Clinicopathological correlation of radiologic measurement of post-therapy tumor size and tumor volume for pancreatic ductal adenocarcinoma

ObjectivesTumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival.Materials and methodsRetrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman’s coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant.ResultsAs a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P < 0.001) and RadV (δ: 0.63, p < 0.0001). However, there was no correlation between RadL and pathologic tumor size in patients with ypT0 and those with pathologic tumor size of ≤1.0 cm. Post-therapy RTS and RadV group correlated with ypT stage, tumor response grades using either CAP or MDA grading system, distance of superior mesenteric artery margin and tumor recurrence/metastasis.ConclusionAlthough RadL tends to understage ypT in PDAC patients who had no radiologically detectable tumor or small tumors (RTS0 or RTS1), radiologic measurement of post-therapy tumor size may be used as a marker for the pathologic tumor staging and tumor response to neoadjuvant therapy.     

Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53.

The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage from exogenous chemical and physical mutagens. Therefore, we hypothesized that p53 performs a similar role in response to putative endogenous mutagens, such as nitric oxide (NO). We report here that exposure of human cells to NO generated from an NO donor or from overexpression of inducible nitric oxide synthase (NOS2) results in p53 protein accumulation. In addition, expression of wild-type (WT) p53 in a variety of human tumor cell lines, as well as murine fibroblasts, results in down-regulation of NOS2 expression through inhibition of the NOS2 promoter. These data are consistent with the hypothesis of a negative feedback loop in which endogenous NO-induced DNA damage results in WT p53 accumulation and provides a novel mechanism by which p53 safeguards against DNA damage through p53-mediated transrepression of NOS2 gene expression, thus reducing the potential for NO-induced DNA damage.     

Development and characterization of nine polymorphic microsatellite markers from the sword prawn Parapenaeopsis hardwickii using PCR-based isolation of microsatellite arrays (PIMA)

Nine polymorphic microsatellite makers were isolated and characterized in 20 individuals of Parapenaeopsis hardwickii collected from the fishing ground near Ilan, Taiwan. Number of alleles per locus ranged from 3 to 8, observed and expected heterozygosities ranged from 0.5263 to 0.7632, and from 0.4225 to 0.8044, respectively. Only one locus showed a Hardy–Weinberg equilibrium deviation. No linkage disequilibrium was found among these studied loci. This set of microsatellites provides a suitable tool for population genetic structure and fishery management of this species in Asian coastal waters.     

Absolute lymphocyte count and risk of short-term infection in patients with immune thrombocytopenia

Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (<1?×?10⁹/l) was an independent risk factor for infection (P?=?0.039; 95 % confidence interval, 1.033–3.599; odds ratio, 1.928). The time to infection event is significant shorter in those of low ALC, compared with those of higher ALC (P?=?0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was significantly higher in those patients who developed an infection (P?=?0.001). ITP patients with a low absolute lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival.     

A “Bone Marrow Score” for Predicting Hematological Disease in Immunocompetent Patients With Fevers of Unknown Origin

Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, “bone marrow (BM) score”, to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease.Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort.For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively.As immunocompetent FUO patients with hematological disease have poor prognoses, the “BM score” is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.     

Gender differences in metabolic syndrome risk factors among patients with serious mental illness

The prevalence of metabolic syndrome and its components continue to increase among patients with serious mental illness. This cross‐sectional study investigated whether metabolic syndrome prevalence and risk factors differ between male and female patients with serious mental illness. In total, 260 eligible patients were recruited from two hospitals. The data on demographic characteristics, lifestyle behaviour factors, biochemistry, and anthropometry were collected. Analyses were performed using multivariate logistic regression. Metabolic syndrome prevalence was 40.8% (35.1% in men and 46.8% in women). Among patients aged 40–49 years, metabolic syndrome prevalence was higher in men; however, the trend was reversed among patients aged 50 years or older. Notably, gender‐specific metabolic syndrome risk factors were observed. In men, they included low education level, high body mass index (BMI), prolonged illness, comorbid physical illness, and diagnosis of bipolar disorder, whereas they included being married, old age, and high BMI in women. Our findings suggest that mental health professionals should consider the gender‐ and age‐based metabolic syndrome prevalence trend in patients with serious mental illness when designing interventions for the study population to minimize metabolic syndrome prevalence.