HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients

Abstract

Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

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Twin pregnancy complicated by esophageal atresia, duodenal atresia, gastric perforation, and hypoplastic left heart structures in one twin: a case report and review of the literature

The antenatal diagnosis of a combined esophageal atresia without tracheoesophageal fistula and duodenal atresia with or without gastric perforation is a rare occurrence. These diagnoses are difficult and can b...

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The relationship between breast cancer molecular subtypes and mast cell populations in tumor microenvironment

Abstract

Mast cells (MCs) are a part of the innate immune system. The MC functions toward cancer are partially based on the release of chymase and tryptase. However, the MC effect on breast cancer is controversial. The aim of our study was to investigate the presence of MCs in breast cancer tumors of different molecular subtypes and their relationships with other pathological prognostic factors. Tryptase- and chymase-positive mast cell densities were evaluated by immunohistochemistry in 108 primary invasive breast cancer tissue samples. Positive cells were counted within the tumor bed and at the invasive margin. For all analyzed MC subpopulations, we observed statistically significant differences between individual molecular subtypes of breast cancer. The significantly higher numbers of intratumoral chymase- and tryptase-positive mast cells were observed in luminal A and luminal B tumors compared to triple-negative and HER2+ non-luminal lesions. A denser MC infiltration was associated with lower tumor grade, higher ER and PR expression, lower proliferation rate as well as the lack of HER2 overexpression. The results obtained in our study indicate a possible association of chymase- and tryptase-positive MCs with more favorable cancer immunophenotype and with beneficial prognostic indicators in breast cancer.

http://ift.tt/2nyPFiE

Transconjunctival versus subciliary approach to the infraorbital margin for open reduction of zygomaticomaxillary complex fractures: a randomized feasibility study

Abstract

Introduction

Although some studies addressed the differences between subciliary and transconjunctival approaches, no previous prospective comparative study on displaced zygomaticomaxillary complex (ZMC) fracture that repaired by three-point internal fixation using also upper gingivolabial incision and upper eye lid incision. So, the effect of these incisions on the comparison was not investigated.

Purpose

The purpose of this study was to compare transconjunctival and subciliary approaches for open reduction and internal rigid fixation (OR/IF) of ZMC fractures.

Methods

This prospective study was carried out on 40 patients had displaced ZMC fractures repaired by OR/IF. Patients were randomly assigned into two equal groups (20 patients for each); subciliary group subjected to subciliary approach and transconjunctival group subjected to transconjunctival approach for inferior orbital rim repair. In both groups, frontozygomatic and zygomaticomaxillary buttresses were also approached by lateral eye brow and superior gingivolabial incision, respectively. Primary outcome measures include accessibility (need for lateral canthotomy), the exposure duration, postoperative pain, early postoperative edema, and operative complications. Secondary outcome measures include dental occlusion, average intrinsic vertical mouth opening, post subciliary scar assessment, late postoperative complication, and opthalmological assessment concerning ectropion, entropion, scleral show, and eye globe affection (enophthalmos or diplopia).

Results

The mean duration from incisions to fracture exposure was 13.7 ± 2.17 min in subciliary approach and 14.6 ± 2.31 min in transconjunctival approach with nonsignificant difference (p = 0.1284). Lateral canthotomy was required for proper exposure of the fracture and OR/IF using transconjunctival approach while not needed with subciliary approach. Ectropion and scleral show occurred in 10 and 15% respectively in subciliary group and were not encountered in transconjunctival group. Although postoperative periorbital edema was significantly more sever in transconjunctival group within the first postoperative week (p = 0.028), no persistent periorbital edema was reported. Infection, hematoma, and globe complication were not detected in any patient. All authors characterized all scars of the subciliary group as unnoticeable.

Conclusion

Transconjunctival approach mostly needs lateral canthotomy that was not needed with subciliary approach. Transient postoperative edema is more in transconjunctival approach while postoperative ectropion and sclera show was detected only with subciliary approach. So, building up of experience in transconjunctival approach will be beneficial for maxillofacial surgeons and more measures to avoid ectropion are needed with subciliary approach.

http://ift.tt/2mUOXJC

Transconjunctival versus subciliary approach to the infraorbital margin for open reduction of zygomaticomaxillary complex fractures: a randomized feasibility study

Abstract

Introduction

Although some studies addressed the differences between subciliary and transconjunctival approaches, no previous prospective comparative study on displaced zygomaticomaxillary complex (ZMC) fracture that repaired by three-point internal fixation using also upper gingivolabial incision and upper eye lid incision. So, the effect of these incisions on the comparison was not investigated.

Purpose

The purpose of this study was to compare transconjunctival and subciliary approaches for open reduction and internal rigid fixation (OR/IF) of ZMC fractures.

Methods

This prospective study was carried out on 40 patients had displaced ZMC fractures repaired by OR/IF. Patients were randomly assigned into two equal groups (20 patients for each); subciliary group subjected to subciliary approach and transconjunctival group subjected to transconjunctival approach for inferior orbital rim repair. In both groups, frontozygomatic and zygomaticomaxillary buttresses were also approached by lateral eye brow and superior gingivolabial incision, respectively. Primary outcome measures include accessibility (need for lateral canthotomy), the exposure duration, postoperative pain, early postoperative edema, and operative complications. Secondary outcome measures include dental occlusion, average intrinsic vertical mouth opening, post subciliary scar assessment, late postoperative complication, and opthalmological assessment concerning ectropion, entropion, scleral show, and eye globe affection (enophthalmos or diplopia).

Results

The mean duration from incisions to fracture exposure was 13.7 ± 2.17 min in subciliary approach and 14.6 ± 2.31 min in transconjunctival approach with nonsignificant difference (p = 0.1284). Lateral canthotomy was required for proper exposure of the fracture and OR/IF using transconjunctival approach while not needed with subciliary approach. Ectropion and scleral show occurred in 10 and 15% respectively in subciliary group and were not encountered in transconjunctival group. Although postoperative periorbital edema was significantly more sever in transconjunctival group within the first postoperative week (p = 0.028), no persistent periorbital edema was reported. Infection, hematoma, and globe complication were not detected in any patient. All authors characterized all scars of the subciliary group as unnoticeable.

Conclusion

Transconjunctival approach mostly needs lateral canthotomy that was not needed with subciliary approach. Transient postoperative edema is more in transconjunctival approach while postoperative ectropion and sclera show was detected only with subciliary approach. So, building up of experience in transconjunctival approach will be beneficial for maxillofacial surgeons and more measures to avoid ectropion are needed with subciliary approach.

http://ift.tt/2mUOXJC

Biological predictors of radiosensitivity in head and neck squamous cell carcinoma

Abstract

Objectives

The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation.

Material and methods

The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed.

Results

Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis.

Conclusions

P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation.

Clinical relevance

The findings may improve patient-specific therapy according to individual tumor characteristics.

http://ift.tt/2mDBwMh

Neuropeptide expression and morphometric differences in crushed alveolar inferior nerve of rats: Effects of photobiomodulation

Abstract

Inferior alveolar nerve (IAN) injuries may occur during various dental routine procedures, especially in the removal of impacted lower third molars, and nerve recovery in these cases is a great challenge in dentistry. Here, the IAN crush injury model was used to assess the efficacy of photobiomodulation (PBM) in the recovery of the IAN in rats following crushing injury (a partial lesion). Rats were divided into four experimental groups: without any procedure, IAN crush injury, and IAN crush injury with PBM and sham group with PBM. Treatment was started 2 days after surgery, above the site of injury, and was performed every other day, totaling 10 sessions. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 70 mWpk, beam spot size at target ∼0.1 cm², a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6 J/cm². Nerve recovery was investigated by measuring the morphometric data of the IAN using TEM and by the expression of laminin, neurofilaments (NFs), and myelin protein zero (MPZ) using Western blot analysis. We found that IAN-injured rats which received PBM had a significant improvement of IAN morphometry when compared to IAN-injured rats without PBM. In parallel, all MPZ, laminin, and NFs exhibited a decrease after PBM. The results of this study indicate that the correlation between the peripheral nerve ultrastructure and the associated protein expression shows the beneficial effects of PBM.

http://ift.tt/2mcr9DZ