Susan McCammon

Artificial Nutrition and Hydration: The Evolution of Ethics, Evidence, and Policy

IntroductionThe debate over use of artificial nutrition and hydration (ANH) in terminal illness, including advanced dementia, remains contentious despite extensive ethical and empirical investigation.MethodsFor this narrative review we undertook a focused, selective review of literature reflecting ethical analysis, empirical assessment of outcomes, legal responses, and thinking within the Roman Catholic religious tradition.ResultsThe history of the debate over the past 60 years results from a complex interplay of ethical concerns, a growing empirical database, legal changes, public opinion, and financial as well as institutional concerns. Discussions of ANH today are often conducted without any understanding of this historical context.DiscussionPatients’ interests could be better protected through remedial action at both the individual and the policy levels.

L-selectin-mediated Lymphocyte-Cancer Cell Interactions under Low Fluid Shear Conditions

Cell migration in blood flow is mediated by engagement of specialized adhesion molecules that function under hemodynamic shear conditions, and many of the effectors of these adhesive interactions, such as the selectins and their ligands, are well defined. However, in contrast, our knowledge of the adhesion molecules operant under lymphatic flow conditions is incomplete. Among human malignancies, head and neck squamous cell cancer displays a marked predilection for locoregional lymph node metastasis. Based on this distinct tropism, we hypothesized that these cells express adhesion molecules that promote their binding to lymphoid tissue under lymphatic fluid shear stress. Accordingly, we investigated adhesive interactions between these and other cancer cells and the principal resident cells of lymphoid organs, lymphocytes. Parallel plate flow chamber studies under defined shear conditions, together with biochemical analyses, showed that human head and neck squamous cell cancer cells express heretofore unrecognized L-selectin ligand(s) that mediate binding to lymphocyte L-selectin at conspicuously low shear stress levels of 0.07–0.08 dynes/cm2, consistent with lymphatic flow. The binding of head and neck squamous cancer cells to L-selectin displays canonical biochemical features, such as requirements for sialylation, sulfation, and N-glycosylation, but displays a novel operational shear threshold differing from all other L-selectin ligands, including those expressed on colon cancer and leukemic cells (e.g. HCELL). These data define a novel class of L-selectin ligands and expand the scope of function for L-selectin within circulatory systems to now include a novel activity within shear stresses characteristic of lymphatic flow.

In vivo layer-resolved characterization of oral dysplasia via nonlinear optical micro-spectroscopy

Optical spectroscopy has proven to be a powerful technique for studying neoplastic transformation in epithelial tissue. Since specific intra-layer precancerous changes originate in the stratified layers of the oral mucosa, layer-resolved analysis will likely improve both our understanding of the mechanism of premalignant transformation, and clinical diagnostic outcomes. However, the native fluorescence signal in linear spectroscopy typically originates from a multi-layered focal volume. In this study, nonlinear spectroscopy was exploited for in vivo layer-resolved discrimination between normal and dysplastic tissue for the first time. Our results revealed numerous intra-layer specific differences.

Multiphoton autofluorescence microscopy and second harmonic generation microscopy of oral epithelial neoplasms

The objective of this study was to evaluate the nonlinear optical microscopy techniques of multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) for noninvasive imaging of oral epithelial carcinogenesis. In vivo imaging was performed in a hamster model for oral carcinogenesis to characterize optical and morphometric alterations during neoplastic transformation. Data is presented showing alterations in morphometry and collagen density during the precancerous phase of neoplastic transformation.

Post-Laryngectomy stricture and pharyngocutaneous fistula: Review of techniques in primary pharyngeal reconstruction in laryngectomy

The purpose of this study was to find a correlation between closure technique in pharyngeal closure and outcomes of both pharyngocutaneous fistula and post‐laryngectomy stricture after laryngectomy.

In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.

The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in early transformation. Further development of the method may also lead to new diagnostic approaches to differentiate non-neoplastic tissue from precancers and neoplasia, possibly with other cellular and layer based indicators of abnormality.

Combination of widefield fluorescence imaging and nonlinear optical microscopy of oral epithelial neoplasia

Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) have shown the potential for noninvasive assessment of oral precancers and cancers. We have explored a combination of these nonlinear optical microscopic imaging techniques with widefield fluorescence imaging to assess morphometry similar to that of pathologic evaluation as well as information from endogenous fluorophores, which are altered with neoplastic transformation. Widefield fluorescence revealed areas of interest corresponding to sites with precancers or early tumors, generally resulting in a decrease in green emission or increase in red emission. Subsequent microscopy revealed significant differences in morphology between normal, dysplastic/neoplastic mucosa for all layers. Combination of a widefield and a microscopic technique provides a novel approach for tissue morphometric analysis along with large area assessment of tissue autofluorescence properties.

Endocrine Surgery in the Geriatric Population

Age must be a factor when considering endocrine surgery. Age itself is a risk factor for complications after thyroidectomy, specifically pulmonary, infectious, and cardiac complications. For this reason, in patients with nodular thyroid disease or thyroid microcarcinoma, length of observation must be measured against age and surgical risk. Outcomes of thyroid surgery in geriatric patients can be improved with several measures, including careful preoperative risk stratification based on comorbidities and frailty. In this population subset, it is imperative to have an earnest discussion with patients, their families, and any surrogate decision maker regarding potential outcomes of treatment versus observation.

A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women: Testosterone therapy ameliorates cancer-related muscle loss

Cancer cachexia negatively impacts cancer‐related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.

The Role of Palliative Care in Oral Cavity Carcinoma

Purpose of ReviewThe purpose of this study is to review the current and future role of palliative care in relation to oral cavity carcinoma (OCC).Recent FindingsPalliative care for patients with OCC has traditionally been reserved for patients with advanced disease, recurrent disease, or poor performance status who are unable to undergo surgical or adjuvant treatments. Patients with early- or mid-stage disease were not typically offered palliative services. However, patients at all stages face quality of life issues including disruption of speech, eating, pain, mood, self-image, social interactions, work, and daily activities. This can directly affect performance status and has been shown to increase length of hospitalizations and decrease overall survival. Recent evidence suggests that involving palliative care earlier may decrease rates of depression, decrease cost, improve communication, and increase overall survival outcomes. Furthermore, new applications and innovations in radiation therapy, immunotherapy, and chemotherapy have broadened the palliative therapies available to patients with incurable disease.SummaryGiven the impact that OCC has on quality of life during all stages of disease, a paradigm shift is occurring to involve palliative care at earlier stages. Recent evidence has shown that upstream palliative care increases quality of life and ultimately overall survival.