Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation?

GOALS OF WORK: In patients with locally advanced esophageal cancer, only those responding to the treatment ultimately benefit from preoperative chemoradiation. We investigated whether changes in subjective dysphagia or eating restrictions after two cycles of induction chemotherapy can predict histopathological tumor response observed after chemoradiation. In addition, we examined general long-term quality of life (QoL) and, in particular, eating restrictions after esophagectomy. MATERIALS AND METHODS: Patients with resectable, locally advanced squamous cell- or adenocarcinoma of the esophagus were treated with two cycles of chemotherapy followed by chemoradiation and surgery. They were asked to complete the EORTC oesophageal-specific QoL module (EORTC QLQ-OES24), and linear analogue self-assessment QoL indicators, before and during neoadjuvant therapy and quarterly until 1 year postoperatively. A median change of at least eight points was considered as clinically meaningful. MAIN RESULTS: Clinically meaningful improvements in the median scores for dysphagia and eating restrictions were found during induction chemotherapy. These improvements were not associated with a histopathological response observed after chemoradiation, but enhanced treatment compliance. Postoperatively, dysphagia scores remained low at 1 year, while eating restrictions persisted more frequently in patients with extended transthoracic resection compared to those with limited transhiatal resection. CONCLUSIONS: The improvement of dysphagia and eating restrictions after induction chemotherapy did not predict tumor response observed after chemoradiation. One year after esophagectomy, dysphagia was a minor problem, and global QoL was rather good. Eating restrictions persisted depending on the surgical technique used.

Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome.

BACKGROUND Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. METHODS We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. RESULTS Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality. CONCLUSION Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.

The association of sexual behavior with oropharyngeal cancer and correlations with HPV-16 serologic status

Objectives. This hospital-based case-case study compared the characteristics of sexual behavior in patients with cancer of the oropharynx to patients with cancers of other head and neck sites. Additionally, the prevalence of certain sexual behaviors of HPV-16 seropositive head and neck cancer patients was compared to that of seronegative patients. ^ Methods. One hundred sixty five oropharyngeal cancer patients and 86 patients with cancers of other head and neck sites completed a sexual history questionnaire. ^ Results. Oropharyngeal cancer patients were significantly more likely to have had a greater number of lifetime sex partners, to have engaged in oral-genital sex, and to have had a greater number of oral-genital sex partners than non-oropharyngeal cancer patients. Oral-genital sex was significantly more common in the HPV-16 seropositive group. ^ Conclusion. These findings add to the evidence that HPV-16 is sexually transmitted to the upper aerodigestive tract and that certain sexual behaviors increase the risk for HPV-associated oropharyngeal cancer. ^

Chemoradiation therapy is effective for the palliative treatment of malignant dysphagia

Between 1993 and 2001, 106 patients with esophageal cancer were reviewed at a multidisciplinary clinic and treated with palliative intent by chemoradiation therapy. This study assesses the palliative benefit on dysphagia and documents the toxicity of this treatment. The study population comprised 72 men and 34 women with a median age of 69 years. Patients were treated with a median radiation dose of 35 Gy in 15 fractions with a concurrent single course of 5 FU-based chemotherapy. Dysphagia was measured at the beginning and completion of treatment and at monthly intervals until death, using a modified DeMeester (4-point) score. Treatment was well tolerated, with only 5% of patients failing to complete therapy. The treatment-related mortality was 6%. The median survival for the study population was 7 months. The median baseline score at presentation was 2 (difficulty with soft food). Following treatment, 49% of patients were assessed as having a dysphagia score of 0 (no dysphagia). Seventy-eight per cent had an improvement of at least one grade in their dysphagia score after treatment. Only 14% of patients showed no improvement with treatment. Fifty-one per cent maintained improved swallowing until the time of last follow-up or death. This single-institution study shows that chemoradiation therapy administered for the palliation of malignant dysphagia is well tolerated and produces a sustainable normalization in swallowing for almost half of all patients.

Clinical progression and outcome of dysphagia following paediatric traumatic brain injury: a prospective study

Objectives : To provide a preliminary clinical profile of the resolution and outcomes of oral-motor impairment and swallowing function in a group of paediatric dysphagia patients post-traumatic brain injury (TBI). To document the level of cognitive impairment parallel to the return to oral intake, and to investigate the correlation between the resolution of impaired swallow function versus the resolution of oral-motor impairment and cognitive impairment. Participants : Thirteen children admitted to an acute care setting for TBI. Main outcome measures : A series of oral-motor (Verbal Motor Production Assessment for Children, Frenchay Dysarthria Assessment, Schedule for Oral Motor Assessment) and swallowing (Paramatta Hospital's Assessment for Dysphagia) assessments, an outcome measure for swallowing (Royal Brisbane Hospital's Outcome Measure for Swallowing), and a cognitive rating scale (Rancho Level of Cognitive Functioning Scale). Results : Across the patient group, oral-motor deficits resolved to normal status between 3 and 11 weeks post-referral (and at an average of 12 weeks post-injury) and swallowing function and resolution to normal diet status were achieved by 3-11 weeks post-referral (and at an average of 12 weeks post-injury). The resolution of dysphagia and the resolution of oral-motor impairment and cognitive impairment were all highly correlated. Conclusion : The provision of a preliminary profile of oral-motor functioning and dysphagia resolution, and data on the linear relationship between swallowing impairment and cognition, will provide baseline information on the course of rehabilitation of dysphagia in the paediatric population post-TBI. Such data will contribute to more informed service provision and rehabilitation planning for paediatric patients post-TBI.

Clinical characteristics of acute dysphagia in pediatric patients following traumatic brain injury

Primary Objective: To document the clinical characteristics of acute dysphagia in a group of pediatric patients after traumatic brain injury (TBI). Research Design: Prospective group study. Methods: Fourteen subjects (7 males, 7 females), aged 4 years 1 month to 15 years, with moderate or severe TBI (Glasgow Coma Scale [GCS] < 12). Subjects were assessed via clinical bedside examination documenting cognitive status, oromotor function, feeding function, dietary recommendations, and an indication of overall feeding severity Results: A pattern of impaired cognition, altered behavior related to feeding, severe tonal and postural deficits, oromotor, respiratory, and laryngeal impairments, and oral sensitivity issues was revealed. Conclusions: Swallowing impairment was affected by multilevel deficits, which both individually and in combination had a negative impact on swallowing competence and safety. In light of deficits identified, which could not be observed on videofluoroscopic investigation alone, this study highlighted the importance of the clinical bedside examination in assessing dysphagia in pediatric patients post-TBI for identifying targets for intervention.

The epidemiology of dysphagia: Describing the problem - are we too late?

The assessment and management of dysphagia is a rapidly growing part of speech pathology clinical practice for both adult and paediatric populations, yet there is limited information available regarding the epidemiology of dysphagia. Very few studies have defined the characteristics of the disorder, its incidence/prevalence in various populations, the natural history of the disorder or the relative risks, comorbidities and outcomes associated with dysphagia. The current paper will identify some fundamental questions that as yet remain unanswered and highlight areas of future research that are required in order for us to have a better understanding of dysphagia and inform assessment and management. In conclusion, the authors propose an epidemiological framework and highlight information needs in the field of dysphagia. This framework urges future dysphagia research to be informed and underpinned by sound epidemiological principles.

Cytokine-specific Gene-knockout Studies in Oropharyngeal Candidiasis

Oropharyngeal candidiasis is a common clinical problem encountered in patients with defects in innate or cell-mediated immunity. We have previously shown that recovery from chronic oropharyngeal candidiasis is dependent on CD4+ T-cell augmentation of neutrophil and macrophage candidacidal activity, and that the immune response is characterised by the production of cytokines such as IL-12 and IFN-gamma by cells in the local draining lymph nodes, and by the expression of TNF-alpha in the oral tissues. Objective: The purpose of this study was to elaborate on the role of these cytokines in recovery from oropharyngeal candidiasis, by using cytokine-specific gene-knockout mice. Methods: These mice are created by targeted gene mutation (tm1) of embryonic stem (ES) cells microinjected into host embryos. IL-4, IL-10, IL-12, IFN-gamma and TNF-alpha knockout mice, and appropriate controls, were infected orally with 108 viable C. albicans yeasts. The infection was quantified by swabbing the oral cavity and plating on Sabouraud's agar. Results: Tnftm1mice developed an acute severe infection characterized by an increased fungal load in the early stages of infection, but cleared the yeast within the same time frame as control mice (21 days). On the other hand, Il12btm1 mice developed a chronic oropharyngeal infection (120 days) similar to that seen in T-cell deficient (Foxn1nu/Foxn1nu) mutant mice. There was no significant difference between Il4tm1, Il10tm1, and Ifngtm1 mice and their respective controls. Conclusions: Tnftm1 mice may be rendered more susceptible through impaired recruitment of phagocytic cells, and/or impaired killing of C. albicans, whereas Il12btm1 mice may not be capable of activating naïve T-cells or inducing an appropriate cellular immune response. Supported by NHMRC and ADRF.

The use of anticholinergic agents to treat excessive oropharyngeal and tracheal secretions in palliative care

Palliative care involves a multi-professional team approach to the provision of active, holistic care for patients and their families when the patient's disease is no longer responsive to curative treatment. Patient care encompasses medical and pharmacological intervention for symptom control, together with psychological, spiritual and social support for patients and families. Care is provided by teams in hospice, hospital or community environments. Although traditionally associated with providing care for cancer patients, palliative care services are increasingly providing for patients with non-malignant disease. Symptoms commonly associated with terminal phase of disease include pain, nausea, agitation, respiratory symptoms and general fatigue. During the last few days of life, patients may become weak, resulting in difficulty taking oral medication and have periods of unconsciousness. Some patients may require drug administration via subcutaneous infusion. A proportion of patients may develop difficulty clearing respiratory secretions causing a characteristic ‘death rattle’, which although not generally considered to be distressing for the patient, is often treated with a variety of anticholinergic drugs in an attempt to reduce the ‘noisy breathing’ for the benefit of relatives and others who may be closely associated with the patient.This study examined treatment of death rattle in two Hospices focusing on objective and subjective outcome measures in order to determine the efficacy of anticholinergic regimens in current use. Qualitative methods were employed to elicit attitudes of professionals and carers working closely with the patient. The number of patients recruited and monitored were small, many confounding factors were identified which questioned firstly the clinical rationale for administering anticholinergic drugs routinely to treat death rattle and secondly, the ethics of administering drug regimens to patients to treat death rattle with the primary aim of relieving distress for others. Ethnical issues, including those of consent are discussed in relation to their impact on the methodology of end of life studies in medicines management in palliative care.