Signet-ring cell or mucinous histology after preoperative chemoradiation and survival in patients with esophageal or esophagogastric junction adenocarcinoma.

PURPOSE: The survival of patients with local-regional adenocarcinoma of the esophagus or esophagogastric junction (EGJ) treated with preoperative chemoradiation is much better in patients with pathologic complete response than those with residual tumor. Some adenocarcinomas have mixed patterns, including signet-ring cell and mucinous histology, but the clinical significance of these subtypes is unknown. EXPERIMENTAL DESIGN: We studied 412 consecutive patients with esophageal or EGJ adenocarcinoma treated with chemoradiation followed by esophagectomy (193 patients) or surgery alone (219 patients). We evaluated signet-ring cell and mucinous histology in the resection and pretherapy biopsy specimens and compared clinicopathologic features with overall survival. RESULTS: The fraction of signet-ring cell and mucinous histology was similar in evaluated specimens of patients treated with preoperative chemoradiation or surgery alone (17% and 18%, respectively). The overall survival rate at 5 years of patients treated with preoperative chemoradiation was significantly better if residual signet-ring cell or mucinous histology was present in the esophagectomy specimen (63% versus 28%; P = 0.02). All 13 patients with acellular mucin pools and no residual carcinoma are still alive after an average follow-up time of 36 months. By contrast, in patients treated with surgery alone, overall survival rate was significantly worse if signet-ring cell or mucinous histology was present (14% versus 30%; P = 0.05). In multivariate analysis, overall survival was independently predicted by presence of signet-ring cell or mucinous histology (P = 0.04). CONCLUSIONS: Our study showed that patients with esophageal or EGJ adenocarcinoma who have signet-ring cell or mucinous histology benefited substantially from preoperative chemoradiation and esophagectomy.     

Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.     

Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Lower functioning patients demonstrate atypical hip joint loading before and following total hip arthroplasty for osteoarthritis

Previous studies have established that up to 1 year post total hip arthroplasty (THA), patients do not recover normal function and the magnitude of hip joint loading remains reduced compared to healthy individuals. However, the temporal nature of the loading profile has not been considered to identify individuals who are at a greater risk of poor functional outcomes following THA. This study aimed to determine changes to the profile and magnitude of the resultant hip joint reaction force before and up to 6 months post-primary THA, and factors associated with atypical loading profiles. Hip joint loading was computed using a personalized lower-limb musculoskeletal model in 43 participants awaiting primary THA for osteoarthritis (mean age: SD = 65, 14 years; body mass index: SD = 30, 5 kg/m²) before and up to 6 months after THA. Atypical, single-peak loading profiles were observed for 11 patients before surgery, where four showed a single peak at 6 months. Patients displaying a single-peak profile walked slower (mean difference: −0.4 m/s) compared to individuals displaying double-peak profile (P = <.001) and had significantly reduced sagittal plane hip range of motion during gait (mean difference −9.6°, P = <.001). Self-reported pain, function, and stiffness did not differentiate between patients with a single or double-peak loading profile. Individuals with a single-peak force profile did not meet the minimal clinically important hip range of motion during gait and would be classified as low-functioning THA patients. Clinical Relevance: The temporal nature of the force profile may help to identify individuals who are at the greatest risk of poor functional outcomes after THA.     

Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer

Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.     

Chiropractic management of postpartum pubic symphysis diastasis: A case report

This case report describes the chiropractic management of a 30-year-old female patient with severe postpartum pelvic pain secondary to pubic symphysis diastasis. No literature was found on the chiropractic management of postpartum symphysis pubis diastasis. The existing literature concerning chiropractic care for symphysis pubis dysfunction during pregnancy is limited and indicates a potential benefit. Separation of the pubic symphysis may include ligamentous injury to the sacroiliac joints and may lead to chronic pain. Pubic symphysis separation of 17 millimeters was present on digital radiograph. Management consisted of chiropractic adjustments, trigger point release, electrical stimulation, moist heat, sacroiliac belt, and specific stabilizing exercises. The patient’s pain improved immediately following treatment on the initial visit. Pain was reduced from 8/10 VAS at the first visit to 2/10 at the fourth visit. She was able to resume normal activities and reached a final pain level of 1/10. The diastasis was reduced by 7 millimeters at 14-weeks post radiograph for a final separation of just under 10 millimeters. Collaboration between obstetricians, midwives and chiropractors may be warranted.