Cervical Endocrine Surgery With a Novel Opioid-Limited Perioperative Protocol.

BACKGROUND: Recent studies have demonstrated that patients undergoing cervical endocrine surgery could be comfortably discharged with minimal opioid analgesia. However, no study to date has examined the efficacy of limiting administration of opioids intraoperatively. We have developed a novel protocol for patients undergoing cervical endocrine surgery that eliminates perioperative opioids. We sought to determine the efficacy of this protocol and its impact on opioid use at discharge. METHODS: We conducted a prospective opt-in opioid-limited surgery program study to opioid-naive patients scheduled for cervical endocrine surgery beginning in August 2019. Postoperatively, nonopioid analgesia was encouraged, but patients were also given a low dose prescription for opioids at discharge. Patients were then matched with 2 retrospective control groups, patients from 2014-2016 and 2017-2018, in order to account for increased public awareness of opioid-prescribing patterns. Primary end points included perioperative opioid use. Secondary end points included postoperative pain scores and complications. RESULTS: 218 patients underwent cervical endocrine surgery with our opioid-limited protocol between August 2019 and February 2020. Nine patients received opioids intraoperatively (4%) and 109 (50%) filled their opioid prescriptions at discharge. Compared to retrospective control groups, the average oral morphine equivalents (OME) administered intraoperatively and prescribed postoperatively were significantly lower (P < .0001). Pain scores and complication rates were similar in all groups (P = .7247). DISCUSSION: Our novel opioid-limited surgery protocol used in conjunction with preoperative counseling is an effective approach for pain control in patients undergoing cervical endocrine surgery and limits opioid exposure throughout the perioperative period.

Vascular invasion predicts advanced tumor characteristics in papillary thyroid carcinoma.

BACKGROUND: The clinical impact of vascular invasion in Papillary Thyroid Carcinoma (PTC) is not well understood. Our aim was to determine if there was an association between vascular invasion and other tumor characteristics and patient outcomes in PTC. METHODS: A retrospective chart review was performed of 536 patients with PTC between January 2007-December 2011. Patient demographics, comorbidities, tumor characteristics, and outcomes were collected. RESULTS: Vascular invasion was associated with lymphatic invasion, capsular invasion, extrathyroidal extension, and the presence of positive lymph nodes. Logistic regression revealed that tumor size was a predictor of vascular invasion. Vascular invasion in PTC tumors was associated with higher tumor recurrence rates, but there were no differences in mortality. CONCLUSION: This study indicates that vascular invasion in PTC is associated with other aggressive pathologic features and an increased recurrence rate. For these reasons, vascular invasion should be an important tumor characteristic when determining extent of treatment.

Outcomes in patients with renal hyperparathyroidism requiring cinacalcet pre-operatively followed by parathyroidectomy.

BACKGROUND: Cinacalcet is an effective treatment for renal hyperthyroidism when traditional medical therapy has failed. We studied the impact of pre-operative cinacalcet administration on post-surgical outcomes. METHODS: A retrospective analysis was performed of patients from 2002 to 2017 diagnosed with renal hyperparathyroidism requiring parathyroidectomy to evaluate the need for post-operative supplementation and outcomes. RESULTS: 102 patients were identified; 34 patients were treated with cinacalcet prior to undergoing parathyroidectomy. The cinacalcet treatment cohort (CT) demonstrated a greater duration of renal replacement therapy (p = 0.03) relative to the untreated cohort (NC). NC had greater proportion receiving peritoneal dialysis (p=<0.0001) compared to other forms of renal replacement, greater pre-operative PTH levels (p = 0.001) and greater decrease in PTH after resection (p = 0.0086). Post-operative vitamin D supplementation was more frequent in the CT group (p = 0.02). After propensity matching for pre-operative PTH and duration of renal replacement therapy, there were no differences in post-operative supplementation or outcomes. CONCLUSIONS: Cinacalcet patients may have advanced disease. These patients have longer duration of renal failure and higher PTH levels. After propensity matching, no significant differences were noted in terms of need for supplementation or outcomes.

Epigenetic Alterations and Canonical Pathway Disruption in Papillary Thyroid Cancer: A Genome-wide Methylation Analysis.

BACKGROUND: Alterations in DNA methylation have been demonstrated in a variety of malignancies, including papillary thyroid cancer (PTC). The full extent of dysregulation in PTC and the downstream affected pathways remains unclear. Here we report a genome-wide analysis of PTC methylation, the dysregulation of various canonical pathways, and assess its potential as a diagnostic test. METHODS: A discovery set utilized 49 PTCs and matched normal controls from The Cancer Genome Atlas. Another set of 16 PTCs and 13 normal controls were used as a replication set. Genome-wide methylation analysis was done using Illumina 450 K methylation chips. Differentially methylated loci (DML) were identified by comparing PTC and matched normal tissues. DML were defined as false-discovery rate p < 0.05 and absolute Δß ≥ 0.2. DML were then analyzed for pathway and disease commonalities using Qiagen Ingenuity Pathway Analysis. RESULTS: Of 485,577 CpG sites analyzed, 1226 DML were identified in our discovery and replication sets, and 1061 (86.5 %) DML showed hypomethylation when comparing tumor with normal tissue. Support vector machine classification was able to differentiate benign from malignant tissue in 107 (94.7 %) of 113 tested samples, including 15 (83.3 %) of 18 samples lacking a clearly deleterious mutation. Statistically significant associations with multiple canonical pathways, diseases, and biofunctions were observed including PI3K, PTEN, wnt/ß-catenin, and p53. CONCLUSIONS: Epigenetic dysregulation of multiple canonical pathways are associated with the development of PTC. This methylation signature shows promise as a future adjunctive screening test for thyroid nodules.

One-hour PTH after thyroidectomy predicts symptomatic hypocalcemia.

BACKGROUND: A major morbidity after total thyroidectomy is hypocalcemia. Although many clinical factors and laboratory studies have been correlated with both biochemical and symptomatic hypocalcemia, the ideal use and timing of these tests remain unclear. We hypothesize 1-h (PACU) parathyroid hormone (PTH) will identify patients at risk for symptomatic hypocalcemia. METHODS: This prospective study evaluated 196 patients undergoing total thyroidectomy. Serum calcium and PTH levels were measured 1 h after surgery and on postoperative day 1 (POD1). Performance of a central compartment lymph node dissection, parathyroid autotransplantation, indication for procedure, pathology, and presence of parathyroid tissue in the pathology specimen were recorded. RESULTS: Of 196 patients, nine (4.6%) developed symptomatic hypocalcemia. Thirty four (17.3%) had a 1-h PACU PTH ≤10 pg/dL, whereas 31 (15.8%) had a POD1 PTH of ≤10. Five (56%) of the nine symptomatic patients underwent central compartment lymph node dissection, four (44%) had parathyroid autotransplantation, and four (44%) had a PACU PTH ≤10. PACU and POD1 PTH levels were correlated (R(2) = 0.682). Multivariate regression identified central compartment dissection, autotransplantation, and PACU or POD1 PTH correlated with symptomatic hypocalcemia. PACU PTH, POD1 PTH, PACU Ca, malignant final pathology, and age ≤45 y correlated with biochemical hypocalcemia. CONCLUSIONS: A 1-h postoperative PACU PTH is equivalent to POD1 PTH in predicting the development of symptomatic hypocalcemia. Biochemical hypocalcemia was not predictive of symptoms in the immediate postoperative period. Lymph node dissection and parathyroid autotransplantation correlated with symptomatic hypocalcemia and improve the sensitivity of biochemical screening alone.

Follicular Thyroid Carcinoma: How Have Histologic Diagnoses Changed in the Last Half-Century and What Are the Prognostic Implications?

BACKGROUND: Follicular thyroid carcinoma (FTC) comprises 10% of differentiated thyroid cancers. Diagnostic controversy and interobserver variability render the practical diagnosis of FTC difficult. Overall survival rates vary (46-97%). The aims of this study were to review FTC histologically at the authors' tertiary care institution and to evaluate long-term survival and recurrence. METHODS: Diagnostic slides from 66 FTC cases (1965-2007) were reviewed by three pathologists from two institutions (blinded to clinical outcomes), and consensus was obtained. Patient demographics, tumor characteristics, and treatment, survival, and recurrence data were collected. Thyroid cancer-specific and recurrence-free survival were calculated by original and reclassified diagnoses. RESULTS: Forty-seven cases (71%) were reclassified: 24 (36%) to papillary thyroid carcinoma (PTC), 18 (27%) to follicular adenoma (FA), and five (8%) to poorly differentiated carcinoma (PDC). Nineteen (29%) maintained a diagnosis of FTC. The extent of surgical resection and rates of radioiodine treatment did not differ by reclassification diagnosis. Pre-review FTC-specific survival was 83.5% and 75.1% at 10 and 20 years, respectively. Following contemporary reclassification, FTC-specific survival was 77% and 33.7% at 10 and 20 years, respectively. There were no cancer-specific deaths in the FA or PTC groups. CONCLUSIONS: Over the past 50 years, changes in our understanding of the pathogenesis, histology, and behavior of thyroid carcinoma may partially account for the changes in histologic diagnosis. Elimination of PTC and FA "contaminants" led to decrease in survival following reclassification. Variability in histologic interpretation contributes to diagnostic challenges in follicular lesions. Histologic review of thyroid tumors for research studies is crucial, especially given the ever-changing diagnostic criteria.

Risk Factors for Decreased Quality of Life in Thyroid Cancer Survivors: Initial Findings from the North American Thyroid Cancer Survivorship Study.

BACKGROUND: The prevalence of thyroid cancer survivors is rising rapidly due to the combination of an increasing incidence, high survival rates, and a young age at diagnosis. The physical and psychosocial morbidity of thyroid cancer has not been adequately described, and this study therefore sought to improve the understanding of the impact of thyroid cancer on quality of life (QoL) by conducting a large-scale survivorship study. METHODS: Thyroid cancer survivors were recruited from a multicenter collaborative network of clinics, national survivorship groups, and social media. Study participants completed a validated QoL assessment tool that measures four morbidity domains: physical, psychological, social, and spiritual effects. Data were also collected on participant demographics, medical comorbidities, tumor characteristics, and treatment modalities. RESULTS: A total of 1174 participants with thyroid cancer were recruited. Of these, 89.9% were female, with an average age of 48 years, and a mean time from diagnosis of five years. The mean overall QoL was 5.56/10, with 0 being the worst. Scores for each of the sub-domains were 5.83 for physical, 5.03 for psychological, 6.48 for social, and 5.16 for spiritual well-being. QoL scores begin to improve five years after diagnosis. Female sex, young age at diagnosis, and lower educational attainment were highly predictive of decreased QoL. CONCLUSION: Thyroid cancer diagnosis and treatment can result in a decreased QoL. The present findings indicate that better tools to measure and improve thyroid cancer survivor QoL are needed. The authors plan to follow-up on these findings in the near future, as enrollment and data collection are ongoing.

Benign and Malignant Thyroid Incidentalomas Are Rare in Routine Clinical Practice: A Review of 97,908 Imaging Studies.

PURPOSE: Thyroid nodules incidentally identified on imaging are thought to contribute to the increasing incidence of thyroid cancer. We aim to determine the true rate of incidental thyroid nodule reporting, malignancy rates of these nodules, and to compare these findings with rates of detection by dedicated radiology review. METHODS: A cross-sectional analysis was done to determine the prevalence of thyroid nodules in radiologist reports by analyzing all reports for CT, PET, and MRI scans of the head, neck, and chest as well as neck ultrasounds performed at a tertiary care center from 2007 to 2012. Retrospective chart review was performed on patients with a reported thyroid nodule to determine clinical outcomes of these nodules. Radiology reports were compared with dedicated radiology review of 500 randomly selected CT scans from the study group to determine the difference between clinical reporting and actual prevalence of thyroid nodules. RESULTS: 97,908 imaging studies met inclusion criteria, and 387 (0.4%) thyroid incidentalomas were identified on radiology report. One hundred and sixty three (42.1%) of these nodules were worked up with fine-needle aspiration, diagnosing 27 thyroid cancers (0.03% of all studies, 7.0% of reported incidentalomas). The prevalence of incidentalomas clinically reported was 142/100,000 CT scans, 638/100,000 MRIs, 358/100,000 PET scans, and 6,594/100,000 ultrasounds. In contrast, review of CT scans screening for thyroid nodules had a prevalence of 10%. CONCLUSION: Routine clinical reporting of incidental thyroid nodules is far less common than on dedicated review. IMPACT: These data contradict the notion that incidentalomas contribute significantly to rising thyroid cancer rates.

A novel, ultrarapid parathyroid hormone assay to distinguish parathyroid from nonparathyroid tissue.

BACKGROUND: Frozen section is the gold standard for distinguishing parathyroid tissue from lymph nodes, thyroid nodules, or fat during parathyroidectomy and thyroidectomy. Although a very accurate procedure, it can be time-consuming and costly. We hypothesize that the extremely high concentrations of parathyroid hormone (PTH) in parathyroid tissue allow for modification of a standard PTH assay that would distinguish parathyroid from nonparathyroid tissue in substantially less time than frozen section or any currently available PTH assay. METHODS: A prospective, single-institution study using a modified PTH assay protocol and a manual luminometer was undertaken by testing 20 parathyroid adenomas and 9 control tissues. Analyses were performed simultaneously by the modified PTH protocol and the conventional intraoperative PTH assay. RESULTS: PTH luminescence values from parathyroid tissue and control tissue aspirates were significantly different at 60 seconds (P = .015). ROC curve analysis showed the assay to be 100% sensitive and 100% specific in differentiating parathyroid from nonparathyroid tissue. CONCLUSION: Our novel PTH assay accurately and reliably differentiates parathyroid from nonparathyroid tissue within 60 seconds of measurement onset. This assay provides a great advantage in time savings compared with frozen section as well as any currently existing PTH assays.

Age of diagnosing physician impacts the incidence of thyroid cancer in a population.

BACKGROUND: Thyroid ultrasound and fine-needle aspiration (FNA) have been implicated in the overdiagnosis of thyroid cancer. To study how the use of diagnostic tools impacts thyroid cancer incidence, we propose using physician age as a surrogate. We aimed to determine whether thyroid cancer incidence is higher in areas with a high density of young physicians compared with areas with a high density of older physicians. METHODS: SEER 13 database was used to determine thyroid cancer incidence. These data were linked to the Area Resource File data (2000), containing information on physician age at a county-specific level. Cohorts were divided by age based on the concentration of physicians within a population of 1,000,000 persons. The study period was divided into two time periods (1992-1995, 2006-2009). RESULTS: The incidence of thyroid cancer was stable in areas with high concentrations of young and older physicians during the 1992-1995 time period [<35: 5.97; 55-64: 6.82; ≥65: 6.70 (per 100,000py)]. Areas with high concentrations of young physicians had an increased incidence of thyroid cancer compared with areas of high concentrations of older physicians during the 2006-2009 period [<35: 13.3; 55-64: 9.86; ≥65: 7.47 (per 100,000py)]. CONCLUSIONS: Thyroid cancer incidence was lower in areas with high concentrations of older physicians. This may be the result of increased adoption of thyroid ultrasound and FNA among younger physicians who have trained after diagnostic tools became common. Age of the diagnosing physician is a surrogate for diagnostic utility contributing to thyroid cancer trends.

A novel technique to improve the diagnostic yield of negative sestamibi scans.

INTRODUCTION: Minimally invasive parathyroidectomy is successful in achieving cure for most patients with primary hyperparathyroidism. Most surgeons rely on preoperative imaging as part of the workup for localization. Ultrasonography and sestamibi are the 2 most commonly used preoperative imaging studies. When these 2 studies are positive and concordant the preoperative localization is straightforward. However, when ≥1 of these studies is negative, the preoperative localization is suspect. We hypothesize that the yield of useful localizing information from "negative" sestamibi scans can be increased in certain situations. Specifically, in cases where the thyroid lobe length seen on sestamibi is discordant from the lobe length of the ultrasonography, this often represents a "hidden" parathyroid adenoma. If our hypothesis is correct, this could lead to decreased resource utilization in cases of nonlocalized parathyroid adenomas. METHODS: We retrospectively analyzed our database of patients with primary hyperparathyroidism who underwent parathyroidectomy from 2005 to 2011. The anteroposterior views of early phase sestamibi were analyzed for thyroid lobe lengths. A ratio of the length of the right lobe to left lobe was calculated. The thyroid lobe lengths on ultrasonography were measured and similar ratios were calculated. The difference in ratios between sestamibi and ultrasonography was calculated for each patient. A difference in ratios from sestamibi and ultrasonography that corresponded with a "hidden" parathyroid on the side of the additional length on sestamibi at the time of surgery was considered a positive finding. When the difference in ratios from the 2 images did not correspond with a "hidden" parathyroid at the time of operation, it was considered a negative finding. RESULTS: There were 59 patients with single-gland disease, negative sestamibi, and images available for review. There were 32 patients (54%) with the positive finding of a "hidden" parathyroid corresponding with a difference in thyroid lobe length ratios from sestamibi and ultrasonography. The overall mean difference in ratios between sestamibi and ultrasonography was 0.37 ± 0.32. The mean ratio difference in the group of patients with a negative "hidden" parathyroid was 0.11 ± 0.02, and the mean ratio difference in the group of patients with a positive "hidden" parathyroid was 0.58 ± 0.05 (P < .001). When a difference in ratios of ≥0.23 was obtained, this predicted a "hidden" parathyroid with a sensitivity of 93.8% and specificity of 85.2%. There were 39 patients with multigland disease, negative sestamibi, and images available for review. None of these patients had a ratio difference of ≥0.23. The mean ratio difference for patients with multigland disease was significantly lower than that of the single-gland disease (0.08 ± 0.06 vs 0.37 ± 0.32; P < .001). CONCLUSION: Discordance between thyroid lobe lengths on the early phase sestamibi compared with ultrasonography has led to successful preoperative identification of parathyroid adenomas, even though the sestamibi was traditionally read as negative. This finding has not been previously described, seems to be reliable, and can lead to improved preoperative localization and decreased resource utilization in this subset patients.

Evaluation of genetic biomarkers for distinguishing benign from malignant thyroid neoplasms.

BACKGROUND: Fine-needle aspiration (FNA) aids in the diagnosis of thyroid nodules. The expression of previously implicated genes was examined to potentially discriminate between benign and malignant thyroid samples. METHODS: Patients included for study had cytology demonstrating follicular cells of undetermined significance, atypical cells of undetermined significance, follicular neoplasm, or suspicion of malignancy with one of the following postoperative diagnoses: follicular thyroid adenomas, follicular thyroid carcinomas, or follicular variant of papillary thyroid carcinomas (FV-PTCs). FNA and tumor expression of human telomerase reverse transcriptase (hTERT), high-mobility group A2 (HMGA2), and trefoil factor 3/3-galactoside-binding lectin (T/G ratio) were analyzed. RESULTS: T/G ratios were not significantly different in the malignant and benign groups. HMGA2 was overexpressed in carcinoma states; however, only FV-PTCs were significant (P = .006). Tumor hTERT expression was detected in 25% of follicular thyroid carcinomas, whereas 5% of FV-PTCs and 10% of follicular thyroid adenomas had expression. FNA aspirates showed similar results. CONCLUSIONS: Although HMGA2 and hTERT showed differential expression, they did not consistently differentiate benign from malignant. Further study based on global gene expression is needed to identify markers that could serve as a diagnostic tool.

A multi-institutional international study of risk factors for hematoma after thyroidectomy.

BACKGROUND: Cervical hematoma can be a potentially fatal complication after thyroidectomy, but its risk factors and timing remain poorly understood. METHODS: We conducted a retrospective, case-control study identifying 207 patients from 15 institutions in 3 countries who developed a hematoma requiring return to the operating room (OR) after thyroidectomy. RESULTS: Forty-seven percent of hematoma patients returned to the OR within 6 hours and 79% within 24 hours of their thyroidectomy. On univariate analysis, hematoma patients were older, more likely to be male, smokers, on active antiplatelet/anticoagulation medications, have Graves' disease, a bilateral thyroidectomy, a drain placed, a concurrent parathyroidectomy, and benign pathology. Hematoma patients also had more blood loss, larger thyroids, lower temperatures, and higher blood pressures postoperatively. On multivariate analysis, independent associations with hematoma were use of a drain (odds ratio, 2.79), Graves' disease (odds ratio, 2.43), benign pathology (odds ratio, 2.22), antiplatelet/anticoagulation medications (odds ratio, 2.12), use of a hemostatic agent (odds ratio, 1.97), and increased thyroid mass (odds ratio, 1.01). CONCLUSION: A significant number of patients with a postoperative hematoma present >6 hours after thyroidectomy. Hematoma is associated with patients who have a drain or hemostatic agent, have Graves' disease, are actively using antiplatelet/anticoagulation medications or have large thyroids. Surgeons should consider these factors when individualizing patient disposition after thyroidectomy.

Hurthle cell carcinoma: an update on survival over the last 35 years.

BACKGROUND: Hurthle cell carcinoma (HCC) of the thyroid is a variant of follicular cell carcinoma (FCC). A low incidence and lack of long-term follow-up data have caused controversy regarding the survival characteristics of HCC. We aimed to clarify this controversy by analyzing HCC survival over a 35-year period using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Cases of HCC and FCC were extracted from the SEER-9 database (1975-2009). Five- and 10-year survival rates were calculated. We compared changes in survival over time by grouping cases into 5-year intervals. RESULTS: We identified 1,416 cases of HCC and 4,973 cases of FCC. For cases diagnosed from 1975 to 1979, HCC showed a worse survival compared with FCC (5 years, 75%; 95% confidence interval [CI], 60.2-85) versus 88.7% (95% CI, 86-90.8; 10 years, 66.7% [95% CI, 51.5-78.1] vs. 79.7% [95% CI, 76.5-82.6]). For cases diagnosed from 2000 to 2004 we found no difference in 5-year survival between HCC and FCC (91.1% [95% CI, 87.6-93.7] vs. 89.1% [95% CI, 86.5-91.2]). For cases diagnosed from 1995 to 1999, there was no difference in 10-year survival between HCC and FCC (80.9% [95% CI, 75.6-85.2] vs. 83.9% [95% CI, 80.8-86.6]). HCC survival improved over the study period while FCC survival rates remained stable (increase in survival at 5 years, 21.7% vs. 0.4%; at 10 years, 21.3% vs. 5.2%). Improvement in HCC survival was observed for both genders, in age ≥45 years, in local and regional disease, for tumors >4 cm, and with white race. CONCLUSION: HCC survival has improved dramatically over time such that HCC and FCC survival rates are now the same. These findings explain how studies over the last 4 decades have shown conflicting results regarding HCC survival; however, our data do not explain why HCC survival has improved.

An analysis of fine needle aspiration versus core needle biopsy in clinically palpable breast lesions: a report on the predictive values and a cost comparison.

BACKGROUND: Although fine-needle aspiration (FNA) is an established tool in the biopsy of breast masses, there has been a trend toward using core-needle biopsy (CNB). The aim of this study was to determine whether FNA has comparable predictive value with CNB and whether FNA is more cost effective. METHODS: A retrospective review was conducted on 162 patients who underwent either FNA or CNB of palpable breast lesions and had histologic confirmation with surgical biopsy in calendar year 2005. RESULTS: There were no false-positives or false-negatives in either group. The sensitivity, specificity, and positive predictive value for FNA were 89%, 98%, and 94%, respectively. CNB had sensitivity, specificity, and positive predictive value of 100%, 90%, and 93%, respectively. The cost to perform FNA was $166.34, compared with $477.92 for CNB. CONCLUSIONS: FNA and CNB had comparable predictive value, with FNA being more cost effective.

Outcomes analysis of intraoperative adjuncts during minimally invasive parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: The aim of this study was to determine whether minimally invasive radioguided parathyroidectomy (MIRP) and intraoperative parathyroid hormone-guided parathyroidectomy (ioPTH) have equivalent intermediate-term outcomes in primary hyperparathyroidism (PHPT). METHODS: A retrospective study of 244 patients who underwent parathyroidectomy for PHPT in a 25-month time period was conducted. Patients who either underwent MIRP- or ioPTH-guided parathyroidectomies were included. The primary outcome was persistent disease. Conversion to bilateral exploration, complications, and multigland disease (MGD) were secondary outcomes. RESULTS: There was 1 MIRP patient and no ioPTH patients who had persistent disease. The ioPTH group had more conversions to a bilateral exploration (bilateral neck exploration [BNE]) (3.7% vs 13%, P = .024). In the MIRP group, no patients were found to have MGD. In the ioPTH group, 7 patients with double adenomas and 6 patients with MGD were found (0 vs 13, P = .0028). CONCLUSIONS: ioPTH facilitates successful minimally invasive parathyroidectomy (MIP) when compared with MIRP and provides cure rates similar to BNE.

A Case of Hemorrhagic Necrosis of Ectopic Liver Tissue within the Gallbladder Wall.

Ectopic liver tissue is a rare clinical entity that is mostly asymptomatic and found incidentally. In certain situations, however, patients may present with symptoms of abdominal pain secondary to torsion, compression, obstruction of adjacent organs, or rupture secondary to malignant transformation. Herein, we report a case of a 25-year-old female that presented with acute onset of epigastric pain found to have ectopic liver tissue near the gallbladder complicated by acute hemorrhage necessitating operative intervention in the way of laparoscopic excision and cholecystectomy. The patient's postoperative course was uneventful. Gross pathology demonstrated a 1.2 × 2.8 × 4.5 cm firm purple ovoid structure that histologically revealed extensive hemorrhagic necrosis of benign ectopic liver tissue.

Factors affecting the severity of spontaneous retroperitoneal hemorrhage in anticoagulated patients.

BACKGROUND: Clinical manifestations of spontaneous retroperitoneal hemorrhage (SRH) range from a small decrease in hemoglobin to hypotension requiring transfer to the intensive care unit (ICU). Our goal was to identify which anticoagulated patients are at increased risk for SRH and its complications. METHODS: We conducted a retrospective review of 180 patients with SRH. Age, sex, presence of comorbidities, hemoglobin decrease, transfusion requirement, ICU stay, and length of ICU stay were recorded. Patients were divided into 5 groups based on their anticoagulants: (1) heparin and Coumadin, (2) heparin only, (3) Coumadin only, (4) heparin +/- Coumadin and aspirin (ASA) +/- Plavix, and (5) other anticoagulants. RESULTS: Group 4 patients were more likely to require ICU admission and have longer ICU stay compared to others (P = .021 & P < or = 0.0001, respectively, by Kruskall-Wallis test). Patients with coronary artery disease were more likely to require ICU admission (P = .01 by chi-square test). CONCLUSIONS: Patients on combined anticoagulant-antiplatelet therapy are more likely to require ICU admission and longer ICU stay. Close observation is warranted in these patients for early detection of SRH.

Silencing near tRNA genes requires nucleolar localization.

Transcription by RNA polymerase II is antagonized by the presence of a nearby tRNA gene in Saccharomyces cerevisiae. To test hypotheses concerning the mechanism of this tRNA gene-mediated (tgm) silencing, the effects of specific gene deletions were determined. The results show that the mechanism of silencing near tRNA genes is fundamentally different from other forms of transcriptional silencing in yeast. Rather, tgm silencing is dependent on the ability to cluster the dispersed tRNA genes in or near the nucleolus, constituting a form of three-dimensional gene control.