Clinical, pathomorphological and immunohistochemical evaluation of tissue repair in diabetic foot ulcers

Background: It is known that wound healing is Impaired in diabetes mellitus. Possible reasons are widely being searched. However, despite all the available data, reliable markers of reparative processes in diabetes mellitus are needed to be found. Aim: To study morphological and some immunohistochemical markers of tissue repair in patients with diabetic foot ulcers after local treatment. Materials and methods: 70 patients with diabetic foot ulcers before and after surgical debridement were included. Histological (light microscopy) and immunohistochemical (CD68, MMP-9, TIMP-1) characteristics of tissue repair processes in soft tissues of the lower extremities in patients with diabetes mellitus were analyzed. Histological and immunohistochemical examination of soft tissues were performed in 63 patients before and after surgical debridement and 10 days after local treatment. Results: After the surgical debridement a significant reduction in the area of wounds was registered by 23.4% (p <0.05), wound depth by 29.4% (p <0.05). Based on the results of the morphological study, the presence of mature granulation tissue in the wounds was confirmed. Immunohistochemical study of wound biopsies demonstrated a significant decrease in proteolytic activity in the wound as a decrease in MMP-9 expression (p <0.05). Statistically significant changes in the number of macrophages against the initial data were not found, as well as increased expression of TIMP-1 was observed (p> 0.05 and <0.05, respectively). Conclusion: According to the data, there was a significant decrease in the area and depth of wounds during local treatment. The intensity of tissue repair was confirmed by the results of histological and immunohistochemical studies. However, the absence of a statistically significant change in the amount of macrophages on the background of treatment suggests that this repair link is disrupted in diabetes mellitus, which is the reason for the "chronic" wounds and requires further studies

Ontogeny of the Human Pancreas

Pancreatic disorders are the most common pathologies in humans worldwide. Detailed information on pancreatic cytoarchitecture, vascularisation, innervation, morphogenesis, and cell differentiation is required for the development of new approaches to the treatment of these diseases. Currently, the majority of studies on pancreas development are performed on experimental animals (mainly rodents). Studies on human pancreatic prenatal development are restricted in number by ethical constraints and some technical difficulties. However, interspecies differences in pancreatic structure and development are considerable. Therefore, data obtained in experiments on animals and cell cultures must be supplemented with information obtained directly from human pancreatic autopsies. In this chapter, we summarise our previous results and the literature data on human pancreatic ontogeny. Special attention has been paid to the endocrine pancreas, which undergoes morphogenetic restructuring during human development. Several forms of structural organisation of the endocrine pancreas (single endocrine cells, small clusters of endocrine cells, mantle, bipolar, and mosaic islets) gradually appear during development. It is important that this restructuring is accompanied by changes in the ratio of pancreatic endocrine cells. The mechanisms of these changes are still unclear. The difficulties in identifying progenitor cells and tracking cell differentiation are the main problems associated with this issue

The case of oncogenic hypophosphatemic osteomalacia

Osteomalacia is a systemic bone disease, characterized by an excessive accumulation of non-mineralized osteoid and an imbalance in the organic matrix formation and mineralization. A rare cause of disease is tumor-induced osteomalacia, most often due to phosphaturic mesenchymal tumors (PMT). Usually there are benign small tumors, affecting the soft tissues and bones of any location. The basic pathogenesis of underlying oncogenic osteomalacia is a decreased renal tubular reabsorption of phosphate consequent to hyperproduction of fibroblast growth factor 23 in PMT. Clinical features are nonspecific, the average period from the symptoms onset to diagnosis reaches 3 years and at least 5 years before surgical treatment. Finding the tumour is crucial, as complete removal is curative. We present a clinical case of tumor-induced osteomalacia due to PMT required the complex differential diagnosis with other rare diseases

Evaluation of the metabolism properties of choline kinase alpha in neoplasms of the parathyroid glands. A pilot study

BACKGROUND: Primary hyperparathyroidism (PHPT) is a widespread endocrine disease characterized by excessive production of parathyroid hormone (PTH) due to parathyroid gland hyperplasia (PGH) or tumor lesions (adenoma or cancer of the parathyroid gland (PG) in 80% and 1–5% of cases respectively). Choline kinase α–alpha (XKα) overexpression is described in tumors of different localization, but there is no data on its expression in PG tumors. AIMS: To study the character of XKα expression in PG neoplasms and its relationship with clinical, laboratory, and visualization characteristics (positron emission tomography combined with computed tomography (PET/CT) with 18F–fluorocholine (18F–FC)). MATERIALS AND METHODS: The material for the study was based on tissue samples from 10 patients of 34–70 years old (Me = 61.5; [48; 66]), with a laboratory–confirmed diagnosis of PHT. An immunohistochemical study (IHC) was carried out on materials from 2 patients with hyperplasia of the main cells, from 5 patients with adenoma of PG, from 1 patient with atypical adenoma and 1 with carcinoma of PG; in 1 case the metastasis of cancer of the neck with lymph node was examined. RESULTS: The expression of XKα is spotted in all types of PG cells (chief cells: active and inactive forms), transitional forms between the chief cells and oxyphil; oxyphil cells, but it was most intense in active chief cells. The expression of XKα was observed in neoplasms of PG of various degrees of malignancy. In the most numerous group of PG formations with a favorable prognosis (11 samples from 7 patients), no statistically significant correlation (p> 0.05) was obtained between the intensity expression of the XKα, of the PTH and the proliferative activity index Ki–67, the level of radiopharmaceutical accumulation in PET/CT with 18F–FC (SUVmax) and laboratory data (PTH, Ca, Ca++). CONCLUSIONS: In the majority of investigated cases, moderate and intensive expression of the XKα was detected in PG cells. A small amount of studied cases does not allow us to identify the connection between the intensity of XKα expression and the malignant potential for the formation of PG

The morphological characteristic of tissue repair in patients with neuropathic and neuroischemic forms of diabetic foot syndrome

Aim. To evaluate the morphological and immunohistochemical features of granulation tissue formation in patients with diabetic foot syndrome. Materials and methods. We analysed the histological (light microscopy) and immunohistochemical (CD31, CD68, osteopontin, MMP-9 and TIMP-1) features of tissue repair processes in patients with diabetes mellitus. The study involved 63 patients with diabetic foot syndrome after surgical debridement. Results. We found severe intercellular oedema, poorly organised extracellular matrix, small amounts of fibroblast-like cells and expressed inflammatory infiltration, along with the presence of young granulation tissue. According to the results of the immunohistochemical studies, there were a moderate number of macrophages (immunopositive with antibodies to CD68), intense staining of MMP-9 and weak staining of TIMP-1 and osteopontin. Conclusion. According to the findings of the histological and immunohistochemical studies, tissue repair processes in patients with diabetes mellitus are decelerated

Genetic parameters of wound healing in patients with neuropatic diabetic foot ulcers

Background. Tissue repair processes are impaired in diabetic foot ulcers (DFUs). Previous research has shown that glycaemic control, cytokines and growth factors play an important role in wound healing. Emerging evidence also suggests that genes play a role via their regulation of cell proliferation, collagen synthesis and granulation tissue formation. Aim. To evaluate collagen genes expression in different stages of wound healing in patients with DFUs. Materials and methods. Prospective study included four patients with neuropathic DFUs after surgical debridement. Tissue samples were taken for morphological and genetic tests on days 0, 10 and 15 of local treatment to evaluate expression of collagen genes (i.e. COL1A1, COL1A2, COL3A1) and to perform morphological tests. Results. The present study confirmed that the size of wounds decreased by 8.8 7% after 10 days of local treatment and by 18.3 8% after 15 days of local treatment. According to histological examination of wound biopsies at day 10, all patients showed a tendency for lower levels of inflammatory infiltrate, increased number of fibroblast-like cells, presence of maturing granulation tissue and emergence of connective tissue fibres. After 15 days, we detected inflammatory infiltration in the wounds, despite the formation of mature granulation tissue. According to results of genetic analysis on day 10 of local wound treatment, we found a tendency for increased expression of collagen genes relative to the baseline: COL1A1 increased by 3.2 1.3 times, COL1A2 by 2.0 1.0 times and COL3A1 by 1.25 1.1 times. On day 15 of local treatment, in contrast, we found a tendency for decreased expression of COL1A1, COL1A2 and COL3A1 relative to the baseline (1.7 0.6, 2.5 2 and 20.0 3 times, respectively). Conclusions. The expression of collagen genes (COL1A1, COL1A2, COL3A1) is more pronounced in proliferation phase and is subsequently reduced towards the end. These data were confirmed by morphological study and clinical pictures

Two cases synchronous atypical parathyroid adenomas and papillary thyroid carcinoma

Most clinicians are well aware of the coexistence of medullary thyroid cancer and hyperparathyroidism in hereditary and sporadic multiple endocrine neoplasia syndromes. Тhe reported incidence of nonmedullary thyroid carcinoma in patients with primary hyperparathyroidism (pHPT) is only approximately 3%. Papillary thyroid carcinomas (PTC) is a malignant epithelial tumour. PTC represent up to 87% of all thyroid carcinomas. Atypical parathyroid adenoma (APA) are a subset of parathyroid neoplasms that exhibit some of the features of parathyroid carcinoma but lack unequivocal invasive growth. APA represents about 0.54% of cases of PHPT. As a group, they may be considered tumors of uncertain malignant potential. The clinical importance, and long-term outcomes as well as appropriate operative management and surveillance are not well defined for APA probably due to the overall low prevalence as well as the lack of a standard definition of APA. We report two cases of a 63-year-old woman and 57-year-old man with a synchronous atypical parathyroid adenoma and papillary thyroid carcinoma. One of this patients had a classic symptoms of pHPT, including severe metabolic bone disease and renal disease, but another didnt have. The mean preoperative calcium was 3,48 and 4,1 (range 2.122.6) mmol/l and a mean parathyroid hormone (PTH) of 1300 and 1533 (range 1565) pg/ml, respectively. Thyroid ultrasound didnt show a nodule with features of the thyroid carcinoma in both cases. The thyroid cancer was suspected after intraoperative revision. The patients underwent a total thyroidectomy and surgical excision of the parathyroid adenoma. Surgical pathology showed papillary microcarcinoma in both cases (in the first unilateral, in the second bilateral) and APA. Awareness of this condition will enable clinicians to evaluate for possible thyroid pathology in patients with primary hyperparathyroidism. Both of these endocrine conditions could then be managed with a single surgery involving concomitant resection of the thyroid and parathyroid glands

Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms

Background and objective: Preoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. Methods: A multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. Results: Patients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. Conclusions: Model can predict adenoma with PPV 100% and PC with PPV 81–92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty