Papillary Thyroid Carcinoma (PTC) in Children and Adults: Comparison of Initial Presentation and Long-Term Postoperative Outcome in 4432 Patients Consecutively Treated at the Mayo Clinic During Eight Decades (1936-2015).

BACKGROUND: Contemporary guidelines for managing PTC advise an approach wherein primary tumor and regional metastases (RM) are completely resected at first surgery and radioiodine remnant ablation (RRA) is restricted to high-risk patients, policies our group has long endorsed. To assess our therapeutic efficacy, we studied 190 children and 4242 adults consecutively treated during 1936-2015. SUBJECTS AND METHODS: Mean follow-up durations for children and adults were 26.9 and 15.2 years, respectively. Bilateral lobar resection was performed in 86% of children and 88% of adults, followed by RRA in 30% of children and 29% of adults; neck nodes were excised in 86% of children and 66% of adults. Tumor recurrence (TR) and cause-specific mortality (CSM) details were taken from a computerized database. RESULTS: Children, when compared to adults, had larger primary tumors which more often were grossly invasive and incompletely resected. At presentation, children, as compared to adults, had more RM and distant metastases (DM). Thirty-year TR rates were no different in children than adults at any site. Thirty-year CSM rates were lower in children than adults (1.1 vs. 4.9%; p = 0.01). Comparing 1936-1975 (THEN) with 1976-2015 (NOW), 30-year CSM rates were similar in MACIS <6 children (p = 0.67) and adults (p = 0.08). However, MACIS <6 children and adults in 1976-2015 had significantly higher recurrence at local and regional, but not at distant, sites. MACIS 6+ adults, NOW, compared to THEN, had lower 30-year CSM rates (30 vs. 47%; p < 0.001), unassociated with decreased TR at any site. CONCLUSIONS: Children, despite presenting with more extensive PTC when compared to adults, have postoperative recurrences at similar frequency, typically coexist with DM and die of PTC less often. Since 1976, both children and adults with MACIS <6 PTC have a <1% chance at 30 years of CSM; adults with higher MACIS scores (6 or more) have a 30-year CSM rate of 30%.

Introducing the SKIN score: a validated scoring system to assess severity of mastectomy skin flap necrosis.

BACKGROUND: With increasing use of immediate breast reconstruction (IBR), mastectomy skin flap necrosis (MSFN) is a clinical problem that deserves further study. We propose a validated scoring system to discriminate MSFN severity and standardize its assessment. METHODS: Women who underwent skin-sparing (SSM) or nipple-sparing mastectomy (NSM) and IBR from November 2009 to October 2010 were studied retrospectively. A workgroup of breast and plastic surgeons scored postoperative photographs using the skin ischemia necrosis (SKIN) score to assess depth and surface area of MSFN. We evaluated correlation of the SKIN score with reoperation for MSFN and its reproducibility in an external sample of surgeons. RESULTS: We identified 106 subjects (175 operated breasts: 103 SSM, 72 NSM) who had ≥1 postoperative photograph within 60 days. SKIN scores correlated strongly with need for reoperation for MSFN, with an AUC of 0.96 for SSM and 0.89 for NSM. External scores agreed well with the gold standard scores for the breast mound photographs with weighted kappa values of 0.82 (depth), 0.56 (surface area), and 0.79 (composite score). The agreement was similar for the nipple-areolar complex photographs: 0.75 (depth), 0.63 (surface area), and 0.79 (composite score). CONCLUSIONS: A simple scoring system to assess the severity of MSFN is proposed, incorporating both depth and surface area of MSFN. The SKIN score correlates strongly with the need for reoperation to manage MSFN and is reproducible among breast and plastic surgeons.

Surgical resection of synchronously metastatic adrenocortical cancer.

INTRODUCTION: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. METHODS: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). RESULTS: We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. CONCLUSION: Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

AACE/ACE disease state clinical review: pancreatic neuroendocrine incidentalomas.

Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well- or intermediately differentiated tumors ≥2 cm with imaging evidence of malignancy or with a Ki-67 >2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs <2 cm with a Ki-67 index ≤2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely.

Reoperative experience with papillary thyroid cancer.

BACKGROUND: Intense postoperative monitoring has resulted in increasing detection of patients with recurrent papillary thyroid cancer (PTC). Our goals included quantifying successful reoperation, and analyzing surgical complications and reasons for relapse. METHODS: From 1999 to 2008, a total of 410 patients underwent reoperation for PTC relapse. We analyzed post-reoperative disease outcomes, reasons for relapse, and complications. RESULTS: Bilateral reoperative thyroidectomy was performed in 13 (3 %) patients; lobectomy, 34 (8 %); central neck (VI) soft tissue local recurrence excision, 47 (11.5 %); bilateral VI node dissection, 107 (26 %); unilateral VI dissection, 112 (27 %); levels II-V dissection, 93 (23 %); levels III-V, 86 (21 %); lateral single- or two-compartment dissection, 51 (12 %); and node picking, 20 (5 %) of level VI and 53 (13 %) lateral neck. Complications occurred in 6 %; including hypoparathyroidism, 3 %; unintentional recurrent laryngeal nerve (RLN) paralysis, 3 %; phrenic nerve injury, 0.5 %; spinal accessory nerve injury, 0.5 %; and chyle leak in 1.6 %. Of 380 (93 %) patients with follow-up (mean 5.2 years); 274 (72 %) patients are alive with no structural evidence of disease, 38 % developed disease relapse (mean 2.1 years), 42 (11 %) died from PTC, and 55 (14 %) are alive with disease. The reason for relapse was a false negative pre-reoperative ultrasound (US) in 18 (5 %), nodal recurrence in the operative field in 37 (10 %), a combination of these two reasons in 10 (3 %), and disease virulence (local or systemic recurrence) in 81 (21 %). CONCLUSIONS: Although 72 % of patients were rendered structurally disease free after reoperation, nearly 40 % suffered additional relapse. Improved surgical technique or preoperative localization might positively affect 15-20 %; at least 20 % reflect the biologic aggressiveness of the disease.

Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer.

BACKGROUND: Traditional drug discovery methods have a limited role in rare cancers. We hypothesized that molecular technology including gene expression profiling could expose novel targets for therapy in adrenocortical carcinoma (ACC), a rare and lethal cancer. SPARC (secreted protein acidic rich in cysteine) is an albumin-binding matrix-associated protein that is proposed to act as a mechanism for the increased efficacy of a nanoparticle albumin-bound preparation of the antimicrotubular drug Paclitaxel (nab-paclitaxel). METHODS: The transcriptomes of 19 ACC tumors and 4 normal adrenal glands were profiled on Affymetrix U133 Plus2 expression microarrays to identify genes representing potential therapeutic targets. Immunohistochemical analysis for target proteins was performed on 10 ACC, 6 benign adenomas, and 1 normal adrenal gland. Agents known to inhibit selected targets were tested in comparison with mitotane in the 2 ACC cell lines (H295R and SW-13) in vitro and in mouse xenografts. RESULTS: SPARC expression is increased in ACC samples by 1.56 ± 0.44 (µ ± SD) fold. Paclitaxel and nab-paclitaxel show in vitro inhibition of H295R and SW-13 cells at IC50 concentrations of 0.33 µM and 0.0078 µM for paclitaxel and 0.35 µM and 0.0087 µM for nab-paclitaxel compared with mitotane concentrations of 15.9 µM and 46.4 µM. In vivo nab-paclitaxel treatment shows a greater decrease in tumor weight in both xenograft models than mitotane. CONCLUSIONS: Biological insights garnered through expression profiling of ACC tumors suggest further investigation into the use of nab-paclitaxel for the treatment of ACC.

Thyroid cancer detection with dual-isotope parathyroid scintigraphy in primary hyperparathyroidism.

BACKGROUND: Thyroid cancer cells have been shown to take up (99m)Tc-sestamibi. The role for (99m)Tc-sestamibi scintigraphy (Tc-MIBI) in the diagnosis of thyroid cancer in patients with primary hyperparathyroidism (PHPT) is unclear. Our aim was to determine whether dual-isotope parathyroid scintigraphy is useful in identifying thyroid cancer. METHODS: A prospective database of 3,187 patients who underwent neck exploration for PHPT was reviewed to identify patients who had concurrent thyroid resection. Patients with benign and malignant thyroid disease were comparatively analyzed. RESULTS: A total of 470 patients underwent both thyroidectomy and parathyroidectomy (reoperations in 21%). Benign disease (n = 391, 83%) was more common than malignancy [papillary thyroid cancer (n = 75) and medullary thyroid cancer (n = 5); 1 had both]. Dual-isotope scintigraphy obtained in 374 patients (80%) had a sensitivity of 67% and a positive predictive value of 66% for parathyroid adenoma localization in these patients with thyroid disease. False-positive scintigraphy occurred in 22% with benign and 45% with malignant thyroid disease (P = 0.002). On Tc-MIBI imaging, 54 (86%) of 63 patients with malignancy had hot nodules, compared to 248 (81%) of 308 patients with benign disease (P = 0.49). On I-123 imaging, 34 (54%) of 63 patients with malignancy had cold nodules, compared to 42 (14%) of 304 patients with benign disease (P < 0.001). A dual-isotype phenotype of both Tc-MIBI-Hot and I-123-Cold had sensitivity 52%, specificity 88%, positive predictive value 47%, and negative predictive value 90% for detecting a thyroid malignancy. CONCLUSIONS: A Tc-MIBI-Hot/I-123-Cold phenotype is very specific for detecting thyroid malignancy. Patients with this imaging phenotype should strongly be considered for preoperative ultrasound-guided biopsy. Patients found intraoperatively to have false-positive parathyroid scintigraphy should be evaluated for thyroid cancer.

Primary hyperparathyroidism and negative Tc99 sestamibi imaging: to operate or not?

BACKGROUND: The indications for surgery in primary hyperparathyroidism (1HPT) are the same for patients with and without localization on imaging. However, patients with negative imaging may not be referred for surgery or the surgeon may be reluctant to operate. We compare outcomes in patients with negative imaging to those with localization. METHODS: A review of patients who underwent primary operation for 1HPT with a preoperative Tc99 sestamibi I-123 (MIBI) scan was conducted. Imaging, laboratory, operative findings, pathologic findings, and outcomes were used to compare patients with negative scans to those with localization. RESULTS: A total of 2,681 patients had an operation for 1HPT with preoperative MIBI. MIBI imaging was negative in 136 (5.7 %). The negative MIBI group had a lower calcium (10.9 vs. 11.0 mg/ml, P=0.02), phosphorus (2.9 vs. 3.1 mg/dl, P<0.001), and urinary calcium (251 vs. 287 mg/ml, P=0.02) and no difference in parathyroid hormone, 25-OH vitamin D, or bone loss. Multigland resection was higher with a negative scan (32 vs. 13 %, P<0.001). A curative operation was performed in 90.4 % with a negative MIBI compared to 97.5 % with localization (P<0.001). Patients who underwent successful surgery despite a negative MIBI scan had lower calcium (10.8 vs. 11.1 mg/ml, P=0.04) and parathyroid hormone (98 vs. 196 pg/ml, P=0.03) than those not cured. Patients with both a negative ultrasound result and negative MIBI had a cure rate of 89 %. CONCLUSIONS: A curative operation is performed at an acceptably lower rate with negative MIBI imaging. A decision for surgery with a negative MIBI finding should consider lower cure rates and symptom severity.

Classification of parathyroid cancer.

PURPOSE: Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 ("Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer," Ann Surg Oncol 2010;17:2156-74) derived from a retrospective literature review of 330 patients. METHODS: This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver-operating characteristic (ROC) analysis. RESULTS: Follow-up ranged 2-347 months (mean 76 months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4-38.4; P < 0.0001), with significantly lower 5-year disease-free survival (χ(2) = 8.7; P < 0.005 for n = 45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P < 0.05 between each class). CONCLUSIONS: This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.

Adrenalectomy improves outcomes of selected patients with metastatic carcinoma.

BACKGROUND: Indications and survival benefit for adrenalectomy (ADX) in the setting of metastasis are not clearly defined. We aimed to determine which patients with primary malignancies may benefit from ADX performed for metastasis. Mayo Clinic institutional outcomes in patients with metastatic disease to the adrenal(s) treated by adrenalectomy were compared to stage-matched historical controls from the Surveillance Epidemiology and End Results (SEER) database. METHODS: A retrospective review (1992-2010) was conducted to identify patients treated with ADX for metastatic cancer at Mayo Clinic, Rochester. Associations of clinical, surgical, and pathologic features with overall survival (OS) were evaluated using Cox proportional regression models. OS for those treated with ADX was compared with that for SEER database stage-matched patients who underwent primary resection without resection of distant disease using log-rank tests. RESULTS: A total of 166 patients underwent ADX for metastatic primaries involving the kidney 60, lung 24, sarcoma 19, colon 15, pancreas 13, and other-35. Patients with sarcoma and kidney, lung, and pancreatic tumors who underwent ADX had better OS at 1, 2, and 3 years than did the SEER-matched controls. Respectively, the rates were for sarcoma (100, 93, 86% vs. 57, 36, 30%), kidney (86, 80, 72% vs. 55, 37, 27%), lung (91, 69, 52% vs. 52, 34, 25%), and pancreas (79, 56, 45% vs. 33, 20, 12%). Univariate analysis identified primary diagnosis <2 years before ADX, other distant site, pancreatic primary, palliative operation, and persistent disease as risk factors for death. CONCLUSIONS: An aggressive surgical approach results in improved OS in patients with metastatic disease arising from soft tissues, kidney, lung, and pancreas. Other tumors may benefit, but larger study cohorts are needed for a meaningful comparison.

Setting the bar for laparoscopic resection of sporadic insulinoma.

BACKGROUND: Laparoscopic insulinoma resection (LIR) for sporadic disease is increasingly supported as a feasible and safe operation in small series of patients. To determine whether LIR is an acceptable alternative to the open operation, it is necessary to compare LIR to historical controls. The purpose of this study was to identify the skills and technology needed for LIR and establish outcome standards. METHODS: A database of patients with benign sporadic insulinoma who underwent an open procedure at the Mayo Clinic was reviewed for demographics, imaging, operative/pathology reports, and outcomes. Outcomes were compared to a world-wide meta-analysis of patients who had undergone LIR reported in the English literature between 1996 and 2009. RESULTS: Two hundred fifteen patients underwent a primary open operation for benign sporadic insulinoma. Solitary tumors were found in 97%. Meta-analysis identified 232 patients who underwent LIR. The open and LIR groups underwent comparable operations that included enucleations (64 vs. 68%) and distal pancreatectomies (28 vs. 35%) (p = 0.06). The mean estimated blood loss, operating time, and length of stay were comparable between the open and LIR groups (p = NS). Pancreatic fistula occurred more often in the LIR group (24 vs. 11%, p < 0.05). A curative operation was performed in 98% of control patients and in 99% of the LIR group (p = NS). CONCLUSIONS: Multiple insulinomas are rare and a focused resection guided by imaging may be performed. LIR is associated with an increased incidence of pancreatic fistula. Success of LIR will depend on accurate multimodality preoperative imaging, skilled use of lap-US to replace palpation for localization, and safe methods to dissect the tumor adjacent to the pancreatic duct.

Malignant adrenal neoplasm masquerading as worrisome adrenal hemorrhage.

BACKGROUND: Adrenal hemorrhage (AH) associated with adrenal neoplasm is rare. This study assesses the clinical and pathological impact of AH in the setting of malignant adrenal neoplasm to establish management strategies. MATERIALS AND METHODS: Patients admitted over a 25-year period with a diagnosis of AH and malignant adrenal neoplasm were retrospectively reviewed. RESULTS: Malignant adrenal neoplasms were reported in 14 of 217 patients (6.4%) presenting with AH. Of these, 4 were women. Mean age was 56 years. The most common presenting symptom was abdominal pain (n = 6), followed by altered mental status and shock (2) and hypercortisolism (1). Five patients were asymptomatic. In 10 patients the adrenal tumor was metastatic. Four patients had adrenocortical carcinoma (ACC). All primary adrenal tumors were unilateral. Risk factors for AH were identified in 5 patients (anticoagulation, 3; trauma, 1; and recent surgery, 1). Computed tomography (n = 12) demonstrated adrenal masses ranging in size from 6.8 to 11.0 cm (mean, 9 cm). Nine patients were managed by surgical resection (adrenalectomy, 4; radical nephrectomy, 2; adrenalectomy/splenectomy, 1; adrenalectomy/bowel resection, 1; and laparotomy and packing, 1) Actual survival time ranged from 9 days to 7.8 years (median 329 days). CONCLUSION: Most patients with AH in the setting of malignant adrenal neoplasm had metastatic tumors to the adrenal glands. These patients do not typically present in hemorrhagic shock, allowing for adequate preoperative evaluation for function and assessment for primary tumors. Long-term survival of these patients is rare.

Axillary recurrence in breast cancer patients with isolated tumor cells in the sentinel lymph node [AJCC N0(i+)].

BACKGROUND: Completion axillary lymph node dissection (CALND) is controversial in patients with sentinel lymph node (SLN) metastases ≤ 0.2 mm [N0(i+)]. Our goal was to characterize patients with SLN isolated tumor cells regarding surgical management and axillary recurrence. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective chart review identified 677 consecutive patients with positive SLN biopsy for breast cancer between October 1997 and June 2004, and N0(i+) patients were identified. Clinicopathologic characteristics, predicted probability of nonsentinel node disease, axillary surgery, and recurrences were recorded. RESULTS: Of 81 patients with SLN N0(i+) metastasis, 31 underwent CALND and 50 did not. The two groups of patients showed no statistical differences in tumor size, stage, grade, number of SLNs removed, and number of positive SLNs. Predicted probability of additional axillary metastasis was somewhat higher among those who underwent CALND compared with those who did not. Patients undergoing CALND were significantly younger than those who did not (mean age 50 vs. 57, P = 0.01). Of the 31 patients with CALND, 4 (12.9%) had additional nodal metastases. Radiation to nodal fields was administered to 8 patients in the CALND group (25.8%) and to 7 in the group without axillary dissection (14.0%, P = 0.44). No axillary recurrences were noted at a median follow-up of 38 months. CONCLUSION: Among breast cancer patients with SLN isolated tumor cells, a small percentage have additional metastasis in other axillary nodes. However, the risk of axillary recurrence appears low in those who do not undergo CALND.

Risks and adequacy of an optimized surgical approach to the primary surgical management of papillary thyroid carcinoma treated during 1999-2006.

BACKGROUND: Intense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an optimized surgical approach including preoperative ultrasonography (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM. METHODS: During 1999-2006, a total of 420 patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow-up 98%, median 4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes. RESULTS: Total or near-total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%. Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size-thyroid tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1 had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%) patients, 11(3%) from disease virulence (LR or DM), preoperative false-negative (FN) US in 12 (3%), and combination of FN-US and recurrence in the operated field in 5 (1%) patients. CONCLUSIONS: Recurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

Hyperinsulinemic hypoglycemia with nesidioblastosis: histologic features and growth factor expression.

Hypoglycemia secondary to nesidioblastosis is rare in adults, and the pathogenesis of this condition is unknown. To determine factors leading to nesidioblastosis in adults, we analyzed 36 cases of nesidioblastosis including 27 cases of postgastric bypass nesidioblastosis and 9 cases of idiopathic nesidioblastosis in adults by immunohistochemistry using antibodies to insulin-like growth factor 1, insulin-like growth factor 2 (IGF2), insulin-like growth factor one receptor-alpha epidermal growth factor receptor, transforming growth factor-beta1 and 2, and transforming growth factor-beta receptor type 3. Fifty-two surgically excised pancreatic specimens from patients with benign exocrine tumors and no evidence of hypoglycemia were used as controls. There was increased IGF2, insulin-like growth factor receptor 1 receptor-alpha and transforming growth factor-beta receptor 3 expression in islets from nesidioblastosis patients compared to controls. Peliosis-type vascular ectasia was more common in nesidioblastosis patients compared to controls. These findings suggest that increased production of growth factors and growth factor receptors may contribute to the development of nesidioblastosis in adults.

Adrenocortical carcinoma survival rates correlated to genomic copy number variants.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02% and 0.2% of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in 40% to 70% of patients at the time of diagnosis. Standard chemotherapy with mitotane is often ineffective with intolerable side effects. The modern molecular technology of comparative genomic hybridization allows the examination of DNA for chromosomal alterations, which can lend biological insight into cancer processes. Genomes of 25 ACC clinical samples were queried on the Agilent 44K Human Genome comparative genomic hybridization array detecting regions of chromosomal gain and loss within the tumor population. Commonly shared amplifications appearing in > or =50% of tumors at P < or = 10(-4) include regions within chromosomes 5, 7, 12, 16q, and 20. Deleted genomic regions within ACC include portions of chromosomes 1, 3p, 10q, 11, 14q, 15q, 17, and 22q. Genomic aberrations in regions associated with differential survival (P < or = 0.05) and presence in > or =20% of tumors include amplifications of 6q, 7q, 12q, and 19p. Deletions within stratified survival groups include localized regions within 3, 8, 10p, 16q, 17q, and 19q. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation-dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors.

Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors.

Pancreatic endocrine tumors (PETs) are uncommon tumors with an annual incidence <1 per 100 000 person-years in the general population. The PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are non-functional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis, and established and novel prognostic markers of PETs are reviewed.

Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience.

BACKGROUND: There has been a rapid shift from open to laparoscopic approaches in adrenal surgery, but the safety and efficacy of bilateral laparoscopic adrenalectomy (BLA) in patients with corticotrophin (ACTH)-dependent Cushing's syndrome continues to be defined. OBJECTIVE: Review outcomes in the largest series of patients reported to date undergoing BLA for ACTH-dependent Cushing's syndrome. DESIGN: Retrospective review study. PATIENTS: Between January of 1995 and October of 2006, BLA was attempted in 68 patients with ACTH-dependent Cushing's syndrome (26 ectopic ACTH syndrome; 42 persistent pituitary-dependent Cushing's syndrome following pituitary surgery). MEASUREMENTS: Review of peri-operative morbidity and mortality, biochemical parameters and patient-reported symptom response from chart review and mailed questionnaire. RESULTS: BLA was successfully completed in 59 of 68 patients (87%); nine (13%) required conversion to open adrenalectomy (OA). Intra-operative complications occurred in three patients (4.4%) (two BLA, one OA), and non-operative complications occurred in 11 (16%) patients (eight BLA, three OA). There were no peri-operative deaths. Median hospitalization was 5.5 days (range, 3-28) and 11.9 days (range, 4-29) for the BLA and OA groups, respectively. In patients with follow-up data available, all achieved biochemical resolution and at least partial clinical resolution of signs and symptoms associated with hypercortisolism. Resolution of hypertension, diabetes and obesity was achieved in 64%, 29% and 35% of patients carrying those diagnoses prior to surgery, respectively. CONCLUSIONS: This study further supports the role of BLA as an effective treatment option for patients with ACTH-dependent Cushing's syndrome.

Percutaneous parathyroid ethanol ablation in patients with multiple endocrine neoplasia type 1.

OBJECTIVE: The objective of our study was to show the efficacy and safety of percutaneous ethanol ablation in managing recurrent primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1 (MEN1) after subtotal parathyroidectomy. CONCLUSION: Ethanol ablation is a viable alternative to reoperation for the management of recurrent primary hyperparathyroidism in patients with MEN1.