Race and Gender Disparities in Access to Parathyroidectomy: A Need to Change Processes for Diagnosis and Referral to Surgeons.

BACKGROUND: Hyperparathyroidism substantially impairs quality of life, and effective treatment depends on timely referral to surgeons. We hypothesized that there would be race and gender disparities in the time from initial diagnosis of hyperparathyroidism to treatment with parathyroidectomy. METHODS: We reviewed administrative data on 2289 patients with hypercalcemia (calcium > 10.5 mg/dL) and abnormal parathyroid hormone levels who were seen at a tertiary referral center from 2011 to 2016. We used two-phase parametric hazard modeling to identify predictors of time from index abnormal calcium until parathyroidectomy. RESULTS: The median age of our cohort was 63 years, and 1685 (74%) were women. Of the total patients, 1301 (57%) were Caucasian, and 946 (41%) were African-American. Only 490 (21%) patients underwent parathyroidectomy. Among patients undergoing surgery, time from index high calcium to surgical treatment was longest for African-American men, who waited a median of 13.6 months (interquartile range IQR 2-28), compared with 2.9 months (IQR 1-8) for Caucasian males (p < 0.05). African-American women waited a median of 6.7 months (IQR 2-16) versus 3.5 months (IQR 2-14) for Caucasian women (p < 0.05). At 1 year after the index abnormal calcium, only 6% of black men underwent surgery compared with 20% of white males (p < 0.05). Similarly, 13% of black women underwent surgery versus 20% of white women (p < 0.05). These differences remained significant after adjusting for age, calcium levels, insurance, and comorbidities. CONCLUSIONS: African-Americans face substantial delays in access to parathyroidectomy after diagnosis with hyperparathyroidism that could impair quality of life and increase health care costs. We must improve systems of diagnosis and referral to ensure timely treatment of hyperparathyroidism.

Novel Findings on SPECT-CT Tc-99 Sestamibi Imaging for Primary Hyperparathyroidism.

BACKGROUND: The addition of SPECT-CT to Tc-99 sestamibi has become a valuable tool for parathyroid localization in primary hyperparathyroidism (PHP). However, the enhanced sensitivity of this test can lead to unexpected and significant findings. We sought to identify the frequency and types of nonparathyroid detections by SPECT-CT. MATERIALS AND METHODS: With institutional approval, we reviewed all SPECT-CT studies performed for PHP between October 2012 and August 2018 for incidental nonparathyroid abnormalities. The electronic medical record was referenced to determine the type of lesion confirmed by additional evaluation. RESULTS: Among 2413 studies, 652 patients (27%) had 677 (28%) nonparathyroid findings. The most common were thyroid nodules (331/677, 49%), including 47 (6.9%) malignancies to date: 40 papillary thyroid cancers (11 microcarcinomas), five follicular thyroid cancers, one medullary carcinoma, and one noninvasive follicular thyroid neoplasm with papillary-like features. One hundred and seventy-seven patients had pulmonary nodules (26%), of whom nine were diagnosed with primary lung lesions (6 non-small-cell cancers, one small-cell cancer, one carcinoid, and one pulmonary sequestration). SPECT-CT revealed 14 patients (2.1%) with breast abnormalities, including three cancers. Nine patients (1.3%) demonstrated metastatic diseases within the lungs (4), bones (3), and mediastinum (2). One patient was diagnosed with follicular lymphoma. Two intracranial tumors were also identified, as well as dysplastic Barrett's esophagitis (1), hiatal hernia (20, 3%), and aortic aneurysm (13, 1.8%). In all, 72/677 (10.6%) PHP patients exhibited premalignant or malignant nonparathyroid SPECT-CT findings. CONCLUSIONS: In patients undergoing localization for PHP with Tc-99 sestamibi SPECT-CT, nonparathyroid findings are frequent (27%) and can lead to newly diagnosed malignant or premalignant lesions in at least 3% of patients to date.

Single-stage management of choledocholithiasis: intraoperative ERCP versus laparoscopic common bile duct exploration.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the criterion standard for treating patients with symptomatic gallstone disease; however, the optimal technique for extracting common bile duct stones remains unclear. Recent studies have noted improved outcomes with single-stage techniques, such as intraoperative endoscopic retrograde cholangiopancreatography (iERCP) and laparoscopic common bile duct exploration (LCBDE); however only few studies have directly compared those two single-stage techniques. OBJECTIVES: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, we retrospectively analyzed the postoperative outcomes of all patients who underwent single-stage LC for choledocholithiasis from 2005 to 2017. Using Current Procedural Terminology (CPT) codes, as well as International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) codes, we stratified patients into two cohorts: those who underwent iERCP and LCBDE. Applying univariate techniques, we evaluated baseline characteristics and postoperative outcomes for both cohorts. Our primary outcomes of interest were 30-day morbidity and 30-day mortality; our secondary outcomes included rates of reoperation, readmission, operative time, and hospital length of stay. RESULTS: Of the 1814 single-stage LC patients during our 13-year study period, 1185 (65.3%) underwent LCBDE; 629 (34.6%) underwent iERCP. Our univariate analysis showed that the two cohorts were homogeneous in terms of baseline characteristics, including demographics, preoperative comorbidities, laboratory values, and American Society of Anesthesiologists (ASA) scores. 30-day postoperative morbidity (including infectious and noninfectious complications) and overall mortality between groups were low and comparable. The mean operative time was slightly longer with LCBDE (125.1 ± 62.0 min) than iERCP (113.5 ± 65.2 min; P < 0.001), however the mean hospital length of stay, readmission rate, and reoperation rate were similar. CONCLUSION: We found that both iERCP and LCBDE resulted in low, comparable rates of morbidity and mortality. Centers with readily available endoscopic expertise might favor iERCP for its ease of access and shorter operative time. However, LCBDE remains an appropriate technique for patients with choledocholithiasis, especially when immediate endoscopic intervention is unavailable.

Failure to Diagnose and Treat Hyperparathyroidism Among Patients with Hypercalcemia: Opportunities for Intervention at the Patient and Physician Level to Increase Surgical Referral.

BACKGROUND: Hyperparathyroidism is both underdiagnosed and undertreated, but the reasons for these deficiencies have not been described. The purpose of this study was to identify reasons for underdiagnosis and undertreatment of hyperparathyroidism that could be addressed by targeted interventions. MATERIALS AND METHODS: We identified 3,200 patients with hypercalcemia (serum calcium >10.5 mg/dL) who had parathyroid hormone (PTH) levels evaluated at our institution from 2011 to 2016. We randomly sampled 60 patients and divided them into three groups based on their PTH levels. Two independent reviewers examined clinical notes and diagnostic data to identify reasons for delayed diagnosis or referral for treatment. RESULTS: The mean age of the patients was 61 ± 16.5 years, 68% were women, and 55% were white. Fifty percent of patients had ≥1 elevated calcium that was missed by their primary care provider. Hypercalcemia was frequently attributed to causes other than hyperparathyroidism, including diuretics (12%), calcium supplements (12%), dehydration (5%), and renal dysfunction (3%). Even when calcium and PTH were both elevated, the diagnosis was missed or delayed in 40% of patients. For 7% of patients, a nonsurgeon stated that surgery offered no benefit; 22% of patients were offered medical treatment or observation, and 8% opted not to see a surgeon. Only 20% of patients were referred for surgical evaluation, and they waited a median of 16 months before seeing a surgeon. CONCLUSION: To address common causes for delayed diagnosis and treatment of hyperparathyroidism, we must improve systems for recognizing hypercalcemia and better educate patients and providers about the consequences of untreated disease. IMPLICATIONS FOR PRACTICE: This study identified reasons why patients experience delays in workup, diagnosis, and treatment of primary hyperparathyroidism. These data provide valuable information for developing interventions that increase rates of diagnosis and referral.

What Does the Average Person Know About Endocrine and Vascular Surgeons?

INTRODUCTION: Surgical fields are becoming increasingly specialized. This can lead to misunderstanding or confusion about the scope of practice of different surgeons by the individual seeking specialized surgical care. To assess public understanding of subspecialty surgeons, we sought to survey general knowledge of the specialty areas of Endocrine Surgery and Vascular Surgery. METHODS: A survey was conducted in three locations in Birmingham, Alabama: a local farmers market, a public park, and the University of Alabama at Birmingham hospital. Fifty people were surveyed at random at each of the three locations, with hospital staff identified by wearing a hospital ID badge recruited at the University of Alabama at Birmingham hospital location. Participants were asked to define both an endocrine surgeon and vascular surgeon, as well as identify aspects of their practice. Participant's answers to the survey were recorded and coded by three evaluators (two MDs, one PharmD candidate). Survey responses were assessed for correct definition of the specialty (yes/no), recognition of being a surgeon (yes/no), spectrum of practice (none, partial, or complete), and presence of a common misconception (yes/no). Interrater reliability (kappa) was calculated for each question. Chi-square test was used to compare the difference in each answer between the two specialties. RESULTS: A total of 150 people participated in the study. The majority were female (58%) and approximately 50 y of age or less (65%). Interrater reliability from 0.32 to 0.84 was observed, and agreement from 40% to 98% between raters was achieved for all questions. Significantly more respondents recognized endocrine surgery as a surgical profession (21%) compared to vascular surgeons (18%) (P < 0.001). However, significantly fewer could define what an endocrine surgeon does (14%) than could define what a vascular surgeon does (57%). Only 3% of respondents could identify the entire spectrum of practice of an endocrine surgeon, with 42% and 55% providing partially or completely incorrect responses, respectively. Significantly more respondents could identify all of a vascular surgeon's spectrum of practice (11%), with 60% and 29% providing partial or completely incorrect responses, respectively (P < 0.001). Endocrine surgeons were most often confused for endocrinologists (40%), whereas vascular surgeons were most often confused for cardiovascular surgeons (22%). CONCLUSIONS: This study reveals an overall lack of understanding among the general public about what endocrine and vascular surgeons are and their spectrum of practice and shows that public understanding of the field of endocrine surgery is very low. More efforts need to be made to increase the visibility of these fields and communicate these surgeons' specialized expertise.

Surgical repair of perforated peptic ulcers: laparoscopic versus open approach.

INTRODUCTION: Perforated peptic ulcers are a surgical emergency that can be repaired using either laparoscopic surgery (LS) or open surgery (OS). No consensus has been reached on the comparative outcomes and safety of each approach. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, we conducted a 12-year retrospective review (2005-2016) and identified 6260 adult patients who underwent either LS (n = 616) or OS (n = 5644) to repair perforated peptic ulcers. To mitigate selection bias and adjust for the inherent heterogeneity between groups, we used propensity-score matching with a case (LS):control (OS) ratio of 1:3. We then compared intraoperative outcomes such as operative time, and 30-day postoperative outcomes including infectious and non-infectious complications, and mortality. RESULTS: Propensity-score matching created a total of 2462 matched pairs (616 in the LS group, 1846 in the OS group). Univariate analysis demonstrated successful matching of patient characteristics and baseline clinical variables. We found that OS was associated with a shorter operative time (67.0 ± 28.6 min, OS versus 86.9 ± 57.5 min, LS; P < 0.001) but a longer hospital stay (8.6 ± 6.2 days, OS versus 7.8 ± 5.9 days, LS; P = 0.001). LS was associated with a lower rate of superficial surgical site infections (1.5%, LS versus 4.2%, OS; P = 0.032), wound dehiscence (0.3%, LS versus 1.6%, OS; P = 0.030), and mortality (3.2%, LS versus 5.4%, OS; P = 0.009). CONCLUSION: Fewer than 10% of patients with perforated peptic ulcers underwent LS, which was associated with reduced length of stay, lower rate of superficial surgical site infections, wound dehiscence, and mortality. Given our results, a greater emphasis should be provided to a minimally invasive approach for the surgical repair of perforated peptic ulcers.

Single-session laparoscopic cholecystectomy and ERCP: a valid option for the management of choledocholithiasis.

BACKGROUND AND AIMS: The option for performing ERCP and laparoscopic cholecystectomy (LC) for the management of choledocholithiasis in the same operative session is often overlooked. We compared the success, safety, and cost of ERCP and LC when performed in either a single session or in separate sessions. METHODS: We conducted a retrospective cohort study at a U.S. tertiary care hospital. We identified patients undergoing ERCP and LC between April 2011 and August 2014 in either a single operative session (n = 33) or in 2 separate sessions within a 30-day period (n = 80). Technical success, total anesthesia duration, operative time, length of hospitalization, cost of care, and morbidity and mortality were evaluated. RESULTS: Bile duct clearance was achieved in all patients at ERCP in the same-session cohort. The separate versus single-session groups, respectively, did not differ in terms of total procedure times (mean ± SD = 142 ± 64 vs 142 ± 58 min; t test, P =.98), anesthesia duration (251 ± 64 vs 225 ± 69 min; P =.06), or overall cost (49.3 ± 24.5 vs 42.3 ± 23.2 ×1000 USD; P =.167), but hospitalization was longer in the separate-sessions group (6.2 ± 3.3 vs 4.8 ± 2.6 days; P =.03). The rates of adverse events were similarly low (7% vs 2%, P =.70). CONCLUSIONS: Performing single-session ERCP and LC is safe, effective, economically viable, and reduces hospital stay compared with performing ERCP and LC during separate sessions.

A Systematic Review of Esophageal MicroRNA Markers for Diagnosis and Monitoring of Barrett's Esophagus.

BACKGROUND: Esophageal epithelial microRNAs may be used to diagnose Barrett's esophagus (BE) and possibly monitor its progression to esophageal adenocarcinoma (EAC). AIMS: We reviewed studies that have investigated this to identify microRNAs with high biomarker potential for screening and disease monitoring in BE. METHODS: PubMed and EMBASE databases were searched for studies that quantified esophageal epithelial microRNAs. Publications reporting microRNA comparisons of normal, non-dysplastic BE, BE with high-grade dysplasia (HGD), and EAC tissues using both unbiased discovery and independent validation phases were reviewed. RESULTS: Eleven studies on microRNA expression differences between normal epithelium and non-dysplastic BE (seven studies), HGD (4) or EAC (7), or between non-dysplastic BE and HGD (3) or EAC (6) were identified, and the findings of their validation phase were analyzed. Increased miR-192, -194, and -215, and reduced miR-203 and -205 expression in BE compared to normal was noticed by all 4-6 of the seven studies that examined these microRNAs. In heterogeneity tests of the reported fold-change values, the I (2) statistics were 7.9-17.1 % (all P < 0.05). Elevated miR-192, -194, and -215, and diminished miR-203 and -205 levels were also noted for comparisons of HGD or EAC against normal. In contrast, a consistent microRNA expression difference was absent for the comparisons of HGD or EAC against BE. CONCLUSIONS: MicroRNAs miR-192, -194, -203, -205, and -215 are promising tissue biomarkers for diagnosing BE. Cross-sectional data suggest that microRNAs may have a limited role in separating BE from HGD/EAC epithelia but need further testing in longitudinal follow-up studies.

Fecal Microbiota Transplantation for Fulminant Clostridioides Difficile Infection: A Combined Medical and Surgical Case Series.

INTRODUCTION: Urgent abdominal colectomy is indicated for patients with fulminant Clostridioides difficile infection (CDI) when other medical therapies fail, yet mortality remains high. Fecal microbiota transplant is a less invasive alternative approach for patients with fulminant CDI. We report the 30-day complications of patients with fulminant CDI who underwent either abdominal colectomy, fecal microbiota transplantation (FMT), or FMT followed by abdominal colectomy (FMT-CO). Methods: We performed a single-center, retrospective case review of combined medical and surgical patients with CDI at a large academic medical center between 2008 and 2016. Cohorts were identified as patients with fulminant CDI who underwent total abdominal colectomy alone (CO), FMT alone (FMT), or FMT-CO. We analyzed patient demographics, history, comorbidities, clinical and laboratory variables, CDI severity scores, and mortality outcomes at 30 days. Results: We identified 5,150 patients with CDI at our center during the review period; 16 patients met the criteria for fulminant CDI and were included in this study, with four patients in the CO cohort, eight patients in the FMT cohort, and four patients in the FMT-CO cohort. Demographics and CDI severity scores were similar for all three groups, although the selected comorbidity profiles differed significantly among the three cohorts. The 30-day mortality rates for patients in the CO, FMT, and FMT-CO groups were 25%, 12.5%, and 25%, respectively. Conclusions: FMT is an alternative or adjunctive therapy to colectomy for patients with fulminant CDI that is not associated with increased mortality. Implementation of FMT protocols in clinical practice would be dependent on the availability of qualified transplant material and successful early identification of patients likely to benefit from FMT.

Detection of microRNAs in dried serum blots.

We observed the preservation of microRNAs in unrefrigerated dried serum blots. Preservation was not adversely affected by drying or storing at 37, 45, or 60°C instead of room temperature, but it was harmed when blots were dried incompletely before storage. Preservation of microRNAs in serum was not diminished if, instead of being kept frozen at -80°C, it was stored as dried blots at room temperature for 5 months or at 37°C for 4 weeks. Thus, dried blots can be a convenient and safer way to save, transport, and store serum for microRNA assays.

MicroRNAs and lung cancer: Biology and applications in diagnosis and prognosis.

MicroRNAs are tiny non-coding RNA molecules which play important roles in the epigenetic control of cellular processes by preventing the translation of proteins from messenger RNAs (mRNAs). A single microRNA can target different mRNAs, and an mRNA can be targeted by multiple microRNAs. Such complex interplays underlie many molecular pathways in cells, and specific roles for many microRNAs in physiological as well as pathological phenomena have been identified. Changes in expression of microRNAs have been associated with a wide variety of disease conditions, and microRNA-based biomarkers are being developed for the identification and monitoring of such states. This review provides a general overview of the current state of knowledge about the biology of microRNAs, and specific information about microRNAs with regard to the diagnosis and prognosis of lung cancer.

Factors associated with late recurrence after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: A recent study with unusually lengthy follow-up after surgery for primary hyperparathyroidism reported higher recurrence rates than previously appreciated. We sought to identify specific factors associated with late recurrence after seemingly curative parathyroidectomy. METHODS: Prospectively collected data were retrieved for patients who had surgical treatment of sporadic primary hyperparathyroidism with ≥ 3-year follow-up (3-17.6 years). Recurrence was defined by 6 months of eucalcemia with subsequent hypercalcemia and a high or unsuppressed parathyroid hormone. Recurrent patients were compared with cured patients (defined by consistent eucalcemia). RESULTS: Among 261 patients, 28 (10.7%) had recurrence and 233 (89.3%) were cured. The mean time to recurrence was 77 months (range 13-170). The mean final intraoperative parathyroid hormone (49.0 pg/mL vs 37.5 pg/mL, P < .01), 6-month calcium levels (9.6 mg/dL vs 9.2 mg/dL, P = .02) and mean 6-month parathyroid hormone levels (86.5 pg/mL vs 59.6 pg/mL, P = .04) were higher for recurrence. By multivariable analysis, 6-month calcium ≥ 9.7 and eucalcemic elevation of the parathyroid hormone at 6 months were independently associated with recurrent primary hyperparathyroidism. CONCLUSION: Long-term follow-up after apparent curative surgery for primary hyperparathyroidism identified a high late recurrence rate (10.7%), up to 17 years later. A 6-month calcium >9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 months may be associated with recurrence, and such findings may help guide management.

Is Frozen-Section Analysis During Thyroid Operation Useful in the Era of Molecular Testing?

BACKGROUND: With the increased use of molecular testing of thyroid fine-needle biopsies, the frequency and extent of thyroid resection for thyroid nodules has changed. Although the role of frozen-section analysis of the thyroid has been reduced markedly in recent years, many surgeons still routinely use it intraoperatively. We sought to determine the utility of frozen section during thyroidectomy in the era of molecular testing. STUDY DESIGN: We reviewed 236 consecutive patients who had thyroidectomy with intraoperative frozen-section analysis at our institution between November 2015 and October 2017. We re-reviewed the preoperative diagnosis, frozen-section diagnosis, final pathology, and whether operative management changed from the initial plan based on frozen section. RESULTS: Mean age of the patients was 55.6 ± 14.1 years, and 83% were female. Of the 236 patients, frozen section did not change the intraoperative management in 225 (95%). Of the 11 patients whose thyroid operation was modified, the operation was either too much or not enough in 6 patients. In only 5 (2.1%) patients, frozen-section analysis correctly changed the extent of thyroidectomy. CONCLUSIONS: Thyroid frozen-section analysis adds cost and time to thyroid operations without notable benefit. In our cohort, only 2.1% of frozen sections accurately changed intraoperative management. We recommend against its routine use.

To admit or not to admit? Experience with outpatient thyroidectomy for Graves' disease in a high-volume tertiary care center.

BACKGROUND: Outpatient thyroidectomy is increasingly performed. Thyroidectomy for Graves' disease, however, has greater risk of periprocedural complications, limiting use of same-day procedures. We sought to demonstrate that these patients may be managed with ambulatory surgery. METHODS: The experience of one endocrine surgeon with thyroidectomy for Graves' was examined from January 2016-November 2017. Forty-one patients met criteria. Patient demographics, perioperative parameters, and postoperative outcomes including emergency department utilization and readmission were recorded. RESULTS: Mean age was 31.5 ±â€¯17.0 years, with 80% females. Mode ASA score was 3, and median operative time was 77 minutes (43-132). Complications included transient hypocalcaemia in 12%, and temporary laryngeal nerve palsy in 9.7%, with no permanent complications. Two patients were admitted immediately postoperatively for non-medical reasons. Thirty-day emergency rdepartment visits were noted in 9.7%, with subsequent readmission of 7%. CONCLUSIONS: Outpatient total thyroidectomy is safe and effective with acceptable morbidity in the Graves' patient.

Whole blood microRNA expression may not be useful for screening non-small cell lung cancer.

At least seven studies have suggested that microRNA levels in whole blood can be diagnostic for lung cancer. We conducted a large bi-institutional study to validate this. Qiagen® PAXgene™ Blood miRNA System was used to collect blood and extract RNA from it for 85 pathologic stage I-IV non-small cell lung cancer (NSCLC) cases and 76 clinically-relevant controls who had a benign pulmonary mass, or a high risk of developing lung cancer because of a history of cigarette smoking or age >60 years. Cases and controls were similar for age, gender, race, and blood hemoglobin and leukocyte but not platelet levels (0.23 and 0.26 million/µl, respectively; t test P = 0.01). Exiqon® MiRCURY™ microarrays were used to quantify microRNAs in RNA isolates. Quantification was also performed using Taqman™ microRNA reverse transcription (RT)-PCR assays for five microRNAs whose lung cancer-diagnostic potential had been suggested in seven published studies. Of the 1,941 human mature microRNAs detectable with the microarray platform, 598 (31%) were identified as expressed and reliably quantified among the study's subjects. However, none of the microRNAs was differentially expressed between cases and controls (P >0.05 at false discovery rate <5% in test using empirical Bayes-moderated t statistics). In classification analyses with leave-one-out internal cross-validation, cases and controls could be identified by microRNA expression with 47% and 50% accuracy with support vector machines and top-scoring pair methods, respectively. Cases and controls did not differ for RT-PCR-based measurements of any of the five microRNAs whose biomarker potential had been suggested by seven previous studies. Additionally, no difference for microRNA expression was noticed in microarray-based microRNA profiles of whole blood of 12 stage IA-IIIB NSCLC cases before and three-four weeks after tumor resection. These findings show that whole blood microRNA expression profiles lack diagnostic value for high-risk screening of NSCLC, though such value may exist for selective sub-groups of NSCLC and control populations.

MiR-205 and MiR-375 microRNA assays to distinguish squamous cell carcinoma from adenocarcinoma in lung cancer biopsies.

INTRODUCTION: Identification of adenocarcinoma (AC) and squamous cell carcinoma (SCC) histology of non-small-cell lung cancer (NSCLC) in biopsies is clinically important but can be inaccurate by routine histopathologic examination. We quantify this inaccuracy at a cancer center, and evaluate the utility of a microRNA-based method to histotype AC/SCC in biopsies. METHODS: RNA was extracted from tissue sections with greater than 90% tumor content that were macro- or micro-dissected from formalin-fixed, paraffin-embedded biopsy specimens. MicroRNAs in RNA from the biopsies and from resected tumors were quantified by TaqMan reverse transcription-polymerase chain reaction assays and normalized against the RNU6B housekeeping RNA. Publicly available microRNA expression datasets were examined. RESULTS: NSCLC subtyping of small biopsy specimens by routine histopathologic examination either failed or mistyped the histology of 21% of 190 cases. Using 77 resectates, an reverse transcription-polymerase chain reaction-based assay of microRNAs miR-21, miR-205, and miR-375 was developed to identify AC and SCC subtypes of NSCLC. This method identified the AC/SCC histotypes of 25 biopsies with an accuracy of 96%, and correctly histotyped all 12 cases for which the histology had been mistyped by routine histopathologic examination of the biopsy. Examination of publicly available datasets identified miR-205 and miR-375 as microRNAs with the best ability to histotype AC and SCC, and that levels of the two microRNAs in AC or SCC are unaffected by the pathologic stage of the tumor or the age or race of the patient. CONCLUSIONS: Histotypic microRNA assays can aid the subtyping of NSCLC biopsies as AC or SCC by standard histopathologic methods.

Regional lung chemotherapy techniques.

Selective delivery of chemotherapy to an affected organ or region of the body promises improved drug efficacy for the targeted area while minimizing the systemic exposure and toxicity. Several intravascular surgical techniques to achieve targeted regional lung chemotherapy have been developed. Investigations have been carried out to determine the feasibility, safety, and efficacy of these techniques in the primary or adjuvant setting with the intent to palliate or cure. This overview describes the history, rationale, technical aspects, and clinical experience of four regional lung chemotherapy techniques delivered by vascular manipulations including bronchial artery infusion, pulmonary artery chemoembolization, isolated lung perfusion, and lung suffusion.

Overexpression of the lung cancer-prognostic miR-146b microRNAs has a minimal and negative effect on the malignant phenotype of A549 lung cancer cells.

INTRODUCTION: Expression levels of miR-146b-5p and -3p microRNAs in human non-small cell lung cancer (NSCLC) are associated with recurrence of the disease after surgery. To understand this, the effect of miR-146b overexpression was studied in A549 human lung cancer cells. METHODS: A549 cells, engineered with lentiviruses to overexpress the human pre-miR-146b precursor microRNA, were examined for proliferation, colony formation on plastic surface and in soft agar, migration and invasiveness in cell culture and in vivo in mice, chemosensitivity to cisplatin and doxorubicin, and global gene expression. miR-146b expressions were assessed in microdissected stroma and epithelia of human NSCLC tumors. Association of miR-146b-5p and -3p expression in early stage NSCLC with recurrence was analyzed. PRINCIPAL FINDINGS: A549 pre-miR-146b-overexpressors had 3-8-fold higher levels of both miR-146b microRNAs than control cells. Overexpression did not alter cellular proliferation, chemosensitivity, migration, or invasiveness; affected only 0.3% of the mRNA transcriptome; and, reduced the ability to form colonies in vitro by 25%. In human NSCLC tumors, expression of both miR-146b microRNAs was 7-10-fold higher in stroma than in cancerous epithelia, and higher miR-146b-5p but lower -3p levels were predictive of recurrence. CONCLUSIONS: Only a minimal effect of pre-miR-146b overexpression on the malignant phenotype was seen in A549 cells. This could be because of opposing effects of miR-146b-5p and -3p overexpression as suggested by the conflicting recurrence-predictive values of the two microRNAs, or because miR-146b expression changes in non-cancerous stroma and not cancerous epithelia of tumors are responsible for the prognostic value of miR-146b.