Ray Blanco

Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma

Purpose: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC). Experimental Design: We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC). Results: Tadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients (P = 0.01), reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients (P = 0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P = 0.04). Conclusions: These findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application. Clin Cancer Res; 21(1); 30–38. ©2015 AACR.

Surgical salvage improves overall survival for patients with HPV‐positive and HPV‐negative recurrent locoregional and distant metastatic oropharyngeal cancer

Human papillomavirus (HPV) tumor status and surgical salvage are associated with improved prognosis for patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC). Current data regarding types of surgery and the impact of surgery for patients with distant metastatic disease are limited.

Transoral Robotic Surgery of the Vocal Cord

The standard endoscopic surgical approach in the management of laryngeal lesions is by the use of a laryngoscope, microscope, and laser. This requires the surgeon to work within the confines of the laryngoscope. At times, it requires repositioning of the laryngoscope and microscope to gain access to a specific area. The surgery also requires line-of-sight observation to complete the operation. The introduction of transoral robotic surgery in head and neck surgery brings the advantages of three-dimensional magnification, increased degrees of freedom with the effector arms, and an articulating distal end that mimics hand movements. To date, transoral robotic surgery of vocal cord surgery requires the use of a tracheostomy in patients. Here we report the use of a CO(2) laser fiber and the Da Vinci robotic platform (Intuitive Surgical) for the surgical management of a T1 glottic squamous cell carcinoma.

Objective assessment in residency‐based training for transoral robotic surgery

To develop a robotic surgery training regimen integrating objective skill assessment for otolaryngology and head and neck surgery trainees consisting of training modules of increasing complexity leading up to procedure‐specific training. In particular, we investigated applications of such a training approach for surgical extirpation of oropharyngeal tumors via a transoral approach using the da Vinci robotic system.

Selective versus comprehensive neck dissection after chemoradiation for advanced oropharyngeal squamous cell carcinoma

OBJECTIVE: To determine whether a comprehensive neck dissection (CND) or a selective neck dissection (SND) is indicated as planned post–primary chemoradiation treatment (CRT) for patients with advanced oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Case series with chart review. SETTING: A community teaching hospital. SUBJECTS: Patients with advanced OPSCC who received a uniform CRT protocol at Greater Baltimore Medical Center (GBMC). METHODS: Medical records of patients treated with primary CRT for locoregionally advanced OPSCC at GBMC between 2001 and 2007 were reviewed. All patients received 7000 to 7500, 6000, and 5000 cGy to primary disease sites, involved cervical lymphatics, and uninvolved cervical and supraclavicular lymphatics, respectively, with concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) given on days one through five and 29 through 33. RESULTS: Seventy-six patients received CRT, and 41 met the criteria for neck dissection. Forty-eight neck dissections were performed (34 unilateral and 7 bilateral), of which 23 (48%) were CNDs and 25 (52%) were SNDs. Residual carcinoma was found in six (26%) of the CND and five (20%) of the SND heminecks. The CND group had six (26%) complications, whereas the SND group had two (8%). CONCLUSION: The high rate of residual disease demonstrated in this study supports the need for post-CRT neck dissection. Although complication rates were not significantly different between the two groups, the trend in this study indicates that SND results in less morbidity. The presumed reduced morbidity and equivalent regional control rate suggest that SND is an appropriate surgical option for OPSCC patients after primary CRT.

Factors associated with pharyngoesophageal stricture in patients treated with concurrent chemotherapy and radiation therapy for oropharyngeal squamous cell carcinoma.

The purpose of this study was to elucidate factors associated with pharyngoesophageal strictures after treatment for head and neck squamous cell carcinoma (SCC).

Transoral Robotic Surgery Experience in 44 Cases

OBJECTIVE To report a single institutions experience with transoral robotic surgery (TORS) and its clinical outcomes. This was a retrospective study carried out at a university-affiliated teaching hospital. SUBJECTS AND METHODS Forty-four consecutive TORS patients with benign and malignant diseases were reviewed. Data on demographics, clinical parameters, and diet were collected. Surgical margins, local and regional recurrence, distant metastasis, 2-year disease-free survival rate, and 2-year survival data were reviewed for the malignant cases. RESULTS Nine benign and 35 proven squamous cell carcinoma (SCCA) cases underwent TORS. The set-up time was 17.12 minutes (range, 10-40 minutes), and operative time was 53 minutes (range, 10-300 minutes). Average length of stay was 2.5 days. There were seven (6.8%) grade 3 surgical complications. Surgical infection rate was 2.3%. Benign cases were on a regular diet after TORS. Of the malignant cases, 94% were taking peroral diet immediately after the TORS procedure. There were no intraoperative complications and no 30-day postoperative mortalities. The mean follow-up time was 25.2 months (range, 16-38 months) for malignant disease. The SCCA sites were in the oropharynx (30/35), larynx (2/35), and unknown primary with neck metastasis (3/35). Unknown primary patients were excluded in the surgical margin analyses. Negative margins were achieved in 91% of cases. The local and regional recurrence rates were 6.3% (2/32) and 3.1% (1/32), respectively. Two patients (6.3%) developed distant metastasis. Oropharyngeal SCCA cases were reviewed, of which 23 were human papillomavirus (HPV)/p16 positive and 7 were HPV/p16 negative. The 2-year actual survival for HPV-positive and -negative patients was 96% (22/23) and 86% (6/7), respectively. The 2-year disease-free survival for HPV-positive and -negative cases was 91% (21/23) and 71.4% (5/7), respectively. All malignant cases that underwent TORS received postoperative adjuvant therapy. CONCLUSIONS TORS is a safe procedure with minimal complications and acceptable clinical and functional outcomes.

Neck dissection through a facelift incision

To determine the feasibility and safety of neck dissection through a facelift incision.

Pharyngocutaneous fistula after total laryngectomy: A single-institution experience, 2001–2012

PURPOSE The purpose of this study was to determine the incidence of and risk factors for pharyngocutaneous fistula in patients undergoing total laryngectomy at a single institution. MATERIALS AND METHODS The records of 59 patients undergoing primary or salvage total laryngectomy at our institution from 2001 to 2012 were retrospectively reviewed. Data collected included patient, tumor and treatment characteristics, and surgical technique. Risk factors were analyzed for association with pharyngocutaneous fistula formation. RESULTS Twenty patients (34%) developed fistulas. Preoperative tracheostomy (OR 4.1; 95% CI 1.3-13 [p=0.02]) and low postoperative hemoglobin (OR 9.1; 95% CI 1.1-78 [p=0.04]) were associated with fistula development. Regarding surgical technique, primary sutured closure of the total laryngectomy defect had the lowest fistula rate (11%). In comparison, primary stapled closure and pectoralis onlay flap over primary closure had nonsignificantly increased fistula rates (43%, OR 6.0; 95% CI 1.0-37.3 [p=0.06] and 25%, OR 2.7; 95% CI 0.4-23.9 [p=0.38], respectively). Pectoralis flap incorporated into the suture line had a significantly increased fistula rate (50%, OR 7.1; 95% CI 1.4-46 [p=0.02]). After stratification for salvage status, patient comorbidities were associated with fistula in non-salvage cases whereas disease-related characteristics were associated with fistula in salvage cases. Fistula development was associated with increased length of hospital stay (p<0.001) and increased time before oral diet initiation (p<0.001). CONCLUSIONS Pharyngocutaneous fistula is a common complication of total laryngectomy. Preoperative tracheostomy, postoperative hemoglobin, and surgical technique are important in determining the risk of fistula.

Transcervical ultrasound identifies primary tumor site of unknown primary head and neck squamous cell carcinoma.

Head and neck squamous cell carcinomas (HNSCCs) of unknown primary site (UP) account for approximately 4% of HNSCCs.1 These cases have historically been subclinical tumors arising from the nasopharynx, hypopharynx, or oropharynx. In the era of human papillomavirus (HPV)–positive HNSCCs, the presence of HPV in cervical malignancy of UP has been strongly associated with oropharyngeal primary tumors.2 Tumors that are HPV–positive are typically small and arise from cryptic lingual and palatine lymphoid tissues, rendering primary tumor detection challenging.3 The traditional diagnostic paradigm for finding the primary tumor consists of a physical examination, fiber-optic laryngoscopy, and imaging. If these techniques are unsuccessful, operative examination under anesthesia is warranted, including direct laryngoscopy with “blind” biopsies directed at the nasopharynx, hypopharynx, oropharynx, larynx, and palatine and lingual tonsillectomy. Failure to identify the primary tumor site subsequently necessitates radiation of Waldeyer’s ring and concurrent chemotherapy. This report shows that transcervical ultrasound (US) can be used to localize oropharyngeal tumors. The study was reviewed and approved by the Greater Baltimore Medical Center Institutional Review Board.