Clinical implications and optimal extent of lymphadenectomy for intrahepatic cholangiocarcinoma: A multicenter analysis of the therapeutic index

Aims Lymph node metastases (LNM) are associated with lethal prognosis in intrahepatic cholangiocarcinoma (ICC). Lymphadenectomy is crucial for accurate staging and hopes of possible oncological treatment. However, the therapeutic implications and optimal extent of lymphadenectomy remain contentious. Methods To clarify the prognostic value and optimal extent of lymphadenectomy, the therapeutic index (TI) for each lymph node was analyzed for 279 cases that had undergone lymphadenectomy in a multi-institutional database. Tumor localization was divided into hilar lesions (n = 130), right peripheral lesions (n = 60), and left peripheral lesions (n = 89). In addition, the lymph node station was classified as Level 1 (LV1: hepatoduodenal ligament node), Level 2 (LV2: postpancreatic or common hepatic artery nodes), or Level 3 (LV3: gastrocardiac, left gastric artery, or celiac artery nodes). Results Lymph node metastases were confirmed in 109 patients (39%). Five-y survival rates were 45.3% for N0 disease, 27.1% for LV1-LNM, 22.9% for LV2-LNM, and 7.3% for LV3-LNM (P 5.0 in LV1 and LV2, whereas bilateral peripheral lesions showed 5-year TI > 5.0 in LV1. Conclusion The implications and extent of lymphadenectomy for ICC appear to rely on tumor location. In the peripheral type, the benefit of lymphadenectomy would be limited and dissection beyond LV1 should be avoided, while in the hilar type, lymphadenectomy up to LV2 could be recommended

Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer.

Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC

Magnetic resonance spectroscopic imaging enables spatial mapping of decreased glutamate levels associated with tau depositions in Alzheimer’s disease brains

Objective: Despite accumulating evidence for impaired glutamatergic neurotransmission in Alzheimer’s disease (AD) brains, its significance in neurofunctional and neuropathological alterations remains elusive. The aim of this study is to evaluate the associations between glutamatergic dysfunctions and tau depositions across cortical regions in AD patients using magnetic resonance spectroscopic imaging (MRSI).Methods: We enrolled 16 patients with AD, consisting of cases with mild cognitive impairment due to AD and AD dementia, and 15 healthy controls (HCs). We performed tau and amyloid-β (Aβ) PET with 18F-PM-PBB3 and 11C-PiB, respectively, and single-plane MRSI for evaluating a glutamate/creatine (Glu/Cr) ratio at the level of the cingulate gyrus. PET probe retentions were quantified as standardized uptake value ratio (SUVR) using the cerebellar cortex as a reference region.Results: Z-score maps of the AD group compared to the HC group showed marked tau and Aβ depositions in extensive cortical gray matter regions, and reduced glutamate levels in more confined areas (Figures 1-3). Glutamate levels were correlated with tau but not Aβ burdens in some regions, including the posterior cingulate cortex (PCC) (Figures 4). In an analysis of combined voxels covering PCC, Glu/Cr ratios were correlated negatively with tau deposits in the AD group (r = -0.53, p < 0.05) and positively with mini-mental state examination scores (r = 0.74, p < 0.05) in AD dementia cases.Conclusions: MRSI revealed the regionally variable vulnerability of the glutamatergic system to tau depositions in AD brains. In PCC, tau accumulations are likely to induce disrupted glutamine transmissions, aggravating cognitive functions.AD/PD 202

Association between tooth loss and cognitive impairment in community-dwelling older Japanese adults: a 4-year prospective cohort study from the Ohasama study

Abstract Background Numerous prospective studies have investigated the association between the number of remaining teeth and dementia or cognitive decline. However, no agreement has emerged on the association between tooth loss and cognitive impairment, possibly due to past studies differing in target groups and methodologies. We aimed to investigate the association between tooth loss, as evaluated through clinical oral examinations, and the development of cognitive impairment in community-dwelling older adults while considering baseline cognitive function. Methods This 4-year prospective cohort study followed 140 older adults (69.3% female) without cognitive impairment aged ≥65 years (mean age: 70.9 ± 4.3 years) living in the town of Ohasama, Iwate Prefecture, Japan. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) in baseline and follow-up surveys. Based on a baseline oral examination, the participants were divided into those with 0–9 teeth and those with ≥10 teeth. To investigate the association between tooth loss and cognitive impairment, we applied a multiple logistic regression analysis adjusted for age, sex, hypertension, diabetes, cerebrovascular/cardiovascular disease, hypercholesterolemia, depressive symptoms, body mass index, smoking status, drinking status, duration of education, and baseline MMSE score. Results In the 4 years after the baseline survey, 27 participants (19.3%) developed cognitive impairment (i.e., MMSE scores of ≤24). Multiple logistic regression analysis indicated that participants with 0–9 teeth were more likely to develop cognitive impairment than those with ≥10 teeth were (odds ratio: 3.31; 95% confidence interval: 1.07–10.2). Age, male gender, and baseline MMSE scores were also significantly associated with cognitive impairment. Conclusions Tooth loss was independently associated with the development of cognitive impairment within 4 years among community-dwelling older adults. This finding corroborates the hypothesis that tooth loss may be a predictor or risk factor for cognitive decline

Glutamatergic dysfunction associated with tau depositions in Alzheimer’s disease

Glutamatergic neurons and cingulate cortices have crucial roles in the cognitive dysfunction of Alzheimer\u27s disease (AD). This study aimed to evaluate regional vulnerabilities of the glutamatergic system in AD at the level of the cingulate gyrus in relation to tau and amyloid-β (Aβ) depositions. Combining MRSI and PET, we found that the glutamatergic system in the posterior cingulate cortex (PCC) is vulnerable to tau deposits but not Aβ from the early stage of AD, and glutamate in the PCC region may be a marker of disease progression in AD.2022 Joint Annual Meeting ISMRM-ESMRM

Preterm Deliveries in Women with Uterine Myomas: The Japan Environment and Children’s Study

This study aimed to clarify the association between uterine myomas and preterm birth (PTB), preterm premature rupture of membranes (pPROM), and intrauterine infection (II). The study was based on data from the Japan Environment and Children’s Study, a nationwide birth-cohort study. Data of 86,370 women with singleton births after 22 weeks of gestation (with uterine myomas, n = 5354) were retrospectively analyzed. Using logistic regression, adjusted odds ratios (aORs) for PTB, pPROM, and II were calculated considering women without uterine myomas as the reference. Additionally, the effects of II on the incidence of PTB and pPROM were evaluated. In women with uterine myomas, the aORs for PTB before 37 and 34 weeks, pPROM, and II were 1.37 (95% confidence interval, 1.22–1.54), 1.61 (1.27–2.05), 1.65 (1.33–2.04), and 1.05 (0.75–1.46), respectively. The aORs for PTB and pPROM in women with II and uterine myomas were not significantly increased. Uterine myomas during pregnancy were associated with an increased incidence of PTB and pPROM. However, II in women with uterine myomas was not associated with an increased incidence of PTB or pPROM. These findings suggest a potential risk of occult PTB in pregnant women with uterine myomas