Vascular invasion and potential for tumor angiogenesis and metastasis in gastric carcinoma

BACKGROUND: Hematogenous metastasis occurs when cancer cells released from the primary site enter blood vessels and are transported to distant organs, where they attach and proliferate. Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. METHODS: We analyzed data on 1184 Japanese adult men and women with gastric cancer with respect to the relation between vascular invasion and the potential for tumor angiogenesis and metastasis. All these patients were treated from 1976 to 1995 in the Department of Surgery II, Kyushu University. In 300 patients, the expression of vascular endothelial growth factor (VEGF) and p53 protein in tumor tissues was examined by using an immunohistochemical staining method or Northern blotting or both. Intratumoral microvessels were stained with anti-CD31 monoclonal antibody. RESULTS: Vascular invasion was evident in 254 patients (21.5%), and in these patients lymphatic invasion was more frequent and the rate of lymph node metastasis was higher in relation to the extent of vascular invasion. The positive findings were directly related to the depth of invasion and the presence of lymph node and liver metastasis. Tumor invasive and metastatic rates increased in relation to the extent of vascular invasion. Expressions of VEGF and p53 protein were higher and microvessel density was more prominent in tumor tissues in relation to the extent of vascular invasion. A close relation between VEGF and p53 protein expressions was also noted in tumors that showed vascular invasion. The expression of VEGF is one of the independent risk factors for vascular invasion. The postoperative outcome was poorer in patients with vascular invasion in relation to the extent of vascular invasion. CONCLUSIONS: Our findings show that gastric cancers with characteristics of vascular invasion have greater intratumoral angiogenesis and that VEGF and p53 overexpression is associated with intratumoral angiogenesis and metastases to distant organs.     

Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Anthropometric characteristics and comorbidities in Japanese patients with neurofibromatosis type 1: A single institutional case–control study

Neurofibromatosis type 1 (NF1) is a well‐known genetic disorder characterized by café‐au‐lait spots and neurofibromas, but many other clinical characteristics and associated comorbidities also have been reported. This study aimed to characterize NF1 further by investigating its association with anthropometric characteristics and other diseases. We performed a case–control study of 227 NF1 patients (101 male, 126 female) and a randomly selected age‐ and sex‐matched control group of 681 non‐NF1 patients (303 male, 378 female) who visited our institution in Japan. We examined adult (≥20 years) height and body mass index (BMI), and, in the total sample, allergic diseases (bronchial asthma [BA], atopic dermatitis [AD] and allergic rhinitis) and other respiratory cardiovascular and psychiatric disorders. In adults, the mean BMI was lower in the NF1 group than in the control group, and was significantly statistically different among men (P = 0.0238). In the whole sample, the prevalences of BA (P = 0.0184), AD (P = 0.0144) and valvular heart disease (P = 0.0166) were significantly greater in the NF1 group than in the control group. To date, no similar research on the BMI or the prevalence of allergic disease in NF1 patients has been reported. Our results suggest that NF1 patients tend to have lower BMI and may have alterations in specific metabolic pathways and altered allergic immunity.     

Leaflet escape in an Edwards TEKNA mitral prosthesis

In almost every type of artificial valve, structural failure has been described. We are reporting on a case of a sudden leaflet escape of an Edwards TEKNA mitral valve prosthesis 12 years after implantation. The patient had a sudden onset of dyspnea and severe pulmonary edema with subsequent cardiogenic shock. An emergency mitral replacement was successfully performed. A multi-detector computed tomography scanning and three-dimensional imaging showed two fragments that had embolized in the terminal aorta and the left common iliac artery. The patient presented visual field abnormality, and postoperative head computed tomography showed watershed cerebral infarction. The escaped leaflet that fractured transversely was removed, following the patient’s recovery, during cardiac surgery.     

Z‐ligustilide ameliorated ultraviolet B‐induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO‐1 and suppression of NF‐κB pathway

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z‐ligustilide (Z‐lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB‐induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z‐lig significantly rescued UVB‐induced NHEKs damage in a dosage‐dependent manner. Pretreatment of NHEKs with Z‐lig inhibited UVB‐induced ROS production in NHEKs. Both silencing the nuclear factor E2‐related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase‐1 (HO‐1) inhibitor, cancelled the inhibitory effect of Z‐lig on UVB‐induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z‐lig reduced UVB‐induced nuclear factor kappa B (NF‐κB)‐dependent inflammatory mediators (IL‐6, IL‐8 and MCP‐1) production at both mRNA and protein level. In the presence of Z‐lig, UVB‐induced NF‐κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z‐lig can suppress UVB‐induced ROS generation through Nrf2/HO‐1 upregulation and inflammation by suppressing the NF‐κB pathway, suggesting that Z‐lig may be beneficial in protecting skin from UVB exposure.     

Neonatal Onset Diffuse Cutaneous Mastocytosis: A Case Report and Review of the Literature

Abstract: Diffuse cutaneous mastocytosis is a rare variant of mast cell disease with widespread erythroderma, which is normally clinically apparent in early infancy. We report the case of a neonate who presented with diffuse erythrodermic rash and bullous lesions. Biopsy specimens showed a dense dermal infiltrate of mast cells. Serum histamine and tryptase levels were elevated. No somatic mutation of the c‐kit gene was found. Blistering ceased at 5 months of age, but atopic dermatitis appeared at 6 months and allergic workup revealed a high level of food‐specific IgE. Herein, we describe the case and provide the first review of the literature on neonatal onset diffuse cutaneous mastocytosis to clarify the prognosis of this condition.     

Anomalous Junction of Pancreaticobiliary Duct without Congenital Choledochal Cyst: A Possible Risk Factor for Gallbladder Cancer

Among 1586 patients subjected to endoscopic retrograde cholangiopancreatography, an anomalous junction of the pancreaticobiliary duct (AJPB) was found in 24 patients (1.5%). Eighteen of the 24 had an associated congenital choledochal cyst, and six did not. Four of these six patients (66.7%) had gallbladder cancer. A clinicopathological study was performed on these four and 43 such cases reported in the literature. The diagnosis of AJPB was made by direct cholangiography. Median age of these 47 (53.5 yr) was younger than those without AJPB. The length of the common channel ranged from 15 to 53 mm. The pancreatic-biliary type junction was present in 36 of 39 cases (92.3%). Gallstones were present in 7 of 40 (17.5%). Levels of amylase in bile were high in 10 of 11. Presence of AJPB without congenital choledochal cyst may be a high risk factor in gallbladder cancer; hence prophylactic cholecystectomy should be considered for patients with AJPB, without congenital choledochal cyst.