Exploring the molecular pathology and tumor microenvironment in gastric cancer liver metastasis

Association of celiac disease and intestinal lymphomas and other cancers

To clarify the clinical and pathological characteristics of gastric cancer in the elderly. Clinical and pathological characteristics of patients who died during 1986-94 with gastric cancer which did not undergo surgery were studied retrospectively. The patients were divided into three groups according to age: A (65-74 years, n = 38), B (75-84 years, n = 77), and C (85 years and over, n = 43). Borrman type-1 was more frequent in group C and Borrman type-4 was frequent in group B. "Early cancer", protruded type (type I or type IIa) was more frequent in group C. In cases of advanced cancer some patients did not undergo surgery because the cancer was to advanced, and others had concomitant diseases that made surgery risky. In all groups, a few patients refused surgery. In cases of "early cancer", the most reason for not undergoing surgery was a concomitant disease in all groups. Other reasons were general weakness and dementia in group C, second malignancy and dementia in group B, and second malignancy in group A. After advanced cancer was diagnosed, 9.6% survived for 1 year, and 1.7% for 2 years. After early cancer was diagnosed, 50.7% survived for 1 year, 15.2% for 3 years and 7.8% for 4 years. The survival rates did not differ by age. In all age groups, gastric cancer was frequently the main cause of death in patients with advanced cancer, but many patients with "early cancer" died of other causes.

BackgroundPrevious studies that examined Parkinson's disease (PD) mortality were mostly conducted in Western countries.ObjectsWe compared mortality rates and causes of death in PD patients and persons without PD from Taiwan over 15 years of follow-up.MethodsWithin the National Health Insurance database, we followed 50,290 incident PD patients (2003-2016) and 201,153 matched non-PD participants (controls) until 31/12/2018. We used multivariable Cox proportional-hazards regression models to compare mortality rates and causes of death in PD patients and controls. Due to non-proportionality, we performed stratification by follow-up duration (≤5/>5 years). We examined interactions between PD status participants' characteristics for all-cause mortality.ResultsPD patients had higher all-cause mortality than controls (HR = 1.40, 95% CI = 1.37-1.42); the association was stronger (p < 0.0001) after the first 5 years of follow-up (HR = 1.49 [1.46-1.53]) than before (HR = 1.34 [1.31-1.37]). The strongest associations were observed for suicide (HR = 1.79 [1.52-2.10]), dementia (HR = 1.69 [1.47-1.93]), and pneumonia (HR = 1.57 [1.49-1.65]). The association between PD and death decreased as age increased, and was stronger in patients without comorbidities, depression, and dementia than in those with.ConclusionsTaiwanese PD patients have reduced life expectancy throughout the course of disease with a stronger association after the first 5 years of follow-up. PD had a stronger impact on mortality in younger persons and in those without comorbidities. Prevention of pneumonia and suicide, and appropriate management of dementia and comorbidities would help reduce PD-related mortality. Our findings may help health authorities allocate resources to improve the management of PD patients in order to address PD-related mortality.

Although the mortality rate in patients on hemodialysis remains extremely high, detailed information on causes of death over long-term periods is limited. The aim of this study was to clarify the underlying causes of death in patients undergoing maintenance hemodialysis in Japan. This was a 10-year, multicenter, observational study of 3528 outpatients undergoing maintenance hemodialysis in Japan. Clinical outcomes were analyzed and causes of death were classified into six broad categories including cardiovascular diseases, infectious diseases, malignant neoplasms, cachexia, trauma/accidents, and other diseases, and more detailed subcategories. During the 10-year follow-up period, 1748 (49.5%) patients died. The most frequent causes of death were cardiovascular diseases (36.1%), followed by infectious diseases (25.8%) and malignant neoplasms (13.5%). In a detailed classification, sudden death, pulmonary infection, and lung cancer were the most common causes of death in cardiovascular diseases, infectious diseases, and malignant neoplasms, respectively. Our study determined details on causes of death in Japanese hemodialysis patients during the 10-year follow-up period. Cardiovascular disease, especially sudden death is noticeable cause of death among patients on hemodialysis.

Infection is considered the second leading cause of death in dialysis patients with end-stage renal disease (ESRD). However, infection prevalence as primary cause of death still seems to be underreported in the literature. We investigated the role of C-reactive protein (CRP) levels shortly before death as predictor of dying from an infection as primary cause of death in this patient group. Between January 1997 through March 2006, we defined the primary causes of death in 231 of the 481 incident patients in our single-center study, who died during this time and assessed the overall prevalence of infection at different predefined CRP cutpoints (between 2 and 300 mg/l). By means of an adjusted multiple logistic regression model, we calculated the odds ratio of (log) CRP for death in 346 survivors and non-survivors with available CRP levels within 5 days of death. In the 96 non-survivors (i.e. cases) of this group, the association of (log) CRP and causes of death was determined by the multiple linear regression model. Infection as a primary cause of death was initially diagnosed in 42% of the 231 non-survivors by standard parameters and clinically. However, the rate of patients possibly dying from this disease increased accordingly when also including cases without any clinical infection signs but with CRP values higher than a given cutpoint (between 2 and 300 mg/l), e.g. when including all cases with CRP cutpoints higher than 100 mg/l, overall prevalence of infection as cause of death increases to 57% (95% CI = 51-64%). Infection was significantly associated with higher CRP levels compared with cardiac death (p < 0.001), with an odds ratio of log CRP for death of 5.4 (95% CI = 3.8-7.7). Prevalence of infection as primary cause of death in ESRD patients may be even higher than currently stated in the literature. Therefore, to reduce mortality, infections should be further avoided and controlled in the future.

Several protozoa have emerged as the major opportunistic infections and cause of death in patients with acquired immunodeficiency syndrome (AIDS). Pneumocystis carinii pneumonia is the leading cause of death in AIDS patients. Electron microscopy (EM) usually shows numerous trophozoites and cysts of Pneumocystis filling up the entire alveolar space, while only cysts are seen under the light microscope. The focal thickening of cyst wall of Pneumocystis, as demonstrated by EM and manifested as a "parentheses" shaped structure with silver stain, serves as a diagnostic marker for Pneumocystis. Freeze-fracture EM has demonstrated the intimate contact between Pneumocystis trophozoites and the type I pneumocytes, which may contribute to the alveolar-capillary block, leading to severe respiratory distress. However, EM is seldom needed for the diagnosis of this infection. Toxoplasma encephalitis, which is an unusual clinical manifestation in cases of toxoplasmosis reported previously, has become a common complication and one of the major causes of death in patients with AIDS. Because subclinical infection by Toxoplasma is common, serologic tests usually offer no definite answers as to whether the infection is acute or chronic, active or past. The small size and its non-specificity in both morphology and tissue affinity make light microscopic diagnosis of toxoplasmosis difficult. Only immunologic staining, such as immunoperoxidase and immunofluorescence, can help to achieve a definite positive identification of the organism. When special antibodies or facility for such staining is not available, EM is the final resort for identifying Toxoplasma by showing the apical complex with the characteristic sausage-shaped rhoptries. Cryptosporidiosis, practically unknown before the AIDS outbreak, has become one of the most common intestinal protozoa in both immunocompromised and immunocompetent patients. The protracted and sometimes fatal course of cryptosporidiosis in immunocompromised patients can be explained by the presence of autoinfective oocysts (thin-walled oocysts), as detected by EM, and by recycling of first-generation schizonts observed experimentally. While diagnosis of cryptosporidiosis can be made by detection of oocysts in stools in most cases, EM is still the last resort for a definitive identification of Cryptosporidium species. While the incidence of isosporiasis is still low, it has been found more frequently in patients with AIDS than in the general population. The parasite, Isospora belli, being a coccidian as is the Cryptosporidium species, is similar to the latter in its life cycle and clinical manifestations.(ABSTRACT TRUNCATED AT 400 WORDS)

The increasing use of highly active antiretroviral therapies (HAARTs) has changed the course of AIDS-related illnesses and enhanced the quality of life of patients infected with human immunodeficiency virus (HIV) and may have changed the causes of deaths in patients with acquired immunodeficiency syndrome (AIDS). The aim of the present study was to investigate causes of deaths in long-term care hospital patients with late-stage AIDS who expired at the Coler-Goldwater Memorial Hospital in New York City in 1995, and in 1998 and 1999, that is, immediately before and the two most recent years after the advent of HAART. Analysis of causes of deaths as recorded on the death certificates of 232 AIDS patients. The overall mortality rate declined from 75.6 deaths per 100 person-years in 1995 to 33.2 deaths per 100 person-years in 1998-1999 (P < .001). The number of AIDS patients who expired because of sepsis and opportunistic infections, which included Pneumocystis carinii pneumonia (PCP), decreased significantly from 30 (26.1%) and 24 (20.9%) in 1995 to 15 (12.8%) and 10 (8.5%) in 1998-1999, respectively (P < .05). In contrast, deaths from hepatic failure increased from 0 (0%) in 1995 to 7 (6%) in 1998-1999 (P < .05). Increases, although not significant statistically, were associated with pneumonias excluding PCP, end-stage AIDS, renal failure, and malignancies. Analysis of cause-specific mortality by gender between 1995 and 1998-1999 revealed very little difference between men and women. This analysis showed, however, that the infectious processes taken together (pneumonias excluding PCP, sepsis, and opportunistic infections including PCP) were significantly less frequent causes of death in 1998-1999 than in 1995 (P < .01). These findings indicate that HAART affected the causes of deaths in patients with AIDS, with "traditional" opportunistic infections diminishing in importance relative to chronic medical conditions and malignancies.

Urological disorders are still the leading cause of death in patients with spinal dysraphism

Performance and Clinical Evaluation of the 92-Gene Real-Time PCR Assay for Tumor Classification

The most common site of hematogenous metastasis of gastric is liver,its prognosis is bad.It is a common cause of death in patients with gastric cancer.In the past few years,along with the development of molecular biology,the mechanism of tumor metastasis has been known gradually.Tumor metastasis is multistep process,the most important condition is cell invading and angiogenesis.Here the author summarize the mechanism of cell invasion and angiogenesis. Key words: Neoplasms; Neoplasm metastasis; Neovascularization, pathologic

Near-Comprehensive Resequencing of Cancer-Associated Genes in Surgically Resected Metastatic Liver Tumors of Gastric Cancer

uated from the medical records and autopsy findings if available. Differences between the two groups were assessed by nonparametric analysis. The characteristics of the patients are shown in table 1 . There were no significant differences in gender, age at onset and age at death between the two groups; however, disease duration was significantly longer in patients with TPPV than without TPPV (Wilcoxon’s test, p ! 0.05). The hospitalization period until death was also significantly longer in patients with TPPV (Wilcoxon’s test, p ! 0.05). All patients with TPPV died in hospital, whereas a few patients without TPPV died at home. Twenty-two patients underwent autopsy and the diagnosis of ALS was confirmed in all patients by pathologic study. The causes of death in this study are shown in table 2 . The most frequent cause of death in patients with TPPV was respiratory failure (46.2%), as well as in patients without TPPV (89.6%). It was previously reported that 81.3% of ALS patients without TPPV died of respiratory failure [4] . Taken together with a previous report [4] and our study, the frequency of respiratory failure as a cause of death in patients with TPPV seems to be lower than in patients without TPPV. In addition, it is notable that all patients with TPPV developed reDear Sirs, Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of upper and lower motor neurons, leading to weakness and wasting of the affected muscles [1] . Previous reports have shown that the most common cause of death in patients with ALS is respiratory failure followed by other causes, including cardiac problems (myocardial infarction, arrhythmia), sepsis and malignancies [2– 5] ; however, knowledge about the causes of death in patients treated with tracheostomy-positive pressure ventilation (TPPV) is very limited. In this study, we investigated the causes of death of ALS patients on TPPV. We retrospectively reviewed the medical records of 112 consecutive patients with ALS referred to our hospital between April 2006 and September 2011. Diagnosis of ALS was made according to El Escorial diagnostic criteria [6] and clinically probable or definite patients were evaluated in this study. We identified 51 patients who died in this period and divided them into two groups: 13 patients who had been assisted with TPPV at the time of death and 38 patients who had not (9 patients had been assisted with noninvasive positive pressure ventilation, and 29 patients had not received any mechanically assisted ventilation). The causes of death were evalReceived: March 14, 2012 Accepted: June 24, 2012 Published online: September 21, 2012

Liver metastasis is a major cause of mortality in gastric cancer (GC), yet the underlying molecular mechanisms remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of gene expression and cancer progression, but their roles in GC liver metastasis are not fully defined. In this study, lncRNA sequencing of primary GC tumors and matched liver metastatic tissues identified PSPC1-AS2 as significantly upregulated. Its elevated expression was further validated across multiple patient cohorts and public datasets. Functional assays demonstrated that PSPC1-AS2 promotes GC cell migration, invasion, and liver metastasis both in vitro and in vivo. Mechanistically, PSPC1-AS2 is predominantly localized in the nucleus and enhances the mRNA stability of its neighboring gene PSPC1 by recruiting the RNA-binding protein EIF4A3. The PSPC1-AS2/PSPC1 axis facilitates tumor progression and induces macrophage polarization toward the pro-tumorigenic M2 phenotype via increased CCL2 secretion. At the molecular level, PSPC1 interacts with PARP1, competitively inhibiting PARP1-mediated PARylation and dephosphorylation of STAT3, thereby sustaining STAT3 activation and promoting CCL2 transcription. Notably, neutralization of CCL2 effectively reverses PSPC1-induced M2 macrophage polarization. Collectively, these findings reveal a novel PSPC1-AS2/PSPC1/STAT3/CCL2 regulatory axis that drives GC progression and liver metastasis through remodeling of the tumor microenvironment, highlighting a potential therapeutic target for advanced gastric cancer.

New technological developments have frequently preceded major advances in biomedical research and medicine [1]. For example, the development of fluorescent DNA sequencing techniques made it possible to establish the large-scale high-throughput technology needed for human genome sequencing. Polymerase chain reaction (PCR), fluorescent DNA sequencing, and other techniques have enabled the discovery of about 1700 mendelian disease genes [2]. The advent of the DNA microarray based technologies has now made it possible to measure simultaneously the expression of tens of thousands of genes in different tissues under a variety of conditions. This high-throughput technology has afforded biomedical scientists a unique opportunity to integrate the descriptive characteristics (i.e. ‘phenotype’) of a biological system under study with the genomic readout (i.e. gene expression). The opportunity to contemplate the integrated view of biological systems has provoked a shift in biological sciences away from the classical reductionism to systems biology [1,3,4]. The systems approach to a disease is based on the hypothesis that disease processes perturb a regulatory network of genes and proteins in a way that differs from the respective normal counterpart. Consequently, by using multi-parametric measurements it may be possible to transform current diagnostic and therapeutic approaches and enable a predictive and preventive personalized medicine [4]. The application of microarray technologies to characterize tumors at the gene expression level has significantly impacted clinical oncology [5,6]. Global gene expression analysis of various human tumors has resulted in

By targeting the underlying etiology, precision therapies offer an exciting paradigm shift to improve the stagnant outcomes of drug-resistant epilepsies, including developmental and epileptic encephalopathies. Unlike conventional antiseizure medications (ASMs) which only treat the symptoms (seizures) but have no effect on the underlying disease, precision therapies have the potential to suppress not only the seizures but also disabling comorbidities, including cognitive and behavioral abnormalities, which share the same causative mechanisms. Monogenic epilepsies are an attractive target for precision therapies because of their well-defined molecular mechanisms which can be tested invitro and can be counteracted by specific drugs. Unfortunately, however, for the vast majority of proposed precision therapies, the evidence for their clinical efficacy is either non-existent or limited to uncontrolled observational accounts. Everolimus is the sole precision therapy with a seizure-related indication with class I evidence of efficacy, highlighting the practical and ethical challenges in obtaining high-level evidence. Here, we review the evidence landscape for candidate precision therapies, including repurposed and innovative treatments currently in development, discuss lessons learned from their use, and highlight strategies to improve their application and evaluation in the clinical setting. PLAIN LANGUAGE SUMMARY: Precision therapies offer a new approach to treat drug-resistant monogenic epilepsies, that is, epilepsies caused by a defect in a single gene. Unlike traditional antiseizure medications, precision therapies target the cause of the disease and have the potential to improve not only seizure control but also concomitant conditions such as cognitive and behavioral disorders. To date, the evidence derived from the clinical use of most proposed precision therapies is limited. This review explores current evidence and strategies to advance their development.