Treatment Outcome of Nab-paclitaxel Plus Gemcitabine for Leptomeningeal Carcinomatosis from Pancreatic Ductal Adenocarcinoma: An Autopsy Case Report.

A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

Lower impact of vonoprazan-amoxicillin dual therapy on gut microbiota for Helicobacter pylori eradication.

BACKGROUND AND AIM: Helicobacter pylori eradication can disrupt the gut microbiome. Here, we investigated the short-term impact of minimum antibiotic treatment-a 7-day vonoprazan and low-dose amoxicillin regimen (VA-dual therapy)-on gut microbiota and compared it with that of vonoprazan-based triple therapy (VAC-triple therapy). METHODS: Fifty-nine patients with H. pylori infection were recruited (UMIN000034140) from March to May 2019 and randomly assigned to the VAC-triple therapy or VA-dual therapy groups, according to the first-line H. pylori treatment received. Fecal samples were collected before treatment initiation and 1 and 8 weeks after eradication therapy completion. The composition ratios of the bacterial taxa and the alpha and beta diversities were evaluated in both groups via polymerase chain reaction amplification of the V3-V4 region of the 16S rRNA gene and sequencing using the MiSeq system. RESULTS: Nineteen patients were assigned to the VA-dual group and 24 to the VAC-triple group. Compared with baseline, the alpha diversity reduced significantly 1 and 8 weeks after VAC-triple therapy. However, for VA-dual therapy, the alpha diversities at 1 and 8 weeks after the treatment did not change significantly compared with those at baseline. Additionally, the beta diversity differed significantly between baseline and 1 and 8 weeks after VAC-triple therapy. VAC-triple therapy led to significant alteration in the relative abundance of Actinobacteria at the phylum level and Collinsella, Blautia, and Streptococcus at the genus level. CONCLUSIONS: Compared with VAC-triple therapy, VA-dual therapy induced minimal changes in the diversity and relative abundance of gut microbiota.

Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

Simple Two-Dimensional Echocardiographic Scoring System for the Estimation of Left Ventricular Filling Pressure.

BACKGROUND: When left ventricular filling pressure (LVFP) increases, the mitral valve opens early and precedes tricuspid valve opening in early diastole. The authors hypothesized that a visually assessed time sequence of atrioventricular valve opening could become a new marker of elevated LVFP. The aim of this study was to test the diagnostic ability of a novel echocardiographic scoring system, the visually assessed time difference between mitral valve and tricuspid valve opening (VMT) score, in patients with heart failure. METHODS: One hundred nineteen consecutive patients who underwent cardiac catheterization within 24 hours of echocardiographic examination were retrospectively analyzed as a derivation cohort. In addition, a prospective study was conducted to validate the diagnostic ability of the VMT score in 50 patients. Elevated LVFP was defined as mean pulmonary artery wedge pressure (PAWP) ≥ 15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0 = tricuspid valve first, 1 = simultaneous, 2 = mitral valve first). When the inferior vena cava was dilated, 1 point was added, and VMT score was ultimately graded as 0 to 3. Cardiac events were recorded for 1 year after echocardiography. RESULTS: In the derivation cohort, PAWP was elevated with higher VMT scores (score 0, 10 ± 5; score 1, 12 ± 4; score 2, 22 ± 8; score 3, 28 ± 4 mm Hg; P < .001, analysis of variance). VMT score ≥ 2 predicted elevated PAWP with accuracy of 86% and showed incremental predictive value over clinical variables and guideline-recommended diastolic function grading. These observations were confirmed in the prospective validation cohort. Importantly, VMT score ≥ 2 discriminated elevated PAWP with accuracy of 82% in 33 patients with monophasic left ventricular inflow in the derivation cohort. Kaplan-Meier analysis demonstrated that patients with VMT scores ≥ 2 were at higher risk for cardiac events than those with VMT scores ≤ 1 (P < .001). CONCLUSIONS: VMT scoring could be a novel additive marker of elevated LVFP and might also be associated with adverse outcomes in patients with heart failure.

A case of immune checkpoint inhibitor-associated gastroenteritis detected by ultrasonography.

While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI-related gastroenteritis.

Reliability of an ultrasonographical scoring system for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation.

PURPOSE: Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. METHODS: Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. RESULTS: The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). CONCLUSION: The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.

The Accuracy of the Serum Antibody Test for Helicobacter pylori Infection among Junior High School Students.

OBJECTIVE: Recently, screening for Helicobacter pylori infection has been performed among children in Japan as a prevention strategy for gastric cancer. However, the diagnostic accuracy of the serum antibody test, using the ELISA-kit, for screening in children has not been confirmed, and it is unknown whether the cutoff value used for adults is appropriate for children. The aim of this study was to evaluate the accuracy of the serum antibody test for H. pylori infection for the mass screening of junior high school students in Japan. SUBJECTS AND METHODS: H. pylori infection testing and eradication therapy in junior high schools began in the 2015 fiscal year for students in Yurihonjo and Nikaho cities, located in the Akita prefecture. The data of 410 students who underwent both stool antigen tests (SATs) and serum antibody test, between 2016 and 2018, were used for analysis. Students who had positive results on the SATs test were diagnosed with H. pylori infection. RESULTS: The rate of H. pylori infection was 3.7% (15/410). The optimal cutoff of serum antibody for children was identified to be 5.4 U/mL, with this cutoff having an area under the curve of 0.94 (95% CI 0.83-1.00), specificity of 99.5% (95% CI 98.2-99.9) and sensitivity of 93.3% (95% CI 68.1-99.8), which was wide because of the small sample size. CONCLUSION: The accuracy of the serum antibody test may be enough for practical use in children 13-14 years old.

Case with long-standing gout showing various ultrasonographic features caused by monosodium urate monohydrate crystal deposition.

Gout, which is characterized by the deposition of monosodium urate monohydrate (MSU) in the synovial fluid and other tissues, is the most common form of inflammatory arthritis. Unlike the easily recognized acute and monoarticular gouty arthritis, advanced gout induces multiple finger joint disorders and may sometimes mimic rheumatoid arthritis (RA) or vice versa. The gold standard for gout diagnosis is the identification of MSU crystals via aspiration in the symptomatic joints or nodules; however, its feasibility and specificity may be inadequate. Recently, there have been important advances in imaging techniques, assisting in the non-invasive diagnosis of gout. Ultrasonography (US) has been known to have the ability to detect deposition of MSU crystals in patients with gout. Herein, we report an evocative case of long-standing gout with precisely detected specific US features indicating MSU crystal deposition and inflammation in multiple joints. Comprehensive US assessment included the bone, hyaline cartilage, soft tissue, subcutaneous nodules and tendon; we also discriminated gouty arthritis from RA.

Reduction in the procedure time of hybrid endoscopic submucosal dissection for early gastric neoplasms: a multi-center retrospective propensity score-matched analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric neoplasms is still a technically difficult and time-consuming procedure. Hybrid ESD (H-ESD) involves circumferential incision with partial submucosal dissection combined with subsequent mucosal resection by snaring, wherein the newly developed device allows us to perform H-ESD using a single device. This study aimed to determine the clinical outcomes of H-ESD compared with conventional ESD (C-ESD) for early gastric neoplasms. METHODS: In this multi-center, retrospective study, using propensity score-matched analysis, we reviewed the charts of patients with early gastric neoplasms smaller than 20 mm treated with H-ESD or C-ESD at three hospitals between January 2017 and October 2018. The primary outcome was the procedure time, and the secondary outcomes were other factors, including the en bloc resection rate, complete resection rate, curative resection rate, and rate of adverse events. RESULTS: Among 215 patients, 29 underwent H-ESD and 186 underwent C-ESD; 29 pairs were created by propensity score matching. In the H-ESD group, 82.8% of lesions met the absolute indication [mucosal lesions limited to 20-mm diameter, dominated by differentiated adenocarcinoma without ulcer (scar)] for endoscopic resection (ER). As a result, the procedure time of H-ESD was significantly shorter than that of C-ESD [20 (interquartile range, 12-27) min versus 40 (30-50) min; p < 0.001]. There was no significant difference in the secondary outcomes between the two groups. CONCLUSION: H-ESD contributed to reduced procedure time. Therefore, H-ESD could be an alternative endoscopic treatment for gastric neoplasms when the lesion fulfils the absolute indication for ER.

The effect of scissor-type versus non-scissor-type knives on the technical outcomes in endoscopic submucosal dissection for superficial esophageal cancer: a multi-center retrospective study.

The Clutch Cutter was invented as a scissor-type knife for endoscopic submucosal dissection (ESD) of gastrointestinal neoplasms. ESD with the scissor-type knife (ESD-S) may be considered a technically easier procedure than ESD with non-scissor-type knives (ESD-NS). Therefore, this study aimed to compare the technical outcomes of ESD-S with those of ESD-NS for superficial esophageal cancer. This was a multicenter retrospective study. Patients with superficial esophageal cancer treated with ESD between October 2015 and March 2018 at three hospitals were retrospectively reviewed. The ESD-S group had 48 patients and the ESD-NS group had 114 patients. A propensity score matching analysis was performed to compensate for the confounding bias between both groups. Multivariate analyses and propensity score matching were used to adjust for age, sex, the tumor size, tumor location, tumor depth, degree of tumor circumference, operator level, usage of the traction method, and the sedation method. The primary outcome was the procedure time of the ESD. Secondary outcomes were the rate of en-bloc/complete resection and the rate of complications including perforation, delayed bleeding, and stricture. Propensity score matching analysis provided 36 matched pairs. Median procedure time in the ESD-S group was significantly shorter than that in the ESD-NS group (44.0 min vs. 66.5 min, P = 0.020). In addition, the treatment outcomes were similar in both groups (en-bloc resection: 100% vs. 97.2%, P = 1; complete resection: 88.9% vs. 86.1%, P = 1; curative resection: 80.6% vs. 77.8%, P = 1; perforation: 0% vs. 5.6%, P = 0.49; delayed bleeding: 0% in both groups; stricture: 2.8% vs. 8.3%, P = 0.61). ESD-S was associated with a shorter procedure time than ESD-NS, without an increase in the incidence of complications. Therefore, the scissor-type knife should be considered as an endo-knife for ESD of superficial esophageal cancers.

Tricuspid regurgitation occurring in the early-diastolic phase in a case of heart failure: Insights from echocardiographic and invasive hemodynamic findings.

Although the presence and physiological significance of late-diastolic tricuspid regurgitation (TR) have been reported, those in TR occurring in early diastole have not been well known. We herein first presented a case of heart failure due to dilated cardiomyopathy showing functional TR occurring in the early-diastolic phase in whom the mechanism for its genesis could be precisely assessed from echocardiographic findings and intra-cardiac pressure recordings.

Simple and noninvasive method to estimate right ventricular operating stiffness based on echocardiographic pulmonary regurgitant velocity and tricuspid annular plane movement measurements during atrial contraction.

It was recently shown that invasively determined right ventricular (RV) stiffness was more closely related to the prognosis of patients with pulmonary hypertension than RV systolic function. So far, a completely noninvasive method to access RV stiffness has not been reported. We aimed to clarify the clinical usefulness of our new echocardiographic index of RV operating stiffness using atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) and tricuspid annular plane movement during atrial contraction (TAPMAC). We studied 81 consecutive patients with various cardiac diseases who underwent echocardiography and cardiac catheterization. We measured PRPGDAC and TAPMAC using continuous-wave Doppler and M-mode echocardiography, respectively, and calculated PRPGDAC/TAPMAC. RV end-diastolic pressure (RVEDP) and RV pressure increase during atrial contraction (ΔRVPAC) were invasively measured, and RV volume change during atrial contraction (ΔVAC) was calculated from echocardiographic late-diastolic transtricuspid flow time-velocity integral and tricuspid annular area; thus ΔRVPAC/ΔVAC was used as the standard index for RV operating stiffness. PRPGDAC/TAPMAC well correlated with ΔRVPAC/ΔVAC (r = 0.84, p < 0.001) and RVEDP (r = 0.80, p < 0.001), and the area under the receiver operating characteristic curve to discriminate RVEDP > 12 mmHg was 0.94. Multivariate regression analysis revealed that PRPGDAC/TAPMAC was the single independent determinant of ΔRVPAC/ΔVAC (ß = 0.86, p < 0.001). PRPGDAC/TAPMAC is useful to estimate RV operating stiffness and a good practical indicator of RVEDP.

Endoscopic Ultrasound-guided Drainage of a Mediastinal Abscess Caused by an Ingested Fish Bone.

Cases of foreign body ingestion are encountered relatively often in clinical settings; however, serious complications are rare. In such cases, mediastinal abscess due to esophageal perforation can become a life-threatening complication. Although highly invasive, surgery is often used as the first-line treatment. We herein report the case of a 65-year-old woman who presented with complaints of progressive odynophagia and dysphagia for 2 weeks following a fish meal. Enhanced cervicothoracic computed tomography demonstrated an enhanced round mass with peripheral contrasted margins. The mass was diagnosed as a mediastinal abscess resulting from esophageal perforation caused by a fish bone. Endoscopic ultrasound-guided abscess drainage (EUS-AD) was performed using a nasobiliary drainage tube (NDT). Two weeks later, the abscess had completely disappeared. EUS-AD was safe and effective in this case; furthermore, external drainage using NDT was suitable for this abscess located very close to the upper esophageal sphincter.

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy.

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

Novel Ultrasonographic Scoring System of Sinusoidal Obstruction Syndrome after Hematopoietic Stem Cell Transplantation.

Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a well-documented complication after hematopoietic stem cell transplantation (HSCT). Transabdominal ultrasonography (US) enables the visualization of blood flow abnormalities and is therefore useful for the diagnosis of SOS/VOD. We herein prospectively evaluated accuracy of a novel US diagnostic scoring system of SOS/VOD based on US findings. We carried out US in 106 patients on day 14 and when SOS/VOD was suspected after allogeneic HSCT. Among 106 patients, 10 patients (9.4%) were diagnosed as SOS/VOD by Baltimore or Seattle criteria. According to univariate analysis of 17 US findings (US-17 screening), we established a novel scoring system (HokUS-10) consisting of 10 parameters, such as gallbladder wall thickening, ascites, and blood flow signal in the paraumbilical vein. The sensitivity and specificity were 100% and 95.8%, respectively. Diagnostic performance of the HokUS-10 was significantly better than US-17 screening. In 4 of 10 patients US detection of SOS/VOD preceded to clinical diagnosis. The HokUS-10 scoring system is useful in the diagnosis of SOS/VOD; however, our results should be validated in other cohorts.