Prophylactic endoscopic gallbladder stent placement for cholecystitis after covered metal stent placement for distal biliary obstruction (with video).

BACKGROUND AND AIMS: Acute cholecystitis is occasionally observed after biliary drainage using a covered self-expandable metal stent (CSEMS) for distal biliary obstruction (DBO). Gallbladder drainage before CSEMS placement may reduce cholecystitis. This study aimed to examine the preventive effect of endoscopic gallbladder stent placement (EGBS) on cholecystitis with CSEMSs. METHODS: We retrospectively analyzed patients with DBO who underwent CSEMS placement across the orifice of the cystic duct between November 2014 and October 2021 and were negative for cholecystitis on biliary drainage. Prophylactic EGBS was attempted before CSEMS placement. The incidence of cholecystitis was compared between patients with and without EGBS. RESULTS: In total, 286 patients (128 men; median age, 75 years) were included in this study. EGBS was attempted in 32 patients before CSEMS placement, and technical success was achieved in 24 patients (75%). Adverse events were noted in 3 patients (9.4%; penetration of cystic duct in 1 and acute pancreatitis in 2). The cumulative incidence of cholecystitis was significantly lower in patients with EGBS than in those without EGBS (1 [4.2%] vs 56 [21.4%], P = .045). In multivariable analysis, EGBS was a significant protective factor against cholecystitis (hazard ratio, .11; 95% confidence interval, .01-.79; P = .028). CONCLUSIONS: Although the transpapillary approach to the gallbladder is not easy for patients with DBO, EGBS is effective in preventing cholecystitis associated with CSEMS placement.

Efficacy of pancreatic duct stenting to prevent postendoscopic retrograde cholangiopancreatography pancreatitis after covered self-expandable metal stent deployment.

OBJECTIVES: Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation. METHODS: This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time. RESULTS: Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034). CONCLUSIONS: Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

A drainage strategy for postoperative pancreatic fistula after left-sided pancreatectomy based on the wall status of collected fluid.

PURPOSE: Postoperative pancreatic fistula (POPF) after pancreatectomy is one of the severe postoperative adverse events. We aimed to clarify the outcomes of a strategy for POPF after left-sided pancreatectomy with one-step endoscopic ultrasonography-guided drainage (EUSD) and percutaneous drainage (PCD) based on the wall status of collected fluid. METHODS: From January 2012 to September 2017, 90 of 336 patients developed grade B/C POPF and were retrospectively analyzed. Primary outcome measures were the technical and clinical success and resolution rates. Secondary outcome measures were time from surgery to intervention, and time from intervention to discharge/resolution or stent/tube removal and adverse events. RESULTS: Seventeen patients underwent EUSD and 73 patients underwent PCD for POPF. The technical success rates were 100% in both the EUSD and PCD groups. The clinical success and resolution rates in the EUSD group were 100%, while those in the PCD group were 98.6%. The time from surgery to intervention was significantly longer in the EUSD group than in the PCD group (20 vs. 11 days, p < 0.001). The time from intervention to discharge/resolution was significantly shorter in the EUSD group than in the PCD group (11 vs. 22 days, p < 0.001/10 vs. 20 days, p < 0.001). The time from intervention to stent/tube removal was significantly shorter in the PCD group than in the EUSD group (20.5 vs. 873 days, p < 0.001). Adverse event rates were similar in the two groups (11.8% vs. 5.5%). CONCLUSION: A drainage strategy for POPF based on the wall status of collected fluid is appropriate.

Prediction of effectiveness of potassium-competitive acid blocker and serotonin noradrenaline reuptake inhibitor on abnormal sensation in the throat: use of patient-reported outcome measures (PROMs).

PURPOSE: To determine patients with abnormal sensation in the throat (AST) who would respond to potassium-competitive acid blocker (P-CAB) or serotonin noradrenaline reuptake inhibitor (SNRI) treatment. METHODS: AST patients were randomly divided into two groups. Thirty-one and 21 patients received P-CAB and SNRI treatment, respectively. GETS-J, the Japanese version of Glasgow Edinburgh Throat Scales (GETS), consisted of three subscales of throat symptoms (globus sensation, pain/swelling of the throat, and dysphagia) and somatic distress due to the disease, Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (FSSG), and Hospital Anxiety and Depression Scale (HADS) were used before and after treatments. Responders to treatments were defined as those who showed 50% or more decrease in symptom scores or somatic distress. RESULTS: Pre-treatment GETS-J pain/swelling scores and FSSG acid reflux scores were higher in P-CAB responders and decreased after treatment. Receiver operating characteristic curve for pain/swelling subscale had an area under the curve (AUC) of 0.792 to predict P-CAB responders and a score of 11 provided the best combination of sensitivity (62.5%) and specificity (80%). Somatic distress and HADS anxiety scores, but no other GETS-J symptom scores, decreased after SNRI treatment. Pre-treatment globus scores were lower in SNRI responders. AUC value for globus subscale to predict SNRI responders was 0.741 and a score of 6.5 provided the best combination of sensitivity (70%) and specificity (73%). CONCLUSIONS: Pain/swelling is a characteristic symptom in AST patients who respond to P-CAB treatment. SNRI treatment would be effective for somatic distress in cases with mild symptoms.

Pathways of Progression From Intraductal Papillary Mucinous Neoplasm to Pancreatic Ductal Adenocarcinoma Based on Molecular Features.

BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are regarded as precursors of pancreatic ductal adenocarcinomas (PDAs), but little is known about the mechanism of progression. This makes it challenging to assess cancer risk in patients with IPMNs. We investigated associations of IPMNs with concurrent PDAs by genetic and histologic analyses. METHODS: We obtained 30 pancreatic tissues with concurrent PDAs and IPMNs, and 168 lesions, including incipient foci, were mapped, microdissected, and analyzed for mutations in 18 pancreatic cancer-associated genes and expression of tumor suppressors. RESULTS: We determined the clonal relatedness of lesions, based on driver mutations shared by PDAs and concurrent IPMNs, and classified the lesions into 3 subtypes. Twelve PDAs contained driver mutations shared by all concurrent IPMNs, which we called the sequential subtype. This subset was characterized by less diversity in incipient foci with frequent GNAS mutations. Eleven PDAs contained some driver mutations that were shared with concurrent IPMNs, which we called the branch-off subtype. In this subtype, PDAs and IPMNs had identical KRAS mutations but different GNAS mutations, although the lesions were adjacent. Whole-exome sequencing and methylation analysis of these lesions indicated clonal origin with later divergence. Ten PDAs had driver mutations not found in concurrent IPMNs, called the de novo subtype. Expression profiles of TP53 and SMAD4 increased our ability to differentiate these subtypes compared with sequencing data alone. The branch-off and de novo subtypes had substantial heterogeneity among early clones, such as differences in KRAS mutations. Patients with PDAs of the branch-off subtype had a longer times of disease-free survival than patients with PDAs of the de novo or the sequential subtypes. CONCLUSIONS: Detailed histologic and genetic analysis of PDAs and concurrent IPMNs identified 3 different pathways by which IPMNs progress to PDAs-we call these the sequential, branch-off, and de novo subtypes. Subtypes might be associated with clinical and pathologic features and be used to select surveillance programs for patients with IPMNs.

Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection.

Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and ß-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.

Interventional endoscopic ultrasonography in patients with surgically altered anatomy: Techniques and literature review.

There are various reconstruction techniques that are used after upper gastrointestinal surgery. In recent years, opportunities for endoscopic diagnosis and treatment have been increasing in patients undergoing gastrointestinal surgery. With the advent of interventional endoscopic ultrasound (IV-EUS), various procedures have been developed mainly for patients in whom endoscopic retrograde cholangiopancreatography is difficult to carry out. Indications for such procedures are expanding. IV-EUS for surgically altered anatomy (SAA) includes EUS-guided fine-needle aspiration, biliary interventions (e.g. biliary drainage, treatment of bile duct stricture, removal of bile duct stones, and the rendezvous technique), and pancreatic interventions (e.g. rendezvous technique after Whipple surgery). In addition, there have been reports of various EUS-related procedures using a forward-viewing curved linear-array echoendoscope that are carried out for postoperative intestinal tract reconstruction. Although interventional EUS is a useful therapeutic procedure for SAA, there are still no dedicated devices, and standardization of the procedure is warranted.

Endoscopic ultrasound-guided fine needle aspiration for diagnosing pancreatic mass in patients with surgically altered upper gastrointestinal anatomy.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. METHODS: Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. RESULTS: Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.

Direct Relay Pathways from Lemniscal Auditory Thalamus to Secondary Auditory Field in Mice.

Tonotopy is an essential functional organization in the mammalian auditory cortex, and its source in the primary auditory cortex (A1) is the incoming frequency-related topographical projections from the ventral division of the medial geniculate body (MGv). However, circuits that relay this functional organization to higher-order regions such as the secondary auditory field (A2) have yet to be identified. Here, we discovered a new pathway that projects directly from MGv to A2 in mice. Tonotopy was established in A2 even when primary fields including A1 were removed, which indicates that tonotopy in A2 can be established solely by thalamic input. Moreover, the structural nature of differing thalamocortical connections was consistent with the functional organization of the target regions in the auditory cortex. Retrograde tracing revealed that the region of MGv input to a local area in A2 was broader than the region of MGv input to A1. Consistent with this anatomy, two-photon calcium imaging revealed that neuronal responses in the thalamocortical recipient layer of A2 showed wider bandwidth and greater heterogeneity of the best frequency distribution than those of A1. The current study demonstrates a new thalamocortical pathway that relays frequency information to A2 on the basis of the MGv compartmentalization.

Otosclerosis: anatomical distribution of otosclerotic loci analyzed by high-resolution computed tomography.

PURPOSE: To clarify the anatomical distribution of otosclerotic loci in otosclerosis. METHODS: Ninety-five patients with surgically confirmed uni- or bilateral otosclerosis were enrolled into the study. Hypodense areas observed in the otic capsule by high-resolution computed tomography (HRCT) were defined as otosclerotic loci. The location and number of lesions were examined, and the probability of lesion overlap and correlation with age/hearing parameters (air and bone conduction threshold, air-bone gaps) were tested. RESULTS: Otosclerotic loci were confirmed by HRCT in 77 out of 115 operated ears. The three commonly affected sites were the anterior part of the oval window (ant-OW), anterior part of the internal auditory canal (ant-IAC), and pericochlear area (PCochA), with lesions detected in 96.1%, 46.8%, and 26.0% of ears, respectively. Only the ant-OW area was affected in 48.1% of the ears; the ant-IAC in 3.9%; and PCochA in none with significant differences (p < 0.01). The ant-OW lesions preferentially overlapped with ant-IAC (44.6%) than PCochA lesions (27.0%) (p < 0.05). Among double sites diseases, triple sites diseases occurred more commonly in the ant-OW + PCochA group (80%) than ant-OW + ant-IAC group (48.5%) (p < 0.05). There was no correlation between a number of lesions and age/hearing parameters. CONCLUSIONS: Based on the probability of lesion overlap, otosclerotic lesions may initiate at ant-OW followed by ant-IAC and later PCochA. Although the number of lesions showed no immediate correlation with hearing level or age, anatomical stage of the disease estimated by the location and the number of otosclerotic loci could be useful in predicting the future hearing status.