Piroxicam and doxycycline treatment for an oral squamous cell carcinoma in an inshore bottlenose dolphin (Tursiops aduncus).

BACKGROUND: The virus family Papillomaviridae has been documented in a wide range of animal species and can cause benign and malignant proliferative lesions. The presence of concurrent lingual papillomas and squamous cell carcinomas (SCC) in cetaceans has also been documented in both wild and captive populations, suggesting malignant transformation of benign papilloma to SCC may occur in this species. CASE REPORT: In 2008, a 38-year-old captive male inshore bottlenose dolphin (Tursiops aduncus) was diagnosed with papillomatous lesions on the intermandibular frenulum rostral to the tongue and an infiltrative SCC of the soft palate following biopsy and histological analysis. A treatment regimen of piroxicam and doxycycline was initiated with misoprostol as a gastroprotectant. The treatment resulted in a marked reduction in tumour size and reversible hepatotoxicosis. Subsequent biopsies revealed the presence of SCC in the oral cavity; however, the disease remains stable at the time of writing. CONCLUSION: To the best of our knowledge, this case is the first report of piroxicam and doxycycline used to treat SCC in a bottlenose dolphin. The treatment was successful in reducing the clinical presentation of the disease.

Processionary caterpillar setae and equine fetal loss: 1. Histopathology of experimentally exposed pregnant mares.

Six pregnant Standardbred mares aged between 6 and 14 years were gavaged with 50 g or 100 g of suspended emulsified whole Processionary caterpillars (Ochrogaster lunifer) for 5 days during 2 experiments undertaken to study the etiology of equine amnionitis and fetal loss (EAFL). The 6 treated mares and 1 untreated mare were between 128 and 252 days gestation. Mare 1 (untreated) was euthanized on day 5 of the treatment period, while the treated mares were euthanized on days 2, 4, 8, 10, 12, and 24 days from their first treatment. Caterpillar setae were not found in the untreated mare. Setal fragments were present in all regions of the gastrointestinal tracts in all treated mares, the uteri and mesenteric lymph nodes of 5 mares, and the liver of 4 mares. Acute gastroenteritis of varying severity was present in all treated mares, and 5 of 6 mares had acute colitis and endometritis. Focal hyperplastic serositis was found in the duodenum, cecum, dorsal colon, and uteri of various mares occasionally with embedded setal fragments. Setal invasion of the mucosa evoked a range of lesions including superficial erosion to deep ulceration. Inflammation in deeper tissues ranged from unapparent to neutrophilic (microabscesses), eosinophilic, or mononuclear (microgranulomas). The finding of setal fragments within the uterus of experimental mares suggests that direct migration of setal fragments acting as a bacterial vector is a likely mechanism for the bacterial abortions that characterize equine amnionitis and fetal loss.

Processionary caterpillar setae and equine fetal loss: 2. Histopathology of the fetal-placental unit from experimentally exposed mares.

Pregnant mares were experimentally exposed to whole caterpillar or exoskeleton of the Processionary caterpillar (Ochrogaster lunifer) via gavage. Tissues were collected from resulting abortions and near or full-term pregnancies consisting of 13 aborted fetuses, 3 fetuses from treated euthanized mares, membranes of 5 foals, and organs from 3 foals. Three control membranes and 1 control fetus and membranes were examined. Caterpillar setal fragments were present in the allantochorion of the 3 fetuses from the euthanized mares and 11 of 12 aborted fetuses (92%) embedded in the chorion (villi or stroma) or allantois (vasculature or stroma). Placental locations of fragments ranged from the cervical pole region to the body encompassing the umbilical insertion and pregnant horn. Numbers in each fetus ranged from 1 to 7 fragments. Setae were present in the allantochorion from 2 to 22 days after the initial treatment. Acute to chronic active inflammation was present in all aborted fetuses, all euthanized fetuses, and within at least 1 tissue level (chorion, allantois, umbilical cord, or amnion) of the membranes from full-term foals. Amnionitis, funisitis, and allantoitis were present in 95% of the examined membranes. Pneumonia was present in 95% of the specimens, and bacteria were present histologically in 90.5% of the specimens with or without accompanying inflammation. The rapid migration of setae within 2 days after mare exposure suggests that direct setal migration into the fetal membranes is a likely initiating factor for equine amnionitis and fetal loss (EAFL).

Equine multinodular pulmonary fibrosis in three horses in Australia.

BACKGROUND: Equine multinodular pulmonary fibrosis (EMPF) is a recently described form of interstitial pneumonia associated with the presence of equine herpesvirus type 5 (EHV-5). Since 2007, several case reports from America, Europe and the United Kingdom have further characterised the clinical presentation and laboratory findings of this disease. CASE REPORTS: Three Thoroughbred broodmares were diagnosed with EMPF. Diagnosis was based on lung histopathology and positive identification of EHV-5 using PCR DNA amplification. There was multiple organ involvement in all three cases, including identification of EHV-5 in hepatic tissue in one case. Two of the three horses died. Treatment with acyclovir was unsuccessful in one horse and one horse survived without antiviral or corticosteroid treatment. CONCLUSION: This case series is, to the authors' knowledge, the first report of EMPF in Australia and adds to the clinical description of the disease.

Bacteria isolated from field cases of equine amnionitis and fetal loss.

BACKGROUND: A series of unusual abortions occurred in Thoroughbred and Quarterhorse mares in the Hunter Valley region of New South Wales from mid-March to November 2004. The initial link between early cases was the microbiological culture of atypical environmental coryneforms from the stomach contents and/or lungs of fetuses aborted on different properties. METHODS: The unique pathologic lesions were described with a case definition and the term 'equine amnionitis and fetal loss' (EAFL) was established. RESULTS: The causal factor was the ingestion of the processionary caterpillar (Ochrogaster lunifer). Bacteria from the Actinomycetales order were isolated from 40% of the combined suspect and confirmed EAFL cases and included Microbacterium arborescens, Cellulomonas sp., Arthrobacter spp. and Cellulosimicrobium sp. Other bacteria isolated included various Gram-negative bacilli and Gram-positive cocci. CONCLUSIONS: Although the predominant type of bacteria isolated from EAFL was environmental coryneforms, it is important to note that a variety of bacteria were associated with the characteristic histopathological changes outlined by the case definition. This highlights the importance of histopathology on both fetal membranes and fetuses, as well as culture to confirm EAFL and to exclude other possible causes of abortion.

Idiopathic haemarthrosis in eight horses.

OBJECTIVES: To review eight horses diagnosed with idiopathic haemarthrosis and to describe the intra-articular use of yttrium-90 ((90) Y) and methylprednisolone acetate (MPA) in recurrent haemarthrosis cases. DESIGN: Retrospective case series. METHOD: The medical records, diagnostic images, histopathology and outcome of all horses diagnosed with idiopathic haemarthrosis between 1998 and 2010 were reviewed. RESULTS: Four Thoroughbred racehorses with haemarthrosis of the antebrachiocarpal joint had severe acute lameness (median, grade 4) and marked joint effusion after high-speed exercise. Another four horses (2 Thoroughbred racehorses, 1 Standardbred racehorse, 1 Warmblood) had haemarthrosis of the tarsocrural joint and presented with mild, intermittent lameness (median, grade 1) and marked, persistent joint effusion. Six of the eight horses had recurrent haemarthrosis prior to treatment. Radiographic and nuclear scintigraphic examinations did not identify bone pathology. Diagnostic arthroscopy (7 cases) identified grossly hypertrophied yellow/brown discoloured synovium. Synovial histopathology of these cases revealed chronic synovial hyperplasia with severe haemosiderosis and granulomatous inflammatory reaction of varying severity. All horses underwent rest, bandaging and phenylbutazone administration. Two horses had subtotal mechanical synovectomy, four horses had intra-articular administration of (90) Y and MPA, and one horse underwent both treatments. Seven cases returned to their previous use (median time, 7 months). Haemarthrosis recurred in three horses, two of which had received the (90) Y and MPA treatment. CONCLUSION: Idiopathic haemarthrosis should be considered a differential for acute and recurrent joint related lameness and effusion. Recurrence appears not uncommon and the use of intra-articular (90) Y and MPA in conjunction with a conservative management treatment protocol warrants further evaluation.

Pathological changes in horses dying with equine influenza in Australia, 2007.

Analysis of pathology results from the 2007 equine influenza (EI) outbreak in Australia indicate that young foals in naïve horse populations are prone to developing broncho-interstitial pneumonia, and that this can be a rare manifestation of EI virus infection in mature horses. All horses may develop secondary bacterial bronchopneumonia, with mature horses more likely to die. EI outbreaks among heavily pregnant mares can result in increased neonatal losses because of premature placental separation and dystocia causing fetal hypoxia.

Acute lameness associated with osseous metastasis of a peri-renal carcinoma in a horse.

We present a case of aggressive metastatic carcinoma in a horse that was initially presented for shoulder lameness. Although radiography and scintigraphy were useful for localising a lesion in the proximal humerus, subsequent development of non-specific signs of systemic disease prompted further evaluation. Haematology and blood biochemistry, urinalysis and ultrasonography were all instrumental in identifying renal involvement. A diagnosis of a peri-renal mass causing secondary renal failure prompted euthanasia of the horse because of the poor prognosis. Antemortem findings were supported by necropsy, with secondary lesions also identified in the spleen, liver, 8th left rib and proximal humerus. Histological examination yielded a diagnosis of undifferentiated metastatic carcinoma.

Retrospective study of 108 foals with septic osteomyelitis.

OBJECTIVE: To determine the clinical characteristics, short-term outcome and future athletic performance of foals with septic osteomyelitis. DESIGN: Retrospective clinical study of 108 Thoroughbred foals with radiographic evidence of bone infection that were presented at the Scone Veterinary Hospital between August 1995 and December 2001. Medical records were reviewed and information concerning signalment, the clinical, laboratory and radiographic findings, treatment and outcome was obtained. Racing records were obtained and evaluated for surviving foals that had reached racing age. RESULTS: Mean age of foals at initial evaluation was 39 days (range 1-180 days); 21 foals had multiple radiographic bone lesions (19.4%), and 76 had concurrent septic arthritis (70.4%). The most frequently affected bones were the femur, tibia and distal phalanx. In total, 87 foals were discharged from the hospital (80.6%), 79 survived long-term to reach racing age and 52 raced (65.8%). Overall, 48% (52/108) of the foals treated for osteomyelitis raced. Foals less than 30 days of age at the time of diagnosis, critically ill foals and those with multiple bones or joints affected were significantly less likely to be discharged from hospital. Multiple septic joints, but not multiple bone involvement, had an unfavourable prognosis for racing. CONCLUSIONS: The prognosis for survival of foals with septic osteomyelitis or osteitis is favourable. Multiple bone or joint involvement is an important short-term prognostic indicator; however, the involvement of multiple joints, but not multiple infected bones, is associated with an unfavourable prognosis for racing.

Equine amnionitis and fetal loss: the case definition for an unrecognised cause of abortion in mares.

A series of abortions occurred in mares in New South Wales during 2004 that involved similar and unusual findings on post mortem examination of aborted fetuses and fetal membranes. The term Equine Amnionitis and Fetal Loss (EAFL) was developed to describe the condition. This form of abortion had not been previously recognised in Australia. The pathology alone is not specific for EAFL and diagnosis requires demonstration of a combination of certain pathological and bacteriological features. The purpose of this paper is to describe patterns considered consistent with EAFL cases as a working case definition for use by veterinarians and veterinary pathologists in identifying future cases of EAFL. More detailed papers are in preparation to fully describe the epidemiological, histopathological, and microbiological aspects of EAFL.

Erythrocytosis and pleural effusion associated with a hepatoblastoma in a Thoroughbred yearling.

A 10-month-old Thoroughbred filly was presented with a 2-month history of recurrent fever and pleural effusion. Major clinical findings were pyrexia and congested mucous membranes. Clinical pathology tests revealed an erythrocytosis, hyperfibrinogenaemia and hyperglobulinaemia. Pleural fluid was seen on ultrasonographic examination of the thorax and analysis of a thoracocentesis sample indicated a lymphocytic, modified transudate. A transtracheal aspirate was normal. The erythrocytosis persisted despite IV fluid therapy. Arterial blood gas analysis and bone marrow aspirate were normal. These findings were indicative of secondary inappropriate erythrocytosis. Ultrasonographic examination of the abdomen showed a large encapsulated heterogeneous mass in the left lobe of the liver. Histopathological evaluation of a biopsy of the mass was indicative of a hepatic carcinoma. The filly was euthanased and necropsy confirmed the presence of a hepatic tumour with no evidence of systemic metastasis. Further histopathological evaluation confirmed the tumour to be an embryonal macrotrabecular epithelial-type hepatoblastoma, a type of hepatoblastoma that has not previously been reported in a horse.

Blood culture isolates and antimicrobial sensitivities from 427 critically ill neonatal foals.

OBJECTIVE: To assist correct decision-making about antimicrobial treatment of equine neonates with septicaemia. DESIGN: Retrospective study of microbial blood culture results obtained from foals less than 7 days of age. METHODS: Microbial blood culture results from foals less than 7 days of age admitted to an intensive care unit between July 1999 and December 2004 were reviewed. Antimicrobial sensitivity was assessed by the Kirby Bauer disc diffusion method. Antimicrobials were defined as an effective first-line choice antimicrobial if greater than 70% of isolates were susceptible. Multiple drug resistance (MDR) was defined as resistance to at least three antimicrobials in different chemical classes or with different mechanisms of resistance. RESULTS: Of the 427 Thoroughbred foals included in the study, a positive blood culture was obtained in 110 foals and 124 microorganisms were isolated. Gram-positive isolates, predominantly Streptococcus/Enterococcus spp, were obtained in 41% of foals. Gram-negative isolates were predominantly of the Enterobacteriaceae family, in particular Escherichia coli. The overall antimicrobial sensitivity of the isolates was low. The Gram-positive organisms had unpredictable sensitivity patterns. MDR was recorded in 32% of isolates. In total, 81% of foals were discharged from hospital and 74.5% of foals with a positive blood culture were discharged. CONCLUSION: With the increasing prevalence of Gram-positive microorganisms and their unpredictable sensitivity patterns, blood cultures remain important in the diagnosis and treatment of equine neonatal septicaemia.

The pathology of bronchointerstitial pneumonia in young foals associated with the first outbreak of equine influenza in Australia.

REASONS FOR PERFORMING STUDY: The first outbreak of equine influenza virus (EIV) infection was confirmed in Australia in 2007. Some EIV-positive young foals died with bronchointerstitial pneumonia, an rare disease process in this age group that is often postulated to be caused by viral infection. OBJECTIVES: The aim of this study was to describe post mortem lesions in EIV-infected foals. METHODS: Post mortem examinations were conducted on 11 young foals (age 2-12 days) submitted to the Scone Veterinary Hospital, NSW over a 2-month period in 2007. The foals had presented with or developed fatal pneumonia, and were known or suspected to be EIV-positive. Equine influenza virus nucleic acid was detected in tissue specimens using an Influenza A group reactive real-time reverse transcriptase PCR assay. RESULTS: Grossly there was diffuse or extensive pulmonary consolidation. Histological changes included: bronchiolar and alveolar necrosis; neutrophilic infiltration; hyaline membrane formation; and hyperplasia and squamous metaplasia of airway epithelium. Tissues for 10 foals were EIV-positive, with a positive nasal swab from the remaining animal. CONCLUSIONS: This is the first detailed pathological description of bronchointerstitial pneumonia associated with EIV infection in young foals. It is also the first series of such cases in which a causative agent has consistently been detected. POTENTIAL RELEVANCE: Given the findings in this outbreak, and a previous outbreak in the UK in 1965 involving a similarly naive population, veterinary clinicians and pathologists should be aware that EIV can cause fatal bronchointerstitial pneumonia in young foals that do not have maternal immunity. The lesions did not differ from those previously reported in foals of various ages with bronchointerstitial pneumonia of other or undefined causes, indicating that this is most likely a stereotypical response to a variety of insults. Therefore, tissue specimens should be obtained from cases of pneumonia in young foals for virological and bacteriological testing.

Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor.

PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.

Insulin for type 2 diabetes: choosing a second-line insulin regimen.

UNLABELLED: Guidance has been published on the choice of initial insulin regimen for patients with type 2 diabetes [NPH (isophane) insulin or a long-acting insulin analogue] but not on how to choose a second regimen when glycaemic control becomes unsatisfactory. AIMS: To develop pragmatic clinical guidance for choosing a second-line insulin regimen tailored to the individual needs of patients with type 2 diabetes after failure of first-line insulin therapy. METHODS: Formulation of a consensus by expert panel based on published evidence and best clinical practice, taking into account patient preferences, lifestyle and functional capacity. RESULTS: Six patient-dependent factors relevant to the choice of second-line insulin regimen and three alternative insulin regimens (twice-daily premixed, basal-plus and basal-bolus) were identified. The panel recommended one or more insulin regimens compatible with each factor, emphasising the fundamental importance of a healthy lifestyle that includes exercise and weight reduction. These recommendations were incorporated into an algorithm to provide pragmatic guidance for clinicians. CONCLUSION: The three alternative insulin regimens offer different benefits and drawbacks and it is important to make the right choice to optimise outcomes for patients.

Serum and plasma cardiac troponin I concentrations in clinically normal Thoroughbreds in training in Australia.

Cardiac troponin I is a potentially useful test to identify cardiac muscle damage in the horse. Measurements of cardiac troponin I from serum or heparinised plasma samples from 23 clinically normal Thoroughbred horses in race training were analysed through a standard Australian commercial laboratory using the ADVIA Centaur Assay. The cardiac troponin I concentrations were < 0.15 microg/L from all samples. The test was then validated using macerated equine myocardium. Cardiac troponin I concentration may be useful in determining whether poor performance in Thoroughbred horses is related to active myocardial disease.

Hypoxia in head and neck cancer: how much, how important?

BACKGROUND: Hypoxia develops in tumors because of a less ordered, often chaotic, and leaky vascular supply compared with that in normal tissues. In preclinical models, hypoxia has been shown to be associated with treatment resistance and increased malignant potential. In the clinic, several reports show the presence and extent of tumor hypoxia as a negative prognostic indicator. This article reviews the biology and importance of hypoxia in head and neck cancer. METHODS: A review of literature was carried out and combined with our own experience on hypoxia measurements using exogenous and endogenous markers. RESULTS: Hypoxia can increase resistance to radiation and cytotoxic drugs and lead to malignant progression, affecting all treatment modalities, including surgery. Hypoxia measurements using electrodes, exogenous bioreductive markers, or endogenous markers show the presence of hypoxia in most head and neck cancers, and correlations with outcome, although limited, consistently indicate hypoxia as an important negative factor. Each hypoxia measurement method has disadvantages, and no "gold standard" yet exists. Distinctions among chronic, acute, and intermediate hypoxia need to be made, because their biology and relevance to treatment resistance differ. Reliable methods for measuring these different forms in the clinic are still lacking. Several methods to overcome hypoxia have been tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins (tirapazamine), and carbogen showing some success. New treatments such as hypoxia-mediated gene therapy await proper clinical testing. CONCLUSIONS: The hypoxia problem in head and neck cancer needs to be addressed if improvements in current treatments are to be made. Increased knowledge of the molecular biology of intermediate, severe, and intermittent hypoxia is needed to assess their relevance and indicate strategies for overcoming their negative influence.

Assessment of postsurgical recovery after discharge using a pen computer diary.

We assessed patients after their return home following gynaecological surgery, using a daily electronic diary. Thirty-two females aged 27-77 years took part. After a hospital stay of 1-6 days (mean 2.3), they were given a pen-based electronic diary and asked to record symptoms and other data over one month. They also completed a questionnaire at the end of the study. Substantial effects on quality and duration of sleep, pain during both the night and day, interference with daily activities, energy, and ability to concentrate were recorded, mostly during the first week of treatment. Symptoms reported in the final questionnaire correlated significantly with diary data. Most patients found the electronic diary easy to use, and none found it difficult. Daily electronic diaries are an acceptable method of obtaining better information on the extent and duration of symptoms and other difficulties after discharge following surgery.

Rapid fluorescence ratio assay for detecting changes in radiosensitivity.

To test modifications in sensitization to radiation or drugs in preclinical studies of cancer therapy, the colony-forming assay is regarded as the gold standard. Because this assay is time consuming, somewhat laborious, and unsuitable for rapid screening, development of other assays is desirable. We describe here an assay based on the detection of enhanced green fluorescence protein (EGFP) with flow cytometry that is particularly suitable for genetic manipulation studies in which the gene of interest is introduced together with EGFP as reporter. It is easily adaptable to other reporters, however, whether naturally fluorescent or requiring immunochemical staining. Cells are irradiated as mixed populations of a known standard cell line (nonfluorescent) together with the genetically manipulated cell line expressing EGFP. Ratios of fluorescent and nonfluorescent cells are measured before treatment and several days after treatment. If the cell populations have equal radiosensitivities, the ratio remains unchanged. Changes in the ratio indicate changes in radiosensitivity. The assay was validated for two situations in which dominant negative peptides inhibiting DNA repair were expressed in A549 human lung cells and affected radiosensitivity.

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation.

Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60 +/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively.