Clinical outcomes following pharyngolaryngectomy reconstruction: a 20-year single-centre study.

BACKGROUND: Advanced malignant neoplasms of the larynx and hypopharynx pose many therapeutic challenges. Total pharyngolaryngectomy and total laryngectomy provide an opportunity to cure these tumours but are associated with significant morbidity. Reconstruction of the pharyngeal defect following total pharyngolaryngectomy demands careful consideration and remains an area of debate within surgical discussions. METHODS: This paper describes a systemic analysis of pharyngeal reconstruction following total pharyngolaryngectomy and total laryngectomy, leveraging data collected over a 20-year period at a large tertiary referral centre. RESULTS: Analysing 155 patients, the results show that circumferential pharyngeal defects and prior radiotherapy have a significant impact on surgical complications. In addition, free tissue transfer in larger pharyngeal defects showed lower rates of post-operative anastomosis leak and stricture. CONCLUSION: Pharyngeal resection carries a substantial risk of post-operative complications, and free tissue transfer appears to be an effective means of reconstruction for circumferential defects.

Pilot Survey of Shared Decision-Making Between Orthopaedic Surgeons and Their Patients in Guatemala.

BACKGROUND: Shared decision-making (SDM) is widely accepted as an essential feature of patient-centered care. However, to our knowledge, there has been no empirical research on the factors that influence orthopaedic surgeons' use of SDM in Guatemala. METHODS: Questions about physician attributes and SDM were included in a 2016 electronic survey distributed to the 221 members of the Asociación Guatemalteca de Ortopedia y Traumatología (AGOT). RESULTS: A total of 114 (52%) of the AGOT-registered orthopaedic surgery residents and orthopaedic surgeons who were sent surveys returned them, and 79 of these surveys contained complete responses to study variables of interest. Of the 79 participants with complete responses, 73% reported that they discussed treatment options most of the time or always with their patients and 81% reported that they explained the reasons for treatment choices. Compared with residents, surgeons who had completed their residency in orthopaedic surgery or had subspecialty training had greater odds (odds ratio [OR] = 9.62; 95% confidence interval [CI] = 1.35, 68.53; p < 0.05) of explaining the reasons for their decisions rather than using other strategies when patients expressed different preferences. Residents and surgeons who discussed treatment choices with their patients were more likely to allow their patients to participate in treatment decisions than those who did not (OR = 2.88; 95% CI = 1.90, 4.36; p < 0.001). CONCLUSIONS: While findings from this exploratory study are limited by its small sample size and its narrow focus on physicians rather than on both patients and physicians, they nonetheless establish a roadmap for future study, particularly with respect to challenges in Guatemala to meaningful SDM that arise from context-specific cultural norms and practices. CLINICAL RELEVANCE: SDM as a tool of practice remains underutilized by orthopaedic surgeons in clinical practice in Guatemala. This study may encourage more discussions regarding SDM in orthopaedic surgery elsewhere in Central America and prompt discussion in the region on the value of and need for postgraduate training in this area.

Provision of physiotherapy rehabilitation following neck dissection in the UK.

BACKGROUND: Neck dissection is associated with post-operative shoulder dysfunction in a substantial number of patients, affecting quality of life and return to work. There is no current UK national practice regarding physiotherapy after neck dissection. METHOD: Nine regional centres were surveyed to determine their standard physiotherapy practice pre- and post-neck dissection, and to determine pre-emptive physiotherapy for any patients. RESULTS: Eighty-nine per cent of centres never arranged any pre-emptive physiotherapy for any patients. Thirty-three per cent of centres offered routine in-patient physiotherapy after surgery. No centres offered out-patient physiotherapy for all patients regardless of symptoms. Seventy-eight per cent offered physiotherapy for patients with any symptoms, with 11 per cent offering physiotherapy for those with severe dysfunction only. Eleven per cent of centres never offered physiotherapy for any dysfunction. CONCLUSION: The provision of physiotherapy is most commonly reactive rather than proactive, and usually driven by patient request. There is little evidence of pre-arranged physiotherapy for patients to treat or prevent shoulder dysfunction in the UK.

Trans-oral robotic assisted tongue base mucosectomy for investigation of cancer of unknown primary in the head and neck region. The UK experience.

OBJECTIVES: The diagnosis of cancer of unknown primary (CUP) in head and neck occurs when the treating clinicians have utilised all available diagnostic tests and failed to identify the origin of the disease. There is no agreed consensus on which diagnostic investigations to use, or the order in which to use them in, although broad recommendations exist. Small tumours arising in the tongue base can be below the limits of resolution of conventional diagnostic techniques. Given the difficulty in targeting the tongue base, current practice involves blind random biopsies, which leads to a variable detection rate. Robotically assisted surgical removal of the tongue base, tongue base mucosectomy (TBM) has been shown to improve diagnostic yield. This study reports the diagnostic hit rate for tongue base primaries using this technique. DESIGN: Retrospective case review. SETTING: UK Head and Neck Centres. PARTICIPANTS: Patients presenting as an unknown primary, investigated with clinical examination, PET-CT and palatine tonsillectomy. MAIN OUTCOME MEASURES: The detection of a primary site of head and neck cancer in the otherwise unknown primary tumour. RESULTS: The primary tumour site was identified in the tongue base in 53% (n=17) of patients. In 15 patients the tumour was in the ipsliateral tongue base (88%) while in two cases (12%) the tumour was located in contra lateral tongue base. CONCLUSIONS: Trans-oral robotic assisted TBM raises the possibility of identifying over 50% of tumours that would otherwise be classified as CUP. Identifying these in the contralateral tongue base has implications for treatment planning and outcome.

Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status.

OBJECTIVE: This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status. METHODS: A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test. RESULTS: Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators. CONCLUSION: The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia.

Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but long-term outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 ± 1,968 preoperatively to 1,068 ± 384 mmol/mol creatinine) and plasma (from 445.9 ± 257.0 to 333.3 ± 117.7 µmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 ± 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 µmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge. CONCLUSION: Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.

Functional outcomes following endoscopic laser cricopharyngeal myotomy with mucosal repair.

Endoscopic laser cricopharyngeal myotomy is an effective treatment for cricopharyngeal dysfunction, but concern remains over the risk of serious complications following the procedure. Some authors have therefore considered endoscopic laser cricopharyngeal myotomy with mucosal repair; however, outcome data for the procedure is scanty. This study aims to identify functional outcomes in a series of patients following endoscopic laser cricopharyngeal myotomy with mucosal repair. Endoscopic laser cricopharyngeal myotomy with mucosal repair was performed on 38 subjects in two centres over a period of 33 months. Pre- and post-operative outcomes were evaluated in 32 subjects using the Sydney Swallow Questionnaire and Reflux Symptom Index. An improvement in swallowing scores was seen in 30 subjects (94%, p < 0.001). The Reflux Symptom Index improved 28 subjects (88%, p < 0.001). Mean procedure time was 58 min. One subject (2.6%) developed mediastinitis following surgery, and four experienced (12.5%) a recurrence of dysphagic symptoms. Endoscopic laser cricopharyngeal myotomy with mucosal repair is an effective treatment for cricopharyngeal dysfunction. The complication rate observed in this study was comparable or lower than previously reported studies into endoscopic laser cricopharyngeal myotomy without mucosal repair. Larger studies may be required to determine the additional benefit of mucosal repair over endoscopic laser cricopharyngeal myotomy alone.

Prospective, randomized, single-blinded study comparing the use of a flexible nasendoscope and a rigid laryngoscope in outpatient laryngeal and pharyngeal examinations.

OBJECTIVE: To compare the quality of the image obtained using a flexible nasendoscope and a rigid laryngoscope when visualizing laryngeal and pharyngeal structures in an outpatient setting. DESIGN: Prospective, randomized, single-blinded study. SETTING: Otolaryngology outpatient clinic. PARTICIPANTS: Patients referred to the otolaryngology clinic with laryngeal symptoms were prospectively recruited and subjected to laryngeal investigation using both the flexible nasendoscope and the rigid laryngoscope. The order of both instruments was randomized, and the investigations were recorded and scored according to a set protocol. MAIN OUTCOME MEASURES: Primary: score of each instrument at visualizing laryngeal structures. Secondary: tolerability of each instrument. RESULTS: Thirty patients (12 males vs 18 females) were recruited, with a median age of 43.5 years. No statistical difference was noted in terms of the tolerability of each instrument (p = .885). Both instruments were similar in terms of the structures identified. The quality of the image was better when using the rigid laryngoscope (p = .009). CONCLUSION: The flexible nasendoscope and the rigid laryngoscope were equally tolerated. The flexible nasendoscope was slightly better at visualizing the laryngeal structures, whereas the rigid laryngoscope provided better image quality.

PDK-1 regulates lactate production in hypoxia and is associated with poor prognosis in head and neck squamous cancer.

Here we describe the expression and function of a HIF-1-regulated protein pyruvate dehydrogenase kinase-1 (PDK-1) in head and neck squamous cancer (HNSCC). Using RNAi to downregulate hypoxia-inducible PDK-1, we found that lactate and pyruvate excretion after 16-48 h of hypoxia was suppressed to normoxic levels. This indicates that PDK-1 plays an important role in maintaining glycolysis. Knockdown had no effect on proliferation or survival under hypoxia. The immunohistochemical expression of PDK-1 was assessed in 140 cases of HNSCC. PDK-1 expression was not expressed in normal tissues but was upregulated in HNSCC and found to be predominantly cytoplasmic with occasional strong focal nuclear expression. It was strongly related to poor outcome (P=0.005 split by median). These results indicate that HIF regulation of PDK-1 has a key role in maintaining lactate production in human cancer and that the investigation of PDK-1 inhibitors should be investigated for antitumour effects.

Quality of life following resection, free flap reconstruction and postoperative external beam radiotherapy for squamous cell carcinoma of the base of tongue.

This study was conducted to evaluate quality of life in a cohort of patients with squamous cell carcinoma of the tongue base, treated with primary surgery, reconstruction and postoperative radiotherapy. Twelve patients were assessed in a cross-sectional study using the University of Washington Quality of Life Instrument (UW-QOL). All patients underwent external beam irradiation following primary resection of their tumour and reconstruction. Patients on average reported their overall and health related QOL to be good. Functionally they had good pain control, speech intelligibility, activity and recreational levels. There were some limitations in chewing, swallowing and taste. The results suggest that surgical resection can offer good functional and overall QOL results for advanced tumours when combined with reconstruction. The morbidity associated with postoperative radiotherapy includes reduced swallowing, taste, saliva production and difficulty chewing.

Treatment of carnitine deficiency.

Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose-response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these concerns. Carnitine treatment of inborn errors of metabolism is a safe and integral part of the treatment regime for these disorders.

Hypohidrotic ectodermal dysplasia associated with squamous cell carcinoma of the trachea.

Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by abnormalities to ectodermal derived tissues although other organs or systems are frequently involved. Patients with HED can have a number of symptoms that may lead them to present to the otolaryngologist. We present a case of a 37-year-old female with HED who initially presented with nasal obstruction but then very rapidly developed stridor due to a tracheal squamous cell carcinoma. We suggest a possible association between HED and carcinoma of the upper respiratory tract that has not previously been reported.

Flexible nasendoscope with a disposable-sheath system versus standard nasendoscopy: a prospective, randomized trial.

There are no published guidelines for the sterilization of the flexible nasendoscope and various techniques exist. We have conducted a randomized, prospective, blinded trial of the barrier Endosheath system versus immersion in Cidex disinfectant. Using a visual analogue assessment, there were no differences at a 99% confidence interval (CI) between the two techniques from the nursing assistant and patient perspectives. Image quality was assessed blinded and no difference could be detected at a 99% CI. The Endosheath offers the advantage of increasing the productivity of each nasendoscope as the sterilization time is reduced. It also provides barrier protection against cross-contamination, including prion diseases.

Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy.

OBJECTIVES: A multicenter retrospective study was conducted to investigate the possible metabolic causes of pediatric cardiomyopathy and evaluate the outcome of patients treated with L-carnitine. METHODS: Seventy-six patients diagnosed with cardiomyopathy were treated with L-carnitine in addition to conventional cardiac treatment, and 145 patients were treated with conventional treatment only. There were 101 males and 120 females between 1 day and 18 years old. Cardiomyopathy diagnoses included dilated (148 patients), hypertrophic (42 patients), restrictive (16 patients), mixed diagnosis (11 patients), and 4 with an unknown type. Of 76 L-carnitine-treated patients, 29 (38%) had evidence to suggest a disorder of metabolism, and of 145 control patients, 15 (10%) were suspected to have a disorder of metabolism. These metabolic disorders were thought to be the cause for the cardiomyopathy of the patients. The duration of L-carnitine treatment ranged from 2 weeks to >1 year. Information was collected on length of survival (time-to-event), clinical outcome, echocardiogram parameters, and clinical assessments. Data were collected at intervals from baseline to study endpoint, death, transplant, or last known follow-up visit. RESULTS: L-Carnitine-treated patients were younger than control patients and had poorer clinical functioning at baseline, yet they demonstrated lower mortality and a level of clinical functioning and clinical severity comparable to control patients on conventional therapy by the end of the study. An analysis of the interaction between clinical outcome and concomitant medications unexpectedly revealed that the population of patients treated with angiotensin-converting enzyme (ACE) inhibitors (40% of patients) had significantly poorer survival (although their greater likelihood for poor survival may possibly have made them more likely to receive ACE inhibitors). CONCLUSION: Results suggest that L-carnitine provides clinical benefit in treating pediatric cardiomyopathy. There is a need for further exploration of potential explanatory factors for the higher mortality observed in the population of patients treated with ACE inhibitors.

Cardiomyopathy in childhood, mitochondrial dysfunction, and the role of L-carnitine.

Cardiomyopathy in childhood is associated with high morbidity and mortality rates. Many metabolic causes have been identified, including genetic or acquired defects in mitochondrial energy production affecting beta-oxidation, carnitine transport, and the electron transport chain. Combining conventional inotropic and antiarrhythmic therapy with metabolic interventions has improved overall outcome. L-carnitine, a natural substance involved in mitochondrial transport of fatty acids, is one such therapy and plays a central role in the regulation of the inner mitochondrial supply of free coenzyme A. Carnitine deficiency can be caused by both genetic and environmental causes with resultant signs and symptoms of metabolic disease, including cardiomyopathy. Administration of L-carnitine can result in improvement or resolution of the cardiomyopathy.

Inborn errors of metabolism: medical and administrative "orphans".

CONTEXT: Inborn errors of metabolism are genetic conditions that affect the normal biochemical functions of the body in any organ and at any age. More than 500 metabolic diseases are known; almost all are classified as orphan diseases under the US Food and Drug Administration guidelines (incidence < 200,000 persons) and each has its own requirements for diagnosis and treatment. Management of these complex, lifelong, multisystem disorders often requires a coordinated, multidisciplinary approach involving several subspecialists and which may include complex laboratory evaluations, genetic counseling, nutritional therapy, and unusual therapeutic approaches that have been used in only a small number of cases. RESULTS: Not infrequently, inborn errors of metabolism fall outside current standard diagnostic and treatment guidelines of managed care plans. This results in delays in diagnosis and appropriate management, with increased costs to patients and to society. CONCLUSIONS: Patients with inborn errors of metabolism should not be discriminated against and all health plans should specify that access to specialists and metabolic centers are a covered benefit of the plan. The acceptance of treatment guidelines, the development of international disease classification codes for the disorders, and the performance of cost-benefit analyses would all greatly facilitate this process. However, without recognition that these disorders require such services, and steps to provide them by the insurance industry, the care of children with metabolic disorders and other chronic diseases will continue to be a source of frustration and anger among the caregivers and the families they serve.