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.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P<0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

Tissue Engineered Airways: A Prospects Article.

An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs, and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularized organs. To date, a number of different decellularization techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however, there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilize in accomplishing the aim of developing an ideal tracheal prosthesis. J. Cell. Biochem. 117: 1497-1505, 2016. © 2016 Wiley Periodicals, Inc.

Immunotherapy of HPV-associated cancer: DNA/plant-derived vaccines and new orthotopic mouse models.

Under the optimistic assumption of high-prophylactic HPV vaccine coverage, a significant reduction of cancer incidence can only be expected after decades. Thus, immune therapeutic strategies are needed for persistently infected individuals who do not benefit from the prophylactic vaccines. However, the therapeutic strategies inducing immunity to the E6 and/or E7 oncoprotein of HPV16 are more effective for curing HPV-expressing tumours in animal models than for treating human cancers. New strategies/technologies have been developed to improve these therapeutic vaccines. Our studies focussed on preparing therapeutic vaccines with low-cost technologies by DNA preparation fused to either plant-virus or plant-toxin genes, such as saporin, and by plant-produced antigens. In particular, plant-derived antigens possess an intrinsic adjuvant activity that makes these preparations especially attractive for future development. Additionally, discrepancy in vaccine effectiveness between animals and humans may be due to non-orthotopic localization of animal models. Orthotopic transplantation leads to tumours giving a more accurate representation of the parent tumour. Since HPV can cause cancer in two main localizations, anogenital and oropharynx area, we developed two orthotopic tumour mouse models in these two sites. Both models are bioluminescent in order to follow up the tumour growth by imaging and are induced by cell injection without the need to intervene surgically. These models were utilized for immunotherapies with genetic or plant-derived therapeutic vaccines. In particular, the head/neck orthotopic model appears to be very promising for studies combining chemo-radio-immune therapy that seems to be very effective in patients.

Managing patients with stable respiratory disease planning air travel: a primary care summary of the British Thoracic Society recommendations.

Air travel poses medical challenges to passengers with respiratory disease, principally because of exposure to a hypobaric environment. In 2002 the British Thoracic Society published recommendations for adults and children with respiratory disease planning air travel, with a web update in 2004. New full recommendations and a summary were published in 2011, containing key recommendations for the assessment of high-risk patients and identification of those likely to require in-flight supplemental oxygen. This paper highlights the aspects of particular relevance to primary care practitioners with the following key points: (1) At cabin altitudes of 8000 feet (the usual upper limit of in-flight cabin pressure, equivalent to 0.75 atmospheres) the partial pressure of oxygen falls to the equivalent of breathing 15.1% oxygen at sea level. Arterial oxygen tension falls in all passengers; in patients with respiratory disease, altitude may worsen preexisting hypoxaemia. (2) Altitude exposure also influences the volume of any air in cavities, where pressure x volume remain constant (Boyle's law), so that a pneumothorax or closed lung bulla will expand and may cause respiratory distress. Similarly, barotrauma may affect the middle ear or sinuses if these cavities fail to equilibrate. (3) Patients with respiratory disease require clinical assessment and advice before air travel to: (a) optimise usual care; (b) consider contraindications to travel and possible need for in-flight oxygen; (c) consider the need for secondary care referral for further assessment; (d) discuss the risk of venous thromboembolism; and (e) discuss forward planning for the journey.

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.

Airway Hemangiomas in PHACE Syndrome: A Multicenter Experience.

OBJECTIVE: To describe the prevalence and clinical characteristics of airway findings in a multi-institutional cohort of PHACE patients. STUDY DESIGN: Multicenter retrospective case series. SETTING: Multidisciplinary vascular anomalies clinics at 2 institutions. METHODS: Data were collected from the electronic medical record, including clinical presentation, airway findings, treatment, and outcomes. RESULTS: Of 55 PHACE patients, 22 (40%) had airway hemangiomas. Patients with airway involvement were more commonly female (P = .034, odds ratio [OR] 23, 95% confidence interval [CI] 1.3-410) and of Caucasian ethnicity (P = .020, OR 5.3, 95% CI 1.3-21). Anatomically, patients with bilateral S3 involvement had higher rates of airway disease (P = .0012, OR 15, 95% CI 2.9-77). Most patients with airway hemangiomas had stridor (68%). Of the patients managed in the propranolol era (2008 or later, n = 35), 14 had airway involvement. All 14 were treated with propranolol, whereas 13 (62%) of 21 nonairway patients were treated with propranolol. The average treatment duration was longer in the airway patients (22.1 vs 16.7 months). All patients who underwent tracheostomy (n = 4) did so before 2008. CONCLUSION: Risk factors for airway involvement in PHACE include female gender, Caucasian ethnicity, and stridor. Since the widespread use of propranolol, fewer patients have required surgical management of their airway disease. Given the high prevalence of airway involvement even in patients without stridor, assessment of the airway is a crucial component of a comprehensive PHACE workup.

Trends in the survival of patients diagnosed with cancers in the respiratory system in the Nordic countries 1964-2003 followed up to the end of 2006.

BACKGROUND: Previous studies have shown that there have been systematic differences between the Nordic countries in population-based relative survival of patients with respiratory cancer (lung, pleura, larynx, nose and sinuses). MATERIAL AND METHODS: Relative survival of patients with respiratory cancer diagnosed in the Nordic countries in 1964-2003 and followed up to the end of 2006 was studied and contrasted with developments in incidence and mortality. RESULTS: For cancer of the lung, relative survival is lower in Danish patients than in the other countries during the first months of follow-up after diagnosis. For cancer of pleura, the relative survival ratios indicate that there may be problems in the official coding of the causes of death in Denmark, Norway and Sweden. There has been little improvement in survival of patients with cancer of the respiratory organs in the Nordic countries over time. CONCLUSIONS: The slightly lower survival of Danish lung cancer patients may be related to a less favourable stage distribution and to an increased prevalence of causal factors, affecting the mortality due to competing risks of death. A reclassification of official causes of death at the cancer registry may be needed for cancer of the pleura in order to make the corresponding mortality rates comparable between countries.

Indications and clinical outcomes of fully covered self-expandable metallic tracheobronchial stents in patients with malignant airway diseases.

BACKGROUND: Airway stenting is an efficacious approach in management of malignant airway disease (MAD) with improvement in survival outcome. OBJECTIVE: To determine the indications and long-term clinical outcomes of tracheobronchial stenting in patients with MAD. METHODS: A cross-sectional review of 51 patients who underwent airway stenting from June 2011 to June 2019 was done. Paired t-test was used to compare mean difference of clinical characteristics between pre- and post-airway stenting. Kaplan-Meier curves were used to assess overall survival. RESULTS: A total of 51 patients had stent insertion with mean age 46.63±17.10years including 27(52.9%) females. Mainly 37(72.5%) patients had esophageal and 06(11.8%) had lung cancer. The main indications were bronchial stenosis 18(35.3%), tracheal stenosis 11(21.6%) and Tracheo-esophageal/bronchial fistula 13(25.5%). Obstruction was intrinsic, extrinsic and mixed in 20(39.2%), 13(25.5%) and 5(9.8%) patients, respectively. There was statistically significant mean difference in pre- and post-procedure oxygen saturation (mean (M)=89.8, standard deviation (SD)=6.70 vs M =95.5,SD=2.54.p =0.001) and performance status (M =3.65,SD =0.6 vs M =2.59, SD=0.83.p =0.001). Overall median survival was 16±3.44 weeks, highest amongst patients with intrinsic obstruction (27±6.51 weeks). CONCLUSION: Airway stenting is an effective endoscopic procedure to re-establish airway patency in MAD with minimal complications..

Palliative aspects of recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a chronic, frequently debilitating, and potentially life-threatening disease. Therapy for RRP has evolved from simply inserting a tracheotomy to provide an airway and plucking out papillomata with cup forceps to provide some degree of voice to the present-day far more sophisticated approaches, along with preventative measures that may someday offer the potential dramatically to decrease disease prevalence. Family dynamics and support and intentional structuring of office protocols to accommodate the unique nature of RRP are as essential as any operative intervention for saving and prolonging life. This article reviews recent developments in the management of RRP and highlights palliative approaches to case management for those patients who are not easily cured with initial endoscopic interventions.

Lung cancer patients with previous or simultaneous the upper aerodigestive cancers.

There have been few reports on clinical characteristics of lung cancer patients with previous or simultaneous upper aerodigestive cancers. To evaluate them, we conducted a retrospective study. The medical records of all lung cancer patients at our division from January 1984 through July 2008 were reviewed. Twenty-one (1.7%) of 1242 patients had previous or simultaneous upper aerodigestive cancers. Twenty patients were smokers. For non-small cell lung cancer (NSCLC), 6 patients underwent surgical resection and 3 were treated with chemotherapy. Three small cell lung cancer (SCLC) patients had chemotherapy. None of the severe complication related to the comorbidities were observed. The median survival for NSCLC and SCLC patients was 15 and 6 months, respectively. For patients with upper aerodigestive cancers, smoking cessation, a chest radiograph or computed tomography scan at least yearly and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended.

An Open-label, Single-arm Study of CRYO2 for Debulking at the Site of Central Airway Obstruction or Stenosis.

BACKGROUND: An open-label, single-arm study was conducted to assess the safety of a cryosurgery unit named CRYO2 for debulking at the site of obstruction or stenosis. PATIENTS AND METHODS: In order to treat central airway tumor-related stenosis, debulking at the stenotic site of the airway was performed using CRYO2 under general or local anesthesia. The primary endpoint was the incidence of moderate to massive hemorrhage. RESULTS: Incidence of moderate to massive hemorrhage during surgery was 3.8% (1/26) (95% confidence interval(CI)=0.1-19.6%). Technical success was 96.2% (25/26), with a 95% confidence interval of 80.4-99.9%. CONCLUSION: CRYO2 for debulking at the site of obstruction or stenosis can be performed safely.

The activator protein-1 transcription factor in respiratory epithelium carcinogenesis.

Respiratory epithelium cancers are the leading cause of cancer-related death worldwide. The multistep natural history of carcinogenesis can be considered as a gradual accumulation of genetic and epigenetic aberrations, resulting in the deregulation of cellular homeostasis. Growing evidence suggests that cross-talk between membrane and nuclear receptor signaling pathways along with the activator protein-1 (AP-1) cascade and its cofactor network represent a pivotal molecular circuitry participating directly or indirectly in respiratory epithelium carcinogenesis. The crucial role of AP-1 transcription factor renders it an appealing target of future nuclear-directed anticancer therapeutic and chemoprevention approaches. In the present review, we will summarize the current knowledge regarding the implication of AP-1 proteins in respiratory epithelium carcinogenesis, highlight the ongoing research, and consider the future perspectives of their potential therapeutic interest.

The epidemiology and treatment of mesothelioma in South East England 1985-2002.

OBJECTIVES: To describe trends in the incidence of mesothelioma for men and women in South East England and the geographical variation at the level of primary care trust. To describe treatment patterns by cancer network of residence, and relative survival by cancer network, disease stage and treatment modality. METHODS: 5753 cases were extracted from the Thames Cancer Registry database. We calculated age standardised incidence rates for each year, age specific incidence rates in 10 year age groups, and we used linear regression to compute the average annual percentage change in age standardised incidence. We used Poisson regression to analyse generational trends in incidence. RESULTS: Men had five times higher incidence of mesothelioma than women. In men, there was an overall 4% increase per year between 1985 and 2002. Over the same period, the overall increase in incidence for women was 5% per year. The incidence was highest in men aged over 70 years, and men aged over 80 years had the highest increase of 8% per year. The incidence rate ratio increased for men born between 1892 and 1942 and started to slow for those born from 1947 onwards. Areas along the Thames and its estuary had the highest incidence. There was some variation by cancer network in the proportion of patients receiving cancer surgery, radiotherapy and chemotherapy. There were no discernable differences in relative survival by cancer network of residence or disease stage but those receiving combined treatment had higher 5 year survival. CONCLUSIONS: Mesothelioma incidence has increased in South East England, particularly for men aged over 70 years. The highest incidence occurs along the Thames and its estuary, reflecting areas of asbestos use in shipbuilding and industry in the past. More research is needed to understand the interrelationships of prognostic factors, treatment choices and survival, and to determine the best care and support for these patients and their families.

Creating a medical home for the child with recurrent respiratory papillomatosis.

Juvenile onset recurrent respiratory papillomatosis is a chronic disease of the pediatric airway caused by human papillomavirus. This paper discusses the etiology, epidemiology, symptomatology, diagnosis, and treatment of this disease. The role of the pediatric nurse practitioner is described in applying the medical home model. Comprehensive primary care is described for children with recurrent respiratory papillomatosis, including well child care, episodic illness management, and care coordination.

[Modern approaches to the organization of oncological care for patients with tumours of upper respiratory tract].

Despite reports of successful treatment of oncological diseases of the upper respiratory tract, many patients with this pathology still apply for medical aid too late. Squamous cell carcinoma remains the predominant problem. Clinical symptoms of metastases are absent in 60% of the lethal cases with locally spreading tumours. The most common causes of death among these patients are obstruction of the upper air passages, invasion of tumour cells into the brain, local and systemic metastasis. It is concluded that the improvement of early diagnosis of malignant neoplasms of the upper respiratory tract and organization of specialized care for subjects with pre-tumor processes requires joint efforts of oncologists and otorhinolaryngologists. The achievement of this goal would enhance the effectiveness of the treatment of this pathology.

Management of Infantile Hemangiomas of the Airway.

Infantile hemangiomas (IHs) of the airway are far less common than their cutaneous counterparts, and their symptoms mimic those of viral croup. As a result, by the time these lesions are diagnosed, they are often advanced and causing airway compromise. Fortunately, the evolution of propranolol as an effective and safe pharmacotherapy has simplified management of IH and reduced the likelihood of complications previously seen with steroid therapy and surgery. Nevertheless, the otolaryngologist must be prepared with an alternate plan to manage lesions refractory to pharmacotherapy. This article reviews the clinical presentation and current management of IHs of the airway.

The Management of Vascular Malformations of the Airway: Natural History, Investigations, Medical, Surgical and Radiological Management.

Vascular malformations may affect nearly all aspects of the upper airway. Each type of malformation has a characteristic pattern of disease. These lesions may be focal or diffuse, and require directed management strategies. Physicians treating these entities should have a high level of suspicion to consider airway evaluation even in the absence of overt symptoms. However, cutaneous head and neck venous malformations or other lesions affecting the lips, oral cavity, or tongue can herald the presence of coexisting airway lesions. A multidisciplinary approach is critical in achieving comprehensive treatment.

Tracheobronchial stents in palliative care: a case series and literature review.

OBJECTIVE: To evaluate the outcomes of tracheobronchial stenting in patients with malignant central airway obstruction and assist practitioners in palliative settings in understanding the indications, contraindications and management of tracheobronchial stents. METHODS: This retrospective study involved a consecutive case series of palliative patients with central airway obstruction secondary to inoperable cancers who underwent tracheobronchial stenting at a single institution. The European Cooperative Oncology Group (ECOG) scale was used to evaluate patient functional status before and after tracheobronchial stenting. RESULTS: Twenty-three patients underwent tracheobronchial stenting for malignant central airway obstruction. The majority of patients presented with symptoms of worsening dyspnoea (21 of 23; 91%). Postoperatively, there was a significant improvement in mean ECOG performance status from 2.88±0.34 to 1.58±0.50 (p<0.01). There was no intraoperative mortality resulting from tracheobronchial stenting. Five patients (21.74%) re-presented to hospital due to worsening symptoms and required emergency bronchoscopy. Two patients had stent migration, requiring stent replacement. One patient restenosed from tumour granulation, requiring microdebrider to debulk the mass. Two patients had stent failure secondary to external tumour compression, leading to death. CONCLUSION: Tracheobronchial stenting is a safe and effective procedure that offers rapid palliation of symptoms and improvement in patient functional status.