New objective simple evaluation methods of amyloid PET/CT using whole-brain histogram and Top20%-Map.

OBJECTIVE: This study aims to assess the utility of newly developed objective methods for the evaluation of intracranial abnormal amyloid deposition using PET/CT histogram without use of cortical ROI analyses. METHODS: Twenty-five healthy volunteers (HV) and 38 patients with diagnosed or suspected dementia who had undergone 18F-FPYBF-2 PET/CT were retrospectively included in this study. Out of them, 11C-PiB PET/CT had been also performed in 13 subjects. In addition to the conventional methods, namely visual judgment and quantitative analyses using composed standardized uptake value ratio (comSUVR), the PET images were also evaluated by the following new parameters: the skewness and the mode-to-mean ratio (MMR) obtained from the histogram of the brain parenchyma; Top20%-map highlights the areas with high tracer accumulation occupying 20% volume of the total brain parenchymal on the individual's CT images. We evaluated the utility of the new methods using histogram compared with the visual assessment and comSUVR. The results of these new methods between 18F-FPYBF-2 and 11C-PiB were also compared in 13 subjects. RESULTS: In visual analysis, 32, 9, and 22 subjects showed negative, border, and positive results, and composed SUVR in each group were 1.11 ± 0.06, 1.20 ± 0.13, and 1.48 ± 0.18 (p < 0.0001), respectively. Visually positive subjects showed significantly low skewness and high MMR (p < 0.0001), and the Top20%-Map showed the presence or absence of abnormal deposits clearly. In comparison between the two tracers, visual evaluation was all consistent, and the ComSUVR, the skewness, the MMR showed significant good correlation. The Top20%-Maps showed similar pattern. CONCLUSIONS: Our new methods using the histogram of the brain parenchymal accumulation are simple and suitable for clinical practice of amyloid PET, and Top20%-Map on the individual's brain CT can be of great help for the visual assessment.

Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat.

Asbestos, especially chrysotile, continues to be exposed to humans globally. Hence, it should be disposed properly to prevent asbestos-related diseases, including mesothelioma and lung cancer. This study aimed to verify whether forsterite, a heating product of chrysotile, can cause carcinogenicity, particularly mesothelioma. Forsterite (FO-1000) and enstatite (EN-1500) produced by heating chrysotile at 1000°C and 1500°C, respectively, were subjected. We injected 10 mg of chrysotile, FO-1000, or EN-1500 in rats intraperitoneally and observed the development of peritoneal mesothelioma until 24 months. The incidence of peritoneal mesothelioma in the chrysotile group was 91.2%, whereas in the FO-1000 and EN-1500 groups, peritoneal mesothelioma did not develop. Urinary 8-hydroxy-2'-deoxyguanosine and serum N-ERC/mesothelin concentrations significantly increased in the chrysotile group that developed peritoneal mesothelioma, while they only temporarily changed in the FO-1000 or EN-1500 groups during early treatment. Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.

Evaluation of arsenic metabolism and tight junction injury after exposure to arsenite and monomethylarsonous acid using a rat in vitro blood-Brain barrier model.

Experimental verification of impairment to cognitive abilities and cognitive dysfunction resulting from inorganic arsenic (iAs) exposure in children and adults is challenging. This study aimed to elucidate the effects of arsenite (iAsIII; 1, 10 and 20 µM) or monomethylarsonous acid (MMAIII; 0.1, 1 and 2 µM) exposure on arsenic metabolism and tight junction (TJ) function in the blood-brain barrier (BBB) using a rat in vitro-BBB model. The results showed that a small percentage (~15%) of iAsIII was oxidized or methylated within the BBB, suggesting the persistence of toxicity as iAsIII. Approximately 65% of MMAIII was converted to low-toxicity monomethylarsonic acid and dimethylarsenic acid via oxidation and methylation. Therefore, it is estimated that MMAIII causes TJ injury to the BBB at approximately 35% of the unconverted level. TJ injury of BBB after iAsIII or MMAIII exposure could be significantly assessed from decreased expression of claudin-5 and decreased transepithelial electrical resistance values. TJ injury in BBB was found to be significantly affected by MMAIII than iAsIII. Relatedly, the penetration rate in the BBB by 24 h of exposure was higher for MMAIII (53.1% ± 2.72%) than for iAsIII (43.3% ± 0.71%) (p < 0.01). Exposure to iAsIII or MMAIII induced an antioxidant stress response, with concentration-dependent increases in the expression of nuclear factor-erythroid 2-related factor 2 in astrocytes and heme oxygenase-1 in a group of vascular endothelial cells and pericytes, respectively. This study found that TJ injury at the BBB is closely related to the chemical form and species of arsenic; we believe that elucidation of methylation in the brain is essential to verify the impairment of cognitive abilities and cognitive dysfunction caused by iAs exposure.

Radiation dosimetry and pharmacokinetics of the tau PET tracer florzolotau (18F) in healthy Japanese subjects.

OBJECTIVE: Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. Florzolotau (18F) (florzolotau, APN-1607, PM-PBB3) has been shown to be a probe for tau fibrils in an animal model and patients with Alzheimer's disease and those with non-Alzheimer's disease tauopathies. The objective of this study is to evaluate the safety, pharmacokinetics, and radiation dose following a single intravenous administration of florzolotau in healthy Japanese subjects. METHODS: Three healthy male Japanese subjects aged between 20 and 64 were enrolled in this study. Subjects were determined to be eligible based on the screening assessments at the study site. Subjects received a single intravenous dose of 195.0 ± 0.5 MBq of florzolotau and underwent the whole-body PET scan 10 times in total to calculate absorbed doses to major organs/tissues and effective dose. Radioactivities in whole blood and urine were also measured for pharmacokinetic evaluation. Absorbed doses to major organs/tissues and effective dose were estimated using the medical internal radiation dose (MIRD) method. Vital signs, electrocardiography (ECG), and blood tests were done for safety evaluation. RESULTS: The intravenous injection of florzolotau was well tolerated. There were no adverse events or clinically detectable pharmacologic effects related to the tracer in any subjects. No significant changes in vital signs and ECG were observed. The highest mean initial uptake at 15 min after injection was in the liver (29.0 ± 4.0%ID), intestine (4.69 ± 1.65%ID), and brain (2.13 ± 0.18%ID). The highest absorbed dose was 508 µGy/MBq of the gallbladder wall, followed by the liver of 79.4 µGy/MBq, the pancreas of 42.5 µGy/MBq, and the upper large intestine of 34.2 µGy/MBq. The effective dose was calculated as 19.7 µSv/MBq according to the tissue weighting factor reported by ICRP-103. CONCLUSION: Florzolotau intravenous injection was well tolerated in healthy male Japanese subjects. The effective dose was determined as 3.61 mSv when 185 MBq florzolotau was given.

Implication of Skeletal Muscle Loss in the Prognosis of Patients with Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy.

Objective The effect of sarcopenia on the prognosis of patients undergoing chemotherapy for unresectable pancreatic ductal adenocarcinoma remains largely unexplored. In this retrospective study, we investigated the relationship between sarcopenia and the prognosis of patients receiving first-line nanoparticle albumin-bound paclitaxel plus gemcitabine for unresectable pancreatic ductal adenocarcinoma. Methods We enrolled 251 patients with unresectable metastatic or locally advanced pancreatic ductal adenocarcinoma who had received chemotherapy between January 2015 and December 2020 at Kitasato University Hospital. Univariate and multivariate analyses were performed using the stratified Cox proportional hazards model to determine variables significantly associated with the progression-free and overall survival. Propensity score matching was performed to mitigate selection bias effects. Results In the propensity score-matched cohort, the progression-free and overall survival were not significantly different between the sarcopenia and non-sarcopenia groups (p=0.335, and 0.679 respectively). The skeletal muscle index decreased by 4.4% and 6.5% in the sarcopenia and non-sarcopenia groups, respectively, during the early treatment phase (p=0.084). There were no significant differences between groups with regard to major adverse events or drug toxicity occurrences. Both the progression-free and overall survival were significantly shorter in the skeletal muscle index loss group than in the non-skeletal muscle index loss group (p=0.026 and 0.045, respectively). Conclusion Skeletal muscle index loss during the initial treatment phase may be an early marker for the long-term prognosis of patients receiving nanoparticle albumin-bound paclitaxel plus gemcitabine as first-line treatment for unresectable pancreatic ductal adenocarcinoma.

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.

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.

New image-processing technology for endoscopic ultrasound-guided fine-needle aspiration biopsy specimen evaluation in patients with pancreatic cancer.

Objectives: We evaluated the usefulness of a newly developed system with which the total amount of whitish cores in endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) samples is automatically calculated (automated multiband imaging system [AMUS]). Methods: From 30 prospectively enrolled patients suspected of having pancreatic cancer, four EUS-FNAB specimens per patient were obtained. Following AMUS calculations, two specimens were prepared after stereomicroscopy-guided manual division into whitish and reddish sections (isolation group), and the other two were prepared without such division (no-isolation group). The relation of the AMUS results pertaining to the length of the manually measured whitish cores (stereo-microscopically visible white core [SVWC]) and the sample suitability for pathologic evaluation were analyzed. Results: Histological diagnostic accuracy was 90%; median SVWC length, 14 mm; and median area of whitish core calculated using the AMUS, 13 mm2. The SVWC length correlated with whitish core amount (ρ = 0.83, p < 0.01) and adequacy score (ρ = 0.50, p < 0.01). The whitish core amount correlated with the adequacy score (ρ = 0.40, p < 0.01). The area under the receiver-operating characteristic curve calculated for whitish core amount with respect to the histological diagnosis was 0.84 (p < 0.01; cutoff ≥ 8 mm2, sensitivity 92.5%). Subgroup analysis (isolation vs. no-isolation group) revealed no significant between-group differences in the median histological adequacy (p = 0.27) or tumor cell content ratio (p = 0.28). The median scores for degree of blood contamination were significantly lower in the isolation group than in the no-isolation group (p < 0.01). Conclusion: AMUS is a simple on-site verification procedure for determining the appropriate sampling tissue quantity for high diagnostic accuracy.

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.

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.).

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.

Histopathological comparison of aspiration and biopsy needles in endoscopic ultrasound-guided tissue acquisition in patients with subepithelial lesions.

BACKGROUND: Information on whether a fine-needle biopsy (FNB) needle can improve histopathological specimen quality or the amount of core tissue collected in the diagnosis of subepithelial lesions (SELs) remains insufficient. In this study, we aimed to compare the procedure outcomes and adequacy of histopathological specimens of fine-needle aspiration (FNA) and FNB needles in endoscopic ultrasound-guided tissue acquisition (EUS-TA) using sample isolation processing by stereomicroscopy (SIPS) in patients with SELs. METHODS: We performed a retrospective comparison of SEL cases registered in two previously conducted prospective studies. Of 61 cases, we identified 56 cases of SELs that involved the muscularis propria layer. Of these, 27 patients who underwent EUS-TA using a 22-gauge FNA needle between July 2016 and December 2017, and 29 patients who underwent the procedure using a 22-gauge FNB needle between March 2018 and January 2019 were included in the FNA and FNB group, respectively. RESULTS: Patient background characteristics did not differ between the groups. The technical success rate was 100% in both groups. The median adequacy score was significantly higher in the FNB group than in the FNA group (P < .01). The histological diagnosis showed no significant difference in the accuracy rate between the groups. CONCLUSIONS: In EUS-TA using the SIPS procedure to target SELs derived from the muscularis propria layer, FNB needles collect more core tissues and significantly improve histopathological specimen quality compared with FNA needles. When combined with SIPS, a high tissue diagnosis rate may be obtained regardless of the type of puncture needle used.

Physiologically decreased F-18 fluorodeoxyglucose uptake in the lower vertebrae associated with daily drinking habit in Japanese men with alcohol flushing reaction.

Alcohol flushing reaction (AFR) is known as one of the risks for esophageal squamous cell cancer, and scientists have been elucidating this issue. However, little attention has been given to relevant imaging features. This study aims to investigate whether physiological 18F-fluorodeoxyglucose (FDG) uptake patterns in vertebrae are associated with drinking habits or AFR. Japanese male patients who underwent FDG positron emission computed tomography for evaluation of their known or suspected malignancies or inflammatory diseases were asked about their drinking habits and AFR. Altogether, 192 patients, 139 every-day drinkers and 53 non-drinkers were evaluated. Comparing the FDG uptake between that in the thoracic region and that in the lumbar region, vertebral uptake was visually classified into four patterns: Ld, dominant in lumbar region; TL, almost equal in both regions; BL, slightly higher in thoracic region (borderline pattern); Td, dominant in thoracic region. The uptake patterns were evaluated according to drinking habit (every-day drinker or non-drinker), AFR (flusher or non-flusher), and the combination of these two factors (habit/reaction: every-day drinker/flusher, every-day drinker/non-flusher, non-drinker/flusher, or non-drinker/non-flusher). There were 95 flushers (51 every-day drinkers and 44 non-drinkers) and 97 non-flushers (88 every-day drinkers and 9 non-drinkers). Ld, TL, BL, and Td patterns were observed in 0, 109 (56.8%), 31 (16.1%), and 52 (27.1%) patients, respectively. Td and BL patterns were more frequently observed in every-day drinkers compared with non-drinkers (p = 0.0467). Though the uptake patterns did not differ between flushers and non-flushers (p = 0.116), the Td pattern was more frequently observed in every-day drinkers/flushers (51%) compared with every-day drinkers/non-flushers (20.5%), non-drinkers/flushers (13.6%), and non-drinkers/non-flushers (22.2%) (p = 0.0014). The Td pattern was observed in patients with various diseases, with higher frequency in esophageal cancer, head and neck cancer, and lung cancer compared with other diseases. In conclusion, drinking habits and AFR were related to the vertebral uptake pattern with decreased uptake in the lumbar region in Japanese male patients.

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.

EUS-guided transanastomotic drainage for severe biliopancreatic anastomotic stricture using a forward-viewing echoendoscope in patients with surgically altered anatomy.

BACKGROUND AND OBJECTIVES: Balloon enteroscopy-assisted ERCP (BE-ERCP) has become the first-line therapy for biliopancreatic anastomotic strictures. However, it is not always successful, and salvage methods have not been established. This study aimed to evaluate the outcomes of EUS-guided transanastomotic drainage using a forward-viewing (FV) echoendoscope. PATIENTS AND METHODS: Of eight cases wherein BE-ERCP treatment failed due to severe or complete benign anastomotic stricture, seven cases underwent EUS-guided choledochojejunostomy, and EUS-guided pancreaticojejunostomy was applied in one case after intubating an FV echoendoscope into the anastomotic site. RESULTS: The success rate of reaching the target site was 100% (8/8) for patients after modified Child resection. The median time to reach the anastomosis was 5 min (range: 3-17 min), and the technical success rate for drainage was 75% (6/8). The median total procedure time was 33.5 min (range: 22-45 min) for six successful cases. Cautery dilatation catheters were necessary to dilate the puncture site in all cases, and no early complications were observed. During the follow-up period (median: 13.3 months [range: 6.5-60.3]), recurrence of the stricture occurred in one case, and a stent-free status was achieved after 6-12 months of stent placement in five cases. CONCLUSIONS: EUS-guided transanastomotic drainage using an FV echoendoscope is a feasible and safe rescue technique for the management of benign severe biliopancreatic anastomotic strictures.

Cholecystitis after Placement of Covered Self-Expandable Metallic Stents in Patients with Distal Malignant Biliary Obstructions.

BACKGROUND/AIMS: Cholecystitis can occur after the placement of covered self-expandable metallic stents for distal malignant biliary obstructions. We aimed to identify risk factors for cholecystitis following covered self-expandable metallic stent placement. METHODS: We investigated risk factors related to cholecystitis following covered self-expandable metallic stent placement in 118 patients with distal malignant biliary obstructions between January 1, 2015 and April 30, 2019. Endoscopic assessments and tumor invasion to the arteries feeding the gallbladder were determined by a pancreaticobiliary endoscopist and a radiologist, respectively. RESULTS: The median patient age was 72 years (men, 61.0%). The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct were observed in 35 (29.7%) and 35 (29.7%) patients, respectively. During the observation period (median, 179 days), cholecystitis occurred in 18 (15.3%) patients. Multivariate analysis revealed the flow of the contrast agent into the gallbladder (p=0.023) and tumor involvement in the orifice of the cystic duct (p=0.005) as significant independent risk factors associated with cholecystitis. CONCLUSION: The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct are potential independent risk factors for cholecystitis following the placement of covered self-expandable metallic stents. A follow-up prospective study is warranted to validate their influence.