Characteristics and Outcomes of Airway Involvement in Esophageal Cancer.

BACKGROUND: Airway involvement, such as airway invasion, compression, and tracheobronchoesophageal fistula (TEF), in esophageal cancer is associated with significant morbidity. However, the risk factors and outcomes of airway complications remain unclear, with limited evidence to guide management. METHODS: This retrospective analysis included 804 patients with a diagnosis of esophageal cancer from 1998 to 2018 at a tertiary care medical center (Singapore General Hospital, Singapore). Patients' demographics, treatment details, and airway involvement, as determined by bronchoscopic evaluation or computed tomographic imaging, were recorded and analyzed to determine risk factors and outcomes of airway involvement. RESULTS: The incidence of airway involvement and TEF was 36.6% and 13.1%, respectively. Airway involvement was associated with reduced survival from the time of diagnosis (hazard ratio, 1.52; 95% confidence interval [CI], 1.30 to 1.79) and increased hospitalizations per year (4.53 ± 4.80 vs 2.75 ± 3.68; P < .001). On multivariate analysis, midesophageal tumors (odds ratio [OR], 11.0; 95% CI, 6.3 to 19.0) and upper esophageal tumors (OR, 8.5; 95% CI, 4.7 to 15.6), previous treatment with esophageal stenting (OR, 17.8; 95% CI, 4.1 to 77.6), and chemotherapy or radiotherapy were associated with development of airway involvement. In patients with TEF, treatment with chemotherapy (OR, 0.34; 95% CI, 0.20 to 0.60) and combined airway and esophageal stenting (OR, 0.48; 95% CI, 0.25 to 0.91) were independently associated with improved survival. CONCLUSIONS: Airway involvement and TEF are common and are associated with increased morbidity and poorer survival. Clinicians should remain vigilant for airway complications after treatment with esophageal stenting, chemotherapy, or radiotherapy, especially in patients with midesophageal and upper esophageal cancers. In patients with TEFs, survival is improved when they are treated with airway stenting, esophageal stenting, or chemotherapy.

Relationship between inflammation and the severity of Recurrent Respiratory Papillomatosis.

OBJECTIVE: To characterize inflammatory cells in Recurrent Respiratory Papillomatosis (RRP) and to correlate it with severity using the Derkay laryngoscopic scale. MATERIALS AND METHODS: The data and biopsies from 36 patients with Juvenile (JRRP) and 56 patients with Adult (ARRP) were collected and analyzed under light microscopy. The patients were separated into groups according to the Derkay index: ≥20 for the most severe and < 20 for the less severe cases. Immunohistochemical analysis using CD3, CD4, CD8, CD15, CD20, CD68, FoxP3 and MUM-1 antibodies was performed, and the inflammatory cells were quantified. All the clinicopathological characteristics and the results of the immunohistochemical analysis were compared among the groups proposed using the Chi-Square test and correlated through the Spearman correlation test. RESULTS: The ARRP showed significantly higher quantities of CD3+, CD8+ and MUM1+ cells (p < .05) than the JRRP samples. The presence of CD15+ cells showed positive correlation with the Derkay index (p < .05), while the MUM-1+ cells showed an inverse correlation (p = .01). CONCLUSION: There are differences between the inflammatory cells population in the juvenile and adult groups and it can be related to disease severity.

Clinical application of photodynamic therapy for malignant airway tumors in China.

With the development of interventional pulmonology, photodynamic therapy (PDT) is gradually being used in the treatment of respiratory malignant tumors because of its low level of trauma, high specificity, and compatibility with traditional or common therapies. However, at present, the data of clinical evidence-based medicine for PDT applied in central airway tumors is very limited, and derives mainly from case reports or series of case studies which lack consensus on clinical diagnosis and treatment. In order to further disseminate China's experience, the Tumor Photodynamic Therapy Committee of China Anti-Cancer Association and the World Endoscopy Association-Respiratory Endoscopy Association invited experts from relevant fields to form an expert committee. After several rounds of discussion and revision by this committee, and following a vote, the consensus was formulated for reference by physicians in respiratory, oncology and other related disciplines to refer to the practice of tumor photodynamic therapy.

Head and neck squamous cell carcinoma and metachronous second primaries.

OBJECTIVES: To assess the rate of second (or more) primaries after treatment for head and neck squamous cell carcinoma (HNSCC), and survival compared to patients with a single head and neck cancer. MATERIAL AND METHOD: A single-center retrospective study was performed in a University Hospital Center in 541 patients between 2002 and 2010. RESULTS: One hundred and forty-one patients (26.06%) presented 172 metachronous cancers. Overall 5-year survival was 20.3% with and 38.1% without metachronous cancer. Median and mean survival were respectively 21.9 and 51 months in patients with a single cancer, versus 13.9 and 26.5 months in case of metachronous cancer. Specific survival was comparable to overall survival. All-cause and specific survival were significantly poorer in metachronous cancer (P=0.001; log-rank α=0.05). CONCLUSION: At least a quarter of HNSCC patients go on to develop a metachronous second primary. These are of poor prognosis, whatever their location.

Performance of Endobronchial Ultrasound Elastography in the Differentiation of Malignant and Benign Mediastinal Lymph Nodes: Results in Real-life Practice.

BACKGROUND: Little data exists regarding the performance of elastography in EBUS-TBNA. The aim of the study was to evaluate the elastography score proposed and previously published by Izumo, in particular its capacity to perfectly identify benign lymph node, and to discriminate malignant ones. METHODS: This study included patients undergoing EBUS-TBNA for mediastinal lymph nodes (LN). Before LN needle aspiration, an elastography was performed which allowed a color elastogram to be superimposed on the ultrasound image. Three blinded assessors classified these elastograms into 3 types using the score published by Izumo: type 1 (predominantly not blue), type 2 (partially blue, partially not blue), or type 3 (predominantly blue). These types were then compared with pathology results. RESULTS: A total of 217 LN (114 patients) were analyzed: histologic findings identified 97 benign LN (44.7% of the lymph nodes) and 120 malignant LN (55.3%). There were 44 elastographies (20.2%) that were classified as type 1, 90 elastographies (41.5%) classified as type 2, and 83 elastographies (38.3%) classified as type 3. Considering type 1 as benign and type 3 as malignant, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 87.0%, 68.0% , 80.0% , and 77.0%. Ten (23%) of the 44 lymph nodes with a type 1 elastogram were malignant. CONCLUSION: Elastography does not preclude performing TBNA of the lymph nodes. It does not preclude EBUS-TBNA when a type 1 elastogram pattern is found. All lymph nodes visualized should be sampled by EBUS-TBNA, regardless of elastography pattern.

Granular cell tumor experience at a comprehensive cancer center.

BACKGROUND: Granular cell tumors (GCTs) are rare lesions occurring almost anywhere in the body. Multiple case reports have been published. However, there are very few large-scale studies regarding GCT. The aim of this study was to define characteristics, treatment patterns and outcomes of patients with GCT. METHODS: An institutional review board-approved retrospective chart review was performed. Descriptive statistics, chi-square analyses, and Kaplan-Meier survival estimates were produced. RESULTS: Fifty patients were treated for GCT at our institution between 1992 and 2015. The median age was 47 y; 62% of patients were female and 64% were whites. Median tumor size was 0.8 cm. Four percent of patients had malignant tumors, 10.0% had atypical tumors, and 86.0% had benign tumors. The most frequent location of tumors was the gastrointestinal tract (n = 30; 60%), followed by skin/subcutaneous tissues (n = 19; 38%), then respiratory tract (n = 1; 2%). Most patients underwent surgical excision or endoscopic removal of their tumors without prior biopsy. Three patients (6%) had multifocal tumors; they were more likely to experience recurrence than patients with unifocal tumors (33.3% versus 10.6%, respectively; P = 0.05). Six patients (12.0%) experienced recurrence, with a median time to recurrence of 13.5 mo. Overall cancer-specific 5-y survival was 98.0%. Overall recurrence-free 5-y survival was 86.4%. Patients with atypical tumors had a lower recurrence-free 5-y survival rate than those with benign tumors (75.0% versus 89.7%, respectively; P = 0.04). CONCLUSIONS: Patients with GCT fair well, particularly when tumors are benign. Patients with multifocal tumors are more likely to experience recurrence and should be closely monitored.

Esophagorespiratory Fistulas: Survival and Outcomes of Treatment.

GOAL: The purpose of this study was to characterize outcomes of esophagorespiratory fistulas (ERF) by etiology and initial treatment strategy. BACKGROUND: ERF is a morbid condition for which optimal treatment strategies and outcomes are still in evolution. STUDY: Medical records and images were reviewed for all patients diagnosed with ERF at Mayo Clinic in Rochester, MN, between September 1, 2001 and January 1, 2012. Fistulas were classified as malignant or benign. Treatment strategies were classified as surgical or nonsurgical (typically esophageal stent placement). Technical and clinical success, survival, and survival free of second intervention were assessed. RESULTS: A total of 123 patients with acquired ERF were identified, of whom 65 (53%) were malignant and 58 (47%) benign. Initial treatment strategy was nonsurgical in 88 (72%) patients and surgical in 35 (28%); lower Charlson comorbidity scores were associated with increased likelihood of surgery. Technical and clinical success was seen in a majority of patients treated both surgically and nonsurgically. Patients with malignant ERF treated surgically survived longer than patients undergoing nonsurgical treatment (hazard ratio=5.6, P=0.005). In contrast, those with benign ERF had similar overall survival regardless of whether they received initial surgical or nonsurgical treatment; reintervention was more common in those who underwent nonsurgical treatment (hazard ratio=2.3, P=0.03). CONCLUSIONS: We conclude that survival in malignant ERF is better with surgical intervention in selected patients. Surgical and nonsurgical techniques achieve similar survival in benign ERF, but reintervention is more common in those treated endoscopically.

The Different Clinical Aspects of Pediatric Primary Airway Tumors in the Larynx, Trachea, and Bronchi.

Primary airway tumors are rare in children and no literature reviewed their characteristics each location. We evaluate the clinical characteristics and outcomes of Korean children with primary airway tumors, from the larynx to bronchi. A retrospective chart review of children with primary tumors of the larynx, trachea, and bronchi at Asan Medical Center from January 2000 to July 2016 was conducted. Nineteen children were diagnosed with primary airway tumors of the larynx (47.4%), trachea (10.5%), and bronchi (42.1%). Median follow-up duration was 2.8 years and there were recurrences in 21.1%. Laryngeal tumors were associated with a younger median age at onset (2 months) and diagnosis (4 months), and most were relatively small (median size = 5.3 mm) and symptomatic. Tracheal and bronchial tumors were found in older children (age at onset and diagnosis > 11 years) and large (> 15.0 mm). Most (75%) patients with bronchial tumors were asymptomatic and all the patients with tracheal tumors were symptomatic. This study suggests that we should consider different the locations in primary airway tumor based on the age at onset and diagnosis, initial symptoms or signs, and size of tumor.

Narrow band imaging for early diagnosis of epithelial dysplasia and microinvasive tumors in the upper aerodigestive tract.

The various stages of tumor growth are characterized by typical epithelial, vascular, and secondary connective tissue changes. Narrow Band Imaging (NBI) endoscopy is a minimally invasive imaging technique that presents vascular structures in particular at a higher contrast than white light endoscopy alone. In combination with high-resolution image recording and reproduction (high-definition television, HDTV; ultra-high definition, 4K), progress has been made in otolaryngological differential diagnostics, both pre- and intraoperatively. This progress represents an important step toward a so-called optical biopsy. Flexible endoscopy in combination with NBI allows for a detailed assessment of areas of the upper aerodigestive tract that are difficult to assess by rigid endoscopy. Papillomas along with precancerous and cancerous lesions are characterized by epithelial and connective tissue changes as well as by typical perpendicular vascular changes. Systematic use of NBI is recommended in the differential diagnosis of malignant lesions of the upper aerodigestive tract. NBI also offers a significant improvement in the pre- and intraoperative assessment of superficial resection margins. In particular, the combination of NBI and contact endoscopy (compact endoscopy) facilitates excellent therapeutic decisions during tumor surgery. Intraoperative determination of resection margins at an unprecedented precision is possible. In addition, assessment of the form and extent of the perpendicular vessel loops stimulated by epithelial signaling enables differential diagnostic decisions to be made, approximating our goal of an optical biopsy.

Space-time variation of respiratory cancers in South Carolina: a flexible multivariate mixture modeling approach to risk estimation.

PURPOSE: Many types of cancer have an underlying spatiotemporal distribution. Spatiotemporal mixture modeling can offer a flexible approach to risk estimation via the inclusion of latent variables. METHODS: In this article, we examine the application and benefits of using four different spatiotemporal mixture modeling methods in the modeling of cancer of the lung and bronchus as well as "other" respiratory cancer incidences in the state of South Carolina. RESULTS: Of the methods tested, no single method outperforms the other methods; which method is best depends on the cancer under consideration. The lung and bronchus cancer incidence outcome is best described by the univariate modeling formulation, whereas the "other" respiratory cancer incidence outcome is best described by the multivariate modeling formulation. CONCLUSIONS: Spatiotemporal multivariate mixture methods can aid in the modeling of cancers with small and sparse incidences when including information from a related, more common type of cancer.

Utilization of ancillary studies in the cytologic diagnosis of respiratory lesions: The papanicolaou society of cytopathology consensus recommendations for respiratory cytology.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for sputum examination, bronchial washings and brushings, CT-guided FNA and endobronchial ultrasound guided fine needle aspiration (EBUS-FNA), as well as recommendations for classification and criteria, ancillary testing and post-cytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of committee members, an extensive literature review, and feedback from presentations at national and international conferences. The guideline documents selectively present the results of these discussions. The present document summarizes recommendations for ancillary testing of cytologic samples. Ancillary testing including microbiologic, immunocytochemical, flow cytometric, and molecular testing, including next-generation sequencing are discussed. Diagn. Cytopathol. 2016;44:1000-1009. © 2016 Wiley Periodicals, Inc.

Combined use of haemostatic system indices for evaluation of upper respiratory tract cancer progression.

AIM: To analyze whether comprehensive assessment of haemostatic system components, in particular, indices of coagulation and fibrinolytic systems along with functionally related proteins, could be indicative of upper respiratory tract (URT) cancer progression. MATERIALS AND METHODS: Indices of coagulation and fibrinolytic systems along with functionally related proteins, in particular, trypsin-like amidolytic activity, trypsin-like proteolytic activity, thrombin-like amidolytic activity, elastase-like amidolytic activity, fibrinolytic activity, potential amidolytic plasmin activity, content of fibrinogen, antithrombin III, α1-proteinase inhibitor, and α2-macroglobulin, and prothrombin time were evaluated in blood plasma of patients with URT cancer of II (n = 10) and III (n = 25) stages with the use of routine biochemical methods. RESULTS: For both groups of patients with URT cancer there have been shown notable differences for the majority of the studied indices, especially the indexes of proteolytic activities, from these of healthy donors, and in the case of URT cancer of III stage they reached statistical significance. In contrary, the changes in the content of antithrombin III, α1-proteinase inhibitor, and α2-macroglobulin were insignificant. In both groups of patients significant increase of fibrinogen content has been registered, while the content of soluble fibrinogen didn't change. Also, in both groups of patients there a significant increase of potential activity of plasminogen was documented, while clot lysis time was significantly increased only in patients with III stage URT cancer. Multifactorial analysis of haemostatic system indices evidenced for efficacy of their combined use for evaluation of URT cancer progression risk. CONCLUSION: Combined use of fibrinogen and α2-macroglobulin content and the level of amidolytic thrombin-like activity could serve as an indicator of URT cancer progression.

Standardized terminology and nomenclature for respiratory cytology: The Papanicolaou Society of Cytopathology guidelines.

BACKGROUND: The Papanicolaou Society of Cytopathology has developed a set of guidelines for respiratory cytology including indications for cytologic testing, techniques for cytologic sampling, terminology and nomenclature for respiratory diseases, ancillary testing, and recommendations for postcytologic diagnosis follow-up and management. METHODS: All documents are based on the expertise of the authors, an extensive literature review and discussions of the draft documents at national and international meetings over a 12-month period. This document selectively presents the results of these discussions and reports a proposed standardized terminology scheme for respiratory cytology that correlates cytologic diagnosis with biologic behavior and patient management. RESULTS: The classification and terminology scheme recommends a six-tiered system composed of: nondiagnostic, negative, atypical, neoplastic (benign and neoplasms of low malignant potential), suspicious, and positive for malignancy. CONCLUSION: The scheme recommends statements on specimen adequacy followed by the major classification category and then a subclassification and/or comments section. Each of the six main diagnostic categories is associated with an estimated risk of malignancy. Subsequent documents will propose ancillary testing recommendations, techniques for cytologic sampling, indications for cytologic study and postcytologic diagnosis management and follow-up recommendations.

Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4.

Aim of this study was the investigation of the genotoxic properties of XLR-11 [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA-damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA-reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers.

Risk Factors for Dysplasia in Recurrent Respiratory Papillomatosis in an Adult and Pediatric Population.

AIM: Recurrent respiratory papillomatosis (RRP) is classically described as a benign neoplasm of the larynx caused by the low-risk human papillomavirus (HPV) viral subtypes. Nevertheless, transformation to dysplasia and invasive carcinoma can occur. We aimed to assess the prevalence of dysplasia and carcinoma-ex-papilloma in both adult-onset and juvenile-onset RRP and identify patient risk factors for this dysplastic transformation. MATERIAL AND METHODS: Ten-year retrospective chart review of a tertiary otolaryngology referral center. Patients with papilloma were identified from a review of a pathology database and clinical records. Patient demographics, pathologic data, and treatment history, including use of cidofovir as an adjunctive therapy for papilloma, were extracted from electronic medical records. RESULTS: One hundred fifty-nine RRP patients were identified, 96 adult-onset (AORRP) and 63 juvenile-onset (JORRP) cases. Of this cohort, 139 (87%) had only benign papilloma as a pathologic diagnosis. In the AORRP cohort, 10 patients (10%) were diagnosed with dysplasia or carcinoma in situ in addition to papilloma, and 5 patients (5%) had malignant transformation to invasive carcinoma-ex-papilloma. There was a significantly higher age of disease onset for those with dysplasia or carcinoma versus those without dysplasia or carcinoma (56 vs 45 years old; P = .0005). Of the 63 JORRP patients, there were no cases of dysplasia but 3 (5%) cases of invasive carcinoma-ex-papilloma, all involving pulmonary disease. The JORRP patients with carcinoma-ex-papilloma had a younger average disease onset (2 vs 6 years old; P = .009) and a higher rate of tracheal involvement than those without carcinoma. Gender, smoking history, number of operations, or use of cidofovir showed no association with the development of dysplasia or carcinoma-ex-papillomatosis in either the AORRP or JORRP population. CONCLUSION: In a large series of RRP, age of disease onset is the strongest predictor of dysplastic transformation in the adult and pediatric population. Carcinoma-ex-papillomatosis was uniformly associated with pulmonary disease in the JORRP population in this series. No other demographic or behavioral factors, including adjunctive therapy with cidofovir, were statistically associated with dysplasia or carcinoma-ex-papilloma.

[Narrow band imaging for early diagnosis of epithelial dysplasias and microinvasive tumors in the upper aerodigestive tract]. / "Narrow band imaging" zur Früherkennung epithelialer Dysplasien und mikroinvasiver Karzinome im oberen Luft-Speise-Weg.

The various stages of tumor growth are characterized by typical epithelial, vascular, and secondary connective tissue changes. Narrow band imaging (NBI) endoscopy is a minimally invasive imaging technique that presents vascular structures in particular at a higher contrast than white light endoscopy alone. In combination with high-resolution image recording and reproduction (high-definition television, HDTV; ultra-high definition, 4K), progress has been made in otolaryngological differential diagnostics, both pre- and intraoperatively. This progress represents an important step towards a so-called optical biopsy. Flexible endoscopy in combination with NBI allows detailed assessment of areas of the upper aerodigestive tract which are difficult to assess by rigid endoscopy. Papillomas, precancerous, and cancerous lesions are characterized by epithelial and connective tissue changes, as well as by typical perpendicular vascular changes. Systematic use of NBI is recommended in the differential diagnosis of malignant lesions of the upper aerodigestive tract. NBI also convinces by a significant improvement in pre- and intraoperative assessment of superficial resection margins. In particular, the combination of NBI and contact endoscopy (compact endoscopy) permits excellent therapeutic decisions during tumor surgery. Intraoperative determination of resection margins at unprecedented precision is possible. In addition, assessment of the form and extent of the perpendicular vessel loops stimulated by epithelial signaling enables differential diagnostic decisions to be made, approximating our goal of an optical biopsy.