Introducing day case thyroid lobectomy at a tertiary head and neck centre.

BACKGROUND: Thyroid lobectomy is considered to be a safe day case procedure by the British Association of Day Surgery. However, currently only 5.5% of thyroid surgeries in the UK are undertaken as day cases. We determine if and how thyroid lobectomy with same-day discharge could safely be introduced in our centre. METHODS: We analysed all thyroid lobectomy surgeries performed between April 2015 and May 2019. Exclusion criteria included completion surgery, revision surgery, additional procedures and disseminated disease. Outcomes were benchmarked against surgeon-reported complications from the British Association of Endocrine and Thyroid Surgery's 5th National Audit. Additionally, we reviewed the number of patients who met day case criteria currently in use at our hospital to determine accessibility to the service. RESULTS: In total, 259 thyroid lobectomy surgeries were undertaken and of these 173 met the inclusion criteria. There was no mortality, return to theatre for evacuation of postoperative haematoma or readmission. There was one postoperative haematoma which was drained at the bedside. Some 47 of the 173 (27.2%) patients met day case criteria currently in use at our centre. CONCLUSIONS: Day case surgery provides a cost-effective solution to rising bed pressures and a coherent protocol can optimise patient safety and experience.

Tracheostomy in the coronavirus disease 2019 patient: evaluating feasibility, challenges and early outcomes of the 14-day guidance.

OBJECTIVES: To report feasibility, early outcomes and challenges of implementing a 14-day threshold for undertaking surgical tracheostomy in the critically ill coronavirus disease 2019 patient. METHODS: Twenty-eight coronavirus disease 2019 patients underwent tracheostomy. Demographics, risk factors, ventilatory assistance, organ support and logistics were assessed. RESULTS: The mean time from intubation to tracheostomy formation was 17.0 days (standard deviation = 4.4, range 8-26 days). Mean time to decannulation was 15.8 days (standard deviation = 9.4) and mean time to intensive care unit stepdown to a ward was 19.2 days (standard deviation = 6.8). The time from intubation to tracheostomy was strongly positively correlated with: duration of mechanical ventilation (r(23) = 0.66; p < 0.001), time from intubation to decannulation (r(23) = 0.66; p < 0.001) and time from intubation to intensive care unit discharge (r(23) = 0.71; p < 0.001). CONCLUSION: Performing a tracheostomy in coronavirus disease 2019 positive patients at 8-14 days following intubation is compatible with favourable outcomes. Multidisciplinary team input is crucial to patient selection.

Tumour assessment and staging: United Kingdom National Multidisciplinary Guidelines.

In general, the first decision to be made in a patient with a confirmed head and neck cancer is whether or not to treat the patient before deciding what form of management strategy is appropriate. There is no more important an aspect of head and neck cancer care than the initial evaluation of the patient and the patient's tumour. The practice requires specific expertise and judgement. The current tumour-node-metastasis system relies on morphology of the tumour (anatomical site and extent of disease) but the final decision on treatment hinges on a full assessment of the patient including physiological age and general condition. The aim of this paper is primarily to describe why and how we appraise a patient and their tumour. It addresses the general principles applicable to the topic of evaluation, classification and staging. In addition, the limitations and pitfalls of this process are described. Recommendations • All patients with head and neck cancer (HNC) should undergo tumour classification and staging prior to treatment. (R) • Pre-therapeutic clinical staging of HNCs should be based on at least a C2 factor (evidence obtained by special diagnostic means, e.g. radiographic imaging (e.g. computed tomography, magnetic resonance imaging or ultrasound scan), endoscopy, biopsy and cytology). (R) • Imaging to evaluate the primary site should be performed prior to biopsy to avoid the effect of upstaging from the oedema caused by biopsy trauma. (G) • Panendoscopy is only recommended for symptomatic patients or patients with primary tumours known to have a significant risk of a second (synchronous) primary tumour. (G).

Oncological safety of the Hayes-Martin manoeuvre in neck dissections for node-positive oropharyngeal squamous cell carcinoma.

INTRODUCTION: The Hayes-Martin manoeuvre involves ligation of the posterior facial vein and superior reflection of the investing fascia below the mandible to preserve the marginal mandibular nerve. The peri-facial nodes thus remain undissected. We perform this manoeuvre routinely during modified radical neck dissection for metastatic oropharyngeal squamous cell cancer. Here, we review the oncological safety and marginal mandibular nerve preservation rates of this manoeuvre from 2004 to 2009. METHOD: Retrospective review of the head and neck oncology database (2004-2009) at Addenbrooke's Hospital, Cambridge, UK, a tertiary referral centre for head and neck oncology. RESULTS: Thirty-four patients underwent modified radical neck dissection for metastatic oropharyngeal squamous cell carcinoma. The primary tumour included the tonsil in 19 cases, base of tongue in 10 and posterior pharyngeal wall in 5. The neck nodal status was N1 in 4 cases, N(2a) in 11, N(2b) in 10, N(2c) in 4 and N(3) in 5. All patients had adjuvant radiotherapy. Median follow up was four years (range, two to five). No peri-facial nodal region recurrences were seen. Four patients had temporary marginal mandibular nerve weakness; beyond two months, no weakness was seen. CONCLUSION: In neck dissections for oropharyngeal squamous cell carcinoma, the marginal mandibular nerve and accompanying facial nodes can be safely preserved without oncological risk using the Hayes-Martin manoeuvre.

Safety of extracapsular dissection in benign superficial parotid lesions.

INTRODUCTION: The current practice for removal of clinically benign superficial parotid lesions is an appropriate superficial parotidectomy with a cuff of normal parotid tissue for complete pathological clearance. This technique requires the identification of the facial nerve at the main trunk and dissection of the segment of the facial nerve deep to the lesion. The reported major complications of this procedure include temporary or permanent facial nerve weakness, Frey's syndrome and salivary leaks. In order to avoid these complications, a local extracapsular dissection technique can be utilised in the management of small inferiorly located benign lesions of the parotid gland. METHODS: A retrospective case note review was performed for all parotidectomies between 2004 and 2009 in Addenbrooke's Hospital, Cambridge by the senior authors. RESULTS: A total of 172 cases were identified out which 46 underwent an extracapsular dissection. The average size of these lesions was 1.9 cm (0.9-2.4 cm) with all universally located inferior or posterior to the angle of the mandible. The pathologies were 14 pleomorphic adenomas, 24 Warthin's tumours, 6 lymphangiomas and 2 simple cysts. There were no post-operative facial nerve weaknesses, Frey's syndrome or salivary leaks within the extracapsular dissection group. The median follow-up of these patients were 4.6 years (2-6 years) with 6 patients lost to follow-up. No recurrences have been noted in the cohort at follow-up.

Laminin 332 deposition is diminished in irradiated skin in an animal model of combined radiation and wound skin injury.

Skin exposure to ionizing radiation affects the normal wound healing process and greatly impacts the prognosis of affected individuals. We investigated the effect of ionizing radiation on wound healing in a rat model of combined radiation and wound skin injury. Using a soft X-ray beam, a single dose of ionizing radiation (10-40 Gy) was delivered to the skin without significant exposure to internal organs. At 1 h postirradiation, two skin wounds were made on the back of each rat. Control and experimental animals were euthanized at 3, 7, 14, 21 and 30 days postirradiation. The wound areas were measured, and tissue samples were evaluated for laminin 332 and matrix metalloproteinase (MMP) 2 expression. Our results clearly demonstrate that radiation exposure significantly delayed wound healing in a dose-related manner. Evaluation of irradiated and wounded skin showed decreased deposition of laminin 332 protein in the epidermal basement membrane together with an elevated expression of all three laminin 332 genes within 3 days postirradiation. The elevated laminin 332 gene expression was paralleled by an elevated gene and protein expression of MMP2, suggesting that the reduced amount of laminin 332 in irradiated skin is due to an imbalance between laminin 332 secretion and its accelerated processing by elevated tissue metalloproteinases. Western blot analysis of cultured rat keratinocytes showed decreased laminin 332 deposition by irradiated cells, and incubation of irradiated keratinocytes with MMP inhibitor significantly increased the amount of deposited laminin 332. Furthermore, irradiated keratinocytes exhibited a longer time to close an artificial wound, and this delay was partially corrected by seeding keratinocytes on laminin 332-coated plates. These data strongly suggest that laminin 332 deposition is inhibited by ionizing radiation and, in combination with slower keratinocyte migration, can contribute to the delayed wound healing of irradiated skin.

Mitigation of radiation injuries via suppression of the renin-angiotensin system: emphasis on radiation nephropathy.

Radiation nephropathy and other normal tissue radiation injuries can be successfully mitigated, and also treated, by antagonists of the renin-angiotensin system (RAS). This implies a mechanistic role for that system in radiation nephropathy, yet no evidence exists to date of activation of the RAS by irradiation. RAS antagonists, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, are the standard of care in the treatment of subjects with other chronic progressive kidney diseases, in which they exert benefit by reducing both glomerular and tubulo-interstitial injury. These drugs are likely to act in a similar way to mitigate radiation nephropathy.

Idiopathic cervical osteomyelitis presenting as dysphagia.

We discuss a case of idiopathic cervical epidural abscess, complicated by osteomyelitis, presenting with dysphagia as the main complaint. No predisposing factors were identified and blood cultures were negative. Case was treated conservatively by long course of IV antibiotics. We present a review of presentation of spinal epidural abscesses and indications for surgical intervention.

Vascular injury after whole thoracic x-ray irradiation in the rat.

PURPOSE: To study vascular injury after whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict the severity of injury. METHODS AND MATERIALS: Rats that received 5- or 10-Gy thorax-only irradiation and age-matched controls were studied at 3 days, 2 weeks, and 1, 2, 5, and 12 months. Several pulmonary vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin-converting enzyme activity, and right ventricular hypertrophy. RESULTS: By 1 month, the rats in the 10-Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin-converting enzyme activity, as well as pulmonary artery distensibility. In contrast, irradiation with 5 Gy resulted in only a modest increase in right ventricular weight and a reduction in lung angiotensin-converting enzyme activity. CONCLUSION: In a previous investigation using the same model, we observed that recovery from radiation-induced attenuation of pulmonary vascular reactivity occurred. In the present study, we report that deterioration results in several vascular parameters for

Treatment of radiation nephropathy with ACE inhibitors and AII type-1 and type-2 receptor antagonists.

Radiation nephropathy has emerged as a significant complication of bone marrow transplantation and radionuclide radiotherapy, and is a potential sequela of radiological terrorism and radiation accidents. In the early 1990's, it was demonstrated that experimental radiation nephropathy could be treated with a thiol-containing ACE inhibitor, captopril. Further studies have shown that enalapril (a non-thiol ACE inhibitor) is also effective in the treatment of experimental radiation nephropathy, as are both AII type-1 (AT(1)) and type-2 (AT(2)) receptor antagonists. ACE inhibitors and AII receptor antagonists are also effective in the mitigation (prevention) of radiation nephropathy. Other types of antihypertensive drugs are ineffective in mitigation, but brief use of a high-salt diet in the immediate post-irradiation period significantly decreases renal injury. There are differences between mitigation and treatment of radiation nephropathy that imply that different mechanisms are operating. First, a high-salt diet is effective in the mitigation of radiation nephropathy, but deleterious on the treatment of established disease. Second, AT(1) blockade is more effective than ACE inhibition for mitigation of radiation nephropathy, but equally effective for treatment. Third, the efficacy of AT(1) blockade and ACE inhibition is highly dependent on drug dose in mitigation of radiation nephropathy, but not so in treatment. Finally, while AT(2) blockade augments the benefit of AT(1) blockade in mitigation of radiation nephropathy, it does not do so in treatment. We hypothesize that while mitigation of radiation nephropathy works by suppression of the renin-angiotensin system, treatment of established radiation nephropathy requires blood pressure control in addition to (or possibly instead of) suppression of the renin-angiotensin system.

Is unilateral tonsillar enlargement alone an indication for tonsillectomy?

INTRODUCTION: Unilateral tonsillar enlargement is often seen in the out-patient setting. Frequently, these patients are listed for tonsillectomy for the purpose of ruling out malignant histology. This study aims to determine the necessity for tonsillectomy. METHOD: This retrospective case-note review looks at all the tonsillectomies performed for histological examination at our institution over a five year period, and analyses the histological findings in those with unilateral tonsillar enlargement (UTE) alone, and those with UTE with other clinical features (history of chronic pain, dysphagia, the presence of tonsillar or peritonsillar mucosal abnormality, those with cervical lymphadenopathy). All patients who underwent tonsillectomy for the purpose of histological examination from 1 June 1998 to 30 May 2003 were identified and their notes reviewed. Exclusion criteria included cases where there were no pre-operative out-patient notes, those patients where the specimens had been sent from other hospitals, those patients who had malignancy already diagnosed, and those cases where tonsillectomy had been performed by other surgical specialties (e.g. maxillofacial, plastics). There were 1475 tonsillectomies, of which 181 performed over this period were sent for histological analysis. After excluding those patients that did not meet our criteria, we were left with 53 patients who had UTE. The primary outcome measure was the rate of malignancy in the two groups. RESULTS: Of these, 33 had UTE alone, 20 had associated clinical features. In the former group, none of the patients were found to have malignancy. In the latter, nine (45 per cent) had a malignancy. Fisher's exact test was used to test for differences between the UTE alone group versus the UTE plus other features group (p<0.001). DISCUSSION: The prevalence of malignancy in tonsils which exhibit asymmetry with no other clinical features is very low; in our study it was zero. However, other studies have found a small percentage representing underlying malignancy. In view of this, we feel that a 'watch and wait' policy is initially more appropriate, and if symptoms or signs are progressive, tonsillectomy should then be advised.

Mechanism of binding of warfarin enantiomers to recombinant domains of human albumin.

Domain fragments of human serum albumin corresponding to domains 1 and 2 (D12) and domains 2 and 3 (D23) were expressed in yeast. The kinetics of warfarin binding to these fragments were investigated using stopped-flow fluorescence spectroscopy. Binding can be characterized by a two-step process, a rapid diffusion-controlled step and a slower rate-limiting step in which a stable drug-protein complex is formed. The equilibrium constant for step 1 is greater for both D12 and D23 than for albumin, probably as a result of reduced steric hindrance offered by the domain fragments. Binding step 2, thought to be the result of a conformational change as warfarin is accommodated by the protein, is faster for D12 and D23. Albumin and the domain fragments show an increased preference for the R enantiomer, but the preference is particularly enhanced for domain fragment D12. These preferences can largely be explained by the domains having different rates for step 2 of the binding process.

ACE inhibitors and AII receptor antagonists in the treatment and prevention of bone marrow transplant nephropathy.

Radiation nephropathy has emerged as a major complication of bone marrow transplantation (BMT) when total body irradiation (TBI) is used as part of the regimen. Classically, radiation nephropathy has been assumed to be inevitable, progressive, and untreatable. However, in the early 1990's, it was demonstrated that experimental radiation nephropathy could be treated with a thiol-containing ACE inhibitor, captopril. Further studies showed that enalapril (a non-thiol ACE inhibitor) was also effective in the treatment of experimental radiation nephropathy, as was an AII receptor antagonist. Studies also showed that ACE inhibitors and AII receptor antagonists were effective in the prophylaxis of radiation nephropathy. Interestingly, other types of antihypertensive drugs were ineffective in prophylaxis, but brief use of a high-salt diet in the immediate post-irradiation period decreased renal injury. A placebo-controlled trial of captopril to prevent BMT nephropathy in adults is now underway. Since excess activity of the renin-angiotensin system (RAS) causes hypertension, and hypertension is a major feature of radiation nephropathy; an explanation for the efficacy of RAS antagonism in the prophylaxis of radiation nephropathy would be that radiation leads to RAS activation. However, current studies favor an alternative explanation, namely that the normal activity of the RAS is deleterious in the presence of radiation injury. On-going studies suggest that efficacy of RAS antagonists may involve interactions with a radiation-induced decrease in renal nitric oxide activity or with radiation-induced tubular cell proliferation. We hypothesize that while prevention (prophylaxis) of radiation nephropathy with ACE inhibitors, AII receptor antagonists, or a high-salt diet work by suppression of the RAS, the efficacy of ACE inhibitors and AII receptor antagonists in treatment of established radiation nephropathy depends on blood pressure control.

Dietary sodium modification and experimental radiation nephropathy.

PURPOSE: To determine whether suppression of the renin-angiotensin system (RAS) with high dietary sodium (salt) has the same beneficial effect on radiation nephropathy as suppression of the RAS with angiotensin-converting-enzyme (ACE) inhibitors or angiotensin II (AII) receptor antagonists. MATERIALS AND METHODS: Normal and irradiated rats were placed on high- or low-salt diets and assessed for effects on blood pressure, on AII levels and on the development of radiation nephropathy. RESULTS: In unirradiated animals, a high-salt diet suppressed AII and caused hypertension, while a low-salt diet produced no detectable effects. Use of a high-salt diet 3-9 weeks after irradiation exacerbated radiation-induced hypertension but attenuated the development of radiation nephropathy. Continuous use of a high-salt diet slowed the progression of radiation nephropathy, but eventually exacerbated radiation-induced hypertension and accelerated renal failure. Use of a high-salt diet in animals with established radiation nephropathy was deleterious. A low-salt diet had no effect on the development of radiation nephropathy. CONCLUSIONS: These studies provide further support for the hypothesis that the beneficial effect of AII receptor antagonists, ACE inhibitors and high dietary sodium in the prophylaxis of radiation nephropathy is due to their suppression of the RAS, not to their anti-hypertensive effects.

B-cell lymphoma of the external auditory meatus.

A 53-year-old female presented with a painful swelling within her external auditory meatus. Biopsies revealed this to be a B-cell lymphoma and she underwent surgical treatment followed by chemotherapy. This is the first reported case of non-Hodgkin's lymphoma of the external auditory meatus in an human immunodeficiency virus (HIV)-negative patient.

Blindness following medial maxillectomy.

Medial maxillectomy via lateral rhinotomy approach is used in the treatment for tumours affecting the lateral nasal wall. The most frequent complications are crusting, epicanthal scarring and epiphora. The authors report a rare case of blindness secondary to indirect optic neuropathy following medial maxillectomy undertaken to treat a malignant melanoma arising in the lateral nasal wall. It is important to keep in mind, the possibility of this rare complication, while patients are being counselled preoperatively for medial maxillectomy.

Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker.

Nephropathy, interstitial pneumopathy, and renal and lung fibrosis are major complications of bone marrow transplantation (BMT). This study evaluated the antifibrotic property of an angiotensin II (A2) type-1 receptor blocker (L-159,809) and compared it with those of Captopril and Enalapril, two angiotensin-converting enzyme (ACE) inhibitors, in a rat model of BMT. Male WAG/Rij/MCW rats received a preparative regimen of 60 mg/kg body wt of cytoxan (i.p., Days 9 and 8) and 18.5 Gy of total body irradiation (TBI) in six twice daily fractions (Days 2, 1, and 0) followed immediately (Day 0) by BMT. Modifiers were given in drinking water from Day 10 until autopsy, 8 weeks after BMT. Rats treated with TBI plus cytoxan alone developed severe nephropathy. Trichrome staining showed marked collagen deposition in glomeruli, renal interstitium, and renal arteries and arterioles (especially in their adventitia). Collagen deposition and renal damage were markedly reduced by the three modifiers. Of the three, L-158,809-treated rats had slightly thinner vessels and slightly less collagen than nonirradiated normal controls. The study shows the effectiveness of these drugs in the protection of the renal parenchyma from the development of radiation-induced fibrosis. It also indicates a role for angiotensin II in the modulation of collagen synthesis.

Induction of heme oxygenase 1 in radiation nephropathy: role of angiotensin II.

Datta, P. K., Moulder, J. E., Fish, B. L., Cohen, E. P. and Lianos, E. A. Induction of Heme Oxygenase 1 in Radiation Nephropathy: Role of Angiotensin II. Radiat. Res. 155, 734-739 (2001). In a rat model of radiation-induced nephropathy, we investigated changes in expression of heme oxygenase 1 (Hmox1, also known as HO-1), an enzyme that catalyzes conversion of heme into biliverdin, carbon monoxide and iron. The study explored whether radiation induces Hmox1 expression in the irradiated kidney and whether angiotensin II (AII) mediates Hmox1 expression in glomeruli isolated from irradiated kidneys. To assess the effects of radiation on Hmox1 expression, rats received 20 Gy bilateral renal irradiation and were randomized to groups receiving an AII type 1 (AT(1)) receptor antagonist (L-158,809) or no treatment. Drug treatment began 9 days prior to bilateral renal irradiation and continued for the duration of the study. Estimation of Hmox1 levels in glomerular protein lysates assessed by Western blot analysis revealed a significant increase in Hmox1 protein at 50 and 65 days postirradiation. In animals treated with the AT(1) receptor antagonist, there was no induction of Hmox1, suggesting that AII may be a mediator of Hmox1 induction. To confirm that AII stimulates Hmox1 expression, animals were infused with 200, 400 or 800 ng/kg min(-1) of AII for 18-19 days, and Hmox1 protein levels in glomeruli were assessed. There was a significant induction of Hmox1 in glomeruli of animals infused with 800 ng/kg min(-1) of AII. These studies demonstrate that glomerular Hmox1 expression is elevated in the middle phase of radiation nephropathy and that AII can increase glomerular Hmox1 levels.

Early detection of radiation-induced glomerular injury by albumin permeability assay.

Renal irradiation leads predictably to glomerular vascular injury, cell lysis, matrix accumulation, sclerosis and loss of renal function. The immediate effects of renal irradiation that may be associated with glomerular pathology and proteinuria are not clear in the human disease or its rat model. We hypothesized that radiation-induced injury causes immediate and subtle alterations in glomerular physiology independent of the neurohumoral and hemodynamic regulatory mechanisms. We employed a sensitive in vitro functional assay of glomerular albumin permeability (P(alb)) to demonstrate radiation-induced damage to the glomerular filtration barrier immediately after total-body irradiation of rats. In blinded experiments, control rats were sham-treated, and experimental rats received 9.5 Gy X rays. Rats were killed humanely at 1 h to 9 weeks after irradiation and glomeruli were isolated. In parallel experiments, glomeruli were isolated from normal rats and irradiated in vitro. The change in glomerular capillary permeability due to an experimental oncotic gradient was determined using videomicroscopy and P(alb) was calculated. Results show that in vivo or in vitro irradiation of glomeruli caused an increased P(alb) at 1 h. Increased P(alb) was observed up to 3 weeks after irradiation. Glomeruli from mice irradiated with 9.5 or 19.0 Gy X rays did not show increased P(alb) at 1 h postirradiation. We conclude that glomerular protein permeability of irradiated rats increases in a dose-dependent manner immediately after irradiation and that it appears to be independent of hemodynamic or systemic influences.