Comparison of IMRT techniques in the radiotherapeutic management of head and neck cancer: is tomotherapy "better" than step-and-shoot IMRT?

Currently, the most common method of delivering intensity-modulated radiotherapy (IMRT) is through step-and-shoot, segmental multi-leaf collimator (SMLC)-based techniques. Although rotational delivery methods such as helical tomotherapy (HT) have been proposed as offering advantages in the treatment of head and neck cancer, a lack of clinical data exists on its potential utility. This study compared dosimetric, clinical, and quality-of-life endpoints among 149 patients treated by HT and SMLC-IMRT for head and neck cancer. Dosimetric analysis revealed that the use of HT resulted in significant improvements with respect to mean dose (23.5 versus 27.9 Gy, p = 0.03) and V30 (30.1 versus 43.9 Gy, p = 0.01) to the contralateral (spared) parotid gland. However, the incidence of grade 3+ xerostomia in the late setting was 10% and 8% among patients treated by HT and SMLC-IMRT, respectively (p = 0.46). There were no significant differences in any of the quality of life endpoints among patients treated by HT and SMLC-IMRT (p > 0.05, for all). Acknowledging the biases inherent in this retrospective analysis, we found that the dosimetric advantages observed with HT compared to SMLC-IMRT failed to translate into significant improvements in clinical outcome. Prospective studies are needed to further evaluate how HT may affect the therapeutic ratio.

Skull base surgery for malignancy: when not to operate.

The purpose of this paper is to detail the contraindications for surgery, with curative intent for those patients who suffer from a head and neck malignancy that invades the intracranial space. This is based on a 30-year experience of over 250 patients. The most important contraindications are anatomical. Surgery is not done if the following structures are invaded: brain stem, eloquent portions of the cerebrum, superior sagittal sinus, both internal carotid arteries, both cavernous sinuses and certain vital bridging veins. Certain tumor factors are absolute but are occasionally relative contraindications: such as distant metastatic disease especially if multiple and at multiple anatomic sites. Some tumors that behave in a particularly virulent fashion that defy complete resection but are often difficult to predict preoperatively. Lack of patient medical fitness or absence of patient commitment to the operative procedure is make-up two serious contraindications to surgery.

Transoral approaches to the clivus and nasopharynx.

This article presents the surgical anatomy of the clivus, nasopharynx, and craniocervical junction as it relates to the transoral approach to the midline basicranium. Particular attention is given to the indications, limitations, and complications of this procedure. The transpalatal approach is discussed in detail. Finally, the transmandibular approach is also briefly discussed.

Maxillary deformities.

The management of congenital maxillary anomalies can be managed with ease by the well trained facial plastic surgeon. An understanding of dental anatomy, occlusion, and the rudiments of cephalometric analysis are important prerequisites for this type of work. A background in the management of facial trauma prepares the surgeon for the surgery involved. A sense of aesthetics is required to adequately anticipate what the final cosmetic and functional outcome should be in these cases. The Le Fort III osteotomy is particularly difficult, especially if there is associated hypertelorism that requires craniotomy. Significant experience in the less demanding operations of the maxilla coupled with experience in skull base surgery is essential before tackling this demanding procedure.

Vascular anomalies of the head and neck.

Vascular abnormalities of the head and neck are relatively uncommon lesions. An understanding of these anomalies based on their pathogenesis and natural history clearly divides them into hemangiomas and vascular malformations. Treatment strategies that are reasonable and predictable can then be devised based on the aforementioned factors.

Sphenoid marsupialization for chronic sphenoidal sinusitis.

OBJECTIVES: To review experience with sphenoid marsupialization and describe the technique using new instrumentation. STUDY DESIGN: Retrospective review of five cases of chronic sphenoid sinusitis that were resistant to standard medical and surgical methods, which were treated by sphenoid marsupialization. METHODS: Charts were reviewed and patients were interviewed regarding postoperative resolution of symptoms. RESULTS: Five cases of recalcitrant sphenoid sinusitis were reviewed. All patients had headache before surgery, and two had visual disturbance. In follow-up ranging from 1 to 87 months, all were free of symptoms related to the sphenoid sinus. CONCLUSIONS: Marsupialization is an effective method of exteriorizing a chronically infected sphenoid sinus. The use of functional endoscopic sinus surgery instruments and the TAC attachment of the Midas Rex drill make this surgery possible.

Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.

Complications in skull base surgery for malignancy.

OBJECTIVES: To review a consecutive series of skull base surgeries, establish the rate of complications, and outline their prevention and management. STUDY DESIGN: A retrospective review of 107 consecutive intracranial/extracranial operations performed for malignancy that transgresses the skull base. METHODS: The hospital charts of 107 operations performed on 98 patients at the University of California at Davis Medical Center. The type of operation, cause of death, and complications were noted. RESULTS: The complication rate was 50.5%. Forty-eight patients had no complications. There were six perioperative deaths. The most common surgical complications were cerebrospinal fluid leak (11.2%), meningitis (4.8%), and wound breakdown (15%). The most common medical complications were pneumonia (6.5%), cardiac disturbance (4.7%), and electrolyte imbalance (3.7%). The only prior treatment that was accompanied by a significant increase in complications was previous surgery. CONCLUSIONS: patients who had cranial base surgery for the intracranial spread of head and neck cancer. The perioperative death rate is less than 4%. The major complications were at an acceptable rate.

Predictive value of cathepsin-D for cervical lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: Prognosis of head and neck squamous cell carcinoma (HNSCC) is strongly associated with cervical lymph node metastasis. Cathepsin-D is a lysosomal protease expressed in all cells. Its role in extracellular matrix degradation is postulated to promote tumor invasion and metastasis. Increased cathepsin-D has been demonstrated in cervical lymph node metastasis in HNSCC. METHODS: Formalin fixed tumor biopsy samples from 34 patients with HNSCC of the oral cavity, oropharynx, or hypopharynx were analyzed for the presence of cathepsin-D by immunohistochemistry (1:8000, Calbiochem, Cambridge, MA). Tumors were considered positive if >50% of cells showed strong cytoplasmic staining. RESULTS: All patients had T1 or T2 lesions ranging in size from 1-4 cm and 19 (56%) had cervical metastasis. Eight (24%) were well differentiated and 26 (76%) were moderately or poorly differentiated. Thirteen tumors (38%) had high cathepsin-D expression that was strongly associated with cervical lymph node metastasis (p = 0.008). When adjusted for tumor stage and grade, cathepsin-D positivity was nearly twice as likely to be associated with node metastasis (p = 0.011). CONCLUSIONS: We demonstrated cathepsin-D expression in biopsies from a subset of patients with HNSCC and a strong association between this protease and cervical lymph node metastases. Cathepsin-D is a potential independent predictor of cervical lymph node metastasis in HNSCC and merits additional study.

Meyer procedure for severe laryngotracheal stenosis.

Many surgical procedures have been devised to manage laryngotracheal stenosis secondary to trauma. Laryngotracheal atresia is the most severe form and the most difficult to repair. The Meyer procedure is a three-stage operation that provides structural support that is covered with mucosa. A laryngotracheal trough is created and a carved trough-shaped cartilage graft is placed above and lateral to it in the first stage. The skin over the graft is replaced by buccal mucosa in the second stage. In the last stage, the cartilage graft with overlying mucosa is swung onto the trough as a composite flap replacing the anterior and lateral laryngeal and tracheal walls. Attempt at reconstruction was made in 8 patients. All but one lesion was secondary to endotracheal intubation. Two patients were unable to be taken to completion of the third stage. Of the remaining 6 patients, all have a functional voice and only 1 remains cannulated at night.

Heat shock protein and p53 expression in head and neck squamous cell carcinoma.

BACKGROUND: Heat shock proteins have been associated with the mutant form of the tumor suppressor gene, TP53, and with resistance to cancer chemotherapy. METHODS: Archival tissues from 50 patients with head and neck squamous cell carcinoma who received primary surgical resection were examined for p53, HSP27, and HSP70 by immunohistochemistry and correlated with tumor stage, grade, and 5-year survival (alive or deceased). RESULTS: Both heat shock proteins were strongly expressed in normal mucosa and in small (T1 and T2) tumors. Thirty (60%) of tumors were positive for p53, 43 (86%) for HSP27, and 34 (68%) for HSP70, with no association between p53 and heat shock protein expression. Twenty-five patients were alive (4 with disease), and 25 patients were deceased (9 from other causes). p53 Protein overexpression correlated with low-grade tumors. Only primary tumor site (i.e., oral cavity > larynx > oropharynx/base of tongue) and N stage were significantly associated with survival. CONCLUSIONS: Heat shock proteins are expressed in normal upper respiratory tract squamous mucosa, and their role in carcinoma remains unclear. None of the markers, p53, HSP27, or HSP70, demonstrated prognostic significance for 5-year survival. We confirm the recognized association of cervical lymph node metastases with decreased survival.

Surgical pathology of the skull base: a 7-year experience.

A significant diversity of tissue types interface at the base of the skull and contribute to the diagnostic challenges of skull base surgical pathology. Advances in surgical technique now permit biopsy and resection of lesions previously termed "inoperable." Retrospective review was made of all pathology specimens from skull base surgeries performed at the University of California Davis Medical Center from 1990 to 1996. Surgical biopsies and resections were performed on 186 patients who had 33 distinctive diagnoses. Any preoperative biopsy or tissue from referring institutions was reviewed prior to skull base surgery. One hundred eighteen patients had benign lesions, the most frequent of which were pituitary adenoma (55) and acoustic neuroma (27). Other benign lesions included angiofibroma, meningioma, fibrous dysplasia, and paraganglioma. Sixty-eight patients had malignant tumors, 32 of which were squamous cell earcinoma. Other malignancies included salivary carcinomas, basal cell carcinoma, neuroblastoma, melanoma, and several sarcomas. Unexpected findings were two metastatic carcinomas and five inflammatory lesions. Nearly 1500 intraoperative consultations were performed to establish resection margins and less commonly to confirm the diagnosis. The discrepancy rate between the intraoperative and final diagnosis was 1.8%. Immunohistochemistry and/or electron microscopy was utilized in 44% of the specimens to confirm the diagnosis. Surgical pathology is an essential ingredient to a successful skull base surgery program. Pathologists are involved in both pre- and intraoperative decisions. The diversity of lesions that arise from the skull base often has overlapping histologies that require careful attention to morphology and the use of ancillary studies for accurate diagnosis. The need for frequent intraoperative interpretations contributes to the significant challenge for the surgical pathologist.

Neural cell adhesion molecule in adenoid cystic carcinoma invading the skull base.

Neural cell adhesion molecules (N-CAMs) are expressed in neuromuscular tissues, neuroblastoma, and small cell lung carcinoma. Adenoid cystic carcinoma may invade the skull by either direct extension or neural involvement, particularly along the second and third divisions of the trigeminal nerve (V2 and V3). Eighteen patients with adenoid cystic carcinoma that invaded the skull base were studied. The tumors were graded into predominantly solid (3), cribriform (11), or tubular-trabecular (4) patterns, and neural involvement was evaluated histologically. Paraffin sections were examined by use of monoclonal antibodies for N-CAM and Ki-67, a proliferation marker, with the avidin-biotin-peroxidase method. Fifteen (83%) tumors showed perineural involvement; in the remaining three cases no nerves were present for histologic examination. Fourteen (93%) of 15 tumors with perineural involvement were reactive with N-CAM. Proliferation, measured by the presence of nuclear Ki-67, was markedly increased in tumors with predominantly solid patterns. We demonstrated that N-CAM is expressed in adenoid cystic carcinoma. The role of N-CAM as a neurodeterminant that facilitates the spread of adenoid cystic carcinoma along nerves, however, remains unanswered and warrants further study.

Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients.

BACKGROUND: Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. METHODS: The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. RESULTS: The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. CONCLUSIONS: Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.