Percutaneous cholecystostomy in the management of high-risk patients presenting with acute cholecystitis: Timing and outcome at a single institution.

BACKGROUND: Cholecystectomy is the standard of care in acute cholecystitis (AC). Percutaneous cholecystostomy (PC) is an effective alternative for high-risk surgical cases. METHODS: A retrospective analysis is presented of AC patients treated with PC drainage at a single tertiary institution over a 21 month period, assessing outcome and complications. RESULTS: Of 119 patients, 103 had clinical improvement after PC insertion. There were 7 peri-procedural deaths (5.9%), all in elderly high-risk cases. Overall, 56/103 cases (54%) were definitively managed with PC drainage with 41 patients (40%) undergoing an elective cholecystectomy (75% performed laparoscopically). The timing of PC insertion did not affect AC resolution or drain-related complications, although more patients underwent an elective cholecystectomy if PC placement was delayed (>24 h after admission). CONCLUSIONS: In AC, drainage by a PC catheter is a safe and effective procedure. It may be used either as a bridge to elective cholecystectomy or in selected cases as definitive therapy.

Intrathyroidal parathyroid glands: small, but mighty (a Napoleon phenomenon).

BACKGROUND: Intrathyroidal parathyroid adenomas (ITPAs) are a rare entity. The aim of this study is to describe the experience of 2 endocrine surgery centers and to distinguish characteristics of intrathyroidal parathyroid adenoma and nonintrathyroidal parathyroid adenomas. METHODS: We included patients who had undergone operations for primary hyperparathyroidism who had intrathyroidal parathyroid adenomas. Patients with single intrathyroidal parathyroid adenomas were also compared to age- and sex-matched controls with nonintrathyroidal parathyroid adenomas. RESULTS: Of 4,868 patients who underwent parathyroidectomy between January 2002 and June 2011, we identified 53 (1%) patients with intrathyroidal parathyroid adenoma. Sestamibi and ultrasound scans correctly identified the adenoma in 35 (70%) and 11 (61%) cases, respectively. Single adenomas were identified in 44 (83%) patients, double adenomas in 4 (8%) patients, and hyperplasia in 5 (9%) patients. Lobectomy was performed in 17 (32%) patients; enucleation was used in 36 (68%) patients. Cure was achieved in all patients and no patients experienced a recurrence. Patients with single intrathyroidal parathyroid adenomas had significantly smaller glands than patients with nonintrathyroidal parathyroid adenomas (325 ± 47 vs 772 ± 61 mg; P < .0001); however, no significant difference was identified between the groups with regard to demographics, symptoms, preoperative laboratory values, or outcomes. CONCLUSION: Single intrathyroidal parathyroid adenomas are smaller than nonintrathyroidal parathyroid adenomas, but patients with intrathyroidal parathyroid adenomas present with similar laboratory values and symptoms. Recognition of this rare entity can lead to a successful surgical outcome.

The quest for diagnostic molecular markers for thyroid nodules with indeterminate or suspicious cytology.

Thyroid nodules are very common and fine needle aspiration (FNA) is a very sensitive means of diagnosis. However, its limitations include the fact that the cytology reports are often indeterminate or suspicious only. The quest for adjunctive measures to improve its specificity has been ongoing for decades, but significant results have remained elusive. The potential use of diagnostic molecular markers appears to be the most promising area of research at this time.

Three-gene molecular diagnostic model for thyroid cancer.

BACKGROUND: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. METHODS: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. RESULTS: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. CONCLUSIONS: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

The role of preoperative neck ultrasounds to assess lymph nodes in patients with suspicious or indeterminate thyroid nodules.

BACKGROUND AND OBJECTIVES: Currently there are no recommendations for obtaining a preoperative neck ultrasound for patients with suspicious or indeterminate thyroid nodules. Because a preoperative surgical ultrasound can detect suspicious lymph nodes that could result in ultimately altering surgical management, we chose to study which variables were predictive of this change. METHODS: Medical records of 173 patients who presented between January 2006 and December 2010 with suspicious or indeterminate thyroid cytology were retrospectively reviewed. Clinicopathological variables were analyzed to determine factors predictive of malignancy and a change in operative approach. RESULTS: One hundred thirty-four of 173 patients were evaluable. Seventeen of 134 (12.6%) of the preoperative ultrasounds were suspicious. Seven of 134 (5.2%) patients underwent a formal lymph node dissection based on ultrasound findings. Size of tumor, Bethesda FNAB category, and male gender were associated with malignancy while thyroid nodule microcalcifications and category of FNAB were associated with performing lymph node dissections. CONCLUSION: Thyroid nodule microcalcifications on ultrasound and category of FNAB appear to be the best predictors of metastatic disease. Because the surgical approach was altered in only a few patients, further analysis is needed to delineate whether performing cervical ultrasound for suspicious/indeterminate nodules is cost effective.

Long-term outcome in patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has become a well-accepted treatment for selected patients with primary hyperparathyroidism (PHPT). However, few studies have evaluated long-term outcomes for this operative approach. We therefore chose to examine both the long-term symptom resolution and biochemical cure following MIP for PHPT. METHODS: A total of 460 PHPT patients who underwent a MIP between 2004 and 2009 were successfully mailed a questionnaire that assessed preoperative and postoperative Parathyroidectomy Assessment of Symptoms (PAS) scores, most recent calcium and parathyroid hormone (PTH) levels, and information about any reoperation for PHPT. Long-term evaluation of symptomatic and biochemical cure was performed. RESULTS: A total of 200 patients (43.5%) responded to our correspondence. The mean age of the patients was 58.7 ± 11.9 years, 74.5% were female, and 78.5% were Caucasian. The mean follow-up was 37 ± 19 months. The mean PAS scores fell by 117 ± 14 at long-term follow-up after MIP (P < 0.0001). All 13 symptoms comprising the PAS score diminished, of which ten did so significantly (P < 0.01). There was a significant drop in the mean serum calcium (preop. 11.1 mg/dl, postop. 9.6 mg/dl; P < 0.0001) and PTH (preop. 130.9 pg/ml, postop. 45.7 pg/ml; P < 0.0001) at long-term follow-up. Five patients (2.5%) developed recurrent disease (calcium > 10.5 mg/dl), and one (0.5%) underwent a reoperation for persistent disease and was subsequently cured. CONCLUSIONS: This study demonstrates that MIP has long-term benefits in terms of excellent symptom resolution and a high biochemical cure rate (97%) in selected patients who have PHPT, preoperative localization with sestamibi scans, and assessment of intraoperative PTH level.

Predictive factors of malignancy in pediatric thyroid nodules.

BACKGROUND: Studies suggest that while most pediatric thyroid nodules are benign, there is a higher rate of malignancy than in adults. We investigate clinical factors that may predict malignancy in pediatric thyroid nodules. METHODS: A retrospective review of 207 pediatric thyroidectomies was conducted over 15 years at 2 tertiary hospitals. Analyses examined predictive values of 16 clinicopathologic factors associated with cancer. Positive predictive values (PPVs) of fine-needle aspiration biopsy specimens (FNABs) were analyzed independently. RESULTS: Malignancy occurred in 41% of patients. After excluding missing data, malignancy was more likely with family history of thyroid cancer (34.2% vs 17.7%; P = .111), palpable lymphadenopathy (34.2% vs 2.9%; P = .001), and hypoechoic nodules (52.2% vs 19.2%; P = .016). Palpable lymphadenopathy indicated greater than 2-fold increased risk for malignancy (relative risk, 2.18; 95% confidence interval, 1.56-3.05). PPVs of FNAB results were 0.94 for malignancy, 0.63 for suspicious for malignancy, and 0.55 for indeterminate lesions. PPV for benign FNAB to be benign on final pathology was 0.71. CONCLUSION: While malignancy is associated with family history of thyroid cancer and hypoechoic lesions, palpable lymphadenopathy had the greatest risk. When compared to adults, a benign FNAB in children is not as accurate and the likelihood that an indeterminate nodule is cancer is greater.

Tumor size and presence of calcifications on ultrasonography are pre-operative predictors of lymph node metastases in patients with papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: Lymph node metastases in papillary thyroid cancer (PTC) are common and their presence can significantly alter the treatment for patients with PTC. We therefore sought to identify pre-operative predictors of lymph node metastases in patients with PTC. METHODS: A thyroid tumor database was queried to identify patients with a pre-operative diagnosis of PTC and underwent thyroidectomy between January 2006 and August 2009. One hundred and three patients who had a pre-operative ultrasound and had lymph nodes surgically resected were identified. Clinical factors and tumor ultrasound characteristics were recorded. The pre-operative ultrasound results, type of operation, and final pathology results were also recorded. RESULTS: Of the 103 patients, 74 (72%) were women and 29 (28%) were men with an age range of 15-78 years (median age of 43). Of the ultrasound characteristics evaluated only calcifications (P = 0.007) and size (P = 0.003) were statistically associated with positive cervical lymph nodes. None of the other demographic or clinical factors were significantly associated with lymph node metastases. CONCLUSIONS: Thyroid nodule size and presence of calcifications on ultrasound were found to have a statistically significant association with lymph node metastases in patients with PTC. This information could be used to guide the surgical management of these patients.

Chasing "shadows": discovering the subtleties of sestamibi scans to facilitate minimally invasive parathyroidectomy.

BACKGROUND: With the advent of sestamibi scans, high-resolution ultrasonography (US), and intraoperative intact parathyroid hormone (PTH) measurements, minimally invasive parathyroidectomy (MIP) is considered the standard of care for patients with primary hyperparathyroidism (PHPT). Preoperative imaging, however, can be negative more than 20% of the time. METHODS: We chose to examine one surgeon's experience with patients who presented with PHPT and negative or indeterminate preoperative imaging from July 1993 to September 2009. A retrospective review of a parathyroid surgery database and patient records was conducted to collect the following information: patient age and sex; calcium and PTH levels; sestamibi and US results; and operative reports. Each sestamibi scan had been re-reviewed preoperatively by the surgeon with a nuclear medicine physician. The study cohort included patients with negative or indeterminate sestamibi results and a negative or no US report in which the surgeon was able to identify a "shadow" or subtlety on sestamibi and plan an MIP. RESULTS: A total of 126 patients had a negative or indeterminate sestamibi scan and a negative or no US report. "Shadows" or subtleties were found in 18 of 44 (41%) of the cases with a negative sestamibi and in 62 of 82 (76%) of cases with an indeterminate sestamibi scan. For these 80 cases a MIP was planned. In all, 7 of 80 (9%) were converted to a bilateral exploration. The remaining 46 patients underwent a planned bilateral exploration. Cure rates were comparable: 99% in the study group compared to 97% in the group who underwent a planned or converted bilateral exploration. CONCLUSIONS: With careful preoperative re-review of a negative or indeterminate sestamibi scan and the identification of subtleties in patients with a negative preoperative US scan, a successful MIP can be performed 91% of the time with a 98% cure rate.

The role of telomeres and telomerase in endocrine tumors.

The enzyme, telomerase, is a reverse transcriptase that synthesizes the telomeric ends of linear chromosomes and compensate for the shortened telomere, thereby immortalizing the cell. It is present at the blastocyst stage of embryological development, low or undetectable in most somatic cells, and activated in cancer. Because of its strong association with cancer cell immortalization and proliferation, numerous attempts have been made to capitalize on its diagnostic, prognostic, and therapeutic potential. Herein we discuss the role of telomerase in normal, benign, and cancerous endocrine tissues.

Thyroid tumorigenesis and molecular markers in thyroid cancer.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on recent advances in the understanding of thyroid cancer tumorigensis and implications in clinical practice. RECENT FINDINGS: Recent novel and promising findings include additional abnormalities in key pathways associated with thyroid tumorigenesis (RET-Ras-BRAF-MEK; RET-beta-cateinin; TRK-PI3K-AKT; and MDM-p53-PTEN), single-nucleotide polymorphisms associated with thyroid cancer susceptibility, epigenetic silencing, alternative splicing, and gene expression abnormalities. Complex regulatory mechanisms and insights into ways in which molecular aberrancies occur are becoming better understood through this research. SUMMARY: With ongoing research, clinical problems such as the suspicious thyroid fine needle aspiration, better treatment algorithms for well differentiated thyroid cancer, and more effective treatment for anaplastic cancer will likely be found.