The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.

OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

Indication and surgical technique for extended hemilaryngectomy.

Previous experience has shown that conservation of the healthy hemilarynx is possible for the treatment of extended lateralized laryngeal and hypopharyngeal cancers. One major indication for supracricoid hemilaryngectomy is glottic cancer involving either the arytenoid or Morgagni's ventricle. Hemilaryngopharyngectomy is also indicated when tumor of the pyriform sinus involves its anterior part, lateral wall, medial wall and ary- and pharyngoepiglottic folds. Supracricoid hemilaryngopharyngectomy was performed in seven cases. The resection consisted of removal of the surpacricoid hemilarynx and ipsilateral pyriform sinus. The reconstruction was performed by elevating the posterior pharyngeal wall and suturing the mucosa to the midline. This surgical technique provided good functional results. Patients had no airway impairments, but the recovery of satisfactory deglutition may require 14-32 days. Phonatory rehabilitation was successful, and each patient had a satisfactory vocal quality. Postoperative irradiation did not affect the functional results.

Investigation of premalignant lesions of larynx epithelium with histoautoradiography and HPV-assay.

The histological evaluation of precancerous alterations of larynx epithelium is, in transitional cases, very difficult. The differentiation of harmless metaplasia, hyperplasia and keratosis from abnormal proliferation depends on the pathologist's training and experience. Fine diagnostic lines separate the different grades of dysplastic epithelial alterations. The tritiated thymidine, 3H-TdR, labelling and histoautoradiographic procedure of biopsy specimens taken from the larynx provide the possibility to recognise the DNA synthetiser cells. The number, location and distribution of 3H-TdR labelled cells in the epithelial layers help us to distinguish with clarity the growth activity, the degree of dysplasia. After 3 weeks' exposition time of sections prepared by photoemulsion and stained with haematoxilin-eosin, the result can be assessed. In addition to histoautoradiography HPV-assay was applied, as HPV may play a role in the pathogenesis of laryngeal preneoplastic alterations.