Mauricio A. Moreno

Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson cancer center

Sinonasal mucosal melanoma is a rare disease associated with a very poor prognosis. Because most of the series extend retrospectively several decades, we sought to determine prognostic factors and outcomes with recent treatment modalities.

MICROVASCULAR FREE FLAP RECONSTRUCTION VERSUS PALATAL OBTURATION FOR MAXILLECTOMY DEFECTS

Palatal obturators and microvascular free flaps are both used to treat patients with maxillectomy defects, however, the optimal technique remains controversial.

In Papillary Thyroid Cancer, Preoperative Central Neck Ultrasound Detects Only Macroscopic Surgical Disease, But Negative Findings Predict Excellent Long-Term Regional Control and Survival

BACKGROUND Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. METHODS A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. RESULTS There were 112 males and 219 females with a median age of 44 years (range 11-87). The median follow-up time for the series was 71.5 months (range 12.7-148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease-free survival (p=0.0005) on bivariate Cox regression. CONCLUSIONS US of the central compartment is an age-independent predictor for survival and CNC recurrence-free survival in PTC. Prophylactic neck dissection of the central compartment does not improve long-term disease control, regardless of the histopathological status of the lymph nodes retrieved. Our findings emphasize the ability of US to clinically detect relevant nodal disease and support conservative management of the CNC in the absence of abnormal findings.

Management of mucosal melanomas of the head and neck: Did we make any progress?

Purpose of reviewPrimary mucosal melanoma of the head and neck is a rare tumor associated with a poor outcome. This diagnosis carries a great deal of anxiety for the patients and puts the clinician in a predicament to find concise and reliable information for adequate risk stratification and treatment. Recent findingsSinonasal mucosal melanomas should be staged according to the tumor node metastasis staging system and could be treated endoscopically with similar results to open surgery. Prophylactic neck dissection could be indicated in oral melanomas, given their tendency to regional failure. Adjuvant radiotherapy improves locoregional control in several series but does not improve survival. Definitive radiation with high linear energy transfer modalities achieves locoregional control rates comparable to surgery. Biochemotherapy improves survival in mucosal melanoma of the head and neck and should be considered for patients with metastatic or extensive locoregional disease. SummaryThe standard therapy for melanoma continues to be surgical resection, possibly associated with adjuvant radiation. Biochemotherapy should be considered for bulky metastatic disease. In the future, definitive radiation regimes, molecular staging and targeted therapy may play a major role.

Compliance With Quality Assurance Measures in Patients Treated for Early Oral Tongue Cancer

The objective of this study was to identify measurable parameters that provide quality data for assessing how well cancer care adheres to accepted treatment guidelines and is delivered to any given patient with oral tongue cancer.

Indocyanine green enhanced near-infrared laser treatment of murine mammary carcinoma.

It is well accepted that near‐infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3–5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7–9 mm) were irradiated with a 808‐nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG‐treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69–70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular‐targeted ICG–NIR laser therapy appears to have potential for treating superficial tumors.

Preoperative lateral neck ultrasonography as a long-term outcome predictor in papillary thyroid cancer.

OBJECTIVE To evaluate the long-term outcomes and prognostic value of our sonographically based surgical approach to the lateral neck for recurrences in papillary thyroid cancer (PTC). DESIGN Retrospective medical chart review. SETTING Tertiary cancer institution. PATIENTS The study population comprised 331 consecutive patients primarily treated for papillary thyroid carcinoma (PTC) at a tertiary cancer institution between 1996 and 2003. The lateral neck compartments were surgically addressed only in the presence of abnormalities on ultrasonography (US). MAIN OUTCOME MEASURES Recurrence-free interval and overall, disease-specific, and recurrence-free survival. RESULTS There were 112 male and 219 female patients, with a median age of 44.7 years (range, 11-87 years). The median follow-up time for the series was 77.9 months (range, 12.7-148.7 months). Preoperative US abnormalities were found in the right neck in 13.3%, in the left neck in 12.3%, and bilaterally in 11.2%; all of these patients underwent a lateral neck dissection at the time of the thyroidectomy. There were 11 recurrences in the series (0.3%), with a median time to presentation of 22.8 months (range, 6.0-55.3 months). Predictors of lateral neck disease-free interval were T stage and distant disease at presentation (P = .01 and P < .001, respectively) and the sonographic status of the ipsilateral and central neck (P = .001 and P < .001). The number of abnormal neck compartments in US correlated with the risk of regional failure (P = .01). The presence of US abnormalities in the lateral neck decreased the 10-year disease-specific survival from 98.3% to 66.9% (P < .001). CONCLUSIONS Preoperative US is an excellent outcome predictor for lateral neck disease-free interval and for disease-specific survival in PTC. Sonographically based surgical approach provides excellent long-term regional control and validates current treatment guidelines.

Chronic mTOR activation promotes cell survival in Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive skin cancer with rising incidence. In this study, we demonstrate that mTOR activation and suppressed autophagy is common in MCCs. mTOR inhibition in two primary human MCC cell lines induces autophagy and cell death that is independent of caspase activation but can be attenuated by autophagy inhibition. This is the first study to evaluate mTOR and autophagy in MCC. Our data suggests a potential role of autophagic cell death upon mTOR inhibition and thus uncovers a previously underappreciated role of mTOR signaling and cell survival, and merits further studies for potential therapeutic targets.

Using 5-Aminolevulinic Acid and Pulsed Dye Laser for Photodynamic Treatment of Oral Leukoplakia

OBJECTIVE To determine the safety and efficacy of photodynamic therapy in the treatment of oral leukoplakia with 5-aminolevulinic acid and pulsed dye laser. DESIGN Nonrandomized, single-arm, single-site phase 1/2 pilot study. SETTING Academic referral center. PATIENTS A total of 23 patients, aged 37 to 79 years, having a confirmed diagnosis of leukoplakia with or without dysplasia measuring at least 10 mm in diameter. INTERVENTIONS Application of 5-aminolevulinic acid to lesions followed by activation with high-power 585-nm pulsed dye laser. MAIN OUTCOME MEASURES Maximum tolerated dose of laser, postprocedure complications, objective response to treatment, and immunohistochemical changes in treated tissue. RESULTS No significant adverse events occurred; minor local adverse effects were observed during and following photodynamic therapy in the safety phase of the study. The maximum tolerated dose was 8 J/cm(2). Of 17 patients, 7 (41%) had more than 75% regression (significant response) and 9 (53%) had more than 25% regression (partial response), for an overall response rate of 94% at 90 days. This response rate was far higher than the null-hypothesis 20% rate (P < 10(-10)) and the alternative-hypothesis 50% rate (P = .0001) for which the study was powered. When compared with baseline levels immunohistochemically, p53 expression was increased in 8 of 11 available samples (73%) and Ki-67 expression was decreased in 7 of 12 available samples (58%). CONCLUSIONS Photodynamic therapy with 5-aminolevulinic acid and pulsed dye laser could be used to achieve regression of oral leukoplakia. The treatment is safe and well tolerated. An application time of 1.5 hours and laser radiant exposure of 8 J/cm(2) with 1.5-ms pulse time were found to be the optimal settings in this study. The high-power laser used in this study allows completion of laser therapy within 1 to 3 minutes. Further studies are necessary to determine the optimal laser radiant exposure and drug application to maximize the response rate.

Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma

Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super-enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor JQ1 disrupts BRD4 association with super-enhancers, downregulates proto-oncogenes, such as c-Myc, and displays antitumor activity in preclinical animal models of human cancers. Here we show that an enhancer proximal to the c-Myc promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and coincides with a putative c-Myc super-enhancer in MCC cells. This observation is mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the putative c-Myc super-enhancer region by JQ1 correlates with decreased c-Myc expression. Thus, our study provides initial evidence that super-enhancers regulate c-Myc expression in MCC.