Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro.

The invasion and migration occurring in primary neoplastic tissue explants were studied by using a three-dimensional collagen matrix model, subsequent time-lapse videomicroscopy, and computer-assisted cell tracking. We show that not only single cells but groups of clustered cells comprising 5 to more than 100 cells detach from the primary tumor lesion and migrate within the adjacent extracellular matrix. These clusters were highly polarized, resulting in a high directional persistence of migration. Locomoting cell clusters were observed in primary cultures from invasive oral squamous cell carcinomas (6 of 9), ductal breast carcinomas (2 of 3), and rhabdomyosarcoma (1 of 1), whereas normal oral mucosa (0 of 4) was cell cluster negative. Thus, locomoting cell clusters could be a novel and potentially important mechanism of cancer cell invasion and metastasis.

Microvascular free tissue transfer in head and neck and esophageal surgery.

Successful reconstruction for excisional defects of the head and neck and esophagus was accomplished in 93 percent of our patients using microvascular free tissue transfer. Complete failure occurred in 7 percent of the patients. Major defects after head and neck cancer surgery constituted the main indication for use of microvascular free tissue transfer for reconstruction. Ninety-four percent of the patients had undergone an extensive excisional procedure. A wide range of cutaneous, myocutaneous, and osteocutaneous free flaps, as well as free bowel autotransfers were used. Complete failure was three times higher in the previously irradiated patients (4 of 41 patients) compared with nonirradiated patients (1 of 34 patients). Morbidity and mortality rates were consistent with expected ranges in patients who were undergoing major head and neck resection. Donor site complications occurred in 23 percent. Thin flaps are favored for reconstruction of anterior defects in the oral cavity, whereas bulkier flaps are more suitable for deeper defects in the oropharynx and hypopharynx. The advantages are both aesthetic and functional. The free jejunal autograft is considered the reconstructive method of choice for defects produced by laryngopharyngoesophagectomy. Highly developed and sophisticated microsurgical skills continue to be the mainstay of success. The implication of free tissue transfer failure, especially for defects of the upper aerodigestive tract, are impressive in terms of morbidity, mortality, and cost. These considerations limit the application of this method of reconstruction to centers that have sophisticated and productive reconstructive surgeons with microsurgical skills.

Long-term outcome following total parathyroidectomy in patients with end-stage renal disease.

Long-term follow up (mean 3.8 years), following elective total parathyroidectomy in thirteen patients with end-stage renal disease is described. Nine patients are alive and all except two have measurable levels of intact parathyroid hormone (PTH). One patient is mildly hyperparathyroid with PTH levels of 143 pg/ml (normal 10-65 pg/ml). All patients did well as far as their bone and mineral metabolism were concerned and there were no fractures, bone pain or metastatic soft tissue calcification. Lumbar spine bone mineral density (BMD) increased above the baseline value and femoral neck bone density was significantly greater than a matched control group of non-parathyroidectomized dialysis patients (1.097 +/- 0.140 versus 0.811 +/- 0.148 g/cm2, Z-score 1.98 +/- 1.64 versus -0.79 +/- 1.07, p < 0.001). Two of the nine patients have been transplanted, both have good allograft function and show increases in BMD. We believe that these findings justify the complete removal of all parathyroid tissue for selected patients with chronic renal failure where medical therapy has failed and aluminium bone disease has been excluded. They also raise the possibility that PTH is necessary for bone loss to occur.

Use of carbon dioxide laser for the treatment of premalignant lesions of the oral mucosa.

The carbon dioxide laser was used for the treatment of 20 lesions of the oral mucosa in 14 patients. These lesions ranged histologically from benign hyperkeratosis to verrucous carcinoma. The patients selected for this treatment were identified at high risk to develop malignant lesions in the oral cavity. Precise vaporization of the affected mucosa were carried out using the Cavitron 40-300-A CO2 Surgical Laser. Destruction of the surface epithelium and submucosa was achieved by using defocused beam at a setting of 10W. Biopsies were taken at 1 cm intervals at the time of laser treatment. Fourteen of the 20 procedures were carried out under local anesthesia on an outpatient basis. Seven procedures were performed under general anesthesia and 2 patients required 24 h postoperative observation. Local control was achieved in 17 of the 20 treated sites. Two of the three treatment failures occurred in patients in whom the final histology revealed either in situ or invasive squamous carcinoma. Only one patient with dysplasia was not controlled after vaporization of the lesion by the carbon dioxide laser. The laser continues to show encouraging results as an alternative to surgical resection of precancerous mucosal lesions of the oral cavity. Vaporization of the dysplastic lesion(s) with carbon dioxide laser is recommended for patients with an identifiable risk for the development of intraoral malignancy. This is an effective, nonmorbid, inexpensive, quick, and relatively painless method of managing this condition.

Early oral and oropharyngeal cancer in nontobacco users.

In order to define the clinical behavior and characteristics of oral and oropharyngeal squamous cancer in nontobacco users, 40 surgically treated American Joint Commission (AJC) stage I and II tumors in 36 nontobacco-using patients were retrosepctively compared with 306 similarly staged and treated tumors in 286 tobacco-using patients. Significantly more nontobacco-associated tumors were found in females (P less than 0.005) whose mean age was significantly greater than that of tobacco users (P less than 0.001). Nontobacco users had proportionately more tumors of the buccal mucosa, oral tongue, and hard palate and fewer of the floor of mouth (P less than .025). There was no difference in the distribution of histologic grades between the two groups. The incidence of initial or subsequent nodal disease and the incidence of second upper aerodigestive tract cancers were similar. Despite similar rates of failure of initial treatment, the mean time to failure was significantly greater in nontobacco users (P less than 0.01). There was no difference in determinate 5-year survival between the two groups. Oral and oropharyngeal cancers in nontobacco users are no more aggressive than similar lesions in tobacco users.

The potential uses of high-dose-rate brachytherapy in patients with head and neck cancer.

Brachytherapy has proven to be an extremely valuable method of treatment for head and neck cancer. The data supporting its application, however, is based on continuous low-dose-rate brachytherapy. To benefit from improved radiation protection, outpatient treatments, and increased patient tolerance of treatment set-up over that encountered in conventional low-dose-rate manually afterloaded brachytherapy, we implemented a high-dose-rate remote afterloading approach in selected patients with head and neck cancers. This treatment was utilized in two different roles in managing 29 patients. In its first role, it was used as the sole treatment in 13 patients with T1-2 N0 malignancies. A total of ten treatments of 450-500 cGy each were delivered twice a day with a minimum of 5-6 h between treatments. With a median follow-up of 9 months, only 1 patient failed locally. In a second role, brachytherapy was applied in a post-operative adjuvant setting following wide local excision of tumors in patients who presented with recurrent disease (12 cases) or a second primary in the head and neck (4 cases). All patients had previously received external irradiation to the head and neck. Due to this previous course of irradiation, only eight treatments of 300 cGy each were delivered, for a total of 2400 cGy over a period of 4 days. However, with a follow-up of 2-16 months, only 3 patients remain disease-free.

Impact of magnetic resonance imaging and computed tomography on the staging of laryngeal cancer.

This retrospective study quantitatively assessed the effects of magnetic resonance imaging (MRI) and computed tomography (CT) on the staging of laryngeal cancer. A blind comparison between CT and MRI was made in a group of previously untreated patients with squamous cell carcinomas of the larynx. From June 1992 to November 1993, 29 patients were eligible for study. Of these, 14 patients (48%) had supraglottic lesions, 11 patients (40%) had glottic lesions and 4 patients (14%) had both. No subglottic lesions were seen. The data suggest that clinical staging of laryngeal tumors is inadequate. MRI proved superior to CT for staging tumors, especially those confined to the supraglottis. Nevertheless, clinically staged T1 or T2 lesions could be adequately assessed by CT alone. Findings also indicate that MRI should be reserved for T3 or T4 clinically staged lesions. Furthermore, most nodal disease can be staged by CT.