Citations

AbstractBackgroundLaparoscopic 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.MethodsA 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.ResultsTwo 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).ConclusionsMultiple 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.

AbstractGenome‐wide association studies (GWAS) are being conducted at an unprecedented rate in population‐based cohorts and have increased our understanding of the pathophysiology of complex disease. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the electronic MEdical Records and Genomics (eMERGE) network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research. Curr. Protoc. Hum. Genet. 68:1.19.1‐1.19.18 © 2011 by John Wiley & Sons, Inc.

Background: Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and <20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease. Methods: Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis. Results: There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed >32 months (range: 32–89 months; median: 44 months) with a median overall Kaplan–Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to <20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions. Conclusions: Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Abstract Background Controversy exists regarding the aggressiveness of initial therapy in childhood papillary thyroid cancer (PTC). Few studies with long‐term outcome exist and second primary malignancies have rarely been analyzed. Methods We studied 215 PTC patients younger than 21 years old managed during 1940 through 2008. The patients were aged 3–20 year old (median age = 16 years); the median follow‐up was 29 years. Recurrence and mortality details were taken from a computerized database. Results Median primary tumor size was 2.2 cm. Six percent had distant metastases at presentation, 5% had incomplete tumor resection, 86% had nodes removed at initial surgery, and 78% had nodal metastases. After complete surgical resection, PTC recurred in 32% by 40 years. At 20 years, the recurrence rates at local, regional, and distant sites were 7, 21, and 5%, respectively. During 1940–1969, local and regional recurrence rates after unilateral lobectomy (UL) were significantly ( P < 0.001) higher than after bilateral lobar resection (BLR). During 1950–2008 radioiodine remnant ablation (RRA) was administered within 18 months to 32%; it did not diminish the 25‐year regional recurrence rate of 16% seen after BLR alone ( P = 0.86). Only two fatal events from PTC occurred at 28 and 30 years, for a cause‐specific mortality at 40 years of only 2%. All‐causes mortality rates did not exceed expectation through 20 years, but from 30 through 50 years, the number of deaths was significantly ( P < 0.001) higher than predicted. Fifteen of 22 deaths (68%) resulted from nonthyroid malignancy. Conclusion Survival from childhood PTC should be expected, but later death from nonthyroid malignancy is disconcerting. Seventy‐three percent of those who died from nonthyroid malignancy had received postoperative therapeutic irradiation.

AbstractBackgroundIntense 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 ultrasonograpy (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM.MethodsDuring 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.ResultsTotal 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.ConclusionsRecurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

Abstract The head and neck region is a frequent site for potentially confusing incidental benign findings not related to the primary pathologic process and having no impact on patient prognosis. Several lesions are thymic in origin. We report 3 cases of lymphocyte-poor thymic remnants identified in central cervical (level VI) lymph node dissections for unrelated benign and malignant pathology. In each, the rests were nearly completely composed of bland epithelial cells with rare admixed lymphocytes. These cells were immunophenotypically similar to thymic epithelial cells, although they differed in the paucity of associated thymic lymphocytes and lack of Hassall corpuscles. Lymphocyte-depleted thymic remnants in the central cervical compartment are not well described in the literature. It is important to be aware of these and other benign inclusions to avoid making incorrect diagnoses of malignancy.