Gastrostomy dependence following pharyngolaryngectomy: The effect of preoperative tube insertion.

BACKGROUND: The aim of this study is to investigate the impact of preoperative gastrostomy in patients undergoing pharyngolaryngectomy (PL) on gastrostomy tube dependence at 6 months postoperatively. METHODS: A retrospective review of patients undergoing PL for laryngeal squamous cell carcinoma between 2005 and 2019 was performed. Parameters were collected and analyzed within the multivariate models. RESULTS: Ninety-three patients (82% male, mean age 63.4 [SD 9.4]) were included. Preoperative tube placement and pharyngocutaneous fistula (PCF) were associated with an increased likelihood of gastrostomy tube dependence at 6 months (odds ratio 6.43, CI 1.1-38.3, p = 0.041) after adjusting for multiple confounding factors. There was no difference in the incidence of delayed oral feeding, PCF, or hospital stay between the groups. CONCLUSIONS: Preoperative tube and PCF are associated with an increased likelihood of tube dependence at 6 months. Patients for preoperative tube insertion should be carefully selected and early oral feeding reintroduction should be encouraged.

Novel Strategies for Managing Retropharyngeal Lymph Node Metastases in Head and Neck and Thyroid Cancer with Transoral Robotic Surgery (TORS).

Retropharyngeal metastases are encountered in a variety of head and neck malignancies, imposing significant surgical challenges owing to their distinct location and proximity to neurovascular structures. Radiotherapy is the recommended treatment in most cases owing to its oncological efficacy. However, retropharyngeal irradiation affects the superior pharyngeal constrictor muscles and parotid glands, with the potential for long-term dysphagia and xerostomia. A younger oropharyngeal and thyroid cancer patient demographic is trending, fueling interest in treatment de-escalation strategies. Consequently, reducing radiotoxicity and its long-term effects is of special relevance in modern head and neck oncology practice. Through its unique ability to safely extirpate these traditionally difficult-to-access retropharyngeal lymph nodes via a natural orifice, TransOral Robotic Surgery (TORS) can considerably lower the surgical morbidity of retropharyngeal lymph node dissection (RPLND), compared with current existing approaches. This review summarizes the latest developments in the field, exposing current research gaps and discusses specific clinical settings where TORS could enable treatment de-escalation. In early-stage node-negative oropharyngeal cancer, single-modality surgical treatment with TORS RPLND may improve risk stratification of metastasis and recurrence in this region. TORS RPLND is also a potentially viable treatment option in salvage of an isolated retropharyngeal node recurrence or in the primary setting of a thyroid malignancy with a single positive retropharyngeal node. In time, TORS RPLND may provide an alternative de-escalation strategy in these three scenarios. However, with the reported morbidities, further prospective trials with long-term follow-up data are required to prove oncological safety and functional benefits over existing strategies.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.

Exploring the Validity and Operational Impact of Using Allied Health Assistants to Conduct Dysphagia Screening for Low-Risk Patients Within the Acute Hospital Setting.

Purpose The purpose of this study was to examine (a) the agreement between allied health assistants (AHAs) and speech-language pathologists (SLPs) when completing dysphagia screening for low-risk referrals and at-risk patients under a delegation model and (b) the operational impact of this delegation model. Method All AHAs worked in the adult acute inpatient settings across three hospitals and completed training and competency evaluation prior to conducting independent screening. Screening (pass/fail) was based on results from pre-screening exclusionary questions in combination with a water swallow test and the Eating Assessment Tool. To examine the agreement of AHAs' decision making with SLPs, AHAs (n = 7) and SLPs (n = 8) conducted an independent, simultaneous dysphagia screening on 51 adult inpatients classified as low-risk/at-risk referrals. To examine operational impact, AHAs independently completed screening on 48 low-risk/at-risk patients, with subsequent clinical swallow evaluation conducted by an SLP with patients who failed screening. Results Exact agreement between AHAs and SLPs on overall pass/fail screening criteria for the first 51 patients was 100%. Exact agreement for the two tools was 100% for the Eating Assessment Tool and 96% for the water swallow test. In the operational impact phase (n = 48), 58% of patients failed AHA screening, with only 10% false positives on subjective SLP assessment and nil identified false negatives. Conclusion AHAs demonstrated the ability to reliably conduct dysphagia screening on a cohort of low-risk patients, with a low rate of false negatives. Data support high level of agreement and positive operational impact of using trained AHAs to perform dysphagia screening in low-risk patients.

The role of multidisciplinary decision making in oropharyngeal cancer: do we follow guidelines and are treatment decisions being implemented?

PURPOSE: A multidisciplinary team (MDT) approach to cancer management is gold-standard. With an increasing disease incidence and growing research into human papillomavirus (HPV)-related oropharyngeal cancer (OPC), updated UK management guidelines were recently published. This study aimed to evaluate the MDT decision-making process among OPC patients at a tertiary centre. METHODS: MDT meetings over a 12-month period were analysed retrospectively. MDT decisions were compared with guidelines and patient records examined to identify decision implementation. Reasons behind any discordant decisions were explored. RESULTS: This study included 140 OPC patients. Thirty-three (23.6%) were not tested for HPV. Patients over 70 years with a smoking history treated palliatively were less likely to be tested (P = 0.017). Eighty-five percent of MDT decisions followed guidelines with the majority not complying (76.2%) related to patient comorbidity. Ten decisions (7.1%) were not implemented. Reasons included: Seven due to patient choice, of which four patients (57.1%) were only seen following the MDT meeting, and three due to clinician decisions as new clinical information emerged. CONCLUSION: The majority of MDT decisions followed guidelines and any discordant decisions were justifiable. Discussing management options with patients beforehand facilitates decision implementation as decisions can potentially change after seeing the patient. Progress is still needed with regards to HPV testing. Reasons for not testing could include subliminal decision-making among clinicians, and patients falling between centres. Crucially, the role of the MDT in head and neck cancer should be to ratify decisions rather than making them, hence the need to see patients prior to MDT discussion.

Enzastaurin (LY317615), a protein kinase Cbeta inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines.

Enzastaurin (LY317615), an acyclic bisindolylmaleimide, is an oral inhibitor of the protein kinase Cbeta isozyme. The objective of this study was to assess the efficacy of enzastaurin in inducing apoptosis in multiple myeloma (MM) cell lines and to investigate possible mechanisms of apoptosis. Cell proliferation assays were done on a variety of MM cell lines with unique characteristics (dexamethasone sensitive, dexamethasone resistant, chemotherapy sensitive, and melphalan resistant). The dexamethasone-sensitive MM.1S cell line was used to further assess the effect of enzastaurin in the presence of dexamethasone, insulin-like growth factor-I (IGF-I), interleukin-6, and the pan-specific caspase inhibitor ZVAD-fmk. Enzastaurin increased cell death in all cell lines at clinically significant low micromolar concentrations (1-3 micromol/L) after 72 hours of treatment. Dexamethasone and enzastaurin were shown to have an additive effect on MM.1S cell death. Although IGF-I blocked the effect of 1 micromol/L enzastaurin, IGF-I did not abrogate cell death induced with 3 mumol/L enzastaurin. Moreover, enzastaurin-induced cell death was not affected by interleukin-6 or ZVAD-fmk. GSK3beta phosphorylation, a reliable pharmacodynamic marker for enzastaurin activity, and AKT phosphorylation were both decreased with enzastaurin treatment. These data indicate that enzastaurin induces apoptosis in MM cell lines in a caspase-independent manner and that enzastaurin exerts its antimyeloma effect by inhibiting signaling through the AKT pathway.

8-amino-adenosine is a potential therapeutic agent for multiple myeloma.

UNLABELLED: Multiple myeloma (MM) is a malignancy of clonal B-cells that accounts for 10% of all hematologic malignancies. We have shown previously that a novel purine analogue, 8-chloro-adenosine, has significant activity for MM in preclinical studies. OBJECTIVE: Using MM cell lines, we investigated the molecular mechanism of related congener of adenosine, 8-amino-adenosine (8-NH2-Ado). METHODS: We employed biological and biochemical assays in MM cell lines to evaluate the clinical potential of 8-NH2-Ado. RESULTS: In MM cell lines both sensitive and resistant to conventional chemotherapies, 8-NH2-Ado is cytotoxic, with IC50 ranging from 300 nmol/L to 3 micromol/L. A mouse leukemic cell line lacking adenosine kinase activity was resistant to 8-NH2-Ado, indicating that phosphorylation of 8-NH2-Ado to its triphosphate form is required for cytotoxicity. A 4-hour incubation of MM cells with 10 micromol/L analogue resulted in an accumulation of >7 mmol/L 8-NH2-ATP with a parallel decline in the endogenous ATP levels. Accumulation of 8-NH2-ATP was dependent on both exogenous concentration of 8-NH2-Ado and incubation time. The accumulation of 8-NH2-ATP was accompanied by a decrease in both RNA and DNA synthesis. The mechanism of 8-NH2-Ado-mediated cytotoxicity was due to apoptosis as measured by an increase in Annexin V binding, a decrease in mitochondrial membrane potential, an increase in caspase activity, cleavage of caspase substrates, and an increase in cells with a sub-G1 DNA content. CONCLUSION: Based on these results, we conclude that 8-NH2-Ado may hold great potential as a therapeutic agent for the treatment of MM.