Immune regulation in gastric adenocarcinoma is linked with therapeutic efficacy and improved recovery.

Adenocarcinomas are one of the most common histological types of gastric cancer. It has been ranked fifth among common cancers and is the third among death causing cancers worldwide. The high mortality rate among patients with gastric cancer is because of its silent evolution, genetic heterogeneity, high resistance to chemotherapy as well as unavailability of highly effective therapeutic strategy. Until now a number of several treatment strategies have been developed and are being practiced such as surgery, chemotherapy, radio therapy, and immunotherapy, however, further developments are required to improve the treatment responses and reduce the side effects. Therefore, novel personal therapeutic strategies based on immunological responses should be developed by targeting different check points and key immune players. Targeting macrophages and related molecular elements can be useful to achieve these goals. In this minireview, we discuss the available treatment options, molecular underpinnings and immunological regulations associated with gastric adenocarcinoma. We further describe the possible check points and immunological targets that can be used to develop novel therapeutic options.

Aluminum phosphate gel reduces early rebleeding in cirrhotic patients with gastric variceal bleeding treated with histoacryl injection therapy.

BACKGROUND: Esophageal-gastro varices bleeding (EGVB) is the most widely known cause of mortality in individuals with cirrhosis, with an occurrence rate of 5% to 15%. Among them, gastric varices bleeding (GVB) is less frequent than esophageal varices bleeding (EVB), but the former is a more critical illness and has a higher mortality rate. At present, endoscopic variceal histoacryl injection therapy (EVHT) is safe and effective, and it has been recommended by relevant guidelines as the primary method for the treatment of GVB. However, gastric varices after endoscopic treatment still have a high rate of early rebleeding, which is mainly related to complications of its treatment, such as bleeding from drained ulcers, rebleeding of varices etc. Therefore, preventing early postoperative rebleeding is very important to improve the quality of patient survival and outcomes. AIM: To assess the efficacy of aluminium phosphate gel (APG) combined with proton pump inhibitor (PPI) in preventing early rebleeding after EVHT in individuals with GVB. METHODS: Medical history of 196 individuals with GVB was obtained who were diagnosed using endoscopy and treated with EVHT in Shenzhen People's Hospital from January 2016 to December 2021. Based on the selection criteria, 101 patients were sorted into the PPI alone treatment group, and 95 patients were sorted into the PPI combined with the APG treatment group. The incidences of early rebleeding and corresponding complications within 6 wk after treatment were compared between both groups. Statistical methods were performed by two-sample t-test, Wilcoxon rank sum test and χ 2 test. RESULTS: No major variations were noted between the individuals of the two groups in terms of age, gender, Model for End-Stage Liver Disease score, coagulation function, serum albumin, hemoglobin, type of gastric varices, the dose of tissue glue injection and EV that needed to be treated simultaneously. The early rebleeding rate in PPI + APG group was 3.16% (3/95), which was much lower than that in the PPI group (12.87%, 13/101) (P = 0.013). Causes of early rebleeding: the incidence of gastric ulcer bleeding in the PPI + APG group was 2.11% (2/95), which was reduced in comparison to that in the PPI group (11.88%, 12/101) (P = 0.008); the incidence of venous bleeding in PPI + APG group and PPI group was 1. 05% (1/95) and 0.99% (1/101), respectively, and there was no significant difference between them (0.999). The early mortality rate was 0 in both groups within 6 wk after the operation, and the low mortality rate was related to the timely hospitalization and active treatment of all patients with rebleeding. The overall incidence of complications in the PPI + APG group was 12.63% (12/95), which was not significantly different from 13.86% (14/101) in the PPI group (P = 0.800). of abdominal pain in the PPI + APG group was 3.16% (3/95), which was lower than that in the PPI group (11.88%, 12/101) (P = 0.022). However, due to aluminum phosphate gel usage, the incidence of constipation in the PPI + APG group was 9.47% (9/95), which was higher than that in the PPI group (1.98%, 2/101) (P = 0.023), but the health of the patients could be improved by increasing drinking water or oral lactulose. No patients in either group developed spontaneous peritonitis after taking PPI, and none developed hepatic encephalopathy and ectopic embolism within 6 wk of EVHT treatment. CONCLUSION: PPI combined with APG can significantly reduce the incidence of early rebleeding and postoperative abdominal pain in cirrhotic patients with GVB after taking EVHT.

Histologic chorioamnionitis and preterm delivery.

Inconsistent findings linking placental histologic chorioamnionitis (HCA) and preterm delivery may result from variations in HCA definition, population studied, and exclusion criteria. This analysis from the 1998-2004 Pregnancy Outcomes and Community Health Study (five Michigan communities) includes the first 1,053 subcohort women (239 preterm, 814 term) with completed placental assessments. Multiple HCA definitions were constructed by 1) varying polymorphonuclear leukocytes/high-powered field thresholds and placenta components included and 2) using polymorphonuclear leukocyte characteristics to assign low/high maternal, fetal inflammation stage and grade. In African Americans, HCA was associated with preterm delivery before 35 weeks. The effect size was modest for polymorphonuclear leukocytes/high-powered field thresholds of greater than 10 and greater than 30 (odds ratios (ORs) = 0.8 and 2.0); larger for greater than 100 (OR = 3.2, 95% confidence interval (CI): 1.4, 7.1); strengthened after excluding medically indicated preterm deliveries (OR = 4.9, 95% CI: 2.0, 11.8); and strongest for high maternal/high fetal HCA (OR = 5.6, 95% CI: 1.4, 22.1). These latter HCA criteria also produced the largest effect size in Whites/others (OR = 2.7, 95% CI: 0.3, 26.9). Among preterm deliveries before 35 weeks excluding those medically indicated, 12% of Whites/others and 55% of African Americans had high maternal HCA. The authors conclude that HCA definition, exclusion criteria, and race/ethnicity influence the HCA-preterm delivery association and that HCA contributes to preterm delivery-related ethnic disparity.

Mathematical model comparisons of potential non-typeable Haemophilus influenzae vaccine effects.

Vaccines to prevent acute otitis media (AOM) caused by non-typeable Haemophilus influenzae (NTHi) are under development. Because NTHi is highly variable and colonization rates are high, special vaccine characteristics and trial designs might be needed. We examined in mathematical models the equilibrium NTHi-caused AOM rate given hypothetical vaccines that generated immunity identical to corresponding maximal naturally acquired immunity. Vaccines were examined with single effects and combinations of immunity affecting (1) AOM rates given colonization (pathogenicity), (2) susceptibility to colonization, and (3) contagiousness given colonization. Percent reductions in AOM across all preschool children were (1) 34%, (2) 31%, (3) 9%, (1 and 2) 57%, (2 and 3) 50%, and (1, 2, and 3) 75%. Effects on children in daycare vs. not in daycare were (1) 18 vs. 48%, (2) -1 vs. 57%, (3) 13 vs. 5%, (1 and 2) 30 vs. 79%, (2 and 3) 33 vs. 60%, and (1, 2, and 3) 64 vs. 85%. Pure pathogenicity effects (1 alone) will need to be supplemented by transmission effects. The effects of susceptibility (2 alone) are diminished or negative because children protected against colonization have lower levels of immunity to (1) and (3) than unvaccinated children. For trials to predict population effects, both colonization and AOM outcomes must be studied and all three effects must be evaluated. This need arises because, unlike H. influenzae type B, high NTHi exposure diminishes cumulative vaccine effects and high colonization rates generate rapid accumulation of natural immunity that alters the indirect effects of vaccine immunity on transmission differently by age and daycare status.

Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: review of disease progression.

Countries in the the Asia-Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia-Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975-2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co-infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Chronic hepatitis B: a long-term retrospective cohort study of disease progression in Shanghai, China.

BACKGROUND AND AIMS: The present study aimed to describe the disease progression of chronic hepatitis B patients without or with compensated cirrhosis at baseline, to estimate the risk of progression to decompensated cirrhosis, hepatocellular carcinoma and death, and to determine prognostic factors of disease progression in patients in Shanghai, China. METHODS: Stored medical records from 322 biopsy-confirmed chronic hepatitis B cases diagnosed between 1981 and 1993 were selected, and the status of patients was tracked in 1999-2000. Among consenting patients, ultrasound examination and laboratory tests were conducted. Person-year incidence rates, Kaplan-Meier analysis, log-rank tests, and Cox regression analysis were conducted. RESULTS: Among chronic hepatitis B patients without compensated cirrhosis, the incidence rates of decompensated cirrhosis, hepatocellular carcinoma, and death were 6.3, 2.8, and 7.6 per 1000 person-years, respectively, while for patients with compensated cirrhosis, the rates were 35.6, 8.2, and 35.2 per 1000 person-years, respectively. The 15-year survival rate was 88% for patients without compensated cirrhosis, compared with 56% for patients with compensated cirrhosis (P < 0.001). Cox regression analysis demonstrated that increased alpha-fetoprotein (AFP) (P < 0.01), gamma-globulin (P < 0.05), and high-level severity of hepatic fibrosis (P < 0.01) at baseline were risk factors of decompensated cirrhosis. Factors associated with a high risk of death included elevated AFP at baseline (P < 0.01), severity of hepatic fibrosis (P < 0.003), and sustained positivity for hepatitis B surface antigen (P < 0.004). CONCLUSION: Increased AFP and severity of hepatic fibrosis at baseline were associated with higher risk of decompensated cirrhosis and death. These data provide rare empirical estimates of the negative long-term outcomes for patients with chronic hepatitis B in Shanghai, China.

[A retrospective cohort study on the natural history of chronic hepatitis Beta in Shanghai, China].

OBJECTIVE: To describe the natural history of chronic hepatitis Beta in patients with chronic hepatitis Beta (CHB) in Shanghai, China. METHODS: 322 cases with biopsy-proven CHB diagnosed from 1981 to 1993 were retrospectively studied. Medical records since the original diagnosis were reviewed and final examination was performed on those who were still living. Survival analysis including life table, Kaplan-Meier method and Log-Rank test was applied to compare the survival rates, and un-happen rates of decompensated cirrhosis and hepatocellular carcinoma between the groups with compensated cirrhosis and without cirrhosis at the original diagnosis. Standardized mortality ratio (SMR) was calculated to reflect the death risks from total death, hepatic disease death and liver cancer death. RESULTS: For CHB without cirrhosis group, the incidence of decompensated cirrhosis and hepatocellular carcinoma were 6.7 per thousand person-year and 2.8 per thousand person-year,respectively. The mortality was 7.6 per thousand person-year. The 5-, 10-, 15- year survival rates were 95.9%, 93.0% and 87.9%, respectively. The 5-, 10-, 15-year decompensated cirrhosis un-happen rates were 97.1%, 95.4% and 88.9%, respectively. The SMRs of total death, liver cancer death and hepatic diseases death were 2.50, 9.73 and 80.38, respectively. For CHB with compensated cirrhosis group, the incidence of decompensated cirrhosis and hepatocellular carcinoma were 35.6 per thousand person-year and 8.2 per thousand person-year, respectively. The mortality was 35.2 per thousand person-year. The 5-, 10-, 15- year survival rates were 85.3%, 69.0% and 55.8%, respectively. The 5-, 10-, 15-year decompensated cirrhosis un-happen rates were 82.0%, 63.8%, and 58.7%, respectively. The SMRs of total death, liver cancer death and hepatic diseases death were 8.09, 30.30 and 312.50, respectively. CONCLUSIONS: CHB with compensated cirrhosis group had a significantly lower survival rates and lower un-happen rates of decompensated cirrhosis as compared with CHB without cirrho s is group through Log-Rank tests. Both groups had remarkable high SMRs of total death, liver cancer death and hepatic disease death.