George Zografos

Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer

Adiponectin has been associated with colorectal cancer (CRC) risk. This study aims to investigate the association of both adiponectin and tissue expression of its receptors with CRC risk as well as clinicopathological characteristics, notably stage and grade. Determination of serum adiponectin and immunohistochemical expression of adiponectin receptors in adenocarcinoma/normal colorectal tissue was performed in samples from 104 newly diagnosed CRC patients and 208 age- and sex-matched controls. Multiple logistic regression odds ratios and 95% confidence intervals for CRC risk were derived, controlling for a series of covariates. Serum adiponectin was negatively associated with CRC risk (odds ratio, 0.72; confidence interval, 0.53-0.99) and also with tumor grade (P = .05). Expression of both adiponectin receptors was stronger in adenocarcinoma vs normal tissue (P = .001). AdipoR1 expression was negatively associated with nodal stage (P = .03); AdipoR2 expression was positively associated with tumor, node, metastasis stage (P = .01). Established positive associations with red meat consumption and diabetes, and negative associations with physical exercise and plant food consumption were confirmed along with a more than 60% higher risk associated with central obesity. Adiponectin levels and tissue expression of hormonal receptors seem to be associated not only with CRC risk but also with components of clinicopathological characteristics; given power limitations, these results should be interpreted with caution. The exact nature of the association and the underlying pathophysiological mechanisms need to be further examined in large prospective studies assessing adiponectin and its receptors as novel targets for exploring CRC growth.

Evidence of Primary Aldosteronism in a Predominantly Female Cohort of Normotensive Individuals: A Very High Odds Ratio for Progression into Arterial Hypertension

CONTEXT Primary aldosteronism (PA) is an established cause of hypertension, whereas high-normal serum aldosterone levels have been linked to an increased risk for hypertension. OBJECTIVE We aimed to define the post-fludrocortisone-dexamethasone suppression test (FDST) normal cutoff values of aldosterone and the aldosterone to renin ratio and evaluate the presence of PA in normotensive individuals. DESIGN This study was designed as a case-control study. SETTING The study was performed in a tertiary general hospital. PATIENTS One hundred normotensive participants (80 females), mean age 53 years, were studied. MAIN OUTCOME MEASURES All participants underwent baseline biochemical and hormonal evaluation, FDST, and adrenal computerized tomography. Blood pressure was assessed at baseline and after 5 years. RESULTS Sixty-nine participants with normal adrenal computerized tomography who remained normotensive after 5 years were used as a control population to calculate the cutoff values of adequate aldosterone suppression. PA was defined as a combination of post-FDST aldosterone to renin ratio of 0.93 ng/dL · μU/mL or greater (100% sensitivity and 96% specificity) and post-FDST aldosterone of 2.96 ng/dL or greater (100% sensitivity and 61% specificity on receiver-operating characteristic analysis). Thirteen of 100 participants had PA at baseline and 11 (85%) developed hypertension, whereas only 20 of 87 without PA (23%) developed hypertension at 5 years [odds ratio (OR) 18.42, 95% confidence intervals (CI) 3.76-90.10, P < .0001]. Logistic regression analysis showed a positive relation of PA [odds ratio (OR) 16.30, confidence interval (CI) 1.78-150.30, P = .01] and a negative relation of serum potassium (OR 0.39, CI 0.19-0.79, P = .01) with the development of hypertension. CONCLUSIONS Normotensive PA represents a clinical entity referring to normotensive individuals with PA who are at increased risk for hypertension.

Total vascular exclusion for liver resections: Pros and cons

Dramatic improvements in morbidity and mortality rates following liver resections have been reported in the past decade. Consequently, the indications for hepatectomy are becoming more liberal. Many techniques of liver resection with or without vascular clamping have been reported with excellent clinical results. Total vascular exclusion (TVE) of the liver during parenchymal transection has been advocated susceptible to increase the resectability of tumors that might not be safely approached by other techniques. Cirrhotic livers are probably more vulnerable to ischemic injury related to TVE than normal livers. The indications and technical and metabolic aspects of the technique are reviewed. J. Surg. Oncol. 1999;72:50–56.

Subclinical Cushing's syndrome: Current concepts and trends

Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5–20% of adrenal incidentalomas present subclinical cortisol hypersecretion which is characterized by subtle alterations of the hypothalamicpituitary-adrenal axis due to adrenal autonomy. This disorder has been described as subclinical Cushing’s syndrome, since there is no typical clinical phenotype. The diagnosis of subclinical Cushing’s syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (DST) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical Cushing’s syndrome. DST is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hypersecretion and these morbidities. Therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. The optimal management of patients with subclinical Cushing’s syndrome is not yet defined. The conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.

Primary aldosteronism in hypertensive patients: clinical implications and target therapy

The prevalence of primary aldosteronism (PA) in hypertensive patients varies according to diagnostic testing and ascertained normal cut‐offs. The aim of this case–control study was to confirm the high prevalence of PA in a large hypertensive population and evaluate the antihypertensive effect of mineralocorticoid receptor antagonists (MRA) treatment.

Neoadjuvant therapy for advanced pancreatic neuroendocrine tumors: an emerging treatment modality?

OBJECTIVE Complete surgical resection is the only potentially curative treatment of localized pancreatic neuroendocrine tumors. Unfortunately, a significant proportion of these patients present with unresectable locally advanced tumors or massive metastatic disease. Recently, a new therapeutic approach for this subset of patients has emerged consisting of neoadjuvant therapy followed by surgical exploration in responders. DESIGN We searched MEDLINE for the purpose of identifying reports regarding neoadjuvant treatment modalities for advanced pancreatic neuroendocrine tumors. RESULTS We identified 12 studies, the vast majority of which were either case reports or small case series. Treatment options included chemotherapy, radiotherapy, peptide receptor radionuclide therapy, biological agents or various combinations of them. CONCLUSIONS Increasing evidence supports the application of neoadjuvant protocols in advanced pancreatic neuroendocrine tumors aiming at tumor downsizing, thus rendering curative resection feasible. Given that prospective and controlled randomized clinical trials from high-volume institutions are not feasible, expert panel consensus is needed to define the optimal treatment algorithm.

Differential Expression of β-Catenin, EGFR, CK7, CK20, MUC1, MUC2, and CDX2 in Intestinal and Pancreatobiliary-Type Ampullary Carcinomas.

Introduction: The purpose of this study was to associate immunohistochemical expression of β-catenin, EGFR, CK7, CK20, MUC1, MUC2, and CDX2 in ampullary adenocarcinomas with the type of differentiation and prognosis. Methods: Forty-seven patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy with curative intent from 1997 to 2014 were included in this study. Nine patients with perioperative death were included in the association analysis but excluded from survival analysis. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers. Results: Eighteen carcinomas were classified as intestinal type and 29 carcinomas as pancreatobiliary type. Univariate analysis revealed that CK20 and CDX2 expression correlates with intestinal type, whereas MUC1 positivity indicates pancreatobiliary type. A marginally significant trend was shown for intestinal-type tumors toward larger size and more frequent MUC2 expression. Using multivariate analysis CK20 (P = .003) and MUC1 (P = .004) were identified as independent predictors of the intestinal and pancreatobiliary types, respectively. Mean and median survival was 90.3 and 55 months, respectively. Overall 5-year survival rate was 48%. On univariate survival analysis, overall survival was adversely influenced by the number of infiltrated lymph nodes, elevated Ca19-9 serum levels, jaundice, poor differentiation, T4 stage, N1 stage, TNM stage III, and CDX2 immunonegativity. Multivariate analysis identified TNM stage as the only independent prognostic factor in ampullary adenocarcinoma (P = .048). Conclusions: Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied had prognostic significance.

Circulating thyroid cancer biomarkers: Current limitations and future prospects

Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly to the use of more sensitive diagnostic modalities. Ultrasound‐guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large‐scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small‐scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.

Laparoscopic surgery for pancreatic insulinomas: an update.

Insulinomas are the most common functioning neuroendocrine tumors of the pancreas, occurring in almost 1–4 per 1 million persons each year. In contrast to other pancreatic neuroendocrine tumors, they are usually benign and solitary at the time of diagnosis. Due to their benign nature, surgical excision is the treatment of choice, with excellent long-term results. The introduction of minimally invasive techniques in the surgical treatment of insulinoma has been gaining popularity due to shorter length of hospital stay and better cosmetic results, with serious complications being comparable to those of open surgery. Preoperative localization is of paramount importance in the determination of the appropriate surgical approach. Many invasive and non-invasive methods exist for localization of an insulinoma. A combination of these modalities is usually adequate to preoperatively localize the vast majority of tumors. Laparoscopic ultrasound is mandatory to localize these tumors intraoperatively. Despite extensive experience in highly specialized centers producing encouraging results, no randomized trials have been realized to conclusively validate these case series, this partly due to the rarity of insulinoma in the population. In this article we present the current state of laparoscopic management of insulinoma delineating still unanswered issues and we underscore some of the technical details of the most common laparoscopic procedures employed.

The acute effect of erythropoietin on mean corpuscular hemoglobin concentration levels during hypoxia - reoxygenation injury in rats

Background: The aim of this experimental study was to examine the effect of erythropoietin on rat model and particularly in an hypoxia reoxygenation (HR) protocol. The effect of that molecule was studied hematologically using mean corpuscular hemoglobin concentration (MCHC) levels. Materials and Methods: 40 rats of mean weight 247.7 g were used in the study. MCHC levels were measured at 60 min (groups A and C) and at 120 min (groups B and D) of reoxygenation. Erythropoietin (Epo) was administered only in groups C and D. Results: Epo administration significantly increased the MCHC levels by 1.73% +0.50% (P = 0.006). Reoxygenation time non-significantly increased the MCHC levels by 0.17%+0.56% (P = 0.7555). However, erythropoietin administration and reoxygenation time together produced a significant combined effect in increasing the MCHC levels by 0.89% +0.31% (P = 0.0061). Conclusion: Erythropoietin administration whether it interacted or not with reoxygenation time has significant increasing short - term effects on recovery pathophysiology of MCHC levels.