Delayed pharyngocutaneous fistula caused by molecular targeted therapy: a case report.

BACKGROUND: Molecular-targeted agents used as a treatment for cancer can cause some rare and serious adverse events such as, delayed wound healing. Depending on the anticancer drug used, temporary withdrawal may be recommended before and after surgery to avoid complications. Once a surgical incision has healed and closed completely, wounds rarely open because of the initiation of molecular targeted therapy several months to years after surgery. Here, we aimed to describe a rare complication of pharyngocutaneous fistula in two patients that was thought to be caused by molecular targeted therapy. CASE PRESENTATION: Case 1 involved a 64-year-old asian man who developed a delayed pharyngocutaneous fistula 3 months after total laryngectomy for laryngeal cancer. Ramucirumab, a vascular endothelial growth factor receptor inhibitor used for recurrent gastric cancer, was speculated to be involved. Case 2 involved a 71-year-old japanese man who developed a delayed pharyngocutaneous fistula 2 years and 1 month after total pharyngeal laryngectomy for pharyngeal cancer. It was speculated that imatinib, a platelet-derived growth factor receptor alpha inhibitor used for chronic myeloid leukemia, was involved. CONCLUSIONS: Although the incidence of late drug-induced anastomotic leakage is very low, when it occurs, it makes oral intake impossible for an extended period and interferes with the appropriate cancer treatment. In this report, we demonstrate the details of these two patients with such a rare complication, which may help accumulate essential data on this topic.

A spontaneous retropharyngeal haematoma: a suspected side-effect of indomethacin.

BACKGROUND: Retropharyngeal haematomas are most commonly associated with trauma and anti-coagulant use. This paper describes the first reported case of a spontaneous retropharyngeal haematoma suspected to be due to indomethacin use. CASE REPORT: It is proposed that the combination of indomethacin affecting platelet aggregation, alongside the patient coughing, may have led to this retropharyngeal haematoma. CONCLUSION: The complexities of management are discussed and the current literature reviewed. In the absence of airway compromise or a rapidly enlarging haematoma, patients can be managed conservatively with observation and close discussion with the haematology department. Follow-up imaging is not necessary if the patient's symptoms settle; however, any increase in parathyroid hormone levels must be investigated to exclude a parathyroid adenoma.

Prevalence of Human Papillomavirus Infection in the Head and Neck Area of Patients After Kidney Transplantation Treated With Immunosuppressive Therapy.

The introduction of new and stronger immunosuppressive agents has significantly improved the overall survival rate of patients with transplanted organs; however, prolonged use of immunosuppressive agents has led to severe complications, such as the development of de novo malignant cancers. The incidence of malignant tumors is 3 to 5 times greater among renal transplant recipients than that of the overall population. Traditional neoplasms of the head and neck region are associated with the addiction to smoking and drinking alcohol. However, recent studies indicate that cancers of the throat, tongue, and tonsils are primarily associated with the human papillomavirus (HPV) infection. At present, approximately 25% of the head and neck squamous cell carcinomas are associated with HPV infection. Therefore, we aimed to determine the incidence of oropharyngeal HPV infection in recipients with kidney transplants treated with immunosuppressive therapy and to determine the factors that may favor the contraction of infectious diseases. Furthermore, we considered the purpose of vaccination against HPV among transplant recipients. A total of 32 recipients with kidney transplants were included in this study. Medical history was obtained and a throat swab was collected from each patient. The presence of the HPV DNA in the throat was determined using the GP5+/GP6+ primers. According to our results, 28% of the recipients with kidney transplants were positive for oropharyngeal HPV infection. In addition, among the investigated risk factors, early commencement of the sexual life (below the age of 16 years) was significantly correlated with the development of oropharyngeal HPV infection.

Pharyngolaryngeal ulcers associated with the improper use of alendronate.

Bisphosphonates can cause mucosal irritation. Although esophageal ulceration is a well-recognized adverse effect of bisphosphonates, pharyngolaryngeal ulcers associated with the improper use of oral bisphosphonates have rarely been described. A previously healthy 78-year-old woman presented with refractory pharyngolaryngeal ulcers. Extensive evaluation, including biopsy, bacterial culture, and blood tests did not identify any findings that indicated a specific disease diagnosis. Antibiotics and oral prednisolone were ineffective. Ultimately, it was found that the patient regularly took a tablet of alendronate, a type of bisphosphonate, by dissolving it in the oral cavity. Within 2 weeks after withdrawal of the use of the medication, her symptoms were eliminated, and the lesions were completely healed. This case illustrates the importance of correct administration of bisphosphonates. Given the widespread use of bisphosphonates, physicians need to be aware that their improper use can cause pharyngolaryngeal ulcers.

Colon bypass with a colon-flap augmentation pharyngoesophagoplasty.

Extensive caustic stricture of the upper aero-digestive system (oro- and hypo-pharynx) is a severe injury with limited surgical options. We adopted augmentation of the cicatrized upper aero-digestive tract with colon as our preferred management option. The aim of this report is to describe our initial experience with the technique of colon-flap augmentation pharyngo-esophagoplasty (CFAP) for selected patients with severe pharyngo-esophageal stricture. Between October 2011 and June 2013, three male patients (aged 16, 4 and 18 years respectively) underwent CFAP following extensive pharyngo-esophageal stricture. Postoperative recovery was uneventful in all three cases and all started swallowing within 7-10 days after surgery without significant dysphagia. Colon-flap augmentation pharyngo-esophagoplasty is an effective procedure for reconstruction of the pharynx and the hypopharynx after extensive caustic pharyngoesophageal structure in selected cases.

[Case of drug-induced angioedema (DIAE) on induction of anesthesia with difficult ventilation due to oropharyngeal edema].

A 69-year-old man with a past history of hypertension on angiotensin II receptor blocker (ARB) for three months presented for radical prostatectomy. Immediately after induction of anesthesia with fentanyl and propofol, mask ventilation became difficult, although no significant hemodynamic changes occurred. Fiberoptic examination revealed severe oropharyngeal edema, but, the trachea was successfully intubated. Afterward, the operation proceeded without complications. He stayed in the ICU for 4 days until the trachea was extubated successfully. He was diagnosed with DIAE because of his history of dyspnea with exclusion of other possible pathophysiological conditions.

Posterior pharyngeal candidiasis in the absence of clinically overt oral involvement: a cross-sectional study.

PURPOSE: Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. METHODS: We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. RESULTS: Median age was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS, and 20 % of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. CONCLUSIONS: This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at bronchoscopy, even in the absence of clinically overt oral involvement.

Sarcoidosis-like granulomatosis of the hypopharynx as a complication of anti-TNF therapy.

INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease of unknown etiology, occasionally presenting with signs and symptoms that occur within the head and neck. Recently, granulomatous reactions and cases of sarcoidosis have been reported in patients treated with anti-TNF agents. METHODS: This report describes a 56-year-old man who developed sarcoidosis in the hypopharynx during adalimumab therapy for psoriatic arthritis. A retrospective review of the literature was performed using the PubMed database. RESULTS: In our patient, a chronic granulomatous reaction consistent with sarcoidosis developed after 2 years of continuous treatment with adalimumab. The diagnosis of sarcoidosis was established by the typical well-formed non caseating granulomas on biopsy, after excluding all other granulomatous conditions. Following withdrawal of anti-TNF agents and a course of steroids, the clinical picture resolved. CONCLUSIONS: The development of sarcoidosis during treatment with TNF-a antagonists represents a rare and paradoxical adverse event. To our knowledge this is the first case of sarcoidosis of the hypopharynx reported in the literature.

Intranasal hydrocodone-acetaminophen abuse induced necrosis of the nasal cavity and pharynx.

OBJECTIVES: Two million new users will abuse prescription narcotics this year, most commonly hydrocodone. The most commonly prescribed form is hydrocodone-acetaminophen (HA). Many individuals crush the tablets and snort the product to take advantage of the rapid transmucosal delivery of narcotics. The resultant pathology of intranasal hydrocodone acetaminophen abuse (INHAA) has been described only in a few case studies. STUDY DESIGN: Retrospective chart review. METHODS: Two private and one academic otolaryngology practices in Kentucky searched their patient charts for patients with morbidity from intranasal abuse of hydrocodone acetaminophen tablets. We identified thirty-five patients who presented for treatment between 2004 and 2011. RESULTS: The majority of patients will initially deny the behavior, frequently delaying diagnosis. Physical exam findings of white powder covering an underlying nasal mucosal necrosis are characteristic of this condition during active INHAA. Follow up was limited as only 26% returned for follow-up care. Patients commonly presented with orofacial-nasal pain (43%) and sino-nasal congestion and discharge (43%). Active necrosis or prior tissue loss was noted in 77% of patients. Fifty-one percent of patients presented with septal perforations, and 26% with palatal perforations. Two cases of invasive fungal sinusitis were clearly documented, with one resulting in death. CONCLUSIONS: The vast majority of cases presented with characteristic physical findings that included acute necrosis of soft tissue, which can progress to destroy oronasal structures. In the absence of invasive fungal disease, the condition is self-limited after cessation of INHAA and performance of local nasal debridement and nasal hygiene.

Colopharyngoplasty for intractable caustic pharyngoesophageal strictures in an indigenous African community--adverse impact of concomitant tracheostomy on outcome.

OBJECTIVES: Surgical management of caustic strictures of the upper digestive tract poses difficult challenges. This is because reconstruction above the cricopharyngeal junction interferes with the mechanisms of swallowing and respiration. This report reviews the outcome of colopharyngeal reconstruction of severe diffuse pharyngoesophageal caustic strictures in an indigenous African community. METHOD: The medical records of patients who underwent colopharyngoplasty from January 2006 to December 2008 were retrospectively reviewed to obtain information on patients' demographics, surgical technique and outcome. RESULTS: In the study period, 20 patients underwent reconstruction for caustic esophageal strictures; in five (three males, two females) colopharyngoplasty was required. Their ages ranged from four to 56 years (mean 25 years). Follow-up ranged from 23 to 94 months (mean 33 months). Colopharyngoplasty using left colon tunneled retrosternally was performed in all patients. Rehabilitative training for deglutition was required for 0.5-5.0 months postoperatively to restore near-normal swallowing in all patients. However, tracheostomy complications caused two deaths (one early, one late) and varicella encephalitis caused another late death. CONCLUSION: In this African community, colopharyngoplasty provided an effective mean of restoration of upper digestive tract continuity in patients with severe caustic pharyngoesophageal strictures. Tracheostomy in this setting portends a significant long-term mortality risk.

Gene expression in the oropharynx of children exposed to secondhand smoke.

OBJECTIVES/HYPOTHESIS: To compare gene expression in oropharyngeal mucosa of children with (ex+) and without (ex-) secondhand smoke exposure. STUDY DESIGN: Prospective case-control. METHODS: Forty-one age- and gender-matched children (2-6 years old) undergoing tonsillectomy for sleep disordered breathing at a tertiary care children's hospital were assessed for secondhand smoke exposure. Parental response to a validated questionnaire relating to secondhand smoke exposure governed inclusion. Sixteen samples were selected for microarray analysis (7 ex+, 9 ex-). Following tonsillectomy, ex vivo brushing of the mucosa isolated total RNA. Genome-wide expression profiles were generated by comparing sample RNA to a reference of all samples, assessing 27,323 cDNA clones. Microarray clones were ranked according to their ability to distinguish between the two groups using a Student t test. RESULTS: A total of 318 cDNA clones distinguished the two groups (P < .01); 180 genes were overexpressed and 138 underexpressed in ex+ samples relative to the ex- group. Independent analysis of these two groups sorted genes into disease processes and molecular functional groups, including cancer (34 genes in the overexpressed group, 29 underexpressed, P < .05), cell cycle (14 and 10), and cell growth and proliferation (7 and 11). Two of the upregulated genes, LCN2 and IQGAP1, have been previously linked to inflammation in smokers and response/repair to cellular injury in bronchial epithelium. CONCLUSIONS: Findings in this pilot study support the hypothesis that secondhand smoke exposure seems to induce gene expression changes in the oropharyngeal mucosa of exposed children, which may have significant implications for current and future disease processes.

Prevalence and associated factors of oropharyngeal side effects in users of inhaled corticosteroids in a real-life setting.

BACKGROUND: Inhaled corticosteroids (ICS) are extensively used to treat asthma, and more recently, chronic obstructive pulmonary disease (COPD). Oropharyngeal disorders represent the most frequent side effect of these drugs, which may have a negative impact on adherence. OBJECTIVES: To evaluate the prevalence of oropharyngeal disorders in users of ICS in a real-life setting and investigate the factors associated with their occurrence. METHODS: For this observational cross-sectional study, general practitioners and pulmonologists were contacted and asked to include patients suffering from asthma or COPD treated by ICS. Physicians collected data during a medical examination. A multivariate regression model for the occurrence of oropharyngeal disorders was constructed. RESULTS: A total of 1778 physicians included 6740 patients. The mean (SD) age was 51.3 (18.5) years, 44.0% had no smoking history, and the ICS indication was asthma in 63.9% of subjects. Of the study subjects, 52.3% used beclometasone (43.4% without a long-acting ss(2)-agonist, LABA); 22.1% used budesonide (18.8% with a LABA), and 25.6% used fluticasone (19.3% with a LABA in a single inhaler). One-third (34.7%) of subjects suffered from at least one oropharyngeal disorder; the most frequently reported were hoarseness, tingling, mouth irritation, and reddening. Multivariate regression analysis found that the factors positively associated with oropharyngeal disorders were COPD indication [odds ratio (OR) 1.600; 95% confidence intervals (95% CI) 1.391, 1.839], nominal daily dose (OR = 1.388; 95% CI 1.227, 1.569), decreased adherence (OR = 1.318; 95% CI 1.104, 1.574) and the use of fluticasone (OR = 1.176; 95% CI 1.008, 1.372), whereas those negatively associated were the absence of smoking history (OR = 0.837; 95% CI 0.742, 0.945), increased adherence (OR = 0.663; 95% CI 0.581, 0.755), and beclometasone use (OR = 0.630; 95% CI 0.543, 0.732). CONCLUSIONS: The high prevalence of oropharyngeal disorders and the association of adherence with these must be taken into account by prescribers, especially in patients suffering from COPD, a relatively new group of ICS users.

Radiologic appearance of chronic parapharyngeal Teflon granuloma.

Although Teflon has been used for almost 5 decades to provide tissue augmentation in various surgical indications, including head and neck surgery, its use has significantly declined in the last 2 decades, primarily because of its implication in granuloma formation. Teflon granulomas have been shown to cause false positives on positron emission tomography imaging and have been reported to have a characteristic magnetic resonance imaging (MRI) appearance. We report a patient with a large chronic Teflon granuloma of the parapharyngeal space that caused significant bony erosion of the atlas vertebra. The lesion's MRI signal characteristics were indistinguishable from those of surrounding tissues, while it showed characteristic hyperdensity on computed tomography due to the presence of fluorine atoms within Teflon. As MRI may supersede or replace computed tomography for a number of indications, and as Teflon has been used in large numbers of patients whose records may not always be available, knowledge of these findings has clinical relevance.

Laryngotracheal canal for hypopharyngoesophageal stricture after corrosive injury.

AIM: To evaluate the application of the laryngotracheal canal on the reconstruction of the hypopharyngoesophageal defect resulting from resection of stricture with corrosive injury. METHOD: Ten patients with the hypopharyngoesophageal stricture after corrosive injury due to ingestion of strong alkali in two cases and strong acid in eight treated surgically from January 2005 to December 2007 were studied. Lipiodol esophagography revealed almost complete obliteration of both sides of sinus piriformis in seven patients and stricture of the lower hypopharynx in two cases, and laryngofiberscopy revealed injury of vocal cord in one case. All patients received the operation of the laryngotracheal canal. As an isoperistaltic conduit in eight and an antiperistaltic in two, the colon was placed retrosternally anastomosed with lower margin of larynx for esophageal substitution. RESULT: All patients healed well. No anastomotic leakage was observed. Normal deglutition and weight gain were achieved in all the patients. Postoperative follow-up endoscopy showed no stricture recurrence of anastomosis. Functional results of nine patients (90%) were categorized as good result; only one (10%) faired. CONCLUSION: The application of the laryngotracheal canal therefore can be advocated as the method for reconstruction of the hypopharyngoesophageal defect after resection of stricture due to corrosive injury.

Sex, age and ABO blood groups in chemotherapy-induced oropharyngeal mucositis.

AIM: The contribution of host genetic factors in oropharyngeal mucositis is not fully understood. Therefore, we conducted this study to determine possible associations of age, sex, underlying disease, type of chemotherapy and ABO blood group antigens with the risk of chemotherapy-induced oropharyngeal mucositis. METHODS: A total of 641 patients (395 boys and 246 girls; mean age 6.82+/-4.08 years) treated by standard chemotherapy for different type of malignancies were enrolled in the study. Mucositis was scored using the WHO scale. RESULTS: Oropharyngeal mucositis was found in 65.4% of our population. Patients with hematological malignancies (RR=1.87; 95% CI 1.33-2.67; P<0.0001) and under antimetabolities drugs (RR=1.88; 95% CI 1.33-2.63; P<0.0001) were associated with increased risk of oropharyngeal mucositis. Also, patients with blood group O were at higher risk (RR=2.86; 95% CI 2.03-4.02; P<0.0001) compared to patients with blood type A (RR= 0.47; 95% CI 0.33-0.66; P<0.0001) and blood type B (RR=0.59; 95% CI 0.38-0.91; P= 0.01). No relationship was found between oropharyngeal mucositis and age or sex. CONCLUSIONS: To our knowledge this is the first report demonstrating an association between ABO blood group and oropharyngeal mucositis. Further investigations are needed for a better understanding of this relationship.

Prevalence of pharyngeal and laryngeal complications in adult asthmatics using inhaled corticosteroids.

OBJECTIVES: To investigate the prevalence in adults of pharyngeal and laryngeal symptoms associated with the use of inhaled corticosteroids. DESIGN: Prospective, observational and based on a structured, specifically designed postal questionnaire. SETTING: University Hospital Aintree, Liverpool, UK. PARTICIPANTS: The questionnaire was distributed to 190 patients on the basis of current inhaled corticosteroid use. Recruitment was from the databases of two local general practices. Individuals were classified as mild, moderate or severe asthmatics, using the guidelines of the British Thoracic Society. MAIN OUTCOME MEASURES: Demographic data, including smoking history, were recorded. The number, type, strength, dosing regime and duration of individual inhaler use were recorded. Specific pharyngeal and laryngeal side effects were enquired about. Co-morbidities and preventive measures were also recorded. Results were analysed using univariate and multivariate statistical tests. RESULTS: There was a 75.8 per cent response rate (144/190 questionnaires); 63 (43.8 per cent) of respondents were male and 81 (56.2 per cent) were female. The majority of our patients were either mild or moderate asthmatics. Longer use of an inhaled corticosteroid predisposed to weak voice (p = 0.0016), hoarseness (p = 0.0001) and throat irritation (p = 0.008). Hoarseness, throat irritation, sore throat and cough were observed much more frequently than anticipated. Severe asthmatics were more likely to use a spacer device compliantly (p = 0.0487; odds ratio 1.53). Side effects were more prevalent as asthma severity worsened (p = 0.0049; odds ratio 1.87). CONCLUSIONS: Inhaled corticosteroids cause sore throats, throat irritation, hoarseness and cough. Further research in this area is required in order to elucidate the mechanism of inflammation. Only then can effective preventive measures be introduced and implemented.

Clinical experience with angiotensin-converting enzyme inhibitor-induced angioedema.

OBJECTIVES: To understand the presentation and clinical course of angiotensin-converting enzyme (ACE) inhibitor-induced angioedema and to determine management factors associated with progression to airway compromise. STUDY DESIGN AND SETTING: Retrospective chart review of patients taking ACE inhibitors who presented to the emergency department with angioedema between December 1999 and July 2004 (n = 228). Clinical presentation, treatment, and clinical course were analyzed. RESULTS: The oral cavity was the most common location of upper-airway angioedema. Twenty-two (10%) patients required intubation, and all were intubated within 12 hours of presentation. Of the patients who required intubation, those who were started on an H(1)-blocker were extubated earlier than those not on an H(1)-blocker (P = 0.05). CONCLUSION: The locations of swelling and drooling on admission are predictive of the need for intubation. Other aspects of presentation, treatment, and disposition can help in management decisions for this potentially fatal condition. SIGNIFICANCE: This is the largest series to date of ACE inhibitor-related angioedema that challenges theories on the etiology and treatment of this condition.

False-positive positron-emission tomography-CT of a Teflon granuloma in the parapharyngeal space occurring after treatment for a patulous eustachian tube.

This report presents a 55-year-old woman who underwent 2 Teflon injections in 1971 for a patulous eustachian tube. The patient returned in 2006 with a bloody left otorrhea. A positron-emission tomography-CT scan demonstrated a 2-cm hypermetabolic parapharyngeal mass, initially interpreted as a skull base tumor. Repeat neck CT confirmed a 2-cm hyperattenuated left parapharyngeal granulomatous mass. This is the first reported case of a Teflon granuloma presenting as a false-positive parapharyngeal mass.