The prognostic role of clinical, morphological and molecular markers in oral squamous cell tumors.

Despite of considerable advances in the diagnostic and therapeutic possibilities, the prognosis of epithelial tumors in the oral cavity is still very poor. A knowledge of the prognostic factors at the beginning of treatment is therefore indispensable for determination of the appropriate therapy for the given patient. These factors may be linked to the patient (e.g. age, sex, general condition and immunological parameters) or to the tumor localization. A survey of the literature reveals that the TNM stage, the grade, the mode of invasion and the depth of the tumor infiltration are generally the most important factors influencing the fate of the patient. The prognosis depends primarily on the clinicopathological parameters, though even if they are known, it is not possible to screen out those patients who are at particular risk of a relapse. During the past 10 years, study of the DNA content distribution, the proliferation markers and certain oncogenes has come into the focus of attention; great interest is also shown in the extracellular matrix components and the metalloproteinases, which play key roles in the invasion and metastasis formation.

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.

Ultrastructural, lectin histochemical and immunohistological observations on Merkel cell tumors.

The clinicopathological and ultrastructural findings of 10 cases of Merkel cell tumor (MCT) are presented. Three patients died rapidly due to tumor dissemination. The tumor cells in eight out of the 10 cases were positive for neuron-specific enolase, however, all were negative for the ten polypeptide hormones examined, as well as for the argentaffin and argyrophil reactions. One of the patients had suffered from chronic lymphocytic leukaemia. Particularly in this case, but also in the others, the differentiation of MCT from a malignant lymphoma necessitated immuno-histological, lectin histochemical and ultrastructural studies. The focal peanut agglutinin positivity of the tumor cells in 6 out of the 10 MCTs seems to be a characteristic feature of these cells.

epsilon-N-trimethyl-lysine: a natural cell component with mitogenic activity.

The blastogenic capacity of a new mitogenic agent, epsilon-N-trimethyl-lysine (TML) was examined on human peripheral blood lymphocytes. The changes in relative DNA and histone content after TML treatment testified that activated lymphocytes passed through the whole cell cycle. The comparison of the 3H-TdR incorporation rate into unseparated T-B lymphocyte and purified T lymphocyte cultures suggested a preferential effect on the thymidine incorporation of T lymphocytes. TML induced preferentially high responses in cases of blood cells taken from women. The possibility of DNA repair mechanism could be excluded. The results of combined TML-PHA treatment experiments suggested a difference in the trigger mechanism of these two mitogenic compounds.

The pathomorphology of a human xenotransplanted basaloid squamous cell carcinoma.

To elucidate some factors related to the malignant phenotype of an oral tumor with mixed cell population the question has been raised whether the biological behavior of the basaloid or the squamous cells show any difference in an immunosuppressed host organism. Basaloid squamous cell carcinoma (BSCC) surgically removed from sublingual location was xenotransplanted either subcutaneously or in the oral submucosa and the histology, ultrastructures, LDH isoenzyme pattern were investigated. The epithelial origin of the established tumor line (HTB-1) could be recognized according to the characteristic epithelial ultrastructures, while the type of the LDH isoenzymes proved its human origin. The squamous cell population dominating the parent surgical specimen of BSCC regressed during xenotransplantation in the subcutan location, on the contrary the basaloid cells grew and maintained the tumor. Interestingly the basaloid cells transplanted from the subcutis to the oral submucosa generated a squamous cell population with an infiltrative growth pattern. The xenografted BSCC offer a promising model to investigate the contribution of each cell populations in the malignant phenotype. The presented data indicate that the basaloid cells are responsible for maintaining the tumor cell population, but certain malignant features (i.e. infiltrative growth) is associated to the squamous cells which are generated from the basaloid cells only under specific circumstances. Thus this particular model system showed that different malignant features could be associated to the basaloid and to the squamous cell component.

Autogenous bone versus beta-tricalcium phosphate graft alone for bilateral sinus elevations (2- and 3-dimensional computed tomographic, histologic, and histomorphometric evaluations): preliminary results.

The aim of this research was to compare 2 different graft materials, beta-tricalcium phosphate (Cerasorb) and autogenous bone, used in the same patient. Bilateral sinus grafting was performed on 4 selected patients; Cerasorb only was used on the experimental side, and autogenous bone only was used on the control side. In all 4 patients, the maxilla was atrophied to such an extent that the reconstruction included not only sinus grafting but also onlay plasty. The procedure was followed by implant placement 6 months later. In addition to routine panoramic radiographs, 2- and 3-dimensional computed tomographic (CT) examinations were performed pre- and postoperatively and after implantation. Information from CTs is necessary when alveolar bone atrophy is extensive, complications appear probable, and in difficult cases, when exact documentation is important. A total of 16 bone biopsies were taken at the time of implant placement. The histologic and histomorphometric results indicated that when the formation of new bone was slow, it was slow on both sides; when it was fast, then it was fast on both sides. Individual patient factors strongly influenced the fates of the various graft materials in the organism. Comparisons of the present results with the findings of other investigators demonstrated that beta-tricalcium phosphate is a satisfactory graft material, even without autogenous bone.

Use of Bioplant HTR synthetic bone to eliminate major jawbone defects: long-term human histological examinations.

This article describes the long-term follow-up of Bioplant HTR Synthetic bone (HTR: hard tissue replacement) in the human organism, as revealed by clinical, radiological and histological examinations and observations over a period of 5 years. Twenty-nine patients with lesions, 9 keratocysts, 16 radicular cysts, 3 traumatic cysts and 1 odontome were followed continuously during this period. All patients selected for follow-up had two criteria in common: the initial intervention had been performed at least 5 years previously; and the largest diameter of the bone defect was at least 2 cm. In all cases, when large bone defects were filled with HTR, the cavity was eventually filled with newly formed and remodelled bone. The process of ossification was relatively slow. In these cases, complete bony regeneration took up to 5 years. Ossification did not continue in the soft parts around the bone cavity. The histological pictures confirmed complete bone healing over the time.

The effects on teeth of radiotherapy for nasal endodermal sinus tumor (yolk sac tumor) in childhood.

A rare case of a 10-year-old girl with an endodermal sinus tumor that occurred in the nasal cavity is presented. She received chemotherapy and radiotherapy at the age of 4. The subsequent abnormal development of the maxillary teeth is described and discussed in the light of the known effects of radiotherapy.

Long-term tissue tolerance of titanium-encapsulated cobalt-samarium implants.

The tissue reactions of titanium-coated cobalt-samarium magnets were investigated following their full-thickness implantation into the skulls of dogs and pigs (six of each species). The implants, together with the surrounding bone, were removed en bloc 1, 2, 3, 6, 9, and 12 months postoperatively. Following physical and radiological examinations, the excised samples were subjected to histologic investigation. The osseointegration process was observed to follow a normal course around the titanium capsule. The magnetic field did not give rise to any tissue changes that could be demonstrated by means of classical histologic methods.

HTR polymer and sinus elevation: a human histologic evaluation.

HTR (hard tissue replacement) polymer was used in a second session to perform 26 sinus floor elevations in 16 patients with dental implantation (Flexiroot, U.S.A.). A period of 6, 8, 10, or 12 months elapsed between the two operations, making it impossible to examine the tissular integration of HTR from both clinical and human histologic aspects. Following the sinus elevation, neither prolonged wound healing nor a rejection reaction was observed in any of the cases. During an 8 to 10 month period, sufficient new bone and fibrous connective tissue had grown between the HTR granules to ensure appropriate supporting tissue for the implantation. Subsequently (12 months), the HTR and the new bone became clinically increasingly harder, forming a union that was difficult to shape. HTR may be stated to be a material suitable for purposes of sinus elevation. In three cases in which the alveolar bone was originally very thin (2 to 3 mm), the resorption of this bone was observed, as a consequence of this the implantation was not performed. The resorption is explained by the inadequate blood supply that developed for surgical-technical reasons, and is not connected with the nature of the material used for the sinus elevation.

[Correlation between tumor regression and survival time after chemotherapy in cancer of the oral cavity]. / A kemoterápiára bekövetkezö daganat-regresszió és a túlélés összefüggése szájüregi rákban szenvedö betegeknél.

The examinations were performed on thirty patients with biopsy-confirmed squamous cell carcinoma of the oral cavity in clinical stage T2-3No-2M0. The aim of the present study was to perform a histological evaluation of the effect of preoperative intra-arterial treatment of surgically removed tumours and to analyse the correlations with the survival of the patients. The tumour regression (R) was evaluated quantitatively on a scale ranging between 1 and 4 points. The evaluation yielded a value of R1 in 8/30 cases (residual tumour was not found histologically). A tumour of microscopic size (R2) was found in 5/30 cases. Partial regression (R3) was established in 12/30 cases, and a slight response (R4) in 5/30 patients. The histologic picture was evaluated qualitatively on the basis of three arbitrarily chosen parameters. Examinations were made on the morphological picture of the residual cancer (C), the inflammatory reaction of the stroma (S) and the demarcation tendency of the tumour (D) and the sum of these values (A). The higher this point score, the poorer the tumour in question responds. Tumours with a score of A3-5 proved to have a very favourable prognosis in contrast with those with a score of A8-9. For the borderline scores of A6-7 the subsequent fate of the patient was decided by the extent of the original tumour and by the occurrence or not metastases. It is noteworthy that, with a comparatively small number of patients, a significant correlation was demonstrated between the survival and the total qualitative point count (A), the S value and the D value.

[Long-term studies after intra-arterial cytostatic therapy of head and neck tumors]. / Hosszú távú vizsgálatok fej-nyak daganatok intra-arterialis cytostaticus kezelése után.

This study on selected tumour patients demonstrates relationship between the effectiveness of preoperative, postoperative and palliative intra-arterial cytostatic treatment of tumours of the head and neck and the long-term survival. During the period ranging between 3.5 and 9 years after preoperative treatment of 11 cases, palliative treatment of 6 cases, resulting in 100% tumour regression, and postoperative-adjuvant treatment of 23 cases (selected from 254 cases receiving intra-arterial treatment), local recurrence was observed in 10 cases. The question is raised of the necessity of radical surgery corresponding to the original tumour after preoperative treatment resulting in a completely tumour-free state.

[Histological evaluation of the effect of intra-arterial cytostatic treatment]. / Az intraarterialis citosztatikus kezelés hatásának szövettani értékelése.

In cases of untreated mouth cavity carcinomas cisplatin, farmorubicin as well as a combination of the two have been administered intra-arterially to three groups of patients. Result of the treatment was similar tumor regression in all three groups. Thrombotic complications were more frequent in cases treated with farmorubicin. Possibilities of preventing vein damages are reported on.

[Gouty tophus of the temporomandibular joint]. / Köszvényes tophus elöfordulása a temporomandibuláris ízületben.

A rare case of gouty tophus localized to the temporomandibular joint is reported on by which alimentary troubles were caused. Establishment of clinical diagnosis was rendered more difficult by lack of gauty anamnesis.

[Degenerated schwannoma of the oral cavity]. / Degenerált schwannomák a szájüregben.

Until now big oral cavity degenerated schwannoms were publishen in the literature. The publication describes two further cases. The x-ray'macroscopic and microscopic images of their cases are known.

[Effectiveness of intra-arterial chemotherapy in the management of intra-oral cancers and their lymphatic metastases]. / Az intraarterialis kemoterápia hatékonysága szájüregi rákok és nyirokcsomó-metasztázisaik komplex kezelése során.

The effect of complex therapy (intra-arterial chemotherapy and radical surgery) on primary tumours and their metastases was studied in 38 oral squamous cell cancer cases. The therapy had different effect on the primary tumours and their lymph node metastases. There was a close correlation between the number of metastatic lymph nodes and survival. The extension and the chemotherapeutic regression rate of metastatic lesions showed a significant correlation with patients' survival.

[Relation of the histological picture of biopsy material and prognosis in cases of squamous cell carcinoma of the oral cavity]. / A próbakimetszés szöveti képe és a prognózis összefüggései szájüregi laphámrákos esetekben.

Biopsy specimens from 42 oral cancer cases were graded by a histological scoring system which was initiated by Bryne et al. This system was based on both the features of the tumor cells and the relationship between tumor cells and connective tissue. The results suggested significant correlation between the histological score values and the survival, the occurrence of recidive tumors and metastatic tumors.

[Experience with the clinical use of HTR (hard tissue replacement) polymer. Sinus elevation, human histological studies]. / Tapasztalatok a HTR polymer klinikai alkalmazásával. Sinus elevatio, human szövettani vizsgálatok.

The HTR polymer was employed under clinical circumstances. Results supported that the HTR polymer may well be employed for bone replacement. The forming of the support tissue between the plastic granulums has been accompanied with biopsies. Though in some cases giant cell reaction of alien body type have been observed, yet this has never been of such degree that it would have impeded the reception of the stuff. According to the authors opinion after reinforcement of the lower wall of the facial cavity with HTR polymert in 8 to 10 months an enduring suitable support tissue is formed.

[The value of beta-tricalcium-phosphate (CERASORB) in pre-prosthetic surgery]. / A beta-tricalcium-foszfát (CERASORB) jelentósége a preprotetikai sebészetben.

Short- and medium-term experience with a pure-phase beta-tricalcium phosphate bone-substitute material (Cerasorb) is reported on the basis of clinical, radiological (panorama, 2-3D CT records) and histological examination on 52 patients. The treatment modes on these patients included the filling of cysts, sinus grafting, augmentation and the filling of parodontal lesions. Disturbance of wound healing was not observed in any of the cases, and both the radiological and the histological examinations revealed that transformation of the implanted beta-tricalcium phosphate into bone could be detected as early as in the second month. During the 10-month follow-up period, this transformation was continuous, but was not complete; completion is to be expected only after 12 months. It is important that load-bearing tissue had already developed after 4-6 months. Studies to date suggest that autologous bone is not necessary for either sinus grafting or the filling of large cysts: Cerasorb alone is suitable for this purpose.