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Background: Adrenocortical carcinoma has a poor prognosis and multiple clinical, pathological, and treatment variables. Currently, we lack a prognostic and treatment calculator to determine the survival and efficacy of adjuvant chemoradiation. We aimed to validate a calculator to assess prognosis and treatment., Methods: We searched the National Cancer Database to identify patients with adrenocortical carcinoma surgically treated from 2004 to 2020 and randomly allocated them into a training (80%) or validation set (20%). We analyzed the variables of age; sex; Charlson Comorbidity Index; insurance status; tumor size; pathologic tumor, node, and metastasis categories; surgical margins; and use of chemotherapy and radiation therapy. We used Cox regression prediction models and bootstrap coefficients to generate a mathematical model to predict 5- and 10-year overall survival. After using the area under the curve analysis to assess the model's performance, we compared overall survival in the training and validation sets., Results: Multivariable analysis of the 3,480 patients included in the study revealed that all variables were significant except sex (P < .05) and incorporated into a mathematical model. The area under the curve for 5- and 10-year overall survival was 0.68 and 0.70, respectively, for the training set and 0.70 and 0.72, respectively, for the validation set. For the bootstrap coefficients, the 5- and 10-year overall survival was 6.4% and 4.1%, respectively, above the observed mean., Conclusion: Our model predicts the overall survival of patients with adrenocortical carcinoma based on clinical, pathologic, and treatment variables and can assist in individualizing treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex., Methods: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex., Results: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation., Conclusion: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied., Methods: Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables., Results: A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P < .01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P < .001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors <2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004)., Conclusion: For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine., (Copyright © 2021. Published by Elsevier Inc.)

Background: The eighth edition American Joint Committee on Cancer tumor-node-metastasis staging for well-differentiated thyroid cancers, no longer considers "minimal" extrathyroidal extension for tumor staging. This change prompted us to examine the effect of extrathyroidal extension on patient outcomes., Methods: Patients (n = 177,497) in the 2016 National Cancer Database with classic papillary thyroid cancer were evaluated to determine the effect of extrathyroidal extension on overall survival and risk for nodal and distant metastases. Kaplan-Meier curves with the log-rank test were used to evaluate survival differences. Multivariable Cox and logistic regression analyses included relevant clinicopathologic variables (e.g. age, sex, race, and Charlson Comorbidity Index)., Results: Patients with "minimal" extrathyroidal extension had worse survival versus patients with no extrathyroidal extension (10-year survival 89.3% vs 93.1%, hazard ratio 1.23; 95% confidence interval, 1.13-1.35; P < .001). Any extrathyroidal extension was associated with higher risks for lymph node (odds ratio 2.78; 95% confidence interval, 2.69-2.87) and distant metastasis (odds ratio 3.5; 95% confidence interval, 3.05-4.04). These associations persisted when comparing "micro" (extension into the thyroid capsule) versus none for nodal risk (odds ratio 1.25; 95% confidence interval, 1.18-1.33) and distant metastasis (OR 1.52; 95% confidence interval, 1.11-2.09)., Conclusion: All levels of extrathyroidal extension, including microscopic, were associated with increased risk for nodal and distant metastasis. Both minimal and macroscopic extrathyroidal extension were also associated with decreased overall survival. Such findings have the potential to affect the clinical decision making for patients diagnosed with papillary thyroid cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study compares pathologic features and overall survival of classic versus aggressive variants of papillary thyroid microcarcinoma (PMTC)., Methods: Patients ≥18 years in the National Cancer Data Base (2004-2015) with the subtypes of classic (cPTMC), tall cell (mTCV), or diffuse sclerosing (mDSV) PTC (≤1 cm) were identified. Overall survival was analyzed by Kaplan-Meier and propensity matched for clinicopathologic and treatment variables., Results: There were 82,056 cPTMC patients, 923 mTCV, and 219 mDSV. Extrathyroidal extension and nodal involvement were more frequent in mTCV and mDSV versus cPTMC (P < .01). mTCV had more distant metastases than cPTMC (P = .02). On multivariable analysis, mTCV (odds ratio 4.19 [3.58-4.92], P < .001) and mDSV (odds ratio 2.76 [1.92-3.97]; P < .01) histologies were predictors of extrathyroidal extension. mTCV was an independent predictor of nodal metastases (odds ratio 1.51 [1.25-1.83], P < .01). Total thyroidectomy and radioactive iodine treatment were more commonly used in mTCV and mDSV patients when compared with cPTMC patients. Despite more aggressive features and more aggressive treatment in mTCV and mDSV patients, there was no difference in overall survival when compared with propensity-matched cPTMC patients., Conclusion: Although mTCV and mDSV have more aggressive pathologic features and were treated more aggressively, there were no differences in overall survival compared with propensity-matched cPTMC patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Fine needle aspiration has been the traditional method for diagnosing thyroid cancer. Epigenetic chromatin conformation changes offer an alternative method of diagnosing cancer. The purpose of this study is to evaluate an EpiSwitch assay of epigenetic markers that can be used to diagnose thyroid cancer in blood samples., Methods: From 2014 to 2016, adult patients with thyroid nodules having thyroidectomy were recruited and grouped based on benign, malignant, and atypia of undetermined significance or follicular lesions of undetermined significance fine needle aspiration cytology. Blood samples were collected before surgery. Final pathologic diagnosis was made from the thyroid specimens. Patients' blood samples were analyzed using the EpiSwitch assay, (Oxford Biodynamics, Oxford, UK), and the results were compared with surgical pathology to determine assay performance., Results: In total, 58 patients were recruited: 20 benign, 20 malignant, and 18 atypia or follicular lesions of undetermined significance. An analysis of the malignant and benign fine needle aspiration groups found 6 epigenetic markers for thyroid. A total of 28 (48%) patients had thyroid cancer. The assay was able to correctly identify 25 of the 28 malignant nodules, showing sensitivity of 89.3% and specificity of 66.7%. The positive predictive value for the assay was 71.4%, whereas the negative predictive value was 87.0%., Conclusion: An epigenetic assay of peripheral blood shows high sensitivity in detecting thyroid cancer and provides an additional method for its diagnosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Histologic subtypes of papillary thyroid cancer affect prognosis. The objective of this study was to examine whether survival is affected by extent of surgery for conventional versus follicular-variant papillary thyroid cancer when stratified by tumor size., Methods: Using the National Cancer Data Base, we evaluated 33,816 adults undergoing surgery for papillary thyroid cancer from 2004 to 2008 for 1.0-3.9 cm tumors and clinically negative lymph nodes. Conventional and follicular-variant papillary thyroid cancers were divided into separate groups. Cox regression models stratified by tumor size were used to determine if extent of surgery affected overall survival., Results: A total of 30,981 patients had total thyroidectomy and 2,835 had thyroid lobectomy; 22,899 patients had conventional papillary thyroid cancer and 10,918 had follicular-variant papillary thyroid cancer. On unadjusted KM analysis, total thyroidectomy was associated with improved survival for conventional (P = 0.02) but not for follicular-variant papillary thyroid cancer patients (P = 0.42). For conventional papillary thyroid cancer, adjusted analysis showed total thyroidectomy was associated with improved survival for 2.0-3.9 cm tumors (P = 0.03) but not for 1.0-1.9 cm tumors (P = 0.16). For follicular-variant, lobectomy and total thyroidectomy had equivalent survival for 1.0-1.9 cm (P = 0.45) and 2.0-3.9 cm (P = 0.88) tumors., Conclusion: Tumor size, histologic subtype, and surgical therapy are important factors in papillary thyroid cancer survival. Total thyroidectomy was associated with improved survival in patients with 2.0-3.9 cm conventional papillary thyroid cancer, and should be considered for 2.0-3.9 cm papillary thyroid cancers when preoperative molecular analysis is not used to distinguish conventional from follicular-variant., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The benefit of adding external beam radiation to adjuvant chemotherapy in patients that have undergone a margin positive resection for early stage, pancreatic ductal adenocarcinoma has not been determined definitively., Methods: The National Cancer Data Base was queried to evaluate the utility of adjuvant radiation in patients with pathologic stage I-II pancreatic ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive margin (margin positive resection) between 2004 and 2013., Results: In the study, 1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node-negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive (pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox modeling stratified by nodal status demonstrated the benefit of radiation to be statistically significant only in node positive patients (hazard ratio 0.81, 95% confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2 months for those receiving adjuvant chemotherapy alone (P=.003). In patients who had negative nodes, there was no difference in overall survival with radiation (22.5 vs 23.6 months, P=.511)., Conclusion: Addition of radiation to adjuvant chemotherapy after a margin positive resection confers a survival benefit albeit limited (about 2 months) in patients with node-positive pancreatic head cancer. (Surgery 2017;160:XXX-XXX.)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Studies evaluating the efficacy of minimally invasive approaches to pancreatoduodenectomy (MIS-PD) compared to open pancreatioduodenectomy (OPD) have been limited by selection bias and mixed outcomes., Methods: ACS-NSQIP 2014-2015 pancreas procedure-targeted data were used to identify patients undergoing PD. Intention-to-treat analysis was performed., Results: Of 7907 PD patients, 1277 (16%) underwent MIS-PD: 776 (61%) robotic or laparoscopic PD, 304 (24%) hybrid, and 197 (15%) unplanned conversions. There were no differences in demographics or comorbidities. Patients undergoing MIS-PD were less likely to have pancreatic ductal adenocarcinoma (30.9% vs 53.9%, P < 0.01) and less likely to have a dilated pancreatic duct (21.8% vs 46.7%, P < 0.01). 30-day morbidity was less for MIS-PD (63.6% vs 76.9%, P < 0.01), due to decreased delayed gastric emptying DGE) in the MIS-PD group (8.6% vs 15.5%, P < 0.01). 30-day mortality, length-of-stay, and readmissions were not significantly different. Patients undergoing MIS-PD had greater rates of CR-POPF (15.3% vs 13.0%, P = 0.03). On adjusted multivariable analysis, MIS-PD was not associated with CR-POPF (OR 1.05, 95% CI 0.87-1.26) but was associated with decreased DGE (OR 0.57, 95% CI 0.46-0.71)., Conclusion: MIS-PD has comparable short-term outcomes to open PD. While CR-POPF rates are greater for MIS-PD, this increased risk appears related to case-selection bias and not inherent to the MIS-approach., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The absolute benefit of adjuvant external beam radiation therapy after a margin-negative resection in early stage pancreatic cancer has not been determined., Methods: We queried the National Cancer Data Base for patients with pathologic stage I-II pancreatic adenocarcinoma who underwent operative resection between 2004 and 2012. Multivariate Cox regression adjusted for age, race, comorbidities, facility type, location and volume, type of pancreatectomy, and tumor grade was used to estimate stage-specific survival., Results: A total of 15,966 patients with stage I-II pancreatic adenocarcinoma underwent upfront operative therapy (no neoadjuvant treatment) and had a margin-negative resection during the study period. A total of 835 (5.2%) patients were pathologic stage IA, 1,539 (9.5%) were stage IB, 3,378 (20.9%) were stage IIA, and 10,214 (63.1%) were stage IIB. Chemoradiation utilization increased with increasing stage (22.8% in stage IA vs 39.6% in stage IIB, P < .01). Chemoradiation was more common at low-volume centers (39.0% vs 31.7% at high-volume centers, P < .01) and with younger age (43.3% of patients <70 years old compared to 25.0% ≥70 years old, P < .01). Treatment at a high-volume center was associated with decreased mortality (hazard ratio 0.80-0.89) across all stages. Age ≥70 years old (hazard ratio 1.18-1.29, P < .01) and higher grade (hazard ratio 1.68-2.69, P < .01) were associated with higher risk of mortality at all stages. Chemoradiation was associated with a benefit in median overall survival over chemotherapy alone for stage IIB disease (21.8 months vs 19.5 months, P < .01). Chemoradiation was not associated with a significant benefit in median overall survival for stage IA, IB, or IIA disease (P > .30)., Conclusion: Addition of radiation to adjuvant chemotherapy after margin-negative resection of pancreatic adenocarcinoma is associated with a limited survival benefit in patients with pathologic stage IIB disease and should be weighed against its associated risks in these patient groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The value of neoadjuvant chemotherapy in the treatment of early stage pancreatic cancer is not yet clear., Methods: We evaluated patients from the National Cancer Data Base who underwent pancreaticoduodenectomy for clinical stage I and II pancreatic adenocarcinoma between 2006 and 2012., Results: In total, 7,881 patients were identified. Of these, 27.5% received no chemotherapy, 57.4% received adjuvant chemotherapy, 10.2% received neoadjuvant chemotherapy alone, and 4.9% received perioperative chemotherapy, both preoperative and postoperative chemotherapy. Neoadjuvant chemotherapy use (neoadjuvant chemotherapy alone and perioperative chemotherapy) increased from 12.0% in 2006 to 20.2% in 2012. Patients who received chemotherapy prior to the operation (neoadjuvant chemotherapy alone and perioperative chemotherapy) had greater rates of margin negative (80.2% vs 73.0%, P < .001) and node negative (58.2% vs 28.7%, P < .001) resections and shorter mean durations of stay (12.0 vs 11.1 days, P = .012) than those receiving either adjuvant chemotherapy or no chemotherapy at all. There were no differences in 30-day unplanned readmissions (P = .074) and 90-day mortality (P = .227). On Cox survival analysis, adjusted for clinical variables including age and comorbid disease, patients undergoing perioperative chemotherapy, adjuvant chemotherapy, and neoadjuvant chemotherapy alone demonstrated significantly improved overall survival relative to that of patients undergoing resection alone (all P < .001). Patients receiving perioperative chemotherapy demonstrated a significant overall survival advantage compared with those receiving adjuvant chemotherapy (hazard ratio 0.75; 95% confidence interval, 0.65-0.85). Neoadjuvant chemotherapy alone had a marginal overall survival benefit compared with adjuvant chemotherapy (hazard ratio 0.89; 95% confidence interval, 0.81-0.98)., Conclusion: Early stage pancreatic cancer patients who receive perioperative chemotherapy have better overall survival than those receiving no chemotherapy, adjuvant chemotherapy, or neoadjuvant chemotherapy alone. Patterns of postoperative morbidity are similar regardless of the sequence of therapy. Neoadjuvant chemotherapy should be considered for patients presenting with early stage pancreatic cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is no consensus regarding prophylactic central lymph node dissection (pCLND) in patients with papillary thyroid carcinoma (PTC). Identification of risk factors for central lymph node metastasis (CLNM) in patients with PTC could assist surgeons in determining whether to perform selective pCLND., Methods: The National Cancer database was queried from 1998 to 2011 for patients with clinical staging T1-4cN0M0 PTC. All patients underwent near, sub-, or total thyroidectomy with or without pCLND. Univariate and multivariable logistic regressions were performed on the following clinical variables: age, sex, race and tumor size as risk factors for pathologic CLNM (pN1a)., Results: In 39,562 patients with T1-4cN0M0 PTC, 61% underwent pCLND. Patients with age >45 years, African American race, tumor size ≤ 1 cm, unifocal tumors, follicular variant PTC, no insurance, and treatment at community cancer facilities were less likely to have pCLND (P < .001). In the pCLND group, 15.6% of patients had CLNM. On adjusted multivariable logistic regression, age ≤ 45 years, Asian race, male sex, and larger tumors were statistically significantly associated with CLNM., Conclusion: Age ≤ 45 years, Asian race, male sex, and larger tumors are associated with the presence of CLNM, which allows for selective pCLND in PTC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: This study compares the predictability of 5 tumor markers for distant metastasis and mortality in pancreatic neuroendocrine tumors (PNETs)., Methods: A total of 128 patients who underwent pancreatectomy for nonfunctioning PNETs between 1998 and 2011 were evaluated. Tumor specimens were stained via immunochemistry for cytoplasmic and nuclear survivin, cytokeratin 19 (CK19), c-KIT, and Ki67. Univariate and multivariate regression analyses and receiver operating characteristics curve were used to evaluate the predictive value of these markers., Results: A total of 116 tumors (91%) were positive for cytoplasmic survivin, 95 (74%) for nuclear survivin, 85 (66.4%) for CK19, 3 for c-KIT, and 41 (32%) for Ki67 >3%. Twelve (9%) tumors expressed none of the markers. Survivin, CK19, and c-KIT had no substantial effect on distant metastasis or mortality. Age >55 years, grade 3 histology, distant metastasis, and Ki67 >3% were associated with mortality (P < .05). A cut-off of Ki67 >3% was the best predictor (83%) of mortality with an area under the curve of 0.85. Ki67 >3% also predicted occurrence of distant metastases with odds ratio of 9.22 and 95% confidence interval of 1.55-54.55 (P < .015)., Conclusion: Of the 5 markers studied, only Ki67 >3% was greatly associated with distant metastasis and death. Survivin, CK19, and c-KIT had no prognostic value in nonfunctioning PNETs., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Endocrine surgery is an evolving subspecialty in general surgery. To determine whether this subspecialty is having an effect on practice patterns of thyroid surgery, we reviewed all thyroidectomies performed in Illinois over an 11-year period., Methods: The Illinois COMPdata database from the Illinois Hospital Association was used to retrieve all the thyroid operations performed in the state of Illinois from 1999 to 2009. Univariate and multivariate logistic regression analyses were performed to assess the effects of surgeon and hospital type on practice patterns of thyroidectomies., Results: In the early period (1999-2004), 5,824 operations were identified compared with 8,454 in the late period (2005-2009; P < .001). Total thyroidectomy represented 2,679 (46%) of the thyroid operations done in the early period compared with 4,976 (59%) in the late period (P < .001). Sixty-two percent of all the thyroid operations were done at community hospitals in the early period compared with 56% in the late period. Endocrine surgeons (ES) performed the greatest rate of thyroidectomies, 0.7 and 0.6/10(5) population, in both early and late periods, respectively., Conclusion: In Illinois, the volume of thyroid operations has increased significantly over the past 10 years with a shift toward total thyroidectomy. Although most thyroidectomies are still performed in community hospitals, this percentage has decreased. ES perform a minority of thyroid operations, but they have the greatest volume of thyroidectomies per surgeon. These findings may represent broader trends in thyroid surgery throughout the United States., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Purpose: The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs., Methods: We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival., Results: The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths., Conclusion: Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Recent studies have shown that the Sonic Hedgehog pathway plays an important role in tumorigenesis and cancer proliferation. The Sonic Hedgehog pathway is required for normal thyroid gland development, but when activated as a result of gene mutation or overexpression, it may stimulate thyroid tumor cell proliferation. This study determines whether 3 molecules, Patched, Smoothened, and Sonic Hedgehog, involved in the Sonic Hedgehog pathway are overexpressed equally in synchronous follicular thyroid adenoma and papillary thyroid carcinoma., Methods: Eighteen patients with synchronous follicular thyroid adenoma and papillary thyroid carcinoma underwent thyroidectomy. Immunohistochemistry was performed on the paraffin-embedded tissue to detect expression of Patched, Smoothened, and Sonic Hedgehog in both tumor types. The expression in these neoplasms was graded by 2 observers., Results: Five patients had insufficient tumor tissue and were removed from the analysis. Patched expression was detected in 5 of 13 (38%) follicular adenomas and 5 of 12 (42%) papillary carcinomas. Smoothened was expressed in 4 of 13 (31%) follicular adenomas and 3 of 13 (23%) papillary carcinomas. Sonic Hedgehog was expressed in 4 of 13 (31%) follicular adenomas and 11 of 13 (85%) papillary carcinomas., Conclusion: Expression of the 3 molecules involved in the Sonic Hedgehog pathway was similar in follicular thyroid adenoma, but Sonic Hedgehog expression was a more sensitive indicator of malignancy in papillary thyroid carcinoma. The Sonic Hedgehog molecule may become a diagnostic marker when the cytologic or histologic features are not characteristic of a papillary carcinoma. Greater understanding of the Sonic Hedgehog pathway may provide molecular methods for preventing or treating papillary thyroid carcinoma., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: The frequency of incidental papillary carcinoma (IPC) has been reported to be between 4.6 % and 10% in operatively treated benign thyroid diseases. This study reviews the occurrence of IPC in thyroid glands removed for benign disease at our institution., Methods: Six hundred and seventy-eight patients underwent partial or total thyroidectomy for benign thyroid diseases. The incidence of IPC was compared among patients with Hashimoto's thyroiditis, multinodular goiter, follicular adenoma, and Graves' disease., Results: Overall, 81 (12.0%) IPCs were recorded with decreasing order of frequency: Hashimoto's thyroiditis, follicular adenoma, goiter, and Graves' disease. Contralateral IPC was detected in 6/15 (40%) patients with follicular adenoma., Conclusion: The overall incidence of IPC in benign operatively resected thyroid disease was 12%. Hashimoto's thyroiditis had the greatest rate of IPC. IPC was encountered in the contralateral lobe in 40% of patients with follicular adenoma. The association of IPCs with Hashimoto's thyroiditis may indicate a link to thyroid cancer. Total thyroidectomy may be considered an appropriate operative treatment in patients with Hashimoto's thyroiditis and follicular adenoma requiring operation owing to the high incidence and frequent contralateral involvement of IPC, respectively.

Background: Sample collection site may affect the dynamics of intraoperative parathyroid hormone monitoring (IPM) and influence surgical decisions., Methods: We prospectively studied 45 patients undergoing parathyroidectomy for primary hyperparathyroidism. The IPM cure criterion was a decrease in peripheral vein (PV) parathyroid hormone (PTH) of >50% at 10 minutes after gland excision. PTH samples were collected simultaneously from PV and central vein (CV) and compared for PTH decay, the incidence of >50% PTH decay, and the incidence of normal PTH values after gland excision., Results: Mean PTH levels were significantly higher from the CV before and after gland excision. Mean PTH decay 10 minutes after gland excision was 89% PV versus 88% CV, resulting in mean PTH levels of 27 +/- 23 and 39 +/- 35 pg/mL, respectively (P < .0001). At 5 minutes, >50% decay in PTH was present in 98% PV versus 88% CV samples. By 10 minutes, the incidence of >50% PTH decay was equivalent (98%). This yielded normal range PTH levels from the PV versus CV in 90% versus 76% of patients at 5 minutes, 96% versus 89% at 10 minutes, and 95% versus 81% at 20 minutes. Of 45 patients, 44 (98%) are normocalcemic at a mean follow-up of 6.3 months. IPM predicted the single operative failure., Conclusions: CV sampling produces significantly higher PTH levels. Surgeons sampling from a PV may observe a >50% decrease in PTH and normal range PTH values starting 5 minutes after gland excision. Surgeons who sample from the CV and require normalization of PTH levels may have to wait longer and/or continue potentially unnecessary neck exploration.

Background: As many as 43% of patients will have normocalcemic intact parathyroid hormone (PTH) elevation after undergoing curative parathyroidectomy for primary hyperparathyroidism. This phenomenon may be due in part to an absolute or relative deficiency of vitamin D, which is under-recognized in patients with primary hyperparathyroidism., Methods: From September 1, 2004, to September 30, 2005, 86 consecutive patients underwent parathyroidectomy for primary sporadic hyperparathyroidism (psHPT). The patients were segregated into 2 groups based on postoperative management. Group 1 was composed of 26 patients who received routine oral calcitriol and calcium carbonate postoperatively. The 60 patients in the second group (group 2) received calcium carbonate postoperatively at the discretion of the primary surgeon., Results: A total of 85 patients (99%) achieved postoperative cure with sustained reduction in serum calcium. Within 30 days postoperatively, mean serum PTH levels normalized in both groups (41 +/- 31 vs 39 +/- 31 pg/ml; P = .91). However, at 1 to 3 months postoperatively, mean serum calcium levels remained similar (9.5 +/- 0.7 vs 9.3 +/- 0.5 mg/dl; P = .39) whereas mean serum PTH levels in groups 1 and 2 were 43 +/- 25 pg/ml and 67 +/- 45 pg/ml (P = .02), respectively. At 4 to 6 months postoperatively, mean PTH was again higher in group 2 (36 +/- 22 vs 67 +/- 35; P = .03), whereas mean serum calcium levels were normal (9.2 +/- 0.8 vs 9.6 +/- 0.4 mg/dl; P = .18). The incidence of postoperative normocalcemic PTH elevation was significantly higher in group 2 at 1 to 3 months (14% vs 39%; P = .04) and at 7 to 12 months (22% vs 83%; P = .04)., Conclusions: Vitamin D supplementation following parathyroidectomy for primary hyperparathyroidism reduces the incidence of postoperative eucalcemic PTH elevation.

Background: Subjective symptoms such as decreased energy, chronic fatigue, and depression are associated with hyperparathyroidism. Studies have shown that these symptoms are improved during short-term follow-up after parathyroidectomy. This study evaluates the durability of this subjective improvement in quality-of-life symptoms in a large population of patients with follow-up greater than 1 year after operation., Methods: Between 2002 and 2005, 258 patients underwent parathyroidectomy, 100 (81 females and 19 males) of whom were available for this study. The patients were evaluated with a survey based on the Health Outcomes Institute Health Status Questionnaire. Some answers were quantified on a 1 to 6 scale, while others consisted of "yes" or "no" responses. Patients completed a questionnaire prior to parathyroidectomy and postoperatively at 1 month, 3 to 6 months, and 1 to 2 years or greater intervals. Statistical analysis was used to detect changes attributable to parathyroidectomy. A P value <.05 was considered statistically significant., Results: At 1-month follow-up, patients' perceptions of their overall health, energy level, and mood significantly improved. At 6-month follow-up, significant improvements in muscle strength, health, endurance, and relief of anxiety were documented. At the interval of 1 to 2 years, overall health, energy level, endurance, and relief of anxiety were improved. There was no significant decrement in the quality of life in these patients after parathyroidectomy., Conclusions: Parathyroidectomy for hyperparathyroidism is associated with significant lasting improvement in subjective symptoms. The potential durable improvement in these quality-of-life symptoms is a valid indication for parathyroidectomy.

Background: Laparoscopic adrenalectomy for small pheochromocytomas, although challenging, is widely accepted. However, its application to pheochromocytomas larger than 6 cm is questioned due to concerns of malignancy and case complexity. Our aim was to examine the impact of pheochromocytoma tumor size (>/=6 cm vs <6 cm) on operative approach and postoperative patient outcomes., Methods: A retrospective review of adrenalectomies performed at 3 university hospitals over 1 decade was analyzed. All pheochromocytomas were identified and then divided based on size into large (>/=6 cm) and small (<6 cm) groups. We examined patient and tumor demographics, pathologic diagnosis, operative approach (laparoscopic vs open), postoperative complications, and biochemical cure rates. Data were analyzed using the Student t test and Fisher exact test with a P value <.05 considered significant., Results: From 1995 to 2005, 65 pheochromocytomas were resected. Of the total, 38% (n = 25) tumors were >/=6 cm and 62% (n = 40) were <6 cm. For the large tumors, 1 out of 25 (4%) was malignant, whereas no small tumors were malignant. There was no statistically significant increased risk of malignancy in tumors >/=6 cm in size (P = .31). Initial operative approach was based on surgeon preference. Of the adrenalectomies performed, 88% were laparoscopic, with 3 of 25 (12%) large tumors requiring conversion from laparoscopic to open for intraoperative bleeding. None of the small tumors required conversion. No major postoperative complications (eg, stroke or myocardial infarction) occurred in either group. Minor complications (eg, wound infections and hematomas) were noted in 16% of large tumors and 12.5% of small tumors (P = .45). A total of 96% (24 of 25) patients with large tumors and 100% with small tumors showed postoperative biochemical cure. Tumor recurrence was noted in 1 patient with a tumor <6 cm., Conclusions: Pheochromocytomas >/=6 cm pose a challenge for laparoscopic resection, and concerns have been raised about the validity of this operative approach. This study demonstrates that there is no significant difference in the rate of malignancy for pheochromocytomas >/=6 cm versus <6 cm. There also were no significant differences identified in complication rates, postoperative biochemical cures, or tumor recurrence rates between these groups. Laparoscopic resection of pheochromocytomas can be safely accomplished regardless of size in centers with surgeons experienced in these procedures.

Background: Intraoperative parathyroid hormone (IOPTH) monitoring in parathyroidectomy for multigland disease is less clear than for single-gland disease. This study assesses the role of IOPTH for hyperplasia., Methods: A prospective database revealed 45 patients with hyperplasia undergoing parathyroidectomy utilizing IOPTH from February 1999 to August 2003., Results: Twenty-six females and 19 males had a mean age of 55 years. Twenty-two patients underwent total parathyroidectomy. Twenty-three patients underwent subtotal parathyroidectomy. Twenty-seven patients (60%) had a drop of IOPTH greater than 50% at 10 minutes after removal of all presumably abnormal parathyroid tissue. Nine additional patients (20%) had an IOPTH drop greater than 50%, but continued exploration revealed more abnormal tissue. Nine patients failed to decrease greater than 50%, and exploration was continued. A final IOPTH less than 35 pg/mL or a greater than 90% decrease from baseline was predictive of a successful operation in 40 patients. The 5 patients who did not meet this criteria remained hyperparathyroid., Conclusions: IOPTH identifies sporadic hyperplasia and guides completeness of resection for patients with known hyperplasia. However, more rigid criteria are required than for adenomas. Failure to achieve appropriate decreases in IOPTH should prompt further neck exploration or a search for a mediastinal gland.

Background: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery., Methods: Between February 2001 and June 2002, 61 patients (14 males and 47 females, mean age of 60.8+/-14.4 years) underwent parathyroidectomy. There were 45 patients with single-gland adenomas, 9 patients with double adenomas, 3 patients with primary hyperparathyroidism from 4-gland hyperplasia, 3 patients with secondary hyperparathyroidism, and 1 patient with tertiary hyperparathyroidism. Patients filled out a 53-question survey based on the Health Outcomes Institute Health Status Questionnaire 2.0 before surgery, 1 month postoperatively, and 3-24 months postoperatively. The survey included questions on overall health, daily activities, mood, and medical conditions. Surveys were analyzed for changes in symptoms attributable to parathyroidectomy. Serum calcium and intact parathyroid hormone levels were obtained preoperatively and at 1- and 3-month follow-up visits., Results: At both postoperative evaluations, patients' perception of general health, muscle strength, energy level, and mood significantly improved (P<.05). Moreover, there was a significant correlation between the changes in serum calcium and intact parathyroid hormone levels and improvement in symptoms., Conclusions: Parathyroidectomy for hyperparathyroidism is associated with significant improvement in patient quality of life. These subjective symptoms represent a valid indication for parathyroidectomy.

Background: Interest in general surgery has declined among US medical students, with the increasing number of female medical students being cited as a causative factor. This study evaluates factors related to choosing a general surgery career and determines if they differ between men and women., Methods: A survey assessing factors that contributed to career choice was distributed to a 2002 graduating medical school class to be returned with their match lists. Students were asked, from a given list, which factors influenced their career choice. Those students who did not pursue a career in general surgery were asked what factors contributed to that decision. The results were stratified by gender., Results: Of 120 surveys, 54 women and 48 men responded (response rate=85%). The reason most commonly cited for a particular career choice by both men and women was the intellectual challenge of the field, chosen by 41 men (85%) and 46 women (85%). The two next most common reasons cited by male students were an elective in the field and practice lifestyle (40 of 48 respondents, or 82%, for each). Practice lifestyle was a contributing factor for 37 of the 54 women, or 69% (P=.132). The other reasons most commonly cited by women were an elective and faculty in the chosen field (46 of 54, or 85%, and 38 of 54, or 70%). Thirty-seven of the 48 men, or 77% (P=.588), felt that faculty in the field contributed to their career choice. The most commonly cited reasons for not choosing general surgery--residency lifestyle, practice lifestyle, and length of training--were the same for both groups., Conclusions: Fewer women than men considered practice lifestyle in choosing their medical career. However, both men and women considered lifestyle, elective in the field of choice, and faculty important in career choice. In 2002, men and women had the same reasons for pursuing a career in general surgery or seeking another specialty.

Background: Early survival after pancreaticoduodenectomy has improved, but its morbidity remains high. The purpose of this study is to determine how the intra-operative (OR) occurrence of major vascular complications affects the outcome of pancreaticoduodenectomy., Methods: The medical records of 180 consecutive patients having pancreaticoduodenectomy from 1991 to 2001 were reviewed. Vascular complications were defined as "an unanticipated injury or thrombosis of a major vessel necessitating intervention." Age, sex, type of pancreaticoduodenectomy, tumor size, estimated blood loss, OR time, time in intensive care, post-OR hospitalization, and survival were compared., Results: Eighteen vascular complications were identified. Differences in age, sex, and type of resection between patients with or without vascular complications were not significant. OR time, estimated blood loss, blood transfusions, tumor size, time in intensive care, and post-OR hospitalization were all significantly greater in patients with vascular complications. Median survival for patients with vascular complications was significantly shorter than for patients without vascular complications. Thirty-day mortality was greater in patients with vascular complications., Conclusion: Vascular complications significantly affect the outcome of pancreaticoduodenectomy increasing OR time, estimated blood loss, blood transfusion requirements, time in intensive care, post-OR hospitalization, and mortality.

Background: Metastasis of malignant breast cells is in part mediated through degradation of the extra-cellular matrix by proteolysis, enabling malignant cells to migrate through the surrounding stroma. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades the heparan sulfate (HS) moiety of proteoglycans, a component of the extracellular matrix and basement membrane., Methods: Fifty-one primary breast tumors, 13 lymph node metastases, 4 ductal carcinoma in situ, 7 benign, and 5 normal specimens were examined for HPR1 expression using immunohistochemical staining. The functional role of HPR1 expression was determined by examining HS deposition using immunofluorescence staining., Results: Sixteen of 30 breast carcinomas (53%) with sentinel node metastasis expressed HPR1. In contrast, only 5 of 21 nonmetastatic primary breast carcinomas (23%) were HPR1 positive. Eighteen of 30 breast carcinomas between 1 and 5 cm expressed HPR1, compared with 3 of 21 HPR1-positive specimens in tumors < or =1 cm. Statistical analysis revealed that HPR1 expression was associated with breast tumor metastases (P =.04) and primary tumors between 1 and 5 cm (P =.002). Ninety percent of HPR1-positive tumors lacked HS deposition, suggesting an inverse correlation between HPR1 expression and HS deposition., Conclusions: HPR1 expression correlates with the lack of HS deposition and with the metastatic potential of breast cancers. The frequency of HPR1 is significantly higher in breast tumors between 1 and 5 cm than in tumors < or =1 cm.

Background: Intraoperative intact parathyroid hormone (iPTH) is being used to confirm complete excision of hyperfunctioning parathyroid tissue. It is uncertain whether normalization of intraoperative iPTH levels accurately predicts long-term postoperative iPTH values., Methods: Fifty-two consecutive patients with primary or secondary hyperparathyroidism underwent parathyroidectomy with measurement of intraoperative iPTH. Ten patients were excluded due to incomplete laboratory follow-up. Follow-up serum calcium and iPTH levels were measured at 1- and 3-month intervals., Results: Before operation, the mean serum iPTH level was 249 pg/mL (SD=208) and mean serum calcium level was 11.4 +/- 0.9 mg/dL (+/- SD). In all but 4 patients, final intraoperative iPTH levels normalized to less than 67 +/- 41 pg/mL (mean, 35 pg/mL). One week after operation, serum calcium levels had returned to normal (mean, 9.4 +/- 1.1 pg/mL), which directly correlated with the final intraoperative serum iPTH values (Pearson correlation, r = -.434; P <.01). By 1 month, all but 2 patients were normocalcemic (mean, 9.4 +/- 0.9 pg/mL) with a mean iPTH level of 74.8 +/- 82 pg/mL. There was no correlation between final intraoperative and postoperative serum iPTH values (r =.099; P <.533). Both patients with persistent hypercalcemia at 1 month had appropriate intraoperative decreases in iPTH values., Conclusions: Intraoperative serum iPTH levels significantly correlate with postoperative serum calcium levels but not with postoperative serum iPTH levels. There was a 4.8% failure rate in the correction of postoperative serum calcium levels and a 29% failure rate in the normalization of postoperative serum iPTH levels.

Background: Reoperative neck exploration for hyperparathyroidism is often difficult even for experienced surgeons. Recent advances in preoperative and intraoperative localization techniques have improved successful resection rates. This prospective study evaluates the accuracy and clinical utility of intraoperative technetium 99m sestamibi scanning for localizing hyperfunctioning parathyroid tissue in reoperative neck explorations., Patients and Methods: Eleven patients underwent reoperative neck exploration for hyperparathyroidism. Two patients had 3 prior neck explorations, 1 had 2 prior neck explorations, and 8 patients had 1 prior neck operation. Preoperative studies included sestamibi scintigraphy and ultrasound in all patients, magnetic resonance imaging in 4, computed tomography scan in 3, parathyroid arteriogram in 1, and selective venous sampling in 1. All patients underwent intraoperative technetium 99m sestamibi scanning and parathyroid hormone assay., Results: Preoperative technetium 99m sestamibi scanning and ultrasound each successfully localized 7 of 11 hyperfunctioning glands (64%). Intraoperative technetium 99m sestamibi scanning correctly localized 10 of 11 hyperfunctioning glands (91%). Intraoperative parathyroid hormone assay confirmed successful excision of hyperfunctioning tissue in all 11 patients. Postoperatively, all 11 patients had low-normal or normal calcium levels., Conclusions: Intraoperative technetium 99m sestamibi correctly localized 91% of hyperfunctioning glands compared with 64% localization for preoperative technetium 99m sestamibi and preoperative ultrasound. Intraoperative technetium 99m sestamibi scanning and parathyroid hormone monitoring are useful in reoperative neck explorations for hyperparathyroidism.

Background: The goal of this study was to evaluate the safety and efficacy of total thyroidectomy performed for benign thyroid disease., Methods: A total of 106 consecutive patients undergoing total thyroidectomy for benign disease from October 1982 to July 1995 were reviewed. The 33 men and 73 women had an average age of 46 years (range, 16 to 82 years). Indications for total thyroidectomy were a thyroid nodule with the history of head and neck radiation in 36 patients, bilateral thyroid nodules in 35, needle biopsy of a follicular neoplasm or frozen section diagnosis of a possible malignancy in 18, and toxic goiter in 17. Total thyroidectomy was performed as the primary operation in 98 patients, and 8 patients had a completion reoperation for recurrent disease., Results: Pathology findings revealed benign nodular goiter in 49 patients, follicular adenoma in 26, hyperplasia in 19, and Hashimoto's thyroiditis in 12. Postoperative hemorrhage requiring operative hemostasis occurred in two patients (1.9%). Two patients had unilateral recurrent laryngeal nerve (RLN) palsy before operation (1.9%). Three patients had unilateral postoperative RLN palsy (2.8%). Two cases resolved in 3 and 4 months. The only permanent RLN injury occurred in a patient reoperated for a compressive goiter. Early postoperative hypocalcemia (8.0 mg/dl or less) was found in nine patients (8.5%). No patient had permanent hypoparathyroidism at long-term follow-up evaluation., Conclusions: Total thyroidectomy for benign thyroid disease can avoid reoperation for nodular goiter and hyperthyroidism and eliminate any subsequent risk of malignant change in radiated thyroid glands. A low complication rate can be achieved with meticulous surgical technique. Total thyroidectomy can be performed safely for bilateral benign thyroid disease.

Background: This study evaluates the indication for frozen section (FSx) in the management of the solitary thyroid nodule given the increasing use of fine-needle aspiration biopsy (FNAB)., Methods: The charts of 561 patients who underwent thyroidectomy for a solitary nodule were reviewed. Each patient underwent either FNAB, FSx, or both. Results were compared to the final diagnosis to evaluate their effectiveness in predicting malignancy., Results: The sensitivity and specificity for FNAB alone (162 patients) were 86% and 91%, respectively, and for FSx (494 patients) 79% and 99%, respectively. The routine use of FSx with diagnostic FNABs did not improve the accuracy over either test alone. Sensitivity, specificity, and accuracy were essentially unchanged when the use of FSx was limited to just atypical FNAB but dropped significantly when FSx was not used., Conclusions: When results of FNAB and FSx are interpreted as benign or malignant, both are highly accurate predictors of malignancy. Routine use of FSx and FNAB does not improve the sensitivity or specificity in the detection of malignancy over that of either examination alone. FSx proved useful in determining the extent of operation only when results of the FNAB were atypical.

Background: Angiogenesis correlates with growth and likely metastases in several tumors. To determine whether it has a similar role in pheochromocytomas, immunohistochemical staining of factor VIII was done on the tumor tissue of 42 patients., Methods: Formalin-fixed, paraffin-embedded tissue was obtained from 29 women and 13 men with 24 primary adrenal and 18 extraadrenal pheochromocytomas. Patients were divided into two groups. Group 1 included 32 patients with benign pheochromocytomas, and group 2 included 10 patients with malignant tumors evidenced by capsular or vascular invasion (six), liver metastases (three), or periaortic lymph node metastases (one). Blood vessels highlighted by factor VIII staining of endothelial cells with labeled streptavidin-biotin were counted under light microscopy. Mean vessel count within a 10 mm2 micrometer disk was calculated under x100, x200, and x400 magnification fields., Results: There were no significant differences in patient age or clinical symptoms between the groups. The mean tumor size in group 2 of 8.8 +/- 5.3 cm was larger than the mean of 4.8 +/- 2.8 cm in group 1 (p < 0.005). The mean counts of vessels in the x100, x200, and x400 magnification fields were 102 +/- 48, 40 +/- 18, and 19 +/- 9 in group 1, and 203 +/- 77, 73 +/- 28, and 37 +/- 15 in group 2. The number of blood vessels in group 2 was significantly higher than in group 1 (p < 0.001) in each studied field., Conclusions: In this study the number of tumor blood vessels correlated with the invasive behavior of pheochromocytomas. Tumor angiogenesis may be useful in determining the likelihood of malignant behavior in pheochromocytomas.

Background: Recently laparoscopy has been described as an alternative approach for performing adrenalectomy. This study attempts to define the frequency and indications for the various approaches to adrenalectomy including laparoscopy., Methods: From October 1992 to December 1995, 43 adrenal glands were excised from 40 patients, of whom 23 were women and 17 were men. Their ages ranged from 16 to 71 years. Nineteen operations were performed for pheochromocytoma, 10 for cortical adenoma (CAd), 6 for aldosteronoma, 4 for adrenocortical cancer (ACC), 1 for Cushing's disease (CD), and 1 for hemorrhagic cyst. Adrenalectomy was accomplished via a laparoscopic operation in 20 patients (8 CAds, 6 pheochromocytomas, 5 aldosteronomas, and 1 HC) and via an open operation in 19 patients (11 pheochromocytomas, 4 ACCs, 2 CAds, 1 CD, and 1 aldosteronoma). One patient with bilateral pheochromocytoma had an open and a laparoscopic adrenalectomy., Results: Open operations included 15 transabdominal, 4 posterior, and 3 thoracoabdominal approaches for 22 glands. Laparoscopic operations included 17 transabdominal and 4 retroperitoneal approaches for 21 glands. Reasons for open operations included obesity (1), patient choice (2), failed laparoscopy (2), previous abdominal surgery (3), extraadrenal location (5); and gland size greater than 8 cm (9). Of these cases, the two patient choices, the two failed laparoscopies, and two of the three previous abdominal operations were appropriate for laparoscopy. Each of the posterior approaches could have been done laparoscopically., Conclusions: More than 60% of surgically treatable adrenal disease may be approached laparoscopically. Transabdominal, and on occasion, thoracoabdominal approaches are indicated for larger adrenal lesions. Surgeons operating on the adrenal gland should be familiar with each of these various approaches for adrenalectomy.

Background: The effect of granulocyte colony-stimulating factor (G-CSF) on the rate of secondary infections in acute pancreatitis was evaluated in a canine model. Infectious complications are the major determinant of morbidity and mortality in severe pancreatitis. Bacterial translocation has been shown to be a cause of these secondary infections. The relative immunosuppression found with pancreatitis may promote translocation and the spread of bacteria to the pancreas., Methods: Thirty-four mongrel dogs were studied. Pancreatitis was induced in 18 dogs; 9 were treated with 100 micrograms G-CSF/day and 9 were given only saline solution. Laparotomy alone was done in 16 dogs of which one half were given 100 micrograms G-CSF/day and one half were given saline solution. Daily blood counts and cultures were obtained. All dogs were killed on day 7, and the mesenteric lymph nodes, pancreas, liver, spleen, and peritoneal fluid were cultured and studied histologically., Results: G-CSF caused a significant and sustained increase in mature granulocytes in dogs given pancreatitis. No difference was found in the rate of translocation to mesenteric lymph nodes in dogs given G-CSF (n = 4) versus dogs given saline solution (n = 6). However, a significant decrease occurred in the spread of bacteria to distant sites in dogs given G-CSF (1 versus 15, p < 0.05)., Conclusions: Although G-CSF does not decrease the rate of translocation, it does decrease the rate of distant infection in severe acute pancreatitis.

Background: Most abnormal parathyroid glands can be removed through the neck, but those deep in the chest have required sternotomy or thoracotomy. To avoid the morbidity of these open procedures, ectopic parathyroid glands deep in the chest were removed with video-assisted thoracoscopy., Methods: Two patients with persistent primary and two with persistent secondary hyperparathyroidism had technetium-thallium scintigraphy and computed tomography of the chest to localize their ectopic glands. Video-assisted thoracoscopy was used for operative removal of these glands in each patient., Results: Parathyroid scans identified a mediastinal gland that was confirmed and localized precisely by the computed tomography scan. An enlarged ectopic gland weighing 1 to 2 gm was removed from each patient with normalization of serum calcium level. Glands were found by the main pulmonary artery, aortopulmonary window, ascending aorta, and aortic arch. One patient had recurrent disease 9 months later., Conclusions: Removal of parathyroid glands deep in the chest with video-assisted thoracoscopy is a safe and successful alternative to median sternotomy.

Background: Adrenalectomy performed by a posterior or transabdominal approach causes substantial postoperative pain. The purpose of this study was to evaluate laparoscopy as a potential approach for adrenalectomy., Methods: We performed 25 consecutive laparoscopic adrenalectomies on 22 patients from April 1, 1992, to March 30, 1993. Laparoscopic surgery was performed by using a lateral decubitus flank approach with four 11 mm trocars., Results: Twelve right and 13 left adrenal glands were removed in a mean time of 2.3 hours. Three patients underwent bilateral adrenalectomies in a mean time of 5.3 hours. The 15 women and 7 men range in age from 31 to 60 years (mean, 42 years). The adrenal gland diseases were nonfunctional adenoma (seven), pheochromocytoma (five), Cushing's disease (four), Cushing's adenoma (four), primary aldosteronism (two), dehydroepiandrostenedione sulfate hypersecretion (one), angiomyolipoma (one), and medullary cyst (one). Average tumor size was 4.1 cm (range, 1 to 15 cm). Laparoscopic adrenalectomy was successful in 96% of patients, with one patient requiring a laparotomy because of inadequate exposure. The median postoperative stay was 4 days (range, 2 to 19), with a mean of five narcotic injections. There were no deaths, and morbidity was minor., Conclusions: Laparoscopy can be used successfully for adrenalectomy. It produces less postoperative pain and rapid return to normal activity. It may be the preferred method for removing most adrenal gland lesions that require operation.

Background: Duodenal somatostatinomas are rare tumors that are often asymptomatic or present with local symptoms rather than with evidence of excess somatostatin production. To characterize the clinical presentation and management of these neoplasms we reviewed the course of four patients., Methods: The records of three men and one woman with duodenal somatostatinomas, who were treated between 1988 and 1992, are reviewed., Results: Three of the patients presented with vague gastrointestinal complaints, and one was free of symptoms. No patient had symptoms of somatostatinoma syndrome, nor did any have associated neurofibromatosis. Three patients were diagnosed after biopsy of a submucosal mass during upper endoscopy. Three patients with tumors that measured less than 2 x 2 cm underwent local resection. One patient with a large tumor and liver metastases underwent a Whipple's operation and resection of the liver lesions. Immunohistochemically all tumors predominantly contained somatostatin, although each had traces of other neuropeptides. All tumors contained psammoma bodies. Follow-up periods ranged from 1 to 4 years., Conclusions: Duodenal somatostatinomas often appear with only local symptoms or are completely asymptomatic. Small tumors may be locally excised. Intraarterial methylene blue injection may help localize very small tumors during operation. Larger tumors, including those with localized metastases, should also be resected when possible.

Background: Reports evaluating the efficacy of fine needle aspiration (FNA) of the adrenal gland have suggested a possible correlation between size of an adrenal mass and the presence of a primary or metastatic malignancy. These studies have focused on FNAs of all adrenal gland masses regardless of clinical history. This study investigates this relationship in a subpopulation of patients with a known history of primary extraadrenal malignancy., Methods: All patients who have undergone computed tomographic-guided FNA biopsy of an adrenal mass at Loyola University Medical Center and Hines Veterans Administration Hospital, from 1985 to 1991, were reviewed., Results: If size was assumed to be an independent predictor for presence of metastases, the highest efficiency was obtained with a cutoff value of 3 cm. This value divided the group into 15 (42%) "low-risk" (< or = 3 cm) and 21 (58%) "high-risk" (> 3 cm) subjects. In the "low-risk" group, 87% of the masses (13 of 15) were benign and 13% (2 of 15) were malignant. Within the "high-risk" group, more than 95% of the masses (20 of 21) were malignant, with a single (5%) benign case (p < 0.05)., Conclusions: There is a significant correlation between the size of an adrenal nodule and the presence of metastases in patients with a known primary extraadrenal malignancy. Nodules greater than 3 cm have a very high probability of involvement by metastatic tumor. Nodules 3 cm or smaller are usually benign, but metastatic tumor can still be found in up to 13%. FNA biopsy is useful in evaluating adrenal masses in this setting.

Background: Computed tomography and endoscopic drainage are used increasingly to treat pancreatic pseudocysts (PP). We reviewed our experience with PP to compare the outcomes of patients operated on initially (group 1) with those whose nonoperative treatment failed (computed tomography-guided or endoscopic drainage) before operation (group 2)., Methods: The records of 70 consecutive patients operated on for PP were reviewed. The 52 patients (74%) in group 1 and 18 (26%) in group 2 were compared in terms of clinical features, laboratory test results on examination and before operation, operative findings, morbidity, mortality, and recurrence rates., Results: Before the initial drainage attempt, mean serum amylase level was higher in group 2 (542 +/- 25 vs 163 +/- 17 IU/L; p = 0.01). All other laboratory values were similar. Before operative drainage, group 2 patients had lower hemoglobin (10.7 +/- 0.5 vs 12.2 +/- 0.3 gm/dl; p < 0.05) and serum albumin level (2.7 +/- 0.2 vs 3.5 +/- 0.1 mg/dl; p < 0.01) than group 1. Morbidity was twice as frequent in group 2 (33% vs 14%). The time from initial attempt at drainage to PP resolution was longer in group 2 (104 +/- 36 vs 20 +/- 4 days; p = 0.01). However, the time from operation to resolution was similar in both groups (21 +/- 8 vs 20 +/- 4 days)., Conclusions: Failed nonoperative drainage is associated with a protracted illness and carries a risk of increased morbidity after operative intervention.

Operative exploration with attempted curative resection should be attempted on virtually all patients with islet cell tumors of the pancreas who do not have metastatic disease evident on preoperative studies. Because of the small size and variable location of many of these neoplasms, localization studies play an important role in ensuring appropriate and successful surgical therapy. A review of currently available preoperative and intraoperative aids for tumor localization is presented. A new technique of selective intraarterial injection of methylene blue is described along with a report of our preliminary results. Further evaluation and use of this technique and other newly developed technologies are warranted to lower the commonly reported 10% to 30% negative exploration rate for these sometimes elusive tumors.

Background: Infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have been proposed as distinct clinical entities in terms of treatment and outcome. To evaluate this classification, we reviewed the clinical course and bacteriologic findings of pancreatic infections., Methods: Of 1299 patients with pancreatitis or a related complication admitted over a 7-year period, 64 (4.9%) with culture-documented secondary pancreatic infections were reviewed with regard to cause, clinical course, bacteriologic findings, and outcomes., Results: Group I consisted of 23 patients with infected pseudocysts; group II, 20 patients with pancreatic abscesses; and group III, 21 patients with infected pancreatic necrosis. The causes were alcohol in 36%, biliary tract disease in 30%, and postoperative in 16%, with no significant difference between groups. Patients in group I had abdominal pain or a mass without accompanying signs of sepsis, whereas patients in groups II and III had sepsis. In group I, 15 patients were treated with internal drainage, four with percutaneous drainage, and four with external drainage. In group II, three had percutaneous drainage, 15 operative drainage, and two open packing. In group III, 19 patients had operative drainage and two had open packing. Morbidity occurred in 26% of patients in group I, 40% in group II, and 90% in group III (p less than 0.001). Mortality rates were 9% in group I, 25% in group II, and 48% in group III (p less than 0.01). Enteric organisms were present in 66% of isolates, with no difference between groups, suggesting a common mode of infection., Conclusions: Despite similar bacteriologic findings, infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have significantly different presentations, clinical courses, and outcomes, confirming that they are distinct entities. This distinction is important when therapeutic outcomes are compared.

Background: Morbid obesity has been considered a contraindication to laparoscopic cholecystectomy (LC)., Methods: To evaluate this we reviewed our first 201 patients undergoing LC and compared the operative procedure and outcome in morbidly obese (greater than or equal to 100 pounds over ideal body weight [IBW]) and nonobese patients. We also compared a group of morbidly obese patients who underwent standard open cholecystectomy (n = 11) with the obese group undergoing LC (n = 21). All groups were comparable in terms of age, sex, and symptoms (acute vs chronic). The obese groups undergoing LC and open cholecystectomy had similar weights (134.0 +/- 9.4 pounds over IBW [range, 100 to 286 pounds] and 133.8 +/- 6.0 pounds over IBW [range, 108 to 170 pounds], respectively) and were significantly different from the nonobese group undergoing LC (28.3 +/- 2.0 pounds over IBW [range, 23 to 98 pounds]). Parameters evaluated included operative time, resumption of normal diet, length of postoperative hospitalization, complications, conversion to open procedure, and ability to perform cholangiography., Results: There were no statistically significant differences between the obese and nonobese groups undergoing LC in any parameters studied (operative time, 151.7 +/- 4.0 minutes vs 160.7 +/- 9.9 minutes; tolerance of diet, 1.2 +/- 0.1 days vs 1.1 +/- 0.1 days; time to discharge, 2.0 +/- 0.1 days vs 1.8 +/- 0.2 days; complications, 7.0% vs 0.0%). Operative time (117.6 +/- 11.6 minutes) was shorter (p = 0.45) in obese patients undergoing open cholecystectomy. However, time to normal diet and length of postoperative hospitalization were significantly longer (3.1 and 4.6 days, respectively; p less than 0.01), and there were more complications (18.2%)., Conclusions: Rather than being contraindicated in the morbidly obese, LC appears to be the preferred method of cholecystectomy.

Calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) are potent hypotensive agents. To determine if they play a counterregulatory role in catecholamine excess in patients with pheochromocytoma, plasma levels were measured in four patients undergoing resection of sporadically occurring tumors. Each patient was prepared with phenoxybenzamine hydrochloride (Dibenzyline); two patients also received propranolol. Blood was obtained for plasma levels of epinephrine, norepinephrine, CGRP, and ANP at induction of anesthesia, skin incision, tumor manipulation, tumor removal, and 24 hours after operation. Baseline plasma norepinephrine and epinephrine levels were markedly elevated and increased significantly with tumor manipulation and decreased significantly 24 hours after operation. CGRP and ANP levels were slightly elevated throughout but did not change significantly with tumor manipulation or early after tumor resection. Circulating CGRP and ANP do not appear to have an acute counterregulatory role in catecholamine excess in patients with pheochromocytoma but may exert some influence on postoperative hypotension after tumor removal.

This report discusses our experience with two patients who had unilateral adrenalectomy during pregnancy as treatment for Cushing's syndrome secondary to an adrenal adenoma. Previously only five patients with this clinical problem who underwent unilateral adrenalectomy during pregnancy had been reported. We have reviewed the world literature on Cushing's syndrome in pregnancy secondary to an adrenal adenoma. A total of 19 patients who had unilateral adrenalectomy for this problem after the completion of pregnancy were identified. The review of world literature and the two patients who are the subject of this report were the basis of our analysis of fetal death, neonatal complications, and maternal complications in seven pregnancies during which unilateral adrenalectomy was performed (group 1) compared to the 19 pregnancies that were associated with unilateral adrenalectomy at the completion of pregnancy (group 2). Of the seven pregnancies in group 1, one fetal death and no neonatal complications occurred, but fetal death and neonatal complications occurred in 12 of the 19 pregnancies in group 2. Four of the seven mothers in group 1 had complications; 16 of the 19 mothers in group 2 had complications. This study suggests that adrenalectomy during pregnancy should be considered as a therapeutic option in the management of Cushing's syndrome secondary to an adrenal cortical adenoma.

Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.

To compare the effectiveness of cystgastrostomy and cystjejunostomy for treatment of pancreatic pseudocysts, 39 patients with cystgastrostomy were compared to 59 patients with cystjejunostomy. The groups were comparable in age, sex, cause of pancreatitis, pseudocyst location, symptoms, and preoperative serum amylase level. Cysts treated with cystgastrostomy were larger (mean diameter, 11.1 +/- 0.9 cm) than cysts treated by cystjejunostomy (mean diameter, 6.7 +/- 0.7 cm) (p less than 0.05). Mean duration of surgery was 148 +/- 11 minutes for cystgastrostomy versus 265 +/- 15 minutes for cystjejunostomy (p less than 0.05). Mean blood loss was 397 +/- 82 ml for cystgastrostomy versus 703 +/- 80 ml for cystjejunostomy (p less than 0.05) Mean intraoperative fluid requirements were 2640 +/- 313 ml for cystgastrostomy and 4403 +/- 362 ml for cystjejunostomy (p less than 0.05). Cyst recurrence was 10% for cystgastrostomy versus 7% for cystgastrostomy. Postoperative gastrointestinal bleeding occurred in 8% of patients with cystgastrostomy and in 2% of patients with cystjejunostomy. Infection problems with cystjejunostomy included two wound infections and one case of septicemia; infection problems with cystjejunostomy included five intraabdominal abscesses, two wound infections, and one case of pneumonia. Two patients died with cystgastrostomy (both from gastrointestinal bleeding); two patients died with cystjejunostomy (one from intraabdominal sepsis and one from pulmonary embolus). Cystgastrostomy was used for significantly larger pseudocysts and was associated with significantly less blood loss and operating time than cystjejunostomy (p less than 0.05). Morbidity and mortality from cystgastrostomy and cystjejunostomy were comparable, although gastrointestinal bleeding was more common with cystgastrostomy and intraabdominal abscess was more common with cystjejunostomy. Since cystgastrostomy can usually be performed more quickly and with less blood loss, it should be considered whenever anatomically feasible.

Although thyroid disease in humans predominates in females, the prognosis of thyroid cancer in males is much less favorable. To further explore the role of male sex hormones, we utilized the experimental model of radiation-induced follicular cancer in the rat, studying the effects of castration on tumor development. Microscopic evidence of tumor formation was correlated with the biochemical parameters serum thyroxine (T4), thyrotropin (TSH), and thyrocalcitonin (TC) at 24 months. The incidence of follicular carcinomas in intact males ws 58%, compared to 28% in comparable females. Castration of males caused a reduction in the incidence to 22%. Mean circulating levels of TSH were markedly elevated in all three irradiated groups. Mean T4 levels were reduced significantly only in irradiated castrated animals. TC levels were reduced in all irradiated groups. We conclude that although elevated levels of TSH probably play a significant role in the development of radioactive iodine-triggered follicular thyroid neoplasms in the rat, male sex hormone may also play an important role beyond their known effect on basal and thyrotropin-releasing hormone-stimulated TSH.