Interferon combined with irradiation in the treatment of operable head and neck carcinoma. A pilot study.

Twenty-two patients with operable head and neck cancer were randomized to receive natural leukocyte alpha interferon (IFN) and radiotherapy, or radiotherapy alone (control) before operation. IFN was administered at 6 MU i.m. daily for 4 weeks and thereafter 3 times per week for 2 months. IFN treatment was introduced simultaneously with radiotherapy (2 Gy daily, 5 fractions per week). The preoperative dose was 30-32 Gy. Tumor response and side-effects were registered. The patients underwent radical surgery 3 weeks after the preoperative irradiation, followed by postoperative irradiation with 22-32 Gy. After preoperative treatment there were one complete response and 4 partial responses among 10 patients receiving IFN and 2 partial responses among 12 patients treated with irradiation alone. No difference in survival was demonstrated between the 2 groups. In the histologic examination of the surgical samples malignant cells were found in 6 of the IFN patients and in 8 of the control patients. The IFN patients had considerably more pronounced mucosal radiation reactions than the controls. The accrual of patients to the study was discontinued due to the side-effects.

A new Finnish computerized rhinomanometer.

We introduce a new sophisticated Finnish rhinomanometer in which the need for routine work has been minimized. Technical information about the instrument is given, recording procedure is described and a normal material and reproducibility test is analyzed.

Radiation-induced morphological changes and radiocurability in squamous cell carcinoma of the head and neck region. A preliminary report.

Tissue samples taken from 22 patients before and during radical irradiation of squamous cell carcinomas in the head and neck region were studied by light and electron microscopy. The changes in keratinization pattern at the ultrastructural level seemed to be correlated with the outcome of the radiotherapy. The irradiation induced several cellular changes, of which nuclear atypia was the most prominent. This atypia was considered to be mainly due to cell death rather than to an aggressive nature of the tumor, because the number of mitoses decreased at the same time. The tumor invasion pattern remained unchanged. The keratinization pattern remained almost unchanged at the light microscopical level, but a slight increase of intracellular filaments and desmosomes was found in the electron microscopic study. The amount of intercellular filaments increased in three patients out of four with complete remission (CR), but in no case with tumor dissemination (n = 3) during radiotherapy. In patients with local persistent tumor or a local recurrence (LP + LR) (n = 15) the filaments either increased, decreased or remained unchanged. The number of desmosomes either increased or remained unchanged in three of four CR patients, in 13 of 15 LP + LR patients and in only one of three patients with tumor dissemination. They decreased in two patients with tumor dissemination, but only in one case with CR and in 2 cases with LP + LR. It is suggested that changes in cytoskeleton and desmosomes might be important in anchorage of tumor cells locally and might have value for prediction of the tumor response to radiotherapy. Further studies on larger materials are, however, needed before more definite conclusions can be drawn.

Frequent irrigation in maxillary sinusitis therapy.

190 cases of maxillary sinusitis with retention of secretions were treated by frequent irrigation through an irrigation tube inserted via inferior turbinate sinus. The technique of the tube insertion through a Lichtwitz needle is described. Repeated irrigations do not need any anaesthesia and are better approved by the patients than the usual puncture irrigation. The response seems to be at least equally good as has been observed in similar patient series by repeated puncture irrigations. The patients' requests of reinsertion of irrigation tube in cases of recurrencies gives addition support to the recommendation to accept such a therapy.

Ultrastructural effects of irradiation on squamous cell carcinoma of the head and neck.

Tissue samples taken before and during the radical irradiation of the squamous cell carcinoma of the head and neck region were studied by light and electron microscopic examination. Radiation-induced cellular changes of which nuclear atypia was most pronounced. The tumor invasion pattern remained unchanged but the number of mitoses decreased. The lymphocytic infiltration increased at the beginning of the therapy (from 10-30 Gy) but decreased at the end of radiotherapy. The amount of neutrofils and the keratinization pattern remained almost unchanged at the light microscopic level, but intracellular filaments and desmosomes slightly increased in electron microscopic study. The changes in nuclear morphologic features pointing in a more undifferentiated direction are considered to be due to cell damage rather than to the more aggressive behavior of the tumor cells. This is in agreement with the decrease of mitoses which is due to radiation-induced arrest of tumor cells to the G2 phase. These changes might be related to the disappearance of tumors during irradiation. The leukocyte compartment seen in the samples might take part in the destruction of the tumor cells and in the removal of the cell debris.

Radiation-induced changes of fibroblasts in the squamous cell carcinoma of the head and neck.

The regrowth of mesenchymal tissue (stroma) surrounding the malignant epithelium is an important step in tissue remodelling during and after irradiation. The radiation-induced fibroblastic changes were studied on tissue samples taken before, during and after the radical irradiation of the squamous cell carcinoma of the head and neck. Elongated fibroblasts with large amount of rough endoplasmic reticulum were seen around the tumor epithelium before radiation. The fibrosis increased during irradiation and at the same time the shape of the fibroblasts changed so that they became more triangular and nuclear structures became more prominent together with hyperchromasia. The amount of cell organelles declined although there was a large amount collagen present. Epithelial cells invaded through the basal lamina. In most samples the basal lamina could not be seen at all and the tumor cells were dispersed between stromal elements. On the other hand there were close contacts between epithelial and mesenchymal cells throughout the study in places where the basal lamina was broken, which might indicate epithelio-mesenchymal interaction. Also the connective tissue formed by fibroblasts and collagen might be part of the radiation induced healing and destruction of the tumor cells.

Combined bleomycin treatment and radiation therapy in squamous cell carcinoma of the head and neck region.

Forty-six patients with squamous cell carcinoma of the head and neck region were randomized to either irradiation or irradiation plus bleomycin. If possible, the patients later underwent radical surgery. In the bleomycin group, significantly fewer patients had remaining tumour cells in the tissue removed at operation, and a longer time elapsed before recurrences occurred. However, bleomycin had no significant effect on the 3-and 5-year survival rates, and it did not significantly reduce the incidence of local recurrences.

Prospidin combined to preoperative irradiation in head and neck cancer.

Twenty-seven patients with operable squamous cell cancer of head and neck were randomized into the study. Twelve patients received Prospidin combined to preoperative radiotherapy and fourteen patients were treated with preoperative radiotherapy alone. The daily dose of the drug was from 0.70 mg/kg to 2 mg/kg and the total dose during preoperative radiotherapy was between 1800 mg and 2250 mg with a mean of 2073 mg. The recurrence rate was in patients receiving Prospidin three out of twelve and in patients treated with irradiation alone four out of fourteen during the observation time of 33 months. In the present study Prospidin combined with preoperative radiotherapy had no advantage as compared to irradiation alone.

Scintigraphy in early detection of mandibular disorders.

Technetium methylenediphosphonate scintigraphy was used to study the effect of irradiation on mandibular uptake. Determination of relative mandibular uptake allows comparison of results in different subjects, while determination of individual normalized mandibular uptake increases the significance of differences found in the same subject at different times. A very uniform increase of about 25% was recorded after radiotherapy of about 50 Gy; the uptake returned to pretherapeutic levels in 9 months. Osteoradionecrosis--and especially osteomyelitis--clearly increases the uptakes above the values of the irradiation effect. To increase the usefulness of scintigraphy in the early detection of an imminent complication, we recommend pretherapeutic control scintigraphy in all cases liable to such complications.

Radiography of the maxillary sinus mucosal surface with Tantalum.

Experiments were made with powdered Tantalum insufflated through a puncture trocar into 12 healthy maxillary sinuses and into 8 diseased sinuses. The spread of the powder was good enough to depict all the surfaces of the sinus if there was no secretion, irrespective of mucosal changes, but unsatisfactory if the sinus contained secretion. The Tantalum powder did not cause any harm to the patients and the clearance of this contrast medium gave additional information on the functional capacity of the sinus.

Tumour regression during radiation treatment as a guide to prognosis.

The response to radiation treatment was studied in 110 patients with head and neck cancer with a minimum follow-up of two years. If the tumour had disappeared by the mid-point of treatment (3000 rad), a significantly more favourable prognosis was found in early (T1-2N0) tumours. On the other hand, whether these tumours had disappeared or were persisting at the end of treatment, there was no difference in the recurrence during the observation time of two years. In advanced tumours there was no significant relationship between disappearance by the mid-point of treatment and recurrence up to two years. But when an advanced tumour had disappeared at the end of treatment, the prognosis was significantly more favourable. The unpredictability and often impossibility of judging the prognosis in individual cases encourages the authors to stress the importance of executing the original individual surgical plan irrespective of radiation response.

Experience with preoperative irradiation in head and neck cancer.

Experience with 47 patients with head and neck carcinoma operated after preoperative megavoltage irradiation of about 3 000 rads over 3 weeks is reported. The 3-year survival for the series was 25/47 (53%), for the cases of Stages I--II 13/19 (68%) and Stages III--IV 12/28 (43%). Neoplastic cells could not be detected in 18% of the cases at operative biopsy. The remaining neoplastic cells were considered to be degenerated and non-vital in 14%, but in 68% of the cases the histological examination revealed a viable neoplasm. Changes in the macroscopic appearance did not correlate very well with the histological findings. Disadvantages of the irradiation were so minimal that the authors consider the general application of preoperative radiation in the therapy of head and neck malignancies to be the treatment of choice.

[Experiences with polyethylene ventilation tubes in children with recurrent middle ear inflammation (author's transl)]. / Erfahrungen mit Dauerdrainage der Paukenhöhle mittels Polyäthylen-Tubus bei Kindern mit rezidivierender Mittelohrentzündung

Middle-ear ventilation tubes (of the Sheehy modification) were placed in 401 ears of 209 children under 16 years of age as treatment for recurrent middle-ear infection. The same procedure was later required in 26% of the cases studied because of further recurrence of middle-ear infection. In four per cent of all patients studied, the ventilating tube failed to cure middle ear disease in spite of controlled concomitant antibacterial therapy. In these cases, an early extrusion of the tube was commonly found. Among all patients, the tube was spontaneously extruded in 76 per cent of the ears, whereas the intubation time was longer than half a year in 53 per cent of the cases. No complications from insertion of the ventilation tubes was seen in the present series of patients. The tympanic membrane was found to be normal in 71 per cent of all cases when follow-up examination was obtained three months after completion in intubation. However, a permanent tympanic membrane perforation was found in five ears (1% of patients). The present study has confirmed the usefulness of middle-ear ventilation tubes, particularly in patients with recurrent middle-ear infections.

Technical variations in clinical ostial patency tests.

The usefulness of nasopharyngeal-antral pressure difference recording as a part of clinical ostial patency testing is demonstrated by statistical calculations from 507 patency tests. This method offers a quick confirmation of the comparison of pressure variation measured by anterior rhinomanometry and by antral pressure recordings which are the main elements of a consecutive patency test. In addition, the nasopharyngeal-antral recording has many of the advantages of a simultaneous patency test. When this difference recording is applied, the nasal reference pressure recording can also be omitted without any loss of information sought by the patency test.