Operative tactics in floor of mouth and tongue cancer resection - the importance of imaging and planning.

Complete tumour resection (R0 margin) is an axiom of surgical oncology. Oral cancer ablation is challenging, due to anatomical, functional, and aesthetic considerations. R0 margin is strongly linked to better survival outcomes with great variation in the R0 % across units. This is commonly attributed to disease biology. Without disputing the importance of biological characteristics, we contend that image-based anatomical surgical planning has an important role to play in achieving complete resection. Here, we present our approach utilising cross-sectional imaging, anatomical characteristics and spatial awareness in planning resections for floor of mouth (FOM) and oral tongue cancers. We highlight the challenge of controlling the deep tumour margin lingual to mandible due to anterior vector constraints and emphasise the importance of resecting the genial muscles in a planned fashion and that any rim resection should be obliquely sagittal. In resecting lateral FOM tumours, assessing extension to the parapharyngeal fat is crucial; and mandibular rim resection at a sagittal plane below the mylohyoid line is often required. Assessing the proximity of the contralateral neurovascular pedicle, pre-epiglottic space and hyoid bone are crucial parameters to determine the extent of tongue tumour resection. Our cohort included 173 patients with FOM SCC and 299 patients with tongue SCC. Six patients (3.5%) from the FOM group and eight patients (3%) from the tongue group had involved (R1) margins following surgery. This was associated with local relapse (p<0.05). In conclusion, we demonstrate that image-based planning can aid achieving R0 resections and reduce disease relapse.

Postoperative delirium in patients with head and neck oral cancer in the West of Scotland.

Our aims were to determine the prevalence and association of postoperative delirium (POD) in head and neck (H&N) cancer patients undergoing free flap reconstruction at the oral and maxillofacial surgery (OMFS) unit, Queen Elizabeth University Hospital (QEUH) Glasgow, and to assess whether these determinants can be modified to optimise patient care and reduce the occurrence of POD. Delirium remains an important problem in the postoperative care of patients undergoing major H&N surgery, and early detection and management improve overall outcomes. The patient database containing details of the preoperative physical status (including alcohol misuse, chronic comorbidity, and physiological status) of 1006 patients who underwent major H&N surgery with free-flap repair at the QEUH from 2009-2019, was analysed. Factors associated with delirium were studied, identifying univariate associations as well as multivariate models to determine independent risk factors. The incidence of POD was 7.5% (75/1006; 53 male:22 female; mean (SD) age 65.41 (13.16) years). POD was strongly associated with pre-existing medical comorbidities, excess alcohol, smoking, a prolonged surgical operating time (more than 700 minutes), tracheostomy, blood transfusion, and bony free flaps. Those with POD were at an increased risk of postoperative wound and lung complications, and were more likely to require a hospital stay of more than 21 days. Presurgical assessment should identify risk factors to optimise the diagnosis and treatment of POD, and will enhance patient care by reducing further medical and surgical complications, and overall hospital stay.

Postoperative risk stratification in oral squamous cell carcinoma.

Postoperative prognostic stratification using the Union for International Cancer Control (UICC) TNM 8th edition staging rules (UICC 8) may identify additional groups of patients who could benefit from adjuvant radiotherapy. Currently, selection for such treatment is not based on all known prognostic factors, and their relative importance may vary depending on the overall risk category. The objective of this study therefore was to evaluate these possibilities. We retrospectively studied 644 patients who had surgery with curative intent for oral squamous cell carcinoma (OSCC) between March 2006 and February 2017. The outcomes of interest were disease-specific survival (DSS) and locoregional recurrence (LRR). Patients were re-staged according to the UICC 8 staging rules. Putative clinical and pathological prognostic variables were evaluated and hazard ratios estimated. Regression analysis was done to identify independent prognostic factors, and iterative analyses identified clinically-relevant risk categories with a minimum of residual prognostic variables. The significance of recognised pathological prognostic factors differed according to the overall risk category. An intermediate risk group comprising patients with pN1 disease as well those with pT3 disease solely on the basis of a depth of invasion (DOI) of more than 10 mm, was identified. A trial to evaluate the benefit or otherwise of adjuvant radiotherapy in this group is now required. Individual prognostic risk factors should be considered within the context of the overall risk category in patients with OSCC.

Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?

Depth of invasion is an important predictor of survival. A study by the International Consortium (ICOR) for Outcome Research proposed incorporation of it (together with the greatest surface dimension, or the anatomical criteria, or both) into the T stage. This has been adopted in part by the 8th edition of the Union for International Cancer Control (UICC) TNM 8 classification of malignant tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of invasion as an independent prognostic factor, and to validate the staging by comparing it with that specified in the 7th edition (TNM 7) and the T-staging model proposed by the International Consortium. We retrospectively studied 449 patients who had had operations for a previously untreated primary oral cancer between 2006 and 2014 at a single centre, and analysed the independent predictive value of depth of invasion for both disease-specific and overall survival. It was an independent predictor of disease-specific survival as were sex, perineural invasion, and N stage. It was also an independent predictor of overall survival together with sex and N status. Staging in TNM 8 gave a better balance of distribution than that in TNM 7, but did not discriminate between prognosis in patients with T3 and T4 disease. The proposed International Consortium rules for T-staging gave an improved balance in distribution and hazard discrimination. The incorporation of depth of invasion into the T-staging rules for oral SCC improved prognostic accuracy and is likely to influence the selection of patients for adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard discrimination in patients with locally-advanced disease because its T4 staging is restricted to anatomical criteria.

Postoperative complications after head and neck operations that require free tissue transfer - prevalent, morbid, and costly.

To understand and reduce the impact of postoperative complications, we studied 568 patients who had had operations over 72 months in our hospital. Multivariate analysis indicated that factors indicative of coexisting conditions (including activated systemic inflammation) and the complexity of the operation are primary determinants of postoperative complications. The enhanced recovery after surgery (ERAS) care pathway did not have an effect on their occurrence or severity. Systematic study of patients' toleration of major head and neck operations is required, as optimal perioperative care pathways remain elusive.

Preparing for a career in oral and maxillofacial surgery: a survey of dentists at medical schools.

A questionnaire was sent to the 112 dental graduates who were doing a second degree in medicine in the United Kingdom (UK) in the academic year 2002-2003. Seventy-four students replied. The most common time from graduating from dental school to returning to medical school was 36 months. Of the 74 respondents 50 (68%) wrote that they intended to return to oral and maxillofacial surgery.

Footshock-induced freezing behavior in rats as a model for assessing anxiolytics.

A number of chemically distinct anxiolytics were examined for effects on defensive behavior (foot-shock-induced freezing) in rats. Central nervous system acting drugs which are not anxiolytics were also studied. Animals were injected with a drug or vehicle (IP) prior to being placed in a chamber with a grid floor through which two footshocks were delivered. Behavior was observed during the pre-shock period (2 min) and for 4 min after the second footshock. The effects of the following drugs on the duration of footshock-induced freezing were studied: diazepam (DZP); 2-amino-4,5-(1,2-cyclohexyl)-7 phosphonoheptonic acid (NPC 12626); 3-((+/-)-2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP); [(+)-5-methyl-10-11,dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10- imine (MK-801); buspirone hydrochloride (BUS); DL-amphetamine sulfate (AMP); haloperidol (HAL); ethyl-beta-carboline-3 carboxylate (beta-CCE). Compounds which reduced the duration of footshock-induced freezing included DZP, BUS, and the competitive NMDA antagonists NPC 12626 and CPP. The non-competitive NMDA antagonist, MK-801, had no effect on the response. The highest dose of amphetamine tested also reduced footshock-induced freezing. However, amphetamine-treated animals did not locomote or rear after footshock, suggesting fear of the environment. Animals injected with DZP, NPC 12626, CPP or buspirone spent at least 1.4 of the 4 post shock minutes locomoting. Haloperidol had no effect on freezing at the doses tested. beta-CCE tended to increase the duration of footshock-induced freezing.(ABSTRACT TRUNCATED AT 250 WORDS)

Opposite effects of spermine and arcaine on responses of N-methyl-D-aspartate receptors expressed in Xenopus oocytes.

The ability of polyamines to modulate N-methyl-D-aspartate (NMDA) receptor function was investigated in Xenopus oocytes injected with rat brain mRNA. Whereas spermine and spermidine augmented NMDA/glycine-induced inwards currents, arcaine (1,4-diguanidinobutane) and 1,10-diaminodecane inhibited the response. The potency of arcaine to inhibit NMDA/glycine-induced currents was unaffected by spermine; similarly, arcaine did not influence the potency of spermine, but did reduce the maximal response to spermine. These findings demonstrate that polyamines exert both positive and negative modulatory control of the NMDA receptor expressed in Xenopus oocytes, and suggest that spermine and arcaine act at distinct sites in the NMDA receptor complex.

Cutaneous allergy to insulin: could statins and ACE inhibitors play a role? A case report.

Insulin allergy is rare. Both statins and angiotensin converting enzyme (ACE) inhibitors may cause local urticarial skin reactions and have been implicated to precipitate local reactions to insulin. We describe a case of a localised urticarial allergic reaction related to insulin use in a patient co-prescribed an ACE inhibitor and statin.

Gastrostomy insertion in head and neck cancer patients: a 3 year review of insertion method and complication rates.

Patients with head and neck cancer who have resection, radiotherapy, chemoradiotherapy, or a combination of these require nutritional support to be implemented before treatment, and this may involve insertion of a prophylactic gastrostomy feeding tube. The aim of this study was to compare the use and complication rates of percutaneous endoscopic gastrostomy (PEG) and radiologically inserted gastrostomy (RIG) in these patients at a tertiary referral centre. We retrospectively reviewed gastrostomy data forms completed by nutritional support nursing staff over a recent 34-month period, which included information on method of insertion, 30-day postoperative serious and minor complications, and mortality. A total of 110 patients had prophylactic insertion of a gastrostomy (21 PEG, 89 RIG) over the study period. In the first 12 months 13 (31%) PEG feeding tubes were placed but in the last 12 months none were inserted using an endoscopic approach. Serious complications occurred with 2 (10%) PEG and 12 (13%) RIG; the most common cause was accidental removal of the tube (n=13, 12%). Minor complications of peristomal infection, leakage, or blockage of the tube occurred in 6 (5%) gastrostomies. No patients died during the study period. In recent years, and in the absence of recommended guidelines, there has been an increase in the elective insertion of RIG in patients with head and neck cancer. Serious complications for both methods of insertion in this study are comparable with similar reports. However, with RIG there is a high rate of tubes becoming dislodged with the potential for serious consequences. The most appropriate method to insert a gastrostomy tube in patients with head and neck cancer remains unclear.

Prevalence of ischaemic heart disease at admission to intensive care and its influence on red cell transfusion thresholds: multicentre Scottish Study.

BACKGROUND: Restrictive transfusion triggers are safe for most critically ill patients, but doubts exist for patients with ischaemic heart disease (IHD). We investigated the prevalence of reported IHD at admission to the intensive care unit (ICU) and investigated how this influenced red cell transfusion triggers. We also compared observed practice with the clinicians' responses to clinical scenarios. METHODS: We studied 1023 sequential ICU admissions over 100 days to 10 Scottish ICUs. Daily haemoglobin, red cell transfusion, and haemorrhage data were available for 99.4% of 5638 ICU patient days. We recorded if IHD was recorded in clinical records at ICU admission. We grouped admissions as having a non-cardiac primary ICU diagnosis and no documentary evidence of IHD (Group 1, n=697), a non-cardiac primary ICU diagnosis with evidence of IHD (Group 2, n=213), or a cardiac primary ICU admission diagnosis (Group 3, n=113). We examined pre-transfusion haemoglobin concentration (Hb) for transfusion episodes not associated with haemorrhage. Clinical transfusion scenarios were sent to intensivists in the ICUs after data collection, which were designed to explore the clinicians' attitude to transfusion triggers in patients with IHD. RESULTS: Previous myocardial infarction was documented in 159 (16%), cardiac failure in 142 (14%), and angina in 167 (16%). Overall, 28.8% of admissions had >/=1 of these documented. The adjusted mean (se) pre-transfusion Hb concentrations varied across the groups. These were 74 (2.2) g litre(-1) in Group 1, 77 (2.3) g litre(-1) in Group 2, and 79 (3.1) g litre(-1) in Group 3 (P=0.003 across the groups). There was concordance between observed practice and responses to the scenario similar to Group 1, but discordance for patients with IHD (Groups 2 and 3). In scenario responses, intensivists stated these patients should have significantly higher transfusion triggers than were actually observed (median [IQR] response for both groups: 90 [80-100] g litre(-1)). CONCLUSIONS: About 29% of patients admitted to Scottish ICUs had documented IHD, which was associated with small adjustments to Hb transfusion triggers. In response to scenarios, clinicians believe that patients with IHD require higher transfusion triggers than are observed in practice.

The chief scientist reports ... hyperbaric oxygen for multiple sclerosis patients.

An 18-month uncontrolled study of the effects of hyperbaric oxygen therapy was conducted in 97 individuals with multiple sclerosis. Two-thirds of the patients were classified as progressive and one-third as stable. Assessment was based mainly on three aspects of activities of daily living: bladder function, mobility and communication. Bladder function showed a tendency to improve over the 12 month period of treatment but there was no evidence that treatment led to an improvement of mobility or communication. There are several reports of immediate improvement in bladder function, objectively and subjectively determined, in response to hyperbaric oxygen. In one study similar to that reported here, lack of deterioration in bladder function amongst progressive patients over two years, was related to continued hyperbaric oxygen treatment.

Outpatient treatment trial of mild and severe hypertension.

Not much is known about the feasibility or the advantages of treatment of subjects with only mild hypertension. There are also many unresolved problems in the outpatient management of hypertension of any severity. In this study an analysis is made of the results of a controlled treatment trial of 56 subjects with mild hypertension, 26 of whom were treated with active drug and 30 initially with placebo, and a treatment programme involving 81 patients with moderate or severe hypertension, all of whom received treatment with active drug. The drugs used in this study were bethanidine, debrisoquine, and guanethidine.Follow-up for 12 months or more was achieved in 87% of individuals admitted to the study with mild hypertension and in 80% with severe hypertension. Many subjects with only mildly raised blood pressure were found to have cardiac enlargement on chest x-ray (up to 45%) and left ventricular hypertrophy on electrocardiogram (up to 51%). Rapid rates of rise of blood pressure were observed in many placebo-treated subjects; but good blood pressure control was achieved in 63 out of 104 patients (61%) receiving active drug in both the mild and the severe hypertension groups. The drugs used showed approximately equal effectiveness in controlling blood pressure.

The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.

Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035; P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 x 10(9)/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32 (P = . 004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.