Chrysanthi Aggeli

Pheochromocytoma associated with neurofibromatosis type 1: concepts and current trends

BackgroundNeurofibromatosis 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 presentationWe 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 × 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.ConclusionNowadays 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.

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

IntroductionPrimary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushings 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 presentationA 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushings 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.ConclusionsEven though primary pigmented nodular adrenocortical disease is a rare cause of Cushings syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushings syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.

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.

Death receptor 5 ( DR5 ) and a 5-gene apoptotic biomarker panel with significant differential diagnostic potential in colorectal cancer

High expression of Inhibitor of apoptosis proteins (IAPs) has been related to colorectal cancer (CRC) progression, resistance to treatment and poor prognosis. TRAIL (TNF-related apoptosis-inducing ligand) through its receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) can selectively induce cancer cell apoptosis. The mRNA expression of DR4, DR5, c-IAP1, c-IAP2, XIAP and BIRC5/Survivin genes was examined in 100 paired (cancerous-normal) colorectal tissue specimens by real-time PCR, 50 of which were KRAS wild-type and 50 KRAS-mutant. DR5, XIAP and BIRC5/Survivin genes are significantly up-regulated (p < 0.0001, p = 0.012 and p = 0.0003, respectively), whereas c-IAP1 and c-IAP2 genes are significantly down-regulated at mRNA and protein levels in CRC (p < 0.0001 for both). ROC analyses showed that DR5, cIAP1 and cIAP2 expression has discriminatory value between CRC and normal tissue (AUC = 0.700, p < 0.0001 for DR5; AUC = 0.628, p = 0.011 for cIAP1; AUC = 0.673, p < 0.0001 for cIAP2). Combinatorial ROC analysis revealed the marginally fair discriminatory value of 5 genes as a panel (AUC = 0.685, p < 0.0001). Kaplan-Meier survival curves revealed significant association of cIAP2 down-regulation in CRC with lower overall survival probability of CRC patients (p = 0.0098). DR5, BIRC5/Survivin, XIAP, c-IAP1 and c-IAP2 mRNA expression are significantly deregulated in CRC and could provide a panel of markers with significant discriminatory value between CRC and normal colorectal tissue.

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.

Surgical Considerations in Subclinical Cushing’s Syndrome. When is it Time to Operate?

Subclinical Cushing’s syndrome (SCS) is a disorder characterized by autonomous cortisol secretion and the presence of an adrenal incidentaloma, in the absence of clinical features of Cushing’s syndrome. SCS is of special interest because it has been associated with several disorders, such as atherosclerosis and arterial hypertension. Despite decades of research, SCS continues to generate controversy regarding its diagnosis and subsequent management. Several issues remain to be resolved. A universal agreement on the hormonal diagnosis of the syndrome remains elusive. Autonomous cortisol secretion has been ill defined and several definitions have been offered. The heterogeneity in diagnostic criteria creates heterogeneity in studies evaluating optimal management. Minimally invasive adrenalectomy has been documented to ameliorate SCS associated disorders in certain patients. Identifying these patients should be the focus of future research on the subject. In this review we summarize current concepts regarding SCS and indications for its surgical management.

A Rare Case of Synchronous Cervical Lymph Node Metastasis from Renal and Thyroid Cancer

Papillary thyroid cancer (PTC) has a propensity to metastasize to the cervical lymph nodes (LNs). Renal cancer (RC) can also spread to the cervical LNs and is the most common cause of metastatic infiltration of the thyroid gland. We describe here the case of a 71-year-old patient with a previous history of surgically treated RC who underwent evaluation of a large left cervical mass. Initial cytological investigation on fine needle aspiration (FNA) indicated metastatic PTC. Computed tomography (CT) scanning revealed no other suspicious foci. The patient underwent total thyroidectomy and central and left lateral cervical LN dissection, during which a large neck mass along the left jugular vein was also removed. Histology demonstrated metastatic spread of RC to the thyroid gland and lateral cervical LNs and concurrent LN metastases from PTC. One LN showed evidence of synchronous RC and PTC metastasis. Only a small papillary thyroid microcarcinoma with no aggressive histological features was detected in the thyroid, raising the possibility that the primary focus of metastatic PTC was the large left lateral neck mass. The patient was discharged after successful treatment for transient hypoparathyroidism. The synchronous presence of RC and PTC in the thyroid and cervical LNs and the concurrent metastases in one of the LNs renders this case unique. Evaluation of a cervical mass in a patient with a prior history of malignancy can prove vexing, and surgery may be the only option for the establishment of a definitive diagnosis.

Surgery for pheochromocytoma: A 20-year experience of a single institution

OBJECTIVEResection of pheochromocytomas is a challenging procedure due to hemodynamic lability. our aim was to evaluate surgical outcomes in 67 patients with pheochromocytoma and to validate the role of laparoscopic surgery in the treatment of these tumors.DESIGNThis study is a retrospective review. A total of 68 procedures for pheochromocytoma were performed between June 1997 and February 2017. All patients were investigated and operated on using an established departmental protocol. Relevant data were retrieved from the hospital records of 533 patients who underwent 541 adrenalectomies for benign and malignant adrenal tumors in the same period.RESULTSSixty-nine tumors were removed from 67 patients. One patient with/MEN2A underwent bilateral resection of pheochromocytomas in two stages. Tumor size in laparoscopic procedures ranged from 1.2 cm to 11.0 cm (mean 5.87 cm). Thirty-seven patients had benign disease, 31 potentially malignant (based on PASS) and 1 malignant with metastasis. Eight were in the context of a familial syndrome. Forty-nine patients underwent laparoscopic adrenalectomy, 8 patients had open approach from the start for recurrent pheochromocytoma or large benign tumor, 1 patient had open approach due to inoperable malignant pheochromocytoma and 10 patients had conversions from laparoscopic to open procedure. Nine patients received sodium nitroprusside intraoperatively to treat hypertension. One patient developed pulmonary embolism and succumbed 1 month later. There were no recurrences of the benign or potentially malignant tumors during the follow-up period.CONCLUSIONSLaparoscopic resection of pheochromocytomas, despite its increased level of difficulty compared to that of other adrenal tumors, is a safe and effective procedure.