Ewing's sarcoma as second malignant neoplasm after retinoblastoma: a case report.

OBJECTIVES: To report a case of a child with the hereditary form of unilateral retinoblastoma (RB), who developed Ewing's sarcoma of the right fibula 3 years after the enucleation of the right eye. CASE PRESENTATION AND INTERVENTION: The child was diagnosed as a case of RB of the right eye at the age of 9 months. He was fully investigated and found to have locally advanced RB with bone marrow involvement (Reese-Ellsworth stage IVA). Enucleation was recommended to the family, but they refused. The patient received chemotherapy and diode laser thermotherapy in Kuwait and the UK. He had a local relapse after 11 months and subsequently underwent enucleation of the right eye. After 3 years, he was investigated for a small swelling in his right lower leg. After extensive investigations, it was reported as Ewing's sarcoma. He was treated with chemotherapy, surgery (complete excision of the fibula) and high-dose chemotherapy followed by autologous stem cell transplantation. The child is now nearly 2 years after completing the treatment and is disease free. CONCLUSIONS: This case confirms the increased risk of a second malignant neoplasm (SMN) in children with hereditary RB. These children need a very close follow-up for the early diagnosis of SMNs or even subsequent malignancies.

Direct evidence on the immune-mediated spontaneous regression of human cancer: an incentive for pharmaceutical companies to develop a novel anti-cancer vaccine.

To develop an effective pharmaceutical treatment for a disease, we need to fully understand the biological behavior of that disease, especially when dealing with cancer. The current available treatment for cancer may help in lessening the burden of the disease or, on certain occasions, in increasing the survival of the patient. However, a total eradication of cancer remains the researchers' hope. Some of the discoveries in the field of medicine relied on observations of natural events. Among these events is the spontaneous regression of cancer. It has been argued that such regression could be immunologically-mediated, but no direct evidence has been shown to support such an argument. We, hereby, provide compelling evidence that spontaneous cancer regression in humans is immunologically-mediated, hoping that the results from this study would stimulate the pharmaceutical industry to focus more on cancer vaccine immunotherapy. Our results showed that patients with >3 primary melanomas (very rare group among cancer patients) develop significant histopathological spontaneous regression of further melanomas that they could acquire during their life (P=0.0080) as compared to patients with single primary melanoma where the phenomenon of spontaneous regression is absent or minimal. It seems that such regression resulted from the repeated exposure to the tumor which mimics a self-immunization process. Analysis of the regressing tumors revealed heavy infiltration by T lymphocytes as compared to non-regressing tumors (P<0.0001), the predominant of which were T cytotoxic rather than T helper. Mature dendritic cells were also found in significant number (P<0.0001) in the regressing tumors as compared to the non regressing ones, which demonstrate an active involvement of the different arms of the immune system in the multiple primary melanoma patients in the process of tumor regression. Also, MHC expression was significantly higher in the regressing versus the non-regressing tumors (P <0.0001), which reflects a proper tumor antigen expression. Associated with tumor regression was also loss of the melanoma common tumor antigen Melan A/ MART-1 in the multiple primary melanoma patients as compared to the single primary ones (P=0.0041). Furthermore, loss of Melan A/ MART-1 in the regressing tumors significantly correlated with the presence of Melan A/ MART-1-specific CTLs in the peripheral blood of these patients (P=0.03), which adds to the evidence that the phenomenon of regression seen in these patients was immunologically-mediated and tumor-specific. Such correlation was also seen in another rare group of melanoma patients, namely those with occult primary melanoma. The lesson that we could learn from nature in this study is that inducing cancer regression using the different arms of the immune system is possible. Also, developing a novel cancer vaccine is not out of reach.

Studies of a human mesothelioma.

Abdominal fluid from a patient with mesothelioma was cultured in vitro, and a cell line designated JMN was established. This cell line has undergone more than 100 passages. Electron microscopic, karyotypic, and heterotransplantation studies as well as the capability of collagen synthesis by this cell line indicated that it is of malignant mesothelial origin. The cell line has proved very useful for the isolation of human pathogenic viruses.

Management of thymoma. A retrospective study.

Thymoma is a relatively rare tumour. Twelve cases seen in Kuwait Cancer Control Centre over a period of 10 years were analyzed. Two patients had Myasthenia gravis at presentation, and one developed it after the treatment, during remission. Six patients had total resection and four had subtotal resection of the tumour; the remaining had only diagnostic biopsy. All the six patients who had total resection were alive, disease-free with three of them Stage III, whereas, of the four cases who had subtotal resection two are dead, one with local disease and the other with pulmonary metastases. Eight patients were given postoperative radiotherapy and none of them relapsed at the primary site. Of the three patients who had chemotherapy, two had partial remission, and the remaining one failed to show any response. Patients with predominantly epithelial type histology fared worse compared to predominantly lymphocytic type and mixed cell type. Histological subtypes, invasiveness of the tumour and completeness of resection and association of Myasthenia gravis as prognostic features are discussed. The role of radiotherapy and chemotherapy as adjunctive treatment to surgery is reviewed.

Serum CA-15.3 and CEA patterns in postsurgical follow-up, and in monitoring clinical course of metastatic cancer in patients with breast carcinoma.

Serum CA-15.3 and CEA levels were longitudinally determined in 307 patients with breast carcinoma during postsurgical follow-up and/or therapy. Of 120 patients with no apparent disease, the specificity of marker levels fluctuating within the normal range (true-negative) was 98% for CA-15.3 alone (P = 0.004) and about 88% for CEA alone or for the tests combined. However, the false-negative levels in patients with progressive cancer reduced the predictive value of the tandem to around 76%, i.e. normal levels of both markers correctly predicted uneventful postsurgical course in only three fourths of the patients. Of 187 patients with active disease, the sensitivity of raised or increasing marker levels was around 70% for CA-15.3 alone or CEA alone, and 82% for the tests combined (P = 0.006). The 11% false-positive rate of CEA in patients with no apparent disease decreased the predictive value of a positive test from 98% for CA-15.3 alone (P = 0.006) to 91% for CEA alone or the tandem. Serum CA-15.3 or CEA paralleled the site of relapse: at least one marker was found elevated in 60% of patients with locoregional disease or with metastases to the lungs or bones exclusively, and in 90% of those with metastases to the lungs and bones or to the liver. A concurrent decrease of both marker levels reflected response to therapy while an increase of at least one marker level reflected treatment failure. It may be concluded that the marker tandem was better than either marker alone for follow-up aimed at detection of relapse, and that the tests were approximately 80% accurate for follow-up and/or monitoring therapy.

A profile of tumor markers in the population of Kuwait.

The tumour markers CEA, AFP, CA 125 and CA 199 were analyzed in a group of apparently healthy subjects in Kuwait. The sample (n = 394) included both genders in the population with a mean age of 38 (S.d. 12.0) years. The distribution of CEA levels values was significant different (Mann-Whitney U test) between Kuwaiti and non-Kuwaiti. The distribution of AFP levels was found to be the same in all groups. The distribution of CA 125 levels was significantly higher in females than in males, both in Kuwaiti and non-Kuwaiti. The distribution of CA 19-9 values was found to be significantly higher in the Kuwaiti female group when compared to the males. The upper reference level was defined as the 95 percentile of the normal values in each group. In the total population the reference level of AFP was 5.6 micrograms/l and of CA 19.9 43 kU/l. The reference level of CA 125 was 16 U/l in males and 24 kU/l in females, respectively. The CEA reference level in Kuwaitis was 6.9 micrograms/l and in non-Kuwaitis 4.4 micrograms/l. The results indicated the importance of determining the reference levels of tumour markers for each individual laboratory. It was also emphasized that care should be taken on the impact of 95 percentiles of normal and benign disease groups.

Reference levels of the tumor markers carcinoembryonic antigen, the carbohydrate antigens 19-9 and 72-4, and cytokeratin fragment 19 using the Elecsys Relecsys 1010 analyzer in a normal population in Kuwait. The importance of the determination of local reference levels.

The tumor markers CEA, CA 19-9, CA 72-4 and CYFRA 21-1 were analyzed in a group of apparently healthy subjects (n=232) in Kuwait using the Elecsys Relecsys 1010 analyzer. The distribution of the tumour marker levels was analyzed separately in Kuwaitis (n=103), non-Kuwaitis (n=129), smokers (n=68), non-smokers (n=164), males (n=138) and females (n=94). The distribution of CEA was significantly different in Kuwaitis vs. non-Kuwaitis in the total population (p=0.033) and in non-smokers (p=0.049); in males vs. females in the total population (p<0.0001) and in non-smokers (p=0.0002); and in smokers vs. non-smokers in the total population (p<0.0001) using the non-parametric Mann-Whitney U test. None of the other tumour markers showed significant differences in the subgroups. The upper reference level was defined as the 95th percentile of the normal values in each group. A higher reference level of CEA was observed in smokers (vs. non-smokers) in the total population. Also higher reference levels of CEA were observed in males (vs. females) both in the total population and in non-smokers. In the total population the respective reference levels were: CEA: 4.4 microg/L, CA 19-9: 35 kU/L, CA 72.4: 2.4 kU/L, and CYFRA 21.1: 2.1 microg/L. These results were compared with data in the kit inserts and literature data. The impact of 95th percentiles in a local heterogeneous population is discussed.

Carcinoembryonic antigen and breast carcinoma antigen (CA 15.3) in preoperative staging and postoperative monitoring of patients with carcinoma of the breast.

Serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen (CA 15.3) were determined in patients with breast carcinoma: in 129 before initial surgical or nonsurgical treatment and in 134 afterwards. Before any initial treatment, CEA was elevated in 15% of patients with Stage IV disease and CA 15.3 was high in 11% with Stage III and 48% with Stage IV. While monitoring management active disease was associated with elevated serum CEA in 66% of the patients, with elevated CA 15.3 in 73% and with at least one of the markers elevated in 86%. Both tests had high specificity (93% and 98%). The rise in serum CEA and, even more so, of serum CA 15.3 roughly paralleled the increase in bulk of the tumor: from locoregional disease through metastases to the lungs, bones, lungs with bones, and liver. Decreases in the levels of serum CEA and CA 15.3 reflected response to therapy, increases in the level of at least one marker-treatment failure, and levels fluctuating above the normal range indicated stationary disease. During follow-up, the predictive value of a negative test (levels within the normal range), suggesting that the patient might be free of disease, was 61% for CEA alone, 67% for CA 15.3 alone, and 80% for the two tests combined. We conclude that an elevated serum level of only one of the markers was useful for staging, implying advanced disease. Determination of both markers jointly was useful for monitoring the effectiveness of the therapy and for follow-up aimed at detection of relapse.

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer.

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.

Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and extragonadal germ cell tumors.

Serum levels of AFP, hCG and CEA were initially and serially measured in 59 patients with testicular germ cell tumors, and serially in 37 with ovarian and 3 with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature teratoma had normal serum AFP and sporadically slightly elevated hCG. Some patients with embryonal carcinoma, pure or with admixture of seminoma, had serum AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited. Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those with choriocarcinoma had elevated hCG, and those with compound tumors had one or more of the markers highly elevated. High AFP and/or hCG levels indicated the presence of the relevant tumor cells both in the primary and in residual tumor and/or metastases, also those missed in histological material, and thus were useful in restaging. Unfortunately, their absence in serum did not exclude the presence of marker-negative subpopulations of tumor cells. Changes in marker values paralleled the effects of treatment: the level increasing from any nadir heralded recurrence in patients in remission; elevated or increasing levels during therapy implied resistance to the therapy; decreasing levels indicated regression even though a return to the normal range did not mean eradication of all tumor cells.

Prognostic significance of CEA and CA 19-9 in colorectal cancer in Kuwait.

Preoperative CEA and CA 19-9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes' stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19-9 have been found than those usually employed. In the present study 62 patients with Dukes' stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes' B (69%) versus Dukes' C (48%) patients (p = 0.09). On the other hand, Dukes' stage B + C patients with elevated preoperative levels of CEA or CA 19-9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p = 0.003); for CA 19-9 levels below or above the cutoff the DFS was 71% versus 33% (p = 0.004). In 54 patients with Dukes' stage B + C for whom preoperative levels of both CEA and CA 19-9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19-9 elevated (chi-square 7.09; p = 0.008), CA 19-9 elevated (chi-square 6.27; p = 0.01), CEA elevated (chi-square 5.47; p = 0.02), and Dukes' C (chi-square 2.08; p = 0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19-9 prior to treatment.

Five-year survival versus initial concentrations and longitudinal serum CEA patterns in patients with colorectal carcinoma.

Patients (n = 464) with colorectal carcinoma in stages A to D2 were studied; 230 had CEA determined preoperatively and 433 serially. Actuarial life table analysis and the Mantel-Cox test showed that overall 5-yr survival was 59.2% and that the differences among the stages were highly significant. Survival rates for patients with CEA over the cutpoints at 3.2, 5, 10, and 20 ng/ml decreased from 53.8% to 21.9%. When analyzed in Cox multivariate regression, stage, initial CEA, age, and location of cancer affected survival. Postoperatively, three CEA patterns were found: 1) CEA was always normal; 2) initially elevated CEA was decreasing to the normal range to remain so thereafter; or 3) CEA started to increase from any nadir some time after surgery. The 5-yr survival rate was 73.3% for patients with the normal, 44.5% with the decreasing, and 30.1% with the increasing CEA pattern. When the postoperative CEA, pattern was added to the preoperative covariates in 196 patients for whom both the initial CEA, and postoperative patterns were available, only the stage, postoperative CEA pattern, and location of cancer affected survival. After elimination of initial CEA 433 patients with postoperative serum were analyzed, and again, only stage, postoperative CEA pattern, and location of cancer appeared to affect survival. Stage of disease, initially elevated serum CEA, age over 60 yr, location of cancer in the rectum, and CEA increasing after surgery appear to be independent ominous prognostic indicators.

Laparoscopic closure of perforated duodenal ulcer.

BACKGROUND: Medical treatment of peptic ulcer is highly successful, and the eradication of Helicobacter pylori (H. pylori) reduces ulcer recurrence. However, the incidence of perforated duodenal ulcer and its associated mortality have not been reduced by modern methods of therapy. Laparoscopic simple closure and omental plug by suturing, fibrin glue, and stapler have been successful. METHODS: Over a 1-year period (1996-97), 21 patients with perforated duodenal ulcer were operated on in our hospital by laparoscopic simple closure and omental patch. The mean age was 36.4 +/- 11.8 years (range, 18-61). Twenty patients were male (93.7%). The mean duration of pain was 9.1 +/- 11.7 hs (range, 2-48). Three patients had a previous history of duodenal ulcer (14.3%), and another three (14.3%) patients had a history of nonsteroidal antiinflammatory drug (NSAID) intake. Erect chest radiograph showed that 19 patients had air under the diaphragm (90.5%). Sixteen patients (76.2%) had frank pus in the abdomen, and five patients had a minimal peritoneal reaction (23.8%). RESULTS: The mean operative time was 71.6 +/- 24.6 mins (range, 40-120), and the mean hospital stay was 5.2 +/- 1.6 days (range, 3-9). The mean time to resume oral fluids was 3.1 +/- 0.8 days (range, 2-4). Only one patient was reoperated due to leakage identified by gastrographin swallow. CONCLUSIONS: This procedure is safe and efficient; however, further study of its long-term effectiveness and comparability to existing therapy is still needed.

Thorotrast-induced oro- and hypopharyngeal fibrosis with recurrent bleeding.

Thorium dioxide, widely used as a contrast material, is a producer of alpha particle radiation. This is well demonstrated by autoradiography. The case described illustrates that life-threatening, thorium dioxide-induced pharyngeal haemorrhage may occur even with an occluded carotid artery. The radiation exposure caused an intense foreign body reaction with a marked cell-deficient fibrosis. The alpha particles are well demonstrated by autoradiography. In addition, we were able to show a defect in the wall of the carotid artery due to the Thorotrast injection, which was closed by cell-depleted connective tissue. As the radioactivity of the nuclides of thorium dioxide peaks 30-40 years after its first application, the morbidity will increase and the disease has to be taken into careful consideration in head and neck tumour lesions.

Metaplastic carcinoma of the breast in a renal transplant recipient. Initial diagnosis by fine needle aspiration cytology and immunocytochemistry.

A 46-year-old woman presented with a mass in the left breast and left axillary lymphadenopathy. Five years earlier she had received a renal transplant from an unrelated donor because of end-stage renal failure secondary to adult polycystic kidney disease. She was on immunosuppression therapy in the form of cyclosporine, azathioprine and prednisolone. Fine needle aspiration cytology of the breast mass showed a metaplastic (sarcomatoid) carcinoma, whereas the axillary lymph node aspirate suggested carcinosarcoma. Immunocytochemical studies revealed dense positivity for vimentin in the sarcomatous component and positivity for epithelial membrane antigen in the epithelial component. Rare cells were positive for cytokeratin. The cytodiagnosis was confirmed by excision biopsy of axillary lymph nodes. The patient died on the fourth postoperative day following left mastectomy and axillary clearance. The histopathology report of the breast tumor showed sarcomatoid carcinoma.

Dietary intake and bioavailability of trace elements.

In order to assess the nutritional importance of trace elements, it is relevant to consider the factors regulating their metabolism. One of the most important factors is the true intake level. Conventional techniques such as diet history and interview studies in conjunction with standard food tables do not provide the true intake levels from prepared meals. Employing the duplicate portion technique, we have investigated the dietary intake of trace elements in prepared meals consumed by children, adults, and elderly in Sweden. The results indicate that the intake of potassium, magnesium, zinc, copper, and selenium is low when compared with the present recommended dietary allowance (RDA) values. It appears that a marginal deficiency of a number of trace elements may exist in the general population of affluent countries. When the dietary intakes are known, it is necessary to consider the bioavailability. This depends on the chemical form as well as the concentration of other dietary constituents such as fiber, phytate, carbohydrates, macrominerals, and vitamins in the diet. Knowledge of these interactions are important to improve the overall nutritional status of the population in general and patients in particular.

The diagnostic value of intranasal tests in allergic rhinopathy.

The method of the intranasal test, used by us, is described. It consists in a direct application of the allergen, which is presumed after a pilot-skin-test. The resulting reaction is documented by rhinomanometry. The special technical aspects of the test and the sources of error are emphasized.

War injuries during the Gulf War: experience of a teaching hospital in Kuwait.

The war injuries of 361 patients admitted to Mubarak Al-Kabeer Teaching Hospital, during the Gulf War are reported. More abdominal and chest injuries were seen in this series in comparison with other conflicts owing to the short evacuation time. Of the injuries, 54% were caused by gunshots, 34% were fragment injuries and 5.5% were glass and stab injuries. Civilians accounted for 50% of the injured. Wound infection rate was 7%, average hospital stay was 8.8 days and hospital mortality was 5.5%. We advocate radical wound excision, exploration of penetrating wounds of neck and abdomen, and mainly conservative management of chest injuries that do not involve the mediastinum.

Effectiveness of laparoscopic fundoplication for gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux (GERD) is a common condition. Many patients respond to conservative therapy. Severe symptomatic cases and those who fail medical treatment are referred to surgery. The long-term results of open fundoplication surgery have been good with a more than 90% response after 10 years of follow-up. The introduction of laparoscopic fundoplication achieved the same results with shorter hospital stay, a better cosmetic result and less cost to the health care providers. PATIENTS AND METHODS: 74 patients who failed medical treatment for GERD were treated by laparoscopic fundoplication. The Toupet procedure was performed in 66 of these patients, the others patients had a Nissen-type fundoplication. The patients were followed up for a mean period (+/- SD) of 14.8 +/- 8.8 months (range 3-33 months). RESULTS: Most of the patients were males (n = 65). The mean age (+/- SD) of all the patients was 36.1 +/- 9.5 years (range 17-60 years). The majority (93.8%) reported disappearance of symptoms and are not using any antireflux medications. Five patients (6.7%) are considered failures of the procedures. Of these, three patients developed recurrence of reflux symptoms during the follow-up period. The other two patients developed complications, i.e. gas bloat, persistent vomiting and dysphagia which warranted taking down the wraps laparoscopically. Two patients developed a small incisional hernia at the site of the 10 mm port. The mean of hospital stay (+/- SD) was 3.1 +/- 1.3 days (range 1-7 days). CONCLUSION: Laparoscopic fundoplication is safe and effectively relieves reflux symptoms in patients who fail medical treatment.