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.

Recurrent angioedema associated with pharmacological inhibition of dipeptidyl peptidase IV.

Angioedema (AE) of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to increased use of medications inhibiting the degradation of vasoactive peptides. Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEI-AAE) is well known, but other pharmaceutical agents also affect the degradation of bradykinin and substance P. We present a middle-aged man with recurrent episodes of severe AE of the oral cavity, hypopharynx and larynx due to pharmacological inhibition of dipeptidyl peptidase IV.

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.

Pharyngeal spasticity due to dantrolene.

WHAT IS KNOWN AND OBJECTIVE: Dantrolene can be combined with baclofen to better treat spasticity, but may cause muscular weakness and dysphagia. We instead describe a pharyngeal spasm due to dantrolene. CASE SUMMARY: A 12-year-old male received dantrolene 3 mg/kg/day in adjunct to baclofen 2 mg/kg/day, to improve spasticity. After 5 days of full-dose dantrolene, his dysphagia worsened and he developed pharyngeal spasm. Dantrolene was suspected for an adverse reaction and removed. The patient subsequently improved. WHAT IS NEW AND CONCLUSION: Causality analysis determined a probable relationship between dantrolene and pharyngeal spasm. This may be due to direct muscle contraction by dantrolene, an effect seen previously in vitro.

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.

Determination of glyphosate and AMPA in blood and urine from humans: about 13 cases of acute intoxication.

Acute intoxications after ingesting glyphosate are observed in suicidal or accidental cases. Despite low potential toxicity of this herbicide, a number of fatalities and severe outcomes are reported. Indeed, some authors have described the clinical features associated with blood and urine concentrations following intoxication. The purpose of this study is to describe the clinical feature and determinate the utility of the glyphosate concentration in blood and urine and the dose taken for predicting clinical outcomes. In 13 glyphosate poisoning cases treated in our laboratory within 7 years period from 2002 to 2009, we registered clinical observations and collected blood and urine samples to HPLC-MS-MS analysis. We classified our patients by the intoxication severity using simple clinical criteria. We obtained clinical observations from 10 patients and the others three patients were treated in forensic cases. Among the 10 patients, one was asymptomatic, 5 had mild to moderate poisoning and 2 had severe poisoning. There were 6 deaths whose 3 were forensic cases. The most common symptoms were oropharyngeal ulceration (5/10), nausea and vomiting (3/10). The main altered biological parameters were high lactate (3/10) and acidosis (7/10). We also noted respiratory distress (3/10), cardiac arrhythmia (4/10), hyperkaleamia, impaired renal function (2/10), hepatic toxicity (1/10) and altered consciousness (3/10). In fatalities, the common symptoms were cardiovascular shock, cardiorespiratory arrest, haemodynamic disturbance, intravascular disseminated coagulation and multiple organ failure. Blood glyphosate concentrations had a mean value of 61 mg/L (range 0.6-150 mg/L) and 4146 mg/L (range 690-7480 mg/L) respectively in mild-moderate intoxication and fatal cases. In the severe intoxication case for which blood has been sampled, the blood glyphosate concentration was found at 838 mg/L. Death was most of the time associated with larger taken dose (500 mL in one patient) and high blood glyphosate concentrations. To predict clinical outcomes and to guide treatment support in patients who ingested glyphosate, blood concentrations of this compound and the taken dose have been useful.

[Systemic and oropharyngeal side effects of inhaled corticosteroids]. / Effets secondaires systémiques et oropharyngés des corticostéroïdes inhalés.

The use of inhaled corticosteroids (ICS) is an important component of asthma management. Although their main impact is on airway inflammation, ICS are not devoid of systemic side effects (adrenal insufficiency, osteoporosis, brittle skin, ocular effects, growth retardation). Oropharyngeal side effects are also reported. These effects appear dose and duration dependent. They also vary according to the type of ICS used, its method of administration and drug interactions. It is recommended to titrate ICS to the lowest effective dose, to regularly reconsider their indication and to be aware of drug interactions. In addition, a change in ICS may have a favorable impact on side effects.

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.

Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block.

In this review, we summarize the clinical implications of residual neuromuscular block. Data suggest that residual neuromuscular block is a common complication in the postanesthesia care unit, with approximately 40% of patients exhibiting a train-of-four ratio <0.9. Volunteer studies have demonstrated that small degrees of residual paralysis (train-of-four ratios 0.7-0.9) are associated with impaired pharyngeal function and increased risk of aspiration, weakness of upper airway muscles and airway obstruction, attenuation of the hypoxic ventilatory response (approximately 30%), and unpleasant symptoms of muscle weakness. Clinical studies have also identified adverse postoperative events associated with intraoperative neuromuscular management. Large databased investigations have identified intraoperative use of muscle relaxants and residual neuromuscular block as important risk factors in anesthetic-related morbidity and mortality. Furthermore, observational and randomized clinical trials have demonstrated that incomplete neuromuscular recovery during the early postoperative period may result in acute respiratory events (hypoxemia and airway obstruction), unpleasant symptoms of muscle weakness, longer postanesthesia care unit stays, delays in tracheal extubation, and an increased risk of postoperative pulmonary complications. These recent data suggest that residual neuromuscular block is an important patient safety issue and that neuromuscular management affects postoperative outcomes.

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.