Barbra S. Miller

Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer

BACKGROUND Prophylactic central lymph node dissection with total thyroidectomy (TT) for the treatment of papillary thyroid cancer (PTC) is controversial because of the possibility of increased morbidity with uncertain benefit. The purpose of this study is to determine whether prophylactic central neck dissection provides any advantages over TT alone. METHODS Retrospective cohort study of patients with PTC without preoperative evidence of lymph node involvement undergoing either TT or TT with bilateral central lymph node dissection (TT + BCLND). RESULTS From 2002 to 2009, 143 patients with clinically node-negative PTC underwent either TT (n = 65) or TT + BCLND (n = 78). The groups were similar in age, gender, tumor size, multifocality, angioinvasion, and metastasis/age/completeness-of-resection/invasion/size score. The presence of involved central neck lymph nodes upstaged 28.6% of patients in the TT + BCLND group to stage III disease, which resulted in higher radioactive iodine ablation doses. Stimulated serum thyroglobulin levels and the number of patients with undetectable stimulated thyroglobulin levels before and 1 year after radioactive iodine ablation were equivalent. CONCLUSION The addition of routine central lymph node dissection to TT for the treatment of PTC upstages nearly one third of patients over the age of 45 thereby changing the dose of radioactive iodine ablative therapy, but does not change postoperative thyroglobulin levels after completion of radioiodine treatment.

The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years.

BACKGROUND The incidence of papillary thyroid cancer (PTC) is growing at a faster rate than any other malignancy. However, it is unknown what effect age is having on the changing PTC incidence rates. With the goal of understanding the role of age in thyroid cancer incidence, this study analyzes the changing demographics of patients with PTC over the past three decades. METHODS This was a retrospective evaluation of the incidence rates of PTC from 1973 to 2006 reported by the National Cancer Institutes Surveillance, Epidemiology, and End Results database. RESULTS From 1973-2006 the age group most commonly found to have PTC has shifted from patients in their 30s to patients in the 40-50-year-old age group. In 1973 60% of PTC cases were found in patients younger than 45, and the majority of cases continued to occur in younger patients until 1999. After 1999 PTC became more common in patients older than 45 years, and in 2006, 61% of PTC cases were in patients older than 45 years. From 1988 to 2003 there has been an increasing incidence of all sizes of PTC in all age groups with the largest increase in tumors <1 cm in patients older than 45. Forty-three percent of tumors in patients older than 45 are now <1 cm, whereas only 34% are <1 cm in patients younger than 45. Of the nearly 20,000 thyroid cancer cases in 2003, 24% were microcarcinomas in patients over the age of 45. CONCLUSIONS The incidence of PTC is increasing disproportionally in patients older than 45 years. The number of PTC tumors smaller than 1 cm is increasing in all age groups, and now the most commonly found PTC tumor in the United States is a microcarcinoma in a patient older than 45 years. These changing patterns relating age and incidence have important prognostic and treatment implications for patients with PTC.

Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy

BACKGROUND Controversy surrounds the use of laparoscopy for resection of adrenocortical carcinoma. We evaluated the hypothesis that outcome is equivalent in patients undergoing laparoscopic adrenalectomy versus open adrenalectomy. METHODS This is a retrospective review of 217 patients (156 patients with stage I-III cancer) with adrenocortical carcinoma referred to a single institution between 2005 and 2011. Outcome and operative data were assessed for the subset undergoing resection with curative intent. Student t and Fisher exact tests and the Kaplan-Meier method were used to compare data (P ≤ .05 was considered statistically significant). RESULTS One hundred fifty-six patients (64% female; median age, 47 years [range, 18-80]; median follow-up, 26.5 months [range, 1-188]) were identified. Forty-six patients underwent laparoscopic adrenalectomy, and 110 underwent open adrenalectomy. Twenty-seven percent of laparoscopic adrenalectomy patients had stage III cancer. After laparoscopic adrenalectomy, 30% had positive margins or intraoperative tumor spill compared to 16% of the open adrenalectomy patients (P = .04). Overall survival for patients with stage II cancer was longer in those undergoing open adrenalectomy (P = .002). Time to visible tumor bed recurrence or peritoneal recurrence in stage II patients was shorter in laparoscopic adrenalectomy patients (P = .002). CONCLUSION Open adrenalectomy is superior to laparoscopic adrenalectomy for adrenocortical carcinoma based on completeness of resection, site and timing of initial tumor recurrence, and survival in stage II patients. Intraoperative evaluation is insensitive for the detection of stage III tumors.

Adjuvant Therapies and Patient and Tumor Characteristics Associated With Survival of Adult Patients With Adrenocortical Carcinoma

CONTEXT Adrenocortical carcinoma is a rare malignant endocrine neoplasia. Studies regarding outcome and prognostic factors rely on fairly small studies. Here we summarize the experience with patients with a diagnosis of adrenocortical carcinoma from a large tertiary referral center. OBJECTIVE The objective of the study was to identify prognostic factors in patients with adrenocortical carcinoma and evaluate adjuvant treatment strategies. DESIGN Patient data were collected in a retrospective single-center study. Epidemiological, patient, and tumor characteristics were analyzed for prognostic factors regarding overall and recurrence-free survival in Cox regression models (multivariable and univariable). RESULTS Three hundred ninety-one adult patients with the diagnosis of adrenocortical carcinoma were identified. Median overall survival was 35.2 months. Cortisol production [hazard ratio (HR) 1.4, HR 1.5], tumor stage (HR stage 3 of 2.1 and 2.1, HR stage 4 of 4.8), and tumor grade (HR 2.4 and 2.0) were identified as negative prognostic factors (HR for death, HR for recurrence). Mitotane therapy increases recurrence-free survival, an effect that was significantly further improved by adjuvant radiation therapy but did not impact overall survival. Patients with open adrenalectomy had improved overall survival. CONCLUSIONS This study increases the evidence for adverse risk factors (cortisol production, high tumor stage, and high tumor grade) and suggests the following therapy approach: adrenocortical carcinoma patients should be treated with open adrenalectomy. Adjuvant therapy, particularly mitotane therapy in conjunction with radiation, should be considered to delay tumor recurrence.

A debate on laparoscopic versus open adrenalectomy for adrenocortical carcinoma

Adrenocortical cancer (ACC) is a rare disease that is difficult to treat. Surgery remains the primary treatment modality and the only chance for cure in these patients. Since the early 1990s, laparoscopic adrenalectomy (LA) has replaced open adrenalectomy (OA) as the gold standard for addressing adrenal disorders of benign origin; however, the oncologic effectiveness of laparoscopic adrenalectomy for resection of primary adrenocortical malignancies remains unclear. Since the initial consensus statement from the International Adrenal Cancer Symposium held in Ann Arbor, MI in 2003, a number of studies have investigated the question of equivalence of LA compared to OA for ACC. Several controversial topics were debated during the 3rd International Adrenal Cancer Symposium held in Wurzburg, Germany in 2011. This debate sought to review the advantages and disadvantages of OA versus LA and review findings of recent studies related to the topic. As all studies involving this topic have methodological flaws, some more than others, the results of each study must be interpreted with caution. In conclusion, this debate will undoubtedly continue well into the future; however, it is clear that an oncologically appropriate surgical resection is of the utmost importance for the treatment of ACC and there is only one chance to achieve this. Poor outcomes will result from inadequate surgery, whether performed by an open or laparoscopic approach. Therefore, there is no doubt that surgery for suspected ACC should only be performed in specialized centers.

The role of radiologic studies in the evaluation and management of primary hyperaldosteronism.

BACKGROUND Surgical treatment of primary hyperaldosteronism (PHA) requires demonstration of unilateral adrenal hypersecretion. Optimal methods for interpretation of imaging and invasive testing are still in development. METHODS A retrospective review from 1996-2007 of 106 patients with PHA was undertaken. Patient demographics, biochemical studies, radiologic imaging, operative reports, and pathology were reviewed and comparisons made. Optimal ratios for adrenal vein sampling were tested with regard to sensitivity and specificity. Preoperative and postoperative medication requirements and blood pressures were compared among different treatment groups. RESULTS Seventy-eight patients (62 surgically treated) met criteria for inclusion. Median arterial blood pressure at diagnosis was 150/86 mm Hg while taking 3 antihypertensive medications. 69.2% required potassium supplementation. Median aldosterone:renin ratio was 107.0. Forty-two AVS procedures changed the management of 15 patients (35.7%) when compared to CT results. AVS accuracy was 96.6 vs 88.9% for NP-59 scintigraphy. Operative patients remained on fewer antihypertensive medications (1 vs 3), and mean systolic pressure was lower (130 vs 146 mm Hg) compared with medically managed patients. CONCLUSION When used together, pre-ACTH aldosterone ratios, normalized A/C:A/C ratios, ratios to define contralateral suppression, and post-ACTH stimulated values allowed for capture of episodically secreting tumors and subtle unilateral or bilateral hyperaldosteronism.

Feasibility of surgeon-performed transcutaneous vocal cord ultrasonography in identifying vocal cord mobility: A multi-institutional experience

BACKGROUND Transcutaneous vocal cord ultrasonography (TVCUS) is a noninvasive study used to identify true vocal cord (TVC) mobility. Its sensitivity in predicting TVC paralysis when compared with indirect flexible laryngoscopy (IFL) ranges from 62 to 93%. This study aimed to evaluate the feasibility of surgeon-performed TVCUS in assessing TVC mobility in the outpatient setting. METHODS At 5 institutions, 510 consecutive patients underwent 887 TVCUS performed by 8 surgeons during initial surgical evaluation. IFL was obtained in selected patients. TVCUS was repeated during the first postoperative visit, and IFL was obtained only when judged necessary. Clinical parameters were collected and later correlated with TVC visualization. RESULTS TVC visualization was possible in 688 of 887 TVCUS (77%); visibility ranged from 41 to 86% among performing surgeons. IFL was done in 81 patients (16%) and TVCUS predicted TVC paralysis in all cases when TVC were seen. TVC visualization was possible more often in females than males (83% vs 17%; P < .0005) and in patients without thyroid cartilage calcification than those with calcification (83% vs 42%; P < .0005). CONCLUSION Experienced surgeon-ultrasonographers can use TVCUS to visualize TVC in most female patients and less so in males. TVCUS is highly sensitive, but operator dependent. This study demonstrates the feasibility of TVCUS and directs further attention to defining its optimal role in assessment of TVC mobility.

Surgical Approach and Perioperative Complications Determine Short-Term Outcomes in Patients with Insulinoma: Results of a Bi-Institutional Study

BackgroundDespite advancements in radiologic imaging and minimally invasive surgery, the evaluation and management of insulinomas is institution and surgeon dependent. Therefore, the reported surgical outcomes are highly variable. We compared the surgical management and outcomes of insulinomas between two international tertiary-care surgical units to better identify the best management as determined by short-term outcomes.MethodsWe performed a retrospective review of patients who underwent surgery for insulinomas over a 117-month period at UT Southwestern Medical Center in Dallas (UTSW) and Queen Mary Hospital in Hong Kong (QMHK). Data collected included imaging studies, operative procedure, complications, and outcomes.ResultsThirty-seven patients were identified. Preoperative localization by computed tomography (CT) scan was successful in 21 patients (63.9%). In Hong Kong, 16 patients underwent selective arterial cannulation and calcium stimulation (SACST) with a success rate of 87.5%. Surgical management consisted of enucleation in 24 patients and distal pancreatectomy in 13 patients. Thirty patients underwent a concurrent intraoperative ultrasound, with localization in 96.7%. Laparoscopic procedures were accomplished in 20 patients. Nine postoperative complications were identified, four occurring in the laparoscopic group. Patients undergoing laparoscopic procedures had a decreased length-of-stay (LOS) compared with patients undergoing an open procedure and patients who had uncomplicated surgery had a trend toward decreased LOS.ConclusionThough the accuracy of CT scans for localizing insulinomas is only 64%, the addition of SACST or intraoperative ultrasound and pancreatic palpation increases accuracy to 97.1%. Compared with open procedures, laparoscopic resection is associated with comparable complication rates and shorter hospital length of stay.

Completion pancreatectomy and duodenectomy for recurrent MEN-1 pancreaticoduodenal endocrine neoplasms

BACKGROUND The purpose of this study is to describe outcomes of MEN-1 patients with recurrence requiring completion pancreatectomy and duodenectomy after initial treatment of pancreatic endocrine neoplasms (PENs) and hypergastrinemia with distal pancreatectomy, enucleation of pancreatic head PENs, and duodenotomy. METHODS After undergoing this initial operation, 8 of 49 patients (16%) have required completion pancreatectomy and duodenectomy for recurrent PENs and hypergastrinemia. Retrospective review was performed. RESULTS Median age was 39 years (27-51) at completion pancreatectomy compared to 31 years (20-40) at initial operation. Pathology revealed multiple PENs in 100%, duodenal neoplasms in 63%, and metastatic lymph nodes in 75%. There was no operative mortality and 88% of patients are currently alive. Preoperative gastrin levels were 934 +/- 847 pg/mL while postoperative levels are 93 +/- 79 pg/mL (normal 25-111 pg/mL). Mean Hemoglobin A1C levels are 8.3 +/- 3.3% (normal 3.8%-6.4%). Mean follow-up is 44 +/- 25 months. CONCLUSION This initial operation may provide tumor control and prevent metastases but recurrent PENs are multifocal and progressive. Completion pancreatectomy and duodenectomy is arduous but outcomes are acceptable. Considering the radical nature of this treatment, individual consideration should be given to MEN-1 patients amenable to initial alternative pancreatic resections that preserve pancreatic mass and allow future pancreas-preserving reoperations.

Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

PURPOSE Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. METHODS AND MATERIALS We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. RESULTS From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. CONCLUSIONS Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.