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Background/Aims The optimal length of the uncovered portion of partially covered self-expandable metal stents (PCSEMSs) used in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) remains unclear. This study investigated the safety and efficacy of PCSEMSs with different uncovered lengths, with a focus on stent migration and time to recurrent biliary obstruction (RBO). Methods Outcomes of patients undergoing EUS-HGS using PCSEMSs with 5-mm and 20-mm uncovered portions at our institution from January 2016 to December 2021 were compared. Results Sixty-two patients underwent EUS-HGS using PCSEMS (5/20-mm uncovered portions: 32/30). Stent migration occurred only in the 5-mm group. There were no differences in RBO rates (28.1% vs. 40.0%) or median time to RBO (6.8 vs. 7.1 months) between the two groups. Median overall survival (OS) was longer in the 20-mm group (3.1 vs. 4.9 months, p=0.037) due to the higher number of patients that resumed chemotherapy after EUS-HGS (56.7% vs. 28.1%, p=0.029). Good performance status, absence of hepatic metastases, and chemotherapy after EUS-HGS were independent predictors of longer OS. Conclusions No migration was observed in patients treated with PCSEMS with 20-mm uncovered portions. Patients treated with PCSEMS with 20-mm uncovered portions performed at least as well as those treated with 5-mm uncovered portions in all material respects.

Background/Aims Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. Methods We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy–endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. Results Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01–7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85–6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. Conclusions Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Background/Aims Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. Methods We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. Results TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. Conclusions The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Abstract Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post‐operative survival outcomes. To test this hypothesis, we utilised a multi‐institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09–1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10–1.46). Compared to cases with 0–2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09–1.51) and 1.47 (95% CI, 1.22–1.78), respectively (ptrend

Abstract Objectives Hepaticojejunostomy anastomotic stricture (HJAS) is a serious adverse event of pancreaticoduodenectomy. Preoperative biliary drainage with a self‐expandable metal stent (SEMS) is often performed before pancreaticoduodenectomy. The purpose of this study is to evaluate the risk factors and impact of preoperative SEMS placement on developing benign HJAS after pancreaticoduodenectomy. Methods We retrospectively analyzed consecutive patients who underwent pancreatoduodenectomy at our institution between July 2014 and June 2020. Risk factors for benign HJAS were identified using univariate and multivariate logistic regression analysis. We also compared outcomes of preoperative biliary drainage using SEMS and non‐SEMS. Results Of the 626 included patients, benign HJAS occurred in 36 patients (5.8%). The median follow‐up time was 36.7 months (interquartile range, 25.4–57.4 months). Multivariate logistic regression analysis revealed that lack of preoperative biliary drainage, preoperative bile duct diameter

Abstract Background 10‐mm self‐expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent‐related adverse events (AEs). Methods We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent‐related non‐event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent‐related AEs). Secondary outcomes included stent‐related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results A total of 76 patients were included (6‐mm group: 23; 10‐mm group: 53). Stent‐related NER (57% vs. 64%, p = 0.610), stent‐related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95–5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk‐reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions Stent‐related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6‐mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Abstract We report a case of ruptured cystic artery pseudoaneurysm after self‐expandable metal stent placement for malignant biliary obstruction. A 78‐year‐old woman on palliative care after chemotherapy for unresectable pancreatic head cancer presented with obstructive jaundice. Imaging revealed a dilated common bile duct and an enlarged gallbladder with cystic wall thickening. Endoscopic retrograde cholangiopancreatography was performed and a fully‐covered self‐expandable metal stent was placed in the bile duct, leading to resolution of jaundice. She presented with hematochezia 7 days later. Contrast‐enhanced computed tomography revealed a cystic artery pseudoaneurysm with extravasation of contrast into a blood‐filled gallbladder. Hemostasis was achieved after emergent transcatheter arterial embolization. Rupture of cystic artery pseudoaneurysm should be raised as a differential diagnosis for hemobilia after self‐expandable metal stent placement, particularly in cases accompanied by inflamed gallbladders.

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3–4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

Background/Aims Digital single-operator cholangioscopy (DSOC)-guided mapping biopsy (DMB) and tube-assisted mapping biopsy (TMB) are two techniques used for preoperative evaluation of biliary tract cancer (BTC). However, data regarding the diagnostic performance of these techniques are limited. Methods We retrospectively examined consecutive patients with BTC who underwent either technique at our institution between 2018 and 2020. We evaluated the technical success rate, adequate tissue acquisition rate, and diagnostic performance of these techniques for the evaluation of lateral spread of BTC. Results A total of 54 patients were included in the study. The technical success rate of reaching the target sites was 95% for DMB and 100% for TMB. The adequate tissue acquisition rate was 61% for DMB and 69% for TMB. The adequate tissue acquisition rate was low, especially for target sites beyond the secondary biliary radicles. The sensitivity of DMB alone was 39%, which improved to 65% when combined with visual impression. Experts demonstrated a higher negative predictive value and diagnostic accuracy with respect to both DSOC visual impression and DMB for the evaluation of lateral spread of BTC compared to trainees. Conclusions Adequate tissue acquisition rates were similar between the two techniques. Since DMB requires expertise, TMB may be an acceptable option when DSOC is unavailable or when DSOC expertise is limited.

Abstract Objectives Duckbill‐type metal stent (DMS) was the first laser‐cut biliary metal stent with an anti‐reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal. Methods We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared. Results Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat‐tooth forceps were applied horizontally across the stent. Conclusions Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal.

Abstract Background The usefulness of duckbill‐type anti‐reflux metal stent (DMS) in self‐expandable metal stent‐naïve pancreatic cancer (PC) patients has not been well‐studied. This study aimed to evaluate the efficacy and safety of DMS in such patients. Methods We analyzed consecutive patients with unresectable PC who received a covered metal stent (CMS) as the initial self‐expandable metal stent at our institution. Technical success, functional success, causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates were compared between DMS and conventional CMS (c‐CMS). Results A total of 69 patients were included (DMS: 28, c‐CMS: 41). Technical success, functional success, and AEs were similar between groups. Tumor ingrowth was more common in the DMS group (18% vs. 0%, p = 0.009), while non‐occlusion cholangitis tended to be more common in the c‐CMS group (0% vs. 15%, p = 0.074). Median time to RBO was similar between groups (276 vs. 273 days, p = 0.915). The anti‐reflux valve of DMS was found torn in 56% of patients. Endoscopic reintervention was successful in all cases, despite failed stent removal in 88% of patients in the DMS group. Conclusions DMS was not associated with longer time to RBO compared to c‐CMS in self‐expandable metal stent‐naïve patients.

Background/Aims Several fine-needle biopsy (FNB) needles are available for endoscopic ultrasound (EUS)-guided tissue acquisition. However, there is disagreement on which type of needle has the best diagnostic yield. The aim of this study was to compare the performance and safety of two commonly used EUS-FNB needles. Methods We retrospectively analyzed consecutive patients who underwent EUS-FNB between June 2016 and March 2020 in our hospital. Two types of needles were evaluated: a 20-gauge Menghini needle with a lateral forward bevel and a 22-gauge Franseen needle. Rapid on-site evaluation was performed in all the cases. A multivariate analysis was performed to clarify the negative predictive factors for obtaining a histological diagnosis. Propensity score matching was performed to compare the diagnostic yields of these two needles. Results We analyzed 666 patients and 690 lesions. The overall diagnostic rate of histology alone was 88.8%, and the overall adverse event rate was 1.5%. Transduodenal access and small lesions (≤2 cm) were identified as negative predictive factors for obtaining a histological diagnosis. After propensity score matching, 482 lesions were analyzed. The diagnostic accuracy rates of histology in the M and F needle groups were 89.2% and 88.8%, respectively (p=1.00). Conclusions Both the needles showed high diagnostic yield, and no significant difference in performance was observed between the two.

Abstract Background There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival. Methods From 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion). Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively. Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Background and study aims Self-expandable metallic stents (SEMS) are now widely used even for patients with borderline resectable (BR) pancreatic cancer (PC), as neoadjuvant therapy has become common. Therefore, we conducted this study to evaluate safety of SEMS placement in the population including BR PC and to explore risk factors for recurrent biliary obstruction (RBO), pancreatitis, and cholecystitis. Patients and methods We retrospectively investigated consecutive patients with PC who received initial SEMS between January 2015 and March 2019. We compared time to RBO (TRBO), causes of RBO, and stent-related adverse events (AEs) according to resectability status. Univariate and multivariate analyses were performed to explore risk factors for TRBO, pancreatitis, and cholecystitis. Results A total of 135 patients were included (BR 31 and unresectable [UR] 104). Stent-related AEs occurred in 39 patients: pancreatitis 14 (mild/moderate/severe 1/6/7), cholecystitis 12, and non-occluding cholangitis 13. TRBO, causes of RBO, and stent-related AEs were not significantly different according to resectability status. Overall rate of RBO was higher in UR PC due to the longer follow-up period. Sharp common bile duct (CBD) angulation was an independent risk factor for short duration of TRBO. High pancreatic volume index and SEMS of high axial force were independent risk factors for pancreatitis, whereas tumor involvement to orifice of cystic duct was the only risk factor for cholecystitis. Conclusions We demonstrated that SEMS can be safely deployed even in patients with BR PC. Sharp CBD angulation and high pancreatic volume index were identified as novel risk factors for RBO and pancreatitis, respectively, after SEMS placement.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition is sometimes required to diagnose small solid pancreatic lesions. The aim of this study was to evaluate the diagnostic yield of EUS-guided tissue acquisition for small solid pancreatic lesions and the differences in diagnostic yield among different needles. Patients and method We retrospectively analyzed consecutive patients who had undergone EUS-guided tissue acquisition for solid pancreatic lesions less than 2 cm between November 2012 and June 2019. Three types of needles were evaluated in this study: a 22-gauge fine-needle aspiration (FNA) Lancet needle, a 20-gauge fine-needle biopsy (FNB) Menghini needle with a lateral forward bevel, and a 22-gauge FNB Franseen needle. We evaluated the diagnostic yield and safety of the procedure using these needles. Results We analyzed 160 patients with 163 lesions. The overall sensitivity, specificity, and accuracy were 92.0 %, 100 %, and 92.6 %, respectively. In the histological plus cytological diagnosis, accuracies of the Lancet, Menghini, and Franseen needles were 92.7 %, 97.0 %, and 85.7 %, respectively (P = 0.10). In the histological diagnosis alone, the negative predictive values (NPVs) of the Lancet, Menghini, and Franseen needles were 13.3 %, 53.3 %, and 27.3 %, respectively (P = 0.08). Adverse events occurred in four cases (2.5 %): one postprocedural bleeding, two cases of pancreatitis, and one pancreatic abscess. Conclusions EUS-guided tissue acquisition for small solid pancreatic lesions has a high diagnostic yield and safety. This study suggested a difference in the diagnostic yield of each needle for small solid pancreatic lesions.

Background and study aims While endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collection (PFC) is recommended to be performed ≥ 4 weeks after onset of acute pancreatitis (AP), early (

Jun Iwamoto1, Yoshihiro Sato2, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: The purpose of the study was to confirm the short-term outcome of conservative treatment in terms of the ability to return to play and factors influencing return to play in athletes with symptomatic lumbar disc herniation. A total of 100 consecutive athletes (72 male and 28 female) who consulted our sports medicine clinic during the 16-year period between September 1993 and October 2009 because of severe low back pain and/or leg pain/numbness due to lumbar disc herniation were studied. The mean age of the subjects was 23 years. All of them were conservatively treated by being advised to discontinue their sporting activities with/without short-term medication. After the subjective symptoms had reduced by more than 80%, individual training was started in order to allow the athletes to return to play. Seventy-nine athletes (79.0%) returned to play at an average of 4.8 months (range 1–12 months) after the start of treatment and were able to sustain the activities for at least 6 months, the minimum duration of follow-up in the study. The outcome of the conservative treatment was not influenced by the intensity of the sporting activity. Multiple logistic regression analyses showed that the severity of the symptoms prior to the start of treatment was the factor influencing the ability of the athletes to return to play. The present study confirmed the satisfactory short-term outcome of conservative treatment in athletes with symptomatic lumbar disc herniation regarding return to play and revealed that subjective symptoms prior to the start of treatment appeared to be a key factor in return to play after conservative treatment.Keywords: lumbar disc herniation, athletes, return to play, conservative treatment, sciatica, low back pain

Jun Iwamoto1, Mitsuyoshi Uzawa2, Yoshihiro Sato3, Tsuyoshi Takeda1, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, Japan Abstract: The antiresorptive drug elcatonin (ECT) is known to relieve pain in postmenopausal women with osteoporosis. A prospective open-labeled trial was conducted to compare the effects of short-term combined treatment with alendronate (ALN) and ECT on bone mineral density (BMD) and bone turnover with those of single treatment with ALN in postmenopausal women with osteoporosis. Two hundred and five postmenopausal osteoporotic women (mean age: 70 years) were recruited in our outpatient clinic. Forty-six women with back pain were treated with ALN and ECT (intramuscular, 20 units a week), and 159 women without obvious back pain were treated with ALN alone. The lumbar BMD, urinary levels of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of alkaline phosphatase (ALP) were measured during the six-month treatment period. The baseline characteristics, except for age, body weight and number of patients with prevalent vertebral fractures, were not significantly different between the two groups. The mean increase rate in the lumbar BMD at six months was similar in the ALN (+4.41%) and ALN+ECT (+5.15%) groups, following similar reduction rates in urinary NTX levels (-40.2% and -43.0%, respectively, at three months) and serum ALP levels (-19.0% and -19.7%, respectively, at six months). These results were consistent even after adjustments for age, body weight, and number of patients with prevalent vertebral fractures. The present study in postmenopausal osteoporotic women confirmed that the effects of short-term combined treatment with ALN and ECT on lumbar BMD and bone turnover in patients with back pain appeared to be comparable to those of single treatment with ALN in patients without obvious back pain.Keywords: alendronate, elcatonin, osteoporosis, postmenopausal women, back pain

Jun Iwamoto1, Yoshihiro Sato2, Tsuyoshi Takeda1, Hideo Matsumoto21Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Department of Neurology, Mitate Hospital, Fukuoka, JapanAbstract: Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.Keywords: hip fracture, bone turnover, bone mineral density, cortical porosity, cortical thickness

The purpose of the present study was to determine the associations of age and history of non- and low-traumatic fractures with the severity of abdominal aortic calcification in Japanese postmenopausal women and men. Four hundred and one Japanese persons (24 men and 377 postmenopausal women, mean age: 73.8 years) for whom thoracic and lumbar spine radiographs had been obtained to evaluate their posture prior to patient participation in a fall-prevention exercise program were enrolled. The associations of sex, age, history of hip fracture, prevalence of vertebral fracture, and spondylosis grade (the Nathan degree) with the severity of abdominal aortic calcification (length of calcification, as evaluated according to the number of vertebral bodies) were analyzed. Nine subjects (2.2%) had a history of hip fracture, and 221 (55.1%) had at least one prevalent vertebral fracture. Two hundred and sixty-seven subjects (66.6%) had first-degree spondylosis. Age and the number of prevalent vertebral fractures, but not sex, history of hip fracture, or spondylosis grade, were significantly associated with the severity of abdominal aortic calcification. The present study confirmed that age and the number of vertebral fractures were associated with the severity of abdominal aortic calcification in Japanese postmenopausal women and men.

Background/Aim: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients. Patients and Methods: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC. Results: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01). Conclusion: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid- induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. Methods: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. Results: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p<.0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. Conclusion: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA. [ABSTRACT FROM AUTHOR]

Background and study aim Endoscopic ultrasound-guided rendezvous (EUS-RV) is increasingly reported as a treatment option after failed endoscopic retrograde cholangiopancreatography. We developed a novel "hitch-and-ride" catheter for biliary cannulation to reduce the risk of guidewire loss during EUS-RV. Patients and methods We retrospectively evaluated safety and technical success of EUS-RV between June 2011 and May 2016. Biliary cannulation during EUS-RV using three methods - over-the-wire, along-the-wire, and hitch-and-ride - were compared. Results A total of 30 EUS-RVs were attempted and the technical success rate was 93.3 %, with two failures (one bile duct puncture and one guidewire insertion). After 28 cases of successful guidewire passage, cannulation was attempted by the over-the-wire (n = 13), along-the-wire (n = 4) or hitch-and-ride (n = 11) method. Only the hitch-and-ride method achieved biliary cannulation without guidewire loss or conversion to the other methods. Time to cannulation was shorter with the hitch-and-ride method (4 minutes) than with over-the-wire and along-the-wire methods (9 and 13 minutes, respectively). The adverse event rate of EUS-RV was 23.3 %. Conclusion A novel hitch-and-ride catheter was feasible for biliary cannulation after EUS-RV. [ABSTRACT FROM AUTHOR]

Six patients with refractory adult-onset Still's disease (AOSD) were treated with tacrolimus (TAC). Patient 1 was pregnant, for whom high-dose corticosteroid (CS) monotherapy did not achieve clinical remission, whereas TAC concomitant with CS was successful, and her baby had no apparent abnormalities. Patient 2 had hemophagocytic syndrome (HPS), for whom high-dose CS monotherapy did not achieve clinical remission, whereas TAC improved HPS, and a complete clinical remission was achieved with concomitant administration of TAC and methotrexate (MTX) with CS. Cases 3 - 5 could not have reduced CS doses due to repeated recurrences and other disease-modifying antirheumatic drugs, including MTX, Cyclosporine A, and tumor necrosis factor alpha inhibitors, did not control disease activity. TAC administration allowed for reduced CS doses. Case 6 experienced adverse effects, and TAC was discontinued due to elevated serum creatinine and potassium levels. TAC was useful for five of six patients, which suggests it as an option for refractory AOSD. [ABSTRACT FROM AUTHOR]

Objective:Neurological diseases such as amyotrophic lateral sclerosis (ALS), stroke, and Parkinson’’s disease cause disability and immobilization that increases the risk of hip fracture. The purpose of the present study was to clarify the efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with such neurological diseases.Methods:A literature search (PubMed) was done from 1995 to the present for randomized controlled trials (RCTs), and a meta-analysis was conducted.Results:Seven RCTs met the criteria, including two of etidronate (ALS and stroke), two of alendronate (stroke and Parkinson’’s disease), and three of risedronate (stroke and Parkinson’’s disease). All of the RCTs were performed on Japanese patients. According to the results of pooled data analysis, the relative risk (95% confidence interval) of hip fracture in patients receiving etidronate, alendronate, and risedronate treatment compared with placebo or active control treatment was 0.16 (0.03––0.87), 0.29 (0.10––0.80), and 0.24 (0.10––0.58), respectively, suggesting a reduction of risk by more than 70% with oral bisphosphonates. There was no statistical evidence of heterogeneity among RCTs, and publication bias was not identified by the funnel plot and Begg’’s rank correlation test. No severe adverse events due to oral bisphosphonate treatment were reported.Limitation:It remains uncertain whether the findings are relevant for Western patients with an increased risk of hip fracture due to neurological diseases.Conclusion:A meta-analysis of RCTs suggested that oral bisphosphonate treatment prevents hip fracture in disabled Japanese patients with neurological diseases, including ALS, stroke, and Parkinson’’s disease. Oral bisphosphonate treatment was well tolerated by such patients. [ABSTRACT FROM AUTHOR]

Objective: Neurological diseases, including Alzheimer's disease, stroke, and Parkinson's disease have been reported to increase the risk for fractures. The purpose of the present study was to clarify the efficacy of risedronate against hip fracture in patients with neurological diseases.Methods: The literature was searched with PubMed from 1995 to the present, with respect to strictly conducted randomized controlled trials (RCTs) with narrow confidence intervals (CIs), and a meta-analysis was conducted.Results: Four RCTs met the criteria; one RCT for Alzheimer's disease (n = 461, mean age = 78 years), two RCTs for stroke (n = 267, mean age = 76 years for men; n = 345, mean age = 71 years for women), and one RCT for Parkinson's disease (n = 223, mean age = 71 years). According to the results of RCTs, the relative risks (95% CI) for hip fracture with risedronate treatment compared with placebo treatment were 0.26 (0.10, 0.69) for Alzheimer's disease, 0.20 (0.04, 0.89) for stroke in men, 0.14 (0.02, 1.16) for stroke in women, and 0.34 (0.09, 1.21) for Parkinson's disease. Overall, the relative risk (95% CI) for hip fracture with risedronate treatment was 0.25 (0.13, 0.48), suggesting 75% of risk reduction rate with risedronate treatment in patients with one of the three neurological diseases (heterogeneity: 0.58, p = 0.9016 and overall effect: 17.36, p < 0.0001). No severe adverse events were reported in the risedronate and placebo groups.Conclusion: The results of a meta-analysis of strictly conducted RCTs suggest that there is efficacy against hip fracture and safety with risedronate treatment in patients with neurological diseases including Alzheimer's disease, stroke, and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract??The purpose of the present study was to determine whether vitamin K2and growth hormone (GH) had an additive effect on the long bones in hypophysectomized young rats. Forty-eight female Sprague?Dawley rats (6 weeks old) were assigned to the following five groups by the stratified weight randomization method: intact controls, hypophysectomy (HX) alone, HX + vitamin K2(30?mg/kg, p.o., daily), HX + GH (0.625?mg/kg, s.c., 5 days a week), and HX + vitamin K2+ GH. The duration of the experiment was 4 weeks. HX resulted in a reduction of the cancellous bone volume/total tissue volume (BV/TV) at the proximal tibial metaphysis, as well as decreasing the total tissue area and cortical area of the tibial diaphysis. These changes resulted from a decrease of the longitudinal growth rate and the bone formation rate (BFR)/TV of cancellous bone, as well as a decrease of the periosteal BFR/bone surface (BS) and an increase of endocortical bone turnover (indicated by the BFR/BS) in cortical bone. Administration of vitamin K2to HX rats did not affect the cancellous BV/TV or the cortical area. On the other hand, GH completely prevented the decrease of total tissue area and cortical area in cortical bone, as well as the decrease of marrow area and endocortical circumference, by increasing the periosteal BFR/BS compared with that in intact controls and reversing the increase of endocortical bone turnover (BFR/BS). However, GH only partly improved the reduction of the cancellous BV/TV, despite an increase of the longitudinal growth rate and BFR/TV compared with those of intact controls. When administered with GH, vitamin K2counteracted the reduction of endocortical bone turnover (BFR/BS) and circumference caused by GH treatment, resulting in no significant difference of marrow area from that in untreated HX rats. These results suggest that, despite the lack of an obvious effect on bone parameters, vitamin K2normalizes the size of the marrow cavity during development of the bone marrow in young HX rats treated with GH. [ABSTRACT FROM AUTHOR]

Immobilization induces a rapid loss of bone density and bone strength in rats. The purpose of the present study was to examine the effects of risedronate (Ris) on the femoral bone density and bone strength of sciatic neurectomized young rats. Forty male Sprague–Dawley rats, 6 weeks of age, were randomized by the stratified weight method into the following four treatment groups of 10 rats each: sham-operation, bilateral sciatic neurectomy (NX), NX + low-dose Ris (0.25mg/kg/day, orally), and NX + high-dose Ris (0.5mg/kg/day, orally). After 8 weeks of feeding, the volumetric bone mineral density (vBMD) and stress strain index (SSI) of the femoral distal metaphysis and middiaphysis of the rats were measured by peripheral quantitative computed tomography. The mechanical properties of the femoral distal metaphysis and middiaphysis were measured by the compression and three-point bending tests, respectively. The femoral length was also measured. As compared with the findings in the sham-operated controls, NX resulted in a loss of femoral length, cancellous vBMD, SSI, maximum load, stiffness, and breaking energy of the femoral distal metaphysis; there was also loss of cortical thickness, SSI, maximum load, and stiffness of the femoral middiaphysis, with no significant effects on the cortical vBMD or breaking energy of the femoral middiaphysis. High-dose Ris increased the vBMD to values higher than those in the sham-operated controls, and prevented the loss of SSI, maximum load, and stiffness of the femoral distal metaphysis, while low-dose Ris prevented the loss of cancellous vBMD of the femoral distal metaphysis. Neither high- nor low-dose Ris affected any of the cortical bone parameters of the femoral middiaphysis, except for cortical thickness, or the femoral length. These findings suggest that Ris may prevent immobilization-induced loss of cancellous bone density and bone strength in a dose-dependent manner without interfering with bone growth, but has no apparent effects on the cortical bone in sciatic neurectomized young rats. The results of the present preclinical study should be taken into consideration prior to the commencement of Ris treatment for disabled children. [ABSTRACT FROM AUTHOR]