Neuronal Alterations in Secondary Thalamic Degeneration Due to Cerebral Infarction: A 11C-Flumazenil Positron Emission Tomography Study.

BACKGROUND: Studies using animal experiments have shown secondary neuronal degeneration in the thalamus after cerebral infarction. Neuroimaging studies in humans have revealed changes in imaging parameters in the thalamus, remote to the infarction. However, few studies have directly demonstrated neuronal changes in the thalamus in vivo. The purpose of this study was to determine whether secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease. METHODS: We retrospectively analyzed the data of 140 patients with unilateral cerebral infarction ipsilateral to internal carotid artery or middle cerebral artery disease. All patients had quantitative measurements of 11C-flumazenil binding potential (FMZ-BP), cerebral blood flow, and cerebral metabolic rate of oxygen using positron emission tomography in the chronic stage. Region of interest analysis was performed using NeuroFlexer-an automated region of interest analysis software using NEUROSTAT. RESULTS: In the thalamus ipsilateral to the infarcts, the values of FMZ-BP, cerebral blood flow, and cerebral metabolic rate of oxygen were significantly lower than those in the contralateral thalamus. Significant correlations were found between the ipsilateral-to-contralateral ratio of FMZ-BP and the ipsilateral-to-contralateral ratio of cerebral blood flow or cerebral metabolic rate of oxygen in the thalamus. Patients with corona radiata infarcts and striatocapsular infarcts had significantly decreased ipsilateral-to-contralateral FMZ-BP ratio in the thalamus compared with those without. The ipsilateral-to-contralateral ratio of FMZ-BP in the thalamus was significantly correlated with the ipsilateral-to-contralateral cerebral metabolic rate of oxygen ratio in the frontal cortex and showed a significant negative correlation with the number of perseverative errors on the Wisconsin Card Sorting Test. CONCLUSIONS: Secondary thalamic neuronal damage may manifest as a decrease in central benzodiazepine receptors in patients with cerebral infarction and internal carotid artery or middle cerebral artery disease, which may be associated with frontal lobe dysfunction.

Misery Perfusion and Tau Deposition in Atherosclerotic Major Cerebral Artery Disease: A 18F-Florzolotau Positron Emission Tomography Study.

BACKGROUND: Studies using animal models have shown that cerebral hypoperfusion causes hyperphosphorylation of tau protein, leading to neuronal damage. However, the relationship between hypoperfusion and tau deposition in humans is unclear. Hence, we aimed to determine whether cerebral hypoperfusion leading to decreased blood flow relative to metabolic demand [increased oxygen extraction fraction (OEF), misery perfusion] is associated with increased tau deposition in patients with atherosclerotic internal carotid artery or middle cerebral artery disease. METHODS: We prospectively evaluated the distribution of tau aggregate deposition using positron emission tomography and 18F-florzolotau (PMPBB3 [1-fluoro-3-((2-((1E,3E)-4-(6-(methylamino)pyridine-3-yl)buta-1,3-dien-1-yl)benzo[d]thiazol-6-yl)oxy)propan-2-ol)]) in 8 patients with atherosclerotic disease of the internal carotid artery or middle cerebral artery. The standardized uptake value ratio of 18F-florzolotau at 100 to 110 minutes after injection was calculated using the cerebellar cortex as a reference region and was correlated with OEF obtained from 15O-gas positron emission tomography in the middle cerebral artery distributions. RESULTS: Significant decreases in cerebral blood flow and cerebral metabolic rate of oxygen and increases in OEF were found in the hemisphere ipsilateral to the arterial lesion. 18F-florzolotau standardized uptake value ratio in this region was also greater than that in the contralateral hemisphere. In the ipsilateral hemisphere, 18F-florzolotau standardized uptake value ratio positively correlated with OEF values. CONCLUSIONS: This pilot study with a small sample size suggests that increases in OEF-misery perfusion-may be associated with increased tau aggregates deposition in atherosclerotic internal carotid artery or middle cerebral artery disease.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Endoscopic re-intervention after stent-in-stent versus side-by-side bilateral self-expandable metallic stent deployment.

BACKGROUND AND AIM: Endoscopic bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is widely performed; however, re-intervention after recurrent biliary obstruction (RBO) is often challenging. We compared stent-in-stent (SIS) and side-by-side (SBS) SEMS placement for MHBO considering re-intervention for RBO. METHODS: One hundred five consecutive patients with MHBO who underwent endoscopic bilateral SEMS placement in our hospital and its affiliated institutions were enrolled in this study; 75 patients underwent partial SIS deployment between December 2005 and December 2012; and 30 underwent SBS deployment between January 2013 and March 2019. Initial treatments and re-interventions in each group were retrospectively evaluated. RESULTS: Technical success rate (92% vs 100%, P = 0.179), procedure duration (46 vs 35 min, P = 0.382), functional success rate (97.1% vs 100%, P = 1.00), complication rate (24.6% vs 20.0%, P = 0.797), time to RBO (260 vs 312 days; Gray test, P = 0.815), and rate of RBO (59.4% vs 70.0%, P = 0.371) were not significantly different between the SIS and SBS groups. However, bilateral re-stenting with plastic stents through SEMS was successful in 63.4% of patients in the SIS group compared with 100% of patients in the SBS group (P = 0.0013). Median time to RBO upon first re-stenting with a plastic stent was 75 days (range, 11-195 days). CONCLUSIONS: Endoscopic re-stenting after RBO was significantly more successful in the SBS group than in the SIS group. SBS method is suitable for MHBO considering revisionary stent placement.

Risk Factors for Perforation During Endoscopic Papillary Large Balloon Dilation and Bile Duct Stone Removal.

BACKGROUND: Stone removal using endoscopic papillary large balloon dilation (EPLBD) is extremely effective. However, limited research exists regarding the risk factors for perforation of the duodenal papilla and bile duct, which may be fatal. AIMS: We aimed to investigate the risk factors for perforation during EPLBD + stone removal. METHODS: We included patients who underwent EPLBD + stone removal at four medical facilities between January 2008 and December 2018. We retrospectively analyzed the risk factors for perforation and their relationship between overdilation and adverse events. Overdilation was defined as a ratio of the balloon diameter to the diameter of the bile duct that exceeded 100%. The diameter of the distal bile duct was measured using the diameter of the intrapancreatic bile duct at a point 10 mm toward the liver from the narrow distal segment on a cholangiogram. RESULTS: We included 310 patients (177 males; median age: 79 years [range: 46-102 years]). Perforation occurred in five patients (1.6%). Multivariate analysis indicated that no surrounding-pancreas (half or less of the circumference of the intrapancreatic bile duct was surrounded by the pancreatic parenchyma) was a significant risk factor (perforation rate: 8.3%, p = 0.011, odds ratio: 12.7 [95% confidence interval: 1.8-90.5]). No significant difference was found between the overdilation and non-overdilation groups regarding the occurrence of pancreatitis, bleeding, and cholangitis. Perforation rate in patients with no surrounding pancreas + overdilation was 16.7% (2/12). Patients with perforation underwent conservative therapy, which improved their conditions. CONCLUSIONS: EPLBD + stone removal should be avoided in patients with no surrounding pancreas. Overdilation is not a risk factor for adverse procedural events; however, it should be limited in patients with surrounding pancreas.

Visit-to-Visit Blood PressureVariations and Hemodynamic Deterioration in Atherosclerotic Major Cerebral ArteryDisease.

OBJECTIVE: Visit-to-visit variations in blood pressure (BP) in patients with atherosclerotic major cerebral artery disease could impair the function of cerebral collaterals, leading to hemodynamic deterioration at follow-up. However, few studies have investigated the relationship between visit-to-visit BP variability and changes in hemodynamic parameters at follow-up. MATERIALS AND METHODS: We evaluated 35 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischemic episodes during follow-up (mean: 35 ± 20 months); these patients had a three-time visit for positron emission tomography examinations with 15O-gas. Differences in the mean hemispheric values of hemodynamic parameters in the cortical territory of the diseased artery between the first and third examinations (changes at follow-up) were correlated with the coefficient of variation (CoV) in three systolic BP (SBP) values at the three examinations (BP variability during follow-up). RESULTS: CoV values were negatively correlated with changes in oxygen metabolism or cerebral blood flow/cerebral blood volume (CBF/CBV) ratio. In 17 patients with higher CoV values (> group median, 0.072), decreases in CBF, cerebral metabolic rate of oxygen, and CBF/CBV ratio were observed at follow-up; CBV decreased in 18 patients without elevated CoV. A higher CoV was associated with a lack of statin use. CONCLUSION: In patients with atherosclerotic major cerebral artery disease, high visit-to-visit SBP variations during follow-up may be associated with deterioration in cerebral hemodynamics and metabolism.

Arsenic metabolism differs between child and adult patients during acute arsenic poisoning.

Epidemiological studies on chronic arsenic poisoning have clarified the relationship between various adverse effects and methylation efficiency or methylation capacity. However, no study has similarly investigated such effects on patients with acute arsenic poisoning. In the present work, we studied 61 patients with acute oral arsenic poisoning occurring after consumption of an arsenic trioxide-laced meal (curry soup). The cohort included children (defined as under 15 year old [y/o], n = 22) and adults (over 16 y/o, n = 39) whose urinary arsenic profiles were analyzed. None of these patients had received treatment with chelating agents. The estimated median (IQR) arsenic intake was 64.5 mg (48.3-80.5 mg) in children and 76.0 mg (56.0-91.0 mg) in adults, and these values were not significantly different. Symptoms of poisoning in children improved approximately 1 week after hospitalization. However, the symptoms in most adults deteriorated with severe signs of arsenic poisoning. Urinary arsenic profiles of all the patients were analyzed to obtain the following information: % monomethylarsonic acid (MMA), % dimethylarsinic acid (DMA), second methylation ratio (DMA/MMA), and secondary methylation index (SMI, DMA/MMA + DMA). The levels of these parameters may help identify patients at risk for worsening symptoms. %MMA, an indicator of incomplete methylation, increased more in adults, who experienced more severe symptom progression, compared with children. In contrast, %DMA, which indicates more complete and efficient methylation, increased particularly in children with mild symptoms. Overall the present results indicate that children possess an excellent capacity for methylation (second methylation ratio) of arsenic to DMA and therefore, experience relatively less severe progression of symptomology during acute arsenic poisoning.

Factors for unsuccessful endoscopic hemostasis in patients with severe peptic ulcer bleeding.

OBJECTIVES: Although the first approach for peptic ulcer bleeding is endoscopic hemostasis, quick determination of a hemostatic strategy is important in patients with vitals indicating shock. However, the unsuccessful factors for endoscopic treatment have yet to be sufficiently examined. We aimed to investigate the factors for unsuccessful endoscopic hemostasis in severe peptic ulcer bleeding. MATERIALS AND METHODS: Unsuccessful factors were retrospectively investigated in 150 eligible patients who underwent endoscopic hemostasis for shock-presenting peptic ulcer bleeding at our critical care center between April 2007 and March 2021. RESULTS: There were 123 and 27 cases of successful and unsuccessful endoscopic hemostasis, respectively. Causative diseases included gastric ulcer bleeding in 124 patients (82.7%) and duodenal ulcer bleeding in 26 patients (17.3%). Shock index (SI) (1.46 vs. 1.60) (p = .013), exposed blood vessel diameter (1.4 mm vs. 3.1 mm) (p < .001) identified on contrast-enhanced computed tomography (CE-CT), duodenal ulcer bleeding (p = .012), and Forrest classification Ia (p = .004) were extracted as independent factors for unsuccessful endoscopic hemostasis. In receiving operating curve analysis, when the cut-off value for the SI was set at 1.53, the sensitivity and specificity were 70.4% and 63.4%, respectively. When the cut-off value for the exposed blood vessel diameter was set at 1.9 mm, these were 88.9% and 83.7%, respectively. CONCLUSIONS: When these factors (SI ≥ 1.53, exposed blood vessel diameter ≥1.9 mm identified on CE-CT, duodenal ulcer bleeding, and Forrest Ia) are present in patients with severe peptic ulcer bleeding, non-endoscopic hemostasis, such as interventional radiology (IVR) and surgery, should be considered.

Nafamostat Mesylate is Not Effective in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with complications such as post-ERCP pancreatitis (PEP). Protease inhibitors, including nafamostat mesylate (NM), have been evaluated for prophylaxis against PEP. AIM: We describe the first multicenter randomized controlled trial assessing the prophylactic efficacy of NM against PEP. METHODS: In this multicenter prospective study, we aimed to enroll 800 patients aged ≥ 20 years with a planned ERCP between December 2012 and March 2019. The primary outcome was the incidence and severity of PEP in patients who did not receive NM (non-NM) versus those who did (NM; 20 mg). Secondary outcomes included the incidence of PEP by NM initiation (pre- and post-ERCP), risk factors for PEP, and NM-related adverse events. RESULTS: Only 441 of the planned 800 patients were enrolled (non-NM: n = 149; NM: n = 292 [pre-ERCP NM: n = 144; post-ERCP NM: n = 148]). Patient characteristics were balanced at baseline with no significant differences between groups. PEP occurred in 40/441 (9%) patients (non-NM: n = 15 [10%]; NM: n = 25 [9%]), including 17 (12%) and eight (8%) in the pre-ERCP and post-ERCP NM groups, respectively. In the NM group, the incidence of PEP was lower in the low-risk group than in the high-risk group. Pancreatic injection and double-guidewire technique were independent risk factors for PEP. NM-related adverse events of hyperkalemia occurred in two (0.7%) patients. CONCLUSIONS: We found no evidence for the prophylactic effect of NM against PEP, regardless of the timing of administration; however, further studies are needed.

Selective neuronal damage and blood pressure in atherosclerotic major cerebral artery disease.

OBJECTIVE: In patients with atherosclerotic major cerebral artery disease, low blood pressure might impair cerebral perfusion, thereby exacerbate the risk of selective neuronal damage. The purpose of this retrospective study was to determine whether low blood pressure at follow-up is associated with increased selective neuronal damage. METHODS: We retrospectively analysed data from 76 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease with no ischaemic episodes on a follow-up of 6 months or more. All patients had measurements of the distribution of central benzodiazepine receptors twice using positron emission tomography and 11C-flumazenil. Using three-dimensional stereotactic surface projections, we quantified abnormal decreases in the benzodiazepine receptors of the cerebral cortex within the middle cerebral artery distribution and correlated these changes in the benzodiazepine receptors index with blood pressure values at follow-up examinations. RESULTS: The changes in the benzodiazepine receptor index during follow-up (mean 27±21 months) were negatively correlated with systolic blood pressure at follow-up. The relationship between changes in benzodiazepine receptor index and systolic blood pressure was different among patients with and without decreased cerebral blood flow at baseline (interaction, p<0.005). Larger increases in benzodiazepine receptor index (neuronal damage) were observed at lower systolic blood pressure levels in patients with decreased cerebral blood flow than in patients without such decreases. CONCLUSION: In patients without ischaemic stroke episodes at follow-up but with decreased cerebral blood flow due to arterial disease, low systolic blood pressure at follow-up may be associated with increased selective neuronal damage.

Stent-induced symptomatic pancreatic duct stricture after endoscopic prophylactic pancreatic duct stent placement for the normal pancreas.

BACKGROUND/OBJECTIVES: Stent-induced pancreatic duct stricture (SI-PDS) is a complication associated with pancreatic stent placement. However, symptomatic SI-PDS associated with prophylactic pancreatic duct stents has not been sufficiently investigated. METHODS: We examined the incidence and characteristics of symptomatic SI-PDS in patients who underwent pancreatic duct stent placement to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) between April 2007 and March 2017. RESULTS: We examined 124 patients with normal pancreases consisting of 75 men and 49 women with a median age of 67.5 years [interquartile range (IQR): 61-74 years]. The median main pancreatic duct (MPD) diameter was 3.3 mm (IQR: 2.6-4.1 mm). The median duration of stent placement was 7 days (IQR: 3-14 days). Spontaneous dislodgment stents were placed in 43.5% of cases (54/124). The diameter of the stent was 5 Fr in 93.5% of cases (116/124) and 7 Fr in 6.5% of cases (8/124). Symptomatic SI-PDS was observed in 2.4% (3/124) of patients overall: 6.5% of patients with an MPD diameter of <3 mm and 0% of patients with an MPD diameter of ≥3 mm. Univariate analysis revealed that an MPD diameter <3 mm was a significant factor for symptomatic SI-PDS (p = 0.048). All cases of symptomatic SI-PDS improved with endoscopic treatment. CONCLUSIONS: Symptomatic SI-PDS occurred in 2.4% of patients who underwent prophylactic pancreatic duct stent placement for normal pancreases. Patients with an MPD diameter of <3 mm may be susceptible to symptomatic SI-PDS.

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy.

BACKGROUND/OBJECTIVES: A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount. METHODS: We conducted the first-ever examination of the feasibility of analyzing BRCAness using multiplex ligation-dependent probe amplification (MLPA). Formalin-fixed paraffin-embedded (FFPE) tissue samples obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) from 20 patients with the highest pancreatic carcinoma cell counts in tissue samples out of 40 consecutive PDAC patients who underwent EUS-FNAB at our hospital were analyzed by MLPA for BRCAness. RESULTS: We were able to accurately analyze BRCAness in 75% of the 20 cases of PDAC using FFPE tissue obtained by EUS-FNAB. BRCAness was observed in one of the 20 cases. CONCLUSIONS: In PDAC, analyzing BRCAness by MLPA using FFPE tissue obtained by EUS-FNAB offers the remarkable benefit of yielding results in a short period of time and at a low cost. In addition, this method of BRCAness analysis may prove to be a feasible and effective approach for performing precision medicine.

On-site stereomicroscope quality evaluations to estimate white core cutoff lengths using EUS-FNA biopsy sampling with 22-gauge needles.

BACKGROUND AND AIMS: Although rapid on-site cytologic evaluation (ROSE) during EUS-guided FNA biopsy (EUS-FNAB) sampling may improve accuracy of pathologic analyses, cytopathologists are not widely available. We calculated the cutoff lengths required for accurate pathologic diagnoses from stereomicroscopically visible white cores (SVWCs) sampled using 22-gauge needles. METHODS: Overall, 118 patients with mediastinal or upper abdominal solid masses requiring pathologic diagnoses were included. EUS-FNAB sampling was performed using 22-gauge needles. SVWCs were isolated and measured using stereomicroscopy, and the utility of calculated cutoff lengths in diagnosis was investigated. RESULTS: The procedure success and SVWC sampling rates were both 100%, and the median SVWC length was 10 mm. Pathologic examination identified 75, 31, and 12 patients with pancreatic neoplasms (PNs), subepithelial lesions (SELs), and other lesions, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosing malignancy using EUS-FNAB sampling were 93.1%, 100%, 100%, 69.6%, and 94%, respectively. The final diagnostic accuracy in the entire cohort, PNs, and SELs was 92.4%, 90.7%, and 93.5%, respectively. Receiver operating characteristic curves demonstrated the overall SVWC cutoff length to be 11 mm (11 mm for PNs, 3.5 mm for SELs). The overall sensitivity according to SVWC cutoff length was 91.4% (87.6% for PNs, 98.8% for SELs). Compared with cutoff length, multivariate analysis confirmed SVWC length to be a stronger independent factor for tissue diagnosis in both groups. CONCLUSIONS: Diagnosis improved significantly with SVWC cutoff lengths ≥11 mm. This may be a useful index for endoscopists, particularly where ROSE is unavailable. (Clinical trial registration number: UMIN000023013.).

Endoscopic Balloon Dilation for Benign Bilioenteric Stricture: Outcomes and Factors Affecting Recurrence.

BACKGROUND: Balloon dilation (BD) is a simple, effective procedure for postoperative benign bilioenteric strictures (BBESs). Factors associated with BBES recurrence after endoscopic BD have not been studied adequately. This study examined the outcomes and 1-year recurrence factors in patients with BBES who underwent endoscopic BD. METHODS: Patients who underwent endoscopic BD as an initial treatment between April 2008 and March 2017 were retrospectively assessed. The median time to recurrence of BBES (RBBES) and recurrence factors were evaluated. RESULTS: The study group comprised 55 patients (median age 72 years). The rate of RBBES was 52.7% (29/55), and the median time to RBBES was 2.78 years (95% confidence interval [CI] 1.17-4.40). RBBES was observed in 32.7% (18/55) within 1 year after endoscopic BD. The significant factors associated with recurrence within 1 year, revealed by multivariate analysis, were: postoperative bile leak (p = 0.001; hazard ratio [HR] 10.94; 95% CI 2.47-48.39); BBES onset within 6 months, postoperatively (p = 0.013; HR 6.18; 95% CI 1.46-26.21); no intrahepatic stones (p = 0.049; HR 3.05; 95% CI 1.01-9.22); and remaining balloon waist (p = 0.005; HR 5.71; 95% CI 1.69-19.31). The median time to RBBES was significantly shorter in patients with these recurrence factors (0.88 years vs. not reached, p = 0.004). Patients exhibiting at least two recurrence factors were significantly more likely to experience recurrence (p < 0.001). CONCLUSION: Endoscopic BD is effective for BBES, especially for patients with no recurrence factors. Consideration of endoscopic BD and additional treatment may be necessary for patients with recurrence factors.

Complications of Long-Term Indwelling Transmural Double Pigtail Stent Placement for Symptomatic Peripancreatic Fluid Collections.

BACKGROUND: Endoscopic transmural drainage is performed for symptomatic peripancreatic fluid collections (PPFCs). Long-term transmural double-pigtail stent (DPS) placement is useful in preventing recurrences. There are few reports on the long-term safety of DPS placement. Thus, this study aimed to examine the complications of long-term indwelling DPS for PPFCs. METHODS: Among 53 patients who underwent endoscopic ultrasound-guided transmural drainage for symptomatic PPFCs between April 2006 and March 2017, those followed up for over one year were included. Complications of long-term indwelling DPS were examined retrospectively. RESULTS: This study enrolled 36 patients [30 men, median age 54 years (range 22-82)]. Walled-off necrosis was present in 22 cases (including 9 disconnected pancreatic duct syndrome cases) and pancreatic pseudocysts, in 14 cases. The median stenting period was 20.9 (range 0.8-142.3) months, and median observation period was 56.2 (range 12.4-147.1) months. Colon perforation due to DPS occurred in 3 cases (8.3%), at 5.8, 17.1, and 33.7 months after indwelling DPS placement; 2 cases developed perforation from the serosal side. In 1 case, the patient was treated surgically, and in 2 cases, the patients underwent endoscopic removal of the stent and showed improvement with conservative treatment. CONCLUSION: Long-term indwelling transmural DPS for symptomatic PPFCs poses a risk of intestinal perforation. Thus, if possible, it may be better to avoid long-term placement.

Transpapillary Biliary Cannulation is Difficult in Cases with Large Oral Protrusion of the Duodenal Papilla.

BACKGROUND: Biliary cannulation failure is a major problem during endoscopic retrograde cholangiopancreatography. It remains unclear how duodenal papilla morphology affects biliary cannulation. Therefore, we proposed a new classification system for the duodenal papilla based on oral protrusion pattern (ratio of the length of the oral protrusion to the transverse diameter of the papilla) and papilla pattern. AIMS: To retrospectively compare biliary cannulation results with regard to classification and operator experience. METHODS: We analyzed 589 naïve major duodenal papillae. Our classification system comprised oral protrusion pattern, classified as small (Protrusion-S), regular (Protrusion-R), or large (Protrusion-L), and the papilla pattern, classified as annular (Papilla-A), unstructured (Papilla-U), longitudinal (Papilla-LO), isolated (Papilla-I), or gyrus (Papilla-G). Intra-evaluator concordance and the results of biliary cannulation were analyzed. RESULTS: The following oral protrusion pattern classifications were observed: Protrusion-S, 11.7%; Protrusion-R, 77.9%; and Protrusion-L, 10.4%. The following papilla patterns were observed: Papilla-A, 67.1%; Papilla-U, 7.0%; Papilla-LO, 7.5%; Papilla-I, 1.2%; Papilla-G, 15.6%; and unclassified, 1.7%. Intra-evaluator concordance value (Fleiss kappa) was 0.788 for oral protrusion pattern and 0.750 for papilla pattern. A logistic regression analysis of cannulations performed by an experienced endoscopist identified Protrusion-L as a significant risk factor for difficult cannulation (odds ratio 2.956; 95% confidence interval 1.115-7.84; p = 0.029). Multivariate analysis confirmed Protrusion-L as an independent risk factor for difficult biliary cannulation (odds ratio 3.772; 95% confidence interval 1.359-10.464; p = 0.011). CONCLUSIONS: We propose a new general classification system for the duodenal papilla. Protrusion-L is a significant risk factor for difficult biliary duct cannulation.

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer.

BACKGROUND: The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) in elderly Japanese patients with pancreatic cancer remain unclear. Therefore, we prospectively investigated the tolerability and efficacy of nab-PTX + GEM in Japanese patients aged ≥ 75 years with non-curatively resectable pancreatic cancer. METHODS: We treated eligible patients (n = 27) with nab-PTX + GEM until disease progression, appearance of adverse events, or withdrawal of consent. The primary endpoints included adverse events as well as dosing- and survival-related parameters. RESULTS: The rates of 2-cycle completion were 48.1% for nab-PTX and 55.6% for GEM; the relative dose intensities for the 7th (median) treatment cycle were 65.1% and 74.1%, respectively, whereas the dose-reduction rates were 81.5% and 48.1%, respectively. Grade 3 or higher hemotoxicity was observed in 14 of 27 subjects (51.9%); moreover, 22% experienced grade ≥ 3 peripheral nerve disorder and 1 patient (3.7%) died owing to chemotherapy-related interstitial pneumonia. The disease control rate was 92.6% (25/27), while the median progression-free and overall survival times were 7 and 10.3 months, respectively. CONCLUSION: The nab-PTX + GEM regimen is as efficacious in elderly patients who meet certain criteria as it is in previously reported non-elderly patients. The regimen is feasible with appropriate dose adjustments and attention to adverse events. TRIAL REGISTRATION: Clinical trial registration number: UMIN000018907.

Efficacy and Long-Term Outcomes of Side-by-Side Self-Expandable Metal Stent Placement Using a 2-Channel Endoscope for Unresectable Malignant Hilar Biliary Obstruction Occurring After Billroth II Reconstruction (with Video).

BACKGROUND: Long-term studies evaluating self-expandable metal stents in patients who have unresectable malignant hilar biliary obstruction (UMHBO) after surgical reconstruction of the intestine remain inadequate. We developed a side-by-side (SBS) technique using a two-channel endoscope to place self-expandable metal stents in patients with UMHBO occurring after Billroth II reconstruction. AIMS: We validated the long-term outcomes obtained with this technique. METHODS: The study group comprised seven patients with UMHBO in whom we attempted to place metal stents by the SBS technique using a two-channel scope. The procedure was validated retrospectively. RESULTS: The technical success rate was 86% and functional success rate was 100%. The median time to recurrent biliary obstruction (RBO) was 222 days (95% CI 4.9-439.1). Besides RBO, there were no other complications. CONCLUSIONS: The SBS procedure performed using a two-channel scope is a safe and useful new technique for the treatment of UMHBO occurring after Billroth II reconstruction.

Therapeutic peroral direct cholangioscopy using a single balloon enteroscope in patients with Roux-en-Y anastomosis (with videos).

BACKGROUND: Peroral cholangioscopic lithotripsy is a useful procedure in patients with a normal gastrointestinal anatomy who have difficult-to-treat stones. We evaluated the usefulness of peroral direct cholangioscopy (PDCS) using single-balloon enteroscope (SBE) in patients with difficult-to-treat stones who had undergone Roux-en-Y reconstruction. METHODS: Among 118 patients (169 sessions) who underwent SBE-assisted endoscopic retrograde cholangiopancreatography to treat biliary stones after Roux-en-Y reconstruction, patients in whom it was difficult to remove biliary stones via a transpapillary or transanastomotic approach and difficult to switch to ultra-slim endoscope, were retrospectively enrolled. The biliary insertion success rate, procedure success rate, procedure time, and procedural complications were assessed. The SBE was inserted into the bile-duct, first using a free-hand technique, second using a guide wire, and third using the large balloon anchoring and deflation (LBAD) technique. RESULTS: A total of 11 patients (14 sessions) were enrolled in this study. The biliary insertion success rate was 100%. Bile-duct insertion was performed using a free-hand technique in 4 sessions, a guide wire in 3 sessions (rendezvous technique, 2 sessions), and the LBAD technique in 7 sessions. The procedure success rate was 86% in first session, and 100% in second session. The median procedure time was 81 min (range 49-137). The median procedure time in the bile-duct was 21.5 min (range 6-60). Mild pancreatitis occurred as a complication in one patient. The median follow-up was 528 days (range 282-764). No patient had stone recurrence. CONCLUSIONS: PDCS using SBE is a useful procedure in patients with Roux-en-Y reconstruction. The LBAD technique is an useful technique of inserting SBE into the bile-duct.