Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.     

Results of a non-controlled trial of hyperthermia combined with radiation for superficial tumours

Fifty-four patients with 65 superficial malignant lesions were treated by local hyperthermia combined with radiation therapy at the National Cancer Center Hospital, Tokyo. Hyperthermia was delivered with an Aloka Model HMS-020 (2450 MHz) or with a horn-type applicator of BSD-1000 (80-90 MHz). Relatively small tumours, those less than 4 cm in thickness, were treated by using 2450 MHz while 80-90 MHz delivered through the horn-type applicator was used for tumours exceeding 5 cm in thickness. The radiation dose was 4 Gy twice a week or 2 Gy five times a week, the total dose being 40-60 Gy. A total of six to 10 hyperthermia treatments ranging from 40 to 60 min each, with the tumour heated to more than 42.5 degrees C, were given twice a week within 1 h following radiation therapy. Complete response was achieved in 16 of the 30 patients (55 per cent) treated with the 2450 MHz microwave, and partial response in seven others (23 per cent). Tumours treated with the BSD-1000 achieved complete response in 10 out of 33 patients (30 per cent) and partial response in nine others (27 per cent). In five out of nine patients classified as partial responders, however, complete disappearance of tumour cells was noted by post-treatment histological examination. Complete plus partial response rates were thus essentially the same with the Aloka HMS-020 and the BSD-1000, though the rate of complete response was apparently higher with the Aloka unit, probably because it was used on smaller tumours.     

Prospective randomized controlled study on bestatin in resectable gastric cancer--third report

The efficacy of Bestatin as adjuvant immunochemotherapy for patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into two groups; a control group and an experimental group, the patients in the experimental group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT). The survival rate of the patients in the MMC + FT + Bestatin group was more favorable than that of the patients in the MMC + FT group, but the difference was not statistically significant. The survival rates of the MMC + FT + Bestatin group patients in the stratification of stage III + IV and positive histological serosal invasion, ps(+), were significantly superior to those of the MMC + FT group patients (Logrank test: p less than 0.05). Moreover, in patients with positive histological serosal invasion, the recurrence of peritoneal dissemination was significantly suppressed in the MMC + FT + Bestatin group.     

A case of double cancer: renal cell carcinoma and transitional cell carcinoma of urinary bladder

This is a case report on a patient with double cancer of kidney and urinary bladder. The patient was a 65-year-old female, and she was admitted with the chief complaint of gross hematuria and right flank pain. After careful examinations, she was diagnosed with right nonfunctioning kidney caused by invasive bladder cancer. Computerized tomography incidentally revealed a mass in the upper pole of the left kidney. Selective left renal arteriography showed stretched arteries and irregularity and tortuosity of the smaller vessels. She was diagnosed with double cancer of bladder and left kidney. Owing to the damage of the right renal function, left partial nephrectomy, total cystectomy, right nephroureterectomy and left ureterocutaneostomy were performed. According to DMSA scintigraphy measured 15 days later, the uptake value of the left kidney was 13.25%, compared to the preoperative value of 25.62%. To date, this case is 36th reported case in Japan.     

Mortality among children with Kawasaki disease in Japan.

BACKGROUND AND METHODS. It is not certain whether patients with Kawasaki disease have a higher death rate than the age-matched healthy population. We therefore undertook a study to investigate this question. Between July 1982 and December 1988, 53 collaborating treatment centers collected data on all patients who had an unequivocal new diagnosis of Kawasaki disease; patients who had recurrent disease or whose first visit to the treatment center occurred more than 14 days after the onset of symptoms were excluded. Patients were followed from the time of the first visit to the treatment center until December 31, 1989, or until death, whichever occurred first. The expected number of deaths was calculated from Japanese vital-statistics data and compared with the number observed. RESULTS. Of 4676 patients who met the eligibility criteria, 4608 (98.5 percent) were followed through either the end of the study or the date of death. Thirteen patients (10 boys and 3 girls) died during the study period. The number of deaths expected was 7.61 (ratio of observed to expected deaths, 1.71; 95 percent confidence interval, 0.91 to 2.92). The ratio was 2.04 (95 percent confidence interval, 0.98 to 3.76) for boys and 1.11 (95 percent confidence interval, 0.23 to 3.23) for girls. During the acute phase of the disease (the first two months after onset), the ratios of observed to expected deaths were higher: 9.86 overall (95 percent confidence interval, 3.95 to 20.31), 13.33 for boys (95 percent confidence interval, 4.89 to 29.07), and 3.85 for girls (95 percent confidence interval, 0.10 to 21.42). After the acute phase, however, both sexes had ratios of observed to expected deaths that were lower than 1, and the difference from the control population was not statistically significant. CONCLUSIONS. The mortality rate among boys with Kawasaki disease in Japan is twice that among healthy boys of the same age, and most deaths occur within two months of diagnosis. The mortality rate among girls with the disease appears similar to that among healthy girls, although the numbers are very small.     

Interleukin-4 as a potent down-regulator for human alveolar macrophages capable of producing tumour necrosis factor-alpha and interleukin-1.

The effects of recombinant human interleukin-4 (IL-4) on the production of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) by human alveolar macrophages (AM) and autologous peripheral blood monocytes (PBM) in response to lipopolysaccharide (LPS) were examined. AM and PBM were obtained by bronchoalveolar lavage and centrifugal elutriation, respectively, from healthy donors. The production of IL-1 (alpha and beta) and TNF alpha by human AM and PBM were quantitated by enzyme immunoassays (EIA). When activated with LPS, AM secreted much more TNF alpha, but less IL-1 beta than PBM. The production of IL-1 (alpha and beta) by activated AM and autologous PBM was suppressed dose-dependently by IL-4. The inhibitory effect of IL-4 was greatest when it was added to AM or PBM simultaneously with LPS or within 3 h after LPS. The suppressive effect of IL-4 was completely neutralized by pretreatment with rabbit anti-IL-4 antiserum. IL-4 also suppressed the production of IL-1 and TNF alpha by monocyte-derived macrophages. As measured by thymocyte co-stimulation assay, the production of cell-associated IL-1 was inhibited by coculture of AM plus LPS with IL-4. Northern blot analysis showed suppression by IL-4 of expression of messenger ribonucleic acid (mRNA) for IL-1 and TNF alpha in LPS-stimulated AM. We conclude that IL-4 is a potent down-regulator for human alveolar macrophages capable of producing IL-1 and TNF alpha.     

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

BACKGROUND: Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut-off point to predict aneurysm formation is not clear. METHODS: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. A total of 2936 patients without Kawasaki disease were recruited from a single hospital as a control group. Odds ratios were calculated for six laboratory data with specific values as cut-off points. Receiver operating characteristic (ROC) curves were observed to determine the most appropriate laboratory tests and cut-off points. RESULTS: Hematocrit, leukocyte count, neutrophil proportion, and hemoglobin had one or more peaks of odds ratio for specific cut-off points, but they did not have a clear cut-off point for the predictor according to the receiver operating characteristic curves. Alanine aminotransferase (ALT) increased the risk of giant coronary aneurysms continuously so no clearly appropriate cut-off point was identified. Serum sodium concentration of 135 mEq/L had a peak of odds ratio, and those with <135 mEq/L had the highest odds ratio (4.78). This value seemed appropriate with a sensitivity of 78% and specificity of 57%, although the predictive positive value was as small as 5%. CONCLUSION: The author's propose that a serum sodium concentration of <135 mEq/L at the patient's first visit to hospital may be a predictor of giant coronary aneurysms due to Kawasaki disease.     

Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR = 1.008, 95% CI 1.002-1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR = 1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR = 0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.     

Analysis of factors influencing the recent decline in birth rate in Tokyo]

This study was undertaken in an attempt to find factors which affected the recent declining birth rate in Tokyo. Vital statistics of the female population, age 20-39, for the period of 1970 through 1985 for Tokyo were compared to national averages. Indices examined were birth rate, percentage of married women, birth rate for married women, and birth rate for married women by live birth order. Results thus obtained were as follows: 1. Birth rates for females aged 20-24 and 25-29 were largely dependent on percentages of married women rather than birth rates for married women both in Tokyo and in the nation as a whole, while the birth rates for females aged 30-34 and 35-39 were more dependent on birth rates for married women. 2. Percentages of married women aged 20-24 and 25-29 decreased during the observation period both in Tokyo and in the nation as a whole. 3. Birth rates for married women aged 30-34 and 35-39 dropped in the first 5 or 10 years of observation in both groups as a result of the reduction in high order live births. Thereafter, the decline changed to an upturn trend. 4. Yearly changes of birth rate, percentage of married women, birth rate for married women, birth rate for married women by live birth order, and birth rate of first child for married women appeared to have the same timing both in Tokyo and in Japan as a whole in each age category.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological circumvention of multiple organ metastases of multidrug resistant human small cell lung cancer cells by mouse-human chimeric anti-ganglioside GM2 antibody KM966

The formation of metastases in multiple organs and acquired multi-drug resistance (MDR) are the major obstacles for treatment of human small-cell lung cancer (SCLC). To explore the possibility of immunological overcoming of multiple-organ metastases produced by refractory SCLC, we established the MDR variant (SBC-3/DOX), expressing P-glycoprotein, of parental SBC-3 cells by culturing with gradually increasing concentration of adriamycin. Both SBC-3 and SBC-3/DOX cells expressed a high amount of ganglioside GM2, an ideal target of SCLC cells. A mouse-human chimeric anti-GM2 monoclonal antibody (KM966) induced antibody-dependent cellular cytotoxicity (ADCC) mediated by human mononuclear cells (lymphocytes and monocytes) and complement-dependent cytotoxicity (CDC) mediated by human AB serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells. Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID) mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype. These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological circumvention of multiple-organ metastases of refractory SCLC. This revised version was published online in July 2006 with corrections to the Cover Date.