Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma.

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.

A Case of Pancreatic Neuroendocrine Tumor with Liver Metastases Demonstrating the Possibility of Enhanced ACTH Production by the SACI Test.

Objective: ACTH-producing pancreatic NETs have a propensity to metastasize, and in patients with metastases, there is no established method yet to precisely determine if the excess ACTH is produced by the primary or the metastatic tumors. Localizing the source of production of ACTH in such cases is important for devising suitable treatment strategies and evaluating the benefit of local therapies from the viewpoint of control of Cushing's syndrome. Methods: We performed the selective arterial calcium injection (SACI) test combined with selective portal and hepatic venous sampling in a 32-year-old female patient with ectopic ACTH-producing pancreatic NET and liver metastases. Results: The blood level of ACTH after Ca loading was significantly elevated only in the vessels thought to be directly feeding the pancreatic tumor, and Ca loading from any artery did not significantly increase ACTH concentrations in the hepatic veins compared to the main trunk of the portal vein. Conclusions: The present case demonstrates that there might be an ACTH-producing p-NET that responds to Ca loading. Further in vitro studies are required to validate this possibility.

Mutations in nuclear pore complex promote osmotolerance in Arabidopsis by suppressing the nuclear translocation of ACQOS and its osmotically induced immunity.

We have previously reported a wide variation in salt tolerance among Arabidopsis thaliana accessions and identified ACQOS, encoding a nucleotide-binding leucine-rich repeat (NLR) protein, as the causal gene responsible for the disturbance of acquired osmotolerance induced after mild salt stress. ACQOS is conserved among Arabidopsis osmosensitive accessions, including Col-0. In response to osmotic stress, it induces detrimental autoimmunity, resulting in suppression of osmotolerance, but how ACQOS triggers autoimmunity remains unclear. Here, we screened acquired osmotolerance (aot) mutants from EMS-mutagenized Col-0 seeds and isolated the aot19 mutant. In comparison with the wild type (WT), this mutant had acquired osmotolerance and decreased expression levels of pathogenesis-related genes. It had a mutation in a splicing acceptor site in NUCLEOPORIN 85 (NUP85), which encodes a component of the nuclear pore complex. A mutant with a T-DNA insertion in NUP85 acquired osmotolerance similar to aot19. The WT gene complemented the osmotolerant phenotype of aot19. We evaluated the acquired osmotolerance of five nup mutants of outer-ring NUPs and found that nup96, nup107, and aot19/nup85, but not nup43 or nup133, showed acquired osmotolerance. We examined the subcellular localization of the GFP-ACQOS protein and found that its nuclear translocation in response to osmotic stress was suppressed in aot19. We suggest that NUP85 is essential for the nuclear translocation of ACQOS, and the loss-of-function mutation of NUP85 results in acquired osmotolerance by suppressing ACQOS-induced autoimmunity in response to osmotic stress.

Computed Tomography-guided Drainage with Modified Trocar Technique Using a Drainaway Drainage Kit.

Purpose: Image-guided percutaneous drainage for abscesses is known as a safe and effective treatment. The computed tomography-guided percutaneous drainage kit Drainaway (SB Kawasumi Co., Ltd.), developed on the basis of a modified trocar method, has made it possible to complete the procedure only under computed tomography guidance without radiographic fluoroscopy. This study investigated the feasibility and safety of Drainaway for abscess drainage. Material and Methods: In this retrospective observational study, 28 procedures in 27 patients (18 men and 9 women; age 67.0 ± 12.3 years) who underwent computed tomography-guided drainage using Drainaway between March and December 2021 at seven affiliated hospitals were analyzed. Patients with symptomatic, puncturable on computed tomography and refractory abscesses were included. Technical success (successful drainage with computed tomography alone), primary clinical success (successful drainage with Drainaway alone), secondary clinical success (avoidance of surgery), and complications were evaluated. Results: The sites of the abscesses were the intraperitoneal, retroperitoneal, and thoracic cavities in 19, 5, and 2 patients, respectively, and subcutaneous tissue in 1 patient. The mean size of the abscesses was 7.1 ± 3.4 cm. The technical success rate was 96.4%; the ligament of the puncture route could not be penetrated in one case. The primary clinical success rate was 77.8%, whereas the secondary clinical success rate of catheter upsizing or replacement was 96.3%. Complications included one case of biliary pleurisy that required drainage. Conclusions: Drainaway is a useful device that allows abscess drainage using only computed tomography guidance without radiographic fluoroscopy.

Relationship between hippocampal subfields volume and balance function in healthy older adults.

BACKGROUND: The volume of the hippocampus and its subfields is known to be affected by aging, disease, and physical training. In regard to training, the differential effects of aerobic exercise and dance training on the subfield volume suggest that balance function may be involved. However, the relationship between balance function and the volume of the hippocampus and its subfields remains unclear. METHODS: Subjects were 30 cognitively intact individuals. They underwent balance tests, cognitive tests and structural MRI scans. The balance index measured was the index of postural stability (IPS) under a visual block condition and/or a proprioception block condition. MR images acquired using a 3-tesla system and three-dimensional T1-weighted images were segmented in the hippocampal subfield with Freesurfer 6.0.0. The relationship between the IPS and hippocampal volume was evaluated. RESULTS: A positive correlation was observed only between the IPS closed eyes/soft surface condition and whole hippocampal volume ratio. In the subfields, positive correlations were found between the IPS and molecular layer of the hippocampus, granule cell layer of the dentate gyrus (GC-ML-DG), and cornu ammonis areas (CA)3 and CA4. These correlations were stronger under the closed eyes/soft surface condition than under the other conditions. CONCLUSIONS: A correlation between balance function and the volume of the hippocampus and subfields was found in healthy elderly subjects. The balance function may be involved in the volume of the whole hippocampus and specific subfields. The IPS closed eyes/soft surface condition is considered to reflect vestibular function. Thus, IPS may be useful in evaluations of the relationship between the vestibular system function via the hippocampus and balance.

Association between behavioural and psychological symptoms of dementia and residence status in patients with Alzheimer's disease.

BACKGROUND: Examining the relationship between the behavioural and psychological symptoms of dementia (BPSD) and residence status is crucial to improving BPSD and reducing the burden on caregivers. However, studies on how BPSD differ between individuals living at home and those in institutional settings are lacking. We conducted a questionnaire survey among healthcare providers (HCPs) involved in dementia care and nursing to clarify the characteristics of BPSD by residence status in patients with Alzheimer's disease (AD) living at home or in facilities. METHODS: We sent questionnaires to HCPs and asked them to answer questions on up to five cases that needed treatment for BPSD and who received long-term care insurance services from 1 April 2016 to 31 March 2017. Responses were received for 371 cases, of which 130 diagnosed with AD were analyzed. The patients were divided into two groups: patients with AD living at home (home care group) and patients with AD living in facilities (facility care group). A Chi-square test was used to identify differences between the two groups. A binomial logistic regression analysis was also conducted to clarify the association between residence status and BPSD. RESULTS: Of the 130 patients, 72 lived at home (home care group) and 58 resided in facilities (facility care group). None of the background factors was significantly different between the two groups. The Chi-square test indicated that sleep disturbance was significantly more common in the facility care group (60.3% in the facility care group vs. 33.3% in the home care group, P = 0.003), while the logistic regression analysis indicated that sleep disturbance was significantly associated with residence status (odds ratio: 2.529, P = 0.038). CONCLUSIONS: Sleep disturbances were more frequently observed among patients with AD living in institutions than among those living in their homes.

Successful Preoperative Partial Splenic Artery and Aneurysm Embolization for Thrombocytopenia Associated with Failed Fontan Circulation.

Long-term complications after the Fontan procedure are important concerns for patients with pediatric and adult congenital heart disease. Although thrombocytopenia due to portal hypertension and hypersplenism is a well-known complication of the Fontan circulation, few studies have reported on its management. Herein we describe a young adult Fontan patient with thrombocytopenia and a splenic artery aneurysm caused by conduit stenosis. The patient required conduit replacement due to high venous pressure. We performed partial splenic artery embolization (PSE) and embolization of the aneurysm preoperatively to reduce the risk of bleeding, resulting in successful subsequent cardiac surgery. Preoperative evaluation of the splenic artery aneurysm was informative, and PSE was a safe and effective treatment option for thrombocytopenia to avoid bleeding during open-heart surgery in this patient.

Oral melanoma: a multicenter study of 69 patients from Japan.

OBJECTIVES: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. MATERIALS AND METHODS: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. RESULTS: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22-96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133-38.522, p < 0.05). CONCLUSIONS: Early detection and radical treatment are essential for improving the prognosis of oral MM patients. CLINICAL RELEVANCE: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients.

Secondary arteriovenous malformation due to subclavian vein occlusion.

An 80-year-old man underwent rectal resection and insertion of a central venous catheter through the left subclavian vein 16 years earlier. Following surgery, he developed edema of his left upper limb that became exacerbated and infected. Computed tomography showed occlusion of the subclavian vein and multiple arteriovenous shunts from the branches of the axillary artery to the venous sac of the axillary vein. Angiography confirmed numerous shunts between the branches of the axillary artery and vein and dilated collateral veins. Embolization of the venous sac was performed using coils, alcohol, and glue. Postprocedural angiography showed complete eradication of the nidus.

Effects of a multicomponent day-care program on cerebral blood flow in patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is a prodromal phase of dementia and is considered an important period for intervention to prevent conversion to dementia. It has been well established that multicomponent day-care programs including exercise training, cognitive intervention and music therapy have beneficial effects on cognition, but the effects on cerebral blood flow (CBF) in MCI remain unknown. This study examined whether a multicomponent day-care program would have beneficial effects on the longitudinal changes of CBF in MCI patients. METHODS: Participants were 24 patients with MCI attending a day-care program; they underwent two 99 mTc-ethyl cysteinate dimer single photon emission computed tomography scans during the study period. We evaluated the association between the changes of regional cerebral blood flow and the attendance rate. RESULTS: There was a significant negative correlation between the reduction of regional CBF in the right parietal region and the attendance rate. We found no significant relation between the baseline CBF images and the attendance rate. CONCLUSIONS: Our results suggest that continuous participation in a multicomponent day-care program might prevent reduction in brain activity in patients with MCI.

Hemoptysis after coil embolization for pulmonary arteriovenous malformation: Histopathological confirmation of bronchial epithelium extension.

Coil embolization is widely performed for pulmonary arteriovenous malformations (PAVMs). We describe herein 2 cases of hemoptysis during long-term follow-up after coil embolization for PAVMs. For both cases, lobectomy was performed and histopathological examinations revealed chronic inflammation and bronchial epithelium extension into the sac of the PAVM. In addition, we performed a systematic review of previous reports of hemoptysis after embolization for PAVMs.

Dynamic balance deficit and the neural network in Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) exhibit balance deficits. Although only a few studies have evaluated the relationship between the brain images and balance indices. In this study, we measured balance indices, including the index of postural stability (IPS) and assessed the relationship between the brain images and their clinical motor and cognitive functional features. METHODS: The study included patients with MCI (N = 14) and patients with AD (N = 19). The primary outcome was IPS under a visual block condition and/or a proprioception block condition. In addition, 9 MCI and 8 AD patients underwent a 1.5-Tesla (1.5-T) Magnetic Resonance Imaging (MRI) scan, and the relationships between the MRI parameters and the balance indices were evaluated. RESULTS: The IPS score was significantly lower in the AD group than the MCI group, but only under the closed eyes/hard surface condition. In terms of MRI, there was a significant positive correlation between the IPS and the regional betweenness centrality in the left hippocampal region. CONCLUSIONS: The finding of a significantly lower IPS score under the closed eyes/hard surface condition in AD than in MCI cases suggests that the vestibular and/or proprioceptive systems were more severely impaired in AD than MCI cases. The results suggest that a dynamic balance disturbance due to deficits of the vestibular hippocampal pathway may be a useful marker for the diagnosis of MCI and detection of disease progression from MCI to AD.

The Multicomponent Day-Care Program Prevents Volume Reduction in a Memory-Related Brain Area in Patients with Mild Cognitive Impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is considered an important period for interventions to prevent progression to dementia. Nonpharmacological interventions for MCI include exercise training, cognitive intervention, and music therapy. These play an important role in improving cognitive function, but their effects on brain plasticity in individuals with MCI are largely unknown. We investigated the effects of a multicomponent day-care program provided by the University of Tsukuba Hospital on the longitudinal brain volume changes in MCI patients. METHODS: MCI patients who participated in the multicomponent day-care program and underwent whole-brain magnetic resonance imaging (MRI) twice during their participation (n = 14), were included. We divided them into two groups according to their attendance rate and conducted a between-group analysis of longitudinal volume changes in the whole cerebral cortex. Regional brain volumes derived from the patients' MRI were calculated with Freesurfer 6.0.0. RESULTS: The neuroimaging analysis demonstrated that the left rostral anterior cingulate cortex volume was significantly preserved in the high-attendance group compared to that of the low-attendance group. CONCLUSION: Our results suggest that continuous participation in a multicomponent day-care program could help prevent a volume reduction in memory-related brain areas in patients with MCI.

Comparison of Foaming Properties Between the Shirasu Porous Glass Membrane Device and Tessari's Three-way Stopcock Technique for Polidocanol and Ethanolamine Oleate Foam Production: A Benchtop Study.

PURPOSE: To compare the characteristics of polidocanol (POL) and ethanolamine oleate (EO) sclerosing foams produced by a Shirasu porous glass membrane (SPGM) device with those made using a 3-way stopcock (3WSC). MATERIALS AND METHODS: Foam half-life times were measured in an ex-vivo benchtop study. Computed tomography (CT) images of each foam were obtained over the time course, and a CT texture analysis was conducted. The bubble size in each foam was measured by an optical microscope. RESULTS: Median foam half-life times were longer in the SPGM group than in the 3WSC group (POL: 198 vs 166 s, P = .02; EO: 640 vs 391 s, P < .01). In the CT texture analysis, median standard deviation (SD) and entropy (randomness) were lower, and median energy (uniformity) and gray-level cooccurrence matrix (GLCM) homogeneity were higher in the SPGM group than in the 3WSC group (POL SD: at 30 s and 50-300 s; POL entropy: at 0-60 s; EO SD: at 0-600 s; EO entropy: at 0-460 s; POL energy: at 0-40 s; POL GLCM homogeneity: at 0-250 s; EO energy: at 0-360 s; EO GLCM homogeneity: at 0-480 s; all P < .05). Median bubble diameters in the SPGM group and in the 3WSC group were 69 and 83 µm (P < .01), respectively, in the POL foam; and 36 and 36 µm (P = .45), respectively, in the EO foam. CONCLUSIONS: POL and EO foams had greater uniformity and longer foam half-life time when prepared with an SPGM device than with a 3WSC.

Relationships between the Fear of COVID-19 Scale and regional brain atrophy in mild cognitive impairment.

BACKGROUND: Several studies have reported that the pandemic of coronavirus disease 2019 (COVID-19) influenced cognitive function in the elderly. However, the effect of COVID-19-related fear on brain atrophy has not been evaluated. In this study, we evaluated the relation between brain atrophy and the effect of COVID-19-related fear by analysing changes in brain volume over time using magnetic resonance imaging (MRI). METHODS: Participants were 25 Japanese patients with mild cognitive impairment (MCI) or subjective cognitive decline (SCD), who underwent 1.5-tesla MRI scan twice, once before and once after the pandemic outbreak of COVID-19, and the Fear of Coronavirus Disease 2019 Scale (FCV-19S) assessment during that period. We computed regional brain atrophy per day between the 1st and 2nd scan, and evaluated the relation between the FCV-19S scores and regional shrinkage. RESULTS: There was significant positive correlation between the total FCV-19S score and volume reduction per day in the right posterior cingulate cortex. Regarding the subscales of FCV-19S, we found significant positive correlation between factor 2 of the FCV-19S and shrinkage of the right posterior cingulate cortex. CONCLUSIONS: There was positive correlation between the FCV-19S score and regional brain atrophy per day. Although it is already known that the psychological effects surrounding the COVID-19 pandemic cause cognitive function decline, our results further suggest that anxiety and fear related to COVID-19 cause regional brain atrophy.

Comparison of Aspiration Catheters with Modified Standard Catheters for Treatment of Large Pulmonary Embolism Using an In-vitro Patho-Physiological Model.

PURPOSE: The presented in-vitro study provides a comparison of various catheters for mechanical treatment of large-burden pulmonary embolism (PE) under standardized conditions, using a new test rig. Dedicated aspiration catheters (JETi®, Penumbra Indigo®, Aspirex®) were compared with standard catheters (Pigtail, Multi-Purpose, Balloon Catheter) applied for embolus fragmentation. MATERIALS AND METHODS: Emboli prepared from porcine blood were washed into the test rig which consists of anatomical models of the pulmonary artery (PA) and of the right heart in combination with a pulsatile drive system. For all catheters, the duration of the recanalization procedure and the weight percentage (wt%) of the remaining, removed and washed-down clot fractions were evaluated. For aspiration catheters, the aspirated volume was measured. RESULTS: All catheters achieved full or partial recanalization. The aspiration catheters showed a significantly (p < 0.05) lower procedure time (3:15 min ± 4:26 min) than the standard fragmentation catheters (7:19 min ± 4:40 min). The amount of thrombus removed by aspiration was significantly (p < 0.001) higher than that by fragmentation, averaging 86.1 wt% ± 15.6 wt% and 31.7 wt% ± 3.8 wt%, respectively. Nonetheless, most of the residue was fragmented into pieces of ≥ 1 mm and washed down. Only in 2 of 36 tests, a residual thrombus of 11.9 wt% ± 5.1 wt% remained in the central PA. CONCLUSION: Comparison under standardized in-vitro patho-physiological conditions showed that embolus fragmentation with standard catheters is clearly inferior to aspiration with dedicated catheters in the treatment of large-burden PE, but can still achieve considerable success. LEVEL OF EVIDENCE: No level of evidence, experimental study.

Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model.

Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6-15.6 kg) via ultrasonography-guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.

A Case of Severe Biliary Anastomotic Stricture after Living Donor Liver Transplantation Successfully Treated Using the Modified Gunsight Technique with Two Balloon Catheters.

Biliary stricture is a serious postoperative complication of liver transplantation. We report the case of a 2-year-old boy with severe biliary anastomotic stricture after left lobe living donor liver transplantation. As cannulation from the occluded B3 into the jejunum was impossible using the conventional technique, a gunsight approach was utilized. By puncturing balloons dilated at the occluded site of B3 and the proximal end of the non-occlusive B2, a tract between B3 and B2 was created, and the catheter was finally successfully inserted from B3 into the jejunum through the dilated tract and B2. The gunsight approach is an option for severe biliary strictures when the conventional approach proves impossible.