Factors Associated With Difficult Endoscopic Ultrasonography-guided Biliary Drainage.

BACKGROUND AND AIMS: When endoscopic retrograde cholangiopancreatography-guided biliary drainage is challenging, endoscopic ultrasound-guided biliary drainage (EUS-BD) can be used as an alternate treatment; however, this method requires operator expertise. Therefore, this study aimed to clarify the factors that are associated with a difficult EUS-BD. PATIENTS AND METHODS: Patients who successfully underwent EUS-BD were enrolled in this study. The patients were divided into the easy group and difficult group depending on whether the procedural time was more than 60 minutes, which was the cutoff value elicited from past reports. Patient characteristics and procedural factors were compared between the two groups. The factors associated with difficult procedures were also investigated. RESULTS: The patient characteristics were not significantly different between the easy group (n=22) and the difficult group (n=19). The diameter of the punctured bile duct was significantly different between the two groups. In the multivariate analysis, the diameter of the punctured bile duct was the only factor associated with a difficult EUS-BD (odds ratio 0.65, 95% confidence interval 0.46-0.91, P value=0.012). The cutoff value for the diameter of the punctured bile duct in predicting a difficult EUS-BD was 7.0 mm (area under the curve: 0.83, sensitivity 84.2%, specificity 86.4%). CONCLUSIONS: A nondilated bile duct might be a predictive factor for a difficult EUS-BD. For beginners of EUS-BD, the cutoff value for the punctured bile duct diameter found in this study, 7.0 mm, might become a barometer for puncture point selection.

Lymphadenopathy Tissue Sampling by EUS-Guided Fine-Needle Biopsy Contributes to Meeting the Conditions for Genomic Profiling.

BACKGROUND AND AIMS: EUS-guided fine-needle biopsy (EUS-FNB) performed with a Franseen needle or Fork-tip needle enables greater tissue acquisition. However, it is unknown whether EUS-FNB could contribute to lymphadenopathy genomic profiling. The aim of this study was to determine the efficacy of EUS-FNB using a Franseen or Fork-tip needle for tissue acquisition and genomic profiling in patients with lymphadenopathy. PATIENTS AND METHODS: Patients with abdominal lymphadenopathy who underwent EUS-guided fine needle aspiration (FNA)/EUS-FNB were included in this study. The amount of acquired tissue and its suitability for genomic profiling were compared between FNA and FNB. Specimen quality was evaluated by a widely used pathologic adequacy scoring system (0: insufficient; 1 to 2: cytologic; 3: limited histologic; 4 to 5: sufficient histologic). The criteria of FoundationOne CDx (F1CDx) and NCC Oncopanel (NOP) were used to assess the suitability for genomic profiling. RESULTS: In total, 72 patients underwent EUS-FNA, and the other 20 patients underwent EUS-FNB. The pathologic adequacy score and suitability for genomic profiling based on the criteria were significantly higher for FNB than for FNA [histologic adequacy score: 5 (4 to 5) versus 3 (0 to 5), P<0.01; F1CDx: 16.7% vs. 0%, P=0.01; NOP: 66.7% vs. 7.5%, P<0.01]. In multivariate analysis, EUS-FNB was identified as the only factor that influenced the suitability for genomic profiling based on the above-mentioned criteria (odds ratio 19.5, 95% CI: 3.74-102, P<0.01). CONCLUSIONS: EUS-FNB performed using Franseen or Fork-tip needles may result in greater lymphadenopathy tissue acquisition and thus enhanced suitability for genomic profiling compared with EUS-FNA.

L-Menthol for Color Difference Change Between Early Gastric Cancer and Surrounding Mucosa: A Prospective Study.

BACKGROUND: L-Menthol sprayed on early gastric cancer (EGC) has been reported to improve the visibility of the lesion. However, its impact when used in combination with novel image-enhanced endoscopy has not been investigated. AIM: This study aimed to evaluate the visual effect of spraying L-menthol on EGC under linked color imaging (LCI). METHODS: This open-label, single-arm, prospective study investigated the color difference between EGC and the surrounding mucosa (ΔEG) before and after spraying L-menthol. The primary endpoint was the percentage of lesions with ΔEG ≥ 5 on LCI. The percentage of lesions with ΔEG ≥ 5 on white light imaging (WLI) and blue laser imaging (BLI), ΔEG before and after spraying L-menthol, and percentage of lesions with increased ΔEG after spraying L-menthol constituted the secondary endpoints. RESULTS: Sixty patients were included in the final analysis. 100% lesions had ΔEG ≥ 5, both before and after spraying L-menthol on LCI, with similar results observed in WLI as well as BLI. The median ΔEG on LCI, WLI, and BLI increased after spraying L-menthol (LCI: 16.9 vs. 21.5, p < 0.01; WLI: 10.4 vs. 13.4, p < 0.01; BLI; 12.1 vs. 15.7, before and after, respectively, p < 0.01); and LCI demonstrated the highest percentage of lesions with increased ΔEG (LCI, WLI, and BLI: 98.3%, 81.7%, and 76.7%, respectively, p < 0.01). CONCLUSION: Although spraying L-menthol did not improve the visibility of EGC under LCI observation, a significant increase in ΔEG was observed in LCI (jRCTs 021200027).

Clinical benefit of subsequent chemotherapy after drug-induced interstitial lung disease in pancreatic cancer patients: a multicenter retrospective study from Japan.

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen. METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups. RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93). CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis.

BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis; therefore, useful biomarkers and treatments are needed. Serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-ß superfamily, are elevated in patients with pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. Therefore, we investigated the effect of MIC-1 on BTC and assessed whether MIC-1 is a biomarker of or therapeutic target for BTC. METHODS: MIC-1 expression in BTC cells was determined by performing histological immunostaining, tissue microarray (TMA), western blotting, and reverse transcription PCR (RT-PCR). Cell culture experiments were performed to investigate the effect of MIC-1 on BTC cell lines (HuCCT-1 and TFK-1). The relationships between serum MIC-1 levels and either the disease state or the serum level of the apoptosis marker M30 were retrospectively verified in 118 patients with pancreaticobiliary disease (individuals with benign disease served as a control group, n = 62; BTC, n = 56). The most efficient diagnostic marker for BTC was also investigated. RESULTS: MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined using TMA, western blotting and RT-PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In serum analyses, serum MIC-1 levels showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved using the combination of MIC-1 and M30. The overall survival was significantly longer in BTC patients with serum MIC-1 < the median than in BTC patients with serum MIC-1 ≥ the median. CONCLUSIONS: MIC-1 is a useful diagnostic and prognostic biomarker and might be a potential therapeutic target for BTC.

Mirogabalin vs pregabalin for chemotherapy-induced peripheral neuropathy in pancreatic cancer patients.

BACKGROUND: The prognosis of pancreatic cancer (PC) has been improved by new chemotherapy regimens (combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel (GnP)). Unfortunately, chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of these two regimens. The efficacy of pregabalin for CIPN has been reported in previous studies. However, the efficacy of mirogabalin for CIPN remains unknown. Thus, in this study, we aimed to clarify which drug (mirogabalin or pregabalin) was more valuable for improving CIPN. METHODS: A total of 163 PC patients who underwent FOLFIRINOX or GnP between May 2014 and January 2021 were enrolled. Among them, 34 patients were diagnosed with CIPN. Thirteen patients were treated with mirogabalin (mirogabalin group), and twenty-one patients were treated with pregabalin (pregabalin group). Treatment efficacy was compared between the two groups. RESULTS: In both the mirogabalin group and the pregabalin group, the grade of patients with CIPN at 2, 4, and 6 weeks after the initiation of treatment showed significant improvement compared to the pretreatment grade. Notably, the rate of CIPN improvement was higher in the mirogabalin group than in the pregabalin group (2 weeks: 84.6% (11/13) vs 33.3% (7/21), P value = 0.005; 4 weeks, 6 weeks: 92.3% (12/13) vs 33.3% (7/21), P value = 0.001). CONCLUSIONS: Although both mirogabalin and pregabalin were effective at improving CIPN, mirogabalin might be a suitable first choice for CIPN in PC patients. TRIAL REGISTRATION: Not applicable.

A simple method for diagnosing gallbladder malignant tumors with subserosa invasion by endoscopic ultrasonography.

BACKGROUND: If the depth of gallbladder malignant tumor (GBMT) invasion is deeper than the subserosa (ss), cholecystectomy is insufficient. In past reports that used endoscopic ultrasonography (EUS) to diagnose the depth of tumor invasion, it was difficult to diagnose GMBT invasion in the ss without a narrow or disrupted lateral hyperechoic layer (LHEL). Therefore, we developed a simple preoperative method to diagnose GBMTs with ss invasion. METHODS: Forty-nine GBMT patients who underwent both EUS and surgery were enrolled: 15 patients whose tumors invaded the mucosa (m) or muscularis propria (mp) were classified as the "shallow group", and 34 patients whose tumors invaded the ss were classified as the "deep group". The EUS findings were compared between the two groups. RESULTS: An irregular (narrow or thickened) LHEL was significantly more frequently observed on EUS in the deep group than in the shallow group. The diagnosis of ss invasion based on an irregular LHEL had the highest sensitivity and accuracy among the EUS imaging parameters (sensitivity 97.1% (33/34), specificity 86.7% (13/15), accuracy 93.8% (46/49)). When the deep group was limited to patients with a tumor depth of ss, the results were similar. When an irregular LHEL was used, the diagnostic accuracy of GBMTs with ss invasion was not significantly different between EUS specialists and beginners. CONCLUSIONS: The observation of an irregular (thickened or narrow) LHEL observed on EUS could be a reliable and simple method of diagnosing GBMTs with ss invasion and could contribute to choosing an appropriate surgical method.

Clinical Characteristics of Intramucosal Gastric Cancers with Lymphovascular Invasion Resected by Endoscopic Submucosal Dissection.

INTRODUCTION: In patients with intramucosal gastric cancer (MGC) who have undergone endoscopic submucosal dissection (ESD), lymphovascular invasions (LVIs) such as lymphatic invasion or venous invasion are considered risk factors of lymph node metastasis (LNM). However, the rate of LNM in MGCs with LVI and their clinicopathological features are unclear. OBJECTIVE: This study aimed to examine the rate of LNM and clinical characteristics of MGCs with LVI as compared to MGCs without LVI and minimally invasive submucosal gastric cancers (mSMGCs) with LVI. METHODS: Among the early gastric cancers excluding the remnant stomach who underwent ESD at our hospital from July 2003 to September 2018, the MGCs with LVI were included as the target in this study. MGCs without LVI and mSMGCs with LVI were also included as control. RESULTS: Seventeen lesions in 17 patients with MGCs with LVI, 1,149 lesions in 865 patients with MGCs without LVI, and 29 lesions in 29 patients with mSMGCs with LVI were analyzed. LVI was noted in 1.5% (17/1,166) of MGC cases. During follow-up of the MGC cases with LVI, there were no LNM or recurrences reported, and 14 patients survived and 3 died of other diseases. However, LNM occurred in 2 cases of mSMGC. Among the MGC cases, univariate analysis showed that the pap component, elevated type, and tumor diameters of 20 mm or more were statistically significant factors with respect to LVI, while multivariate analysis showed that the pap component was the only significant factor. CONCLUSION: Careful follow-up may be appropriate for MGCs with LVI due to the low risk of LNM. Additionally, the pap component is a significant factor in MGCs with LVI.

Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial.

INTRODUCTION: Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD. METHODS: A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1-10 points), adverse events, and rate of ulcer healing 8 weeks after ESD. RESULTS: A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group. CONCLUSION: SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.

Efficacy of EUS-guided FNB using a Franseen needle for tissue acquisition and microsatellite instability evaluation in unresectable pancreatic lesions.

BACKGROUND: The efficacy of immune checkpoint blockade in the treatment of microsatellite instability (MSI)-high tumors was recently reported. Therefore, the acquisition of histological specimens is desired in cases of unresectable solid pancreatic lesions (UR SPLs). This study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for UR SPL tissue acquisition and MSI evaluation. METHODS: A total of 195 SPL patients who underwent EUS-guided fine-needle aspiration (EUS-FNA) or EUS-FNB (EUS-FNAB) between January 2017 and March 2020 were enrolled in this study. Among them, 89 SPL patients (FNB: 28, FNA: 61) underwent EUS-FNAB using a 22-G needle (UR SPLs: 58, FNB: 22, FNA: 36) (UR SPLs after starting MSI evaluation: 23, FNB: 9, FNA: 14). RESULTS: The puncture number was significantly lower with FNB than with FNA (median (range): 3 (2-5) vs 4 (1-8), P <  0.01, UR SPLs: 3 (2-5) vs 4 (1-8), P = 0.036). Histological specimen acquisition was more commonly achieved with FNB than with FNA (92.9% (26/28) vs 68.9% (42/61), P = 0.015, UR SPLs: 100% (22/22) vs 72.2% (26/36), P <  0.01). The histological specimen required for MSI evaluation was acquired more often with FNB than with FNA (88.9% (8/9) vs 35.7% (5/14), P = 0.03). CONCLUSIONS: EUS-FNB using a Franseen needle is efficient for histological specimen acquisition and sampling the required amount of specimen for MSI evaluation in UR SPL patients.

Prognostic influence of endoscopic ultrasound-guided fine needle aspiration in IPMN-derived invasive adenocarcinoma.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for mucinous cystic neoplasm of the pancreas carries a potential risk of inducing peritoneal tumor cell dissemination. We investigated the diagnostic yield and safety of EUS-FNA-based cytology of cells obtained from the pancreatic invasion site of intraductal papillary-mucinous neoplasm-derived adenocarcinoma (IPMC). METHODS: We included 22 surgically resected IPMCs and 84 pancreatic ductal adenocarcinomas (PDACs). Among the IPMC cases, 14 did not undergo EUS-FNA before surgical resection. The diagnostic yield of EUS-FNA was compared between IPMC and PDAC. Additionally, prognosis (relapse-free and overall survival time after resection) and the rate of peritoneal dissemination were compared among IPMC with EUS-FNA, IPMC without EUS-FNA, and PDAC. A survival analysis was performed using the Kaplan-Meier method and log-rank test. RESULTS: (EUS-FNA diagnosis) There were no significant differences in the number of needle passages (PDAC 2.5 vs. IPMC 2.0 passages, P = 0.84) or puncture route (stomach/duodenum: 2/6 vs. 45/39, P = 0.29). However, the correct diagnosis rate was significantly higher in PDAC (92.9%) than in IPMC (62.5%) (P = 0.03). No procedure-related adverse events occurred. Peritoneal lavage cytology performed during the operation was negative in all cases. (Prognosis) Among IPMC with EUS-FNA, IPMC without EUS-FNA, and PDAC, there were no significant differences in relapse-free survival (21.0 vs. 22.4 vs. 12.5 months, respectively; P = 0.64) or overall survival time (35.5 vs. 53.1 vs. 35.9 months, respectively; P = 0.42), and peritoneal dissemination was detected during the observation period in 25%, 28.5%, and 21.4% cases, respectively (P = 0.82). CONCLUSION: Even though a correct diagnosis was more difficult to obtain in IPMC than in PDAC, IPMC allows specimens to be obtained without influencing the rate of recurrence and prognosis.

Endoscopic Ultrasonography-Guided Fine Needle Aspiration Can Be Used to Rule Out Malignancy in Autoimmune Pancreatitis Patients.

OBJECTIVES: The aim of this study was to review the suitability of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) for ruling out malignancy in autoimmune pancreatitis patients. METHODS: We retrospectively reviewed 40 autoimmune pancreatitis patients (type 1:37 patients; type 2: two patients; possible autoimmune pancreatitis: one patient) who received EUS-FNA. Among the 40 autoimmune pancreatitis patients, 34 were not histopathologically diagnosed with autoimmune pancreatitis by EUS-FNA, and they were followed up for more than 6 months in our hospital. Moreover, 14 pancreatic cancer patients who were not diagnosed by EUS-FNA were selected as a control group. These 14 patients constituted 3.9% of the 360 pancreatic cancer patients who received EUS-FNA. We evaluated the prognoses of the 34 autoimmune pancreatitis patients and the clinical differences between these 34 autoimmune pancreatitis patients and the 14 pancreatic cancer patients. RESULTS: All 34 autoimmune pancreatitis patients showed reduced pancreatic swelling. The main pancreatic duct dilation ( > 3 mm), the diameter of the main pancreatic duct, the capsule-like rim sign, and serum CA19-9 levels were significantly different between the autoimmune pancreatitis and pancreatic cancer patients (2.9% versus 69.2%, P < .01; 1.7 ± 1.6 mm versus 6.8 ± 5.0 mm, P < .01; 79.4% versus 0%, P < .01; 41.4 ± 79.0 U/mL versus 2079.1 ± 275.3 U/mL, P = .02). CONCLUSIONS: Almost all pancreatic cancers can be diagnosed by EUS-FNA. Furthermore, other clinical characteristics of pancreatic cancer undiagnosed by EUS-FNA were different from autoimmune pancreatitis undiagnosed by EUS-FNA. Endoscopic ultrasonography-guided FNA can be used to rule out malignancy in autoimmune pancreatitis patients.

Clinical significance of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein in pancreatic ductal adenocarcinoma.

BACKGROUND: Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA+-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. METHODS: In this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA+-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA+-M2BP, we investigated the presence of WFA+-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53). The bio-physiological effects of MDA-PATC53 supernatant were evaluated. Finally, the difference in the expression of glycosylation enzymes between MDA-PATC53 and Panc-1 were analyzed by cDNA microarray. RESULTS: We found that the serum WFA+-M2BP level could distinguish the 2 groups. The median serum COI of WFA+-M2BP was 0.98 and 0.51 in PDAC and CP, respectively. Additionally, WFA+-M2BP positive PDACs were more frequently associated with metastatic lesions than the WFA+-M2BP negative PDACs (91.6% vs. 41.7%, P = 0.009). The MDA-PATC53 cells alone produced WFA+-M2BP. However, we found that MDA-PATC53 supernatant containing WFA+-M2BP (1.0 COI) did not alter the biological behavior of cancer cell lines. The results of cDNA microarray revealed that several glycosylation enzymes with pro-oncologic function were highly expressed in MDA-PATC53 compared to Panc-1. CONCLUSIONS: Serum WFA+-M2BP can be a useful biomarker for the diagnosis of PDAC and the prediction of disease progression since it potentially reflects altered pro-oncologic glycosylation enzymes.

Possible participation of IgG4 in the activation of complement in IgG4-related disease with hypocomplementemia.

OBJECTIVE: To investigate which IgG subclasses contribute to the activation of the complement pathway in IgG4-related disease (IgG4RD) patients with hypocomplementemia. METHODS: Sera of IgG4RD patients were analyzed for the binding ability of IgG subclasses to complement component 1q (C1q). Polyethylene glycol (PEG) precipitates containing immune complexes (ICs) in sera of IgG4RD patients were analyzed for IgG subclass composition by Western blotting. PEG precipitates containing ICs (PEG-ICs) in sera of patients were also analyzed for their ability to consume complement in normal human serum (NHS) using a total complement hemolytic (CH50) assay and a commercial kit to measure the complement capacity of all three individual complement pathways. RESULTS: The C1q binding assay revealed high serum levels of C1q-binding IgG4 in IgG4RD patients with hypocomplementemia. ICs in PEG precipitates were formed with IgG4 in IgG4RD patients, regardless of the presence or absence of hypocomplementemia. We observed a marked reduction of CH50 and reduced complement activity in the classical complement pathway as well as the mannan-binding lectin complement pathway in NHS incubated with PEG-IC isolated from IgG4RD patients with hypocomplementemia. CONCLUSION: Our results suggest that IgG4 may participate in the activation of complement in IgG4RD patients with hypocomplementemia.

Conventional versus contrast-enhanced harmonic endoscopic ultrasonography-guided fine-needle aspiration for diagnosis of solid pancreatic lesions: A prospective randomized trial.

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) has been used to diagnose solid pancreatic lesions (SPLs). The aim of this study was to investigate the efficacy of CEH-EUS-guided fine-needle aspiration (CEH-EUS-FNA) compared with that of conventional EUS-FNA for the diagnosis of SPLs. METHODS: Forty patients with solid pancreatic lesions who visited Fukushima Medical University between September 2013 and June 2014 were recruited for this prospective study. Twenty patients underwent CEH-EUS-FNA, and 20 patients underwent conventional EUS-FNA. The sampling rate, sensitivity, accuracy, and number of needle passes required to obtain sufficient samples were compared between the two groups. RESULTS: Patient characteristics, sampling rate, accuracy, and sensitivity were not significantly different between the two groups. The final diagnosis of patients who underwent CEH-EUS-FNA was pancreatic cancer in 19 and intraductal papillary mucinous carcinoma in one. Nineteen patients who underwent conventional EUS-FNA were finally diagnosed with pancreatic cancer and one was diagnosed as cancer of the common bile duct. There was a significant difference in the number of needle passes required. A sufficient sample was obtained on one needle pass in 60% (12/20) of CEH-EUS-FNA group compared with 25% (5/20) of the conventional EUS-FNA group. CONCLUSIONS: Fewer needle passes were required to obtain samples from solid pancreatic lesions using CEH-EUS-FNA than those required using conventional EUS-FNA. Therefore, CEH-EUS-FNA may be more efficient and safer than conventional EUS-FNA for the diagnosis of solid pancreatic lesions.

Relationship of complement activation route with clinical manifestations in Japanese patients with systemic lupus erythematosus: a retrospective observational study.

OBJECTIVES: To assess the relationship between the complement activation route and clinical manifestations in systemic lupus erythematosus (SLE). METHODS: Patients with SLE in whom complement activation occurred were divided into two groups: those in whom the complement system was mainly activated through the classical pathway (low serum C3 and C4 levels; CP group); and those in whom the complement system was solely activated through the alternative pathway (low serum C3 with normal C4 levels; AP group). Clinical manifestations were compared between the groups. RESULTS: The CP group had higher frequencies of arthritis, serositis, and nephritis, and a higher prevalence of anti-DNA antibodies compared to the AP group (arthritis: 50.0% vs. 13.0%, p = 0.0014; serositis: 37.5% vs. 13.0%, p = 0.0257; nephritis: 63.6% vs. 21.7%, p = 0.0003; anti-DNA antibodies: 73.9% vs. 30.4%, p = 0.0001). In contrast, the AP group had a higher frequency of anti-phospholipid (anti-PL) antibodies and a higher prevalence of antiphospholipid syndrome (APS) (anti-PL antibodies: 70.6% vs. 37.3%, p = 0.0136; APS: 39.1% vs. 5.7%, p < 0.0001). CONCLUSIONS: Our results suggest that a different complement system mechanism may act in the pathogenesis of APS in patients with SLE.

[A study of endoscopic therapy for bile duct stones in elderly patients].

AIM: To evaluate the safety and efficacy of endoscopic therapy for bile duct stones in elderly patients aged over 80 years. METHODS: We enrolled 20 elderly patients aged over 80 years and 50 patients who were younger than 79 years of age who had received their first endoscopic therapy for bile duct stones at our hospital from February 2012 to December 2013. A retrospective analysis was performed which included the following clinical parameters: the use of antithrombotic drugs; a past history of abdominal surgery; performance status (PS); the shortest diameter of the largest stone; and the total number of stones. The treatment outcomes of operations with endoscopic sphincterotomy, endoscopic papillary balloon dilation, or endoscopic papillary large balloon dilation were compared. The operative time, complete stone clearance rate, operative success rate (complete stone clearance or bile duct stent insertion), and adverse events were compared as treatment outcomes. RESULTS: There was no significant difference in the use of antithrombotic drugs, past history of abdominal surgery, number of stones, or treatment received between the age groups, while PS was significantly lower, and the diameter of the largest stone was significantly greater in the patients over 80 years of age. The operative time, complete stone clearance rate, operative success rate, and the number of adverse events did not differ significantly between the age groups. CONCLUSION: Endoscopic therapy for bile duct stones was found to be safe and effective in elderly patients over 80 years of age.

Novel Photodynamic Therapy for Esophageal Squamous Cell Carcinoma following Radiotherapy.

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently selected as treatments for esophageal squamous cell carcinoma (ESCC). However, salvage treatment remains challenging when endoscopic resection is not indicated for residual or recurrent ESCC following RT or CRT. Recently, owing to the emergence of second-generation photodynamic therapy (PDT) using talaporfin sodium, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. In this study, the effectiveness and safety of second-generation PDT in patients with residual or recurrent ESCC following RT or CRT were examined. Local complete response (L-CR) rates, procedure-related adverse events, and prognosis were evaluated. In 12 patients with 20 ESCC lesions, the L-CR rates were 95.0%. Perforation, postoperative bleeding, and photosensitivity were not observed. Esophageal stricture following PDT developed in one patient, but this could be addressed using balloon dilation. During a median follow-up period of 12 (range, 3-42) months, the 3-year cause-specific survival rate was 85.7%. Even in patients with a Charlson comorbidity index score ≥ 3, the 2-year overall survival rates were 100%. In conclusion, PDT was an efficacious and a safe salvage treatment in patients with local residual or recurrent ESCC following RT or CRT.

Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in patients with cirrhosis and esophageal varices.

Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell carcinoma (SESCC). However, the treatment strategy for SESCC complicated by esophageal varices (EVs) has not been established. We report two cases of SESCC in patients with alcoholic cirrhosis complicated by EVs who underwent ESD. Case 1 presented with EVs on the anal side of the SESCC, and endoscopic variceal ligation (EVL) was performed before ESD. After EVL, the SESCC was successfully treated by ESD without any adverse events. Case 2 presented EVs from the anal side of the SESCC to the submucosa just below the SESCC. Then, EVL and endoscopic injection sclerotherapy with polidocanol were performed before ESD. However, ESD was not completed because of severe bleeding by uncontrolled blood flow below and around the SESCC. Bleeding during ESD was controlled in case 1, but not in case 2.

Comparison of time to recurrent biliary obstruction between plastic stents and metallic stents for endoscopic ultrasound­guided biliary drainage.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) may prevent stent placement at the bile duct stricture. Therefore, whether a plastic stent (PS) or metallic stent (MS) should be used for EUS-BD remains to be undetermined. The present study aimed to clarify whether a PS or MS was more efficient for EUS-BD. Patients with malignant biliary obstruction who were successfully treated with EUS-BD were enrolled in the present study. The clinical characteristics, procedural outcomes and time to recurrent biliary obstruction (TRBO) were compared between patients treated with a PS (PS group) and patients treated with an MS (MS group). Consequently, 28 patients underwent PS placement and 11 patients underwent MS placement. In the PS group, 12 patients also underwent EUS-antegrade stenting (AGS) using an MS. The TRBO was not significantly different between the two groups (P=0.25). When the patients with AGS were excluded, the TRBO was significantly longer in the MS group than in the PS group (P=0.036). However, the TRBO was not significantly different between the patients in the MS group and those in the PS group who underwent AGS (P=0.61). In EUS-BD, MS is expected to be associated with a longer TRBO than PS. However, combining EUS-BD with AGS may help overcome the shorter TRBO associated with the use of PS.