Clinicopathologic and Molecular Characteristics of Resected Thoracic Mass Lesions in the Pediatric Population: A 25-Year Institutional Experience From a Tertiary Care Center.

CONTEXT.­: Primary thoracic neoplasms are rare in children, whereas nonneoplastic mass lesions or cysts and metastases are more common, and there is a relative paucity of comprehensive histopathologic and molecular data. OBJECTIVE.­: To define the clinicopathologic spectrum of neoplastic and nonneoplastic diseases observed in resected mass lesions in the chest of pediatric patients, and to identify somatic alterations observed in primary neoplasms. DESIGN.­: Clinicopathologic features of thoracic mass lesions (n = 385) resected from 373 patients aged ≤21 years in a 25-year period (1993-2018) were included. Primary neoplasms having sufficient material were tested by a laboratory-developed comprehensive genomic profiling assay that assesses tumor mutational burden, microsatellite instability, somatic sequence variants, gene amplifications, fusions, and specific transcript variants. RESULTS.­: The most commonly resected space-occupying lesions were nonneoplastic mass lesions and cysts or malformations, resected in 117 (31.4%) and 58 of 373 patients (15.5%) respectively. Metastatic neoplasms were observed in 169 of 373 patients (45.3%; mean age 14.4 years, range 1-21 years); the most common was osteosarcoma (68 of 169; 40.2% of metastases). Primary lung neoplasms occurred in 24 of 373 patients (6.4%; mean age 14.5 years, range 6 months-21 years), and 16 patients had primary extrapulmonary thoracic tumors. Carcinoid tumor was the most common primary lung neoplasm (7 typical, 3 atypical). Molecular testing showed a prevalence of somatic pathogenic or likely pathogenic mutations and copy-number alterations. No fusions or splice variants were identified. Tumors were microsatellite-stable with low tumor mutational burden. CONCLUSIONS.­: Resected pediatric thoracic mass lesions are more likely to be metastatic lesions, congenital cysts or malformations, or nonneoplastic lesions compared to primary thoracic neoplasms, which are encountered at a low frequency and tend to have relatively simple genetic profiles.

Development of a tool to calculate the probability of hypocalcemia after total thyroidectomy: a prospective study.

PURPOSE: This study aimed to evaluate the ability of the percentage of decrease in serum PTH level in the first 8 h after total thyroidectomy (TT) to predict hypocalcemia requiring Ca supplementation and develop a tool to predict it. METHODS: 97 patients who underwent TT with measurement of preoperative parathyroid hormone (PTH) levels were prospectively evaluated 1 and 8 h after TT; postoperative magnesium (Mg2PO) and phosphorus levels were evaluated on the 2nd day after surgery. The percentage of decrease in PTH level 1 h (%dPTH1h) and 8 h (%dPTH8h) postoperatively and predictors of hypocalcemia requiring Ca supplementation were evaluated and an equation was developed to predict this outcome. RESULTS: %dPTH1h (p = 0.002), %dPTH8h (p = 0.001) and (Mg2PO) (p < 0.01) were isolated predictors of postoperative hypocalcemia requiring Ca supplementation. The data obtained led to the development of two tools to predict this complication. CONCLUSIONS: The percentage of decrease in PTH level 1 h and 8 h postoperatively and the magnesium level on the 2nd day after surgery were predictors of more severe hypocalcemia, and an auxiliary tool for predicting this complication was developed.

Basal or stimulated thyroglobulin in evaluating response to treatment in papillary thyroid carcinoma? A retrospective cohort study.

OBJECTIVE: It is not clear whether response to initial treatment in papillary thyroid carcinoma (PTC) patients is best evaluated by measuring thyroglobulin (Tg) in the presence of levothyroxine (BTg) or when stimulated by elevated TSH (STg). The aim of this study was to evaluate whether response to therapy 1 year after initial treatment changes with the use of STg in relation to BTg in PTC patients treated with total thyroidectomy (TT) and radioiodine (131I), and, if observed, to assess which response is better associated with clinical course. SUBJECTS AND METHODS: This is a retrospective study of 148 PTC patients submitted to TT and 131I. We analyzed the response to therapy (excellent, biochemical incomplete, or indeterminate) at 1 year after initial treatment, using BTg or STg, and compared which method was better associated with "excellent response at final evaluation." RESULTS: Twenty-eight patients (20.4%) presented change in response to therapy, with 17 of these (60.7%) presenting a worse response. Response using STg was 1.6 times better associated with proposed outcome [odds ratio (OR) = 4.61; confidence interval 95% (IC95%): 2.13-9.98] than with BTg (OR = 2.84; IC95%: 1.33-6.06). CONCLUSION: Response to therapy at 1 year using STg was altered in approximately 20% of cases and therefore proved to be a better predictor of excellent response in the last evaluation.

Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study

ABSTRACT Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusions: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement.

Association between Clinical and Histopathological Findings in Intestinal Neuronal Dysplasia Type B: An Advance towards Its Definition as a Disease.

INTRODUCTION: Intestinal neuronal dysplasia type B (IND-B) is a controversial entity that affects the submucosal nerve plexus of the distal intestine. The lack of definition of the causal relationship between histological findings and clinical symptoms has been identified as the primary point to be elucidated in the scientific investigation related to IND-B, which is essential for it to be considered a disease. OBJECTIVE: To investigate the relationship between histopathological findings and symptoms in a series of patients with IND-B. METHODS: Twenty-seven patients with histopathological diagnosis of IND-B, according to the Frankfurt Consensus (1990), who underwent surgical treatment through colorectal resections were included. Data from medical records regarding the clinical picture of the patients at the time of diagnosis, including the intestinal symptom index (ISI) and a detailed histopathological analysis of the rectal specimens, were retrieved. Exploratory factor analysis was performed, applying the principal components method for clusters with Varimax rotation. RESULTS: Two factors were determined: the first, determined by histopathological and clinical variables, and the second, composed of the main symptoms presented in patients with IND-B, including ISI. Factorial rotation showed the association between the two factors and, through a graph, demonstrated the proximity between ISI values and histopathological alterations. CONCLUSION: There was evidence of an association between the clinical features presented by patients with IND-B and the histopathological findings of the rectal samples. These results support the understanding of IND-B as a disease.

Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study.

Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusion: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement.

Agreement between histopathological and intraoperative classifications for pediatric appendicitis and its relationship with the post-operative clinical outcome.

Introduction: Some studies have shown poor agreement between intraoperative and histopathological classifications for appendicitis, despite their routine use in clinical practice. Objective: To investigate the agreement between histopathological and intraoperative classifications for pediatric appendicitis and evaluate the predictive potential of these classifications for the post-operative outcome. Methods: A retrospective, longitudinal, observational single-center study, carried out with 485 patients up to15 years of age, with a confirmed diagnosis of acute appendicitis by histopathological evaluation. The histopathological results classified the appendices as uncomplicated appendicitis when there was confirmation of the diagnosis of appendicitis without necrosis or perforation and complicated appendicitis when there was extensive necrotic tissue in the outer layer of the appendix or signs of perforation. The intraoperative findings were classified as uncomplicated appendicitis when the appendix presented with hyperemia and edema or fibrinous exudate and complicated appendicitis when the appendix showed necrosis, abscess, or perforation. The kappa index determined the agreement and the prediction relationships using a generalized linear model. Results: 43.9% of cases were classified as complicated appendicitis by histopathological evaluation and 49.7% by intraoperative classification. The agreement analysis between the histopathological and intraoperative classification showed a moderate agreement, with a Kappa index of 0.419 (0.337-0.501). There was an association (P < 0.05) between the intraoperative classification and the post-operative clinical outcomes (time to start feeding, fever, intraabdominal collection, length of stay, the need for antibiotic therapy changing, and need for ICU). There was no association between histopathological classification and post-operative outcomes. Conclusion: The agreement between the two classifications was moderate, and the intraoperative classification was able to predict the post-operative clinical outcomes.

PTEN Immunohistochemistry.

CONTEXT.­: Intestinal neuronal dysplasia type B (IND B) is a complex entity involving the enteric nervous system, clinically manifested with constipation in infancy. Diagnosis has been established by histopathologic analysis of rectal biopsies. However, the criteria for the diagnosis have been questioned and modified, hindering diagnostic practice. OBJECTIVE.­: To analyze the applicability of PTEN immunohistochemistry in the diagnosis of IND B and to compare with control cases and cases of Hirschsprung disease (HD). DESIGN.­: PTEN immunohistochemical expression was analyzed in colorectal samples from 29 cases of IND B and compared with 4 control cases and 6 cases of HD. The pattern of PTEN immunoexpression was analyzed in glial cells of the submucosal and myenteric nerve plexuses and in neural fibrils of the muscularis propria using a scoring system. RESULTS.­: Marked reduction or absence of PTEN expression was observed in glial cells of the submucosal nerve plexuses in all cases of the IND B group and in the myenteric nerve plexuses in 28 of 29 cases (96.5%). Lack of PTEN expression was detected in neural fibrils within the muscularis propria in 21 of 29 cases (72%) of the IND B group. PTEN expression was positive in the same neural structures of the control and HD groups. CONCLUSIONS.­: PTEN immunohistochemistry may be a valuable tool in the diagnostic evaluation of IND B. Lack of or reduction of PTEN expression in neural fibrils within the muscularis propria suggests that involvement of the neuromuscular junction may be a key event in the pathogenesis of the motility disturbance occurring in IND B.

Loss of Methylthioadenosine Phosphorylase by Immunohistochemistry Is Common in Pulmonary Sarcomatoid Carcinoma and Sarcomatoid Mesothelioma.

OBJECTIVES: Differentiating malignant pleural mesothelioma from benign reactive mesothelial processes can be quite challenging. Ancillary tests such as BRCA1-associated protein 1 (BAP1) immunohistochemistry and p16 fluorescence in situ hybridization (FISH) are helpful tools to aid in this distinction. Immunohistochemistry for methylthioadenosine phosphorylase (MTAP) has recently been proposed as an effective surrogate marker for p16 FISH and is an attractive alternative test due to shorter turnaround time. There are little data regarding the specificity of MTAP loss for mesothelioma or whether it may be useful to distinguish mesothelioma from the most common entity in the differential diagnosis, sarcomatoid carcinoma. METHODS: We studied well-characterized cases of sarcomatoid carcinoma (n = 34) and sarcomatoid mesothelioma (n = 62), which were stained for MTAP (clone 2G4) and BAP1 (clone C-4). RESULTS: Loss of MTAP expression was observed in 17 (50%) of 34 pulmonary sarcomatoid carcinomas; BAP1 expression was retained in all of the cases in which it was performed (n = 31). MTAP expression was lost in 38 (61%) of 62 sarcomatoid mesotheliomas; BAP1 was lost in 6 (10%) of 62. In the six cases with BAP1 loss, five also had loss of MTAP, while MTAP expression was retained in one. CONCLUSIONS: Loss of MTAP expression by immunohistochemistry is common in pulmonary sarcomatoid carcinoma, as it is present in half of cases. This rate is similar to what is observed in sarcomatoid mesothelioma (61%). Therefore, this stain is not useful to distinguish between these two malignancies. MTAP loss is more common than BAP1 loss in the setting of sarcomatoid mesothelioma (61% vs 10%, respectively).

Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells.

Intestinal neuronal dysplasia type B (IND-B) is a controversial condition among gastrointestinal neuromuscular disorders. Constipation is its most common clinical manifestation in patients. Despite intense scientific research, there are still knowledge gaps regarding the diagnostic criteria for IND-B in the histopathological analysis of rectal biopsies. The guidelines published in the past three decades have directed diagnostic criteria for quantifying the number of ganglion cells in the nervous plexus of the enteric nervous system. However, it is very complex to distinguish numerically what is pathological from what is normal, mainly because of the difficulty in determining a reliable control group composed of healthy children without intestinal symptoms. Thus, a series of immunohistochemical markers have been proposed to assist in the histopathological analysis of the enteric nervous system. Several of these markers facilitate the identification of other structures of the enteric nervous system, in addition to ganglion cells. These structures may be related to the etiopathogenesis of IND-B and represent new possibilities for the histopathological diagnosis of this disease, providing a view beyond the number of ganglion cells. This review critically discusses the aspects related to the disease definitions and diagnostic criteria of this organic cause of constipation.

SATB2 Is Expressed in a Subset of Pulmonary and Thymic Neuroendocrine Tumors.

OBJECTIVES: To evaluate SATB2 expression and prognostic implications in a large cohort of thoracic neuroendocrine tumors. METHODS: Surgical pathology files (1995-2017) and an institutional thymic epithelial tumor database (2010-2020) were searched for resected neuroendocrine tumors. Cases were stained with SATB2 (clone EP281). Percent SATB2-positive tumor cells and expression intensity were scored. RESULTS: In the lung, SATB2 was expressed in 5% or more of tumor cells in 29 (74.4%) of 39 small cell carcinomas and 9 (22.5%) of 40 atypical and 26 (40.6%) of 64 typical carcinoid tumors. SATB2 percent tumor cell expression and intensity were higher in small cell carcinomas than in carcinoid tumors (both P < .001, respectively). After adjusting for tumor subtype, SATB2 expression did not correlate with outcome. In the thymus, four (100%) of four atypical carcinoid tumors and one large cell neuroendocrine carcinoma but no small cell carcinoma (n = 2) expressed SATB2 in 5% or more of tumor cells. CONCLUSIONS: SATB2 (clone EP281) is expressed in a large subset of pulmonary and thymic neuroendocrine tumors and therefore does not appear to be a useful marker to identify the origin of neuroendocrine tumors. Validation studies are needed, specifically including thymic neuroendocrine tumors, as the expression pattern might be different in those tumors.

Utility of Immunohistochemistry for MUC4 and GATA3 to Aid in the Distinction of Pleural Sarcomatoid Mesothelioma From Pulmonary Sarcomatoid Carcinoma.

CONTEXT.­: Distinguishing pulmonary sarcomatoid carcinoma from pleural sarcomatoid mesothelioma is challenging because of overlapping histology, immunophenotype, and clinical features. Reliable immunohistochemical markers to aid in this distinction would be very valuable. Recent studies have proposed that MUC4 expression is common in sarcomatoid carcinoma but not in sarcomatoid mesothelioma, with the converse pattern reported for GATA3. OBJECTIVE.­: To further explore the utility of MUC4 and GATA3 in distinguishing pulmonary sarcomatoid carcinoma from sarcomatoid mesothelioma. DESIGN.­: Well-characterized cases of sarcomatoid carcinoma (n = 32) and sarcomatoid mesothelioma (n = 64) were included. Diagnoses were confirmed by thoracic pathologists with incorporation of immunophenotype, clinical, and radiographic features. Whole-tissue sections were stained for GATA3 and MUC4. RESULTS.­: Patients with sarcomatoid carcinoma and sarcomatoid mesothelioma had similar mean age and male predominance. GATA3 was positive in 63 of 64 sarcomatoid mesotheliomas (98%; 42 diffuse, 16 patchy, 5 focal), and 15 of 32 sarcomatoid carcinomas (47%; 3 diffuse, 8 patchy, 4 focal). MUC4 was positive in 2 of 64 sarcomatoid mesotheliomas (3%; 1 patchy, 1 focal), and in 12 of 32 sarcomatoid carcinomas (38%; 5 diffuse, 6 patchy, 1 focal). CONCLUSIONS.­: Diffuse GATA3 expression favors sarcomatoid mesothelioma over sarcomatoid carcinoma, which rarely shows diffuse expression (sensitivity and specificity of diffuse staining 66% and 94%, respectively). Focal and patchy GATA3 expression is observed in both tumor types, and therefore is not helpful in this distinction. Sensitivity of MUC4 for sarcomatoid carcinoma was low in our cohort, positive in only 38% with frequent patchy staining, but it was quite specific.

What should be the treatment for intestinal neuronal dysplasia type B? A comparative long-term follow-up study.

PURPOSE: To present the long-term follow-up outcomes of patients with intestinal neuronal dysplasia type B (IND-B) managed either conservatively or surgically. METHODS: We conducted an ambispective, observational, longitudinal, and comparative study. Clinical data were reviewed at the start of treatment. After a minimum period of five years, the patients participated in semi-structured interviews in which the bowel function score (BFS) was applied to assess intestinal function, a proposed intestinal symptom index (ISI) to assess clinical symptoms, and a classification of clinical prognosis to assess treatment success. Comparisons between the two types of treatment were performed by evaluating pre- and post-treatment criteria. RESULTS: Fifty patients diagnosed with IND-B were included in the study. Thirty-eight patients underwent surgical treatment (26 elective surgical treatment for primary colorectal resection and 12 emergency colostomies for intestinal obstruction or enterocolitis). Twelve patients were managed conservatively. With the exception of the patients who required an emergency operation (n = 12), the two groups were composed of patients with severe constipation who had similar clinical and functional characteristics at the time of IND-B diagnosis. A better clinical response was observed in patients submitted to conservative treatment, with a greater increase in the BFS (16.5 [-4/+18] versus 4 [-15/+17]; p = 0.001), indicating better bowel function and a more pronounced drop in ISI (-6 [-7/-4] versus -4 [-6/+1]; p = 0.015), suggesting fewer symptoms. The percentage of patients who had a successful treatment was higher in the group treated conservatively (72.7% versus 42.3%; p = 0.03). CONCLUSION: Conservative management showed better long-term outcomes than surgical management in children with IND-B.

Are biopsies always necessary in upper and lower gastrointestinal endoscopy in children? A retrospective 10-year analysis.

Little attention has been given to the efficiency and validity of performing routine endoscopic biopsies in normal areas in children. This study aimed to investigate the need to perform routine biopsies in upper gastrointestinal endoscopy (UDE) and colonoscopy in normal areas by comparing macroscopy and histology. It was a 10-year retrospective analysis with the inclusion of 761 UDEs and 177 colonoscopies. Considering all segments, UDEs showed false-positive result rates of 73.11% and false-negative result rates of 14.34%. The histological results modified the initial management in 53.95% of patients. Considering all segments, colonoscopies showed false-positive result rates of 63.64% and false-negative result rates of 30.97%. The histological results modified the initial management in 34.45% of patients.Conclusion: If biopsies were obtained only in abnormal areas, the diagnosis would be lost in 53.95% of the patients in upper endoscopies and 85.7% of the colonoscopies, which justifies routine maintenance of biopsies in macroscopically normal areas in children. What is Known: • Little attention has been given to the efficiency and validity of endoscopic biopsies of normal areas during pediatric exams. • Only a few pediatric studies have correlated macroscopic and histological findings from endoscopic biopsies, and low sensitivity and specificity, as well as poor agreement, were reported. What is New: • Our study confirms the evidence that routine biopsies from macroscopically normal areas during upper and lower digestive endoscopies can lead to histopathological diagnoses and different medical management. • This is the first research on this topic in a Latin population, from a developing country, reassuring the results obtained in previous papers from other countries.

Ultrastructural analysis of bone formation around dental implants in nondiabetic rats, severe diabetics not controlled and controlled with insulin.

PURPOSE: To evaluate bone formation through ultrastructural analysis around titanium implants in severe alloxanic uncontrolled diabetic rats, and controlled with insulin, in comparison with nondiabetic rats. METHODS: Thirty-six male Wistar rats, weighing between 200 and 300 g, divided into three experimental groups: normal control group (G1), a diabetic group without treatment (G2), and a diabetic group treated with insulin (G3). The animals received titanium implants in the right femur, and osseointegration was evaluated at 7, 14, and 21 days after surgery, through ultrastructural analysis using scanning electron microscopy. RESULTS: The ultrastructural analysis showed a dense bone structure in the G1, few empty spaces and a small number of proteoglycans; G2 presented bone matrix with a loose aspect, irregular arrangement, thin trabeculae, empty spaces and a large number of proteoglycans; G3 obtained similar results to G1, however with a higher number of proteoglycans. CONCLUSION: Severe diabetes caused ultrastructural changes in bone formation, and insulin therapy allowed an improvement in osseointegration, but it was not possible to reach the results obtained in the control group.

Acute aortic wall injury caused by aortic cross-clamping: morphological and biomechanical study of the aorta in a swine model of three aortic surgery approaches.

BACKGROUND: Aortic cross-clamping and balloon occlusion of the aorta could lead to damage to the aorta wall. OBJECTIVE: The aim of this study was to investigate changes to the aorta wall related to the method used to interrupt flow (clamping or balloon) in the different techniques available for aortic surgery. METHODS: Experiments were performed on 40 female pigs, weighing 25-30kg, which were randomly allocated to 4 study groups: S (n=10), no intervention (sham group); C (n=10), midline transperitoneal laparotomy for infrarenal abdominal aortic access with 60 min of cross-clamping; L (n=10), laparoscopic infrarenal abdominal aortic surgery with 60 min of cross-clamping; EV (n=10), remote proximal aortic control with transfemoral arterial insertion of aortic occlusion balloon catheter, inflated to provide continued aortic occlusion for 60min. After euthanasia, the aortas were removed and cross-sectioned to obtain histological specimens for light microscopic and morphometric analyses. The remaining longitudinal segments were stretched to rupture and mechanical parameters were determined. RESULTS: We observed a reduction in the yield point of the abdominal aorta, decrease in stiffness and in failure load in the aortic cross-clamping groups (C and L) compared with the EV group. CONCLUSIONS: Aortic cross-clamping during open or laparoscopic surgery can affect the mechanical properties of the aorta leading to decrease in resistance of the aorta wall, without structural changes in aorta wall histology.

MicroRNA expression profiles in the esophagus of children with caustic stenosis: A pathway towards esophageal cancer?

BACKGROUND: Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression. STUDY DESIGN/AIMS: This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease. RESULTS: Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer. CONCLUSION: miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection.

Ki-67 Labeling Index in Pulmonary Carcinoid Tumors: Comparison Between Small Biopsy and Resection Using Tumor Tracing and Hot Spot Methods.

CONTEXT.­: Pulmonary carcinoids are classified as typical or atypical by assessing necrosis and mitoses, which usually cannot be adequately assessed on small biopsies. Ki-67 is not currently used to grade pulmonary carcinoids, but it may be helpful to determine preliminary grade in biopsies. However, the rate at which Ki-67 could underestimate or overestimate grade on small biopsies has not been well studied. OBJECTIVE.­: To compare Ki-67 labeling obtained on small biopsies to subsequent resection. DESIGN.­: Ki-67 was performed on paired biopsy and resection specimens from 55 patients. Slides were scanned using Aperio ScanScope. Labeling index was determined using automated hot spot and tumor tracing methods. RESULTS.­: The study included 41 typical and 14 atypical carcinoids. Atypical carcinoids were larger and had more distant metastases. Death from disease occurred in 3 patients (all had atypical carcinoids). Median hot spot Ki-67 labeling index was greater in resection compared with biopsy by 0.7% (P = .02). Median tumor tracing Ki-67 was lower in resection compared with biopsy by 0.5% (P < .001). Receiver-operating characteristic analysis showed similar hot spot Ki-67 cutoffs to predict atypical histology (3.5% for biopsy, 3.6% for resection; area under the curve [AUC], 0.75 and 0.74, respectively). Different optimal cutoffs were needed for tracing method based on biopsy (2.1%; AUC, 0.75) compared with resection (1.0%; AUC, 0.67). CONCLUSIONS.­: Hot spot Ki-67 tends to underestimate grade on small biopsies, whereas grade is overestimated by tumor tracing. Hot spot Ki-67 cutoff of 3.5% predicted atypical histology for both biopsy and resection. Different biopsy and resection cutoffs were necessary for tumor tracing, which would make clinical implementation more difficult.