Clinical application of decellularized and lyophilized human amnion/chorion membrane grafts for closing post-laryngectomy pharyngocutaneous fistulas.

BACKGROUND AND OBJECTIVES: Squamous cell carcinoma is the most common pathological type among the cancers of the larynx. Standard treatment for squamous cell carcinoma of the larynx is the combination of chemotherapy, radiotherapy, and laryngectomy. Pharyngocutaneous fistula is a common complication of laryngectomy. We hypothesized that decellularized and lyophilized human amnion/chorion membrane can be an effective, non-invasive method of treating pharyngocutaneous fistula. METHODS: A total of 67 patients with laryngeal squamous cell carcinoma were retrospectively analyzed after treatment in a prospective trial. After preoperative chemotherapy, radiotherapy, and total or extended laryngectomy, primary wound healing occurred in 42 (62.7%) patients. Pharyngocutaneous fistula developed in 8 (11.9%) patients. Decellularized and lyophilized human amnion/chorion membrane grafts were used to reconstruct the fistulas. RESULTS: The average time for the full healing of the wound in all patients after transplantation of these grafts was 18 days. CONCLUSION: The advantages of using these grafts over other existing methods of pharyngocutaneous fistula treatment are that they are non-invasive, prevent donor morbidity, and enable management of the wound without using classical wound gauze. J. Surg. Oncol. 2016;113:538-543. © 2016 Wiley Periodicals, Inc.

Possible Markers for Distinguishing benign and Malignant Thyroid Tumors and Predicting Malignancy in Patients with Genetic Predisposition to Cancer.

BACKGROUND: We hypothesized that mutations in several genes disrupt oxidative metabolism, increasing the risk of developing tumors and their malignancy in patients with a family predisposition to cancer. The purpose of our study was to assess the characteristics of oxidative metabolism in patients with malignant and benign tumor with and without a family history of cancer and identify the marker predicting the likelihood of malignancy. METHODS: We conducted a study on patients with thyroid pathology (thyrotoxicosis, benign tumor pathology of the thyroid gland, and thyroid cancer) who underwent treatment at LLC "Oncology Scientific Research Center" in Tbilisi, Georgia between 2020-2021.  In patients' blood the thyroid hormones content, the oxidative metabolism parameters (activity of nonenzymatic antioxidant system (TAA), malondialdehyde (MDA) content),  geometrical and rheological (deformability index (EDI), membrane proteins content) characteristics of erythrocytes were determined. RESULTS: in the patient's blood serum with benign tumor (47 patients) MDA exceeded (p<0.005) and TAA decreased (p<0.005) in comparison to the control level; in patients with thyroid cancer (35 patients), MDA also exceeded (p<0.005), while TAA increased (p<0.005) up to the control level. In patients with benign and malignant tumors, the size of erythrocytes increased compared to the control indicators (p<0.005); in patients with thyroid cancer and benign tumors with a family history of cancer (29 patients) EDI increased (p<0.005), content of GLUT1 in erythrocyte membranes decreased (p<0.005) compared to the control level. CONCLUSIONS: Alterations in redox metabolism play a crucial role in tumor formation; an imbalance between anti-/pro-oxidant systems may contribute to tumor formation and support its progression into a more malignant state. Thyroid cancer is characterized by a reduction in erythrocyte deformability, related to TSH levels. These alterations are less detectable in patients with benign thyroid tumors with a family history of cancer.

Local drug delivery system for the treatment of tongue squamous cell carcinoma in rats.

The present study describes a local drug delivery system with two functions, which can suppress tumor growth and accelerate wound healing. Thе system consists of a two-layer multicomponent fibrin-based gel (MCPFTG). The internal layer of MCPFTG, which is in direct contact with the wound surface, contains cisplatin placed on a CultiSpher-S collagen microcarrier. The external layer of MCPFTG consists of a CultiSpher-S microcarrier with lyophilized bone marrow stem cells (BMSCs). The efficacy of MCPFTG was evaluated in a rat model of squamous cell carcinoma of the tongue created with 4-nitroquinoline 1-oxide. The results of the study showed that, within 20-25 days, a non-healing wound of the tongue was formed in animals that underwent only 85% resection of squamous cell carcinoma, while rapid progression of the residual tumor was concomitantly observed. Immunohistochemical methods revealed high expression of cyclin D1 and low expression of E-cadherin in these animals. Additionally, high expression of p63 and Ki-67 was noted. In 80% of animals with squamous cell carcinoma of the tongue that were treated with MCPFTG after 85% tumor resection, a noticeable suppression of tumor growth was evident throughout 150 days, and tumor recurrence was not detected. Immunohistochemistry revealed low or moderate expression of cyclin D1, and high expression of E-cadherin throughout the whole observation period. The MCPFTG-based local drug delivery system was shown to be effective in suppressing tumor growth and preventing recurrence. MCPFTG decreased the toxicity of cisplatin and enhanced its antitumor activity. In addition, lyophilized paracrine BMSC factors present in MCPFTG accelerated wound healing after tumor removal. Thus, the present study suggests novel opportunities for the development of a multifunctional drug delivery system for the treatment of squamous cell carcinoma.

Reconstruction of mandibular defects with autogenous bone and decellularized bovine bone grafts with freeze-dried bone marrow stem cell paracrine factors.

The gold standard following segmental mandibulectomy is vascularized autologous bone graft in the form of the fibula flap. However, in bone reconstruction the use of autogenous bone does not always guarantee a successful outcome. The aim of the present investigation was to develop a novel biologically active bone (BAB) graft, and to use it for the reconstruction of large size defects of the mandible bone following tumor resection. In the first part of the present study, biologically active bone graft was developed by using human freeze-dried bone marrow stem cells (BMSCs) paracrine factors and three-dimensional bone scaffold derived from cancellous bovine bone following decellularization. In the second part of the research, one male and three female patients with primary tumors of the mandible underwent hemimandibulectomy. The mandibular bone defects following tumor resection were reconstructed with autogenous rib grafts in three patients and BAB graft was used in one patient. The graft-host interfaces were covered with decellularized human amnion/chorion membrane graft. All patients were followed-up every five months following the reconstruction of the mandible, with no complications observed. Preliminary clinical investigations demonstrated that a BAB graft containing freeze-dried BMSC paracrine factors may be used for the reconstruction of large mandibular bone defects following tumor resection.

Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury.

Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury.

Benign osteoblastoma of the mandible in a 12-year-old female: A case report.

Benign osteoblastoma refers to a benign tumor of the bone. Osteoblastoma most commonly affects the vertebrae and long tubular bones, however, in rare cases is observed in the facial bones. The current study presents the case of a 12-year-old female patient with a tumor in the mandibular body. Radiological imaging revealed a lesion with regular contours. The lesion was radically resected and histological analysis of the specimen demonstrated features that are typical of a benign osteoblastoma. The consequential defects of the jaw were reconstructed using titanium implants and autologous bone transplantation. The patient remains disease free subsequent to a five-month follow-up period. The aim of the present report is to present a rare case of benign osteoblastoma of the mandible. This study demonstrated that correct diagnosis and complete surgical excision are important to reduce the risk of recurrence of a benign osteoblastoma.