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.

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.

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.

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.

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.

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.

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.

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.

Surgical treatment of potentially primary malignant adrenal tumors: an unresolved issue.

Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors.The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality.

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 hypothalamic-pituitary-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.

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.

Laparoscopic resection of pheochromocytomas with delayed vein ligation.

OBJECTIVE: Laparoscopic adrenalectomy has been established as the surgical procedure of choice for benign adrenal diseases. Laparoscopic adrenalectomy for pheochromocytoma has been the subject of debate, due to potential systemic consequences of pneumoperitoneum in patients with catecholamine-secreting tumors and a perceived increased risk of malignancy for large-sized tumors. In this study we present our experience for laparoscopic resection of pheochromocytomas, and evaluate the safety of delayed adrenal vein ligation. METHODS: A total of 32 adrenalectomies for pheochromocytoma were performed between June 1997 and December 2009. Four paragangliomas, operated in the same period are not included in this series. All patients were investigated and operated on using an established departmental protocol. Preoperative diagnosis, operative details, complications, length of hospital stay, morbidity, and follow-up were documented from the hospital records of 200 patients who underwent 208 adrenalectomies for benign and malignant adrenal tumors in the same period. RESULTS: Thirty-two tumors were removed from 31 patients (17 men; mean age, 54 y; range, 19 to 72 y). One patient with MEN IIA underwent bilateral resection of pheochromocytomas in 2 stages. Tumor size in laparoscopic procedures ranged from 2.2 to 10.5 cm (mean, 4.97 cm). Operative time was from 55 to 210 minutes (mean, 110 min).Twenty-seven patients had sporadic disease (2 potentially malignant, 2 malignant), and 4 in the context of a familiar syndrome (2 MEN IIA syndrome, 1 Von Hippel Lindau syndrome and Recklinghausen disease, respectively). Twenty-four patients underwent laparoscopic adrenalectomy, 2 patients had open approach from the start for recurrent malignant pheochromocytoma and large benign tumor respectively, 1 patient had open approach due to inoperable malignant pheochromocytoma, and 4 patients had conversions from laparoscopic to open procedure. All patients with paragangliomas underwent open approach from the start. The mean hospital stay was 2 days (range, 1 to 3 d) for the laparoscopic procedures. All patients underwent late ligation of the main adrenal vein. Five patients received sodium nitroprusside intraoperatively to treat hypertension. One patient developed pulmonary embolism after the operation, and succumbed 1 month later. There were no recurrences for the benign tumors during the follow-up period. CONCLUSIONS: Laparoscopic adrenalectomy for pheochromocytoma although safe, should be converted to open for difficult dissection, to avoid tumor disruption, and recurrence. Hemodynamic instability can be prevented and is not influenced by early or late ligation of the adrenal vein. Delayed main adrenal vein ligation is a safe alternative to the "vein first" technique.

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.

Multiplex RT-PCR-based detections of CEA, CK20 and EGFR in colorectal cancer patients.

AIM: To develop a multiplex reverse transcription polymerase chain reaction (RT-PCR) method detecting circulating tumor cells in the peripheral blood of colorectal cancer (CRC) patients. METHODS: Peripheral blood samples were collected from 88 CRC patients and 40 healthy individuals from the blood donors' clinic and subsequently analyzed by multiplex RT-RCR for the expression of carcinoembryonic antigen (CEA), cytokeratin 20 (CK20) and epidermal growth factor receptor (EGFR) mRNA. The analysis involved determining the detection rates of CEA, CK20 and EGFR transcripts vs disease stage and overall survival. Median follow-up period was 19 mo (range 8-28 mo). RESULTS: Rates of CEA, CK20 and EGFR detection in CRC patients were 95.5%, 78.4% and 19.3%, respectively. CEA transcripts were detected in 3 healthy volunteer samples (7.5%), whereas all control samples were tested negative for CK20 and EGFR transcripts. The increasing number of positive detections for CEA, CK20 and EGFR transcripts in each blood sample was positively correlated with Astler-Coller disease stage (P < 0.001) and preoperative serum levels of CEA (P = 0.029) in CRC patients. Data analysis using Kaplan-Meier estimator documented significant differences in the overall survival of the different CRC patient groups as formed according to the increasing number of positivity for CEA, CK20 and EGFR transcripts. CONCLUSION: These data suggest that multiplex RT-PCR assay can provide useful information concerning disease stage and overall survival of CRC patients.

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.

Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report.

INTRODUCTION: Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature. CASE PRESENTATION: A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease. CONCLUSIONS: Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.

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.