Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma.

OBJECTIVE: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD). METHODS: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized. RESULTS: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer. CONCLUSIONS: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.

Intergenerational support, satisfaction with parent-child relationship and elderly parents' life satisfaction in Hong Kong.

OBJECTIVES: This study examines in what exchange patterns that three types of intergenerational support are associated with elderly parents' life satisfaction, and whether elderly parents' evaluation on parent-child relationship plays a mediation role on those associations. METHOD: Data were drawn from Hong Kong Panel Survey for Poverty Alleviation. Respondents aged 65 and over were included ( N=504). Three types of support, namely, daily-living, financial, and emotional support were examined in four patterns-the over-benefited , under-benefited , reciprocal and no flow of exchange. A multivariable linear regression was applied to investigate the association between pattern of intergenerational exchange and life satisfaction, and mediation analysis was employed to examine the mediating role of satisfaction with parent-child relationship on their associations. RESULTS: Elderly parents were less satisfied with their lives when they had no flow of exchange in daily-living support, and more satisfied when they were under-benefited in financial support, and over-benefited or reciprocal in emotional support. Elderly parents' satisfaction with parent-child relationship mediated the association between exchange of emotional support and life satisfaction; but not the association between daily-living or financial support and life satisfaction. CONCLUSION: Different types of intergenerational support are associated with elderly parents' life satisfaction in different patterns.

Containment, Health, and Social Policies in the Time of COVID-19 - Determinants and Outcomes of Initial Responses across 120 Countries.

The coronavirus disease 2019 (COVID-19) pandemic has triggered an unprecedented number of policy responses around the world across multiple policy domains. While governments have combined containment and health policies with social policies (CHSPs) during the initial phase of the pandemic in various ways, the current literature offers little knowledge of the patterns of these combinations and their determinants and outcomes. This paper fills this gap by investigating CHSP combinations across ≥120 countries. We further examined whether the CHSP response was determined by political regimes or compensation hypotheses-serving the purposes of responding to pre-existing economic downturns, inequality or social unrest. We also investigated the associations between CHSP responses and mobility, virus infection and unemployment. Using policy data from the Oxford COVID-19 Government Response Tracker, results from sequence analysis indicated that governments' CHSP responses could be clustered into five categories: high social policies (SPs), middle SPs, containment and health (CH) leading SPs, low SPs and gradual high SPs. We used multinomial regression models to investigate determinants of CHSP responses. We found that CHSP responses did not differ by political regimes, and CHSP combinations were not driven by compensation hypotheses. Instead, gross domestic product per capita and government effectiveness were the key drivers for high levels of policy responses. We also found that low SP responses were associated with fewer mobility changes. Taken together, our findings suggest that lower-income countries required more support and resources in order for them to adopt necessary CH and SP responses.

Mechanisms connecting objective and subjective poverty to mental health: Serial mediation roles of negative life events and social support.

BACKGROUND: Mental health and poverty remain pressing global challenges yet, their relationship has been neglected by international development policies, even in high income societies. This study aims to investigate the relationship between objective/subjective poverty and mental health and its potential mechanism. METHODS: A population-based data including 1,605 household heads extracted from the Hong Kong Panel Survey for Poverty Alleviation in 2015 were used. Multiple linear regression was conducted to examine the associations among poverty, negative life events, social support and mental health. Serial multiple mediation models were analyzed by the bootstrapping method to assess whether negative life events and social support mediate the relationship between objective/subjective poverty and mental health. RESULTS: Subjective and objective poverty were significantly associated with higher risks of negative life events, less social support and mental distress (p < 0.001). Negative life events and social support in serial partially mediated the relationship between subjective poverty and mental health (total effect: Standardized ß = 0.41,Standardized SE = 0.05, ß = 2.07, 95% CI [1.59, 2.55]; total direct effect: Standardized ß = 0.26, Standardized SE = 0.04, ß = 1.34, 95% CI [0.86, 1.81]; total indirect effect: Standardized ß = 0.14, Standardized SE = 0.04, ß = 0.73, 95% CI [0.51,0.97]). By contrast, even though the total direct effect of objective poverty on mental distress was not statistically significant (Standardized ß = 0.08, Standardized SE = 0.05, ß = 0.41, 95% CI [-0.12, 0.94]), this relationship was also mediated by negative life events and social support (total effect: Standardized ß = 0.21, Standardized SE = 0.06, ß = 1.08, 95% CI [0.52, 1.65]; total indirect effect: Standardized ß = 0.13, Standardized SE = 0.02, ß = 0.67, 95% CI [0.43, 0.92]). CONCLUSIONS: Social support including informational, instrumental and financial could be effective buffers that confer resilience against the negative effects of poverty and adverse life events on mental health. In addition, reducing perceived poverty seemed to be more effective in improving mental health compared to the objective poverty alleviation, and further research are needed to confirm this conclusion.

HER2 and topoisomerase IIalpha: possible predictors of response to neoadjuvant chemotherapy for breast cancer patients.

BACKGROUND: Surrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study was to evaluate HER2 and topoisomerase IIalpha (Topo IIalpha) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients. METHODS: Between 1999 and 2006, seventy-six breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given in more than three cycles to this group of patients. Protein expression of HER2 and Topo IIalpha were determined by immunohistochemistry. The primary endpoint was pathological and clinical response. RESULTS: Of 76 primary breast cancer samples, 27 (35.5%) showed overexpression of either HER2 (25%) or Topo IIalpha protein (10.5%), whereas in 7 tumors (9.2%) both proteins were found to be overexpressed. Ten patients (13.2%) had a clinical complete response and 21 (27.6%) had a clinical partial response. Five women (6.6%) had a pathological complete response, 5 (6.6%) had microscopic residual disease, and 46 (60.5%) had macroscopic residual disease. HER2 and Topo IIalpha overexpression was significantly associated with a favorable response (P < 0.001 and P = 0.005 respectively). CONCLUSION: Our study suggests that HER2 and Topo IIalpha overexpression could be predictors of the response to neoadjuvant chemotherapy in both the CEF and CMF arms.

[The expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma].

OBJECTIVE: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and judge whether they may be used as valuable markers in predicting postoperative metastasis and recurrence of HCC. METHODS: Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (S-P method) were used to measure the expressions of the HPA mRNA and nm23-H1 protein in the primary tumor tissue and paracancer tissue of 33 cases of HCC. The paracancer tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up. RESULTS: The expression of HPA gene was positive in 16 cases of primary tumor tissues of HCC with a positive rate of 48.5%, significantly higher than those in paracancer tissues of HCC cases and in normal controls (P < 0.01). The HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and the group with metastasis or recurrence during follow-up were significantly higher than that in the group with low tendency to metastasis or recurrence group (P < 0.05) and that in the group without metastasis or recurrence (P < 0.01). The poorly differentiated tumor and tumor of TNM stage III-IV had higher positive rates of HPA gene expression than the well-mediate differentiated tumor and tumor of TNM stage I-II (P < 0.05). The positive expression rates of nm23-Hl protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (P < 0.05). nm23-Hl expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P > 0.05). The positive rate of nm23-Hl in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during follow-up was obviously higher than that in the group with low tendency to metastasis and recurrence (P = 0.018) and that in the patients without metastasis and recurrence (P = 0.024), but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rates of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 were 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9) respectively. CONCLUSION: Expression of HPA and/or nm23-Hl are related with metastasis and recurrence of HCC. Combining the expression rate of HPA with the expression rate of nm23-H1 may increase the accuracy in predicting HCC postoperative metastasis and recurrence.

Clinical and pathological analysis of 27 patients with combined hepatocellular-cholangiocarcinoma in an Asian center.

BACKGROUND: Our purpose was to assess the clinicopathological features and surgical outcomes of combined hepatocellular-cholangiocarcinoma (HCC-CC) in an Asian center. METHODS: Between 1998 and 2009, 27 patients were diagnosed with combined HCC-CC at our hospital. Their medical records were reviewed and clinicopathological data retrospectively analyzed. RESULTS: The 27 patients included 24 (88.9%) males and 3 (11.1%) females with a mean age of 58.26 ± 11.18 years. Cirrhosis was present in 10 patients (37.0%), and 12 patients had hepatitis C or hepatitis B virus infection. Serum alpha fetoprotein was >20 ng/ml in 7 of the 19 patients in whom it was measured (36.8%). Twenty-five patients underwent hepatic resections and 2 received liver transplantations. Five (18.5%) patients had separate HCC and CC within the same liver (type I), 21 (77.8%) had tumors with mixed components (type II), and 1 patient had a type III tumor (3.7%). Of 22 patients with immunohistochemical data, 19 (86.4%) were cytokeratin (CK) 7-positive, 20 (90.9%) were CK19-positive, and 4 (18.2%) were CK20-positive. Mean follow-up was 25.8 months. The 1- and 2-year survival rates were 72.5 and 49.4%, respectively. The 1- and 2-year disease-free survival rates were 54.2 and 41.3%, respectively. Symptoms at the time of diagnosis, and regional lymph node metastases, were associated with higher mortality and recurrence. CONCLUSIONS: Lymph node metastasis and positive resection margins are important factors affecting HCC-CC surgical outcomes.

Multiple endocrine neoplasia type 1 simultaneous with various types of enteropancreatic endocrine tumors: one case report: lessons learned.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by the development of parathyroid hyperplasia, pancreatic endocrine tumors, pituitary adenomas, and adrenal adenomas. We reported 1 case of MEN 1 simultaneous with gastrinoma and insulinoma; meanwhile, insulinomas were ectopic and recurrent. The genetic screening showed the mutation of 427del AT of the MEN 1 gene. Surgical removal is considered the treatment of choice, with limited adverse effects and relatively low morbidity and mortality. She was treated by means of several surgical strategies, resulting in improvement of the frequency and severity of the hypoglycemic episodes and a better quality of life.

Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China.

PURPOSE: To evaluate current selection criteria for patients undergoing liver transplantation (LT) in response to hepatocellular carcinoma (HCC), and to analyze the prognostic factors for successful transplantation. METHODS: We evaluated the outcome of 1,078 consecutive patients with HCC from the Shanghai Multi-Center Collaborative LT Group who underwent LT over a 6-year period. Clinicopathologic data for these patients were evaluated. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Multivariate study with Cox's proportional hazard model was used to evaluate the prognosis-relative aspects. RESULTS: We determined that expansion of Milan criteria to include: a solitary lesion < or = 9 cm in diameter, no more than three lesions with the largest < or = 5 cm, a total tumor diameter < or = 9 cm without macrovascular invasion, lymph node invasion and extrahepatic metastasis (referred to as the "Shanghai criteria"), resulted in overall survival (OS) and disease-free survival (DFS) rates that were similar to the Milan criteria. Multivariate analysis using the Cox proportional hazards regression model showed that the Child-Pugh-Turcotte classification (P = 0.010, 0.000), tumor differentiation (P = 0.001, 0.000), tumor size (P = 0.000, 0.000) and number (P = 0.014, 0.016), macrovascular invasion (P = 0.022, 0.000) and alpha-fetoprotein (AFP) levels (P = 0.031, 0.003) were independent predictors of OS and DFS, while post-LT chemotherapy (OS, P = 0.000) and tumor encapsulation (DFS, P = 0.038) were independent predictors of OS or DFS. CONCLUSION: Shanghai criteria expanded the current criteria while maintaining similar survival.