Faculty Bibliography

PURPOSE: Head and neck neoplasms requiring surgical resection of the mandible can have negative consequences on patient quality of life. For patients with segmental resections, the vascularized fibular free flap and nonvascularized iliac crest are frequently used. The fibula has surpassed the iliac crest in popularity due to the success associated with a vascularized graft; however, there still remain significant advantages with the nonvascularized graft. There has not been a study comparing the quality of life associated with these two methods of mandibular reconstruction. We carried out the following study to compare quality of life of both grafts in an attempt to help guide therapeutic decisions. PATIENTS AND METHODS: Twenty-nine patients at the University of California, San Francisco undergoing mandibular resection with subsequent reconstruction with either a vascularized fibular free flap or nonvascularized iliac crest bone graft were identified. Patient quality of life was assessed with a modified version of the University of Washington Quality of Life Questionnaire, version 4. RESULTS: Eighteen patients responded (10 reconstructed previously with a fibula, 8 with iliac crest reconstructions). Patients with an iliac crest bone graft had significantly better chewing and swallowing scores (P = .04, P = .049 respectively). There was also a trend for better taste (P = .067). When patients with a history of radiation therapy were excluded, differences in chewing and swallowing were not significant (P = .26 and P = .31 respectively), whereas taste was (P = .038). CONCLUSIONS: These findings suggest that reconstruction with the iliac crest had benefits in improved function (chewing, swallowing, and taste) rather than esthetics, donor site morbidity, or psychologic discomfort as was anticipated. However, prior radiation, a relatively frequent therapy in this patient population, presents an important confounding factor. Radiation therapy is difficult to control for without limiting an already scarce patient pool, and bears with it significant morbidity that likely influenced these findings. Further study is warranted to confirm the results and further distinguish the 2 groups

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize to the neck, an event that dramatically worsens prognosis. Metastasis occurs even in earlier stages when no neck lymph node involvement is clinically detectable (N0). Management of the N0 neck, namely when and how to electively treat, has been debated extensively. This article presents the controversies surrounding management of the N0 neck, and the benefits and pitfalls of different approaches used in evaluation and treatment. As current methods of assessing the risk for occult metastasis are insufficiently accurate and prone to underestimation of actual risk, and because selective neck dissection (SND) is an effective treatment and has minimal long-term detriment to quality of life, the authors believe that all patients who have oral SCC, excluding lip SCC, should be prescribed elective treatment of the neck lymphatics. However, this opinion remains controversial. Because of the morbidity of radiation therapy and because treatment of the primary tumor is surgical, elective neck dissection is the preferred treatment. In deciding the extent of the neck dissection, several retrospective studies and one randomized clinical trial have shown SND of levels I through III to be highly efficacious

In this study, we investigated the role of the peripheral endothelin-1 (ET-1) concentration in a cancer pain model. To test the hypothesis that the concentration of ET-1 in the tumor microenvironment is important in determining the level of cancer pain we used two cancer pain mouse models that differed significantly in production of ET-1. The two mouse cancer models were produced by injection of cells derived from a human oral squamous cell carcinoma (SCC) and melanoma into the hind paw of female mice. Pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, was significantly greater in the SCC group than the melanoma group. The peripheral concentration of ET-1 within the cancer microenvironment was significantly greater in the SCC group. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly higher in the SCC model compared to the melanoma model. ET receptor antagonism was effective as an analgesic for cancer pain in the SCC model only. To address the potential confounding factor of tumor volume we evaluated the contribution of tumor volume to cancer pain in the two models. The mean volumes of the tumors in the melanoma group were significantly greater than the tumors in the SCC group. In both groups, the pain level correlated with tumor volume, but the correlation was stronger in the melanoma group. We conclude that ET-1 concentration is a determinant of the level of pain in a cancer pain mouse model and it is a more important factor than tumor volume in producing cancer pain. These results suggest that future treatment regimens for cancer pain directed at ET-1 receptor antagonism show promise and may be tumor type specific

PURPOSE: Squamous cell carcinomas of the hard palate, maxillary gingiva, and maxillary alveolus occur at relatively low rates compared with squamous cell carcinomas in other oral sites. There is little within the surgical literature to guide treatment for maxillary squamous cell carcinoma. To date, only 1 other group has addressed neck management in the oral maxillary squamous cell carcinoma patient presenting with a clinically negative neck. Adequate characterization of maxillary gingival carcinoma behavior with respect to regional cervical metastasis is wanting. PATIENTS AND METHODS: We present a retrospective review of our own clinical experience as well as a review of the existing literature. RESULTS: In our University of California San Francisco patient group, cervical disease was detected in 20% of those individuals with maxillary squamous cell carcinoma presenting for initial consultation. After ablative surgery, those individuals who presented with clinically negative necks had a 21.4% rate of regional node metastasis. Ultimately, 50% of our patients with squamous cell carcinomas of the palate, maxillary gingiva, and maxillary alveolus developed regional or metastatic distant disease; 42.9% of the patients manifested disease to the cervical lymph nodes alone. CONCLUSIONS: The cases of oral maxillary squamous cell carcinomas reviewed herein exhibit aggressive regional metastatic behavior comparable to that of such carcinomas of the tongue, floor of the mouth, and mandibular gingiva. Based on the findings presented herein, we recommend selective neck dissection in the setting of a clinically negative neck as a primary management strategy for patients with oral maxillary squamous cell carcinomas involving the palate, maxillary gingiva, and maxillary alveolus

We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain

PURPOSE: Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and making the decision regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. The goal of this study is to quantify and compare the amount of margin discrepancy observed based on tumor location and staging. MATERIALS AND METHODS: Forty-one patients who underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1 cm margin by one attending surgeon. Specimens were then submitted for processing and reviewing and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine percentage discrepancy. Percent discrepancies were grouped by locations (buccal mucosa, mandibular alveolar ridge, and retromolar trigone in group 1; maxillary alveolar ridge and palate in group 2; and oral tongue in group 3) and analyzed. Percent discrepancies grouped by stages T1/T2 or T3/T4 were compared. RESULTS: The mean discrepancy for all patients was a statistically significant 59.02% (P < .0001). The mean discrepancy was 71.90% for group 1, 53.33% for group 2, and 42.14% for group 3 (P = .0133). The mean discrepancy in T1/T2 tumors was 51.48% and in T3/T4 tumors was 75.00% (P = .0264). CONCLUSIONS: Oral SCC margin discrepancies after resection and specimen processing are highly significant. Tumors located in the buccal mucosa, retromolar trigone, and mandibular alveolar ridge show significantly greater discrepancies than tumors of the maxilla or oral tongue. Late stage tumors also show significantly greater margin discrepancies. These findings suggest that it might be prudent to consider oral site and staging when outlining margins to ensure adequacy of resection

Oral health care professionals could drastically improve the quality of life for patients with potentially malignant oral lesions by using a noninvasive test that could be used to detect cancer using saliva. Promoter DNA hypermethylation is a critical step in oral carcinogenesis and has a number of significant advantages over genetic and protein diagnostic markers. Methylight is a recently developed assay that rapidly quantifies promoter hypermethylation and could potentially be applied into a clinical setting

The aim of this study was to validate the published University of California San Francisco (UCSF) Oral Cancer Pain Questionnaire. To test for validity of the questionnaire, 16 patients with oral cancer completed the 8-item questionnaire immediately before and after treatment (surgical resection) of their oral cancer. For all 8 questions, the difference between mean preoperative and mean postoperative responses were statistically significant (P < .05), confirming the validity of the questionnaire to measure oral cancer pain. Internal consistency of the questionnaire was evaluated by using Cronbach's alpha, which provides an estimate of reliability based on all correlations between the items (questions) of the instrument (questionnaire). In the oral cancer pain questionnaire, questions 1, 3, and 5 evaluate the intensity, sharpness, and throbbing nature of pain when the patient is not engaged in oral function (talking, eating, and drinking). Questions 2, 4, and 6 measure the intensity, sharpness, and throbbing nature of pain during oral function. Cronbach's alpha for questions 1, 3, and 5 is 0.87 and Cronbach's alpha for questions 2, 4, and 6 is 0.94; values greater than 0.7 indicate reliability. In this study, we have validated the UCSF Oral Cancer Pain Questionnaire as an effective tool in quantifying pain from oral cancer. PERSPECTIVE: The study validates an oral cancer pain questionnaire. The questionnaire can be used to reliably measure pain levels before and after surgical resection in patients with oral cancer