Expression of UGP2 and CFL1 expression levels in benign and malignant pancreatic lesions and their clinicopathological significance

Abstract

Background

This study investigated UGP2 (uridine diphosphate-glucose pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal tissue (NT) and their clinicopathological significance.

Methods

Surgical specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35 cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional paraffin-embedded sections. EnVision immunohistochemical was used to stain for UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the correlation of expression pattern with survival.

Results

We found that positive UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL, and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe atypical hyperplasia or intraepithelial neoplasia of grades II–III was observed in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high differentiation, no lymph node metastasis, no surrounding invasion, and TNM (tumor-node-metastasis) staging I or/and II were significantly lower than those in cases with poor differentiation, lymph node metastasis, surrounding invasion, and TNM stage III and/or IV. Positive UGP2 expression in male patients was significantly lower than that in female patients. UGP2 and CFL1 expression in PDC were positively correlated. Kaplan-Meier survival analysis showed the degree of differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and surrounding invasion, and UGP2 and CFL1 expression were closely related to the average survival time of patients with PDC. The survival time of patients with positive UGP2 and CFL1 expression was significantly shorter than that of patients with negative expression. Cox multivariate analysis showed that poor differentiation, tumor maximal diameter ≥ 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was negatively correlated with the postoperative survival rate and positively correlated with the mortality of patients with PDC.

Conclusion

Positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer.

http://ift.tt/2DkEXoi

Early assessment of post-surgical outcomes with pre-pectoral breast reconstruction: A literature review and meta-analysis

Background

Pre-pectoral breast reconstruction is an emerging surgical approach. This study provides an early assessment of outcomes with the technique.

Methods

A comprehensive literature review was performed through searches of PubMed^®/MEDLINE^® to identify studies on pre-pectoral reconstruction. Patient characteristics and outcomes were extracted from studies and pooled. Linear relationships between complication rates and patient characteristics with pre-pectoral reconstruction were analyzed. A meta-analysis compared complication rates between pre-pectoral and dual-plane reconstruction.

Results

Fourteen studies (406 women/654 breasts) were included. The most common complications with pre-pectoral reconstruction were flap necrosis (7.8%), seroma (6.7%), capsular contracture (5.8%), and explantation (4.6%). No hyperanimation was reported. Significant correlation between previous radiation and flap necrosis, post-operative chemotherapy and infection, hypertension and flap necrosis, diabetes and dehiscence, and smoking and explantation were found. A meta-analysis of four studies comparing pre-pectoral (135 women/219 breasts) and dual-plane (230/408) reconstruction found no significant difference for likelihood of infection (odds ratio, 0.46; 95% confidence interval, 0.16-1.30), explantation (0.83; 0.29-2.38), necrosis (1.61; 0.77-3.36), seroma (1.88; 0.71-5.02), dehiscence (1.84; 0.68-4.95), or capsular contracture (0.14; 0.02-1.14).

Conclusions

Complication rates are comparable following pre-pectoral and dual-plane reconstruction, indicating the pre-pectoral technique may be a feasible option for appropriate patients.

http://ift.tt/2mMpOkN

18 F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma

Abstract

Background

The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by ¹⁸F–FDG-PET/CT and diffusion-weighted MRI (DW-MRI).

Methods

Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by ¹⁸F–FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq ¹⁸F–FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density – CD31; tumor cell proliferation – Ki-67).

Results

Tumor glucose uptake was significantly suppressed under therapy (∆TTL_Therapy − 1.00 ± 0.53 vs. ∆TTL_Control 0.85 ± 1.21; p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (∆ADC_Therapy 0.12 ± 0.14 × 10⁻³ mm²/s; ∆ADC_Control − 0.12 ± 0.06 × 10⁻³ mm²/s; p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 ± 48 vs. 287 ± 92; p = 0.001) and proliferation (Ki-67, 3718 ± 998 vs. 5389 ± 1332; p = 0.007) in the therapy compared to the control group.

Conclusion

A novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by ¹⁸F–FDG-PET/CT and DW-MRI.

from Cancer via ola Kala on Inoreader http://ift.tt/2DpeR3J
via IFTTT

Early assessment of post-surgical outcomes with pre-pectoral breast reconstruction: A literature review and meta-analysis

Background

Pre-pectoral breast reconstruction is an emerging surgical approach. This study provides an early assessment of outcomes with the technique.

Methods

A comprehensive literature review was performed through searches of PubMed^®/MEDLINE^® to identify studies on pre-pectoral reconstruction. Patient characteristics and outcomes were extracted from studies and pooled. Linear relationships between complication rates and patient characteristics with pre-pectoral reconstruction were analyzed. A meta-analysis compared complication rates between pre-pectoral and dual-plane reconstruction.

Results

Fourteen studies (406 women/654 breasts) were included. The most common complications with pre-pectoral reconstruction were flap necrosis (7.8%), seroma (6.7%), capsular contracture (5.8%), and explantation (4.6%). No hyperanimation was reported. Significant correlation between previous radiation and flap necrosis, post-operative chemotherapy and infection, hypertension and flap necrosis, diabetes and dehiscence, and smoking and explantation were found. A meta-analysis of four studies comparing pre-pectoral (135 women/219 breasts) and dual-plane (230/408) reconstruction found no significant difference for likelihood of infection (odds ratio, 0.46; 95% confidence interval, 0.16-1.30), explantation (0.83; 0.29-2.38), necrosis (1.61; 0.77-3.36), seroma (1.88; 0.71-5.02), dehiscence (1.84; 0.68-4.95), or capsular contracture (0.14; 0.02-1.14).

Conclusions

Complication rates are comparable following pre-pectoral and dual-plane reconstruction, indicating the pre-pectoral technique may be a feasible option for appropriate patients.

from Cancer via ola Kala on Inoreader http://ift.tt/2mMpOkN
via IFTTT

18 F–FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6 inhibitor combination therapy in a murine model of human melanoma

Abstract

Background

The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by ¹⁸F–FDG-PET/CT and diffusion-weighted MRI (DW-MRI).

Methods

Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by ¹⁸F–FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq ¹⁸F–FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density – CD31; tumor cell proliferation – Ki-67).

Results

Tumor glucose uptake was significantly suppressed under therapy (∆TTL_Therapy − 1.00 ± 0.53 vs. ∆TTL_Control 0.85 ± 1.21; p < 0.001). In addition, tumor diffusivity was significantly elevated following the BRAF and CDK 4/6 inhibitor combination therapy (∆ADC_Therapy 0.12 ± 0.14 × 10⁻³ mm²/s; ∆ADC_Control − 0.12 ± 0.06 × 10⁻³ mm²/s; p < 0.001). Immunohistochemistry revealed a significant suppression of microvascular density (CD31, 147 ± 48 vs. 287 ± 92; p = 0.001) and proliferation (Ki-67, 3718 ± 998 vs. 5389 ± 1332; p = 0.007) in the therapy compared to the control group.

Conclusion

A novel BRAF and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic and anti-proliferative effects in experimental human melanomas, monitored by ¹⁸F–FDG-PET/CT and DW-MRI.

http://ift.tt/2DpeR3J

Early assessment of post-surgical outcomes with pre-pectoral breast reconstruction: A literature review and meta-analysis

Background

Pre-pectoral breast reconstruction is an emerging surgical approach. This study provides an early assessment of outcomes with the technique.

Methods

A comprehensive literature review was performed through searches of PubMed^®/MEDLINE^® to identify studies on pre-pectoral reconstruction. Patient characteristics and outcomes were extracted from studies and pooled. Linear relationships between complication rates and patient characteristics with pre-pectoral reconstruction were analyzed. A meta-analysis compared complication rates between pre-pectoral and dual-plane reconstruction.

Results

Fourteen studies (406 women/654 breasts) were included. The most common complications with pre-pectoral reconstruction were flap necrosis (7.8%), seroma (6.7%), capsular contracture (5.8%), and explantation (4.6%). No hyperanimation was reported. Significant correlation between previous radiation and flap necrosis, post-operative chemotherapy and infection, hypertension and flap necrosis, diabetes and dehiscence, and smoking and explantation were found. A meta-analysis of four studies comparing pre-pectoral (135 women/219 breasts) and dual-plane (230/408) reconstruction found no significant difference for likelihood of infection (odds ratio, 0.46; 95% confidence interval, 0.16-1.30), explantation (0.83; 0.29-2.38), necrosis (1.61; 0.77-3.36), seroma (1.88; 0.71-5.02), dehiscence (1.84; 0.68-4.95), or capsular contracture (0.14; 0.02-1.14).

Conclusions

Complication rates are comparable following pre-pectoral and dual-plane reconstruction, indicating the pre-pectoral technique may be a feasible option for appropriate patients.

http://ift.tt/2mMpOkN

Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population Women

Abstract

Background

The cost-effectiveness of population-based panel testing for high- and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is unknown. We evaluate the cost-effectiveness of population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical criteria/family history (FH) testing in unselected general population women.

Methods

A decision-analytic model comparing lifetime costs and effects of criteria/FH-based BRCA1/BRCA2 testing is compared with BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical criteria/strong FH of cancer (≥10% BRCA1/BRCA2 probability) and all women age 30 years or older. Analyses are presented for UK and US populations. Identified carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers can opt for magnetic resonance imaging/mammography, chemoprevention, or risk-reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled model uncertainty evaluation. Outcomes include OC, BC, and additional heart disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence, and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon is lifetime and perspective is payer.

Results

Compared with clinical criteria/FH-based BRCA1/BRCA2 testing, clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER = £7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population-based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most cost-effective strategy compared with current policy: ICER = £21 599.96/QALY or $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At £30 000/QALY and $100 000/QALY willingness-to-pay thresholds, population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in 83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred in 16.2% and 5.8% of simulations, respectively. Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and 3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases prevented per million.

Conclusions

Population-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any clinical criteria/FH-based strategy. Clinical criteria/FH-based BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than BRCA1/BRCA2 testing alone.

http://ift.tt/2ERn78P