Surgery for multiple gastric gastrointestinal stromal tumors and large esophageal diverticulum related to germline mutation of the KIT gene: a case report.

BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the digestive tract caused by germline gain-of-function mutations in the KIT gene or platelet-derived growth factor receptor alpha gene (PDGFRA). These mutations cause not only multiple GISTs but also diffuse hyperplasia of interstitial cells of Cajal (ICCs), which is related to esophageal motility disorder. CASE PRESENTATION: A 53-year-old man was referred to our hospital because of anemia and dysphagia. Fifteen years earlier, he had undergone a laparoscopic partial gastrectomy for multiple gastric GISTs with a germline mutation in exon 17 of the KIT gene. An upper gastrointestinal endoscopy revealed that the patient had multiple gastric GISTs and a large esophageal diverticulum directly above the esophagogastric junction. The largest gastric tumor was 7 cm, with a delle that might cause bleeding. Because the patient presented with dysphagia, we performed video-assisted thoracic esophagectomy and laparoscopic-assisted proximal gastrectomy simultaneously. The patient had survived without metastasis for 4 years after surgery and dysphagia had improved. CONCLUSIONS: This is the first report of successful laparoscopic-thoracoscopic surgery for a patient with familial gastric GISTs accompanied with a large esophageal diverticulum.

Facilitating ab initio configurational sampling of multicomponent solids using an on-lattice neural network model and active learning.

We propose a scheme for ab initio configurational sampling in multicomponent crystalline solids using Behler-Parinello type neural network potentials (NNPs) in an unconventional way: the NNPs are trained to predict the energies of relaxed structures from the perfect lattice with configurational disorder instead of the usual way of training to predict energies as functions of continuous atom coordinates. An active learning scheme is employed to obtain a training set containing configurations of thermodynamic relevance. This enables bypassing of the structural relaxation procedure that is necessary when applying conventional NNP approaches to the lattice configuration problem. The idea is demonstrated on the calculation of the temperature dependence of the degree of A/B site inversion in three spinel oxides, MgAl2O4, ZnAl2O4, and MgGa2O4. The present scheme may serve as an alternative to cluster expansion for "difficult" systems, e.g., complex bulk or interface systems with many components and sublattices that are relevant to many technological applications today.

[A case of IgG4-related disease exclusively affecting pia matter and cerebral parenchyma].

A 61-year-old man presented with slowly progressive cognitive decline. Brain MRI revealed left frontal lobe lesions with gadolinium enhancement along pia mater. Brain biopsy was performed and histopathological findings was compatible with the diagnosis of IgG4-related disease (IgG4-RD). Serum IgG4 level was within a normal range, and no other systemic organs were suggested to be involved by clinical symptoms or laboratory findings. Intravenous methylprednisolone therapy followed by oral prednisone induction markedly improved the cognitive functions and MRI findings detected at the initial diagnosis. Our case highlights the importance of including IgG4-RD as one of the differential diagnosis when encountering the patients suffering from isolated cranial lesions even in the absence of normal serum IgG4 level.

Comparison of "click-to-sense" assay with frozen section analysis using simulated surgical margins in breast cancer patients.

PURPOSE: We have shown that "Click-to-sense" (CTS) assay based on the visualization of cancer cells by fluorescence probe targeted for acrolein is useful for differentiating between the malignant and benign lesions of the breast. In the present study, we aimed to apply CTS assay to the examination of the simulated surgical margins, being compared with frozen section (FS) analysis. EXPERIMENTAL DESIGN: The simulated surgical margin samples (n = 300) were obtained from 1 to 2 cm distant sites from the tumor margin in the mastectomy specimens of breast cancer patients, and divided into the training (n = 150) and validation (n = 150) set. The samples were subjected to CTS assay, subsequently to FS analysis and finally to permanent section (PS) analysis. RESULTS: Diagnostic accuracy of the CTS assay and FS analysis was evaluated in the examination of the simulated surgical margin status finally determined by the PS analysis. In the training set, sensitivity, specificity, and accuracy was 89.3%, 98.4%, and 96.7% for the CTS assay and 89.3%, 98.4%, and 96.7% for the FS analysis. In the validation set, sensitivity, specificity, and accuracy was 93.3%, 98.3%, and 97.3% for the CTS assay, and 93.3%, 99.2%, and 98.0% for the FS analysis. CONCLUSIONS: The CTS assay is as accurate as the FS analysis in the examination of the simulated surgical margins in breast cancer patients, and it seems to have a potential to replace the FS analysis for the intra-operative examination of surgical margins in breast-conserving surgery since it is less labor-intensive and more time-saving than the FS analysis.

Label-free multiphoton excitation imaging as a promising diagnostic tool for breast cancer.

Histopathological diagnosis is the ultimate method of attaining the final diagnosis; however, the observation range is limited to the two-dimensional plane, and it requires thin slicing of the tissue, which limits diagnostic information. To seek solutions for these problems, we proposed a novel imaging-based histopathological examination. We used the multiphoton excitation microscopy (MPM) technique to establish a method for visualizing unfixed/unstained human breast tissues. Under near-infrared ray excitation, fresh human breast tissues emitted fluorescent signals with three major peaks, which enabled visualizing the breast tissue morphology without any fixation or dye staining. Our study using human breast tissue samples from 32 patients indicated that experienced pathologists can estimate normal or cancerous lesions using only these MPM images with a kappa coefficient of 1.0. Moreover, we developed an image classification algorithm with artificial intelligence that enabled us to automatically define cancer cells in small areas with a high sensitivity of ≥0.942. Taken together, label-free MPM imaging is a promising method for the real-time automatic diagnosis of breast cancer.

A clinicopathological study of ALS with L126S mutation in the SOD1 gene presenting with isolated inferior olivary hypertrophy.

We report an autopsy case of amyotrophic lateral sclerosis with L126S mutation in the superoxide dismutase 1 (SOD1) gene (SOD1). The patient was a 69-year-old Japanese man without relevant family history, who initially presented with slow progressive muscle weakness of the lower extremities without upper motor neuron signs, and died of respiratory failure 6 years after the onset. Neuropathological examination revealed a loss of lower motor neurons and degeneration of Clarke's column commensurate with that of the posterior spinocerebellar tract and the middle root zone of the posterior column. The primary motor area was minimally affected. Characteristic SOD1-immunopositive neuronal intracytoplasmic inclusions, mixed with neurofilament accumulation, were present in the affected areas. Isolated inferior olivary hypertrophy was observed, but did not involve the contralateral dentate nucleus, or the ipsilateral red nucleus and central tegmental tract, where no neuronal inclusions were found. In combination with data from a previous autopsy case, this study suggests that the L126S mutation may cause focal neuronal degeneration in the brainstem.

Marked Hypergastrinemia with G-cell Hyperplasia in Two Autoimmune Gastritis Patients.

Gastrin regulates gastric acid secretion, and gastrin secretion itself is regulated by the negative feedback system of gastric acidity. Autoimmune gastritis (AG) is a disease where parietal cells are destroyed, resulting in decreased acid production and an elevated serum gastrin level. We herein report 2 AG cases with marked hypergastrinemia (>5,000 pg/mL). In both cases, 24-hour gastric pH monitoring showed no time when gastric pH was <2, and immunohistochemistry revealed more than 140 gastrin-positive cells per linear millimeter at the antral mucosa. This is the first report to confirm the relationship between marked hypergastrinemia and G-cell hyperplasia with AG.

Serum deprivation-response protein regulates aldehyde dehydrogenase 1 through integrin-linked kinase signaling in endometrioid carcinoma cells.

Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. We reported previously that aldehyde dehydrogenase 1 (ALDH1), a predominant isoform of the ALDH family in mammals and a potential marker of normal and malignant stem cells, is related to the tumorigenic potential of EC. We compared the levels of various proteins in human EC cells with high and low ALDH1 expression using shotgun proteomics and found that serum deprivation-response protein (SDPR) was preferentially expressed in cells with high ALDH1 expression. Also known as cavin-2, SDPR is a member of the cavin protein family, which is required for the formation of caveolae. Using SDPR-knockout EC cells generated using the CRISPR/Cas9 system, we revealed that SDPR was correlated with invasion, migration, epithelial-mesenchymal transition, and colony formation, as well as the expression of ALDH1. RNA sequencing showed that integrin-linked kinase (ILK) signaling is involved in the effect of SDPR on ALDH1. Immunohistochemical analysis revealed that the localization of ILK at the cell cortex was disrupted by SDPR knockout, potentially interfering with ILK signaling. Moreover, immunohistochemical analysis of clinical samples showed that SDPR is related to histological characteristics associated with invasiveness, such as poor differentiation, lymphatic invasion, and the microcystic, elongated, and fragmented histopathological pattern. This is, to our knowledge, the first report that SDPR is related to tumor progression.

Path-integral Monte Carlo method for the local Z2 Berry phase.

We present a loop cluster algorithm Monte Carlo method for calculating the local Z(2) Berry phase of the quantum spin models. The Berry connection, which is given as the inner product of two ground states with different local twist angles, is expressed as a Monte Carlo average on the worldlines with fixed spin configurations at the imaginary-time boundaries. The "complex weight problem" caused by the local twist is solved by adopting the meron cluster algorithm. We present the results of simulation on the antiferromagnetic Heisenberg model on an out-of-phase bond-alternating ladder to demonstrate that our method successfully detects the change in the valence bond pattern at the quantum phase transition point. We also propose that the gauge-fixed local Berry connection can be an effective tool to estimate precisely the quantum critical point.