Outcomes of oral squamous cell carcinoma arising from oral epithelial dysplasia: rationale for monitoring premalignant oral lesions in a multidisciplinary clinic

Surveillance of oral epithelial dysplasia results in a number of newly diagnosed cases of oral squamous cell carcinoma (SCC). The clinical stage of oral SCC at diagnosis influences the magnitude of treatment required and the prognosis. We aimed to document the stage, treatment, and outcome of oral SCC that arose in patients who were being monitored for oral epithelial dysplasia in a dedicated multidisciplinary clinic. Those with histologically diagnosed lesions were enrolled on an ethically approved protocol and molecular biomarker study. Details of clinical and pathological TNM, operation, radiotherapy, recurrence, second primary tumour, and prognosis, were recorded in patients whose lesions underwent malignant transformation. Of the 91 patients reviewed (median follow-up 48 months, IQR 18-96), 23 (25%) had malignant transformation. All were presented to the multidisciplinary team with stage 1 disease (cT1N0M0). Of these, 21 were initially treated by wide local excision, 2 required resection of tumour and reconstruction, and 2 required adjuvant radiotherapy. At follow-up 3 had local recurrence, one had regional recurrence, one had metachronous lung cancer, and 5 had second primary oral SCC. There were further diagnoses of oral dysplasia in 5 during follow-up, and it is estimated that 76% of patients will have one or other event in 5 years. Disease-specific survival was 100% and overall survival was 96% (22/23). Median follow-up after diagnosis of oral SCC was 24 months (IQR 11-58). Specialist monitoring of oral epithelial dysplasia by a multidisciplinary team allows oral SCC to be detected at an early stage, and enables largely curative treatment with simple and usually minor surgical intervention. The high incidence of second primary oral SCC in high-risk patients with oral epithelial dysplasia further supports intensive targeted surveillance in this group.     

Immediate and Longer‐Term Stressors and the Mental Health of Hurricane Ike Survivors

Previous research has documented that individuals exposed to more stressors during disasters and their immediate aftermath (immediate stressors) are at risk of experiencing longer‐term postdisaster stressors. Longer‐term stressors, in turn, have been found to play a key role in shaping postdisaster psychological functioning. Few studies have simultaneously explored the links from immediate to longer‐term stressors, and from longer‐term stressors to psychological functioning, however. Additionally, studies have inadequately explored whether postdisaster psychological symptoms influence longer‐term stressors. In the current study, we aimed to fill these gaps. Participants (N = 448) were from population‐based study of Hurricane Ike survivors and completed assessments 2–5 months (Wave 1), 5–9 months (Wave 2) and 14–18 months (Wave 3) postdisaster. Through path analysis, we found that immediate stressors, assessed at Wave 1, were positively associated with Wave 2 and Wave 3 stressors, which in turn were positively associated with Wave 2 and Wave 3 posttraumatic stress and depressive symptoms. Wave 2 posttraumatic stress symptoms were positively associated with Wave 3 stressors, and Wave 1 depressive symptoms were positively associated with Wave 2 stressors. The findings suggest that policies and interventions can reduce the impact of disasters on mental health by preventing and alleviating both immediate and longer‐term postdisaster stressors.     

Outcomes of obese versus non-obese subjects undergoing robotic-assisted hysterectomy: a multi-institutional study

The goal of our study was to determine whether there was a difference in operative outcomes in obese versus non-obese subjects undergoing robotic-assisted hysterectomies of varying levels of difficulty. Secondarily, we sought to analyze the published outcomes between robotic-assisted hysterectomy and total laparoscopic hysterectomy in obese women at each of these levels of difficulty. This was a multi-institutional retrospective cohort study of all patients undergoing robotic-assisted hysterectomy by five gynecologic oncologists at four geographically separate locations from April 2003 to March 2008. The cohort was stratified into obese vs. non-obese groups, and defined surgical outcomes compared between groups, then further divided into three subgroups based on case difficulty level. Univariate analysis and regression analysis using SAS 9.1 was performed. We then conducted a literature search of total laparoscopic hysterectomy outcomes in obese women, dividing the resulting studies into three comparative subgroups based on surgical difficulty levels for comparison with our robotic-assisted hysterectomy results. Our cohort had 228 obese and 323 non-obese subjects. Overall, the obese group had higher blood loss and longer operative time. When further stratified by level of difficulty, obese subjects also had a higher average blood loss and longer operative time in the hysterectomy-alone subgroup. No clinically significant differences in operative outcomes exist between obese and non-obese women when utilizing the da Vinci robotic system to perform a hysterectomy, independent of case difficulty level. More prospective, controlled studies which compare the two surgical approaches of robotic-assisted and laparoscopic hysterectomy approaches are needed.     

Can sleep disturbance in depression predict repetitive transcranial magnetic stimulation (rTMS) treatment response?

Treatment for depression is not effective in all patients and it is therefore important to identify factors that can be used to tailor treatments. One potential factor is insomnia. Several repetitive transcranial magnetic stimulation (rTMS) studies have reported on this symptom, however, they did not take into account the presence of hypersomnia or that insomnia was related to their outcome measure. Our aim was to investigate whether baseline sleep disruption was related to rTMS treatment response. We pooled data from four clinical trials using rTMS to treat depression, including 139 subjects in data analysis. Insomnia was measured using the Hamilton Depression Rating Scale (HamD) sleep questions and hypersomnia from the Beck Depression Inventory (BDI). To reduce the possible impact of insomnia on our treatment response outcome we created an adjusted HamD score which omitted sleep items. Sleep disturbances were common in our study: 66% had insomnia and 38% hypersomnia. Using regression analysis with our adjusted HamD score we found no relation between baseline insomnia or hypersomnia and rTMS treatment response. Our data are consistent with previous studies; however, this is the first rTMS study to our knowledge that has attempted to dissociate baseline insomnia from the HamD outcome measure and to report no relationship between hypersomnia and rTMS outcome.     

Patients' perspective of financial benefits following head and neck cancer in Merseyside and Cheshire

The aim of this interview study was to ask patients with head and neck cancer in the Mersey region about their need for financial benefits, the advice they were given about benefits and financial matters, and the financial burden of the disease. Stratified quota sampling was by employment status, whether work had been affected by the cancer, and by sex. Of 51 interviewees (mean (SD) age 61(8) years) 20 were retired, 11 were unemployed, 13 worked full-time, and 7 worked part-time. Cancer had affected the work status of 24. Since diagnosis 57% had suffered financially; this was particularly high in those who had retired (65%), and in those whose work had been affected by cancer (79%). Quality of life had decreased in 53% as a result of the financial impact of the disease. This was most common in the unemployed (64%), and in those whose work was affected by cancer (83%). Only a quarter had been given adequate help and information about finance; this was lowest in the unemployed (18%) and highest in those who were fully employed (39%). One third (17/51) had never claimed benefits. The most common benefits were Disability Living Allowance and Incapacity Benefit. Two-thirds (21/31) had applied for benefits after diagnosis, 18 of these were directly as a result of the disease. The median (IQR) weekly income from benefits was ￡88 (￡60-170). Patients and carers need better access to financial advice. We suggest that each multidisciplinary team should have a designated benefits or financial advisor who is readily available to patients in the clinic and on the ward.     

Identifying appearance-related concerns in routine follow-up clinics following treatment for oral and oropharyngeal cancer

Facial disfigurement can be a consequence of treatment for oral or oropharyngeal cancer. Patients' concerns about appearance and the impact this has on quality of life are very important, but are often not recognised in a busy outpatient clinic. We aimed to assess concerns about appearance using the University of Washington Quality of Life questionnaire version 4 (UW-QoL) and the Patient Concerns Inventory (PCI), a self-administered questionnaire that allows patients to choose what they would like to discuss in their consultation. Prospective data were collected from 204 patients who attended routine follow-up clinics from August 2007 to mid-July 2009. Fifty-seven percent were male, 68% had cancer of the oral cavity, 78% had clinical T1-T2 tumours, 19% had node positive tumours, 44% had had radiotherapy since diagnosis, and 48% had had free-flap reconstructive surgery. They all completed the questionnaires using touch-screen computer technology at 454 clinic appointments. Appearance was raised on the inventory at 9% (42/454) of clinics, and at 10% (47/454) it was indicated as a serious problem on the UW-QoL questionnaire. Concerns about appearance were raised on the inventory or were shown to be a serious problem on the UW-QoL in 14% (64/454) of patients. The main factors associated with those who reported concerns about appearance were age (younger patients), sex (female), T stage (III and IV), and site (oropharynx). Patients who choose concerns about appearance for discussion on the UW-QoL questionnaire and not on the PCI risk being missed if only the PCI is completed. Both tools compliment the screening of patients who have problems with facial disfigurement; failure to identify them can have serious clinical and psychosocial implications.     

The absence of endogenous beta-endorphin selectively blocks phosphorylation and desensitization of mu opioid receptors following partial sciatic nerve ligation

Phosphorylation of specific sites in the second intracellular loop and in the C-terminal domain have previously been suggested to cause desensitization and internalization of the mu-opioid receptor (MOP-R). To assess sites of MOP-R phosphorylation in vivo, affinity-purified, phosphoselective antibodies were raised against either phosphothreonine-180 in the second intracellular loop (MOR-P1) or the C-terminal domain of MOP-R containing phosphothreonine-370 and phosphoserine-375 (MOR-P2). We found that MOR-P2-immunoreactivity (IR) was significantly increased within the striatum of wild-type C57BL/6 mice after injection of the agonist fentanyl. Pretreatment with the antagonist naloxone blocked the fentanyl-induced increase. Furthermore, mutant mice lacking MOP-R showed only non-specific nuclear MOR-P2-IR before or after fentanyl treatment, confirming the specificity of the MOR-P2 antibodies. To assess whether MOP-R phosphorylation occurs following endogenous opioid release, we induced chronic neuropathic pain by partial sciatic nerve ligation (pSNL), which caused a significant increase in MOR-P2-IR in the striatum. pSNL also induced signs of mu opioid receptor tolerance demonstrated by a rightward shift in the morphine dose response in the tail withdrawal assay and by a reduction in morphine conditioned place preference (CPP). Mutant mice selectively lacking all forms of the beta-endorphin peptides derived from the proopiomelanocortin (Pomc) gene did not show increased MOR-P2-IR, decreased morphine antinociception, or reduced morphine CPP following pSNL. In contrast gene deletion of either proenkephalin or prodynorphin opioids did not block the effects of pSNL. These results suggest that neuropathic pain caused by pSNL in wild-type mice activates the release of the endogenous opioid beta-endorphin, which subsequently induces MOP-R phosphorylation and opiate tolerance.