ABSTRACT
Recent studies have suggested that gastric cancer does not occur in patients with Helicobacter pylori-negative autoimmune gastritis (AIG); however, this notion is controversial. We encountered a case of gastric cancer associated with AIG in which H. pylori infection was excluded. A woman in her 70s was referred to our hospital for endoscopic resection of an antral adenoma. An H. pylori antibodies test, stool antigens test, H. pylori culture, and histological analysis using Giemsa staining yielded negative results. AIG was suspected because the antrum was endoscopically normal but the body was severely atrophic, which are typical findings of AIG. Anti-parietal cell antibodies were 40-fold positive, the gastrin level was 2950 pg/ml, and the pepsinogen I level, pepsinogen II level, and pepsinogen I/II ratio were 6.3 ng/ml, 5.7 ng/ml, and 1.1, respectively. A pathological examination of the gastric body revealed severe oxyntic atrophy with hyperplasia of enterochromaffin-like cells, whereas the antrum showed no pyloric gland atrophy or inflammation. These findings indicated that the patient had H. pylori-negative AIG. Four years later, a depressed lesion in the lower body and a flat lesion at the angle were observed; the former was a poorly cohesive carcinoma, and the latter was a differentiated adenocarcinoma. Surgical resection revealed that the lesion in the lower body was a poorly cohesive carcinoma invading the submucosa with vascular involvement, whereas the lesion in the angle was an intramucosal differentiated adenocarcinoma. A review of previous studies of gastric cancer with H. pylori-negative AIG suggested that patients with histologically and serologically advanced gastritis are at high risk for carcinogenesis. Even in H. pylori-negative cases, severe gastric mucosal atrophy in AIG cases may indicate a carcinogenic risk; therefore, surveillance for gastric cancer is especially recommended for these cases. Large cohort studies on the association between H. pylori-negative AIG and gastric cancer are warranted.
ABSTRACT
AIMS: Patients with atrophic gastritis unrelated to autoimmune gastritis (AIG) and without active Helicobacter pylori (H.pylori) infection or previous eradication therapy are considered to have previous Helicobacter pylori infection-induced atrophic gastritis (PHIG). This study aimed to clarify the clinical characteristics of patients with PHIG. METHODS: Consecutive patients who underwent upper gastrointestinal endoscopy during the study period were enrolled in the study. Pepsinogen and gastrin levels, H. pylori serology, and endoscopic atrophic grade were assessed. Patients were divided into five groups based on their H. pylori status and disease history (PHIG, without H. pylori infection, with active H. pylori infection, with successful H. pylori eradication, and AIG). Their gastric cancer risk status was classified according to the ABC method of serological gastric cancer screening. RESULTS: Of 536 consecutive patients who underwent upper gastrointestinal endoscopy during the study period, 318 were included (31 with PHIG, 77 without H. pylori infection, 101 with active H. pylori infection, 80 with successful H. pylori eradication, and 29 with AIG). Of the 31 patients with PHIG, 21 (68%) were H. pylori-seronegative, and 20 (65%) were classified as group A (normal pepsinogen, H. pylori-seronegative). Patients with PHIG accounted for 90.1% of the patients at high risk for gastric cancer misclassified as group A. The pepsinogen and H. pylori serological profiles of patients with PHIG were similar to those of patients with successful H. pylori eradication more than six years previously. A receiver-operating characteristic curve (ROC) analysis that included 13 patients with AIG and without active H. pylori infection and no previous eradication therapy and 31 patients with PHIG revealed that an endoscopic atrophy grade of O-III or greater according to the Kimura-Takemoto classification can predict AIG. CONCLUSIONS: Two-thirds of the patients with PHIG were misclassified as being at low risk (group A) according to the ABC method, suggesting that endoscopy is necessary for group A patients. The results of the serological evaluation of PHIG indicated that patients with PHIG may have experienced spontaneous H. pylori eradication, possibly because of the use of antibiotics for other conditions. Autoimmune gastritis should be considered in the presence of grade 0-III or greater gastric mucosal atrophy in patients with suspected PHIG, even if the autoantibody and histological findings are not available.
ABSTRACT
The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited. Here, we show that isobutyric acid has the strongest effect among SCFAs on both immune activity and tumour growth. In vitro, cancer cell numbers were suppressed by approximately 75% in humans and mice compared with those in controls. Oral administration of isobutyric acid to carcinoma-bearing mice enhanced the effect of anti-PD-1 immunotherapy, reducing tumour volume by approximately 80% and 60% compared with those in the control group and anti-PD-1 antibody alone group, respectively. Taken together, these findings may support the development of novel cancer therapies that can improve the response rate to ICIs.
Subject(s)
Immune Checkpoint Inhibitors , Programmed Cell Death 1 Receptor , Tumor Microenvironment , Animals , Mice , Humans , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Cell Line, Tumor , Female , Gastrointestinal Microbiome/drug effects , Immunotherapy/methods , Neoplasms/drug therapy , Neoplasms/immunology , Neoplasms/pathology , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/pharmacology , Drug SynergismABSTRACT
Monosodium glutamate (MSG), a salt form of a non-essential amino acid, is widely used as a food additive, particularly in Asian cuisines, due to its unique flavor-enhancing qualities. Type I allergic reactions to MSG have not previously been reported. Our patient, a 21-year-old woman, was 14 years old when she first noticed swelling of her tongue (but no oral itching, diarrhea, or abdominal pain) after eating various snack foods. Current skin prick testing elicited a weak positive reaction to MSG. We then performed an oral challenge test during which our patient ingested potato snacks. Subsequent histology showed telangiectasia of the buccal mucosa, interstitial edema in the subepithelial submucosa, and mast cell infiltration. Oral mucosal challenge tests using sodium glutamate confirmed oral swelling in this patient. This report is the first to confirm a case of type 1 allergy to MSG by combining pathology findings with the results of challenge testing.
ABSTRACT
BACKGROUND: We previously conducted a retrospective study investigating pancreatic morphological abnormalities that lead to early diagnosis of pancreatic cancer (PC) using computed tomography (CT). We reviewed 41 of 308 PC patients between 2011 and 2017 who had previously undergone CT to look for morphological changes leading to cancer development. In 24 patients (58.5%), a K-shaped constriction of the pancreas ("K-sign") was observed before the appearance of cancer. This study aimed to investigate whether an early PC diagnosis is possible by prospective CT follow-up of patients with the K-sign. METHODS: We investigated PC development through prospective surveillance of patients exhibiting K-signs identified on CT. RESULTS: Of approximately 87 000 CT scans performed between April 2019 and August 2022, the K-sign was observed in 54 patients. A total of 30 patients provided informed consent and were subsequently monitored using CT. Five patients (16.7%) were diagnosed with PC and underwent surgery after 3-24 months follow-up. Pathologically, four of five patients (80%) were diagnosed with early-stage pancreatic cancer (stage 0-IA). All patients exhibited defects in acinar structure, fibrous tissue, fat replacement, and inflammatory cells, suggesting their potential involvement in PC development. CONCLUSION: The detection and surveillance of the K-sign may be helpful for early PC diagnosis.
Subject(s)
Early Detection of Cancer , Pancreatic Neoplasms , Humans , Prospective Studies , Retrospective Studies , Pancreas , Pancreatic Neoplasms/surgery , Tomography, X-Ray Computed/methodsABSTRACT
This case report focuses on a 15-year-old competitive-level high school basketball player who experienced chronic low back pain. Diagnostic imaging revealed osteoid osteoma in the L5 posterior element, causing osteosclerotic deformity of the left lamina and more inferior facet. To return him to the condition of sports activity, less invasive surgery of microscopic tumor resection with autologous bone grafting was planned instead of CT-guided ablation, which can cause thermal injury to nearby tissues. This procedure could preserve spinal structures, including the facet, pedicle, and paravertebral muscles. The day after surgery, the patient experienced a complete resolution of lower back pain. He gradually resumed light exercise two months postoperatively. Three-month follow-up CT imaging revealed bone remodeling at the resection site, to return to complete basketball activities. Over five years, no tumor recurrence or symptoms were observed, and he maintained his competitive activity level.
ABSTRACT
We present a case of life-threatening gastrointestinal bleeding caused by a penetrating atherosclerotic ulcer (PAU) that ruptured into the esophagus. A 65-year-old man presented with pyrexia and nausea. Contrast-enhanced computed tomography (CT) performed on admission revealed a hematoma between the lower esophagus and descending aorta due to a contained rupture of a PAU, which was undiagnosed at that time. Esophagogastroduodenoscopy (EGD) performed on the fifth day of admission revealed a subepithelial lesion in the lower esophagus, further complicated by ulcer formation. Biopsy did not reveal any malignant findings. On the eighth day of admission, the patient experienced substantial hematemesis with vital signs indicative of shock. Emergency EGD was performed, which revealed life-threatening bleeding in the lower esophagus. Contrast-enhanced CT revealed an aortoesophageal fistula with massive hematemesis, after which the patient died. An autopsy revealed perforation of the PAU into the esophagus without aortic dissection or a true aneurysm.Patients with atherosclerosis who develop recent-onset gastrointestinal symptoms, progressive anemia, and/or periaortic lesions should be carefully evaluated using contrast-enhanced CT, and PAU should be considered in the differential diagnosis.
Subject(s)
Aortic Diseases , Penetrating Atherosclerotic Ulcer , Male , Humans , Aged , Hematemesis/etiology , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Esophagus/pathology , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/complications , Ulcer/complications , Ulcer/diagnostic imagingABSTRACT
Organophosphate (OP) agents are continuously utilized in large amount throughout the globe for crop protection and public health, thereby creating a potential concern on human health. OP agent as an anticholinesterase also acts on the endocannabinoid (EC)-hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), to reveal unexpected adverse effects including ADHD-like behaviors in adolescent male rats. The present investigation examines a hypothesis that OP compound inhibiting the EC-hydrolase(s) dysregulates the EC-signaling system, triggering apoptosis in neuronal cells. Ethyl octylphosphonofluoridate (EOPF), as an OP probe, preferably acts on FAAH over MAGL in intact NG108-15 cells. Anandamide (AEA), an endogenous FAAH substrate, is cytotoxic in a concentration-dependent manner, although 2-arachidonoylglycerol, an endogenous MAGL substrate, gives no effect in the concentrations examined here. EOPF pretreatment markedly enhances AEA-induced cytotoxicity. Interestingly, the cannabinoid receptor blocker AM251 diminishes AEA-induced cell death, whereas AM251 does not prevent the cell death in the presence of EOPF. The consistent results are displayed in apoptosis markers evaluation (caspases and mitochondrial membrane potential). Accordingly, FAAH inhibition by EOPF suppresses AEA-metabolism, and accumulated excess AEA overstimulates both the cannabinoid receptor- and mitochondria-mediated apoptotic pathways.
Subject(s)
Endocannabinoids , Organophosphates , Rats , Male , Humans , Animals , Adolescent , Endocannabinoids/pharmacology , Endocannabinoids/metabolism , ApoptosisABSTRACT
OBJECTIVES: Secondary lymph node metastasis (SLNM) indicates a poor prognosis, and limiting it can improve the survival rate in early-stage tongue squamous cell carcinoma (TSCC). Many factors have been identified as predictors of SLNM; however, there is no unified view. Ras-related C3 botulinum toxin substrate 1 (Rac1) was found to be a promoter of the epithelial-mesenchymal transition (EMT) and is also attracting attention as a new therapeutic target. This study aims to investigate the role of Rac1 in metastasis and its relationship with pathological findings in early-stage TSCC. MATERIALS AND METHODS: Rac1 expression levels of 69 cases of stage I/II TSCC specimens and their association with clinicopathological characteristics were evaluated by immunohistochemical staining. The role of Rac1 in oral squamous cell carcinoma (OSCC) was examined after Rac1 in OSCC cell lines was silenced in vitro. RESULTS: High Rac1 expression was significantly associated with the depth of invasion (DOI), tumor budding (TB), vascular invasion, and SLNM (p < 0.05). Univariate analyses revealed that Rac1 expression, DOI, and TB were factors significantly associated with SLNM (p < 0.05). Moreover, our multivariate analysis suggested that Rac1 expression was the only independent determinant of SLNM. An in vitro study revealed that Rac1 downregulation tended to decrease cell migration and proliferation. CONCLUSION: Rac1 was suggested to be an important factor in the metastasis of OSCC, and it could be useful as a predictor of SLNM.
Subject(s)
Squamous Cell Carcinoma of Head and Neck , Tongue Neoplasms , rac1 GTP-Binding Protein , Humans , Lymphatic Metastasis , Neoplasm Invasiveness/genetics , Prognosis , rac1 GTP-Binding Protein/genetics , rac1 GTP-Binding Protein/metabolism , Squamous Cell Carcinoma of Head and Neck/pathology , Tongue Neoplasms/pathologyABSTRACT
INTRODUCTION AND IMPORTANCE: Infarction occurs occasionally in benign mammary tumors but is extremely rare in breast cancer, with few cases having been reported. PRESENTATION OF CASE: A 53-year-old woman presented to our hospital with a mass and pain in the upper lateral region of the right breast. She underwent a needle biopsy and was histologically diagnosed as having invasive carcinoma. A ring-enhancing spherical mass was seen on contrast-enhanced computed tomography and magnetic resonance images. She underwent a right partial mastectomy with sentinel lymph node biopsy for T2N0M0 breast cancer. Macroscopically, the tumor was a yellow mass. Histopathologically, the site contained extensively necrotic tissue with foam cell aggregation, lymphocytic infiltration, and fibrosis in the periphery. No viable tumor cells were observed. The patient was followed up without postoperative chemotherapy or radiotherapy. CLINICAL DISCUSSION: Ultrasound examination performed before the biopsy showed blood flow inside the tumor, but a review of the histopathological tissue after surgery revealed generally low viability of the tumor cells in the biopsy specimen, and the possibility that the tumor had a strong tendency to be necrotic from the beginning was considered. It is presumed that some immunological mechanism was working. CONCLUSION: We have encountered a case of breast cancer with complete infarct necrosis. Infarct necrosis may be present if a contrast-enhanced image shows ring-like contrast.
ABSTRACT
Microcystis aeruginosa is predicted to interact and coexist with diverse broad- and narrow-host-range viruses within a bloom; however, little is known about their affects on Microcystis population dynamics. Here, we developed a real-time PCR assay for the quantification of these viruses that have different host ranges. During the sampling period, total Microcystis abundance showed two peaks in May and August with a temporary decrease in June. The Microcystis population is largely divided into three phylotypes based on internal transcribed sequences (ITS; ITS types I to III). ITS I was the dominant phylotype (66% to 88%) except in June. Although the ITS II and III phylotypes were mostly less abundant, these phylotypes temporarily increased to approximately equivalent abundances of the ITS I population in June. During the same sampling period, the abundances of the broad-host-range virus MVGF_NODE331 increased from April to May and from July to October with a temporary decrease in June, in which its dynamics were in proportion to the increase of total Microcystis abundances regardless of changes in host ITS population composition. In contrast, the narrow-host-range viruses MVG_NODE620 and Ma-LMM01 were considerably less abundant than the broad-host-range virus and generally did not fluctuate in the environment. Considering that M. aeruginosa could increase the abundance and sustain the bloom under the prevalence of the broad-host-range virus, host abundant and diverse antiviral mechanisms might contribute to coexistence with its viruses. IMPORTANCE The bloom-forming toxic cyanobacterium Microcystis aeruginosa interacts with diverse broad- and narrow-host-range viruses. However, the dynamics of the Microcystis population (at the intraspecies level) and viruses with different host ranges remain unknown. Our real-time PCR assays unveiled that the broad-host-range virus gradually increased in abundance over the sampling period, in proportion to the increase in total Microcystis abundance regardless of changes in genotypic composition. The narrow-host-range viruses were considerably less abundant than the broad-host-range virus and did not generally fluctuate in the environment. The expansion and maintenance of the Microcystis bloom even under the increased infection by the broad-host-range virus suggested that highly abundant and diverse antiviral mechanisms allowed them to coexist with viruses under selective pressure. This paper expands our knowledge about the ecological dynamics of Microcystis viruses and provides potential insights into their coexistence with their host.
Subject(s)
Bacteriophages , Microcystis , Microcystis/genetics , Host Specificity , Bacteriophages/genetics , Real-Time Polymerase Chain Reaction , Antiviral AgentsABSTRACT
INTRODUCTION: Malignant melanoma in the male breast is extremely rare. Here we report a case of malignant melanoma in which a small cystic lesion in the male breast gradually increased during follow-up and was difficult to distinguish from breast cancer. CASE: A 65-year-old male was diagnosed with a tumor in the right breast and was referred to our department for further examination. At 42 years of age, he underwent tumor resection of a malignant melanoma of the abdominal skin. Mammary ultrasonography showed a 0.6 cm cystic mass in his right breast. Eight months later, the right breast mass had increased to 1.4 cm, and a core needle biopsy suggested breast cancer. Total mastectomy with axillary lymph node dissection was performed. HE staining of the resected tumor showed intranuclear inclusion bodies and some large nucleoli. On the basis of various immunostaining methods, malignant melanoma was diagnosed instead of breast cancer. After surgery, adjuvant chemotherapy with molecularly targeted drugs was administered. DISCUSSION: This might have been a case of male breast metastasis of malignant melanoma with very late recurrence.
Subject(s)
Breast Neoplasms, Male , Melanoma , Skin Neoplasms , Aged , Humans , Male , Mastectomy , Melanoma/diagnosis , Melanoma/surgery , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/surgery , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/surgery , Diagnosis, DifferentialABSTRACT
We present a case of early gastric cancer resembling a subepithelial lesion (GCSEL) derived from the submucosal ectopic gastric glands (SEGGs), diagnosed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). A 55-year-old woman was referred to our hospital for the investigation of a subepithelial lesion (SEL). Contrast computed tomography and esophagogastroduodenoscopy revealed two SELs in the greater curvature of the fundus and the posterior wall of the upper body of the stomach. EUS revealed a hypoechoic lesion in the submucosa and suggested partial invasion into the muscularis propria of the greater curvature of the fundus, and an anechoic lesion in the submucosa of the posterior wall of the upper body. The different diagnosis for the SEL in the fundus was GCSEL, neuroendocrine tumor, malignant lymphoma, and gastric adenocarcinoma of fundic gland type. EUS-FNA findings suggested adenocarcinoma. The patient underwent a laparoscopic proximal gastrectomy. Pathological findings confirmed a differentiated tubular adenocarcinoma derived from the SEGG, which partially invaded into the submucosa of the surrounding gastric wall without lymphovascular invasion or lymph node metastasis. The patient has been recurrence-free after 10 months of follow-up. EUS should be performed for SELs followed by EUS-FNA for lesions, such as GCSEL, that require early intervention.
Subject(s)
Adenocarcinoma , Stomach Neoplasms , Female , Humans , Middle Aged , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Stomach Neoplasms/pathology , Gastrectomy , Gastric Mucosa/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathologyABSTRACT
A 6-month-old girl was presented to our hospital due to a presacral mass found 5 months after surgery of sacrococcygeal teratoma. The original tumor was a 63 x 50 mm sized round cyst connecting to the coccyx, observed with computed tomography. The initial operation was performed with en bloc removal of the tumor along with the coccyx in the prone position. During a routine follow up, ultrasonography indicated a possible local recurrence, 5 months after the initial operation. The magnetic resonance imaging revealed a polycystic formation with a diameter of 20 x 11 x 17 mm in the presacral space. The laparoscopic operation was conducted with the patient in the lithotomy and Trendelenburg position. The broad ligament of uterus was fixed to the abdominal skin and the rectum was mobilized to identify the tumor, which was resected laparoscopically. A histopathological examination showed the tumor to be a mature cystic teratoma. We observed her without any additional treatment and no recurrence is seen after 6 months.
Subject(s)
Laparoscopy , Spinal Neoplasms , Teratoma , Female , Humans , Infant , Sacrococcygeal Region/pathology , Sacrococcygeal Region/surgery , Spinal Neoplasms/diagnosis , Spinal Neoplasms/surgery , Teratoma/diagnostic imaging , Teratoma/surgery , Tomography, X-Ray ComputedABSTRACT
Maternal obesity is an important risk factor for childhood obesity and influences the prevalence of metabolic diseases in offspring. As childhood obesity is influenced by postnatal factors, it is critical to determine whether children born to women with obesity during pregnancy show alterations that are detectable at birth. Epigenetic mechanisms such as DNA methylation modifications have been proposed to mediate prenatal programming. We investigated DNA methylation signatures in male and female infants from mothers with a normal Body Mass Index (BMI 18.5-24.9 kg/m2) compared to mothers with obesity (BMI≥30 kg/m2). BMI was measured during the first prenatal visit from women recruited into the Ontario Birth Study (OBS) at Mount Sinai Hospital in Toronto, ON, Canada. DNA was extracted from neonatal dried blood spots collected from heel pricks obtained 24 hours after birth at term (total n = 40) from women with a normal BMI and women with obesity matched for parity, age, and neonatal sex. Reduced representation bisulfite sequencing was used to identify genomic loci associated with differentially methylated regions (DMRs) in CpG-dense regions most likely to influence gene regulation. DMRs were predominantly localized to intergenic regions and gene bodies, with only 9% of DMRs localized to promoter regions. Genes associated with DMRs were compared to those from a large publicly available cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC; total n = 859). Hypergeometric tests revealed a significant overlap in genes associated with DMRs in the OBS and ALSPAC cohorts. PTPRN2, a gene involved in insulin secretion, and MAD1L1, which plays a role in the cell cycle and tumor suppression, contained DMRs in males and females in both cohorts. In males, KEGG pathway analysis revealed significant overrepresentation of genes involved in endocytosis and pathways in cancer, including IGF1R, which was previously shown to respond to diet-induced metabolic stress in animal models and in lymphocytes in the context of childhood obesity. These preliminary findings are consistent with Developmental Origins of Health and Disease paradigm, which posits that adverse prenatal exposures set developmental health trajectories.
Subject(s)
Mothers , Pediatric Obesity , Animals , Child , Cohort Studies , DNA Methylation , Female , Humans , Longitudinal Studies , Male , Ontario , Pediatric Obesity/genetics , PregnancyABSTRACT
Antenatal corticosteroids (ACS) are used to treat women at risk of preterm birth to improve neonatal survival. Though affected children may be at long-term risk of neurobehavioural disorders, the driving mechanisms remain unknown. Animal studies have shown that ACS exposure can lead to overlapping changes in DNA methylation between the blood and the brain, identifying gene pathways for neurodevelopment, which highlights the potential to examine peripheral blood as a surrogate for inaccessible human brain tissue. We hypothesized that differential methylation will be identified in blood of term-born neonates following ACS. Mother-infant dyads that received ACS were retrospectively identified through the Ontario Birth Study at Sinai Health Complex and matched to untreated controls for maternal age, BMI, parity and foetal sex (n = 14/group). Genome-wide methylation differences were examined at single-nucleotide resolution in DNA extracted from dried bloodspot cards using reduced representative bisulfite sequencing approaches. 505 differentially methylated CpG sites (DMCs) were identified, wherein 231 were hypermethylated and 274 were hypomethylated. These sites were annotated to 219 genes, of which USP48, SH3PXD2A, NTM, CAMK2N2, MAP6D1 were five of the top ten genes with known neurological function. Collectively, the set of hypermethylated genes were enriched for pathways of transcription regulation, while pathways of proteasome activity were enriched among the set of hypomethylated genes. This study is the first to identify DNA methylation changes in human neonatal blood following ACS. Understanding the epigenetic changes that occur in response to ACS will support future investigations to delineate the effects of prenatal glucocorticoid exposure on human development.
Subject(s)
DNA Methylation , Premature Birth , Adrenal Cortex Hormones/therapeutic use , CpG Islands , Female , Genome-Wide Association Study , Humans , Infant, Newborn , Mothers , Pregnancy , Premature Birth/genetics , Retrospective Studies , Sex FactorsABSTRACT
Simple objective modalities are required for evaluating suspected autoimmune gastritis (AIG). This cross-sectional study aimed to examine whether pepsinogen, gastrin, and endoscopic findings can predict AIG. The diagnostic performance of endoscopic findings and serology in distinguishing AIG was evaluated. AIG was diagnosed in patients (N = 31) with anti-parietal cell antibody and/or intrinsic factor antibody positivity and histological findings consistent with AIG. Non-AIG patients (N = 301) were seronegative for anti-parietal cell antibodies. Receiver operating characteristic curve analysis of the entire cohort (N = 332) identified an endoscopic atrophic grade cutoff point of O3 on the Kimura-Takemoto classification (area under the curve [AUC]: 0.909), while those of pepsinogen-I, I/II ratio, and gastrin were 20.1 ng/mL (AUC: 0.932), 1.8 (AUC: 0.913), and 355 pg/mL (AUC: 0.912), respectively. In severe atrophy cases (≥ O3, N = 58, AIG/control; 27/31), the cutoff values of pepsinogen-I, I/II ratio, and gastrin were 9.8 ng/mL (AUC: 0.895), 1.8 (AUC: 0.86), and 355 pg/mL (AUC: 0.897), respectively. In conclusion, endoscopic atrophy is a predictor of AIG. High serum gastrin and low pepsinogen-I and I/II ratio are predictors even in the case of severe atrophy, suggesting their usefulness when the diagnosis of AIG is difficult or as serological screening tests.
Subject(s)
Autoimmune Diseases , Gastritis, Atrophic , Atrophy , Autoantibodies , Autoimmune Diseases/diagnosis , Cross-Sectional Studies , Gastrins , Gastritis, Atrophic/diagnosis , Gastritis, Atrophic/pathology , Helicobacter Infections , Humans , Pepsinogen AABSTRACT
BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma mainly treated via surgical resection. Herein, we report a case of MPNST wherein a massive tumor thrombus extended to the major veins and heart. CASE PRESENTATION: A 39-year-old female with a history of neurofibromatosis type 1 developed MPNST from the right radial nerve. In addition to adjuvant chemotherapy, she underwent wide tumor resection and concomitant radial nerve resection, followed by postoperative radiotherapy. Histological evaluation revealed marked venous invasion. The 2-year follow-up CT revealed an asymptomatic recurrent tumor thrombus extending from the right subclavian vein to the heart. An urgent life-saving operation was performed to ligate the base of the right subclavian vein and remove the entire intravenous thrombus that extended to the right ventricle. The remaining tumor in the right subclavian vein increased in size 3 months after thrombectomy. After confirming the absence of any metastatic lesions, the patient underwent extended forequarter amputation to achieve surgical remission. One year later, a new metastasis to the right diaphragm was safely resected. The patient remains alive without any evidence of disease 2 years after the extended forequarter amputation. CONCLUSIONS: In cases of a previous history of microscopic venous invasion, recurrence can occur as a massive tumor thrombus that extends to the great vessels.
Subject(s)
Neurofibromatosis 1 , Neurofibrosarcoma , Soft Tissue Neoplasms , Thrombosis , Adult , Female , Humans , Neoplasm Recurrence, Local/surgery , Thrombosis/etiology , Thrombosis/surgeryABSTRACT
Brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC) is usually associated with a poor prognosis. A 55-year-old Japanese man visited Tokyo Dental College Ichikawa General Hospital with complaints of motor aphasia and fatigue. Enhanced magnetic resonance imaging of the brain revealed multiple tumors. The patient's medical history included lung cancer surgery performed at another hospital 3 months prior to his visit to our hospital. Total resection of the left frontal tumor revealed BM from lung adenocarcinoma. Stereotactic radiosurgery (SRS) was performed for the remaining three BMs. At 9 months after SRS, another new BM was discovered, and SRS was again performed. More than 13 years have elapsed since the last SRS was performed, and the patient has remained relapse-free. To the best of our knowledge, this is the first case report describing a patient with NSCLC with multiple BMs who has remained relapse-free for >13 years with no neurological dysfunction, including cognitive deficit.
ABSTRACT
Osteosarcoma is the most common malignant primary bone tumor that occurs most frequently in the second decade of life but rarely in patients over 40 years of age. The most common primary sites of osteosarcoma are the distal femur followed by proximal tibia and proximal humerus, and involvement of the wrist is extremely rare. Moreover, dedifferentiated osteosarcoma is also a rare condition that progresses to high-grade osteosarcoma from low-grade osteosarcoma, usually central low-grade osteosarcoma or parosteal osteosarcoma that bears MDM2 and/or CDK4 gene amplifications. We herein report an extremely rare case of dedifferentiated osteosarcoma arising in the distal ulna of an adult over 40 years of age. The patient was a 46-year-old man with a 2-month history of pain in his left swollen wrist. The initial radiological findings suggested a benign bone tumor in the distal ulna, and the lesion was marginally excised at the nearby hospital. Although the pathological diagnosis at the nearby hospital suggested a benign cartilaginous tumor, the tumor recurred in an aggressive manner 8 months after the initial surgery. The patient was referred to our hospital, and an incisional biopsy showed a high-grade osteosarcoma. The primary tumor was retrospectively re-evaluated at our hospital and diagnosed as low-grade osteosarcoma. Since neoadjuvant chemotherapy failed to shrink the tumor, the patient had to undergo below the elbow amputation to cure the disease. Although the tumor was negative for MDM2 nor CDK4, the definitive diagnosis of dedifferentiated osteosarcoma was made according to the clinical course and the histological findings. Lung metastases were found 10 months after the amputation, which were successfully treated by neoadjuvant chemotherapy and surgery. The patient has been doing well with no evidence of disease for 1 year and 6 months. Surprisingly, the literature review revealed that many low-grade osteosarcomas of the distal ulna progressed to high-grade dedifferentiated osteosarcomas. One should bear in mind that the diagnosis and treatment for bone-forming tumors of the distal ulna should be made very carefully because, although rare, it is possible that the tumor may initially appear as a benign or low-grade malignant tumor and may progress to high-grade osteosarcoma.