May - July 2018
Vlad C. Sandulache, M.D., Ph.D.
July 16 - July 20, 2018
Specific question: What is the potential for erroneously staging laryngeal cancer using pre-treatment imaging?
Laryngeal cancer remains a challenging disease to treat and cure. Due to the significant morbidity and decreased quality of life associated with laryngeal surgery (i.e. laryngectomy), over the last few decades we have witnessed a dramatic shift toward organ preservation radiation-based treatment algorithms for both early-stage and advanced-stage disease. However, this shift toward non-surgical treatment modalities has removed an important tool in our ability to accurately stage laryngeal cancer patients (pathologic report). It is therefore critically important that clinicians appropriately understand the limitations of diagnostic imaging as it relates to laryngeal cancer staging. The most critical aspect of this represents cartilage involvement which has become even more important in the most recent AJCC Staging Manual which distinguishes T3 tumors which involve the inner cortex of the thyroid cartilage from T4a tumors which involve both the inner and outer cortices.
Kuno et al. discuss the limitations associated with imaging based identification of cartilage invasion/destruction and determine a specificity of 96% and a sensitivity of 86% when combining weighted average image analysis with iodine overlay acquired using dual-source dual-energy CT. The authors showed in 2018 that CT maintained higher specificity compared to MRI (985%) for cartilage involvement with a sensitivity of 81%. Koopman et al. identified a specificity of 89% and a sensitivity as low as 46% for cartilage involvement for CT. Sensitivity has been shown to be higher for MRI compared to CT with respect to early stage laryngeal lesions which may or may not involve the anterior commissure, but this comes at the expense of specificity, primarily due to the inability of MRI to distinguish tumor from tumor related inflammation (Wu et al. 2016)
For both early- and advanced stage disease it is therefore critical that clinicians set appropriate patient expectations with regard to treatment selection and clinical outcomes that take into account expected imaging accuracy and limitations.
Kuno H, Onaya H, Fujii S, Ojiri H, Otani K, Satake M. Primary staging of laryngeal and hypopharyngeal cancer: CT, MR imaging and dual-energy CT. Eur J Radiol. 2014 Jan;83(1):e23-35. doi: 10.1016/j.ejrad.2013.10.022. PMID: 24239239.
Kuno H, Sakamaki K, Fujii S, Sekiya K, Otani K, Hayashi R, Yamanaka T, Sakai O, Kusumoto M. Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma. AJNR Am J Neuroradiol. 2018 Jan 25. doi: 10.3174/ajnr.A5530. PMID: 29371253.
Koopmann M, Weiss D, Steiger M, Elges S, Rudack C, Stenner M. Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy. Eur Arch Otorhinolaryngol. 2016 Nov;273(11):3789-3794. PMID: 27256366.
Wu JH, Zhao J, Li ZH, Yang WQ, Liu QH, Yang ZY, Liao B, Li XL, Wang B, Qin H, Luo J, Lv KX, Wen WP, Lei WB. Comparison of CT and MRI in Diagnosis of Laryngeal Carcinoma with Anterior Vocal Commissure Involvement. Sci Rep. 2016 Aug 2;6:30353. doi: 10.1038/srep30353. PMID: 27480073.
Head and Neck Cancer Surgical Complications
Vlad C. Sandulache, M.D., Ph.D.
June 18 - June 22, 2018
Specific Question: What are the management options for post-operative chyle leaks?
Neck dissection is a critical component of surgical management of head and neck squamous cell carcinoma (HNSCC) as well as thyroid carcinoma (TC). Extensive dissection of lower cervical nodal basins (i.e. level IV, V, VI, VII) can occasionally result in intentional or accidental injury to the main thoracic duct (left) or large accessory lymphatic channels (bilateral) and the development of a chyle leak. The reported rate of chyle leaks following HNSCC and TC surgery varies widely in the literature (1-10%) based on extent of disease, extent of surgical dissection, and history of previous surgery or radiation.
When the injured channels are of large caliber (i.e. thoracic duct), an intra-operative chyle leak can be observed and addressed at the time of surgery using ligation, with or without local muscle flaps, sclerosing or inflammatory agents, or biologically compatible sealants. Chyle leaks can also occur in the absence of an obvious large caliber ductal injury, most likely secondary to inadvertent injury to smaller accessory channels. Post-operative chyle leaks are generally divided into low output (500ml/day).
Optimal management of chyle leaks remains poorly defined at the present time. Most surgeons will intervene for persistent high-output leaks through a combination of wound re-exploration along with ligation and potential application of sclerosing agents or alternatively via intra-thoracic thoracic duct ligation. For most patients however, management of chyle leaks relies heavily on conservative management with a reported success rate from 50-100%. Delaney et al. provide a recent review (2016) of the available literature on conservative management of chyle leaks, including diet modification (non-fat or medium-chain fatty acid) and the utilization of octreotide. Jain et al. provide a detailed discussion regarding the role of octreotide (100µg SC TID) for both low and high-output leaks. Lacking high-quality, prospective studies, existing literature supports a step-wise approach: 1) immediate intra-operative repair, 2) continued drainage of the surgical space, 3) diet modification (which can be escalated to total parenteral nutrition (TPN)) and 4) octreotide. Failure of conservative management to resolve or substantially reduce the output of a chyle leak over a 7-10 day period should prompt attempts at intervention (re-exploration, thoracic approach, percutaneous approach).
Diagnosis of Oral Cancer
Vlad C. Sandulache, M.D., Ph.D.
June 4 - June 8, 2018
Specific Question: What alternate tests can be utilized to accurately diagnose oral cancer?
Oral cavity squamous cell carcinoma (OCSCCA) affects approximately 20,000 individuals in the United States each year. Despite numerous advances in surgical and radiation techniques, and the introduction of targeted agents and most recently immunotherapy, survival outcomes for OCSCCA have remained essentially unchanged over the last three decades. In part, this is due to a high proportion of advanced-stage disease at the time of initial presentation, which portends a high rate of recurrence despite multi-modality treatment regimens. The current approach for diagnosis of OCSCCA generally revolves around a clinical exam by a trained otolaryngologist or oral surgeon followed by biopsy of the suspicious lesion/s. Unfortunately, many early stage OCSCCAs can be relatively asymptomatic and thus presentation to a surgical specialist can occur in a delayed fashion. As a result, clinicians and scientists throughout the world have continually sought to identify rapid, simple diagnostic tests which can increase the fraction of early-stage disease. The gold standard for such an approach is the Papanicolaou test, which has been shown to reduce cervical cancer mortality by over 50% when applied consistently in the appropriate patient population.
Macey et al. conducted a Cochrane review of diagnostic tests for OCSCCA in 2015. Three diagnostic tests were evaluated based on the available studies: vital staining, oral cytology and light-based (i.e. VELscope) evaluation of the oral cavity. The aggregate sensitivity and specificity values were as follows: vital staining 84% / 70%, oral cytology 91% / 91%, light-based evaluation 91% / 58% respectively. The authors appropriately concluded that none of the three methodologies fulfill the requirements for clinical utility by non-specialists in the diagnosis of OCSCCA. In addition to the highly variable sensitivity and specificity values among individual studies, some of these methods suffer from intrinsic limitations. For example cytology cannot reliably distinguish dysplasia from carcinoma, and provides no information on the issue of invasion. Both vital staining and light-based evaluation are highly operator dependent and thus their sensitivity and specificity can vary greatly from clinician to clinician and institution to institution.
Unfortunately, despite significant advances in other areas of cancer diagnosis and treatment, for OCSCCA diagnosis, there remains no substitute for detailed clinical evaluation by a well-trained specialist with targeted invasive biopsy of suspicious mucosal lesions.
Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JL, Lingen MW, Ogden GR, Warnakulasuriya S, Scully C. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database Syst Rev. 2015 May 29;(5):CD010276. PMID 26021841
Antibiotic Use in Head and Neck Cancer Surgery
Vlad C. Sandulache, M.D., Ph.D.
May 7 - May 11, 2018
Specific Question: What is the role of perioperative antibiotics in head and neck cancer surgery?
Surgery is an important treatment modality for cancers of the oral cavity, oropharynx, larynx, hypopharynx and sinonasal cavity. Surgical resections performed in these sites generate wounds heavily contaminated with upper aerodigestive tract flora. Oral and oropharyngeal flora in particular, consist of a wide variety of bacteria ranging from Actinomyces to Peptococcus and fungi ranging from Candida to Cryptococcus. In healthy patients, with functional immune systems and a normal mucosal barrier, these colonizing organisms do not present a significant threat. The presence of a head and neck cancer disrupts the normal symbiosis between host and colonizing organisms in several ways. Advanced tumors often lead to malnutrition, failure to thrive and an impaired immune system. Decreased oral hygiene secondary to painful tumors shifts the balance in the normal flora toward more aggressive species. Mucosal ulcerations associated with tumor formation generate pathways for bacterial and fungal penetration into the soft tissues of the head and neck.
Surgical intervention for head and neck tumors therefore occurs in a context far removed from the normal homeostasis of the upper aerodigestive tract. This generates a significant risk for post-operative infections which can lead to catastrophic, life threatening events in a significant subset of patients (i.e. laryngectomy patients, patients with free flap reconstructions). To reduce this risk, perioperative antibiotics are routinely employed by head and neck surgeons. As early as 1973, Dor and Klastersky demonstrated that perioperative antibiotics with Gram negative coverage reduced the frequency of postoperative wound infections following head and neck cancer surgery. In 1992 Weber et al. demonstrated a reduction in wound infections from 27% to 13% through increased Gram negative coverage (ampicillin-sulbactam vs clindamycin). The study utilized an antibiotic regimen which extended coverage for approximately two days post-surgery.
Langerman et al. (2015) summarized data from 439 antibiotic regimens over nearly 1900 admissions following laryngectomy across multiple institutions. Utilization of peri-operative antibiotics decreased the risk of surgical site infection and clindamycin was shown to be inferior to other antibiotic regimens. Among academic medical centers the most common duration of antibiotic use was four days. A more comprehensive analysis performed by Langerman et al. in 2016 across multiple head and neck sites demonstrated that prolonging ampicillin-sulbactam treatment past the day of surgery dramatically reduced surgical site infection risk.
Although the optimal perioperative antibiotic regimen and duration remains unclear at this time, utilization of perioperative antibiotics is critical to reducing surgical site infections in head and neck cancer and clindamycin has repeatedly been shown to be substantially inferior to regimens with broader Gram negative coverage.
Weber RS, Raad I, Frankenthaler R, Hankins P, Byers RM, Guillamondegui O, Wolf P, Smith T, Goepfert H. Ampicillin-sulbactam vs clindamycin in head and neck oncologic surgery. The need for gram-negative coverage. Arch Otolaryngol Head Neck Surg. 1992 Nov;118(11):1159-63. PMID: 1418893
Langerman A, Ham SA, Pisano J, Pariser J, Hohmann SF, Meltzer DO. Laryngectomy Complications Are Associated with Perioperative Antibiotic Choice. Otolaryngol Head Neck Surg. 2015 Jul;153(1):60-8. PMID: 25944348
Langerman A, Thisted R, Hohmann S, Howell M. Antibiotic and Duration of Perioperative Prophylaxis Predicts Surgical Site Infection in Head and Neck Surgery. Otolaryngol Head Neck Surg. 2016 Jun;154(6):1054-63. PMID:26932957