Characterization and prognosis of estrogen receptor-positive/progesterone receptor-negative male breast cancer: a population-based study

Background

The aim of this study was to explore the characteristics and prognostic information of estrogen receptor-positive/progesterone receptor-negative (ER+/PR?) male breast cancer.

Methods

Using the US National Cancer Institute’s Surveillance, Epidemiology, and End Results database, we compared the demographics, clinical characteristics, and outcome of estrogen receptor-positive/progesterone receptor-positive (ER+/PR+) patients with ER+/PR? male breast cancer patients from 1990 to 2010. Two thousand three hundred twenty-two patients with ER+/PR+ tumors and 355 patients with ER+/PR? tumors were included in our study.

Results

ER+/PR? patients were younger (P?=?0.008) and more likely to be African American (P?<?0.001) while presented with higher histological grade (P?<?0.001), larger tumor size (P?=?0.010), and more invasion to the lymph nodes (P?=?0.034) and distant sites (P?<?0.001), thus later stage (P?=?0.001). Despite higher chance of receiving chemotherapy (51.0% vs 36.5%, P?<?0.001), ER+/PR? patients experienced significantly worse breast cancer-specific survival (BSCC) (P?<?0.001) and shorter overall survival (OS) (P?=?0.003). Multivariate Cox model confirmed that tumor size, lymph node invasion, metastasis, and surgery were independent prognostic factors of both BSCC and OS for ER+/PR? male breast cancer. Age at diagnosis and chemotherapy were significantly associated with OS but not with BSCC.

Conclusion

ER+/PR? male breast cancer was more aggressive and experienced shorter survival than ER+/PR+ patients. The prognosis was mainly associated with tumor size, lymph node invasion, metastasis, and surgery.

     

Expression of hypoxia-inducible factor-1α and vascular density in mammary adenomas and adenocarcinomas in bitches

Background

The study aimed at examining hypoxia-inducible factor (HIF)1α expression in adenocarcinomas and adenomas in bitches in regard to tumour malignancy grade, proliferation, apoptosis and vascularisation. Therefore, paraffin sections of 15 adenomas and 64 adenocarcinomas sampled from 79 dogs aged 6 to 16 years were analysed.

Results

A significantly higher HIF-1α expression was noted in adenocarcinomas in comparison to adenomas (P?<?0.0004). Moreover, HIF-1α expression in adenocarcinomas correlated positively with tumour malignancy grade (r?=?0.59, P?<?0.05), Ki-67 antigen expression (r?=?0.43; P?<?0.0005), TUNEL-positive cells (r?=?0.62, P?<?0001) and tumour vascularity measured by quantification of vessels characterized by the expression of von Willebrand Factor (r?=?0.57, P?<?0.05).

Conclusion

Results of this study indicate a similar biological role of HIF-1α in dogs and in humans, which may confirm suitability of the animal model in investigations on progression of tumours in humans.

     

Over-expression of miR-146b and its regulatory role in intestinal epithelial cell viability,proliferation, and apoptosis in piglets

Background

Weaning stress affects the small intestine of piglets. MiR-146b is differentially expressed in suckling and weaned piglets. In this study, we evaluated the effects of miR-146b on cell viability, proliferation, and apoptosis in IPEC-J2 cells.

Results

Transfection with miR-146b mimics successfully increased miR-146b levels by 1000× (P?<?0.001). The over-expression of miR-146b significantly promoted the apoptosis (P?<?0.01) of IPEC-J2 cells, with no significant effects on cell viability or proliferation. MiR-146b suppressed the luciferase activity of the miR-TLR4-wt by 57% compared with the negative control, while mutation of the miR-146b binding site significantly blocked the suppressive effect (P?<?0.05). Western blot results showed that TLR4 levels decreased in IPEC-J2 cells transfected with miR-146b mimics (P?<?0.05).

Conclusions

The over-expression of miR-146b promotes IPEC-J2 cell apoptosis. TLR4 is a direct target of miR-146b in IPEC-J2 cells.

Reviewers

This article was reviewed by Eugene Berezikov and Jan B Hoek.

     

Single-dose acarbose decreased glucose-dependent insulinotropic peptide and glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus after a mixed meal

Background

Acarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

In this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n?=?11) and the mixed meal test (MMT) group (n?=?12). Fourteen subjects with normal OGTT were included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0 (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later, controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose, and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers were measured again.

Results

No significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of glucose (P?<?0.01), insulin (P?<?0.01), glucagon at 15 min (P?<?0.05), glucagon area under the curve (AUC) (P?<?0.05), GIP levels at 30 min (P?<?0.05), and GIP AUC (P?<?0.05) were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change.

Conclusions

Single-dose acarbose could reduce the secretion of GIP and glucagon after a mixed meal in patients with newly diagnosed T2DM. The influence of acarbose on incretin levels could be related to the types of carbohydrate being consumed.

Trial registration

This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR-TRC-14004260, Date of Registration: 2014-01-19).

     

Gastrointestinal specific anxiety in irritable bowel syndrome: validation of the Japanese version of the visceral sensitivity index for university students

Objective

The visceral sensitivity index (VSI) is a useful self-report measure of the gastrointestinal symptom-specific anxiety (GSA) of patients with irritable bowel syndrome (IBS). Previous research has shown that worsening GSA in IBS patients is related to the severity of GI symptoms, suggesting that GSA is an important endpoint for intervention. However, there is currently no Japanese version of the VSI. We therefore translated the VSI into Japanese (VSI-J) and verified its reliability and validity.

Material and methods

Participants were 349 university students aged 18 and 19 years and recruited from an academic class. We analyzed data from the VSI-J, Anxiety Sensitivity Index (ASI), Hospital Anxiety and Depression scale (HAD), and Irritable Bowel Syndrome Severity Index (IBS-SI). The internal consistency, stability, and factor structure of the VSI-J and its associations with anxiety, depression and severity measures were investigated.

Results

The factor structure of the VSI-J is unidimensional and similar to that of the original VSI (Cronbach’s α?=?0.93). Construct validity was demonstrated by significant correlations with ASI (r?=?0.43, p?<?0.0001), HAD-ANX (r?=?0.19, p?=?0.0003), and IBS-SI scores (r?=?0.45, p?<?0.0001). Furthermore, the VSI-J was a significant predictor of severity scores on the IBS-SI and demonstrated good discriminant (p?<?0.0001) and incremental (p?<?0.0001) validity.

Conclusion

These findings suggest that the VSI-J is a reliable and valid measure of visceral sensitivity.

     

Robotic total gastrectomy with <Emphasis Type="Italic">π</Emphasis>-shaped esophagojejunostomy using a linear stapler as a novel technique

Objective

To evaluate the intraoperative and short-term postoperative outcomes of a novel robotic intracorporeal π-shaped esophagojejunostomy (EJS) after D2 total gastrectomy (TG) using the Da Vinci robotic surgical system for intracorporeal anastomosis after TG.

Background

Intracorporeal π-shaped EJS, using a linear stapler, was recently reported for laparoscopic total gastrectomy in patients with gastric cancer. However, robotic intracorporeal π-shaped EJS using a linear stapler has not been reported. This report aimed to describe the use of a novel technique for π-shaped EJS using the Da Vinci robotic system.

Methods

Robotic intracorporeal π-shaped esophagojejunostomy after total gastrectomy was performed in 11 consecutive patients diagnosed with early gastric cancer, and their perioperative outcomes were analyzed.

Results

All the operations were successful without conversion to open or laparoscopic surgery and postoperative complications. The total number of patients was 11 (7 males and 4 females). The mean age of the patients was 63.36?±?10.56?years old. Seven patients were diagnosed with cardia cancer, 3 patients were diagnosed with gastric body cancer, and 1 patient was diagnosed with gastric antrum cancer. The patients’ mean proximal resection margin was 3.18?±?1.17?cm, the distal resection margin was 6.18?±?1.40?cm, the mean length of the incision was 4.55?±?0.69?cm, the mean operative time was 287.27?±?30.69?min, the mean day of first flatus was 3.27?±?0.79?days, the mean day of the start of diet was 2.91?±?0.94?days, the mean postoperative hospital stay was 11.45?±?5.13?days, and the mean operative blood loss was 47.27?±?31.33?ml. No complications were observed during anastomosis, and the median anastomosis time was 19.5?min. The mean number of lymph node dissections was 17.91?±?4.59, the mean number of positive lymph nodes was 0.45?±?0.69, all patients were diagnosed with stage I–II gastric cancer, and the mean maximum diameter of the tumor was 2.67?±?1.30?cm. All the patients had a smooth hospital discharge.

Conclusion

A novel robotic gastrectomy with intracorporeal π-shaped EJS for esophagojejunal anastomosis described and shows acceptable resulted. This technique has the potential to offer better short-term surgical outcomes and overcomes the drawbacks of laparoscopy with a decreased risk of complications during and after surgery.

     

Overexpression of the recently identified oncogene <Emphasis Type="Italic">REDD1</Emphasis> correlates with tumor progression and is an independent unfavorable prognostic factor for ovarian carcinoma

Background

Regulated in development and DNA damage response (REDD1), a gene responding to hypoxia or multiple DNA damage events, was recently implicated in cancer development and progression. Previously, in vivo and in vitro experiments indicated that REDD1 functions as an oncogene in ovarian cancer cells. However, the role of REDD1 in cancer cell migration and invasion and in clinical significance of prognostic values is not examined in detail.

Methods

We detected the REDD1 protein expression by immunohistochemistry in 18 normal ovarian surface epithelium or fallopian tube epithelium specimens, 24 ovarian borderline tumors, and 229 ovarian cancers. Fisher’s exact test, logistic regression analysis, the Kaplan–Meier method, and the log-rank test were used to evaluate the association of REDD1 with clinical factors, overall survival and disease-free survival. The prognostic predictive value of REDD1 for ovarian cancer patients was evaluated using multivariate Cox proportional hazard regression models. REDD1 expression in HEY, HEY A8, SKOV3, SKOV3 ip1, OVCA429, OVCA433 and A2780 human ovarian epithelial cancer cell lines was detected by western blotting. The role of REDD1 in cell invasion and migration was assessed by transwell migration and invasion assays using SKOV3, A2780, HEY, HEYA8, and SKOV3-REDD1 with parental A2780-REDD1 HEY-REDD1i and HEY A8-REDD1i.

Results

High expression of REDD1 was observed in 35.4% of primary ovarian carcinoma samples. Overexpression of cytoplasmic REDD1 in ovarian cancer was significantly associated with serous carcinoma (P?<?0.001), late-stage disease (P?<?0.001), ascites (P?<?0.001), and partial or non-response to chemotherapy (P?<?0.001). High cytoplasmic expression of REDD1 was correlated with poorer overall survival (P?<?0.001) and disease-free survival (P?<?0.001). The multivariate Cox proportional hazards regression analysis indicated that patients with high cytoplasmic REDD1 expression had a high risk of death (P?<?0.001) and high risk of an event (i.e., recurrence, progression, or death) (P?<?0.001). REDD1 was first reported as an independent prognostic factor in ovarian cancer patients. In addition, REDD1 overexpression enhanced ovarian cancer cell migration and invasion.

Conclusion

REDD1 is an independent unfavorable prognostic factor in ovarian carcinoma and may promote ovarian cancer metastasis.

     

Role of perfusion parameters on DCE-MRI and ADC values on DWMRI for invasive ductal carcinoma at 3.0 Tesla

Background

The value of apparent diffusion coefficient (ADC) values and quantitative parameters (Ktrans, Kep, Ve) in detecting prognostic factor at 3.0 Tesla remains unclear, especially in predicting prognosis of breast cancer.

Methods

A total of 151 patients with IDC underwent breast DCE-MRI and DWI-MRI at 3.0 Tesla following surgery. The ADC values were acquired with b values of 0 and 1000?s/mm². The relationship between ADC values or DCE-MRI quantitative parameters and size, histologic grade (HG), lymph node metastasis (LNM), ER, PR, and Ki67 was evaluated. The predictive values of ADC, Ktrans, Kep, and Ve to prognosis of IDC were assessed.

Results

ADC value was positively related to size (P?=?0.04) and HER2 (P?=?0.046) expression and negatively related to ER (P?=?0.012) and PR (P?<?0.001) expression. Ktrans value has positive correlation with size (P?<?0.001), HG (P?<?0.001), LNM (P?<?0.001), HER2 (P?=?0.007), and Ki67 (P?<?0.001) expression and negative correlation with ER (P?<?0.001) and PR (P?<?0.001) expression. Kep value was positively related to size (P?<?0.001) and negatively related to ER (P?<?0.001) and PR (P?<?0.001) expression. Ve value was negatively related to HER2 expression (P?=?0.004). The Cox hazard ratio (HR) of ADC, Ktrans, Kep, and Ve values on survival was 5.26 (P?=?0.093), 1.081 (P?=?0.002), 1.006 (P?=?0.941), and 0.883 (P?=?0.926), respectively.

Conclusions

Ktrans value was a best predictive indicator of HG, LNM, ER, PR, and Ki67 expression, and ADC value was the best predictive indicator of HER2. Preoperative use of the 3.0 Tesla could provide important information to determine the optimal treatment plan.

     

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia

Background

The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD).

Methods

Adult (≥18?years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density. CT-density scores were calculated using fixed and adapted thresholds based on various combinations of histogram characteristics, such as mean lung density (MLD), skewness, and standard deviation (SD). Additionally, visual scoring using the Bhalla score was performed by 2 independent radiologists. Correlations between CT scores, forced expiratory volume in 1?s (FEV₁) and forced vital capacity (FVC) were evaluated.

Results

Sixty-two adult patients with PCD were included. Of all histogram characteristics, those showing good positive or negative correlations to both FEV₁ and FVC were SD (R?=???0.63 and???0.67; p?<?0.001) and Skewness (R?=?0.67 and 0.67; p?<?0.001). Among all evaluated thresholds, the CT-density score based on MLD?+?1SD provided the best negative correlation with both FEV₁ (R?=???0.68; p?<?0.001) and FVC (R?=???0.71; p?<?0.001), close to the correlations of the visual score (R?=???0.60; p?<?0.001 for FEV₁ and R?=???0.62; p?<?0.001, for FVC).

Conclusions

Automated CT scoring of lung structural abnormalities lung in primary ciliary dyskinesia is feasible and may prove useful for evaluation of disease severity in the clinic and in clinical trials.

     

Long-term follow-up in adults after tetralogy of Fallot repair

Background

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and the population of ToF repair survivors is growing rapidly. Adults with repaired ToF develop late complications. The aim of this study was to describe and analyze long-term follow-up of patients with repaired ToF.

Methods

This is a retrospective cohort study. Consecutive 83 patients with repaired ToF who did not undergo pulmonary valve replacement were included. Mean age of all patients was 30.5?±?10.7. There were 49 (59%) male. Patients were divided into two groups according to the time since the repair (<?25 years and?≥?25 years). The electrocardiographic (ECG), cardiopulmonary exercise testing (CPET), echocardiographic and cardiac magnetic resonance (CMR) data were reviewed retrospectively.

Results

In CPET values were not significantly different in the two groups. In CMR volumes of left and right ventricles were not significantly different in the two groups. There were no differences between the groups in ventricular ejection fraction, mass of ventricles, or pulmonary regurgitation fraction. Among all the patients, ejection fraction and left and right ventricle mass, indexed pulmonary regurgitation volume measured by CMR did not correlate with the time since repair. In ECG among all the patients, ejection fraction of the RV, measured in CMR, negatively correlated with QRS duration (r?=???0.43; p?<?0.001). There was a positive correlation between QRS duration and end diastolic volume of the RV (r?=?0.30; p?<?0.02), indexed end diastolic volume of the RV (r?=?0.29; p?=?0.04), RV mass (r?=?0.36; p?<?0.001) and left ventricle mass (r?=?0.26; p?=?0.04).

Conclusion

Long-term survival and clinical condition after surgical correction of ToF in infancy is generally good and the late functional status in ToF – operated patients could be excellent up to 25 years after the repair. QRS duration could be an utility and easy factor to assessment of right ventricular function.

Trial registration

The study protocol was approved by the local Ethics Committee. Each participant provided informed consent to participate in the study (license number 122.6120.88.2016 from 28.04.2016).

     

Validation of the Chinese version of the FOUR score in the assessment of neurosurgical patients with different level of consciousness

Background

The Glasgow Coma Scale (GCS) is currently the most widely used scoring system for comatose patients. A decade ago, the Full Outline of Unresponsiveness (FOUR) score was devised to better capture four functional aspects of consciousness (eye, motor responses, brainstem reflexes, and respiration). This study aimed to validate the Chinese version of the FOUR score in patients with different levels of consciousness.

Methods

The study had two phases: (1) translation of the FOUR score, and (2) assessment of its reliability and validity. The Chinese version of the FOUR score was developed according to a standardized protocol. One hundred-twenty consecutive patients with acute brain damage, admitted to Nanfang Hospital (Southern Medical University, Guangdong, China) from November 2014 to February 2015, were enrolled. The inter-rater agreement for the FOUR score and GCS was evaluated using intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were established to determine the scales’ abilities to predict outcome.

Results

The rater agreement was excellent both for FOUR (ICC?=?0.970; p?<?0.001) and GCS (ICC?=?0.958; p?<?0.001). The FOUR score yielded an excellent test-retest reliability (ICC?=?0.930; p?<?0.001). Spearman’s correlation coefficients between GCS and the FOUR score were high: r?=?0.932, first rating; r?=?0.887, second rating (all p?<?0.001). Areas under the curve (AUC) for mortality were 0.834 (95 % CI, 0.740–0.928) and 0.815 (95 % CI, 0.723–0.908) for the FOUR score and GCS, respectively.

Conclusions

The Chinese version of the FOUR score is a reliable scale for evaluating the level of consciousness in patients with acute brain injury.

     

Clinicopathological characteristics and prognosis of primary appendiceal stromal tumors

Background

Gastrointestinal stromal tumors (GISTs) account for less than 1% of all gastrointestinal tumors. The biological behaviors of GISTs vary from benign to malignant. GISTs are common in the stomach (55.6%) and small intestine (31.8%), but rarely in the rectum, colon (6%), and other sites (5.5%). Currently, the majority of published reports of primary appendiceal stromal tumors (PASTs) are case reports or case series.

Methods

The PASTs described in this study were identified from a literature review (23 cases) and our center (one case). The relationship between PAST gross types and clinicopathological factors was analyzed and summarized. At the same time, the study also analyzed the related risk factors and survival of PASTs and GISTs.

Results

Twenty-four cases of PASTs were compared with 254 cases of GISTs from our center. The results showed that there was a significant difference between the two groups in tumor size (P?<?0.001), histological type (P?=?0.013), CD34 expression (P?<?0.001), and DOG-1 expression (P?<?0.001). Disease-free survival (DFS) analysis of 11 cases of PASTs and 227 cases of GISTs found that a comparison of 3-year and 5-year DFS was not statistically significant (P?=?0.894 and P?=?0.846, respectively). In the DFS multivariate analysis, tumor mucosal ulceration, tumor size, and NIH risk classification were independent prognostic factors in 3-year and 5-year DFS.

Conclusion

In this study, there was no significance in the survival of patients with appendix and gastric stromal tumors, which we hypothesized to be associated with the low sample size and incomplete follow-up records. Based on this, we conclude that the prognosis of primary appendiceal stromal tumors may be better than gastric tumors, but this needs to be confirmed in further prospective studies.

     

Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer

Background

Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.

Methods

We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.

Results

Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z?=???8.635, p?<?0.001) and peritumoral (median 113.53 vs. 82.48; Z?=???3.741, p?<?0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z?=???0.817,p?=?0.414) and peritumoral (median 402.56 vs. 390.84; Z?=???1.138,p?=?0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z?=???2.009, p?=?0.045) and peritumoral areas(median 63.31 vs. 98.48; Z?=???2.469, p?=?0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR?=?0.297; 95% CI, 0.109–0.810, p?=?0.018) and overall survival (HR?=?0.078; 95% CI, 0.010–0.598, p?=?0.014).

Conclusions

NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.

     

Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (<Emphasis Type="Italic">UBE2E1</Emphasis>) as a prognostic factor in acute myeloid leukemia

Background

Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions.

Methods

We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis.

Results

Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p?<?0.05). Next, we validated our findings in an independent cohort of AML samples collected in our hospital. We found that ubiquitin-conjugating enzyme E2E1 (UBE2E1) expression was adversely correlated with AML survival (p?=?0.04). Multivariable analysis showed that UBE2E1 ^high patients had a significant shorter OS and shorter progression-free survival after adjusting other known prognostic factors (p?=?0.03). At last, we found that UBE2E1 expression was negatively correlated with patients’ response to induction chemotherapy (p?<?0.05).

Conclusions

In summary, we demonstrated that UBE2E1 expression was a novel prognostic factor in adult, non-APL AML patients.

     

Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications

Background

Adipose tissue, an endocrine organ of the body, is involved in some obesity-related disease states such as insulin resistance, diabetes mellitus, and atherosclerosis. Vaspin is a novel adipocyte with insulin sensitizing effects. In this study, we planned to estimate serum vaspin concentrations as related to glycemic status and the presence of macrovascular complications among elderly patients with type-2 diabetes mellitus (T2DM).

Methods

A total of 230 elderly patients with T2DM were evaluated. These patients were divided into two groups: patients without complications (T2DM group, n?=?110), and patients with macrovascular complications (T2DM + MC group, n?=?120). In addition, 60 healthy elderly subjects were enrolled and assigned into the control group (NC group). Relevant parameters were matched for age and gender ratio. Serum vaspin concentrations were measured by Enzyme-linked immunosorbent assay (ELISA). Anthropometric measurements, plasma glucose and HbA_1C levels, insulin concentration, liver and kidney functions, and lipid profile were measured for each participant.

Results

Serum vaspin concentrations were significantly higher in the T2DM group than in the T2DM + MC group (F?=?13.122, P?<?0.01). These concentrations were also significantly higher among females, compared to males (T?=?3.567, P?<?0.05). Logistic regression analysis revealed that serum vaspin concentration, systolic blood pressure, HDL-C and T2DM duration were independent influencing factors for diabetic macrovascular complications.

Conclusion

Serum vaspin may be considered as a potential marker to assess the status of elderly patients with T2DM and the risk of developing serious macrovascular complications. Further prospective studies are warranted.

Trial registration

ChiCTR-OPC-14005698, retrospectively registered on 20 Dec. 2014.

     

Toward the precision breast cancer survival prediction utilizing combined whole genome-wide expression and somatic mutation analysis

Background

Breast cancer is the most common type of invasive cancer in woman. It accounts for approximately 18% of all cancer deaths worldwide. It is well known that somatic mutation plays an essential role in cancer development. Hence, we propose that a prognostic prediction model that integrates somatic mutations with gene expression can improve survival prediction for cancer patients and also be able to reveal the genetic mutations associated with survival.

Method

Differential expression analysis was used to identify breast cancer related genes. Genetic algorithm (GA) and univariate Cox regression analysis were applied to filter out survival related genes. DAVID was used for enrichment analysis on somatic mutated gene set. The performance of survival predictors were assessed by Cox regression model and concordance index(C-index).

Results

We investigated the genome-wide gene expression profile and somatic mutations of 1091 breast invasive carcinoma cases from The Cancer Genome Atlas (TCGA). We identified 118 genes with high hazard ratios as breast cancer survival risk gene candidates (log rank p?<? 0.0001 and c-index?=?0.636). Multiple breast cancer survival related genes were found in this gene set, including FOXR2, FOXD1, MTNR1B and SDC1. Further genetic algorithm (GA) revealed an optimal gene set consisted of 88 genes with higher c-index (log rank p?<? 0.0001 and c-index?=?0.656). We validated this gene set on an independent breast cancer data set and achieved a similar performance (log rank p?<? 0.0001 and c-index?=?0.614). Moreover, we revealed 25 functional annotations, 15 gene ontology terms and 14 pathways that were significantly enriched in the genes that showed distinct mutation patterns in the different survival risk groups. These functional gene sets were used as new features for the survival prediction model. In particular, our results suggested that the Fanconi anemia pathway had an important role in breast cancer prognosis.

Conclusions

Our study indicated that the expression levels of the gene signatures remain the effective indicators for breast cancer survival prediction. Combining the gene expression information with other types of features derived from somatic mutations can further improve the performance of survival prediction. The pathways that were associated with survival risk suggested by our study can be further investigated for improving cancer patient survival.

     

Associating liver partition and portal vein ligation for staged hepatectomy versus conventional two-stage hepatectomy: a systematic review and meta-analysis

Background

It is generally accepted that an insufficient future liver remnant is a major limitation of large-scale hepatectomy for patients with primary hepatocellular carcinoma. Conventional two-stage hepatectomy (TSH) is commonly considered to accelerate future liver regeneration despite its low regeneration rate. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which is characterized by a rapid regeneration, has brought new opportunities.

Methods

Relevant studies were identified by searching the selected databases up to September 2017. Then, a meta-analysis of regeneration efficiency, complication rate, R0 resection ratio, and short-term outcomes was performed.

Results

Ten studies, comprising 719 patients, were included. The overall analysis showed that ALPPS was associated with a larger hyperplastic volume and a shorter time interval (P?<?0.00001) than TSH. ALPPS also exhibited a higher completion rate for second-stage operations (odds ratio, OR 9.50; P?<?0.0001) and a slightly higher rate of R0 resection (OR 1.90; P?=?0.11). Interestingly, there was no significant difference in 90-day mortality between the two treatments (OR 1.44; P?=?0.35).

Conclusions

These results indicate that compared with TSH, ALPPS possesses a stronger regenerative ability and better facilitates second-stage operations. However, the safety, patient outcomes, and patient selection for ALPPS require further study.

     

Laparoscopic intersphincteric resection versus an open approach for low rectal cancer: a meta-analysis

Aim

The aim of this study was to compare the short-term and mid-term effects of laparoscopic intersphincteric resection with the conventional open approach for patients with low rectal cancer through a meta-analysis.

Methods

The PubMed, EMBASE, Cochrane, and Ovid databases were searched for eligible studies until March 2017. Operation time, blood loss, circumferential resection margin-positive rate, distal margin length, number of resected lymph nodes, diverting stoma rate, postoperative overall morbidity, anastomotic leakage, and hospital stay were the main short-term effect endpoints. We also examined disease-free survival, overall survival, local recurrence, and post-operational anal function as secondary outcomes to evaluate the mid-term effects of laparoscopic surgery.

Results

Five studies involving 620 patients were included in the analyses. Compared with the open approach, the laparoscopic ISR had less blood loss (weighted mean difference [WMD]?=???214.65 ml, 95% CI [??370.44, ??196.13], p?<?0.01), less postoperative overall morbidity (OR?=?0.58, 95% CI [0.40, 0.86], p?<?0.01), and shorter duration of hospital stay (WMD?=???5.87 days, 95% CI [??11.35, ??0.40], p?<?0.05); however, the operation time was significantly longer in the laparoscopic group (WMD?=?47.34 min, 95% CI [4.10, 90.58], p?<?0.05). No other significant differences were observed.

Conclusion

Laparoscopic ISR for low rectal cancer offers fewer complications and faster recovery, with similar operation quality and mid-term oncological results than the conventional approach. Although this technique is comparatively more complex than the conventional approach and requires practice, laparoscopic ISR shows great potential as a surgical option and deserves further clinical study.

     

Effect of RSK4 on biological characteristics of colorectal cancer

Background

This study aimed to investigate the expression of P90 Ribosomal Protein S6 kinase 4 (RSK4) in colorectal cancer cells and its biological function.

Methods

We selected early SW480 and HCT116 colorectal cancer cell lines, using Lipofectamine? 2000 transfection reagent carrying RSK4 gene transfected into cells to establish the colorectal cancer cell lines with high expression of RSK4. RT-PCR and western blot (WB) analysis confirmed RSK4 expression in SW480 and HCT116 cancer cell lines. We used methylthiazoltetrazolium (MTT) assay and flow cytometry to detect the proliferation of colorectal cancer cells. After transfection of RSK4, the effect of RSK4 on the RNA levels associated with epithelial–mesenchymal transition (EMT) of colorectal cancer cells was analyzed by real-time fluorescence quantitative PCR and the expression of EMT-related protein was detected by WB analysis.

Results

After transfection of RSK4 overexpression, the MTT assay detected that RSK4 could significantly inhibit the growth of colorectal cancer cells in vitro; flow cytometry detected that S-phase cells decreased significantly, and G0/1 cells increased significantly (P?<?0.05). The invasion ability of SW480 and HCT116 cells transfected with RSK4 was markedly lower than that in the control group, and the difference was statistically significant (P?<?0.05). Fluorescent quantitative PCR and WB analysis showed that the expression of EMT-associated molecular E-cadherin was remarkably increased and the expression of Snail was significantly decreased (P?<?0.01).

Conclusion

RSK4 gene in colorectal cancer cell lines with low expression of RSK4 after transfection can inhibit the growth and invasion of tumor cells. RSK4 gene may inhibit EMT and inhibit metastasis of colorectal cancer cells, may be a potential tumor suppressor gene and inhibit tumor distant metastasis, and may provide the biological basis for new therapeutic targets.