Primary Gastric Synovial Sarcoma in a Young Male: a Rare Case Report and Review of Literature.

We are reporting a rare case of primary gastric synovial sarcoma in a young male. Synovial sarcoma of the stomach is a very rare tumor. The common involved sites of occurrence of synovial sarcomas are upper and lower extremities. In the English literature, only 47 cases of primary synovial sarcoma of stomach have been reported. Spindle-shaped tumor cells are the basic content of synovial sarcomas with varying degrees of epithelial differentiation. The basic classification of synovial sarcoma depends on the histological pattern and the degree of differentiation and it is classified as monophasic, biphasic, and poorly differentiated. Synovial sarcoma presents with classical chromosomal translocation where they form fusion genes of SS18-SSX1, SS18-SSX2, and SS18-SSX4. Fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR) are the molecular analysis techniques to detect these fusion genes. As the available literature support is limited, the role of adjuvant chemotherapy, radiation therapy, and intra-operative lymphadenectomy is still unclear. However, surgical resection with clear margin is the gold standard treatment.

Modified Radical Mastectomy vs Breast-Conserving Surgery: Current Clinical Practice in Women with Early Stage Breast Cancer at a Corporate Tertiary Cancer Center in India.

Breast cancer is the most common cancer in women in urban India and surgery has one of the definitive roles in treating this cancer. Over the decades, multiple studies have been published and they have shown that BCS followed by radiotherapy has equivalent disease-free survival (DFS) and overall survival (OS) as compared with MRM. The surgeon has the main role in explaining the treatment options to the patient. It is a prospective study conducted at Vedant Cancer and Multispeciality Hospital in a metropolitan city, Thane, India. Patients with stage I or II breast cancer with tumor size less than 5 cm were included in the study. Patients with locally advanced and metastatic breast cancer were excluded from the study. The study population was early breast cancer patients registered and waiting for surgery (n = 86) at Vedant Cancer and Multispeciality Hospital from November 2019 to end of April 2020. The total number of females enrolled in the study were 86 and out of this, 79.1% (n = 68) females opted for MRM and 20.9% (n = 18) females opted for BCS in which 8 patients had changed their decision after re-counseling in the ward from MRM to BCS. The most common reasons selected by patients to undergo MRM were fear of cancer recurrence (30.2%, n = 26), avoidance of side effects of radiation therapy (25.5%, n = 22) and fear of radiation therapy (23.2%, n = 20). Surgeon had decided the surgical option in 79.1% (n = 68) cases. The study shows that the treating surgeon and patient's husband are the principal persons who decide the surgical option and active participation of women during counseling is an important factor. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-021-01457-8.

Functional Malignant Retroperitoneal Paraganglioma with Liver Metastasis: a Rare Case Report.

Paragangliomas are rare neoplasms. Their specific annual incidence is still unclear. These are rare neuroendocrine tumors which arise from extra-adrenal paraganglioma and they have the ability to secrete catecholamines. Most of them are diagnosed in the 3rd to 5th decades of life with mean age around 47 years. Majority of them are benign; however, malignant tumors with metastatic behavior are very rare. The incidence of malignant paraganglioma is estimated around 93/400 million people. The clinical course of metastatic malignant disease is variable and the reported 5-year survival is around 12-84%. There is no curative treatment option for malignant metastatic paraganglioma. If resectable, both, primary and metastasis should be resected. The only criteria which defines its malignancy is the presence of metastatic spread of chromaffin cells in tissues that normally do not contain such cells. Functional paraganglioma secretes excessive catecholamines which clinically manifest as paroxysmal hypertension, headache, sweating, and palpitations. We reported a case of young male who presented with huge left retroperitoneal mass and after evaluation found to have a functional malignant paraganglioma with liver metastasis. Surgical resection of the primary malignant paraganglioma with metastatectomy helps in decreasing the complications, improving the symptoms and prolonging the survival.

Does Preoperative Diagnosis Will Change the Treatment Plan of Clear Cell Carcinoma of Endometrium Masquerading as Desmoid Tumor of Anterior Abdominal Wall?: a Case Report.

Clear cell carcinoma (CCC) of the female genital tract can arise in the ovary, endometrium, cervicovaginal region, in peritoneal and other extra pelvic sites. However, CCC involving anterior abdominal wall is a very rare entity. We are reporting a case of 55-year-old postmenopausal lady with ECOG PS-I with no comorbidity had history of cesarean section about 30 years back and presented with pain in abdomen at periumbilical region about 9 months back. She underwent evaluation at outside clinic with finding of an anterior abdominal wall swelling of size approximately 3 × 3 cm which was completely neglected by the patient. In the next period of 2 months, the swelling suddenly increased in size. CECT/PET CT showed a solid cystic mass involving anterior abdominal wall with possibility of desmoid tumor. We had decided to plan for surgical excision of the tumor. Intraoperatively we found that there was bicornuate uterus. The lesion was arising from one of the cornue of uterus and it was extended anteriorly to anterior abdominal wall with no ascites, no pelvic, or retroperitoneal lymphadenopathy. She underwent hysterectomy with bilateral salpingo-oophorectomy and defect was closed with bioabsorbable mesh. Final histopathology report was clear cell endometrial carcinoma mostly mullerian tract origin arising from endometriosis focus. Tumor cells were diffusely positive for PAX-8 and Napsin-A and negative for WT 1 with patchy positivity for P53 (wild type expression). She had received adjuvant chemotherapy and she is disease free after 2 years of completion of the treatment. Clear cell endometrial carcinoma arising from malignant transformation of an endometriosis focus to anterior abdominal wall is a very rare phenomenon and it is a difficult task to reach its final diagnosis.

Bioconductive 3D nano-composite constructs with tunable elasticity to initiate stem cell growth and induce bone mineralization.

Bioactive 3D composites play an important role in advanced biomaterial design to provide molecular coupling and improve integrity with the cellular environment of the native bone. In the present study, a hybrid lyophilized polymer composite blend of anionic charged sodium salt of carboxymethyl chitin and gelatin (CMChNa-GEL) reinforced with nano-rod agglomerated hydroxyapatite (nHA) has been developed with enhanced biocompatibility and tunable elasticity. The scaffolds have an open, uniform and interconnected porous structure with an average pore diameter of 157±30µm and 89.47+0.03% with four dimensional X-ray. The aspect ratio of ellipsoidal pores decrease from 4.4 to 1.2 with increase in gelatin concentration; and from 2.14 to 1.93 with decrease in gelling temperature. The samples were resilient with elastic stain at 1.2MPa of stress also decreased from 0.33 to 0.23 with increase in gelatin concentration. The crosslinker HMDI (hexamethylene diisocyanate) yielded more resilient samples at 1.2MPa in comparison to glutaraldehyde. Increased crosslinking time from 2 to 4h in continuous compression cycle show no improvement in maximum elastic stain of 1.2MPa stress. This surface elasticity of the scaffold enables the capacity of these materials for adherent self renewal and cultivation of the NTERA-2 cL.D1 (NT2/D1), pluripotent embryonal carcinoma cell with biomechanical surface, as is shown here. Proliferation with MG-63, ALP activity and Alizarin red mineralization assay on optimized scaffold demonstrated ***p<0.001 between different time points thus showing its potential for bone healing. In pre-clinical study histological bone response of the scaffold construct displayed improved activity of bone regeneration in comparison to self healing of control groups (sham) up to week 07 after implantation in rabbit tibia critical-size defect. Therefore, this nHA-CMChNa-GEL scaffold composite exhibits inherent and efficient physicochemical, mechanical and biological characteristics based on gel concentrations, gelatin mixing and gelling temperature thus points to creating bioactive 3D scaffolds with tunable elasticity for orthopedic applications.

Bifunctional Polysulfone-Chitosan Composite Hollow Fiber Membrane for Bioartificial Liver.

Hollow fiber membranes are widely used as assist devices for bioartificial liver application. Asymmetric porous polysulfone and polysulfone-tocopheryl polyethylene glycol succinate (Psf-TPGS) composite hollow fiber and flat membranes were prepared by phase inversion procedure and subsequently surface modified with chitosan using sulfonation with concentrated sulfuric acid. Sulfonation induces negative charge on the prepared membrane surface and facilitates the attachment of chitosan amine groups by electrostatic interaction. The surface modification of membrane is stable at room temperature as dictated by presence of nitrogen in XPS analysis and amide linkages in FT-IR spectra. Further, biological studies of the membranes were performed using HepG2 cell line. Chitosan is biocompatible and shows structural similarity to glycosaminoglycans, a native liver ECM component. The chitosan-modified composite Psf and Psf-TPGS membranes have shown enhanced attachment and proliferation of HepG2 cells on outer surface as confirmed by the cell counting, DNA content, confocal microscopy, and SEM micrographs. The cells form a 3D multicellular spheroid structure on the chitosan-modified membranes in significantly larger number as seen in the SEM micrographs. Also, the hemocompatibility of the modified composite membranes were comparable to the unmodified membranes. Thus, the chitosan-modified composite membranes we have developed are bifunctional and have the potential to be used in bioartifical liver application.

Hardystonite improves biocompatibility and strength of electrospun polycaprolactone nanofibers over hydroxyapatite: a comparative study.

The aim of this study was to compare physico-chemical and biological properties of hydroxyapatite (HA) and hardystonite (HS) based composite scaffolds. Hardystonite (Ca2ZnSi2O7) powders were synthesized by a sol-gel method while polycaprolactone-hardystonite (PCL-HS) and polycaprolactone-hydroxyapatite (PCL-HA) were fabricated in nanofibrous form by electrospinning. The physico-chemical and biological properties such as tensile strength, cell proliferation, cell infiltration and alkaline phosphatase activity were determined on both kinds of scaffolds. We found that PCL-HS scaffolds had better mechanical strength compared to PCL-HA scaffolds. Addition of HA and HS particles to PCL did not show any inhibitory effect on blood biocompatibility of scaffolds when assessed by hemolysis assay. The in vitro cellular behavior was evaluated by growing murine adipose-tissue-derived stem cells (mE-ASCs) over the scaffolds. Enhanced cell proliferation and improved cellular infiltrations on PCL-HS scaffolds were observed when compared to HA containing scaffolds. PCL-HS scaffolds exhibited a significant increase in alkaline phosphatase (ALP) activity and better mineralization of the matrix in comparison to PCL-HA scaffolds. These results clearly demonstrate the stimulatory role of Zn and Si present in HS based composite scaffolds, suggesting their potential application for bone tissue engineering.

Bio-origami hydrogel scaffolds composed of photocrosslinked PEG bilayers.

We describe the self-folding of photopatterned poly (ethylene glycol) (PEG)-based hydrogel bilayers into curved and anatomically relevant micrometer-scale geometries. The PEG bilayers consist of two different molecular weights (MWs) and are photocrosslinked en masse using conventional photolithography. Self-folding is driven by differential swelling of the two PEG bilayers in aqueous solutions. We characterize the self-folding of PEG bilayers of varying composition and develop a finite element model which predicts radii of curvature that are in good agreement with empirical results. Since we envision the utility of bio-origami in tissue engineering, we photoencapsulate insulin secreting ß-TC-6 cells within PEG bilayers and subsequently self-fold them into cylindrical hydrogels of different radii. Calcein AM staining and ELISA measurements are used to monitor cell proliferation and insulin production respectively, and the results indicate cell viability and robust insulin production for over eight weeks in culture.

In vivo evaluation of the biocompatibility of surface modified hemodialysis polysulfone hollow fibers in rat.

Polysulfone (Psf) hollow fiber membranes (HFMs) have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate) composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC) coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications.

The biocompatibility and separation performance of antioxidative polysulfone/vitamin E TPGS composite hollow fiber membranes.

The extended interaction of blood with certain materials like hemodialysis membranes results in the activation of cellular element as well as inflammatory response. This results in hypersensitive reactions and increased reactive oxygen species, which occurs during or immediately after dialysis. Although polysulfone (Psf) hollow fiber has been commercially used for acute and chronic hemodialysis, its biocompatibility remains a major concern. To overcome this, we have successfully made composite Psf hollow fiber membrane consisting of hydrophilic/hydrophobic micro-domains of Psf and Vitamin E TPGS (TPGS). These were prepared by dry-wet spinning using 5, 10, 15, 20 wt% TPGS as an additive in dope solution. TPGS was successfully entrapped in Psf hollow fiber, as confirmed by ATR-FTIR and TGA. The selective skin was formed at inner side of hollow fibers, as confirmed by SEM study. In vitro biocompatibility and performance of the Psf/TPGS composite membranes were examined, with cytotoxicity, ROS generation, hemolysis, platelet adhesion, contact and complement activation, protein adsorption, ultrafiltration coefficient, solute rejection and urea clearance. We show that antioxidative composite Psf exhibits enhanced biocompatibility, and the membranes show high flux and high urea clearance, about two orders of magnitude better than commercial hemodialysis membranes on a unit area basis.

Islet neogenesis from the constitutively nestin expressing human umbilical cord matrix derived mesenchymal stem cells.

The scarcity of islets for transplantation calls for an alternative sources of islets. The human umbilical cord has been shown to be a reservoir of multipotent stem cells with capacity to differentiate into ectodermal, mesodermal and endodermal lineages. The present investigation deals with isolation and characterization of mesenchymal stem sells (MSC) derived from human umbilical cord and their differentiation into functional islets. Since these MSCs were found to constitutively express nestin we hypothesized that these would be ideal candidates for islet neogenesis without any further manipulation. Human umbilical cord matrix stem cells (hUCMSCs) were found to express CD29, CD44, CD73, CD90, CD105, smooth muscle actin, nestin, vimentin, proliferation marker Ki67 and embryonic markers Oct4, SSEA4. These were found to be negative for CD33, CD34, CD45 and HLA DR. Human UCMSCs exhibited high proliferating capacity for extended period indicating potential for scaling up. When subjected to a cocktail of specific differentiating factors, these cells differentiated into fat, cartilage, bone, neurons and islet like clusters (ILCs). These ILCs stained positive for diphenylthiocarbazone (DTZ) and expressed human C-peptide, insulin and glucagon. Real time qPCR analysis of newly generated islets further demonstrated abundance of Pdx-1, Ngn3, insulin, glucagon and somatostatin transcripts. On transplantation in experimental diabetic mice these ILCs restored normoglycemia, body weight and exhibited normal glucose tolerance test indicating their functional status. Thus, the present study demonstrates potential of constitutively expressing nestin positive progenitor from umbilical cord as a novel source for islet neogenesis and their usage in cell replacement therapy for diabetes.

Reversal of experimental diabetes in mice by transplantation of neo-islets generated from human amnion-derived mesenchymal stromal cells using immuno-isolatory macrocapsules.

BACKGROUND AIMS: The ethical and biologic limitations with current sources of stem cells have resulted in a quest to look for alternative sources of multipotent stem cells of human origin. Amniotic membrane is of interest as a source of cells for regenerative medicine because of its ease of availability, plasticity and inexhaustible source that does not violate the sanctity of independent life. Although researchers have shown the stem cell-like potential of human amniotic epithelial cells, the mesenchymal part of amnion has remained less explored. METHODS: We established a long-term culture of mesenchymal-like stem cells derived from full-term human amniotic membrane and their differentiation into functional pancreatic lineage. RESULTS: The amnion-derived mesenchymal-like stem cells expressed various mesenchymal markers and demonstrated multilineage differentiation capacity. We also observed that these cells could form islet-like clusters (ILC) on exposure to serum-free defined media containing specific growth factor and differentiating agents. Differentiated ILC showed expression of human insulin, glucagon and somatostatin by immunocytochemistry, while quantitative reverse transcription/real-time-polymerase chain reaction (qRT-PCR) data demonstrated the expression of insulin, glucagon, somatostatin, Ngn3 and Isl1. Moreover, encapsulation of the ILC in polyurethane-polyvinyl pyrrolidone macrocapsules and their subsequent transplantation in experimental diabetic mice resulted in restoration of normoglycemia, indicating their ability to respond to high glucose without immunorejection. CONCLUSIONS: Our results demonstrate that amnion-derived mesenchymal stromal cells can undergo islet neogenesis, indicating amnion as an alternative source of islets for cell replacement therapy in diabetes.

Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord.

The umbilical cord represents the link between mother and fetus during pregnancy. This cord is usually discarded as a biological waste after the child's birth; however, its importance as a "store house" of stem cells has been explored recently. We developed a method of simultaneous isolation of endothelial cells (ECs) from the vein and mesenchymal stem cells from umbilical cord Wharton's jelly of the same cord. The isolation protocol has been simplified, modified, and improvised with respect to choice of enzyme and enzyme mixture, digestion time, cell yield, cell growth, and culture medium. Isolated human umbilical vascular ECs (hUVECs) were positive for von-Willibrand factor, a classical endothelial marker, and could form capillary-like structures when seeded on Matrigel, thus proving their functionality. The isolated human umbilical cord mesenchymal stem cells (hUCMSCs) were found positive for CD44, CD90, CD 73, and CD117 and were found negative for CD33, CD34, CD45, and CD105 surface markers; they were also positive for cytoskeleton markers of smooth muscle actin and vimentin. The hUCMSCs showed multilineage differentiation potential and differentiated into adipogenic, chondrogenic, osteogenic, and neuronal lineages under influence of lineage specific differentiation medium. Thus, isolating endothelial cells as well as mesenchymal cells from the same umbilical cord could lead to complete utilization of the available tissue for the tissue engineering and cell therapy.

Who is the culprit for post menopausal syndrome? Uterus/Ovary!

The uterine endometrium of placental mammals in general and human in particular is a highly dynamic, proliferative and regenerative tissue. It undergoes cycles of growth and regression during each menstrual cycle with a growing capacity from 0.5-1mm in the proliferative phase to 5-7 mm during the secretory (leutal) phase. These phases are characterized by cyclic processes of cellular proliferation, differentiation and shedding. Recent studies have revealed that the endometrium harbours a large population of mesenchymal stromal cells. There are several reports indicating the homing of bone marrow stem cells and endothelial progenitor cells in regenerating endometrium. However, it is not clear whether endometrial cells mobilise to participate in the repair and regeneration of vital organs/tissues. We hypothesize that a very small percentage of the endometrial cells may set in circulation during menstrual cycle to facilitate endogenous regeneration of vital organs in the body. These cyclical events may be responsible for providing a protective barrier to women during her child-bearing age. Disappearance of this barrier after menopause probably makes her vulnerable for post menopausal symptoms. There is a circumstantial evidence to vouch for the presence of circulating stem/progenitor cells in peripheral blood which are likely to lodge in injured organs for their possible repair. As the endometrium harbors a large population of mesenchymal stromal cells, it is possible that retention of the uterus through secretion of reparative/growth promoting factors, may provide legitimate stem cells to enter circulation and "set up shop" in other tissues like bone marrow stem cells. In this context we propose uterus to be the culprit for the postmenopausal syndrome.