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Background: We describe a simple and novel technique for cerebral protection during left subclavian artery (SA) stenting by inflation of a balloon-guiding catheter inside the aortic arch at the SA origin. Methods: A total of 12 patients with left SA stenosis underwent SA stenting with inflation of a balloon-guiding catheter inside the aortic arch at the left SA origin between January 2020 and December 2020. The SA stenting procedures under proximal protection were retrospectively reviewed to assess ischemic complications, hyperintense spots on diffusion-weighted imaging (DWI), and flow direction of left vertebral artery (VA) during balloon-guiding catheter inflation using ultrasonography (US). Results: The success rate of the SA stenting procedure was 100% with no symptomatic ischemic complications. None of the 12 patients showed small hyperintense spots in DWI. In all patients, the left VA on US during balloon inflation showed retrograde blood flow. Conclusions: The left VA on US had retrograde blood flow during inflation of the balloon-guiding catheter inside the aortic arch at the SA origin. Therefore, the proximal balloon protection inside the aortic arch at the SA origin is a simple and maybe a safe technique for cerebral protection during SA stenting.

Psychological factors might be involved in some oral mucosal diseases, such as recurrent aphthous stomatitis (RAS) and oral lichen planus (OLP). However, there is little information about the psychosomatic approaches to manage these oral mucosal diseases. This review summarizes the reports on the psychological statuses of patients with oral mucosal diseases, including RAS and OLP and others, and discusses the appropriate psychosomatic approaches for the management of these diseases. The psychosomatic background is probably involved in onset and course of inflammatory oral mucosal diseases, and can be called as “psychosomatic diseases”. The field of psychosomatic medicine for oral mucosal diseases may be termed “psychostomatology”.

New approaches beyond PD-1/PD-L1 inhibition are required to target the immunologically diverse tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC). In this study, we explored the immunosuppressive effect of B7-H3 (CD276) via the CCL2–CCR2–M2 macrophage axis and its potential as a therapeutic target. Transcriptome analysis revealed that B7-H3 is highly expressed in PD-L1–low, nonimmunoreactive HGSOC tumors, and its expression negatively correlated with an IFNγ signature, which reflects the tumor immune reactivity. In syngeneic mouse models, B7-H3 (Cd276) knockout (KO) in tumor cells, but not in stromal cells, suppressed tumor progression, with a reduced number of M2 macrophages and an increased number of IFNγ+CD8+ T cells. CCL2 expression was downregulated in the B7-H3 KO tumor cell lines. Inhibition of the CCL2–CCR2 axis partly negated the effects of B7-H3 suppression on M2 macrophage migration and differentiation, and tumor progression. In patients with HGSOC, B7-H3 expression positively correlated with CCL2 expression and M2 macrophage abundance, and patients with B7-H3–high tumors had fewer tumoral IFNγ+CD8+ T cells and poorer prognosis than patients with B7-H3–low tumors. Thus, B7-H3 expression in tumor cells contributes to CCL2–CCR2–M2 macrophage axis–mediated immunosuppression and tumor progression. These findings provide new insights into the immunologic TME and could aid the development of new therapeutic approaches against the unfavorable HGSOC phenotype.

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Background Associations have been observed between obesity defined by the body mass index (BMI) and the incidence of endometrial cancer. However, the impact of obesity on the prognosis of endometrial cancer is not yet clear. Recently, visceral fat has been considered to have a greater impact on malignant disease in obese patients than subcutaneous fat. In this study, we investigated the association between prognostic factors of type 1 and type 2 endometrial cancer and obesity parameters. Methods The impacts of clinical factors on the progression-free survival (PFS) and overall survival (OS) were analyzed retrospectively in 145 primary endometrial cancer patients. The factors included age, BMI, pathological findings, Federation of Gynecology and Obstetrics (FIGO) stage, status of lymph node metastasis, and the amounts of visceral and subcutaneous fat obtained from computed tomography (CT) data. Results Only the visceral-to-subcutaneous fat ratio (V/S ratio) (cutoff value 0.5) corresponded to a significant difference in OS and PFS in type 1 endometrial cancer (p = 0.0080, p = 0.0053) according to the results of log-rank tests of Kaplan–Meier curves. The COX regression univariate analysis revealed that only the V/S ratio was a significant prognostic factor for PFS, but not OS (p = 0.033 and p = 0.270, respectively). Conclusion A V/S ratio > 0.5 is a possible factor for poor prognosis in type 1 endometrial cancer. Further research is needed to investigate the preventive and therapeutic effects of reducing visceral fat on the prognosis of this type of cancer.

Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

Lymphoepithelioma-like carcinoma of the uterine cervix is a rare variant of squamous cell carcinoma. Herein, we describe three cases of lymphoepithelioma-like carcinoma of the uterine cervix and review relevant literature. All three patients initially presented with postmenopausal bleeding. Gross appearances were endophytic with ulcerated mucosa in case 1, exophytic with polypoid morphology in case 2, and unremarkable even using colposcopy and hysteroscopy in case 3. Magnetic resonance imaging demonstrated well-demarcated cervical masses with high-intermediate intensity on T2-weighted images and high intensity on diffusion-weighted images in all three cases. In case 3, biopsy referring to local information from magnetic resonance images was required for preoperative diagnosis. We reviewed the literature of 59 lymphoepithelioma-like carcinoma cases in 19 papers published between 2001 and 2020. Preoperative diagnosis of lymphoepithelioma-like carcinoma is sometimes challenging, although magnetic resonance imaging findings may help determine the location of the tumor and obtain a successful biopsy.

Preserved ratio impaired spirometry (PRISm) is associated with an increased mortality rate; however, its characteristics have not been clearly identified in Japan. This cross-sectional study of community-dwelling older adults compared physical function between people with PRISm and those with no respiratory issues, from 2014 to 2019. We collected demographic data through interviews and measured respiratory and physical functions. We included 668 older adults (male, 23.5%; mean age, 72.8 ± 5.6 years); the prevalence of PRISm was 12%, while the prevalence of obstruction was 6.9%. Propensity score matching was used to identify control subjects with normal spirometry (n = 80) while minimizing the effects of confounders during comparisons with the PRISm population (n = 80). Compared with community-dwelling older adults with normal lung capacity, older adults with PRISm had a lower forced vital capacity (%FVC; 68.7 ± 9.1% vs. 92.5 ± 12.7%, p p = 0.032), and a longer one-leg stance duration (52.4 ± 41.1 s vs. 36.4 ± 34.1 s, p = 0.008). In multivariable logistic regression, %FVC and increased one-leg stance were independent predictors of PRISm status. The prevalence of PRISm among community-dwelling elderly Japanese exceeds that of obstructive lung disease and is associated with reduced %FVC and better performance on balance testing.

Background Based on our previous phase II clinical trial of anti-programmed death-1 (PD-1) antibody nivolumab for platinum-resistant ovarian cancer (n=19, UMIN000005714), we aimed to identify the therapeutic response biomarkers to nivolumab in ovarian cancer. Methods Tumor gene expressions were evaluated by proliferative, mesenchymal, differentiated, and immunoreactive gene signatures derived from high-grade serous carcinomas in The Cancer Genome Atlas and a signature established prior to ovarian clear cell carcinoma. Gene sets were scored using the single-sample gene set enrichment analysis, and resulting scores were used to assess the correlation between each gene set and the clinical response to nivolumab therapy. Statistical analyses were performed to identify pathways differentially expressed by either the complete response (CR) or progressive disease (PD) groups. Results The clear cell gene signature significantly had higher score in the CR group, and the proliferative gene signature had significantly higher score in the PD group where nivolumab was not effective (respective p-values 0.005 and 0.026). Combinations of gene signatures improved correlation with response, where a projection of immunoreactive, proliferative, and clear cell signatures differentiated clinical response. Conclusion Ovarian cancer-specific gene signature and related pathway scores provide a preliminary indicator for ovarian cancer prior to receiving anti-PD-1 antibody therapy.

Background/aim During pregnancy, uterine leiomyomas may cause problems and treatment typically entails uterine conservation. However, for cases of leiomyomas larger than a particular size with some clinical symptoms, enucleation should be performed. In clinical practice, the importance of postpartum follow-up of pregnancies with uterine fibroids must be established. Patients and methods A 47-year-old female visited an obstetrics and gynecology clinic with a primary complaint of irregular bleeding. We suspected an 8.4×6.6 cm myoma uteri and recommended immediate surgery. During the next visit, a pregnancy test was positive and the patient requested a follow-up for her myoma uteri diagnosis. Because of a breech presentation, we performed an elective cesarean section (CS) at 38 weeks and 1 day. The patient's myoma uteri was stable throughout the pregnancy, and after delivery, we continued to follow her up as an outpatient. Results Two years after the CS, the myoma uterus was 6 cm in size, and 6 months later, it had increased to 10 cm. Magnetic resonance imaging (MRI) supported a diagnosis of uterine leiomyosarcoma and she underwent surgery. Ultimately, she was pathologically diagnosed with uterine leiomyoma, uterine leiomyoma with bizarre nuclei, and uterine leiomyosarcoma following examination of the excised tissue by using molecular pathological examination with anti-cyclin E antibody and anti-Ki-67 antibody. Conclusion Notably, this case demonstrated the usefulness of cyclin E and Ki-67 as biomarkers for the malignancy of uterine mesenchymal tumors. Presently, she is being monitored for tumor recurrence and metastases on a quarterly basis. In order to detect the rapid increase in uterine mesenchymal tumor, regular follow-up after birth is important.

Objectives Epigenetic phenomena are changes in gene expression not involving the DNA sequence. DNA methylation is a major occurrence underlying epigenetic changes in human cells. Although aberrant DNA methylation is well documented in malignant lesions, limited information has been shown on the involvement of DNA methylation in oral lichen planus and oral lichenoid lesions (OLP). The present study aimed to investigate DNA methylation of E‐cadherin and p16 in OLP, and compare the findings with those in non‐inflamed gingiva (Non), radicular cyst (RC), and oral squamous cell carcinoma (SCC). Materials and methods Paraffin‐embedded surgical biopsy specimens were sliced, DNA was extracted, bisulfite treatment was applied, and methylation‐specific polymerase chain reaction was performed. Immunohistochemistry was performed to observe the relative expression patterns of these genes. Results E‐cadherin was hypermethylated in OLP (p

BackgroundClavicle fractures (CF) after radical neck dissection (RND) for oral cancer are rare but are thought to occur as a result of myotonia and decreased blood supply to the muscles around the clavicle after RND. The current report presents a rare case of a non-neoplastic pathological CF after RND, and discusses the role of imaging examinations for the timely detection of CF.Case reportAn 82-year-old Japanese man underwent RND followed by chemotherapy without radiotherapy for secondary metastasis of the right cervical lymph node after resection of tongue cancer. Computed tomography at 6 months after RND revealed a fracture with bone destruction in the proximal end of the right clavicle. He had no history of trauma at the site of the fracture and no symptoms. The possibility of bone metastasis of the clavicle was considered; however, the bone destruction had not advanced 6 years after the discovery of the fracture. The CF was thus finally considered to be a side effect of RND, rather than metastasis.ConclusionCF is a rare complication following treatment for head and neck cancer but can be caused by neck dissection. Regular imaging examinations, including the clavicular region, are therefore needed before and after surgery to ensure the timely detection of CF.

The diagnosis of insulinoma in perinatal women can be difficult, as hypoglycemic symptoms may be masked by pregnancy‐associated insulin resistance. In addition, when multiple insulinomas are observed, it is necessary to consider the possibility not only of MEN1, but also of insulinomatosis.

Acanthopanax senticosus (Rupr. et Maxim) Harms (ASH), also known as Siberian ginseng or eleuthero, is a hardy shrub native to China, Korea, Russia and the northern region of Japan. ASH is used for the treatment of several diseases such as heart disease, hypertension, rheumatoid arthritis, allergies, chronic bronchitis, diabetes and cancer. In the present study, the inhibitory effect of the root extract of ASH (ASHE) on HuH‑7 and HepG2 liver cancer cells was examined. ASHE suppressed liver cancer cell proliferation by inducing cell cycle arrest at the G0/G1 phase, as well as apoptosis, as indicated by the increased number of Annexin V and 7‑AAD‑positive cells. Furthermore, the expression of LC3‑II, an autophagy marker, in these cells also increased post treatment with ASHE. LC3‑II induction was further enhanced by co‑treatment with chloroquine. Fluorescence and transmission electron micrographs of ASHE‑treated liver cancer cells showed the presence of an increased number of autophagic vesicles. A decreased protein expression level of run domain Beclin‑1‑interacting and cysteine‑rich domain‑containing, an autophagy inhibitor, with no change in RUBCN mRNA expression was observed, indicating activation of the autophagosome‑lysosome fusion step of autophagy. In conclusion, ASHE exerts cytostatic activity on liver cancer cells via both apoptosis and autophagy, and may serve as a potential therapeutic agent for management of liver cancer and autophagy‑related diseases.

Objective The need for tailoring ovarian cancer treatments to individual patients is increasing. This study aimed to evaluate the prognostic value of pretreatment laboratory test data for predicting the response and survival outcomes of platinum-based chemotherapy in ovarian cancer. Methods We enrolled 270 patients with ovarian cancer diagnosed at the Kyoto Medical Center (n=120; group A) and Kyoto University (n=150; group B). Data on 9 blood parameters (neutrophil to lymphocyte ratio [NLR], platelet to lymphocyte rate [PLR], C-reactive protein, lactate dehydrogenase [LDH], glucose, total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein, and triglyceride levels), cancer pathology, cancer stage, cytoreduction outcomes, serum cancer antigen 125 levels, platinum-free interval (PFI), disease-free survival (DFS), and overall survival were assessed retrospectively. Results NLR, PLR, LDH, and HDL were significantly different in advanced stage patients (P

AIM: To evaluate the efficacy of a prototype root canal dressing containing surface pre-reacted glass-ionomer (S-PRG) fillers on repairing induced periapical lesions in a rat model. Calcium hydroxide [Ca(OH)2 ] was applied as a comparison in the healing process. METHODOLOGY: The pulp chambers of the maxillary first molars in 64 male Wistar rats aged 16 weeks were opened to induce periapical lesions. After 28 days, the mesial canal of each tooth was prepared, irrigated with 2.5% sodium hypochlorite (NaOCl) only (control group: irrigation) or followed by the respective dressing [Ca(OH)2 group, irrigation + Ca(OH)2 ; S-PRG group, irrigation + S-PRG], and restored with composite resin for 3 or 7 days (10/group). Four rats with healthy molars were used as blank controls. Descriptive analysis of the periapical radiographs, haematoxylin and eosin staining, and immunohistochemical observation were performed 3 and 7 days after treatment. The periapical gray value, CD68 macrophages, and osteoclasts (cathepsin-K) were quantified and statistically analyzed with Tukey's honest significant difference test. A significant difference was achieved when p values were

Hallux valgus (HV) is a foot deformity with deviation of the greater toe and the first metatarsal. There is little evidence on training the abductor hallucis muscle (AbdH) to treat HV because of the difficulty in implementing the necessary interventions. Although neuromuscular electrical stimulation (NMES) has been used to induce voluntary exercise, there is currently no study on NMES for AbdH. We aimed to verify the immediate effect of NMES on the AbdH muscle function. For the NMES group (n = 15), electrical stimulation was applied for 20 min. In the sham group (n = 15), the stimulating device was set but not turned on. Electromyogram, HV angle (HVA) at rest and during abduction of the big toe, and strength of the AbdH were evaluated. Analysis of covariance was used to investigate differences within groups using the baseline as the covariate. NMES significantly improved the maximal voluntary isometric contractions (%MVIC), HVA at exercise, and muscle strength (%MVIC

Several studies have demonstrated increased pericardial effusion during anti‐PD‐1 immunotherapy, and treatment in patients who have developed pericardial tamponade is controversial. In this study, we describe a 63‐year‐old woman with stage IVA lung adenocarcinoma given pembrolizumab as a first‐line therapy. After four cycles of pembrolizumab treatment, the patient suddenly developed a pericardial tamponade. Although pericardial effusion was increased, her tumor lesions were reduced. After an emergency pericardiocentesis, she continued the pembrolizumab therapy without recurrent pericardial effusions for three months until the primary tumor and lymph node metastasis progressed. Nine months after the pericardiocentesis, the patient died of progressive lung cancer, but pericardial effusion did not recur throughout the treatment course. This case study suggests that pembrolizumab therapy can be continued with a strict follow‐up in some patients with pembrolizumab‐induced pericardial tamponade. Key points • Significant findings of the study Our patient developed pericardial tamponade during pembrolizumab treatment but continued pembrolizumab treatment after emergency pericardiocentesis without recurrent pericardial effusions. • What this study adds Pembrolizumab treatments may be resumed with a strict follow‐up in some patients with treatment‐related pericardial tamponade.

Background Biliary bleeding is a condition reported by Sandblom as hemobilia. The most common cause of hemobilia is iatrogenicity. But it has also been reported as a rare complication after laparoscopic cholecystectomy (LC). Case presentation A man in his 60s underwent a LC. He was taking a direct Xa inhibitor for paroxysmal atrial fibrillation (pAf) and had a history of thrombectomy. There was variation in the bifurcation of the hepatic artery and cystic artery. The right hepatic artery branches from the common hepatic artery by itself, and the cystic artery is double. He complained of right upper quadrant pain, nausea, and vomiting on the third postoperative day (3POD). Non-contrast computed tomography (CT) showed that a high absorption area was found to fill the common bile duct. Contrast CT showed no pseudoaneurysm formation. Ultimately, he was diagnosed with postoperative hemobilia. Angiographic examination selective for the cystic artery branching from the middle hepatic artery revealed leakage of the contrast agent and a micro-pseudoaneurysm. Conclusions We encountered a case of hemobilia after LC. In this case, it was presumed that in addition to the chronic inflammatory changes of the gallbladder wall, extraordinary bifurcation of the hepatic artery and the cystic arteries and easy bleeding due to resumption of a direct Xa inhibitor synergistically caused a micro-pseudoaneurysm and postoperative hemobilia. It was difficult to identify the cause of hemobilia by contrast CT alone. Angiographic examination was useful for identifying and treating the causative artery and needs to perform aggressively.

Computed tomography (CT) is a primary imaging modality for the diagnosis of aortic diseases, because of its minimal invasiveness and agility. Prompt and accurate diagnosis is crucial especially for acute aortic diseases, and the guidelines for acute aortic dissection recommend the use of CT for initial diagnosis. For the follow-up observation of longstanding aortic diseases, the strategy of imaging management by CT must be different from that for emergency and acute phases. In this review, we document the differences in characteristics and clinical course between aortic aneurysm and aortic dissection and explain the use of recent CT techniques in diagnosing short- and longstanding aortic diseases.

BackgroundThe mechanism of resistance development to anti-VEGF therapy in ovarian cancer is unclear. We focused on the changes in tumour immunity post anti-VEGF therapy.MethodsThe frequencies of immune cell populations and hypoxic conditions in the resistant murine tumours and clinical samples were examined. The expression profiles of both the proteins and genes in the resistant tumours were analysed. The impact of granulocyte–monocyte colony-stimulating factor (GM-CSF) expression on myeloid-derived suppressor cell (MDSC) function in the resistant tumours was evaluated.ResultsWe found a marked increase and reduction in the number of Gr-1 + MDSCs and CD8 + lymphocytes in the resistant tumour, and the MDSCs preferentially infiltrated the hypoxic region. Protein array analysis showed upregulation of GM-CSF post anti-VEGF therapy. GM-CSF promoted migration and differentiation of MDSCs, which inhibited the CD8 + lymphocyte proliferation. Anti-GM-CSF therapy improved the anti-VEGF therapy efficacy, which reduced the infiltrating MDSCs and increased CD8 + lymphocytes. In immunohistochemical analysis of clinical samples, GM-CSF expression and MDSC infiltration was enhanced in the bevacizumab-resistant case.ConclusionsThe anti-VEGF therapy induces tumour hypoxia and GM-CSF expression, which recruits MDSCs and inhibits tumour immunity. Targeting the GM-CSF could help overcome the anti-VEGF therapy resistance in ovarian cancers.

We analyzed the cell characteristics, neuroprotective, and transplantation effects of human cranial bone-derived mesenchymal stem cells (hcMSCs) in ischemic stroke model rats compared with human iliac bone-derived mesenchymal stem cells (hiMSCs). The expressions of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF ) as neurotrophic factors were analyzed in both MSCs. hiMSCs or hcMSCs were intravenously administered into ischemic stroke model rats at 3 or 24 h after middle cerebral artery occlusion (MCAO) and neurological function was evaluated. The survival rate of neuroblastoma × glioma hybrid cells (NG108-15) after 3 or 24 h oxidative or inflammatory stress and the neuroprotective effects of hiMSCs or hcMSCs-conditioned medium (CM) on 3 or 24 h oxidative or inflammatory stress-exposed NG108-15 cells were analyzed. The expressions of BDNF and VEGF were higher in hcMSCs than in hiMSCs. hcMSCs transplantation at 3 h after MCAO resulted in significant functional recovery compared with that in the hiMSCs or control group. The survival rate of stress-exposed NG108-15 was lower after 24 h stress than after 3 h stress. The survival rates of NG108-15 cells cultured with hcMSCs-CM after 3 h oxidative or inflammatory stress were significantly higher than in the control group. Our results suggest that hcMSCs transplantation in the early stage of ischemic stroke suppresses the damage of residual nerve cells and leads to functional recovery through the strong expressions of neurotrophic factors. This is the first report demonstrating a functional recovery effect after ischemic stroke following hcMSCs transplantation.

BackgroundTertiary lymphoid structures (TLSs) are transient ectopic lymphoid aggregates whose formation might be caused by chronic inflammation states, such as cancer. The presence of TLS is associated with a favorable prognosis in most solid malignancies. The recognition of the relevance of TLS to cancer has led to a growing interest in TLS as an immunomodulatory target to enhance tumor immunity, although how TLSs are induced in the tumor microenvironment (TME) and how they affect patient survival are not well understood.MethodsTLS distribution in relation to tumor infiltrating lymphocytes (TILs) and related gene expression were investigated in high grade serous ovarian cancer (HGSC) specimens. CXCL13 expression, which is strongly associated with TLS, and its localization in immune cells, were examined. We explored the tumor microenvironment for CXCL13 secretion by adding various inflammatory cytokines in vitro. The induction of TLS by CXCL13 was examined in a mouse model of ovarian cancer.ResultsCXCL13 gene expression correlated with TLS formation and the infiltration of T cells and B cells, and was a favorable prognostic factor for HGSC patients. The coexistence of CD8+ T cells and B-cell lineages in the TME was associated with a better prognosis of HGSC and was closely related to the presence of TLSs. CXCL13 expression was predominantly coincident with CD4+ T cells in TLSs and CD8+ T cells in TILs, and shifted from CD4+ T cells to CD21+ follicular dendritic cells as the TLS matured. Although TGF-β was reported to stimulate CXCL13 production, our in vitro results revealed that CXCL13 secretion was promoted in CD4+ T cells under TGF-β + IL-2-restricted conditions and in CD8+ T cells under TGF-β + IL-12-rich conditions. In a mouse model of ovarian cancer, recombinant CXCL13 induced TLSs and enhanced survival by the infiltration of CD8+ T cells.ConclusionsTLS formation was promoted by CXCL13-producing CD4+ T cells and TLSs facilitated the coordinated antitumor responses of cellular and humoral immunity in ovarian cancer.

In Asia, including Japan, dementia incidence peaks in older adults over ≥75 years, it is therefore important to detect mild cognitive impairment (MCI), and prevent its onset in this age group. Our study hypothesized that physical and psychological status would be associated with MCI incidence among community-dwelling people aged 75 years and older. The study population comprised 291 such individuals. Participants with a Mini-Mental State Examination score of 28 or more were considered non-MCI, and those with a score of less than 28 and greater than 24 were considered to have MCI. Several other measures were also evaluated, including information about their current medical visits due to diseases, depressive symptom severity, various physical functions (trunk function, 30 s chair-stand test, one-legged stance test, timed up and go test time, 5 m walking time, grip strength, knee-extension strength, and toe-grip strength), and body composition (body fat and skeletal muscle mass). Participants suspected of having MCI had significantly shorter educational histories, higher rates of medical visits due to hypertension, and poorer balance abilities. The results suggest that these indices can be considered screening indicators for detecting MCI in people aged 75 years and older, which may be useful for planning intervention programs for this population.

Background/Aim: Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma, including its subtypes, is the most common uterine tumor. The subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, this intravenous leiomyomatosis’ oncological features resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. Materials and Methods: We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. Result: CD44-positive mesenchymal tumor stem-like cells were detected in both intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological nature of intravenous leiomyomatosis was found to be similar to the oncological properties of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, Cyclin E and Ki-67-positive cells were rare, and no pathological findings suspected to be malignant were observed. Conclusion: It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

A giant omphalocele was successfully treated with a two-step procedure. The first step was a three-staged operation with Gore-tex® sheet to elongate the abdominal muscular layer, and the second step was conservative treatment using the artificial dermis (Terudermis®) to attain effective epithelization at the residual skin defect areas. The proper combination therapy of surgical and conservative treatments may be effective for giant omphalocele because some novel materials and methods including silver-containing materials, povidone-iodine, artificial dermis and negative pressure wound therapy have become available. We report one optional treatment here. The best combination of these strategies for the treatment of giant omphalocele should be sought in the future.

Pancreatic arteriovenous malformation (PAVM) is defined as a vascular anomaly with an abnormal anastomosis of the arterial and portal networks within the pancreas. Treatment modalities of PAVM include transarterial embolisation (TAE), irradiation and operation. Most patients treated with TAE alone will experience recurrence, so surgery is the best radical treatment. A female patient was admitted to our institution for the treatment of haematemesis. Examination revealed varices in the oesophagus and stomach, collateral circulation development caused by portal hypertension and PAVM of the pancreas. Surgical treatment was intended to reduce left portal hypertension. In this case, collateral circulation were considered dangerous points for unexpected bleeding. TAE was performed on the splenic artery before surgery to reduce blood flow in the areas with collateral circulation. En bloc resection of retroperitoneal tissue using the surgical procedure of radical antegrade modular pancreatosplenectomy was effective to minimise blood loss.

Ovarian clear cell carcinoma (CCC) exhibits an association with endometriosis, resistance to oxidative stress, and poor prognosis owing to its resistance to conventional platinum‐based chemotherapy. A greater understanding of the molecular characteristics and pathogenesis of ovarian cancer subtypes may facilitate the development of targeted therapeutic strategies, although the mechanism of drug resistance in ovarian CCC has yet to be determined. In this study, we assessed exome sequencing data to identify new therapeutic targets of mitochondrial function in ovarian CCC because of the central role of mitochondria in redox homeostasis. Copy number analyses revealed that chromosome 17q21‐24 (chr.17q21‐24) amplification was associated with recurrence in ovarian CCC. Cell viability assays identified an association between cisplatin resistance and chr.17q21‐24 amplification, and mitochondrion‐related genes were enriched in patients with chr.17q21‐24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2) had a worse prognosis than those with low PDK2 expression. Furthermore, inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species. Mouse xenograft models showed that inhibition of PDK2 with cisplatin inhibited tumor growth. This evidence suggests that targeting mitochondrial metabolism and redox homeostasis is an attractive therapeutic strategy for improving drug sensitivity in ovarian CCC., Copy number analyses and cell viability assays identified an association between cisplatin resistance and chromosome 17q21‐24 (chr.17q21‐24) amplification, and mitochondrion‐related genes were enriched in patients with chr.17q21‐24 amplification. Patients with high expression of pyruvate dehydrogenase kinase 2 (PDK2), a key enzyme that inhibits acetyl‐CoA from entering the tricarboxylic acid cycle and is located on chr.17q23, had a worse prognosis than did those with low PDK2 expression. Inhibition of PDK2 synergistically enhanced cisplatin sensitivity by activating the electron transport chain and by increasing the production of mitochondrial reactive oxygen species.

Oral cenesthopathy (OC) is characterized by unusual oral discomfort without corresponding evidence, and it has often been categorized as “delusional disorder, somatic type”. Regarding possible causative factors of OC, involvement of neurovascular contact (NVC) of the trigeminal nerve, which transmits not only pain but also thermal, tactile, and pressure sensations, has never been observed yet. This study aimed to investigate the relationship between clinical characteristics of unilateral OC and the presence of trigeminal nerve NVC. This is a retrospective comparative study that involved 48 patients having predominantly unilateral OC who visited the Psychosomatic Dentistry Clinic of Tokyo Medical and Dental University between April 2016 and February 2019. Magnetic resonance imaging was performed to assess NVC presence. The Oral Dysesthesia Rating Scale (Oral DRS) was used to assess the various oral sensations and functional impairments besides psychometric questionnaires. Clinical characteristics were retrospectively obtained from the patients' medical charts. NVC was present in 45.8% (22/48) of the patients. There was no significant difference in sex, age, psychiatric history, oral psychosomatic comorbidity, and psychometric questionnaire scores between patients with and without NVC. However, compared to the patients with NVC, the patients without NVC had significantly higher scores for overall subjective severity of OC symptoms (p = 0.008). Moreover, patients having predominantly unilateral OC without NVC showed significantly higher scores in symptom severity and functional impairment of the following parameters: movement (p = 0.030), work (p = 0.004), and social activities (p = 0.010). In addition, compared with the patients with NVC, the patients without NVC showed significantly higher averages of the total symptom severity scale (SSS) and functional impairment scale (FIS) scores in the Oral DRS (p = 0.015 and p = 0.031, respectively). Furthermore, compared with the patients with NVC, the patients without NVC had significantly higher numbers of corresponding symptoms in both the SSS and FIS (p = 0.041 and p = 0.007, respectively). While NVC may be involved in the indescribable subtle OC symptoms, more complex mechanisms may also exist in OC patients without NVC, which yield varying and more unbearable oral symptoms.

To clarify the impact of blood pressure (BP) management ranges on pregnancy outcomes, we conducted a multicenter retrospective analysis of 215 women with singleton pregnancies diagnosed with essential hypertension either before or within 14 weeks of gestation. Patients were classified according to systolic BP (sBP

We reported an extremely rare case regarding intraosseous clear cell variant of mucoepidermoid carcinoma in maxilla.

Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006–2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20+ B cells, CD8+ T cells, CD4+ T cells, and CD38+ plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044–0.536; P = 0.003). Patients with TLSs that included CD23+ germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20+ B cells was significantly larger in patients with TLSs than in those without TLS (P + B cells numbers were positively correlated with other TLSs. The larger number of CD20+ B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer.

Side population (SP) cells harbor malignant phenotypes in cancer. The aim of this study was to identify genes that modulate the proportion of ovarian cancer SP cells. Using a shRNA library targeting 15,000 genes, a functional genomics screen was performed to identify genes whose suppression increased the SP percentage. The biological effects caused by alteration of those identified genes were investigated in vitro and in vivo. We found that suppression of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 increased the proportion of SP cells. Newly generated SP cells exhibit greater capacity for sphere formation, single cell clonogenicity, and in vivo tumorigenicity. On the contrary, overexpression of MSL3, VPS45, ITGB3BP, TLE2, and ZNF498 decreased the proportion of SP cells, sphere formation capacity and single cell clonogenicity. In ovarian cancer cases, low expression of MSL3, ZNF691 and VPS45 was related to poor prognosis. Suppression of these six genes enhanced activity of the hedgehog pathway. Cyclopamine, a hedgehog pathway inhibitor, significantly decreased the number of SP cells and their sphere forming ability. Our results provide new information regarding molecular mechanisms favoring SP cells and suggest that Hedgehog signaling may provide a viable target for ovarian cancer.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancers harboring highly metastatic and chemoresistant features. Our previous study showed that STAT1 is highly expressed in USC and acts as a key molecule that is positively correlated with tumor progression, but it remains unclear whether STAT1 is relevant to the malicious chemorefractory nature of USC. In the present study, we investigated the regulatory role of STAT1 toward platinum-cytotoxicity in USC. STAT1 suppression sensitized USC cells to increase cisplatin-mediated apoptosis (p < 0.001). Furthermore, phosphorylation of STAT1 was prominently observed on serine-727 (pSTAT1-Ser727), but not on tyrosine-701, in the nucleus of USC cells treated with cisplatin. Mechanistically, the inhibition of pSTAT1-Ser727 by dominant-negative plasmid elevated cisplatin-mediated apoptosis by increasing intracellular accumulation of cisplatin through upregulation of CTR1 expression. TBB has an inhibitory effect on casein kinase 2 (CK2), which phosphorylate STAT1 at serine residues. Sequential treatment with TBB and cisplatin on USC cells greatly reduced nuclear pSTAT1-Ser727, enhanced intracellular accumulation of cisplatin, and subsequently increased apoptosis. Tumor load was significantly reduced by combination therapy of TBB and cisplatin in in vivo xenograft models (p < 0.001). Our results collectively suggest that pSTAT1-Ser727 may play a key role in platinum resistance as well as tumor progression in USC. Thus, targeting the STAT1 pathway via CK2 inhibitor can be a novel method for attenuating the chemorefractory nature of USC.

Primary signet ring cell carcinoma of uterine cervix (SRCCC) is extremely rare. We present two cases of primary SRCCC that were treated with robot-assisted laparoscopic radical hysterectomy (RALRH). Case 1 had stage IB2 cervical adenocarcinoma, in which signet ring cell (SRC) was predominant. As adjuvant chemotherapy was not successful, she twice underwent surgical excision of recurrent tumors in pararectal lymph node and periureteral space 11 months and 27 months after RALRH, respectively. There were only SRCs observed in recurrent tumors. Case 2 had stage IB1 cervical adenocarcinoma, in which SRCs were detected only in the biopsy specimen, and no relapse occurred at 15 months after RALRH. PET/CT was useful for tumor detection in both cases, and the amount of SRC components was associated with the prognostic outcome. Considering the high recurrence rate and few complications at secondary surgery, minimally invasive surgery would be preferred as the primary surgery for SRCCC.

Aim To examine the hysteroscopic morphological features in each histological grade of endometrial cancer, and to distinguish high- and low-grade cancer and low-grade cancer and atypical endometrial hyperplasia (AEH), using hysteroscopy. Methods In total, 135 patients who underwent hysterectomy after hysteroscopy were analyzed. They were divided into four categories: benign lesion; AEH; low-grade cancer, including endometrioid carcinoma grades 1 and 2 (G1/2); and high-grade cancer, including endometrioid carcinoma grade 3 and other high-grade carcinomas (G3/others). Three blinded gynecologic oncologists independently evaluated hysteroscopic video images for abnormal vessels, surface smoothness, papillary structure and polypoid structure. Prevalence rates of each finding were compared between the four categories. The accuracy of blind biopsy in outpatient settings and hysteroscopic endometrial biopsy in the four categories were also investigated. Results The number of patients with benign lesions, AEH, G1/2 and G3/others was 8, 7, 84 and 36, respectively. Patients with G3/others exhibited more polypoid (86% vs 61%, P = 0.0095) and less papillary (59% vs 80%, P = 0.023) structures than those exhibited by patients with G1/2. AEH and G1/2 were indistinguishable using hysteroscopy. Hysteroscopic biopsy was more accurate than outpatient biopsy in patients with G3/others (84% vs 52%, respectively, P = 0.010). Both biopsies were not sufficiently accurate to diagnose AEH (outpatient; 0%, hysteroscopic; 57%). Conclusion Hysteroscopic papillary and polypoid structures can help distinguish between high- and low-grade cancer. Hysteroscopic differentiation between AEH and low-grade cancer is difficult. These findings are considerable in preoperative assessment to determine adequate surgical strategies.

RNase 7 is a skin-derived antimicrobial peptide expressed in various epithelial tissues. It is upregulated by stimulation with microbes and pro-inflammatory cytokines. Herein, we examined the expression levels of RNase 7 in tissues from normal and inflamed oral epithelia and salivary glands via immunohistochemistry. RNase 7 was expressed mainly in the surface layers of the parakeratinized and orthokeratinized oral epithelium. In addition, it was strongly and weakly expressed in oral lichen planus and radicular cysts, respectively. RNase 7 was constitutively expressed in salivary glands, particularly in the serous and duct cells. In the case of Sjogren's syndrome, RNase 7 was strongly expressed in serous, ductal, and mucous cells in areas with lymphocytic infiltration. The localization patterns of RNase 7 were similar to those of other epithelial antimicrobial peptides, including beta-defensins. Thus, epithelial antimicrobial peptides may act against microbial infections in a coordinated manner in oral epithelia and salivary glands.

Solitary fibrous tumors (SFT) rarely arise in the pelvis. Here, we report two cases of SFT arising from the pelvic retroperitoneum. The first case involves a 64-year-old woman diagnosed with a 5-cm pelvic mass. Magnetic resonance imaging revealed a solid and cystic mass with marked enhancement, but limited water restriction. During surgery, intraligamental tumor arising near the round ligament was resected. Pathologically, the tumor comprised dilated vessels and spindle-shaped cells positive for STAT6 and CD34. The second case involves a 53-year-old woman diagnosed with a 4.5-cm pelvic mass through computed tomography. Magnetic resonance imaging demonstrated a solid mass with multiple cysts with strong enhancement and slight water restriction. During surgery, the tumor was found in the retroperitoneum. Pathologically, spindle-shaped tumor cells positive for STAT6 and CD34 had proliferated around the prominent hyalinized vessels. Although rare in the pelvis, SFT should be suspected when a mass with strong enhancement is found.

We report a case of aggressive adult granulosa cell tumor (AGCT) of the ovary. On presentation, the tumor was localized in the right ovary; a total abdominal hysterectomy, bilateral salpingo-oophorectomy and partial omentectomy were performed. While some areas of the tumor represented typical AGCT, other areas showed enlarged and hyperchromatic nuclei with numerous mitoses (>10/high-power field) with marked necrosis. The results of immunohistochemical analysis were compatible with AGCT, except that, in the necrotic portion, p53 was strongly positive, and the Ki-67 index was high. Four months after laparotomy, recurrent tumors developed in the bones, liver, lungs and dura mater. The patient responded well to chemotherapy consisting of five cycles of paclitaxel and carboplatin, but later, the tumors rapidly proliferated, and the patient died of disease 11 months after laparotomy. FOXL2 examination demonstrated that both portions of the primary tumor did not have a point mutation (402C→G) specific to AGCT.

There has never been evidence for aneurysmal subarachnoid hemorrhage (aSAH) by endovascular coiling compared to surgical clipping with all grade. The present study and meta-analysis aimed to clarify the in-hospital mortality and poor outcome in the nationwide databases of patients with all grade aSAH between them. The outcome of modified Rankin scale (mRS) at discharge was investigated according to the comprehensive nationwide database in Japan. The propensity score-matched analysis was conducted among patients with aSAH in this database registered between 2010 and 2015. Meta-analysis of studies was conducted based on the nationwide databases published from 2007 to 2018. According to this propensity score-matched analysis, no significant association for poor outcome of mRS > 2 was shown between surgical clipping and endovascular coiling (47.7% vs 48.3%, p = 0.48). However, significantly lower in-hospital mortality was revealed after surgical clipping than endovascular coiling (7.1% vs 12.2%, p

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM–receptor interaction, and focal adhesion signalling. The protein–protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan–Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets., peer-reviewed

Background: Burning mouth syndrome (BMS) is a common condition of predominant oral pain without evident cause, that maxillofacial surgeons and otolaryngologists often refer to psychiatrists as somatic symptom disorder. In very rare cases, its typical burning symptom mimics those of other diseases in which serious fatal comorbidities may be missed. We encountered three rare cases of oral squamous cell carcinoma (OSCC) with the first symptom of burning tongue.Case Presentation: Case 1: A 68-year-old woman had burning pain on the left lingual margin for 8 years. Antidepressant treatment was not efficacious. Cytology and biopsy revealed OSCC. Case 2: A 70-year-old man had burning sensation and paralysis of the tongue for 6 months. Magnetic resonance imaging (MRI) revealed a 37 × 23-mm mass under the floor of the mouth and enlargement of lymph nodes on both sides. Case 3: A 90-year-old man had burning sensation of the tongue for 1 year. MRI revealed a 12 × 12-mm mass on the mandible with bone absorption.Conclusion: This case series suggests that psychiatrists must always be careful in regarding BMS as somatic symptom disorder and be cautious of the possibility of OSCC, especially in elderly patients.

Recent advances in endoscopic intranasal technology have allowed for a safe approach to the pterygopalatine fossa lesion. However, we consider that there is still scope of improvement to approach a broader area with better operability and minimal invasiveness. A 51-year-old man underwent endoscopic endonasal surgery due to the recurrence of chordoma at the left pterygopalatine fossa. To access the lower and lateral part of the pterygopalatine fossa, we performed endoscopic endonasal transmaxillary removal via an inferior turbinate incision. During surgery, a wide operative field and good operability could be secured by inserting an endoscope from the right nostril through a window of the nasal septum. Subtotal removal of the tumor was achieved without any complication during the surgery. Endoscopic endonasal transinfraturbinate approach with nasoseptal window was effective in the removal of the pterygopalatine fossa tumor because it is less invasive and provides a good surgical view with better operability.

Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.

Diagnosis by biopsy is difficult in the ovary, since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the omentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favourable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PDligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

The sirtuins (SIRTs) family proteins are class III histone deacetylases (HDACs) and comprise seven members (SIRT1–7). They are widely expressed in normal tissues and are involved in several biological processes, including cancers. SIRTs play fundamental roles in carcinogenesis by mainly participating in cancer cell viability, apoptosis, invasion, and metastasis. A disequilibrium of SIRTs expression was previously documented in oral cancer. SIRT1 and SIRT3 have been the most extensively studied and are considered to be promising strategies against this cancer. There are, however, conflicting results regarding the association between SIRT1 and SIRT3. These SIRTs are known to suppress or promote oral cancer depending on their cellular content or type. In this report, we will describe the fundamental roles of SIRT1 and SIRT3 in oral carcinogenesis and provide critical discussion of their dual roles, tumor suppression, and tumor promotion.