Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_892_Библиотеки_им_академика_М_И_Перельмана

Postoperative pain control following cleft lip and palate repair has undergone signi­cant scrutiny in recent years. Enhanced Recovery After Surgery (ERAS) protocols have become pervasive across surgical disciplines. ERAS was rst introduced in 2001 by a group in Northern Europe among patients undergoing colonic resection with the goal of reducing postoperative morbidity in relation to pain [27]. Over the last two decades, a multitude of ERAS protocols have since been utilized to improve patient outcomes across various postoperative surgical populations. ERAS protocols include patient-centered, evidence-based pain management plans organized by mul­tidisciplinary care teams. Recent advances in ERAS protocols for cleft lip and palate postoperative patients have been tailored to minimize the use of opioids and subse­quently decrease the length of stay and complication rates. An ERAS protocol that seeks to minimize the use of opioids for postoperative palatoplasty patients was described by Hush etal. This protocol included: Gabapentin 10mg/kg/dose q8, acet­aminophen 10mg/kg/dose q4 PRN, and Ketorolac 0.5mg/kg/dose IV q6 PRN for severe pain (max of 3 doses). Alternatively, a regime of Ibuprofen 10mg/kg/dose q6 for mild–moderate pain was available. Postoperatively, a daily regimen of gabapen­tin, acetaminophen, and ibuprofen were prescribed as needed [28]. Overall applica­tion of ERAS led to a 95.7% reduction in narcotic administration and a 31.7% decrease in LOS when compared to controls. Our group utilized an ERAS protocol for palatoplasty patients that had a multimodality regime of Morphine 0.05–0.1mg/ kg IV q1 PRN and acetaminophen 10mg/kg IV q6 scheduled during the immediate postoperative period. Depending on postoperative pain, acetaminophen or ibuprofen 10mg/kg PO q6 PRN (FLACC score 1–5) or oxycodone 0.1mg/kg PO q4–6 PRN (FLACC pain score 6–10) was administered. Patients in the ERAS protocol received signicantly less mg of morphine on postoperative Day 1 through 4 than those on the ad lib pathway. Return visits to the hospital for pain management following primary palatoplasty decreased from 7.1% to 0% with the ERAS protocol [29].

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common can­cer worldwide, with over 60,000 new cases in the United States each year [1]. HNSCC includes distinct disease sub-types, each located in different anatomic loca­tions, with different etiology, patient demographics, and molecular proles. Oral squamous cell carcinoma (OSCC) is a distinct sub-type that has remained particu­larly treatment resistant. Even when compared to other subsets of HNSCC, such as oropharyngeal cancer, OSCC remains one of the deadliest, without signicantly improved outcomes in recent years. Furthermore, OSCC is on the rise. In the last 20years, the OSCC incidence has increased by two-thirds, most dramatically in young patients, and has resulted in 400,000 new annual cases globally [2]. Of the

30,000 Americans newly diagnosed with OSCC each year, half will die of this dis­ease, resulting in approximately one death per hour [3]. This high mortality is com­pounded by signicant morbidity due to OSCC treatment that often results in cosmetic and functional deformities affecting patients’ ability to eat, taste, speak, and relate to others. Taken together, the signicant burden of this disease necessi­tates the development of improved diagnostic tools and targeted treatment options.

Advances made in recent years have the potential to transform all phases of patient care, from innovations in patient diagnosis with the discovery of novel bio­markers and the development of noninvasive biopsy techniques to advances in can­cer treatment with the development of vaccines, immunomodulatory drugs, and injectable biomaterials. We review these advances and more in this chapter.

The majority of biomarker studies have not focused on early-stage OSCC patients. However, this patient population has the potential to benet most from biomarker-based evaluation. Unlike late-stage (III/IV) OSCC patients who rou­tinely receive triple-modality therapy (surgery, radiation, and chemotherapy), treat­ment recommendations for early-stage OSCC patients are highly variable due to the lack of accurate and individualized metrics to measure risk. To address this vari­ability in disease outcome, recent studies have focused on identifying biomarkers that distinguish high- versus low-risk early-stage OSCC patients. Yoon etal. pub­lished a study focusing on early-stage OSCC patients that used differences in miRNA patterns to predict 5-year survival [3]. The group discovered a 3 miRNA

A recent study, however, demonstrated clinical signicance and prognostic potential when using epigenetic biomarkers to predict 5-year mortality in early­stage (I/II) OSCC patients. In this study, patients’ mortality risk scores were deter­mined by combining both molecular and nonmolecular features. The molecular panel consisted of a 12-gene methylation signature. Notably, all 12 genes had been previously linked to patient survival in other cancers. However, 11 of the 12 had never been previously linked to OSCC.The study’s nonmolecular panel consisted of the following clinicopathologic features: age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. When assessing 5-year mortality using patients’ clinicopatho­logic features alone, the c-index from this study was 0.67, which was not different from previous studies using clinicopathologic features to predict risk (Fig. 3.1). Importantly, the c-index increased to 0.915 when the clinicopathologic features were combined with the 12-gene molecular panel [8]. This data highlights the criti­cal role of molecular biomarkers in determining patient risk and demonstrates how utilizing molecular information as part of a risk score has the potential to mitigate overtreatment in low-risk patients while preventing undertreatment in high-risk patients. Work is currently being done to validate this risk score with a larger multi­institutional cohort.

One advantage of treating OSCC is that the oral cavity is easily accessible and, thus, lends itself well to the development of noninvasive biopsy techniques. Such techniques would allow frequent sample harvesting not only for initial diagnosis but also to monitor treatment response and recurrence. Importantly, samples har­vested via these techniques could allow for risk score calculation prior to surgery. Since it is standard of care for adjuvant treatments to occur within several weeks of surgery, it is essential that the patient’s risk score be calculated beforehand if it is to

play a role in determining the need for adjuvant treatment. Collecting samples via noninvasive biopsy at the time of diagnosis allows for this to occur, in contrast to waiting for data from formalin-xed, parafn-embedded (FFPE) tissue samples following tumor resection, which could result in the delay of potentially necessary treatment.