Behavior and reproductive function of rat male offspring treated prenatally with 5-bromo-2''-deoxyuridine

OBJECTIVE: The aim of this study was to determine the effects of radiation on the secretion of saliva from mucous salivary glands in comparison with serous salivary glands. STUDY DESIGN: The minor salivary glands of the palate were used as an example of mucous glands, while the parotid glands were used as an example of a serous secretion organ. Serial flow rate measurements of the parotid and palatal glands were taken over a period of approximately 9 months in 13 patients who suffered from malignancies of the head and neck region. Twelve patients consented to take part in a second study in which salivary flow was stimulated by oral pilocarpine before and at the conclusion of radiotherapy and 7 months later. Complaints and symptoms were recorded at each time of measurement. RESULTS: After radiotherapy, the secretory performance of the parotid glands dropped off rapidly and irreversibly. Salivary secretion from the palatal glands was not totally diminished as a result of radiation. Clinical complaints and histologic findings indicate a serious alteration of the tissues irradiated; however, residual secretion from the remaining parenchyma of the mucous glands still remains. Pilocarpine produced a clinically significant increase of salivary flow from the palatal glands before and 7 months after radiation. Secretory performance of the parotid glands could not be sufficiently increased by stimulation with pilocarpine after radiotherapy. Clinical side effects and risks for the treatment of symptomatic postradiation xerostomia with pilocarpine were minimal. CONCLUSIONS: These findings emphasize the greater resistance and recoverability of the mucous secreting minor palatal glands in comparison with the serous secreting parotid glands. They also indicate the significant postradiation ability of the mucous secreting glands to be stimulated by pilocarpine.     

Enhancement of fractionated-dose irradiation by retinoic acid plus interferon

PURPOSE: To evaluate the relative cytotoxicity of fractionated-dose radiation in the presence and absence of 13-cis-retinoic acid (RA) plus alpha-2a-interferon (IFN), as a function of overall treatment time. METHODS AND MATERIALS: Studies were performed with the human squamous cell carcinoma line FaDu, in vitro. Attached exponential phase cells were treated with RA + IFN for 8-10 h and then exposed to single graded doses of radiation, or 1 to 6 doses of radiation at 2 Gy per dose, or to 5 doses of radiation at 2 Gy/dose with a time interval of 4-24 h between treatments. Following irradiation, the cells were incubated with drugs present throughout colony formation, and the fraction of survivors in the presence and absence of the combined drugs was calculated. RESULTS: For single graded-dose irradiation, the surviving fraction ratio at 2 Gy in the absence vs. presence of drugs was 1.27 +/- 0.19 in 3 repeat experiments. Following administration of 6 doses of radiation at 2 Gy/fraction with a 5-h time interval between treatments and, after correcting for cell proliferation between treatments, the surviving fractions differed by a factor of 3.25, again indicating an average difference in survival of 1.26 after each of the 6 2-Gy/fractions. Treatment with 5 2-Gy doses of irradiation with 24 vs. 4 h elapsing between doses, resulted in a 3-fold greater decrease in survival in the presence of drugs vs. no drug. The relatively greater cell kill due to 24 vs. 4 h between treatments was due to drug inhibition of cell proliferation between the more prolonged treatments. CONCLUSIONS: The results of this study indicate that retinoic acid plus interferon both sensitizes and inhibits cell proliferation during treatment. These results suggest that this combination of radiation and drugs, when used concurrently, may be effective for inhibiting tumor cell proliferation or accelerated repopulation during clinical fractionated radiotherapy.     

Paclitaxel enhances in vitro radiosensitivity of squamous carcinoma cell lines of the head and neck

Squamous cell carcinoma of the head and neck is the fourth most common cancer in the United States, and therapy for very advanced cases is relatively ineffective. Paclitaxel has activity against cancers of the breast, lung, prostate, cervix, and ovary. The activity of paclitaxel for squamous cell carcinoma of the head and neck is less certain, and results of its radiosensitization properties have been variable. The radiation responses of two squamous carcinomas, SCC-9 (oropharynx) and HEP-2 (larynx), were examined to determine the radiosensitizing potential of paclitaxel. In vitro exposures for 24 and 48 h with paclitaxel concentrations of 10(-4) to 6 x 10(-2) microg/ml were followed by irradiation of 0.1-10 Gy. Percent survival was calculated by colony count, and the paclitaxel-radiation interaction was quantitated by the median effect principle and the combination index method of Chou and Talalay. The paclitaxel-radiation combination resulted in multiphasic interactions in both 24 and 48 h paclitaxel pretreatment in SCC-9 and HEP-2 cell lines. In general there was slight synergism [combination index (CI) <1] at low dose-low effect levels (e.g., at a paclitaxel concentration of 0.002 microg/ml or lower and radiation of 0.1-0.3 Gy), moderate antagonism (CI >1) at median dose ranges and strong synergism (CI <1) at high dose ranges (e.g., at a paclitaxel concentration of 0.012-0.06 microg/ml and radiation doses of 3-10 Gy), especially at a surviving fraction of <0.1, which is therapeutically relevant. The median effect principle and combination index method provided a simple way to quantitate the synergism or antagonism of a paclitaxel-radiation interaction under various conditions. This analysis demonstrated that paclitaxel-radiation synergy exists at doses that are readily achievable in the clinical scenario for both agents and that greater synergy occurred at high dose-high effect levels. These results suggest that the combination of both therapies should be explored further in clinical trials assessing the treatment of squamous cell carcinomas of the head and neck.     

Concurrent radiotherapy and chemotherapy with protracted continuous infusion of 5-fluorouracil in inoperable esophageal squamous cell carcinoma

PURPOSE: The feasibility of a concurrent chemoradiotherapeutic protocol for patients with inoperable esophageal squamous cell carcinoma was tested. METHODS AND MATERIALS: Concurrent chemoradiotherapy using protracted low-dose continuous infusions of five-fluorouracil (5-FU; 250-300 mg/m2/24 h) and standard external beam irradiation was given to 28 patients with inoperable esophageal squamous cell carcinoma between November 1991 and June 1993. RESULTS: For 25 patients receiving a total dose of > or = 60 Gy and concurrent 5-FU infusion for more than 5 weeks, the complete response rate was 52%. Local progression-free rate in this chemoradiotherapy group was significantly higher than the historical controls treated by radiotherapy alone (p < 0.05). A multivariate analysis revealed the treatment scheme (concomitant chemoradiotherapy vs. radiotherapy alone) to be a significant factor in local control (p < 0.01). Swallowing pain (39%), anorexia (39%), and nausea (32%) were the most frequent early reactions. Serious late radiation complications have not been observed. CONCLUSION: The concurrent chemoradiotherapy using protracted low-dose continuous infusion of 5-FU and standard radiotherapy is an effective and safe method to obtain a local control in inoperable esophageal squamous cell carcinoma.     

Radiation rendered more cytotoxic by fludarabine monophosphate in a human oropharynx carcinoma cell-line than in fetal lung fibroblasts

PURPOSE: Fludarabine monophosphate (fludarabine-P) is a relatively new drug in the treatment of different haematological diseases. The mechanism of action also implies a possible role of this drug as a radiosensitizer. Up to now no in vitro investigations dealing with radiosensitizing effects of fludarabine-P in carcinoma cell lines and fibroblasts have been published. The aim of our studies was to analyse the cytotoxic and radiosensitizing effects of different dosages and application schedules of fludarabine-P in a human squamous carcinoma cell line of the oropharynx (ZMK-1) and of fetal lung fibroblasts (MRC-5) in vitro. Possible mechanisms of interaction of fludarabine-P and radiation were investigated. METHODS: ZMK-1 and MRC-5 cells were cultured under standard conditions with different concentrations of fludarabine-P in combination with escalating doses of radiation. Cytotoxic effects were measured by colony-forming assays. Induction and rejoining of radiation-induced DNA double-strand breaks after incubation with fludarabine-P were measured using constant-field gel electrophoresis. Incubation times for rejoining varied from 0 h to 24 h. RESULTS: Fludarabine-P showed a radiosensitizing activity in ZMK-1 tumour cells and MRC-5 fibroblasts. The observed effects depended on the concentration and the incubation time. The largest effect was demonstrable for an incubation of 5 days, which started shortly before irradiation, whereas an incubation solely before irradiation did not have a clear effect on the cellular survival. The sensitizer enhancement ratio, at the 10% survival level, in the ZMK-1 cells was 2.2 in comparison to 1.6 in MRC-5 cells. The analysis of the interaction of fludarabine-P and ionising radiation by means of the isobologram approach, revealed an overadditive effect in the tumour cell line and an additive effect in the lung fibroblasts. Fludarabine-P did not modify the rejoining of radiation-induced DNA double-strand breaks in either cell line. CONCLUSIONS: We conclude that fludarabine-P in clinically attainable doses is a strong radiosensitizer in ZMK-1 cells and has a lower activity in the MRC-5 fibroblasts in vitro. The radiosensitization of fludarabine-P seems to be over additive in the malignant cells and additive in normal fetal fibroblasts. This would indicate that fludarabine-P might enhance the therapeutic ratio of radiation. Further investigations are warranted to identify the potential of this drug as a radiosensitizer in vivo and to elucidate the mechanism of interaction of the drug and radiation.     

Effect of pilocarpine on anterior chamber angles

Pilocarpine is widely used in the treatment of glaucoma, especially for the acute form of angle-closure glaucoma. Previous studies have shown that pilocarpine decreases central anterior chamber depth. In the present study, a quantitative measurement method, applying Scheimpflug photography, was used to report whether pilocarpine also affected the anterior chamber angles. Twenty-nine normal Chinese subjects, 17 female and 12 male with an age range from 11 to 63 years old, were enrolled. One eye of each subject was treated with one drop of 2% pilocarpine. Photographs of each of four quadrants were taken prior to, and after, pilocarpine treatment in both eyes, using a rotating slit-lamp video camera based on the Scheimpflug principle. The slit beams were set at 0 degrees and 90 degrees. The eyes which did not receive pilocarpine treatment served as control. The angles of the four quadrants were calculated for both eyes both prior to, and after, pilocarpine treatment, and results were compared by Student's paired t-test. The comparison of angles between the eyes prior to, and after, pilocarpine treatment indicated that there is a significant narrowing of angles in all quadrants. The complex factors involved in the change of anterior chamber angle are reviewed in the light of muscarinic action of pilocarpine.     

Inhibition of human oral squamous carcinoma cell (SCC-25) proliferation by prostaglandin E2 and vitamin E succinate

The primary objective of this investigation was to study the effect of D-alpha-tocopherol acid succinate (vitamin E succinate) and prostaglandin E2 (PGE2), individually and in combination, on the proliferation of human tongue squamous carcinoma cells (SCC-25) in vitro. Test compounds in varying concentrations were incubated with cells in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (50:50), supplemented with 0.1% albumin for sixteen hours. Cell proliferation was measured by the incorporation of [3H] thymidine in acid-insoluble material (i.e. DNA). Prostaglandin E2 and vitamin E succinate, individually at 10(-9)-10(-6) M, caused significant dose-dependent inhibition in DNA synthesis. A combined dose of each compound at 10(-5) M resulted in significant additive inhibition which averaged 43.53% (p < 0.005). Addition of indomethacin (INDO) to cell cultures induced significant dose-dependent stimulation in DNA synthesis. Hence, we might suggest that the overall potential of vitamin E in controlling malignant cell proliferation in vivo could be due to its own effect combined with that of endogenous PGs which are normally produced in excessive amounts by malignant cells.     

Postoperative radiation for squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site: outcomes and patterns of failure

BACKGROUND: This retrospective study assesses the outcomes and patterns of failure in patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site treated with combined surgery and postoperative radiotherapy. METHODS: One hundred thirty-six patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary source were treated postoperatively with radiotherapy at the University of Texas M. D. Anderson Cancer Center between the years 1968 and 1992. Stage distribution was: N1, 31 patients; N2a, 49; N2b, 25; N2c, 3; N3, 18; and Nx, 10. Thirty-nine patients had excisional biopsies only, 64 patients underwent modified neck dissections, and 33 had radical neck dissections. Extracapsular extension was present in 87 cases. Fifty-nine patients had multiple nodes involved. The median duration of follow-up for surviving patients was 8.7 years. RESULTS: Twelve patients, all with extracapsular nodal disease, developed regional relapse. The 5-year actuarial rates of regional relapse in patients with and without extracapsular nodal disease were 16% and 0%, respectively (p = .004). Nine patients (22%) with extracapsular disease and multiple nodes relapsed compared with three patients (7%) with extracapsular disease and a solitary node (p = .02). None of the patients treated with excisional biopsy and radiotherapy relapsed regionally. No statistically significant relationship between dose, treatment duration, time interval between surgery, and the start of radiotherapy and relapse was detected. The 2-, 5-, and 10-year actuarial disease-specific survival rates were 82%, 74%, and 68%, respectively. Fourteen patients developed cancers in head and neck mucosal sites; six of these cancers were located in unirradiated tissues. CONCLUSIONS: Relapse occurred infrequently in patients treated with excisional biopsies and postoperative radiotherapy. Extracapsular extension and multiple nodes were associated with worse regional control and disease-specific survival. These results appear consistent with those expected for patients with advanced neck disease and a known primary site, and the absence of a primary site should not exclude patients from studies aiming to improve outcomes in patients with extensive neck disease from a head and neck squamous cell cancer. We continue to recommend radiation to the necks and pharyngeal axis for patients suspected of having residual microscopic disease following surgery for squamous cell carcinoma metastatic to the neck from an unknown primary site.     

In vivo modulation of several anticancer agents by beta-carotene

The ability of the collagenase inhibitor minocycline and of beta-carotene to act as positive modulators of cytotoxic anticancer agents was assessed in vitro and in vivo. Cell-culture studies were conducted using the human SCC-25 squamous carcinoma cell line. Simultaneous exposure of the cells to minocycline and beta-carotene or 13-cis-retinoic acid along with cisplatin (CDDP) resulted in a small decrease in the cytotoxicity of the CDDP. The addition of each of the modulator combinations for 1 h or 24 h to treatment with melphalan (L-PAM) or carmustine (BCNU) resulted in greater-than-additive cytotoxicity with each of four regimens. The modulator combinations of minocycline and beta-carotene applied for 1 h or 24 h and the modulator combination of minocycline and 13-cis-retinoic acid produced greater-than-additive cytotoxicity at 50 microM 4-hydroperoxycyclophosphamide (4-HC), whereas minocycline and 13-cis-retinoic acid applied for 1 h was antagonistic with 4-HC and the other modulator treatments at low concentrations of 4-HC resulted in subadditive cytotoxicity. The effect of treatment with beta-carotene alone and in combination with several different anticancer agents was examined in two murine solid tumors, the FSaII fibrosarcoma and the SCC VII carcinoma. Administration of the modulators alone or in combination did not alter the growth of either tumor. Whereas increases in tumor growth delay occurred with the antitumor alkylating agents and beta-carotene and with minocycline and beta-carotene, a diminution in tumor growth delay was produced by 5-fluorouracil in the presence of these modulators. The modulator combination also resulted in increased tumor growth delay with adriamycin and etoposide. Tumor-cell survival assay showed increased killing of FSaII tumor cells with the modulator combination and melphalan or cyclophosphamide as compared with the drugs alone. These results indicate that further investigation of this modulator strategy is warranted.     

Management for stage II glottic carcinoma: radiation therapy or surgery

AIM: To analyze the results of stage II glottic carcinoma treated with radiotherapy or surgery. PATIENTS AND METHOD: One hundred thirty-four patients with squamous cell carcinoma of the T2N0M0 glottic carcinoma treated at the Osaka Medical Center for Cancer and Cardiovascular Diseases from 1979 through 1991 were reviewed. The 5-year disease-free survival and laryngeal preservation rate and prognostic factors were examined. Treatment was radiation therapy with salvage surgery for failure or surgery alone. RESULTS: The 5-year disease-specific survival rate for the radiotherapy group was 100% and for the surgery group, 93% (p = 0.055). In the surgery group 5-year disease-specific survival rate for the subgroup of cord mobility was 94% and that of impaired cord mobility, 89% (p = 0.5354). Concerning laryngeal preservation the radiotherapy group showed better preservation rate than the surgery group in the subgroup of cord mobility, i.e., 41/51 (80%) versus 6/55 (11%) (p < 0.001) although significant difference was not observed in the lesion with impaired cord mobility, 2/5 versus 4/22 (p = 0.171). CONCLUSION: We recommend radiation therapy for stage II glottic carcinoma with normal cord mobility, although further study is needed to improve the preservation rate of the larynx with keeping the disease-specific survival for the lesion with impaired cord mobility.     

Thymic carcinoma. Ten years' experience in twenty patients

Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To evaluate the outcome of treatment in thymic carcinoma, we reviewed a 10-year (1982 to 1992) experience with 20 consecutive patients in Taichung Veterans General Hospital. There were 9 men and 11 women: ages ranged from 34 to 70 years old (mean 51.4 years). None of these patients had concomitant myasthenia gravis. All of the patients received surgical intervention, and the diagnosis was made by pathologic study. Postoperative staging was made according to the modified Masaoka staging system. None of our patients were in stage I. One patient (5%) had stage II disease, 12 (60%) stage III, and 7 (35%) stage IV. The pathologic subtypes of thymic carcinoma included eight squamous cell carcinomas, seven undifferentiated carcinomas, one lymphoepithelioma-like carcinoma, one clear-cell carcinoma, 1 mucoepidermoid carcinoma, and two carcinoid tumors. Curative resection could be done in seven patients (35%). The overall cumulative survival was 45.9% at 3 years and 34.4% at 5 years. The median survival times for patients with complete and incomplete resection were 39.0 months and 14.3 months, respectively (p = 0.1752). The median survival times of patients with postoperative radiotherapy and without postoperative radiotherapy were 39.3 months and 15.0 months, respectively (p = 0.0738). The median survival times of patients with squamous cell carcinoma and undifferentiated carcinoma were 25.4 months and 11.3 months, respectively (p = 0.1464). Our data show that complete resection, postoperative radiotherapy, and squamous cell carcinoma do not indicate a significantly favorable result, even though they result in longer median survival times. Yet a positive trend of favorable outcome in patients who received postoperative radiotherapy is ambiguously shown.     

The effect of local radiotherapy on kallikrein activity in saliva secreted by parotid gland in patients with head and neck cancers

The samples of parotid gland saliva, collected from control human subjects and those taken from patients with head and neck cancers were submitted to the assay of protein concentration and kininogenase and amidolytic kallikrein activities. No patients with parotid gland tumours were included. The effect of pilocarpine stimulation on these parameters was studied. It was found that the saliva secreted by parotid gland of the investigated patients contains less protein and lower kininogenase activity in comparison to control subjects. Pilocarpine administration resulted in an increase of protein concentration and a decrease of kallikrein activity both in control and investigated subjects. Radiotherapy did not evoke any significant changes in spontaneously secreted saliva. The radiotherapy resulted in a progressive decrease of protein concentration and kallikrein activity in saliva secreted by pilocarpine stimulated glands. The kallikrein activity per mg of protein contained in spontaneously secreted saliva increased significantly during radiotherapy but it distinctly decreased in the saliva of pilocarpine-treated patients. It allows to conclude that the parotid glands do not lose their ability to synthesize and secrete kallikrein during radiotherapy of head and neck cancers.     

A 2-week pretreatment with 13-cis-retinoic acid + interferon-alpha-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers

BACKGROUND: We have evaluated the tumor tissue pO2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-alpha-2a prior to and during radiotherapy. PATIENTS AND METHODS: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-alpha-2a (IFN-alpha-2a) as part of a phase-II protocol. cRA/IFN-alpha-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6 x 10(6) IU IFN-alpha-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-alpha-2a treatment was continued with 50% of the daily doses. Tumor tissue pO2-measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO2-histograph. RESULTS: In 11 out of the 22 patients, pO2-measurements were performed prior to the cRA/IFN-induction therapy. The median pO2 of these untreated tumors was 17.7 +/- 16.3 mm Hg. The relative frequency of hypoxic readings with pO2-values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3 +/- 21.0%). After the 2-week induction period with cRA/IFN, the median pO2 had increased from 17.7 +/- 16.3 mm Hg to 27.6 +/- 19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO2 of 10 mm Hg or less), the median pO2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO2 increased from 6.3 +/- 2.7 mm Hg to 27.0 +/- 5.6 mm Hg (p = 0.004, t-test for paired samples). The frequency of hypoxic readings (pO2-values < 5 mm Hg) decreased from 44.7 +/- 17.1% to 2.0 +/- 2.5% (p = 0.012, t-test for paired samples). There was, however, no obvious volume reduction after 14 weeks of cRA/IFN on clinical examination. A complete clinical remission of the local tumor was observed in 19/22 patients after radiotherapy and additional cRA/IFN-alpha-2a-treatment. In primarily hypoxic tumors (with a median pO2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. CONCLUSIONS: Pretreatment with cRA/IFN improves oxygenation of primarily hypoxic cervical cancers. The mechanisms of action remain unclear and further investigation of the combination regimen is recommended.     

A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction

PURPOSE: To compare the outcome for patients with squamous cell carcinoma of cervical lymph nodes metastatic from an unknown primary site who were irradiated to both sides of the neck and potential mucosal sites with opposed photon beams, and for those irradiated to the ipsilateral side of the neck alone with an electron beam. METHODS AND MATERIALS: Fifty-two patients with squamous cell carcinoma metastatic to cervical lymph nodes from an unknown primary site were irradiated by two different methods. Thirty-six were irradiated with a bilateral technique (BT), i.e., to both sides of the neck, including the naso-oro-hypopharyngeal mucosa, and 16 were irradiated with an electron beam (EB) to the ipsilateral side of the neck alone. Twenty patients of the BT group and 11 of the EB group had cervical lymph node dissections, and the remaining 21 patients had lymph node biopsies, prior to radiotherapy. RESULTS: Tumor control in the ipsilateral side of the neck did not differ for either radiation technique, but was significantly higher after lymph node dissection than after biopsy (90 vs. 48%; p = 0.0004). Control of subclinical metastases in the contralateral cervical lymph nodes was higher for patients irradiated with BT than for patients irradiated with EB (86 vs. 56%; p = 0.03). The occult primary was later discovered in 8% of the patients in the BT group and 44% of the EB group (p = 0.0005). The disease-free survival rate at 5 years for patients who had lymph node dissection prior to irradiation was 61%, and was 37% for those who had biopsy (p = 0.05). Only 20% of patients who subsequently developed an occult primary were salvaged and survived for 5 years after salvage treatment. CONCLUSION: Bilateral neck and mucosal irradiation is superior to ipsilateral neck irradiation in preventing contralateral cervical lymph node metastases and the subsequent appearance of an occult primary cancer. Both techniques combined with cervical lymph node dissection were equally effective in controlling the ipsilateral neck disease.     

Prognostic significance of S-phase fraction detected by antithymidine antibodies in epidermoid cervix carcinomas

PURPOSE: To assess the predictive value of pretreatment proliferative activity of epidermoid cervix carcinoma cells with respect to short- and long-term results of radiotherapy. METHODS AND MATERIALS: The proliferative activity of 25 epidermoid cervix carcinomas was evaluated as the immunofluorescent labeling index (LI) by rabbit antithymidine antibodies reacting specifically with single-stranded DNA of replication forks in S-phase cells. The short-term clinical outcome was estimated at 3-6 months after treatment by visual and palpatory examination. Three-year follow-up data were obtained through hospital charts and correspondence with referring physicians for only 19 patients. RESULTS: There was no statistically significant association between LI and such conventional prognostic factors as clinical stage. The LI value of cervix carcinomas was significantly associated with complete regression at 3-6 months after radiotherapy and 3-year disease-free survival. Complete regression at 3-6 months was observed in 87.5% patients with fast proliferating tumors (LI > 7.0%), and only in 41.2% patients with slowly proliferating tumors (p = 0.03). Probability of 3-year disease-free survival was 85.7% in patients with fast proliferating tumors and 50.0% in those with slowly proliferating tumors (p = 0.05). CONCLUSIONS: The immunofluorescent LI of epidermoid cervix carcinoma is able to provide prognostic information on short-term tumor response to radiotherapy and disease-free survival.     

Effects of argipressin injected into medial amygdaloid body on blood pressure and heart rate in rats

Thirteen patients with primary carcinoma of the hard palate were seen over an 18-year period at the Mallinckrodt Institute of Radiology. Nine patients had adenoid cystic carcinoma, three had squamous cell carcinoma, and one patient had mucoepidermoid carcinoma. The median tumor size was 3 cm3. The patients were clinically staged: T = 1, T2 = 5, T3 = 3, T4 = 4. All were N0M0. Ten patients underwent excision and postoperative irradiation. The remaining three patients were treated definitively with radiotherapy. The 10-year disease-free survival is 77% with an actuarial local control rate of 92%. Patients with negative surgical margins had an improved local control and disease-free survival. Duration of radiation therapy, total tumor dose or histology had no impact on outcome. We conclude that combined surgery and irradiation gives good 10-year local control and disease-free survival rates in patients with this disease.     

Combined chemotherapy and radiotherapy, followed or not by surgery, in squamous cell carcinoma of the esophagus

BACKGROUND: This study was designed to evaluate the feasibility of a neo-adjuvant combined chemo-radiotherapy in patients with localized squamous cell carcinoma of the esophagus. PATIENTS AND METHODS: Forty-two patients with squamous cell carcinoma of the esophagus, stages II and III (or stage I if considered to be poor candidates for immediate curative surgery), age less than 70 years and WHO performance status 0 to 2, were enrolled in a study of radiotherapy combined with chemotherapy, consisting of 2 (operated patients) or 3 (nonoperated patients) courses of cisplatin, vindesine, mitomycin-C or cisplatin, vinblastine. Surgery was routinely proposed to patients. RESULTS: Thirty-seven patients (88%) received full preoperative therapy. Of 30 patients responding to this preoperative therapy, 12 had a third cycle of treatment and 15 had esophagectomy. Three of the operated patients had no pathological evidence of residual tumour. Median survival of all 42 patients is 11 months and the 2-year survival rate is 29%. There is no difference in survival among responding operated or non-operated patients. Our group represents 95% of all eligible cases of squamous cell carcinoma of the esophagus occurring in Geneva during the study period. CONCLUSION: Our series gives a realistic view of the median survival of a population of patients eligible for neo-adjuvant therapy of esophagus cancer, and suggests that secondary surgery might not improve the patient survival. Furthermore, non-selected patients are at high risk for therapy-related death.     

The alterations in the activity of amylase and its salivary isoenzyme in the serum of patients with ovarian carcinoma, submitted to radiotherapy

Total activity of alpha-amylase and its salivary isoenzyme in the serum of patients with ovarian carcinoma of various types were evaluated before radiotherapy, in the middle of radiotherapy period, in the last day and 2 months after radiotherapy. Before radiotherapy the activity of these enzymes were significantly higher in patients with ovarian serous cystadenocarcinoma. It was found that irradiation resulted in a decrease of both total amylase activity and its salivary isoenzyme in the serum. The proportional participation of salivary isoenzymes in total amylase activity was normalized. It is suggested that the assay of salivary alpha-amylase activity may be useful in the evaluation of radiotherapy effectiveness.     

Irradiation-induced damage to the salivary glands: the role of redox-active iron and copper

The mechanism of irradiation-induced hypofunction of the salivary glands is a process that is not fully understood. Here we examine the hypothesis that intracellular and redox-active ions of iron and copper, which are associated with the secretion granules, play a catalytic role in the irradiation-induced damage. Rats were subjected to head and neck irradiation (15 Gy X rays) and allowed to recover for 2 months. The function of the parotid and submandibular glands was then determined by pilocarpine-stimulated salivary secretion. A 45% decrease in the function of both glands was obtained when compared to nonirradiated controls. Treatment prior to irradiation (90 min) with cyclocytidine (200 mg/kg) led to a massive degranulation of the parotid gland and yielded nearly complete protection from radiation-induced damage. In contrast, pilocarpine stimulation prior to irradiation led to a marginal degranulation of the parotid gland and yielded only 13% protection. Neither agent caused degranulation of the submandibular gland mucous cells or yielded functional protection of this gland. Treatment with both agents yielded a marked increase in iron, copper and manganese levels in the parotid gland saliva. An analogous marked increase in the redox activity of iron and copper ions was recorded for the parotid saliva stimulated by pilocarpine and cyclocytidine. Pilocarpine-stimulated submandibular gland saliva contained metal levels similar to those of the parotid gland saliva. However, no redox activity and no increase in metal mobilization could be demonstrated in the submandibular gland saliva stimulated by both agents. The correlation between the patterns of gland degranulation, mobilization of redoxactive metals and the protection of gland function, for both parotid and submandibular glands, focuses attention on the catalytic roles played by transition metal ions in promoting free radical reactions, which likely participate in the process of injury to the tissue.     

Pancreatic duct antibodies and subclinical insufficiency of the exocrine pancreas in Sj?gren''s syndrome]

AIM: To investigate prognostic factors and complications after radical hysterectomy followed by postoperative radiotherapy for carcinoma of the uterine cervix. PATIENTS AND METHODS: One hundred twenty-eight patients with T1b-2b carcinoma of the uterine cervix following radical hysterectomy with bilateral pelvic lymphadenectomy and postoperative radiation therapy were reviewed. Pathologic and treatment variables were assessed by multivariate analysis for local recurrence, distant metastases and cause specific survival. RESULTS: The number of positive nodes (PN) in the pelvis was the strongest predictor of pelvic recurrence and distant metastases. These 2 failure patterns independently affect the cause specific survival. The 5-year cumulative local and distant failure were PN(0): 2% and 12%, PN(1-2): 23% and 25%, PN(2 <): 32% and 57%, respectively (p = 0.0029 and p = 0.0051). The 5-year cause specific survival rates were PN(0): 90%, PN(1-2): 59% and PN(2 <): 42% (p = 0.0001). The most common complication was lymphedema of the foot experienced by one-half of the patients (5-year: 42%, 10-year: 49%). CONCLUSION: These results suggest that patients with pathologic T1b-T2b cervix cancer with pelvic lymph node metastases are at high risk of recurrence or metastases after radical hysterectomy with pelvic lymphadenectomy and postoperative irradiation.