Publications by authors named "Takuji Iwashita"

102 Publications

Disconnected pancreatic duct syndrome and outcomes of endoscopic ultrasound-guided treatment of pancreatic fluid collections: Systematic review and meta-analysis.

Dig Endosc 2021 Sep 20. Epub 2021 Sep 20.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: Disconnected pancreatic duct syndrome (DPDS) frequently occurs in patients with acute necrotizing pancreatitis and resultant pancreatic fluid collection (PFC). We performed a systematic review and meta-analysis to evaluate outcomes of endoscopic ultrasound-guided treatment of PFCs according to the presence of DPDS.

Methods: Using PubMed, Embase, and the Cochrane database, we identified clinical studies published until January 2021 with data comparing outcomes of endoscopic ultrasound-guided drainage of PFCs between DPDS and non-DPDS patients. We pooled data on technical and clinical success rates, PFC recurrence, and adverse events using the random-effects model.

Results: We identified five eligible articles including 941 PFC patients treated with endoscopic ultrasound-guided interventions. Clinical success, defined as resolution of the PFC and symptoms, was achieved in a majority of the cases irrespective of DPDS (pooled odds ratio [OR] comparing DPDS to non-DPDS patients, 0.77; 95% confidence interval [CI] 0.33-1.81). Compared to patients without DPDS, patients with DPDS were more likely to undergo PFC recurrence (pooled OR 6.72; 95% CI 2.72-16.6) after clinical resolution of PFC. Prolonged plastic stent placement following the clinical resolution was more frequently performed in DPDS patients than in non-DPDS patients (pooled OR 15.9; 95% CI 2.76-91.9). No statistically significant difference was observed between the groups in terms of the rate of technical success, adverse events, or mortality.

Conclusion: Disconnected pancreatic duct syndrome was associated with higher rate of PFC recurrence after successful endoscopic treatment of PFCs. Future studies should evaluate effectiveness and optimal duration of long-term placement of transmural plastic stents for PFCs with DPDS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.14142DOI Listing
September 2021

Automatic Segmentation of Pancreatic Tumors Using Deep Learning on a Video Image of Contrast-Enhanced Endoscopic Ultrasound.

J Clin Med 2021 Aug 15;10(16). Epub 2021 Aug 15.

Department of Electrical, Electronic and Computer Engineering, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan.

Background: Contrast-enhanced endoscopic ultrasound (CE-EUS) is useful for the differentiation of pancreatic tumors. Using deep learning for the segmentation and classification of pancreatic tumors might further improve the diagnostic capability of CE-EUS.

Aims: The aim of this study was to evaluate the capability of deep learning for the automatic segmentation of pancreatic tumors on CE-EUS video images and possible factors affecting the automatic segmentation.

Methods: This retrospective study included 100 patients who underwent CE-EUS for pancreatic tumors. The CE-EUS video images were converted from the originals to 90-s segments with six frames per second. Manual segmentation of pancreatic tumors from B-mode images was performed as ground truth. Automatic segmentation was performed using U-Net with 100 epochs and was evaluated with 4-fold cross-validation. The degree of respiratory movement (RM) and tumor boundary (TB) were divided into 3-degree intervals in each patient and evaluated as possible factors affecting the segmentation. The concordance rate was calculated using the intersection over union (IoU).

Results: The median IoU of all cases was 0.77. The median IoUs in TB-1 (clear around), TB-2, and TB-3 (unclear more than half) were 0.80, 0.76, and 0.69, respectively. The IoU for TB-1 was significantly higher than that of TB-3 ( < 0.01). However, there was no significant difference between the degrees of RM.

Conclusions: Automatic segmentation of pancreatic tumors using U-Net on CE-EUS video images showed a decent concordance rate. The concordance rate was lowered by an unclear TB but was not affected by RM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10163589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397137PMC
August 2021

Macroscopic visible core length can predict the histological sample quantity in endoscopic ultrasound-guided tissue acquisition: Multicenter prospective study.

Dig Endosc 2021 Aug 26. Epub 2021 Aug 26.

Division of, Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan.

Objectives: Measurement of the macroscopic visible core (MVC) length during macroscopic on-site quality evaluation (MOSE) may allow estimation of sample adequacy for next-generation sequencing (NGS), and prediction of correct diagnosis in endoscopic ultrasound-guided tissue acquisition (EUS-TA) of pancreatic masses.

Methods: This multicenter prospective study included consecutive patients who underwent EUS-TA for pancreatic masses using a 22-G Franseen needle. MVC length and pathological samples obtained from two needle passes were analyzed on a per-pass basis. Outcome measures included respective correlations of MVC length with histological sample quantity and diagnostic yields.

Results: The analysis included 204 passes from 102 EUS-TAs. MVC length correlated positively with histological sample quantity (P < 0.01). On the receiver operating characteristic curve for MVC length, the cut-off value and area under the curve for obtaining a candidate sample for NGS were 30 mm and 0.74 (95% confidence interval [CI] 0.65-0.83), respectively. On multivariate analysis, MVC length ≥30 mm was a significant factor affecting suitability for NGS (odds ratio 6.19; 95% CI 2.72-14.10). Histologic diagnostic yield correlated positively with MVC length (P = 0.01); however, there was no positive correlation between MVC length and overall (histology plus cytology) diagnostic yield.

Conclusions: Measuring MVC length to predict histological sample quantity on MOSE may be of clinical significance during EUS-TA using a 22-G Franseen needle. It may be an effective method, particularly while submitting samples for NGS. Registration: University Hospital Medical Information Network Trials Registry (UMIN000036528).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.14116DOI Listing
August 2021

Risk of pancreatitis following biliary stenting with/without endoscopic sphincterotomy: A randomized controlled trial.

Clin Gastroenterol Hepatol 2021 Aug 12. Epub 2021 Aug 12.

Department of Gastroenterology, Tokyo Medical University Hospital, Tokyo, Japan.

Background And Aims: The efficacy of endoscopic sphincterotomy before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing endoscopic sphincterotomy before biliary stent/tube placement on the occurrence of PEP.

Methods: Three-hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the endoscopic sphincterotomy group (ES group, n = 185) or non-endoscopic sphincterotomy group (non-ES group, n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement.

Results: PEP occurred in 36 (20.6%) patients in the non-ES group and in 7 (3.9%) patients in the ES group (P < .001). The difference in the incidence of PEP between the two groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups.

Conclusion: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture.; University Hospital Medical Information Network Number, UMIN000025727.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.08.016DOI Listing
August 2021

Anorexia, pain and peripheral neuropathy are associated with a decrease in quality of life in patients with advanced pancreatic cancer receiving outpatient chemotherapy - a retrospective observational study.

J Pharm Health Care Sci 2021 Aug 2;7(1):27. Epub 2021 Aug 2.

Department of Pharmacy, Gifu University Hospital, Yanagido 1-1, Gifu, 501-1194, Japan.

Background: Cancer chemotherapy usually improves clinical outcomes in patients with advanced pancreatic cancer (APC), but can also cause moderate-to-severe adverse events (AEs). We investigated the relationship between moderate-to-severe AEs and quality of life (QOL) in patients with APC who received outpatient chemotherapy.

Methods: We recruited APC patients who received outpatient chemotherapy in Gifu University Hospital between September 2017 and December 2018. Adverse events related to chemotherapy were assessed by a pharmacist collaborating with a physician using common terminology criteria for AEs (CTCAE) ver 4.0, and QOL of patients was self-assessed by patients using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L Japanese edition 2). Associations between the EQ-5D-5L utility value and serious AEs were assessed using proportional odds logistic regression.

Results: A total of 59 patients who received 475 chemotherapy cycles were included. The proportional odds logistic regression indicated that grade ≥ 2 anorexia, pain and peripheral neuropathy were significantly correlated with a decreased EQ-5D-5L utility value. Pharmaceutical intervention for these AEs significantly improved the patients' EQ-5D-5L utility value.

Conclusions: Anorexia, pain and peripheral neuropathy were significantly associated with a decrease in QOL. It is assumed that appropriate pharmaceutical intervention with particular emphasis on these AEs can improve the QOL of pancreatic cancer patients receiving outpatient chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40780-021-00210-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327438PMC
August 2021

Utility of dedicated bougie dilator for a 0.018-inch guidewire during EUS-guided biliary drainage: A multi-center retrospective cohort study.

J Hepatobiliary Pancreat Sci 2021 Jul 17. Epub 2021 Jul 17.

Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.

Background: During endoscopic ultrasound-guided biliary drainage (EUS-BD), a combination of a 19-gauge needle and a 0.025-inch guidewire is generally used. However, a 19-gauge needle has poor maneuverability because of their stiffness and rigidity and might have poor penetrability in non-dilated bile ducts because of their large bore. In contrast, the application of a 22-gauge needle is expected to have improved maneuverability. However, only a 0.018-inch guidewire, which has less supportability, is applicable in the subsequent guidewire selection. This study aimed to evaluate the feasibility and safety of a dedicated bougie dilator for a 0.018-inch guidewire.

Methods: From September 2019 to May 2020, 26 patients underwent fistula dilation using the dilator after accessing the bile duct using a 22-gauge needle and a 0.018-inch guidewire during EUS-BD. The success and adverse event rates of EUS-BD were evaluated.

Results: Biliary access with a combination of a 22-gauge needle and a 0.018-inch guidewire was successful in all with a median bile duct diameter of 5 mm. Dilation of the fistula using the dedicated dilator was also successful in all cases. Subsequently, the dilator was successfully exchanged to an ERCP catheter that allowed for exchange to a 0.025-inch guidewire, except in one case where the catheter did not cross the fistula and a dilation balloon was inserted for an exchange to a 0.025-inch guidewire. The technical success rate of the EUS-BD was 100%. The adverse event rate was 19%.

Conclusion: The application of the dedicated dilator for a 0.018-inch guidewire was considered feasible and safe for EUS-BD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.1021DOI Listing
July 2021

Trial protocol: a randomised controlled trial to verify the non-inferiority of a partially covered self-expandable metal stent to an uncovered self-expandable metal stent for biliary drainage during neoadjuvant therapy in patients with pancreatic cancer with obstructive jaundice (PUN-NAC trial).

BMJ Open 2021 07 8;11(7):e045698. Epub 2021 Jul 8.

Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan.

Introduction: Neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (NAC/NACRT) for resectable/borderline resectable pancreatic cancers was recently performed to improve clinical outcomes and led to good results, although it remains controversial whether NAC/NACRT is beneficial for resectable pancreatic cancer. A few recent studies revealed longer patency and lower cost related to the stent occlusion of a metal stent than those of a plastic stent during NAC/NACRT. It also remains controversial which type of self-expandable metal stent (SEMS) is the most suitable for patients with resectable/borderline resectable pancreatic cancer during NAC/NACRT: an uncovered SEMS (USEMS), a fully covered SEMS (FCSEMS) or a partially covered SEMS (PCSEMS). So far, two randomised controlled trials indicated that a USEMS and an FCSEMS were similar in preoperative stent dysfunction and adverse event rate. Thus, we aimed to verify the non-inferiority of a PCSEMS to a USEMS in this multicentre randomised controlled trial.

Methods And Analysis: We designed a multicentre randomised controlled trial, for which we will recruit 100 patients with resectable/borderline resectable pancreatic cancer and distal biliary obstruction scheduled for NAC/NACRT from 13 high-volume institutions. Patients will be randomly allocated to the PCSEMS group or USEMS group. The primary outcome measure is the preoperative biliary event rate. Data will be analysed after completion of the study. We will calculate the 95% CIs of the incidence of preoperative biliary events in each group and analyse whether the difference between them is within the non-inferiority margin (10%).

Ethics And Dissemination: This study has been approved by the institutional review board of Hokkaido University Hospital. The results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal.

Trial Registration Number: UMIN000041737; jRCT1012200002.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-045698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268904PMC
July 2021

Comparison of Chemotherapy-induced Nausea and Vomiting Between Gemcitabine Plus Nab-paclitaxel Combination Chemotherapy and Gemcitabine Monotherapy in Patients With Advanced Pancreatic Cancer.

Anticancer Res 2021 Jul;41(7):3643-3648

Department of Pharmacy, Gifu University Hospital, Gifu, Japan.

Background/aim: To clarify the risk of chemotherapy-induced nausea and vomiting (CINV) with GnP therapy, gemcitabine (GEM) plus nab-paclitaxel (nab-PTX), we compared CINV between GEM and GnP therapy.

Patients And Methods: Patients who had received an initial course of GEM and GnP therapy were enrolled. Primary endpoint was the incidence of nausea, and secondary endpoints were the incidence of vomiting and rescue. In addition, the association between nausea and combination therapy with GEM and nab-PTX was evaluated by multivariate logistic regression with adjustment for covariates. All patients received anti-cancer drugs under guideline-consistent, low-risk antiemetic measures.

Results: Data from 105 patients were analyzed (GEM group, 44 patients; GnP group, 61 patients). The incidence of nausea, vomiting, and rescue did not significantly differ between the two groups during the acute, delayed or overall periods. The multivariate logistic regression analysis showed that combination therapy with GEM and nab-PTX was not significantly associated with nausea compared to GEM alone.

Conclusion: Under guideline-consistent, low-risk antiemetic measures, GnP therapy-induced nausea and vomiting can be controlled similarly to when induced by GEM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15154DOI Listing
July 2021

Preoperative perihilar cholangiocarcinoma assessment using virtual endoscopic imaging magnetic resonance cholangioscopy.

Endosc Int Open 2021 Jul 21;9(7):E1158-E1163. Epub 2021 Jun 21.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Preoperative assessment of the superficial ductal spread (SDS) of perihilar cholangiocarcinoma (PCCA) is important for determining its resectability. A virtual endoscopic imaging method, magnetic resonance cholangioscopy (MRCS), wherein a three-dimensional image is created from magnetic resonance imaging (MRI) data, can evaluate all aspects of arbitrary bile ducts. Overall, 15 patients with PCCA who underwent preoperative MRI were enrolled. All patients underwent surgical treatment. MRCS could be performed based on preoperative MRI data in all patients. MRCS could not be used in one patient due to debris in the obstructed bile duct. The remaining 14 patients (93 %) were diagnosed with obstructed bile duct or irregular surface of the bile duct, signifying tumor invasion. The accuracy rate of diagnosing the SDS was 93 % (14/15). Seven patients underwent preoperative peroral cholangioscopy; the scope could not pass through the tumor in three patients. In these three patients, MRCS was able to be use dtoevaluate the obstructed side of the bile duct and faciliated accurate diagnosis of SDS. MRCS can be used to noninvasively evaluate the bile duct in all directions. This novel method makes it easy to create virtual images and can be useful for diagnosing the preoperative SDS of PCCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1401-9962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218596PMC
July 2021

Clinical Outcomes of Conversion Surgery after FOLFIRINOX in Patients with Unresectable Advanced Pancreatic Cancer: A Retrospective Cohort Study at a Single Center.

J Clin Med 2021 Jun 27;10(13). Epub 2021 Jun 27.

First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan.

Pancreatic cancer is one of the most lethal cancers. To improve its prognosis, conversion surgery for initially unresectable advanced pancreatic cancer (UAPC) after chemotherapy has been reported in recent years.

Methods: A retrospective analysis of the patients with initially UAPC underwent conversion surgery after the first-line modified FOLFIRINOX (mFX) was conducted at a single tertiary care center between January 2014 and March 2020.

Results: Among 79 patients with UAPC who had mFX, 8 patients with a median age of 63 years, including 5 males (3 with locally advanced and 5 metastatic lesions), underwent conversion surgery after a median of 20 cycles of mFX. Conversion surgery was performed in 10.1% of patients (8/79) and surgical resection was successful in all with R0 resection. Postoperative major adverse events were seen in 2 patients, but no perioperative deaths were recognized. Recurrence was confirmed in 3 patients, and these 3 patients died due to cancer recurrence in 17.7, 30.6 and 57.8 months after mFX initiation. 5 patients were still alive without recurrence. The median OS in the patients who underwent conversion surgery was estimated as 65.9 months and was significantly longer than that of the patients without conversion surgery or that in the patients who had a partial response for mFX but did not have conversion surgery. The median follow-up period for the patients who had conversion surgery was 35.2 months.

Conclusion: Conversion surgery achieved long-term survival in patients with UAPC who were treated with the first-line mFX, although controversy still remained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10132848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267793PMC
June 2021

Peroral endoscopic retrieval of two duodenal stents migrated into jejunum.

Dig Endosc 2021 Sep 18;33(6):e127-e128. Epub 2021 Jun 18.

Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.14049DOI Listing
September 2021

Multiple transluminal gateway technique with transplantation of lumen-apposing metal stent for direct endoscopic necrosectomy in a patient with infected walled-off pancreatic necrosis.

Dig Endosc 2021 Sep 15;33(6):e123-e124. Epub 2021 Jun 15.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.14014DOI Listing
September 2021

Initial experience of endoscopic ultrasound-guided antegrade covered stent placement with long duodenal extension for malignant distal biliary obstruction (with video).

J Hepatobiliary Pancreat Sci 2021 Jun 12. Epub 2021 Jun 12.

Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Background/purpose: This study aimed to evaluate the feasibility of endoscopic ultrasound (EUS)-guided antegrade covered stent placement with long duodenal extension (EASL) for malignant distal biliary obstruction (MDBO) with duodenal obstruction (DO) or surgically altered anatomy (SAA) after failed endoscopic retrograde cholangiopancreatography (ERCP).

Methods: Outcomes were technical and clinical success, reintervention rate, adverse events, stent patency, and overall survival. Inverse probability of treatment weighting (IPTW) and competing-risk analysis were performed to compare with conventional EUS-BD.

Results: Twenty-five patients (DO, n = 18; SAA, n = 7) were included. The technical and clinical success rates were 96% and 84%, respectively. Reintervention occurred in two patients (8.3%). Adverse events occurred in six patients (24%; two cholangitis, 16%; four mild postprocedural pancreatitis [24% (n = 4/17) in patients with non-pancreatic cancers]). The median patency was 9.4 months, and the overall survival was 2.73 months. After IPTW adjustment, the median patency in the EASL (n = 25) and conventional EUS-BD (n = 29) were 10.1 and 6.5 months, respectively (P = .018).

Conclusions: EASL has acceptable clinical outcomes with a low reintervention rate but higher rate of postprocedural pancreatitis in patients with non-pancreatic cancers. Randomized trials comparing EASL and conventional EUS-BD for MDBO with pancreatic cancers and DO/SAA after failed ERCP are needed to validate our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.1011DOI Listing
June 2021

Micro-RNA Analysis of Pancreatic Cyst Fluid for Diagnosing Malignant Transformation of Intraductal Papillary Mucinous Neoplasm by Comparing Intraductal Papillary Mucinous Adenoma and Carcinoma.

J Clin Med 2021 May 22;10(11). Epub 2021 May 22.

First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan.

Although intraductal papillary mucinous neoplasm (IPMN) is thought to be a precursor lesion of pancreatic cancer, diagnosing malignant transformation of IPMN using non-invasive diagnostic methods is difficult and complicated. Micro-RNAs (miRNAs) are currently recognized as biomarkers and molecular targets of various diseases, including malignancy. In this study, we investigated a potential diagnostic approach using miRNA in pancreatic cyst fluid as a marker for evaluating malignant alternation of IPMN. Cystic fluid was sampled mainly during surgical resection. The collected samples were evaluated by performing comprehensive analysis of miRNA using a highly sensitive DNA chip. miRNA expression was compared between IPM adenoma (IPMA) and IPM carcinoma (IPMC) to evaluate the related biomarkers for malignant transformation of IPMN. miRNA analysis revealed that six miRNAs (miR-711, miR-3679-5p, miR-6126, miR-6780b-5p, miR-6798-5p, and miR-6879-5p) in IPMC were significantly enriched compared to those in IPMA. The difference was validated using quantitative real-time PCR. Cyst fluid miRNA analysis might be useful for diagnosing malignant alteration of IPMN. Further evaluations of diagnostic capability as well as functional analysis using the identified miRNAs are required with larger cohorts to confirm its efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10112249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196884PMC
May 2021

Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Focal Liver Lesions: The Expanding Light Over the Shadow.

Clin Endosc 2021 May 20;54(3):299-300. Epub 2021 May 20.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5946/ce.2021.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182257PMC
May 2021

Permanent endoscopic gallbladder stenting versus removal of gallbladder drainage, long-term outcomes after management of acute cholecystitis in high-risk surgical patients for cholecystectomy: Multi-center retrospective cohort study.

J Hepatobiliary Pancreat Sci 2021 Apr 12. Epub 2021 Apr 12.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Background: Endoscopic transpapillary gallbladder drainage (EGBD) has been reported as an effective gallbladder drainage treatment option for acute cholecystitis in high-risk surgical patients. However, the long-term outcomes such as cholecystitis' recurrence rate after placement of EGB stenting (EGBS) have not been well studied yet.

Aims: The aim of the present study was to compare the long-term outcome of EGBS and removal of gallbladder drainage after percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic nasogallbladder drainage (ENGBD) for acute cholecystitis in high-risk surgical patients and clarify the usefulness of long-term placement of EGBS.

Methods: We retrospectively studied 180 high-risk surgical patients with acute cholecystitis between January 2010 and December 2018. The patients were divided into two groups: EGBS group (long-term placement of EGBS) or Removal group (removal of drainage tube after PTGBD or ENGBD). Clinical outcomes, including long-term results, were compared between the groups.

Results: The cumulative late adverse event (AE) rates were 5.0% and 22.1% in the EGBS and Removal group (P = .002), with a median follow-up period of 375 and 307 days in the two groups, respectively. The cumulative cholecystitis recurrence rate was 5.0% (2/40) in the EGBS group and 16% (21/131) in the Removal group (P = .024), respectively. In the multivariate analysis for late AE, only EGBS was an independent risk factor with a decreasing value.

Conclusion: The permanent EGBS in high-risk surgical patients with acute cholecystitis was considered effective in reducing the risk of late AE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.967DOI Listing
April 2021

[Endoscopic management of difficult common bile duct stone].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(4):303-311

First Department of Internal Medicine, Gifu University Hospital.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11405/nisshoshi.118.303DOI Listing
April 2021

Efficacy of Contrast-Enhanced Harmonic Endoscopic Ultrasound for Pancreatic Solid Tumors with a Combination of Qualitative and Quantitative Analyses: A Prospective Pilot Study.

Dig Dis Sci 2021 Mar 17. Epub 2021 Mar 17.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Introduction: Image evaluation of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and additional time-intensity curve (TIC) analysis enable qualitative and quantitative analyses of pancreatic tumor based on real-time perfusion imaging.

Aims: To evaluate the efficacy of CEH-EUS with a combination of qualitative and quantitative analyses of pancreatic solid tumors.

Methods: Patients were scheduled to undergo EUS-guided fine needle aspiration (FNA) for pancreatic solid tumors were prospectively enrolled between 11/2016 and 12/2018 and underwent CEH-EUS. The vascular and enhancement patterns were qualitatively evaluated and heterogeneous enhancement was defined to be indicative of malignancy. The echo intensity change during 60 s in the tumor was quantitatively evaluated by time intensity curve analysis.

Results: In total, 100 patients were enrolled in this study. The final diagnoses were malignant lesions in 87 patients and benign legions in 13 patients. There were four categories of enhancement and patterns: hypovascular with heterogeneous, hypovascular with homogeneous, hypervascular heterogeneous, and hypervascular homogeneous enhancement. The diagnostic capability of qualitative analysis was the sensitivity, specificity, and accuracy of 89%, 62%, and 85%, respectively. With respect to time intensity curve analysis, the time to peak of malignant lesions was significantly shorter than those of benign lesions (P = 0.0009) with an optimal cutoff value of 12.81 s on the receiver operating characteristic curve analysis. With the combination of qualitative and quantitative analyses, the sensitivity, specificity, and accuracy were improved to 100%, 54%, and 94%, respectively.

Conclusions: CEH-EUS with combined qualitative and quantitative analyses for pancreatic tumors might be useful as a complement for EUS-FNA. The UMIN Clinical Trials Registry (UMIN000025192).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-021-06931-5DOI Listing
March 2021

Unilateral versus Bilateral Endoscopic Nasobiliary Drainage and Subsequent Metal Stent Placement for Unresectable Malignant Hilar Obstruction: A Multicenter Randomized Controlled Trial.

J Clin Med 2021 Jan 8;10(2). Epub 2021 Jan 8.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

(1) Background: Endoscopic management of hilar biliary obstruction is still challenging. Compared with unilateral drainage, bilateral drainage could preserve larger functional liver volume and potentially improve clinical outcomes. To evaluate the effectiveness of bilateral drainage, we conducted this multicenter randomized controlled study. (2) Methods: Patients with unresectable malignant hilar biliary obstruction were assigned to unilateral or bilateral group. At first, patients underwent endoscopic nasobiliary drainage (ENBD), and subsequently underwent self-expandable metallic stent (SEMS) deployment. Primary outcomes were the functional success rate of ENBD and time to recurrent biliary obstruction (TRBO) after SEMS deployment. (3) Results: During the study period, 38 and 39 patients were enrolled in the unilateral and bilateral groups. The functional success rate was similar in the uni- and bi-ENBD group (57% vs. 56%; = 0.99), but the rate of additional drainage was higher in uni-ENBD group. Although TRBO and overall survival time after SEMS deployment were not different between the groups ( = 0.11 and 0.78, respectively), the incidence of early adverse events tended to be higher in the bi-SEMS group (5.3% vs. 28%; = 0.11). (4) Conclusions: Our study failed to demonstrate the superiority of bilateral over unilateral biliary drainage in terms of functional success rate and TRBO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10020206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827318PMC
January 2021

Endoscopic ultrasound-guided fine-needle aspiration of pelvic lesions via the upper and lower gastrointestinal tract approaches.

BMC Gastroenterol 2021 Jan 6;21(1):18. Epub 2021 Jan 6.

First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.

Background: Combining upper and lower gastrointestinal tract (GI) approaches allows expansion of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) indications for pelvic lesions. The upper GI approach has been used for pelvic lesions around the level of the aortoiliac bifurcation in our institution. The aim of this study is to evaluate the feasibility and safety of EUS-FNA for pelvic lesions via the upper and lower GI approaches.

Methods: All consecutive patients who underwent EUS-FNA for the pelvic lesion between January 2008 and December 2018 were retrospectively analyzed. Pelvic lesions were defined as lesions located around and below the aortoiliac bifurcation level. The primary outcome was technical success rate, and the secondary outcomes were the diagnostic capability of EUS-FNA for malignancy and the safety.

Results: EUS-FNA for pelvic lesions was performed in 49 patients: upper and lower GI approaches were used in 28 and 21 patients, respectively. The technical success rates were 91.8% (45/49) in all patients: 89.3% (25/28) and 95.2% (20/21) with the upper and lower GI approaches, respectively. Among patients who achieved technical success, the diagnostic accuracy for malignancy was 97.8% (44/45) in all patients: 100% (25/25) and 95.0% (19/20) with the upper and lower GI approaches, respectively. One (2.0%) patient developed an adverse event of sigmoid colon perforation.

Conclusions: EUS-FNA for pelvic lesions via the upper and lower GI approaches was a safe, feasible, and effective method, although careful endoscopic manipulation is required to avoid perforation, especially with the lower GI approach. Further large-scale, well-designed studies are needed to validate our findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12876-020-01582-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788968PMC
January 2021

Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: Multicenter retrospective study.

Dig Endosc 2020 Dec 7. Epub 2020 Dec 7.

Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan.

Background And Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses.

Methods: A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis.

Results: Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA.

Conclusions: This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/den.13912DOI Listing
December 2020

Endoscopic ultrasound guided-antegrade biliary stenting vs percutaneous transhepatic biliary stenting for unresectable distal malignant biliary obstruction in patients with surgically altered anatomy.

J Hepatobiliary Pancreat Sci 2020 Dec 4;27(12):968-976. Epub 2020 Oct 4.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Background/purpose: Unresectable distal malignant biliary obstruction (DMBO) in patients with surgically altered anatomy is traditionally managed with percutaneous transhepatic biliary drainage (PTBD) and stenting because the anatomical features complicate the endoscopic approach to the biliary orifice. EUS-guided approaches recently emerged as alternative treatments; however, limited data comparing the procedures are available. The aim of this study was to compare EUS-antegrade biliary stenting (ABS) with PTBD for DMBO in patients with surgically altered anatomy.

Methods: The medical records of patients who underwent EUS-ABS or PTBD for the management of DMBO and had a history of upper intestinal surgery at two tertiary centers between 2007 and 2019 were retrospectively evaluated. The study outcomes were technical, clinical, and internalization success rates and adverse event rates.

Results: Of the 64 enrolled patients, 35 underwent EUS-ABS and 29 had PTBD. Basic characteristics including age, sex, performance status, primary malignancy, and reconstruction method did not differ significantly between groups. The technical, clinical, and internalization success rates in the EUS-ABS and PTBD groups were 97.1% vs 96.6% (P = 1.00), 97.1% vs 93.1% (P = .586), and 97.1% vs 75.9% (P = .01), respectively. The adverse event rate was 11.4% vs 27.6% (P = .119). No significant long-term difference was seen in time to recurrent biliary obstruction and survival. Multivariate analysis confirmed EUS-ABS was not an independent risk factor for survival.

Conclusions: Similar to PTBD, EUS-ABS can effectively and safely manage DMBO in patients with surgically altered anatomy. Further well-designed trials are warranted to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.823DOI Listing
December 2020

The impact of sarcopenia and decrease in skeletal muscle mass in patients with advanced pancreatic cancer during FOLFIRINOX therapy.

Br J Nutr 2021 05 4;125(10):1140-1147. Epub 2020 Sep 4.

First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan.

Sarcopenia, defined as decrease in skeletal muscle mass (SMM) and strength, might be associated with reduced survival. We investigated the impact of sarcopenia and decrease in SMM in patients with advanced pancreatic cancer during FOLFIRINOX (FX) therapy. Consecutive sixty-nine patients who received FX were evaluated. Skeletal muscle index (SMI) (cm2/m2) was used to evaluate SMM. The cut-off value of sarcopenia was defined as SMI <42 for males and <38 for females, based on the Asian Working Group for sarcopenia criteria. Sarcopenia was diagnosed in thirty-three (48 %) subjects. Comparison of baseline characteristics of the two groups (sarcopenia group: non-sarcopenia group) showed a significant difference in sex, tumour size and BMI. There was no significant difference in the incidence of adverse events with grades 3-5 and progression-free survival (PFS) during FX between the two groups (PFS 8·1 and 8·8 months; P = 0·88). On the multivariate analysis, progressive disease at the first follow-up computed tomography (hazard ratio (HR) 3·87, 95 % CI 1·53, 9·67), decreased SMI ≥ 7·9 % in 2 months (HR 4·02, 95 % CI 1·87, 8·97) and carcinoembryonic antigen ≥ 4·6 (HR 2·52, 95 % CI 1·10, 6·11) were significant risk factors associated with poor overall survival (OS), but sarcopenia at diagnosis was not. OS in patients with decreased SMI of ≥7·9 % and <7·9 % were 10·9 and 21·0 months (P < 0·01), respectively. In conclusion, decrease in SMM within 2 months after the initiation of chemotherapy had significantly shorter OS, although sarcopenia at diagnosis did not affect OS. Therefore, it might be important to maintain SMM during chemotherapy for a better prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0007114520003463DOI Listing
May 2021

Endoscopic ultrasound-guided tissue acquisition with or without macroscopic on-site evaluation: randomized controlled trial.

Endoscopy 2020 10 4;52(10):856-863. Epub 2020 Jun 4.

Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

Background: The use of macroscopic on-site evaluation (MOSE) to estimate the adequacy of a specimen for histological diagnosis during endoscopic ultrasound (EUS)-guided fine-needle tissue acquisition (FNTA) has recently been advocated. This study aimed to evaluate the diagnostic yield of MOSE compared with conventional EUS-FNTA without rapid on-site evaluation (ROSE).

Methods: This was an international, multicenter, prospective, randomized controlled study. After providing informed consent, consecutive adult patients referred for EUS-FNTA for solid lesions larger than 2 cm were randomized to a MOSE arm or to a conventional arm without ROSE. A designated cytopathologist from each center performed all cytopathological examinations for that center and was blinded to the randomization results. The primary outcome measure was the diagnostic yield, and the secondary outcomes included sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, and the rate of procedure-related complications.

Results: 244 patients (122 conventional, 122 MOSE) were enrolled during the study period. No significant differences between the two arms were found in procedure time or rate of procedure-related adverse events. The diagnostic yield for the MOSE technique (92.6 %) was similar to that for the conventional technique (89.3 %;  = 0.37), with significantly fewer passes made (median: conventional 3, MOSE 2;  < 0.001).

Conclusions: EUS-FNTA with the MOSE technique provided a similar diagnostic yield to conventional EUS-FNTA technique in the absence of ROSE but with fewer passes. This technique can be used when ROSE is not available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1172-6027DOI Listing
October 2020

Factors affecting technical success of endoscopic transpapillary gallbladder drainage for acute cholecystitis.

J Hepatobiliary Pancreat Sci 2020 Jul 26;27(7):429-436. Epub 2020 May 26.

First Department of Internal Medicine, Gifu University Hospital, Gifu, Japan.

Background/purpose: Endoscopic transpapillary gallbladder drainage (ETGBD), including endoscopic nasogallbladder drainage (ENGBD) and endoscopic gallbladder stenting (EGBS), has been reported to be an effective treatment for acute cholecystitis. However, ETGBD is considered to be more difficult than percutaneous transhepatic gallbladder drainage (PTGBD), and few studies have evaluated the factors that affect technical success of the procedure. We investigated the factors predicting its technical success from among patient characteristics and image findings before treatment.

Methods: Three hundred twenty three patients who underwent ETGBD for acute cholecystitis from November 2006 to December 2018 were analyzed retrospectively.

Results: The technical success rate was 72.8% (235/323). The technical success rate by cystic duct direction was as follows: proximal/distal, 65.9%/93.6%; right/left: 74.0%/65.2%; cranial/caudal, 83.5%/20.0%. The clinical response rate was 96.2% (226/235). Adverse events were encountered in 5.9% of cases (19/323), including cystic duct injury (11 patients), pancreatitis (five patients), and bleeding (three patients). In both univariate and multivariate analysis, presence of cystic duct stone, dilation of the common bile duct (CBD), and cystic duct direction (proximal and caudal branches) were identified as significant factors affecting technical failure of ETGBD.

Conclusion: Although ETGBD was an effective and safe procedure for acute cholecystitis, it has a limited success rate. The presence of cystic duct stone, dilation of CBD, and cystic duct direction (proximal and caudal branches) can serve as important predictors of ETGBD difficulties. These findings should be considered before procedures and the necessary adaptation of ETGBD made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jhbp.744DOI Listing
July 2020

Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trial.

Endoscopy 2020 09 16;52(9):736-744. Epub 2020 Apr 16.

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

BACKGROUND : Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. METHODS : This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥ 10 mm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. RESULTS:  171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7 % vs. 78.8 %;  = 0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2 % vs. 48.2 %;  = 0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3 % vs. 9.4 % and of pancreatitis were 4.7 % vs. 5.9 % in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively ( = 0.12). CONCLUSION : EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1145-3377DOI Listing
September 2020

Endoscopic ultrasound-guided fine needle aspiration for the diagnosis of bowel endometriosis: a case report.

Med Ultrason 2020 May 4;22(2):243-246. Epub 2019 Aug 4.

Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.

Bowel endometriosis is a condition caused by endometrial glands and stroma infiltrating the bowel wall and reaching the subserous fat tissue or the adjacent subserous plexus. A 42-year-old woman with changes in stool habits, nausea, and stomach aches experienced complete obstruction in the rectum. Endoscopic ultrasound demonstrated a low echoic lesion outside the rectal mucosa and endoscopic ultrasound-guided fine needle aspiration confirmed the diagnosis of bowel endometriosis. The clinical characteristics of bowel endometriosis are unspecific and this condition is sometimes misdiagnosed as a malignant tumor, irritable bowel syndrome, or any other colorectal disorder. Our aim is to show that endoscopic ultrasound-guided fine needle aspiration might be helpful for bowel endometriosis diagnosis and exclusion of other malignant disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11152/mu-2000DOI Listing
May 2020

The Efficacy of Over-the-Scope Clip Closure for Gastrointestinal Iatrogenic Perforation During Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for Pancreaticobiliary Diseases.

Surg Laparosc Endosc Percutan Tech 2020 Jun;30(3):257-262

First Department of Internal Medicine, Gifu University Hospital.

Background: Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied.

Aims: To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy.

Patients And Methods: This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC.

Results: Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d).

Conclusion: OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLE.0000000000000771DOI Listing
June 2020

Multicentre prospective observational study protocol for radiation exposure from gastrointestinal fluoroscopic procedures (REX-GI study).

BMJ Open 2020 02 26;10(2):e033604. Epub 2020 Feb 26.

Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan.

Introduction: Recently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan.

Methods And Analysis: This is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose-area product (Gycm) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement.

Ethics And Dissemination: Approval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the method of each hospital website.

Trial Registration Number: The UMIN Clinical Trials Registry, UMIN000036525.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-033604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202697PMC
February 2020
-->