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.

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.

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.

Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography for asymptomatic common bile duct stones on surgically altered anatomy: A high risk factor for post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is more common in patients with asymptomatic common bile duct stones (CBDSs) and normal anatomy than in those with symptomatic CBDS; however, studies on the effect of surgically altered anatomy are lacking. We aimed to investigate whether asymptomatic CBDS in balloon enteroscopy-assisted ERCP cases for surgically altered anatomy also has a high incidence of PEP and analyze the risk factors for PEP. METHODS: We retrospectively analyzed 108 consecutive patients who underwent initial ERCP for CBDS with surgically altered anatomies and with naive papilla at Kitasato University Hospital from April 2015 to December 2022. RESULTS: Study participants were as follows: 92 (85%) patients with symptomatic CBDS and 16 (15%) patients asymptomatic CBDS. The overall bile duct cannulation success rate was 89.8%, with PEP occurring in 7.4% of patients (symptomatic CBDS: 3.3%, asymptomatic CBDS: 31.3%). PEP incidence was significantly higher for asymptomatic CBDS (p = .0017). Multivariate analysis identified asymptomatic CBDS and precut sphincterotomy as significant risk factors for PEP. CONCLUSIONS: Asymptomatic CBDS may be a risk factor for PEP onset in balloon enteroscopy-assisted ERCP with surgically altered anatomy. Therefore, the procedure should be performed after obtaining sufficient informed consent and adequate preparation.

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.

Pancreatic Cancer Cells May Adhere to the External Surface of the Puncture Needle After Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

OBJECTIVE: We prospectively investigated whether cells derived from pancreatic cancers adhered to the puncture needle's external surface after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and whether wiping the needle with alcohol swabs removed residual cancer cells. METHODS: The participants were 100 consecutive patients who underwent EUS-FNA for suspected pancreatic ductal adenocarcinoma. In the first pass of EUS-FNA, we prepared aspiration and lavage cytological diagnosis materials from the lumen and external surface of the puncture needle, respectively. This was repeated in the second pass, although the needle's external surface was wiped with an alcohol swab. RESULTS: The positivity rates of aspiration cytological diagnosis for the first and second passes were 67% and 72%, respectively. The positivity rates of lavage cytological diagnosis of the needle's external surface on the first and second passes were 20% and 3%, respectively. Wiping the needle's external surface with alcohol swabs significantly reduced the proportion of cancer cells detected ( P < 0.001). The accuracy rate based on all the collected specimens was 90%. There were no EUS-FNA-related adverse events. CONCLUSION: Pancreatic cancer cells may adhere to the puncture needle's external surface after EUS-FNA. Wiping the needle with alcohol swabs after each puncture effectively removes residual cancer cells.

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.

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.

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.

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.

A probable hydrogen-bonded Meisenheimer complex: an unusually high S(N)Ar reactivity of nitroaniline derivatives with hydroxide ion in aqueous media.

Observations show that nitroanilines exhibit an unusually high S(N)Ar reactivity with OH(-) in aqueous media in reactions that produce nitrophenols. S(N)Ar reaction of 4-nitroaniline (2a) in aqueous NaOH for 16 h yields 4-nitrophenol (4a) quantitatively, whereas a similar reaction of 4-nitrochlorobenzene (1a) gave 4a in 2% yield together with recovered 1a in 97%, suggesting that the leaving ability of the NH(2) group far surpasses that of Cl under these conditions. An essential feature of S(N)Ar reactions of nitroanilines is probably that the NH(2) leaving group participates in a hydrogen-bonding interaction with H(2)O. Density functional theory (DFT) calculations for a set of 4-nitroaniline, OH(-), and H(2)O suggest a possible formation of a Meisenheimer complex stabilized by hydrogen-bonding interactions and a six-membered ring structure. The results obtained here contrast with conventional S(N)Ar reactivity profiles in which nitroanilines are nearly unreactive with nucleophiles in organic solvents.

Contrasting intermolecular and intramolecular exciplex formation of a 1,4-dicyano-2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad.

An intramolecular exciplex is formed upon excitation of the cyclohexane solution of the 1,4-dicyano-2-methylnaphthalene-N,N-dimethyl-p-toluidine dyad, but little if any intramolecular CT complex exists in the ground state of this substance in solution. In contrast, in the crystalline state, the dyad forms an intermolecular mixed-stack CT complex in the ground state and an intermolecular exciplex when it is photoexcited.