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OBJECTIVE: The objective of this study is to prove that rigid bronchoscopy is a relatively safe procedure in experts' hands and should be carried out in children whenever symptoms like persistent cough, chest infection or stridor persist despite proper antibiotic therapy. METHODS: A review of 534 bronchoscopies in children was carried out between August 1988 and May 1995. Three hundred and fifteen were male and 219 were female children. The most common age was between 1 and 2 years while the mean age being 1 year 10 months. RESULTS: Out of 534 bronchoscopies, 332 were positive for foreign bodies in the tracheosbronchial tree and 202 were negative. The most common site of lodgment of foreign body was the right bronchus. The clinical presentation was variable. An increase in the number of cases was observed. A variety of foreign bodies were encountered, the majority being peanuts. CONCLUSION: In our opinion rigid bronchoscopy is a relatively safe procedure and should be carried out in children whenever symptoms like persistent cough, chest infection or stridor persist despite proper antibiotic therapy.

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BACKGROUND: Earlier stages cervical cancer has been customarily treated with radiation therapy, surgery, or combination thereof. We present our experience in the management of stage-I and -II patients in a major cancer center in the Kingdom of Saudi Arabia. METHODS: Between 1979 and 1991, 164 patients were treated and closely followed at a tertiary care medical center. RESULTS: Patients accounted for 0.78 % of all cancer patient referral. More cases with earlier stages (41.3 %) were referred since 1986, compared to a lower referral (26.1%) during the earlier part of the study (p=0.027). Age ranged from 21 to 80 years with a median of 46.5 years. Clinical stages at presentation included Stage-IA (3.0%), IB (28.7%), IIA (11.6%), and IIB (56.7%). Majority (87.2%) had squamous cell carcinoma, while the rest, had adenocarcinoma (9.1%) or other malignancies (3.6%). Among the 143 patients with squamous cell cancer, eighteen had attempted radical resection, 101 were treated with radiation, and 24 had both modalities. For squamous cancer patients, fifty-one (35.7%) had disease relapse either locally (19 cases), distally (23 patients) or both combined (9 patients). The pattern of failure was unrelated to stage of disease, histological diagnosis or the mode of therapy initially administered. The cumulative five and ten year's survival for squamous cancer patients was 68.3% and 57.9% respectively. Better survival was noted for patients with smaller sized tumors, free parametrium, and Stage-I disease. When all factors were considered in the regression model, only the status of parametrial involvement was found to be of significance. CONCLUSIONS: Cervical cancer is relatively rare in Saudi Arabia. With the improvement in health care delivery, more patients were lately seen at earlier stages of disease. With radiation therapy, two thirds of patients survived five years. The extent of parametrial involvement was the best predictor for long term survival.

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BACKGROUND/AIMS: Gastrointestinal lymphoma is a rare disease. A study was conducted to assess its prevalence and clinical features in adult patients with lymphoma. METHODS: Retrospective analysis of 1352 patients with adult non-Hodgkin's lymphoma showed 300 (22%) cases with gastrointestinal involvement at initial presentation. RESULTS: Of the 185 patients with primary gastrointestinal lymphoma, 94 (51%) had gastric primary lymphoma and the rest (49%) had a lymphoma of intestinal origin. Patients with intestinal lymphoma were considerably younger (median age, 35.0 years), frequently had multifocal disease (14%), and had a 10-year survival rate of 48%. Cases with gastric primary lymphoma had a median age of 54.5 years (P < 0.001) and rarely had multifocal disease (1%; P < 0.001) but had an equal 10-year survival rate of 53% (P = 0.431). For both groups, the combined surgical resection followed by chemotherapy led to better 10-year survival (45%) compared with either modality used alone (0% and 35%, respectively; P < 0.05). Better survival was also noted in ambulatory patients, younger patients, those with localized disease, and those without intestinal perforation. Another 115 patients had gastrointestinal involvement secondary to disseminated disease with frequent high-grade histology (29%) and a poor 10-year survival rate of 22%. CONCLUSIONS: Gastrointestinal involvement is relatively common in patients with adult lymphoma. Multimodality treatment appeared superior to therapy with either surgery or chemotherapy used alone.

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Cultured fibroblast cells from 19 patients with non-Hodgkin's lymphoma (NHL), 3 patients with ataxia telangiectasia (AT), 3 AT heterozygotes and 11 (presumed) normal subjects were studied for impaired colony-forming ability after chronic gamma irradiation. Five cell lines from the NHL patients were also examined for the sensitivity to acute gamma irradiation, as compared with those of normal subjects. To ascertain the degree of radiosensitivity of different cell lines, a comparison was made of the D10 values (radiation dose resulting in 10% survival) for each cell line, estimated "by eye" from the actual survival curves, and also from the calculated curves fitted to a log-linear model. It was observed that the acute gamma irradiation failed to show any appreciable difference in the radiation response of the cell lines from NHL patients as compared with those of normal subjects. However, chronic irradiation demonstrated significantly increased radiosensitivity in at least 10-12 NHL patients with a p value of less than 0.05, when the D10 values of each patient's cell line were compared with the calculated composite values for the normals. When the D10 values of the NHL patients and the normal subjects were compared as 2 groups, the former appeared to be significantly more sensitive to chronic gamma irradiation (p less than 0.0001). The same level of significant difference in radiosensitivity was found between the 2 groups when their D37 values (radiation dose resulting in 37% survival) were compared. In general, the radiation response of the NHL patients was similar to that of the AT homozygotes and heterozygotes used as a positive control group. Our data thus show that increased radiosensitivity is associated with the NHL patients studied, indicating an underlying abnormality of their DNA repair.

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Between January 1980 and December 1982, 183 patients with histologically confirmed carcinoma of the esophagus who were referred to a tertiary referral hospital were studied. Thirty-two (17%) patients were referred from Gassim Region at the north central part of Saudi Arabia. In contrast, only 5% of total cancer patient referrals were from this area. A case-control study showed a significant regional difference within Saudi Arabia and the most referrals from Gassim area. A prospective case-control study showed persistently high numbers of referrals from that region during 1983-1987. When patients from Gassim Region were compared with those referred from other locations, no statistical differences were noted between the two groups except for the source of drinking water. Water analysis from Gassim area showed a high solid content with elevated levels of calcium, magnesium, and to a lesser extent, chromium iron, cadmium, and cobalt. Traces of petroleum oil were found in five of six water samples from Gassim during 1983, compared with 3 of 49 samples from other areas. Mutagenicity tests on water specimens form Gassim Region indicated the presence of possible carcinogens. It is being suggested that the high prevalence of esophageal cancer in this region may be related to contamination of water by impurities such as petroleum oils. Malnutrition, particularly vitamin A deficiency, as well as other factors may have promoted such malignancies.

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Peripheral blood lymphocytes (PBLs) from 28 patients with non-Hodgkin's lymphoma (NHL) were compared with those of 28 healthy subjects (controls) for their responsiveness to the T cell mitogen phytohemagglutinin (PHA) before and after treatment with gamma-radiation and mitomycin C. PBLs from 9 of the 28 patients with NHL exhibited almost a total failure to respond to PHA while mitogenic stimulation in the rest varied from 7 to 90% relative to the controls. PBLs from 19 NHL patients and 28 healthy subjects were compared for their radiosensitivity by measuring postirradiation uptake of [3H]-thymidine. Increased sensitivity to gamma-radiation was observed in more than half of the NHL patients studied. Increased sensitivity to mitomycin C was also noted in 5 of the 7 patients analyzed compared to the respective controls. Poor mitogenic responsiveness and hypersensitivity of blood lymphocytes to the carcinogens (gamma-rays and mitomycin C) are suggestive of a severe immunological abnormality and defective DNA repair in these Saudi NHL patients.

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Cultured skin fibroblasts from 11 patients with non-Hodgkin's lymphoma (NHL), 3 with ataxia telangiectasia (AT), 3 AT heterozygotes and 6 healthy subjects were studied for impaired colony-forming ability upon chronic exposure to gamma-radiation. A comparison of survival curves of the different cell lines revealed an AT heterozygote-like response (intermediate radiosensitivity) in 8 (73%) out of 11 NHL patients. These results suggested that the majority of the NHL patients may have an underlying abnormality of DNA repair.

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Mutagenicity of cisplatin and carboplatin was compared by using the drugs alone and in combination with bleomycin, 5-fluorouracil, vincristine and methotrexate in the Ames Salmonella assay employing the tester strains TA98, TA100 (excision deficient) and TA102 (excision proficient). Cisplatin showed the maximum yield of histidine revertants in TA98 and TA100 at 2 micrograms/plate followed by a decrease in the number of mutants/plate with increasing concentrations. In the excision proficient strain TA102, there was no decline in the number of mutants/plate even at a concentration of 8 micrograms/plate. Basically, similar results were also obtained with carboplatin but using higher concentrations of the drug. When cisplatin or carboplatin was combined with other anticancer drugs, there was no differential modification of mutagenicity of the 2 platinum compounds in any of the bacterial tester strains.

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A retrospective review was performed of the medical records of 166 adult patients with biopsy-proven carcinomas of the nasopharynx treated with curative intent at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. All patients were treated between June 1975 and December 1985 using megavoltage therapy equipment. Most patients presented with advanced nodal disease: 23 patients (13.9%) were N0, 16 patients (9.6%) were N1, 29 patients (17.5%) were N2, and 98 patients (59%) were N3. The overwhelming majority of patients had nonkeratinizing lesions (158/166). At the time of analysis, mean follow-up time was 24.2 months (range 2-108). Actuarial curves are presented for local/regional control as a function of T-stage and N-stage and for survival and time to development of distant metastases as a function of N-stage. At 4 years local/regional control was 70% for T1 lesions, 59% for T2 lesions, 30% for T3 lesions, and 35% for T4 lesions. There was little correlation between local/regional control and N-stage being about 50% at 4 years for all nodal subgroups. Only six patients exhibited an isolated first failure in the regional nodes alone, whereas 60 patients failed initially at the primary site (either alone or in conjunction with a simultaneous nodal failure). The development of distant metastases correlated to some extent with nodal disease ranging from 20% at 4 years for T1/T2 N0 patients to 70% for patients who initially presented with N3 disease. Survival data was more difficult to obtain due to cultural biases in a medically unsophisticated patient population. True survival curves are bounded by calculating actuarial curves in two ways: death as the failure endpoint and death plus lost-with-active-disease as failure endpoints. In terms of the latter curves, at 4 years "survival" ranged from 39% for patients with T1/T2 N0 lesions to 23% for patients with N3 lesions.

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Cytotoxicity of cisplatin and carboplatin was compared using each drug alone and in combination with either 5-fluorouracil (5-FU) or methotrexate (MTX) and with 5-FU, vincristine (VCR) and bleomycin (BLM) together in the mouse embryo fibroblast line C3H10T1/2. The survival curves, drawn on the basis of the colony-forming ability of cells, indicated that carboplatin was about 25 times less effective in cell killing compared to cisplatin. Dose-response curves obtained with different concentrations of cisplatin combined with 5-FU or MTX showed a dose modification factor (DMF) of 1.8. A DMF of 5.7 was obtained when cisplatin was combined with 5-FU + VCR + BLM. A combination of carboplatin with 5-FU and MTX resulted in DMFs of 3.4 and 2.4, respectively, while a DMF of 4.8 was obtained by combining the platinum analogue with 5-FU + VCR + BLM. Initial shoulders in the cell survival curves resulting from treatments with cisplatin, carboplatin and 5-FU used as single agents disappeared after combined drug treatments. While the data generally indicated a higher cytotoxic effectiveness of combined drug treatments, there was no great difference between the DMFs for cisplatin and carboplatin when used in different combination protocols. These results may reflect the functional similarity of the two platinum compounds and suggest that the replacement of one with the other may not significantly alter the cytotoxic effectiveness in combined treatments.

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Histological changes were studied in experimental animals following the intraperitoneal administration of high-dose cisplatin with or without high-dose methotrexate and citrovorum factor. There were pronounced renal toxicities with high-dose (10 mg/kg) cisplatin, particularly involving distal tubules with glomerular congestion. However, lower toxicities were noted with reduced dosage of cisplatin (5 mg/kg) and especially if given once as a single bolus injection instead of a 5-day regimen. Renal and hepatic toxicities were marked with concomitant methotrexate administration leading to hemorrhagic diathesis and shorter survival. However, toxicities were relatively reduced when cisplatin was given as a single bolus injection instead of a 5-day divided course. Such information may prove helpful in future planning of combination chemotherapy in patients with malignancies using these two agents.

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A total of 7251 histologically confirmed new cases of cancer (4117 males and 3134 females) were seen in the 6-year period 1979 to 1984 at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. The crude relative frequencies of cancer at various primary sites have been determined with reference to sex, age, geographic origin, and year of diagnosis. The most common cancer sites among males were non-Hodgkin's lymphomas, esophagus, lung, liver, stomach, and nasopharynx. Breast cancer was the most common tumor among the females, followed by non-Hodgkin's lymphomas and cancers of the thyroid, esophagus, cervix, and ovary. The most marked deviations were found in the Southern Region for cancers of the oral cavity (2.4 times higher), bladder (1.8 times higher), and lung (4.3 times lower). Known etiologic factors, such as local chewing, smoking habits, and schistosomiasis are likely to be responsible for these differences. Upward trends in cancers of lung, breast, colon and rectum, and the downward trend in esophageal cancer may reflect the rapid pace of modernization.

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Sunlight-related biological effects such as skin cancer, sunburning, and synthesis of vitamin D in the body have been found to be very low in people in the midregion of Saudi Arabia. The present studies were undertaken to measure the sunburning-carcinogenic ultraviolet light (UV) radiation (UV-B) in natural sunlight in the city of Riyadh (25 degrees north latitude). The average noontime incidence of UV-B, measured with a sunburn UV-meter, was found to be between 1.9 and 3.4 sun units/hr in the months of March to May. Concomitantly with the UV measurements, a bioassay using a wild-type and an excision repair-deficient diploid strain of the yeast, Saccharomyces cerevisiae, was carried out to detect both lethal and genotoxic effects (mutation and mitotic gene conversion) of the sunlight. Exposure of the yeast cells to sunlight 30 to 180 min resulted in a significant level of cell death and a dose-dependent induction of mutations and mitotic gene conversion. The use of a Mylar filter cutting off virtually all of the wavelengths below 312 nm greatly reduced the lethal and genotoxic effects of sunlight. The results of UV measurements and biological studies suggest that an appreciable amount of potentially carcinogenic short UV wavelengths is present in sunlight in the Riyadh area. Therefore, factors other than the lack of biologically significant UV radiation in sunlight appear more likely to be responsible for the reduced incidence of sunburning and skin cancer in this geographical area.

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A retrospective analysis of all breast cancer patients who died of their disease at Harper Grace Hospital during 1962 to 1976, was conducted to determine the pattern of metastases and its relation to chemotherapy. The autopsy incidence of distant metastases, to all organ sites, was noted to be higher among patients who previously received cytotoxic therapy, compared with those among patients who previously received cytotoxic therapy, compared with those who did not. Such incidence was unrelated to differences in patients' age, menopausal status, and disease-free interval. It is postulated that chemotherapy contributes to the wider metastases, especially to the central nervous system and meninges, in a breast cancer patient. This is possible due to a longer survival of patients treated.

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Twenty-eight consecutive patients with advanced head and neck epidermoid carcinoma were treated with a single course of combination chemotherapy which included high dose cis-platinum II, vincristine, and bleomycin. All patients except one were evaluable for drug response and toxicity. The overall toxicity was mild and tolerable except in one patient who had fatal nephrotoxicity. Thirteen patients (48%) had a partial regression, and five with minimal response did improve, giving an overall response rate of 67%. More responses were noted in previously untreated patients, especially those with oral or hypopharyngeal tumors without distant metastases. Definite histological changes were seen in a few patients in remission. Objective tumor response was associated with subjective improvement, and possibly, a prolonged survival.

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A retrospective study of the clinical findings and natural history of 140 patients with disseminated malignant melanoma treated at Wayne State University over a ten year period was done. Multiple organ metastases were diagnosed clinically in 78 per cent of all patients and seen at all autopsies. Routine roentgenograms of the chest did not diagnose metastases to the lung in 27 per cent of the patients. The concimitant elevation of alkaline phosphatase, serum glutamic-oxalacetic transaminase and serum glutamic-pyruvic transaminase enzymes is suggestive of underlying metastases to the liver even with a negative liver scan or normal liver size. Electroencephalography was found to be sensitive in predicting and confirming metastases to the central nervous system prior to clinical manifestation with a 97 per cent accuracy rate in clinically confirmed instances as compared with a 60 per cent accuracy rate with brain scan. Age, sex and primary site of melanoma did not influence the survival once the disease became disseminated. Patients with a disease-free interval of more than six months statistically have a better chance of survival from the onset of systemic metastases, p = 0.001. Patients with a poor performance status of less than or equal to 40 per cent had a median survival period of one month as compared with six months with 90 per cent performance, p = 0.001. Patients who initially presented with metastases to the skin or lymph nodes without other visceral involvement had a 14 month median survival rate as compared with eight months in patients with metastases to the central nervous system only, four months with metastases to the liver and only one month in patients with multiple organ involvement, p = 0.0001.

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A review of 164 patients with far advanced head and neck cancer, treated by a cytotoxic chemotherapy over a ten year period, at WAyne State University, Detroit, Michigan, was done in an attempt to determine factors that may influence the response to chemotherapy and subsequent survival. Response rate to methotrexate was 28%, 5-FU 31%, and porfiromycin 13%. Improved responses were noted with combination chemotherapy. Patients who failed to first line therapy rarely responded to other single agent or combination chemotherapy. Those who did not have prior surgery and/or radiotherapy had better results from drug therapy. Patients with good performance status at the time of initial chemotherapy, had better response to treatment (32% vs. 13% PR & CR) and longer survival (28 weeks vs. 9 weeks, p = 0.01) when compared to those with poor status. Patients who responded to chemotherapy have better survival compared to nonresponders (29 weeks vs. 16 weeks, p = 0.002). This information may prove helpful in future planning of multidisciplinary approach in the treatment of patients with head and neck cancer.

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