Addressing positive multi-cancer early detection tests in head and neck Surgery: Experience with head and neck work up for high-risk referrals.

OBJECTIVES: Blood-based multi-cancer early detection (MCED) tests are now commercially available. However, there are currently no consensus guidelines available for head and neck cancer (HNC) providers to direct work up or surveillance for patients with a positive MCED test. We seek to describe cases of patients with positive MCED tests suggesting HNC and provide insights for their evaluation. METHODS: Retrospective chart review of patients referred to Otolaryngology with an MCED result suggesting HNC. Patients enrolled in prospective MCED clinical trials were excluded. Cancer diagnoses were confirmed via frozen-section pathology. RESULTS: Five patients were included (mean age: 69.2 years, range 50-87; 4 male) with MCED-identified-high-risk for HNC or lymphoma. Only patient was symptomatic. After physical exam and follow-up head and neck imaging, circulating tumor HPV DNA testing, two patients were diagnosed with p16 + oropharyngeal squamous cell carcinomas and underwent appropriate therapy. A third patient had no evidence of head and neck cancer but was diagnosed with sarcoma of the thigh. The remaining two patients had no evidence of malignancy after in-depth workup. CONCLUSIONS: In this retrospective study, 2 of 5 patients referred to Otolaryngology with a positive MCED result were diagnosed with HPV + oropharyngeal squamous cell carcinoma. We recommend that positive HNC MCED work up include thorough head and neck examination with flexible laryngoscopy and focused CT or MRI imaging. Given the potential for inaccurate MCED tissue of origin classification, PET/CT may be useful in specific situations. For a patient with no cancer identified, development of clear guidelines is warranted.

Free Functioning Gracilis Muscle Transfer for Elbow Flexion Reconstruction after Traumatic Adult Brachial Pan-Plexus Injury: Where Is the Optimal Distal Tendon Attachment for Elbow Flexion?

BACKGROUND: Reconstruction after pan-plexus root avulsions often includes gracilis free functioning muscle transfer. For elbow flexion reconstruction, the free functioning muscle transfer distal tendon is inserted into the biceps tendon or more distally (i.e., flexor digitorum profundus/flexor pollicis longus tendons) for combined elbow and finger flexion; the theoretical drawback of the latter approach is weaker elbow flexion. The authors compared elbow flexion strength with a biceps tendon versus a flexor digitorum profundus/flexor pollicis longus tendon attachment to determine which insertion point resulted in better elbow flexion. METHODS: Thirty-nine patients underwent free functioning muscle transfer with either a biceps tendon or a distal attachment. Groups were compared on postoperative elbow flexion strength, preoperative and postoperative Disabilities of the Arm, Shoulder, and Hand questionnaire scores, range of motion, and other surgical and demographic characteristics. A biomechanical analysis simulating different tendon attachments determined which reconstruction resulted in optimal elbow flexion mechanics. RESULTS: Distal tendon attachment was associated with M3 or M4 elbow flexion and greater range of motion compared with the biceps tendon attachment (p < 0.05). There were no statistically significant improvements in Disabilities of the Arm, Shoulder, and Hand questionnaire scores. Biomechanical analysis demonstrated that all distal tendon attachments studied generated a 15 to 30 percent greater torque compared with the biceps tendon attachment; this was true for attachments either at the flexor digitorum profundus/flexor pollicis longus tendon, or directly at the radius at 10 cm or 15 cm from the elbow axis of rotation. CONCLUSIONS: The flexor digitorum profundus/flexor pollicis longus tendon attachment of the gracilis free functioning muscle transfer distal tendon was superior in achieving elbow flexion strength. Patients with only elbow flexion reconstruction may also benefit from a flexor digitorum profundus/flexor pollicis longus tendon attachment or from a more distal attachment to the radius. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Nitric Oxide Synthase Type III Overexpression By Gene Therapy Exerts Antitumoral Activity In Mouse Hepatocellular Carcinoma.

Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO) synthase type III (NOS-3) overexpression induces cell death in hepatoma cells. The study developed gene therapy designed to specifically overexpress NOS-3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration in mice. Hepa 1-6 cells were used for in vitro and in vivo experiments. The first generation adenovirus was designed to overexpress NOS-3 (or GFP) and luciferase cDNA under the regulation of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters, respectively. Both adenoviruses were administered through the tail vein two weeks after orthotopic tumor cell implantation. AFP-NOS-3/RSV-Luciferase increased oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8 activity in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and caspase-8 activity was abolished by l-NAME or p53 siRNA. The tail vein infusion of AFP-NOS- 3/RSV-Luciferase adenovirus increased cell death markers, and reduced cell proliferation of established tumors in fibrotic livers. The increase of oxidative/nitrosative stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L expression and cell death in hepatocellular carcinoma cells. The effectiveness of the gene therapy has been demonstrated in vitro and in vivo.