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.

Interleukins as markers of inflammation in malignant and benign thyroid disease.

BACKGROUND: Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation. OBJECTIVE: This study aims to investigate the role of inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions. METHODS: Serum levels of ten interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology. RESULTS: Serum IL-1ß, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1ß, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90). CONCLUSIONS: Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.

Laparoscopic adrenalectomy in patients with subclinical Cushing syndrome.

BACKGROUND: Subclinical Cushing syndrome in patients with adrenal incidentalomas has been associated with an increased prevalence of the metabolic syndrome and cardiovascular risk. The management of these patients, be it conservative or surgical, is still debated, but there is accumulating evidence that surgery is best and that laparoscopic adrenalectomy, when possible, is the most preferred procedure. Here we present the short- and long-term results of laparoscopic adrenalectomy for subclinical Cushing syndrome and determine the effect of this procedure on components of the metabolic syndrome. METHODS: Twenty-nine patients, 8 men and 21 women with adrenal incidentalomas and subclinical Cushing syndrome who underwent laparoscopic adrenalectomy, were studied retrospectively. They had undergone postoperative follow-up for improvement or worsening of their arterial blood pressure, body weight, and fasting glucose level for a mean period of 77 months. RESULTS: Preoperatively, 17 patients (58.6 %) had arterial hypertension, 14 (48.3 %) had a body mass index exceeding 27 kg/m(2), and 12 (41.4 %) had diabetes mellitus. Postoperatively, a decrease in mean arterial pressure was found in 12 patients (70.6 %), a decrease in body mass index in 6 patients (42.9 %), and an improvement in glycemic control in 5 patients (41.7 %). CONCLUSIONS: Laparoscopic adrenalectomy is beneficial in many patients with subclinical Cushing syndrome because it reduces arterial blood pressure, body weight, and fasting glucose levels. Prospective randomized studies are needed to compare laparoscopic adrenalectomy with a conservative approach and to confirm these results.

Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas.

OBJECTIVE: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6 to 16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone saline infusion test (DSIT) by applying both tests on the same subjects. METHODS: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls with normal adrenal imaging. Serum cortisol, aldosterone, and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean ± 2 s.d. values from the controls, we defined the upper normal limits for cortisol, aldosterone, and PRC for both the SIT and DSIT. RESULTS: In the controls, the post-DSIT aldosterone levels and the ARR were approximately two-fold and three-fold lower, respectively, than the corresponding post-SIT values (all P = 0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion (ACS). Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. CONCLUSIONS: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk of developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant ACS.

Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series.

PURPOSE: Pheochromocytomas are rare tumors and biochemically silent ones with normal catecholamine levels are even rarer. Up to date, biochemically inactive pheochromocytomas are poorly investigated. We aimed to systematically assess the pre- and peri-operative characteristics and the outcomes of patients with these tumors who had been treated and followed-up in 2 tertiary centers. METHODS: Clinical, laboratory and imaging data, treatment outcomes and follow-up of biochemically silent pheochromocytoma patients were recorded. RESULTS: Ten patients (5 men) [median age at diagnosis 52.5 years (24-72)] were included. Adrenal masses were incidentally discovered in all patients except from one who presented with pheochromocytoma-related manifestations. Twenty-four-hour urine metanephrine and normetanephrine levels were in the low-normal, normal and high-normal range in 4, 4 and 2 patients and in 1, 6 and 3 patients, respectively. Tumors were unilateral [median size 46 mm (17-125)] and high density on pre-contrast CT imaging or high signal intensity on T2-weighted MRI scans were found in all cases. Pre-operatively, 5 patients were treated with phenoxybenzamine [median total daily dose 70 mg (20-100)]. Intra-operatively, 4 patients developed hypertension requiring vasodilator administration and 8 developed hypotension; vasoconstrictors were required in 5 cases. One patient, not pre-operatively treated with phenoxybenzamine, developed Takotsubo cardiomyopathy. During a median 24-month (12-88) follow-up period, one patient had disease progression. CONCLUSIONS: The majority (90%) of patients with biochemically silent pheochromocytomas developed hemodynamic instability during adrenal surgery. In patients with biochemically silent adrenal lesions and a high suspicion index for pheochromocytoma based on tumor imaging characteristics, pre-operative alpha-blockade treatment may be advisable.

Cholangiocarcinoma: principles and current trends.

BACKGROUND: Cholangiocarcinoma (CCA) is a lethal cancer of the biliary epithelium, originating from the liver (intrahepatic), at the confluence of the right and left hepatic ducts (hilar) or in the extrahepatic bile ducts. It is a rare malignancy associated with poor prognosis. DATA SOURCES: We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008. The search terms used were related to "cholangiocarcinoma" and its "treatment". Although no language restrictions were imposed initially, for the full-text review and final analysis, our resources only permitted the review of articles published in English. This review deals with the treatment of cholangiocarcinoma, the principles and the current trends. RESULTS: The risks and prognostic factors, symptoms and differential diagnosis are thoroughly discussed. In addition, the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography, digital image analysis, fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed. Moreover, the treatment of CCA is discussed. CONCLUSIONS: The only curative treatment available is surgical management. Unfortunately, many patients present with unresectable tumors, the majority of whom die within a year of diagnosis. Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity. However, in selected cases and where indicated, appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy.

Surgical treatment outcome of primary aldosteronism assessed using new modified diagnostic tests.

PURPOSE: Primary aldosteronism (PA) is the most frequent type of endocrine hypertension. In our previous studies, we introduced two modified diagnostic tests for PA, the post-dexamethasone saline infusion test (DSIT) and the overnight dexamethasone, captopril, and valsartan test (DCVT). In this study, we aimed to validate both tests in respect to the biochemical and clinical response of a cohort of hypertensive patients in pre- and post-surgical setting. METHODS: We retrospectively studied 41 hypertensive patients (16 males), with a median (IQR, range) age of 50 (16, 35-74) years and positive histology for adrenal adenoma. Preoperatively, all patients had a single adenoma on CT and a diagnosis of PA with either DSIT or DCVT. The defined daily dose (DDD) of hypertensive drugs was assessed pre- and postoperatively. DSIT or DCVT and basal ARR were reassessed postoperatively. RESULTS: Two of the 41 patients failed to suppress aldosterone post-surgery, leading to a post-adrenalectomy biochemical cure rate of 95%, while blood pressure was improved in 36 patients, leading to a clinical cure rate of 88% as assessed by the DDD methodology. CONCLUSIONS: The present study was a proof-of-concept process to validate two modified diagnostic tests for PA in clinical practice. These tests, used to diagnose a group of patients with PA, successfully assessed their biochemical cure post-adrenalectomy at rates similar to those reported in the literature.

Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends.

BACKGROUND: Neurofibromatosis Type 1(NF-1) has autosomal dominant inheritance with complete penetrance, variable expression and a high rate of new mutation. Pheochromocytoma occurs in 0.1%-5.7% of patients with NF-1. CASE PRESENTATION: We present the case of a 37-year-old patient with laparoscopically resected pheochromocytoma. He was investigated for hypertension, flushing and ectopic heart beat. Abdominal CT and MRI revealed a mass measuring 8 x 4 cm in the right adrenal gland. The diagnosis of pheochromocytoma was confirmed by elevated 24-hour urine levels of VMA, metanephrines and catecholamines as well as positive MIBG scan. The patient presented with classic clinical features of NF-1, which was confirmed by pathologic evaluation of an excised skin nodule. The patient underwent laparoscopic right adrenalectomy through a transabdominal approach and was discharged on the second postoperative day, being normotensive. The patient is normotensive without antihypertensive therapy 11 years after the procedure. CONCLUSION: Nowadays in the era of laparoscopy, patients with pheochromocytoma reach the operating theatre easier than in the past. Despite, the feasibility and oncological efficacy of the laparoscopic approach to the adrenals, continued long term follow-up is needed to establish the minimally invasive technique as the preferred approach. Furthermore, these patients should be further investigated for other neoplasias and stigmata of other neurocutaneous syndromes, taking into account the association of the familial pheochromo-cytoma with other familial basis inherited diseases.

Pancreatic insulinoma: current issues and trends.

BACKGROUND: Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms. The incidence in general population is 1-4 per 1,000,000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features, and the current WHO classification has been re-evaluated. This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas. DATA SOURCES: A Medline search using terms "insulinoma", "treatment" and "neuroendocrine tumors" was conducted. Additional references were sourced from key articles. RESULTS: Surgery is the treatment of choice for insulinoma and has an extremely high success rate. Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment. Preoperative localization is necessary for planning the surgical approach. Many methods exist for localization of an insulinoma and can be invasive and non-invasive. The combination of biphasic thin section helical CT and endoscopic ultrasonography (EUS) has an almost 100% sensitivity in localizing insulinomas. Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors. EUS-guided fine needle tattooing is an alternative method of localization in case of lack of laparoscopic ultrasound. CONCLUSION: Laparoscopic resection for benign insulinomas is the procedure of choice, whereas pancreatectomy is reserved for large, potentially malignant tumors.

Swordfish bill injury involving abdomen and vertebral column: case report and review.

BACKGROUND: Penetrating injuries of the abdomen and spinal canal that involve organic material of animal origin are extremely rare and derive from domestic and wild animal attacks or fish attacks. CASE PRESENTATION: In this case report we present the unique, as far as the literature is concerned, unprovoked woman's injury to the abdomen by a swordfish. There are only four cases of swordfish attacks on humans in the literature - one resulted to thoracic trauma, two to head trauma and one to knee trauma, one of which was fatal - none of which were unprovoked. Three victims were professional or amateur fishermen whereas in the last reported case the victim was a bather as in our case. Our case is the only case where organic debris of animal's origin remained in the spinal canal after penetrating trauma. CONCLUSIONS: Although much has been written about the management of penetrating abdominal and spinal cord trauma, controversy remains about the optimal management. Moreover, there is little experience in the management of patients with such spinal injuries, due to the fact that such cases are extremely rare. In this report we focus on the patient's treatment with regard to abdominal and spinal trauma and present a review of the literature.

Laparoscopic resection of large adrenal tumors.

BACKGROUND: Laparoscopic adrenalectomy has rapidly replaced open adrenalectomy as the procedure of choice for benign adrenal tumors. It still remains to be clarified whether the laparoscopic resection of large (≥ 8 cm) or potentially malignant tumors is appropriate or not due to technical difficulties and concern about local recurrence. The aim of this study was to evaluate the short- and long-term outcome of 174 consecutive laparoscopic and open adrenalectomies performed in our surgical unit. METHODS: Our data come from a retrospective analysis of 174 consecutive adrenalectomies performed on 166 patients from May 1997 to December 2008. Fifteen patients with tumors ≥ 8 cm underwent laparoscopic adrenalectomy. Sixty-five patients were men and 101 were women, aged 16 years to 80 years. Nine patients underwent either synchronous or metachronous bilateral adrenalectomy. Tumor size ranged from 3.2 cm to 27 cm. The largest laparoscopically excised tumors were a ganglioneuroma with a mean diameter of 13 cm and a myelolipoma of 14 cm. RESULTS: In 135 patients, a laparoscopic procedure was completed successfully, whereas in 14 patients the laparoscopic procedure was converted to open. Seventeen patients were treated with an open approach from the start. There were no conversions in the group of patients with tumors > 8 cm. Operative time for laparoscopic adrenalectomies ranged from 65 minutes to 240 minutes. In the large adrenal tumor group, operative time for laparoscopic resection ranged from 150 minutes to 240 minutes. The postoperative hospital stay for laparoscopic adrenalectomy ranged from 1 day to 2 days (mean, 1.5) and from 5 days to 20 days for patients undergoing the open or converted procedure. The mean postoperative stay was 2 days for the group with large tumors resected by laparoscopy. CONCLUSION: Laparoscopic resection of large (≥ 8 cm) adrenal tumors is feasible and safe. Short- and long-term results did not differ in the 2 groups.

Solitary fibrous tumor of the liver expressing CD34 and vimentin: a case report.

A case of a successfully treated solitary fibrous tumor (SFT) of the liver is reported. An 82-year-old female presented with left upper abdominal discomfort, a firm mass on palpation, and imaging studies revealed a large tumor, 15 cm in diameter, arising from the left lobe of the liver. A formal left hepatectomy was performed. Microscopic evaluation showed spindle and fibroblast-like cells within the collagenous stroma. Immunohistochemistry disclosed diffuse CD34 and positive vimentin, supporting the diagnosis of a benign SFT. The patient remained well 21 months after surgery. SFT of the liver is a very rare neoplasm of mesenchymal origin. In most cases it is a benign lesion, although some may have malignant histological features and recur locally or metastasize. With less than 30 reported cases in the literature, little can be said regarding its natural history or the benefits of adjuvant radiochemotherapy. Complete surgical resection remains the cornerstone of its treatment.

Open and laparoscopic approach in incisional hernia repair with ePTFE prosthesis.

BACKGROUND: The aim of this retrospective study was to analyze the results of incisional hernia laparoscopic and open surgery, focusing on the morbidity and postoperative implications. MATERIALS AND METHODS: A group of 106 (42 men, 64 women) patients suffering from incisional hernias were treated with either a laparoscopic (30) or an open (76) placement of a prosthetic mesh between January 1997 and December 2004. The age and gender of the patients, the size and type of the mesh, operation note, the length of postoperative hospital stay, and morbidity were recorded. RESULTS: An expanded polytetrafluoroethylene (ePTFE) mesh was used in 103 patients, whereas a polypropylene mesh was used in 3 patients. In the open technique, 3 patients with the ePTFE prosthetic material developed a mesh infection and required a mesh removal, which was easily performed under local anesthesia. Moreover, 2 patients from the same group developed a hernia recurrence. As for the laparoscopic approach, the only complication observed was one hernia recurrence. Finally, it should be mentioned that 1 patient with a polypropylene mesh developed a colocutaneous fistula. CONCLUSIONS: The benefits of the laparoscopic mesh technique, compared to the open technique, include a shorter hospital stay, less postoperative pain, and possibly, a reduction in wound and mesh complications. Regarding the recurrence rate, the two techniques show similar results.

Differential Expression of ß-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 ß-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.

Laparoscopic surgery for adrenal tumors. A retrospective analysis.

OBJECTIVE: Laparoscopic adrenalectomy has rapidly replaced open adrenalectomy as the procedure of choice for benign adrenal tumors. The aim of this study was to evaluate the short- and long-term results of 100 consecutive laparoscopic and open adrenalectomies performed during a period of 8.5 years in our Surgical Unit. DESIGN: A retrospective analysis of patients operated on for adrenal tumors was conducted. From May 1997 to August 2005, one hundred adrenalectomies were performed on 95 patients. Five patients underwent either synchronous or metachronous bilateral adrenalectomy. There were 38 men and 57 women, aged 16 to 80 years. The size of tumors in our series ranged from 3.2 to 27 cm. The largest laparoscopically excised tumor was a ganglioneuroma with a diameter of 13 cm. RESULTS: In 73 patients laparoscopic procedure was completed successfully. In 8 cases the laparoscopic procedure was converted to open. Fourteen patients were treated with open approach. One patient with pheochromocytoma succumbed following pulmonary embolus. In one patient with morbid obesity, Cushing's syndrome, and bilateral adrenal macronodular hyperplasia, the left laparoscopic adrenalectomy was complicated by a low output pancreatic fistula, conservatively treated. All other patients had an uneventful course. Operative time for laparoscopic adrenalectomies ranged from 65 to 180 minutes. The average postoperative hospital stay for laparoscopic adrenalectomy ranged from 1 to 2 days (1.5 days), versus 5 to 20 days for patients who underwent open or converted procedure. CONCLUSIONS: Laparoscopic adrenalectomy should be the treatment of choice for all benign adrenal tumors. Laparoscopic resection of large adrenal tumors necessitates experience in open surgery and advanced laparoscopic surgery.

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.

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.

Differentiation and prognostic markers in ampullary cancer: Role of p53, MDM2, CDX2, mucins and cytokeratins.

INTRODUCTION: Subclassification of ampullary adenocarcinomas into intestinal and pancreatobiliary type has prognostic and therapeutic implications. Immunohistochemical staining against specific biomarkers has been proven to be a useful adjunct in determining the exact histotype. Furthermore the immunohistochemical profile is suggestive of the molecular pathogenic mechanisms through which the tumor evolved. The aim of this study was to correlate p53, MDM2, CK7, CK20, MUC1, MUC2 and CDX2 expression in ampullary adenocarcinomas with the type of differentiation and patients' survival. MATERIAL AND METHODS: Forty-seven radically resected ampullary adenocarcinomas were included in this study. Thirty-eight of them were eligible for survival analysis. Patients' data were retrospectively collected. All tumors were classified as intestinal or pancreatobiliary type, according to histologic criteria, and immunohistochemically stained against the aforementioned markers. RESULTS: There were 18 intestinal and 29 pancreatobiliary type ampullary adenocarcinomas. A trend was found between intestinal type tumors and large tumor size. CK20, MUC2 and CDX2 expression was more prevalent in intestinal type tumors, while MUC1 was more frequently expressed in pancreatobiliary type tumors. Neither p53 nor MDM2 differential expression between the two histotypes reached statistical significance. Multivariate analysis indicated CK20 and MUC1 as independent predictors of the histotype. Mean and median survival was 90.3 and 55 months respectively. Overall 5-year survival rate was 48%. Survival analysis indicated TNM stage as the only independent prognostic factor. Although significant difference in survival rates among the two histotypes was implied based on survival plots, this difference could not gain statistical significance. CONCLUSION: Immunoreactivity against CK20 and MUC1 in ampullary carcinomas is a useful adjunct to histologic examination in determining histotype. None of the immunohistochemical markers studied has prognostic significance. Future studies focused on other signaling pathways should seek further evidence of distinct tumorigenic mechanisms between histotypes of ampullary adenocarcinoma.

Preoperative imaging and localization of small sized insulinoma with EUS-guided fine needle tattoing: a case report.

We report a case of an insulinoma that was not identified on either Computerized Tomography (CT) scan and Magnetic Resonance Imaging (MRI). Endoscopic ultrasonography (EUS) revealed a small insulinoma located at the body of the pancreas, which was histologically confirmed. The patient underwent a laparotomy but no tumour was identified either on palpation or with intra-operative ultrasound (IOUS). Subsequently, a further EUS was performed and after the tumour was identified was injected with blue dye. The patient then underwent a second exploratory laparotomy and a tumour at the posterior aspect of the pancreas close to the left side of the portal vein was identified and was successfully excised. Histology confirmed the presence of an endocrine tumour staining for chromogranin A and insulin. The patient had an uneventful postoperative recovery and has developed no further episodes of hypoglycemia 3 years after surgery.