Case presentation of the smallest non-functional parathyroid carcinoma and review of the literature.

INTRODUCTION: Non functional parathyroid carcinoma (PC) is one of the rarest malignant neoplasms. Due to the lack of symptoms and laboratory findings, it is mostly diagnosed in late AQ2 stages, when local invasion and dissemination are already present. However, our case is an exception, because it was detected in early stage, with no local invasion present. We present a case of the smallest non-functional PC yet reported and review of the literature. CASE PRESENTATION: A 47-year-old woman was admitted to outpatient Clinic where fine-needle aspiration biopsy (FNAB) of bilateral thyroid nodules (slide 1) and central neck mass (slide 2), which was suspected to be an enlarged lymphatic nodule or parathyroid gland was performed. Results came back as Bethesda I-colloid (slide 1), and Bethesda IV (slide 2), stating that it is hard to distinguish thyroid gland oxyphil lesions from parathyroid cells. Total thyroidectomy was performed as well as excision of the left central neck mass, without any involvement of surrounding structures. Pathological examination revealed bilateral thyroid follicular nodular disease, papillary microcarcinoma, and parathyroid carcinoma with vascular and capsular invasion, measuring 10 × 8 × 7 mm. The immunohistochemical profile included positive PTH, Chromogranin A, and negative TTF1. CONCLUSION: Non-functional PC is usually diagnosed in advanced stages, already involving adjacent structures; however, this case presents a rare example. It is important not to exclude PC as a differential diagnosis in the absence of elevated Ca and PTH serum levels. Follow-up will be difficult, since there are no prognostic parameters to rely on.

Health care access of thyroid disease patients in Serbia during the COVID-19 pandemic.

PURPOSE: The aim of this study was to assess the impact of repurposing health care facilities in response to COVID-19 on the access of patients with thyroid disease to health care. METHODS: This study consisted of a web-based survey. The survey was anonymous and consisted of forty questions. RESULTS: This survey included 206 respondents. 91.3% of the respondents had health insurance through the Republic Fund of Health Insurance, 9.7% had private or both health insurances, and 3.4% did not have any health insurance. A significant proportion of respondents (60.4%) had to switch from public to private health care to reach a physician and 73.8% had to switch from public to private laboratories. For the 91.9%, this was perceived as a financial burden. Before the pandemic, 83.1% of respondents reported regular follow-up by physicians, which decreased to 44.9% during the pandemic (p < 0.01). 76.3% of the respondents regarded that their thyroid disease was managed optimally before the pandemic, while this figure declined to only 48% during the pandemic (p < 0.01). CONCLUSIONS: The COVID-19 pandemic disrupted the medical care of thyroid patients in Serbia. For the patients treated in the public health care system, access to general practice was hindered, while access to specialist care was disrupted. It led to a switch from public to private health care, which was perceived as a financial burden for almost all the respondents. However, private health care proved to be an important safety net when the public system was overwhelmed.

Serum Insulin-Like Growth Factor-1 (IGF-1) Age-Specific Reference Values for Healthy Adult Population of Serbia.

Context: Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population- and assay-specific reference values requires sizable representative cohort of healthy subjects. Subjects and Methods: In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5th - 95th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods. Results: IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use. Conclusions: Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI- and WHR-specific reference ranges. Population-based data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets.

Considerations for the design and conduct of human gut microbiota intervention studies relating to foods.

With the growing appreciation for the influence of the intestinal microbiota on human health, there is increasing motivation to design and refine interventions to promote favorable shifts in the microbiota and their interactions with the host. Technological advances have improved our understanding and ability to measure this indigenous population and the impact of such interventions. However, the rapid growth and evolution of the field, as well as the diversity of methods used, parameters measured and populations studied, make it difficult to interpret the significance of the findings and translate their outcomes to the wider population. This can prevent comparisons across studies and hinder the drawing of appropriate conclusions. This review outlines considerations to facilitate the design, implementation and interpretation of human gut microbiota intervention studies relating to foods based upon our current understanding of the intestinal microbiota, its functionality and interactions with the human host. This includes parameters associated with study design, eligibility criteria, statistical considerations, characterization of products and the measurement of compliance. Methodologies and markers to assess compositional and functional changes in the microbiota, following interventions are discussed in addition to approaches to assess changes in microbiota-host interactions and host responses. Last, EU legislative aspects in relation to foods and health claims are presented. While it is appreciated that the field of gastrointestinal microbiology is rapidly evolving, such guidance will assist in the design and interpretation of human gut microbiota interventional studies relating to foods.

Rare renal cell carcinoma metastasis to mandibular gingiva: A case report and literature review.

Metastatic lesions represent approximately 1% of all the intraoral lesions. They most commonly originate from lung and breast carcinomas, while the third most common source is the renal cell carcinoma. In this paper, we present the rare case of metastases of renal cell carcinoma in the mandibular gingiva of a 53-year-old male patient.

CUSHING'S SYNDROME, A RISK FACTOR FOR VENOUS THROMBOEMBOLISM IS A CANDIDATE FOR GUIDELINES.

OBJECTIVES: The present paper aims to review important contemporary information about VTE risk in endogenous and exogenous CS, as a substantial discrepancy exists between the results of a recent meta-analysis confirming the increased risk for VTE and the absence of CS in VTE guidelines. METHODS: An extensive search of relevant databases (e.g. PubMed, Google Scholar, and Scopus) was performed in order to establish the interconnectedness of the following terms: Cushing's syndrome, venous thromboembolism, deep vein thrombosis, pulmonary embolism. RESULTS: The analysis demonstrated that patients with CS have about ten times the risk for VTE, particularly during the first year following the diagnosis of CS. Oral glucocorticoid users (with iatrogenic CS) have a 3-fold increase in risk of VTE in comparison with non-users. The most recent 2019 meta-analysis encompassed 7142 patients with endogenous CS (including Cushing's disease) undergoing transsphenoidal surgery or adrenalectomy, and their risk of unprovoked VTE was almost 18 times higher in comparison with a healthy population. CONCLUSION: Over the past 50 years considerable evidence of increased VTE risk in CS has been accumulated. It pertains to both endogenous and exogenous type of CS and has been confirmed in the vast majority, if not all the available studies, including meta-analyses. Nevertheless, official CS guidelines make no mention of CS as a VTE risk factor, even though it is important that not only physicians who treat CS, but also physicians who manage patients with suspected VTE be aware of increased VTE risk.

FROM DIABETES INSIPIDUS TO SELLAR XANTHOGRANULOMA - A "YELLOW BRICK ROAD" DEMANDING TEAM-WORK.

Xanthogranulomas are inflammatory lesions exceptionally rarely occurring in the sellar region. Sellar xanthogranulomas (SXG) result from secondary hemorrhage, infarction, inflammation or necrosis upon existing craniopharyngioma (CP), Rathkès cleft cyst (RCC) or pituitary adenoma (PA), or represent a stage in xanthomatous hypophysitis evolution. "Pure SXG" are independent of a preexisting lesion. A 70 year old male patient, laryngeal cancer survivor, presented with central diabetes insipidus (CDI). MRI revealed an intra-suprasellar mass of uncertain origin. Transsphenoidal surgery resulted in an efficient lesion resection with maximal pituitary sparing. Pathological report has confirmed SXG without conclusive identification of preexisting sellar lesion. Age at presentation and gender were atypical for SXG. The most frequent presenting signs of SXG were absent. Most SXG are initially misdiagnosed as CP, RCC or PA. Preoperative clinical and radiological uncertainty may impact operative planning. Differentiating from CP is crucial, due to divergent operative target goals and prognosis. Intraoperative frozen section analysis could guide surgical extensiveness. Close collaboration must include endocrinologist, neuroradiologist, neurosurgeon and pathologist. Quantity and quality of provided tissue are essential for avoiding bias in pathohistological analysis of cystic or heterogenous lesions. Awareness is needed of new pathological entities in the sellar-parasellar region. SXG should be considered in differential diagnosis of CDI-causing sellar lesions.

Subchronic methionine load induces oxidative stress and provokes biochemical and histological changes in the rat liver tissue.

The aim of this study was to assess the effects of L-cysteine (Cys) (7 mg/kg) and N-acetyl-L-cysteine (NAC) (50 mg/kg) in the rat liver caused by subchronic i.p. application of methionine (Met) (0.8 mmol/kg) during 21 days. Malondialdehyde (MDA) concentration, glutathione content (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and acetylcholinesterase (AchE) activities were determined in the liver tissue and activities of liver enzymes (AST, ALT, ALP, and GGT) and concentrations of total proteins and albumin were determinated in plasma/serum. Catalase, superoxide dismutase, and acetylcholinesterase activities were increased by Cys and NAC. Met caused periportal mononuclear infiltration and rare focal necrosis of hepatocytes. In Cys- and NAC-supplemented groups, intracellular edema and microvesicular fatty changes without necrosis were noticed. We observed decrease of AST, ALT, and ALP activity in the methionine-treated group. Our results indicate that Cys and NAC application can increase activity of antioxidative enzymes and prevent intensive histological changes in liver in condition of subchronic methionine exposure.

The role of oxidative stress as a risk factor for rupture of posterior inferior cerebellar artery aneurysms.

Cerebral aneurysm affects 2-5% of the population and posterior inferior cerebellar artery (PICA) aneurysms account for 1-3% of all intracranial aneurysms. Oxidative stress is known to contribute to the progression of cerebrovascular disease and it may be increased by inflammation, a key contributor to cerebral aneurysm development and rupture. The aim of this study was to examine the role of overall oxidative stress as a risk factor for rupture of PICA aneurysms. This study included 29 patients with PICA aneurysms: 18 ruptured and 11 unruptured. We determined catalase, malondialdehyde, myeloperoxidase and carbonyl groups in homogenates of excised aneurysm tissue after surgery and plasma levels of C reactive protein and fibrinogen. The patient's age and sex, size of aneurysms, multiplicity, history of previous subarachnoidal hemorrhage (SAH) and risk factors for oxidative stress such as hypertension and smoking were compared between unruptured and ruptured aneurysms. Maximal diameter and SAH history were independent predictors for aneurysm rupture. Activity of catalase was decreased while activity of myeloperoxidase, levels of malondialdehyde, carbonyl groups in aneurismal tissue and plasma levels of C reactive protein and fibrinogen were increased in patients with ruptured aneurysms. Plasma levels of C reactive protein and fibrinogen showed positive correlation with myeloperoxidase, malondialdehyde, carbonyl groups and PHASES score and negative correlation with catalase. These findings suggest that oxidative stress may contribute importantly to rupture of PICA aneurysms and plasma levels of C reactive protein and fibrinogen correlate with oxidative stress markers in tissue.

Extracranial meningiomas in the head-and-neck region: A 15 years' experience.

Meningiomas constitute a large group of tumors of the central nervous system, with the prevalence of 18%-20%. Extracranial localization of meningeomas could appear due to their extracranial origin or due to the spreading of intracranial meningeomas. In this paper, we present our 15 years' experience in the diagnosis and treatment of extra- and intracranial meningiomas invading the head-and-neck region. In the period from 2001 to 2016 at our clinic, there were five patients (three men and two women), with meningiomas of extracranial origin or meningiomas of intracranial origin, spreading into the head-and-neck region. All patients were surgically treated, with the addition of adjuvant radiation therapy in some of the cases. Postoperative and postirradiation complications were described as well.

Flexible memory-alloy instrumentation for unilateral transpedicular kyphoplasty and guided cement augmentation of the thoracic spine.

The purpose of this novel study was to investigate the feasibility of unilateral transpedicular balloon kyphoplasty particularly of the upper thoracic vertebrae using an 11- gauge balloon and cement inserter, and to study the morphological parameters of the thoracic spine pedicles. We used four fresh frozen cadaveric thoracic spines with intact rib cages and skin for kyphoplasty from T1 to T12 vertebrae under C-arm fluoroscopy. The most limiting width of the pedicles 2.46+/-0.32mm was in the middle levels (T5-T8). The absolute minimum height of the pedicles was at T1 (3.80-3.87mm). All regions of the vertebral body were effectively targeted for cement augmentation. The average cement load of all the vertebral bodies was 43,22%. Using the kyphoplasty technique in combination with the pre-bent 11mm memory-alloy cement inserter allowed targeting of the desired position of the vertebral body for effective vertebral body cement augmentation.

Should ALPPS be Used for Liver Resection in Intermediate-Stage HCC?

BACKGROUND: Extended liver resections in patients with hepatocellular carcinoma (HCC) are problematic due to hepatitis, fibrosis, and cirrhosis. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) has been promoted as a novel method to induce hypertrophy for patients with extensive colorectal liver metastases, but outcomes in HCC have not been well investigated. METHODS: All patients registered in the international ALPPS Registry ( www.alpps.org ) from 2010 to 2015 were studied. Hypertrophy of the future liver remnant, perioperative morbidity and mortality, age, overall survival, and other parameters were compared between patients with HCC and patients with colorectal liver metastases (CRLM). RESULTS: The study compared 35 patients with HCC and 225 patients with CRLM. The majority of patients undergoing ALPPS for HCC fall into the intermediate-stage category of the Barcelona clinic algorithm. In this study, hypertrophy was rapid and extensive for the HCC patients, albeit lower than for the CRLM patients (47 vs. 76 %; p < 0.002). Hypertrophy showed a linear negative correlation with the degrees of fibrosis. The 90-day mortality for ALPPS used to treat HCC was almost fivefold higher than for CRLM (31 vs. 7 %; p < 0.001). Multivariate analysis showed that patients older than 61 years had a significantly reduced overall survival (p < 0.004). CONCLUSION: The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

Relationships among hygiene indicators in take-away foodservice establishments and the impact of climatic conditions.

AIMS: This paper examined the relationships among hygiene indicators in take-away foodservice establishments and the impact of climatic conditions. METHODS AND RESULTS: A total of 7545 samples were collected encompassing 2050 from food handlers' (HF) hands, 3991 from stainless steel food contact surfaces (FCS) and 1504 samples from plastic FCS. The study covered a period of 43 months. Hygiene-indicator bacteria (total plate count, Enterobacteriaceae Staphylococcus) were determined from the samples collected from 559 different take-away establishments. Climatic conditions were evaluated in respect to the outside temperature, pressure, humidity and precipitation. Logistic regression confirmed that the presence of precipitation was associated with an increased likelihood of exhibiting both Enterobacteriaceae and Staphylococcus on HF' hands as well as exhibiting Enterobacteriaceae on both types of FCS. Numerable Enterobacteriaceae and Staphylococcus levels on HF' hands were detected when higher outside temperatures and higher precipitations occurred. Higher outside temperatures were observed when Enterobacteriaceae were detected on both plastics (P < 0·05) and stainless steel (P > 0·05). Higher precipitation was observed when Enterobacteriaceae was detected on stainless steel while in contrast, this indicator was detected on plastics in periods with lower precipitation. CONCLUSIONS: This research confirms relationships between hygiene indicators in take-aways and climatic conditions, mostly temperature and precipitation. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides another perspective into the possible nature of cross-contamination and foodborne outbreaks originating in foodservice establishments and brings to attention the necessity of analysing various climatic conditions.

Umbilical endometriosis associated with large umbilical hernia. Case report.

Umbilical endometriosis is a rare condition, usually following laparoscopic and surgical procedures involving the umbilicus.Spontaneous umbilical endometriosis occurring without any previous abdominal or uterine surgery is extremely rare. The maximal depth of penetration of the umbilical endometriosis described is up to fascial level. There have been only two cases of endometriosis reported arising within umbilical hernia. The authors report a case of a patient with spontaneous umbilical endometriosis associated with a large umbilical hernia, treated by surgical excision and mesh repair of the abdominal wall. To the best of our knowledge, this is the first described case of the association of umbilical endometriosis with a large umbilical hernia that requires prosthetic mesh repair of the abdominal wall defect.

Role of plasma exchange in autoimmune hyperthyroidism complicated by severe tiamazol-induced cholestatic jaundice.

Therapeutic plasma exchange (TPE) is an alternative treatment for hyperthyroidism, resulting in a rapid decline in plasma thyroid hormones and anti-thyroid antibodies. TPE has also been used both in primary liver disease and in drug-induced cholestasis. Data on thyrotoxic patients with severe hepatic complications are scarce. Cholestasis induced by imidazol-derived anti-thyroid drugs is extremely rare. The use of TPE for treating this complication was not previously reported. We report the experience of one such patient with a favorable response to TPE. A 45-year-old male patient with Graves' disease, presented with severe jaundice and extremely high serum bilirubin levels due to hepatotoxicity induced by tiamazol. Through extensive investigation primary liver disease, including viral, metabolic, neoplastic and autoimmune disease, as a cause of cholestasis were all ruled out. The patient underwent total of 6 TPEs which in combination with low dose of glucocorticoids and standard supportive measures, resulted in normalization of thyroid hormones and normal liver function tests. TPE provided a safe, rapid and effective treatment of severe drug-induced cholestasis and auto immune hyperthyroidism. From this case we conclude that TPE should be considered as a valuable alternative therapeutic option in thyrotoxic patients with severe complications. Guidelines and indication criteria for TPE treatment in patients with hyperthyroidism are still lacking.

Intermittent or continuous occlusion of hepatic inflow.

THE AIM OF THE STUDY: The aim was to compare the effects of intermittent and continuous inflow occlusion on liver I/R injury in an experimental model. METHOD: The experiment was done using the Wistar rats that underwent continuous and intermittent inflow liver vascular occlusion. Blood and liver tissue samples were taken and parameters of hepatic ischemia/reperfusion injury were analyzed and compared. RESULTS: Serum activities of ALT, AST and LDH were significantly higher and ALP activity and albumin concentration were markedly lower in rats with continuous liver ischemia. Also, histopathological examination revealed more severe changes in animals with continuous liver vascular occlusion. CONCLUSION: The results of biochemical assay and histopathological examination were concurrent, both indicating more serious parenchymatous damage caused by continuous hepatic pedicle clamping. Study results clearly demonstrated a better tolerance of the liver to intermittent Pringle maneuver (Tab. 1, Fig. 5, Ref. 9).

Correlation of nuclear morphometry of primary melanoma of the skin with clinicopathological parameters and expression of tumor suppressor proteins (p53 and p16(INK4a)) and bcl-2 oncoprotein.

PURPOSE: To determine the correlation of nuclear morphometry of primary cutaneous malignant melanoma (CMM) with clinicopathological parameters and the expression of p53, p16INK4a, and bcl-2. METHODS: Image analysis and computerized nuclear morphometry were used in a series of 53 primary CMM (nodular melanoma/NM, N=33, and superficially spreading melanoma/SSM, N=20). The clinicopathological parameters determined for each tumor were histological type, maximal tumor diameter, Breslow thickness, Clark level, ulceration, mitotic index (MI) and pathological disease stage. Measured nuclear features included size, shape and optical density (OD). The results were correlated with the expression of p53, p16INK4a and bcl-2. RESULTS: Significant differences between NM and SSM were found for the nuclear area, OD, and perimeter (p<0.05). MI showed significant correlations with nuclear area, perimeter and Feret diameter (p<0.05). In relation to the Clark level, significant differences were found for OD (p<0.01) and circularity of nuclei (p<0.05) between levels II and IV, while the Breslow thickness was not significantly correlated with nuclear morphometric variables. Significantly negative correlations were observed between OD and the expression of p53 and bcl-2, while significant positive correlation was found between the nuclear circularity and p53 immunoreaction intensity. There was no significant correlation between the expression of p16INK4a protein and karyometric variables. CONCLUSION: OD and circularity are significantly correlated with p53 and bcl-2, and nuclear area with MI. These karyometric variables may determine a more aggressive phenotype of melanoma cells.

Tuberculous lymphadenitis as a cause of obstructive jaundice.

Obstructive jaundice secondary to abdominal tuberculosis is extremely rare. We present a patient with jaundice secondary to compression of the common bile duct by TB lymphadenitis. A 49-year-old woman was admitted to our department for nausea,epigastric pain and jaundice. Abdominal ultrasonography and computer tomography scan were suggestive of stenosis of the distal common bile duct caused by a retro pancreatic mass. At laparotomy, an enlarged lymph node behind the head of the pancreas was found, causing compression and stenosis of the distal parts of the choledochus. The lymph node frozen section analysis showed epithelioid granuloma with caseous necrosis,strongly suggesting tuberculous origin. Choledochoduodenal anastomosis was performed. Definitive pathohistological examination confirmed TB lymphadenitis. ATB should be considered as a potential cause of jaundice especially in immuno compromised patients and endemic areas. Diagnosing abdominal tuberculosis can be a challenging task. No satisfactory diagnostic gold standard is available so that in most cases the diagnosis cannot be reached before exploratory laparotomy.Early detection enables successful conservative treatment and eliminates the necessity of surgery.