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.

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.

Prevalence of Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release With Amyloid Deposition.

BACKGROUND: Carpal tunnel syndrome (CTS) is considered an early sign of cardiac amyloidosis (CA) because amyloid deposition is often confirmed in the tenosynovium removed during carpal tunnel release (CTR); however, the prevalence of concomitant CA is unclear.Methods and Results: We prospectively examined 700 patients who underwent CTR and evaluated amyloid deposition after tenosynovium removal. Amyloid deposition was observed in 261 (37%) patients, who were significantly older and predominantly male (P<0.05). Of them, 120 agreed to cardiac screening. We performed 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy in 12 patients who met either of the following criteria: (1) interventricular septal diameter (IVSd) ≥14 mm or (2) 12 mm ≤ IVSd < 14 mm with above-normal limits in high-sensitivity cardiac troponin T (hs-cTnT). Six patients (50%) had positive findings on 99 mTc-PYP scintigraphy and were diagnosed with wild-type transthyretin CA. Concomitant CA was observed in 6/120 (5%) CTR patients with amyloid deposition and 50% (6/12) in patients with left ventricular hypertrophy (≥12 mm) with increased hs-cTnT levels. CONCLUSIONS: Amyloid deposition was frequently observed in the removed tenosynovium of elderly men with CTS. Cardiac screening may be useful for early diagnosis of CA in patients undergoing CTR with amyloid deposition.

A neonate with multiple hand flexor tendon ruptures due to methicillin-susceptible Staphylococcus aureus sepsis: a case report.

BACKGROUND: Neonatal pyogenic tenosynovitis is a highly emergent soft tissue infection. We report a case of a neonate with pyogenic tendinopathy and tendon rupture diagnosed by ultrasonography (US). He subsequently developed pyogenic arthritis and osteomyelitis during antimicrobial therapy. CASE PRESENTATION: A 7-day-old boy was admitted to our hospital with redness and swelling of the right index finger. US on admission showed rupture of the flexor tendon of the right index finger with inactivity. The day after admission, he developed pyogenic arthritis of the right elbow and, subsequently, pyogenic osteomyelitis. Staphylococcus aureus was identified through bacterial culture, and the patient was treated with intravenous antibiotics for 6 weeks. However, after discharge from our hospital, rupture of the flexor tendon of the left thumb was confirmed. A two-stage flexor tendinoplasty was completed at the age of 2 years and 1 month for the flexor tendon rupture on his right index finger. CONCLUSIONS: In addition to blood culture, ultrasonographic evaluation should be performed in neonates with erythematous and swollen joints to identify the focus of infection as soon as possible. Moreover, repeated regular US examination is important in the follow-up of bone and soft tissue infections.

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.

Acquired resistance to trastuzumab/pertuzumab or to T-DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728.

HER2-targeting antibodies (trastuzumab, pertuzumab) and a HER2-directed antibody-drug conjugate (trastuzumab emtansine: T-DM1) are used for the treatment of HER2-overexpressing breast cancer. However, these treatments eventually become ineffective due to acquired resistance and there is an urgent need for alternative therapies. TAS0728 is a small-molecule, irreversible selective HER2 kinase inhibitor. In the present study, we established new in vivo models of cancer resistance by continuous exposure to a combination of trastuzumab and pertuzumab or to T-DM1 for evaluating the effect of TAS0728 on HER2 antibody-resistant populations. Treatment with trastuzumab and pertuzumab or with T-DM1 initially induced tumor regression in NCI-N87 xenografts. However, tumor regrowth during treatment indicated loss of drug effectiveness. In tumors with acquired resistance to trastuzumab and pertuzumab or to T-DM1, HER2-HER3 phosphorylation was retained. Switching to TAS0728 resulted in a significant anti-tumor effect associated with HER2-HER3 signal inhibition. No alternative receptor tyrosine kinase activation was observed in these resistant tumors. Furthermore, in a patient-derived xenograft model derived from breast cancer refractory to both trastuzumab/pertuzumab and T-DM1, TAS0728 exerted a potent anti-tumor effect. These results suggest that tumors with acquired resistance to trastuzumab and pertuzumab and to T-DM1 are still dependent on oncogenic HER2-HER3 signaling and are vulnerable to HER2 signal inhibition by TAS0728. These results provide a rationale for TAS0728 therapy for breast cancers that are refractory to established anti-HER2 therapies.

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.

TAS05567, a Novel Potent and Selective Spleen Tyrosine Kinase Inhibitor, Abrogates Immunoglobulin-Mediated Autoimmune and Allergic Reactions in Rodent Models.

Spleen tyrosine kinase (Syk) is involved in regulation of B-cell receptor (BCR) and Fc receptor downstream signal pathways. Syk plays an essential role in production of inflammatory mediators and differentiation in various immune cells and is therefore an attractive target for treating inflammatory conditions, such as autoimmune and allergic diseases. We identified TAS05567 as a highly selective Syk inhibitor and evaluated its therapeutic potential in animal models. In vitro biochemical assays were performed with available kinase assay panels. Inhibitory effects of TAS05567 on immune cells were analyzed by assessing the Syk downstream signaling pathway and production of inflammatory factors. In vivo effects of TAS05567 were evaluated in animal models of autoimmune diseases and antigen-specific IgE transgenic mice. TAS05567 inhibited only 4 of 191 kinases tested but inhibited Syk enzymatic activity with high potency. TAS05567 inhibited BCR-dependent signal transduction in Ramos cells, FcγR-mediated tumor necrosis factor-α production in THP-1 cells, and FcεR-mediated histamine release from RBL-2H3 cells. In rheumatoid arthritis models, TAS05567 suppressed hind-paw swelling in a dose-dependent manner compared with vehicle. Moreover, TAS05667 markedly reduced histopathologic scores in an established rat arthritis model. In a mouse immune thrombocytopenic purpura model, platelet counts were reduced with injection of anti-platelet antibody. TAS05567 prevented the platelet count decrease in a dose-dependent manner. Finally, TAS05567 treatment suppressed IgE-mediated ear swelling in vivo. Collectively, our data indicate TAS05567 is a selective Syk inhibitor and potential therapeutic candidate for treating humoral immune-mediated inflammatory conditions such as autoimmune and allergic diseases.

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.

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.

A multicenter comparative study of endoscopic ultrasound-guided fine-needle biopsy using a Franseen needle versus conventional endoscopic ultrasound-guided fine-needle aspiration to evaluate microsatellite instability in patients with unresectable pancreatic cancer.

BACKGROUND/AIMS: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. METHODS: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018-2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. RESULTS: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. CONCLUSION: EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Intracellular C3 Modulates EMT via the Akt/Smad Pathway in Pancreatic Cancer Cells.

BACKGROUND/AIM: We aimed to explore the role of intracellular C3 in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: We evaluated C3 expression in PDAC using a gene expression database and tissue microarray. To clarify the role of C3 expression in PDAC, we conducted knockdown experiments using C3 short hairpin RNA (shRNA) in BxPC-3 cells. Differences in protein expression and cell behaviours were analysed. RESULTS: C3 was highly expressed in PDAC and correlated with cancer metastasis. In vitro experiments using BxPX-3 cells showed that C3 and its active form, C3a, were expressed in tumour cells. C3 knockdown reduced cell migration and invasion by inhibiting Akt/Smad pathway activation. TNF-α, not IL-6, enhanced C3 expression in this PDAC cell line. CONCLUSION: Intracellular C3 may regulate epithelial-mesenchymal transition in pancreatic cancer.

Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in the Remnant Stomach.

Endoscopic submucosal dissection (ESD) in patients with early gastric cancers (EGCs) in the remnant stomach is technically difficult, owing to the limited space and fibrosis under the suture lines and anastomoses. Conversely, ESD for patients with EGCs in the remnant stomach is less invasive and provides better quality of life than completion total gastrectomy. To clarify the effectiveness and safety of ESD, we reviewed the medical records of patients with EGCs in the remnant stomach who underwent ESD between July 2006 and October 2020 at our institution. All identified patients were included in the analysis. Of 25 patients with 27 lesions, the en bloc and R0 resection rates were 88.9% and 85.2%, respectively. Neither perforation nor postoperative bleeding was observed. During a median follow-up period of 48 (range, 5-162) months, the 5-year overall survival rate was 71.0%, whereas the 5-year cause-specific survival rate was 100%. No obvious differences in the outcomes of procedures with suture line involvement and without suture line or anastomosis involvement were noted. In conclusion, ESD was effective and safe in patients with EGCs in the remnant stomach despite the suture line involvement.