Elevated circulating CD19+ lymphocytes predict survival advantage in patients with gastric cancer

Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be aprognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocytesubset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patientshospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient’s disease freesurvival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model.Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantlyincreased proportion of CD4+, CD19+, CD44+, CD25+, NK cells, and an increased CD4+/CD8+ ratio in GC patientsas compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated withsex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicatedsignificantly higher DFS for patients with high circulating CD19+ lymphocytes compared to those with lowCD19+ lymphocytes (P=0.037), with CD19+ showing an important cutoff of 7.91±2.98% Conclusion: Circulatinglymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorablesurvival.     

Combined Therapy of Transcatheter Arterial Chemoembolization and Radiofrequency Ablation versus Surgical Resection for Single 2–3 cm Hepatocellular Carcinoma: A Propensity-Score Matching Analysis

Purpose

To compare therapeutic outcomes of radiofrequency (RF) ablation combined with transcatheter arterial chemoembolization vs surgical resection (SR) for single 2–3 cm hepatocellular carcinoma (HCC).

Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck

CD9 is a transmembrane protein that has been implicated in cell adhesion, motility and proliferation, and numerous studies have demonstrated the prognostic value of its expression in different solid tumours. The purpose of this study is to determine the predictive value of CD9 in squamous cell carcinoma (SCC) of the head and neck. A total of 153 cases were examined for CD9 expression using immunohistochemistry applied on formalin-fixed, paraffin-embedded tissue. Cases were stratified in two categories depending on CD9 expression, as positive (>/=50% positive cells) or reduced (<50%). In all, 108 cases were positive for CD9 (85 cases with membranous, and 23 with both membranous and cytoplasmic staining) and 45 reduced expression. Reduced CD9 expression was significantly associated with high grade (P=0.0007) and lower disease-free survival (DFS) (P=0.017). The latter retained its significance in the multivariate analysis. When the 23 cases with both membranous and cytoplasmic patterns were studied as a separate subgroup, there were significant associations between CD9 expression and tumour grade (P=0.025) (95% CI 11-68), tumour stage (P=0.08) (95% CI 3.5-86) and the occurrence of any failure (P=0.083) (95% CI -1.7-57). Immunohistochemical CD9 expression proved to be an independent prognostic factor in SCC of the head and neck, and it may detect patients at a high risk of recurrence. In addition, the cytoplasmic pattern seems to have an even more significant value. However, this finding is limited to the small number of cases with this pattern.     

Recent Dental Caries and Treatment Patterns in US Children

This report presents dental caries and treatment patterns found in a longitudinal study of US children between 1978 and 1982 who were geographically dispersed across several fluoridated and nonfluoridated sites. The analyses include first- and fifth-grade children examined annually for four years in the National Preventive Dentistry Demonstration Program and who did not receive effective preventive procedures. The results indicate that in association with the caries decline in US children, treatment ratios increased by over 20 percent during the study period. FS/DFS ratios averaged 79 percent for the four grade/fluoridation status cohorts analyzed and were significantly higher in fluoridated than in nonfluoridated sites. The single-fissured surface was the dominant treatment or disease area observed and these surfaces tended to be restored early. In assessing tooth-surface status changes annually, tooth surfaces were more than twice as likely to change from sound to filled than from sound to decayed between yearly examinations at fluoridated sites. The lower levels of decay and higher degree of restorative care observed were not observed in lower SES and black children nearly to the extent as those for higher SES and white children in the population. The dental profession should shift its emphasis from the early restoration of fissured-surface defects to an expanded use of sealants for those with reduced decay and focus resources on a minority of the population with high caries levels who receive limited care.     

Treatment of hepatic metastases from colorectal cancer: many doubts, some certainties

About 50% of patients with colorectal cancer (CCR) are destined to develop hepatic metastases during the course of the disease. Surgery is currently the only potentially curative treatment with a five year survival rate after hepatectomy from 26% to 49%. The criteria for resectability are now less rigid than in the past and the tendency to adopt a more aggressive treatment of metastatic lesions is the rule. Systemic infusion chemotherapies based on 5-fluorouracil (5-FU), oxaliplatin (OHP) and irinotecan (CPT-11) are well tolerated and have been shown to be effective in non-operable patients. These regimens allow surgery for patients who are initially not suitable for resection, giving them a probability of survival at five years similar to that of patients operated on at diagnosis. Intra-arterial infusion chemotherapy (HAI) is very effective in inducing objective responses, but is costly, difficult to manage and encumbered by major side effects, so that its application is necessarily limited to centres with specific experience. However, despite the broader criteria and recent advances of chemotherapy, surgery is not possible in most patients. The role of other local therapeutic techniques like cryosurgery (CS) and radiofrequency ablation (RF), alone or combined with surgery or chemotherapy, is not yet established in a multidisciplinary therapeutic approach. Roughly two thirds of patients relapse during the first two years after surgery suggesting appropriate post-operative chemotherapy treatment after hepatic resection may be indicated, but no randomised studies have been published to date. In case of relapse, another hepatectomy should be considered. The role of novel targeted therapies in pre-operative, post-operative and palliative management has yet to be evaluated.     

Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer.

BACKGROUND & AIMS: Recent in vitro studies showed that beta-catenin translocated into the tumor cell nucleus functions as an oncogene by transactivating oncogenes, including MMP-7. We conducted a large-scale analysis of beta-catenin and MMP-7 expression in human colon cancer to determine the potential clinical importance of these molecules. METHODS: In 202 colon cancer patients with known postoperative outcomes, we determined the expression of beta-catenin and MMP-7 in the tumors immunohistochemically and correlated the findings with the patients' clinicopathological characteristics and survival. RESULTS: We found 2 distinct patterns of beta-catenin nuclear accumulation (NA) in the colon cancers: diffuse NA (NAd) in 89 cases (44%) and selective NA at the invasion front (NAinv) in 18 cases (9%). The presence of the NAinv pattern was significantly correlated with advanced Dukes' stage (P = 0.0187) and tumor recurrence (P = 0.0005) as well as with MMP-7 expression in the tumor invasion front (P = 0.0025), resulting in extremely unfavorable clinical outcomes. A multivariate analysis determined that the NAinv expression pattern and Dukes' C stage were independent prognostic factors. CONCLUSIONS: Oncogenic activation of beta-catenin in the tumor invasion front, as represented by its NAinv pattern of expression, may be an independent and reliable indicator of membership in a subset of colon cancer patients who are highly susceptible to tumor recurrence and have a less favorable survival rate.     

Updates in the Evaluation and Management of Breast Cancer

Breast cancer is the most commonly diagnosed cancer worldwide. More than 200,000 new cases of invasive breast cancer are diagnosed annually in the United States; approximately 40,000 patients die of the disease. The etiology of most breast cancer cases is unknown, although multiple factors predisposing to the disease have been identified. Apart from increasing age and female sex, these other factors account for only a minority of breast cancer diagnoses. This article provides an overview of the management of noninvasive and invasive breast cancer, which is often complex and varies according to patient factors, disease stage, and breast cancer subtype. Although much progress has been made, continued research endeavors are ongoing; enrollment of eligible patients in prospective clinical trials is an essential way to improve patient outcomes.     

Mutation analysis in patients with total sperm immotility

Purpose

Perform the genetic characterization of five patients with total sperm immotility using Sanger sequencing and Whole Exome Sequencing (WES), in order to increase the knowledge on the genetics of sperm immotility and, ultimately, allow the identification of potential genetic markers for infertility.

Methods

Prospective study at a University Medical school. We analysed five men with total sperm immotility, four with dysplasia of the fibrous sheath (DFS), associated with disruption of several axonemal structures, and one patient with situs inversus totalis, which showed absence of dynein arms (DA) and nexin bridges. We screened 7 genes by Sanger sequencing, involved in sperm motility and associated to ultrastructural defects found in these patients (CCDC39, CCDC40, DNAH5, DNAI1, RSPH1, AKAP3 and AKAP4). Additionally, we performed WES analysis in the patient with situs inversus.

Results

We identified nine new DNA sequence variants by WES. Two of these variants were considered particularly relevant: a homozygous missense change in CCDC103 gene (c.104G > C, p.R35P) probably related with absence of dynein arms; the other in the INSL6 gene (c.262_263delCC) is thought to be also involved in sperm immotility.

Conclusions

Our work suggests that WES is an effective strategy, especially as compared with conventional sequencing, to study highly heterogenic genetic diseases, such as sperm immotility. For future work we expect to expand the analysis of WES to the other four patients and complement findings with expression analysis or functional studies to determine the impact of the novel variants.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0474-6) contains supplementary material, which is available to authorized users.