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.

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).

[Intestinal malrotation accompanied by a right paraduodenal hernia in an adult: a case report].

A 72-year-old woman was admitted to our department in March 2020 for an evaluation of nausea, vomiting, diarrhea, liver dysfunction, and hypokalemia, which had persisted intermittently since 2013. Thickening of the descending duodenal wall and a sac-like appearance the intestinal tract in the vicinity of the duodenal papilla were observed in abdominal computed tomography. No duodenojejunal curvature, with two intestinal loops identified in the descending region, was detected in contrast-enhanced upper gastrointestinal imaging. Based on these imaging findings, the patient was diagnosed with intestinal malrotation (incomplete rotation and fixation) accompanied by a right paraduodenal hernia based on the Nishijima classification. Thus, surgery was performed at our hospital. Gastrointestinal symptoms did not recur, and liver dysfunction and hypokalemia improved postoperatively.

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.

Association between time to stent dysfunction and the anti-tumour effect of systemic chemotherapy following stent placement in patients with pancreaticobiliary cancers and malignant gastric outlet obstruction: a retrospective cohort study.

BACKGROUND: Malignant gastric outlet obstruction (MGOO) occasionally occurs due to pancreaticobiliary cancer. Endoscopic duodenal stenting (DS) is a common treatment for MGOO. However, it has been reported that DS does not have sufficient patency time for it to be used in patients who have a potentially increased lifespan. Nowadays, systemic chemotherapy for pancreaticobiliary cancer has developed, and its anti-tumour effect would make time to stent dysfunction longer. Therefore, we retrospectively evaluated the association between objective response to systemic chemotherapy, followed by DS and time to stent dysfunction in patients with advanced pancreaticobiliary cancer. METHODS: This retrospective study included 109 patients with advanced pancreaticobiliary cancer who received systemic chemotherapy after DS. Patients who showed complete or partial response were defined as responders. The rest were defined as non-responders. Time to stent dysfunction was compared between responders and non-responders using the landmark analysis at 2 months after DS. Death without recurrence of MGOO was considered as a competing risk for time to stent dysfunction. RESULTS: Combination and monotherapy regimens were adopted for 46 and 63 patients, respectively. Median progression-free survival and overall survival were 3.2 months (95% confidence interval [CI], 2.4-4.0) and 6.0 months (95% CI, 4.6-7.3). Objective response was observed in 21 patients (19.3%). Median time to stent dysfunction was 12.5 months (95% CI, 8.4-16.5) in the entire cohort. In 89 patients, responders had a lower cumulative incidence of stent dysfunction than non-responders: 9.5 and 19.1% at 6 months, and 19.0 and 27.9% at 1-year, respectively. There was difference of time to stent dysfunction between responders and non-responders among patients who received combination regimen as the first-line treatment with p-value of 0.009: cumulative incidence was 0 and 42.9% at 6 months, and 9.3 and 57.1% at 1-year, respectively. CONCLUSIONS: Longer time to stent dysfunction is expected when systemic chemotherapy following DS suppresses tumour progression; DS is slated to be a standard treatment for MGOO even in patients with pancreaticobiliary cancer and a long lifespan.

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.

Repeated Lusutrombopag Treatment for Thrombocytopenia in Patients with Chronic Liver Disease.

BACKGROUND/AIMS: Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is used to treat thrombocytopenia based on the results of a phase 3 trial, including data for single-use administration in patients with chronic liver disease (CLD) undergoing invasive procedures. We aimed to evaluate the efficacy and safety of repeated lusutrombopag use. METHODS: Lusutrombopag was administered repeatedly in patients undergoing multi-cycle invasive procedures at intervals >1 month. RESULTS: Data from 8 patients (median platelet count at baseline, 44.0 [range, 35-49] × 109/L) and 25 cycles of invasive procedures, including 2 cycles in 3 patients, 3 cycles in 4 patients, and 7 cycles in 1 patient, were retrospectively evaluated. The procedures included 18 transarterial chemoembolizations, 5 radiofrequency ablations, and 2 liver needle biopsies. Platelet counts increased significantly compared with baseline, and median changes in platelet counts were 46.0 × 109/L (p = 0.012) in cycle 1, 44.0 × 109/L (p = 0.012) in cycle 2, and 42.0 × 109/L (p = 0.008) in cycles 3-7. No severe adverse events, including portal vein thrombus or bleeding, were observed. CONCLUSIONS: Repeated use of lusutrombopag might be safe and effective against thrombocytopenia in patients with CLD undergoing multi-cycle invasive procedures, although long-term data from more patients are required.

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.

MicroRNA let-7d targets thrombospondin-1 and inhibits the activation of human pancreatic stellate cells.

OBJECTIVES: The microRNA (miRNA) let-7d is linked to the formation of pancreatic cancer-related fibrosis. In this study, the mechanism by which let-7d regulates the activation of the human pancreatic stellate cell (hPSC) was evaluated. METHODS: The transient transfection of a let-7d mimic in the hPSCs was performed, and the altered thrombospondin 1 (THBS1) expression was confirmed by western blotting and real-time qPCR. Targeting of the 3'-untranslated region (UTR) of THBS1 by let-7d was investigated by the luciferase assays. After hPSC transfection using THBS1 siRNA, the fibrosis markers (α-SMA and collagen 1A1) were evaluated by western blotting and real-time qPCR. The correlation between tumor fibrosis and let-7d or THBS1 was estimated using the data from The Cancer Genome Atlas project. Finally, the effects of genistein on the hPSCs were evaluated. RESULTS: We found that a let-7d mimic inhibits THBS1 expression by targeting its 3'-UTR. THBS1 inhibition by siRNA inhibited hPSC activation. An in silico analysis revealed that let-7d and THBS1 expression are negatively correlated. Additionally, let-7d was negatively correlated with the stromal score, while THBS1 was positively correlated with this score. Genistein substantially induced let-7d and decreased the expression of fibrosis marker along with the inhibition of THBS1. CONCLUSIONS: Let-7d inhibited hPSC activation by targeting THBS1. Genistein induced the expression of let-7d and might modulate pancreatic fibrosis.

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.

[Nonalcoholic steatohepatitis after pancreatoduodenectomy with rapid progression of hepatic fibrosis: a case report].

A 64-year-old woman who had undergone pancreatoduodenectomy for intraductal papillary mucinous carcinoma 10 months previously was referred to our department complaining of ascites and general malaise. Abdominal computed tomography (CT) showed a markedly decreased hepatic CT value. Liver biopsy revealed nonalcoholic steatohepatitis. Treatment with nutritional control and pancreatic enzyme supplements improved liver function. Exocrine pancreatic enzyme insufficiency from chronic pancreatitis is considered to be a cause of rapid progression of hepatic steatosis.

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.

Sarcopenia: Prognostic Value for Unresectable Pancreatic Ductal Adenocarcinoma Patients Treated With Gemcitabine Plus Nab-Paclitaxel.

OBJECTIVE: The aim of the study was to clarify the association of skeletal muscle mass and the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) treated with gemcitabine plus nab-paclitaxel (GnP). METHODS: We included 124 unresectable PDAC patients who received GnP chemotherapy. Skeletal muscle mass of the third lumbar vertebrae (L3) level was measured by computed tomography immediately before GnP initiation, and the skeletal muscle index (L3-SMI) was calculated. Sarcopenia was defined as L3-SMI less than 42 cm2/m2 in male patients and less than 38 cm2/m2 in female patients. RESULTS: Sarcopenia was found in 63 patients (50.8%). There was no significant difference in overall survival (OS) between sarcopenia and nonsarcopenia patients; however, in elderly patients (>70 years), the OS of sarcopenia patients was significantly poorer than that of nonsarcopenia patients (390 vs 631 days, respectively; hazard ratio, 2.64; 95% confidence interval, 1.33-5.23). Multivariate analyses in elderly patients revealed that sarcopenia and tumor stage were independent poor prognostic factors. Despite the short OS of elderly sarcopenia patients, there were no significant differences in progression-free survival or response rate. CONCLUSIONS: Sarcopenia diagnosed by L3-SMI is a prognostic factor in elderly patients who receive GnP for unresectable PDAC. However, GnP exhibits a certain efficacy in sarcopenia and nonsarcopenia patients.

Biliary metal stents should be placed near the hilar duct in distal malignant biliary stricture patients.

BACKGROUND: Endoscopic biliary drainage using a self-expandable metallic stent (SEMS) has been widely performed to treat distal malignant biliary obstruction (DMBO). However, the optimal position of the stent remains unclear. AIM: To determine the ideal position for SEMS placement. METHODS: In total, 135 DMBO patients underwent SEMS (uncovered or covered) placement over a ten-year period. A total of 127 patients with biliary obstruction between the junction of the cystic duct and Vater's papilla were enrolled. An SEMS was placed through the upper common bile duct 2 cm from the biliary hilar duct in 83 patients (Hilar group) or near the top of the biliary obstruction in 44 patients (Lower group). Technical and functional success, adverse events, and risk factors for SEMS dysfunction were evaluated. RESULTS: The stent patency period was significantly longer in the Hilar group than in the Lower group (P value < 0.01). In multivariate analysis, the only statistically significant risk factor for SEMS dysfunction was being in the Lower group (hazard ratio: 9.94, 95% confidence interval: 2.25-44.0, P < 0.01). CONCLUSION: A longer patency period was achieved by positioning the SEMS near the biliary hilar duct.

Drug treatment for chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer.

Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future.

Efficacy of a novel large-cell Niti-S stent with a slim delivery system for hilar biliary obstruction: a preliminary study.

OBJECTIVES: The large-cell Niti-S stent is useful for multiple stenting in patients with malignant hilar biliary obstruction (MHBO). Recently, a novel uncovered self-expandable metallic stent (USEMS) (a Niti-S large-cell SR slim delivery system) was developed. In this study, we aimed to evaluate the efficacy of this USEMS slim delivery system in MHBO patients. MATERIALS AND METHODS: Outcomes related to USEMS placement, the clinical course, and the period to recurrent biliary obstruction (RBO) were evaluated in MHBO patients who received multiple USEMSs with the Niti-S large-cell SR slim delivery system. RESULTS: Twenty-two MHBO patients underwent the placement of multiple USEMSs, including the novel slim-delivery stent. Six patients had a past history of upper gastrointestinal reconstruction (Billroth I: 1, Billroth II: 4, Roux-en-Y: 1). The number of USEMSs placed in each patient was 2-6. Three procedures were reinterventions. The new slim delivery system was placed as the first stent in ten patients and as an additional stent in the remaining patients. Seven patients were drained using only Niti-S large-cell SR slim delivery stents. The technical and clinical success rates were both 100%. CONCLUSIONS: Placing multiple USEMSs in patients with a past history of abdominal surgery or in reintervention is difficult. Although difficult cases were included in this study, stent-in-stent placement with the novel Niti-S large-cell SR slim delivery system was useful in treating MHBO patients. In addition, this novel stent might be the first choice for MHBO patients.KEY MESSAGESEndoscopic multistenting for MHBO is challenging. In addition, reintervention or multistenting for MHBO patients with a past history of abdominal surgery becomes more difficult.The novel Niti-S large-cell SR slim delivery USEMS is useful as an additional stent because the delivery system is thin and suitable for a 0.025 guidewire. In addition, the novel stent is of the braided type and has a large mesh. Therefore, the novel stent is expected to have strong radial force and can be used as the first SEMS.The Niti-S large-cell SR slim delivery stent is long enough to be used in patients with upper gastrointestinal reconstruction. Although this study included patients with reintervention or a past history of upper gastrointestinal reconstruction, the technical success rate of multiple stenting for MHBO patients was 100%. The slim-delivery stent might overcome several difficulties of endoscopic multistenting.