Neoadjuvant chemotherapy plus conventional radiotherapy or accelerated hyperfractionation in stage III and IV nasopharyngeal carcinoma--a phase II study.

A prospective phase II trial was initiated in previously untreated patients with locally advanced nasopharyngeal carcinoma (NPC). The goal was to achieve improvement in locoregional control, disease-free interval and overall survival using induction chemotherapy and to compare conventional fractionation (CF) with an accelerated hyperfractionation (AHF) regimen. Fifty patients were treated (5 AJCC Stage III, 45 Stage IV) with induction chemotherapy consisting of two cycles of cisplatin and 5-fluorouracil. Patients were then randomized between CF and AHF therapy. A clinical response to induction chemotherapy was reported in 86% of patients prior to radiotherapy (44% complete response, 42% partial response). Patients with complete or major partial responses to induction chemotherapy had a significantly better 5-year overall survival (60%) and disease-free interval (59%) than those with no response or minor partial response (15% and 18% p = 0.009 and 0.0009). Acute radiation reactions were more pronounced in the AHF group (p = 0.0002), and the incidence of late normal tissue injury was more frequent (p = 0.08). At 5 years, the locoregional control rate was higher in the AHF arm (76%) than in the CF group (54%), but the difference was not significant (HR, 0.52; 95%, Cl, 0.15-2.83; p = 0.186). With a median follow-up period of 55 months (range 4-120), the 5-year disease-free interval and overall survival rates were more favorable in the AHF group than in the CF group, but the differences were not significant (59% and 54% vs. 34% and 36%, respectively, HR for disease-free interval = 0.71; 95% CI, 0.27-1.88; p=0.198 and HR for overall survival = 0.81; 95% CI, 0.37-1.78; p=0.433). The overall treatment failure rate was 48%. Locoregional failures occurred in 12 patients (24%) and the incidence of distant metastases reached 30%. Response to induction chemotherapy is strongly predictive for locoregional control, disease-free interval and overall survival. Accelerated hyperfractionation was associated with high incidence of acute and late toxicity without significant improvement in locoregional control rate. The optimal chemotherapy dose and sequencing with radiotherapy needs to be investigated in future studies. Distant metastases remain the main cause of treatment failure in NPC.

Reduced expression of mismatch repair genes in colorectal cancer patients in Egypt.

An Egyptian hospital-based pilot case-control study was conducted to investigate the relationship between the expression level of mismatch repair (MMR) genes and the risk of colorectal cancer. The relative expression of five known MMR genes, i.e., hMSH2, hMLH1, hPMS1, hPMS2, and GTBP/hMSH6, was measured by a multiplex reverse transcriptase (RT)-polymerase chain reaction (PCR) in peripheral blood lymphocytes from 31 colorectal cancer patients and 47 age- and-sex matched controls. The expression of hMSH2, GTBP/hMSH6, hPMS1 and hPMS2 tended to be lower in patients than controls, but only the difference in hPMS2 expression was statistically significant (p<0. 01). Although 50% of the cases had chemotherapy or radiotherapy within the last six months before the blood was drawn, their gene expression was not statistically different from those who had not undergone such therapies. After adjustment for age and sex, the odds ratios (OR) calculated from a logistical regression model, using the median levels of gene expression of controls as cut-off values, indicated that increased risk was associated with reduced expressions of both hPMS1 (OR = 3.97, 95% confidence interval (CI) = 1.04 to 7.65) and hPMS2 (OR = 2.86, 95% CI = 1.05 to 7.76). Although the results of this study were inconclusive because of the small sample size and use of prevalent cases, it is biologically plausible that patients with colorectal cancers may have a lower expression of MMR genes than healthy controls because malfunction of these genes has been shown in hereditary nonpolyposis colon cancer. The involvement of low hPMS2 expression in colon cancer risk seems to be unique in the Egyptian population. Further studies with newly diagnosed patients before they begin therapy will provide more convincing data about the role of MMR gene expression in the etiology of colorectal cancers in Egypt.

HELLP syndrome: Clinical profile of seven patients.

HELLP syndrome is a multi-organ disorder unique to pregnancy. It is characterized by hemolysis, elevated liver enzymes, and low platelets in patients with pre-eclampsia or eclampsia. In King Abdulaziz Oncology Center, Jeddah, seven patients with HELLP syndrome were admitted over a period of four years (1991-94). Retrospective analysis of data was done to study the clinical profile of HELLP syndrome. The incidence of HELLP syndrome in our institution was 1 per 2285 deliveries. One patient was Saudi and six were non-Saudis. The age range was 23 to 44 years, with a mean of 29 years. All patients were multipara. The disorder occurred between 24 to 33 weeks of gestational age, the average being 29 weeks. The most commonly encountered clinical feature was right upper quadrant/epigastric pain. Other features included nausea/vomiting, jaundice, hepatic encephalopathy, azotemia, hypotension and grand mal convulsions. All patients had severe pre-eclampsia pr eclampsia. Indirect hyperbilirubinemia was in the range of 2 to 8 mg/dL and elevated transaminases up to 229 U/L (n<40 U/L) were noted. Various degrees of peripheral thrombocytopenia (<150x10(9)/L) were present in seven patients. Four patients had elevated prothrombin and partial thromboplastin time with postive fibrinogen degradation products. Laboratory abnormalities returned to normal within 10 days following delivery. Four patients were delivered by cesarean section and three had vaginal deliveries. We had two maternal deaths (mortality 34%). One died of multi-organ failure and the other with adult respiratory distress syndrome. There was one stillbirth and the second baby died soon after birth due to prematurity (infant perinatal mortality 34%). We conclude that HELLP syndrome is rare among pregnant women in our institution. It should always be suspected in women with pre-eclampsia or eclampsia when they present with upper abdominal pain. Multipara seem to be more afflicted. Subclinical disseminated intravascular coagulation was detected in 55% of the patients. A majority of our patients presented late to the hospital.

Endemic juvenile hypothyroidism in a severe endemic goitre area of Sudan.

OBJECTIVE: The aim of the study was to assess thyroid function, iodine intake and exposure to dietary goitrogens of children living in an area with a high prevalence of goitre, in the region of Darfur, Sudan. DESIGN: In a village where goitre affected approximately 85% of children, a cross-sectional survey of thyroid function was performed in children 0-7 years old. PATIENTS: Twenty neonates and 190 children, aged 1 month to 7 years, were included. MEASUREMENTS: Thyroid hormones, urinary iodide and thiocyanate excretion were measured. RESULTS: Mean +/- SD serum T4 was below the normal range at birth (82 +/- 50 nmol/l) and in the age group less than 2 years (73 +/- 46). Children older than 2 years had even lower serum T4: 37 +/- 37 (P < 0.001) at 3-4 years and 36 +/- 38 (P < 0.001) at 5-7 years. Mean serum TSH was 25.8(6.2-107.7) mU/l at birth, 8.3(2.5-27.8) in the group less than 2 years, 15.3(2.9-79.1) at 3-4 years and 16.4(2.7-98.3) at 5-7 years. The overall prevalence of hypothyroidism (TSH > 50 mU/l) was 24%. Mean urinary thiocyanate was high at birth (107 +/- 69 mumol/l), normal in the group less than 2 years and higher in children older than 2 years (126 +/- 69 mumol/l) (P < 0.001). All age groups had a low urinary iodide concentration. CONCLUSION: Hypothyroidism was very frequent in each age group. The higher frequency of hypothyroidism observed in weaned children (> 2 years) was attributed to the combined effects of iodine deficiency and goitrogens (thiocyanate and glycosylflavones) derived from millet.

Serum and salivary IgG and IgA response to radiation therapy.

Patients undergoing radiotherapy for malignant tumors of the head and neck invariably develop extensive oral and dental diseases particularly when the major salivary glands are within the radiation fields. Unless the patient receives a strict oral hygiene home care and the teeth are protected by topical application of fluoride gel, caries or gingival disease onset inevitably follows radiation induced xerostomia is. The importance of saliva as a controlling factor in the development of oral diseases is underscored by the dramatic increase in dental decay and gingival diseases that inevitably follows the surgical extirpation of the major salivary glands in animals and the onset of xerostomia in man.

Pediatric non-Hodgkin's lymphoma abdominal presentations: a comparative study between two treatment regimens at the National Cancer Institute Cairo.

Abdominal presentations of pediatric NHL are rarely amenable to complete surgical resection. Chemotherapy is the hallmark of treatment for pediatric NHL. Treatment of various types of this disease including intra-abdominal NHL in children with various protocols have not exceeded 54 per cent two-year disease-free survival. We have attempted to study and compare the effects of two treatment regimen upon two groups of previously untreated children up to the age of 16 years who presented to the Pediatric Oncology Unit at the NCI. The first group included 18 children who presented between 1983 and 1985 and were treated by a modified St Jude regimen: while the second group of patients was comprised of 19 children who presented between 1985 and 1987 and were treated by a multi-national protocol: the MCP 842. The two groups will be compared with respect to various patient characteristics, response to therapy and their two-year disease-free survival as well as overall survival.

Lineage ambiguity in acute leukemia.

Two cases of acute nonlymphocytic leukemia that showed surface phenotypes characteristic of lymphoid cells are reported. The cases, both involving female patients were studied by a variety of methods including flow cytometry and karyotyping. In Case 1, the patient, a 10-year-old girl, had poorly differentiated myeloblasts (FAB M1), which were weakly positive for Sudan black B (SBB), but negative for alpha naphthyl acetate esterase (NAE) and naphthol ASD chloroacetate esterase (CAE). Myeloperoxidase was demonstrated ultrastructurally in some of the blasts. In Case 2, the 30-year-old patient had typical myelomonocytic leukemia (FAB M4), with SBB-, NAE-, and CAE-positive blasts. Both cases were negative for terminal deoxynucleotidyl transferase. Case 1 was negative for myeloid membrane markers, whereas Case 2 was strongly positive for My7 and My9. Surprisingly, both cases showed significant positivity for B-cell restricted antigens B1, B2, and B4. These findings suggest ambiguous or dual lineage, supporting the concepts that some leukemias could arise from a pluripotent hematopoietic progenitor cell (Case 1) or from cells that though differentiated in some respects, could still preserve some early antigens (Case 2).

Red blood cell distribution width index in some hematologic diseases.

The red blood cell distribution width index (RDW) was determined in a group of anemic male patients and normal male blood donors. Elevated mean RDW values were found in the anemic patients, with the highest value seen in sickle cell anemia, sickle cell-beta thalassemia, sickle cell trait, beta-thalassemia trait, and iron deficiency in decreasing order of magnitude. The mean RDW of the normal male subjects was 11.3. It was found that the RDW was proportional to the reticulocyte count, with the highest values in the patients with the highest reticulocyte count (sickle cell anemia). One clinical value of the RDW therefore may lie in its capacity for reflecting active erythropoiesis. For example, patients with normal or near-normal hemoglobin and with high RDWs may be suspected of having an elevated reticulocyte count that may indicate a hemoglobinopathy, such as sickle cell trait or thalassemia trait.

Squamous cell carcinoma of the pyriform sinus.

This is a review of 418 patients with cancer of the pyriform sinus who had complete treatment at University of Texas M. D. Anderson Hospital, treated over a 28-year time span. Treatment modalities used included radiation therapy, surgery, and planned combined treatment, primarily in the form of surgery and postoperative radiation therapy. Superficial lesions, with no impairment of laryngeal motility, are suitable for irradiation therapy planned for cure. (The policies of treatment have changed throughout the years). Analysis is made comparing the results of the larger groups of patients treated by surgery only, or surgery followed by postoperative radiation therapy. There is a significant lower incidence of failure above the clavicle in the combined treatment group, and a better 5-year survival. Rate of recurrences and the specific sites of failure above the clavicles are discussed, as well as the means of preventing such. The causes of death between 2 and 5 years are presented.

Testicular tumors in undescended testes.

Twelve cases of malignant tumors in undescended testes were studied. Early diagnosis of these tumors was usually difficult as the testes were intrabdominal and the symptoms vague. Sixty percent of the seminoma cases were of the anaplastic aggressive variant. Early treatment of undescended testes included either orchiopexy or orchidectomy in early childhood. Exploratory laparotomy and frozen section examination of the abdominal nodes, followed by silver clip application, aided in better staging and the planning of further treatment.