regimen is feasible with appropriate dose adjustments and attention to adverse events. TRIAL REGISTRATION: Clinical trial registration number: UMIN000018907.