Clinical characteristics and the prognosis of rhabdomyosarcoma - a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

AIM: There have been no nationwide group studies for patients with rhabdomyosarcoma in Japan. This study aims to assess the actual state of treatments and their outcome. PATIENTS AND METHODS: From 1982 to 1996, 79 rhabdomyosarcomas were registered by the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area. The prognostic factors and treatments were assessed based on the 5-year survival rate. The staging was done according to the Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification. RESULTS: The 5-year survival rate for all patients was 39.1 %. The survival rates for each factor were as follows, according to 1) group; 77.8 % for Group I, 51.9 % for Group II, 33.7 % for Group III, and 20.2 % for Group IV; 2) primary site: 56.3 % for the head and neck, 43.8 % for the parameningeal region, 12.5 % for the extremity, 58.3 % for the genitourinary region, and 30.5 % for the others; 3) histology: 35.8 % for the embryonal type, 36.8 % for the alveolar type. CONCLUSIONS: Altogether, the outcome of this study was poor. To improve outcomes, a new nationwide group study for rhabdomyosarcoma, which we belong to, has just started in Japan.

Ultrasound biomicroscopy in the diagnosis of persistent hypotony after vitrectomy.

PURPOSE: To describe a case of persistent hypotony after an otherwise successful vitreous surgery for epiretinal membrane, in which ciliochoroidal detachment was detected by ultrasound biomicroscopy but not by ophthalmoscopy. METHOD: We used ultrasound biomicroscopy to determine the cause of persistent postoperative hypotony. RESULTS: Ultrasound biomicroscopy clearly disclosed ciliochoroidal detachment. In an attempt to resolve ciliochoroidal detachment, we performed vitrectomy and fluid-gas exchange combined with diathermy around the sites of sclerotomy. Postoperatively, the regression of ciliochoroidal detachment was confirmed by ultrasound biomicroscopy. CONCLUSIONS: Using ultrasound biomicroscopy, we were able to visualize ciliochoroidal detachment and its regression clearly, which we had not observed during ophthalmoscopy.

Branched-chain amino acids metabolic support in surgical patients: a randomized, controlled trial in patients with subtotal or total gastrectomy in 16 Japanese institutions.

A prospective, randomized, controlled trial of nutritional effects of branched-chain-enriched amino acid (BCAA) solution was undertaken in 173 surgical patients with gastric cancer. Eighty-six and 87 patients underwent subtotal and total gastrectomy, respectively. The effects were evaluated in total parenteral nutrition (TPN) in an isocaloric/isonitrogenous setting where the major difference between the group was the amount of BCAA received. Each 80 patients in the control and the BCAA groups completed the trial. The group receiving BCAA-enriched amino acid solution demonstrated a statistically significant improvement on days 2 and 3 in nitrogen balance in patients with total gastrectomy. Three-methyl-histidine excretion gradually decreased after day 1, and the values on day 7 were significantly lower than those on day 1 in the BCAA group in both those receiving subtotal and total gastrectomy. There were no significant differences of serum albumin and rapid turnover proteins between the control and BCAA groups in both those receiving subtotal and total gastrectomy. Plasma BCAA level and BCAA to aromatic amino acid (AAA) ratio were significantly higher, and AAA level was significantly lower in the BCAA group than in the control group. There were no serious complications encountered during the observation period in both groups. These results indicated that a BCAA-enriched amino acid solution can improve metabolism and maintains good nitrogen retention without increasing side effects as compared with a conventional amino acid solution for nutritional support of patients who have received subtotal or total gastrectomy.

Neuroblastoma in infants aged less than 6 months: is more aggressive treatment necessary? A report from the Pediatric Oncology Study Group of the Kyushu area.

Infants with neuroblastoma are known to have a better prognosis than older children. In Japan in 1985, mass screening for neuroblastoma in infants aged 6 months was introduced. With this policy, there has been an increase in the number of patients seen with neuroblastoma between 6 and 11 months of age. In a previous report the authors described the management and prognosis of infants with disease detected by mass screening, but there is still little information regarding the strategies of management for infants with neuroblastoma aged less than 6 months. The authors analyzed the data regarding 27 patients aged less than 6 months registered in their region (population 15 million) from 1985 to 1992, and compared it with that of the previous 8-year period. In the younger age group, there was a significantly higher rate of advanced disease stages (III and IV). In spite of the variation in treatment related to the choice of individual institutions, infants with stages I, II, and III disease had a good outcome, suggesting that aggressive chemotherapy is not necessary unless poor prognostic factors are present. One patient with stage IV disease died of disseminated disease and one with stage IVs and 22 copies of N-myc oncogene also died of tumor relapse in spite of aggressive chemotherapy. It is therefore concluded that the prognosis in infants with stage IV and IVs neuroblastoma under the age of 6 months is not as good as had previously been believed, and that such patients, therefore, require special consideration.

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

Improved survival for patients with advanced neuroblastoma after high-dose combined chemotherapy based in part on N-myc amplification.

BACKGROUND/PURPOSE: In spite of many different kinds of chemotherapy for neuroblastoma, the prognosis for advanced neuroblastoma remains unsatisfactory. In particular, the outcome of advanced neuroblastoma with high copies of the N-myc gene tend to be poor. Therefore, the new high-dosage combined chemotherapy regimens for advanced neuroblastoma based in part on the N-myc amplification status has been utilized in the Kyushu area of Japan since 1991. This study aims to investigate whether these new regimens based in part on N-myc amplification have improved the survival rate of stage III and stage IV patients in comparison with the old regimens. METHODS: Between 1983 and 1995, 77 patients over 1 year of age and with stage III or IV neuroblastoma were registered in the Kyushu Area. Between 1983 and 1990, 49 patients received 1 of 2 combined chemotherapy regimens consisting of cyclophosphamide, cisplatin plus VM-26, and Adriamycin plus DTIC. Since 1991, two new regimens (New A1 and A3) have been administered based on the N-myc amplification status in a total of 28 patients. The New A1 regimen, which consists of cyclophosphamide, cisplatin, Adriamycin, and VP-16 has been administered in cases of less than 10 copies of N-myc, whereas the A3 regimen, consisting of a higher dose of cyclophosphamide, cisplatin, Adriamycin, and VP-16, has been administered in cases of more than 10 copies of N-myc. The survival rate was then compared between the old regimens and the new regimens. RESULTS: The 3-year survival rate (61.5%) for patients treated by the new regimens was significantly higher than that (32.7%) for patients treated by the old regimens (P <.01). Regarding the 24 cases of more than 10 copies of N-myc, the 3-year survival rate (35.9%) of the 13 patients treated by the A3 regimen was higher than that (0%) of the 11 patients treated by the old regimens (P <.05). However, in the 19 stage IV patients treated by the new regimens, the 3-year survival rate (11.1%) of the 9 cases of more than 10 copies was significantly lower than that (77.8%) of the 10 cases of less than 10 copies of N-myc (P <.01). CONCLUSIONS: These results suggest that high-dose combined chemotherapy based in part on the N-myc amplification status significantly improved the prognosis of patients with advanced neuroblastoma. However, stage IV patients with N-myc amplification still require a more effective treatment modality.

Mass screening for neuroblastoma at 6 months of age: difficult to justify.

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS: These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.

Bilateral choroidal osteomas associated with histiocytosis X.

A 15-year-old Japanese girl complained of decreased visual acuity in the left eye of 1-month duration. Histiocytosis X had been diagnosed when she was 2 years old based on examination of biopsies of skin and cervical lymph nodes and bone marrow aspirations. She had been in complete remission for 7 years. She exhibited the characteristic ophthalmoscopic, ultrasonographic, and radiologic features of bilateral choroidal osteomas.

Retinal detachment with tear in the posterior fundus following ocular contusion.

Two unusual cases of rhegmatogenous retinal detachment following contusion to the eyeball showed retinal tears at the posterior fundus close to the optic disc and the large retinal blood vessels. In both cases, the tears were not detected immediately after the injury due to a coexisting vitreous hemorrhage. Both patients were successfully treated by pars plana vitrectomy, air-fluid exchange, and endolaser photocoagulation. During vitrectomies, an adhesion of the vitreous to the flap or the operculum of the tear was observed, with detachment of the remainder of the posterior vitreous from the retina. Vitrectomy allowed a more complete resolution of posterior tractional forces than scleral buckling, and eliminated the vitreous hemorrhage.

Involvement of CD8+ RT1.B+ and CD4+ RT1.B+ cells of cervical lymph nodes in the immune response after corneal transplantation in the rat.

Graft rejection reactions have been observed with concomitant lymphocyte infiltrations after allogenic corneal transplantation, although the cornea is considered to be relatively protected from the systemic immune response. In order to characterize the lymphocytes that accumulate in cervical lymph nodes following transplantation, we used a model of orthotopic penetrating keratoplasty in inbred rats. After grafting, the time course of the pathological scoring was monitored, and subpopulations of CD4+ RT1.5+ and CD8+ RT1.B+ cells were analyzed in the cells harvested from the cervical lymph nodes. The number of CD8+RT1.B+ cells increased 1 week after grafting, reaching the maximum at 3 weeks; whereas CD4+ RT1.B+ cells were induced 1 week after the grafting and remained constant during the next 3 weeks. There were four times as many CD4+ RT1.B+ cells as CD8+ RT1.B+ cells 1 week after grafting when there was no rejection. Therefore, it appears that CD8+RT1.B+ and CD4+RT1.B+ cells in the cervical lymph nodes do participate in ocular immunologic responses.

The characteristics of mediastinal neuroblastoma.

The prognosis of mediastinal neuroblastoma has been reported to be better than for other neuroblastomas. The reason for this is however not clear. Furthermore, a comparison between mediastinal neuroblastoma and the other neuroblastomas has been rarely reported so far. In this study, the characteristics of mediastinal neuroblastoma (84 cases) are investigated and compared with those of other neuroblastomas (440 cases). Regarding clinical factors, the age distribution and the rate of cases detected at mass screening were similar in both groups. According to Evan's staging system, the rates of early stage (I, II) were 62% in the mediastinal neuroblastoma and 38% in the other neuroblastomas (p<0.001). Regarding the biological prognostic factors, a favorable histology based on Shimada's classification was found in 100% (35/35) of the mediastinal neuroblastoma cases and in 85% (112/132) of the other neuroblastoma cases (p<0.05). With regard to N-myc amplification, all of the examined 42 cases in mediastinal neuroblastoma had a N-copy number of less than 10 copies, while 32 of the examined 263 cases (12%) in the other neuroblastomas had an amplification of N-myc of more than 10 copies (p<0.05). The 5-year survival rates were 78% in the mediastinal neuroblastoma and 59% in the other neuroblastomas, respectively. Of the cases who underwent an incomplete resection of primary tumors in localized neuroblastoma, the 5-year survival rate of the mediastinal neuroblastoma cases was significantly more favorable than that of the other neuroblastomas. The majority of mediastinal neuroblastoma cases showed an early stage and favorable prognostic factors. It is likely that the clinical and biological prognostic factors of the tumor are therefore more closely correlated with the outcome of mediastinal neuroblastoma rather than the degree of the surgical resection. Regarding the treatment for mediastinal neuroblastoma, it is most important to evaluate the biology of the tumor after surgical resection.

Multiple organ failure (MOF) after intestinal operations--a clinical and statistical study of the past 5 years.

Multiple Organ Failure that occurred in 35 cases out of a total of 1498 cases after intestinal surgery were studied by an analysis of the clinical and statistical data from the past 5 years (1984-1988). 1. The incidence of MOF after intestinal surgery was 2.3%. 2. Twenty-eight of MOF resulted from severe infections. 3. The incidence of infection was highest after esophageal operations. 4. Hepatic failure was the most common type of primary organ failure and renal failure was the second most common. 5. The prognosis for MOF was very poor with a survival rate of 8.7%.

[The strategy against post-operative infection in the patients with esophageal cancer].

Post-operative infection with esophageal cancer patients was investigated. The subjects were 325 esophageal cancer patients. The most frequent infectious complication after the surgery was pneumonia, followed by anastomosis between the cervical esophagus and plastic stomach tube. The bacteria frequently found in infectious lesions were pseudomonas or staphylococcus. The more severe infection the patients had, the more gram negative bacteria were found. Bacterial examination during operation showed that more than 80% bacteria was gram negative. Since esophageal cancer patients had a low nutritional state, their immune function was impaired and infection was apt to occur post-operatively. Therefore, special nutritional care was indispensible, such as essential fatty acid, BCAA, and glutamine supplementation.

[Protein turnover and amino acids metabolism in septic rats].

This study was carried out to elucidate the protein and amino acids metabolism in septic rats, using constant infusion of 1-13C-leucine (4mg/hr), 5-13C-glutamine (2mg/hr), 1,2-13C-leucine (4mg/hr), or U-14C-leucine (2.0uCui/hr). Whole body protein kinetics showed that protein breakdown rate was increased in sepsis, but no change was found on protein synthesis rate (PSR). Intestinal mucosal fractional synthesis rate (FSR) was increased with sepsis. However, sepsis caused significant decrease of muscle FSR. Both leucine and glutamine oxidation rates were significantly increased in sepsis. Fraction of leucine degradation via glutamine was significantly increased in sepsis. We concluded that 1) both leucine and glutamine were utilized as important energy fuels in sepsis, 2) whole body PSR was influenced by the change of PSR in each organ, 3) the pathway from leucine to glutamine was significant in the degradation of leucine.

[Glutamine (Gln) supplementation in septic rats].

The objectives of these experiments were to investigate the effect of Gln supplementation on protein metabolism and immune function in septic rats. (Experiment 1): 73 SD female rats were catheterized for TPN into the jugular vein on day 1. On day 4, the rats were randomized into 4 group: 1) control (C)+Standard TPN (STPN), 2) (C)+Gln TPN (GTPN), 3) sepsis (S)+STPN, 4) S+GTPN. Sepsis was induced by injection of 10(10) C. Coli/kg from the TPN catheter. U-14C-leucine or 15N2-Urea was given before sacrifice on day 5. (Experiment 2): 48 SD male rats were randomized into 3 groups, 1) normal control rat (NC), fed as lib. 2) peritonitis (P)+STPN, 3) P+GTPN. On day 1, 34 rats were catheterized and either STPN or GTPN was begun. On day 3, 6 hours after serum cecum ligation and puncture, resuscitation was done. On day 5, rats were sacrificed. The results were as follows: 1) FSR of ileum, proximal colon, distal colon and muscle were augmented by GTPN, 2) Sepsis caused a significant increase of urea production, but GTPN prevented this increase, 3) lymphocyte blastogenation was decreased with sepsis, but GTPN improved this reduction, 4) Phagocytic index was higher with GTPN than STPN. We concluded that Gln supplementation would prevent from leading the patients with severe infection to the multiple organ failure.

[Surgical infection and its backgrounds].

The backgrounds of surgical infection of esophageal cancer patients are studied for host factors (relation of nutrition and immune response) and parasite factors surgical parts which are easily contaminated, the differences of serum concentration with 3 methods of antibiotics administration, and the relations about the bacteria in mouth and upper esophagus in operation and bacteria which were found in the respiratory system after operation). The results are as follows. The preoperative nutritional support was effective to rapid recovery of cytological immune functions. But in the post-operative infected cases, immunological recovery delayed and they nutritionally needed BCAA, glutamine, and essential fatty acids. For the study of parasite factors, surgical wounds (neck, chest wall, abdominal wall) were more easily contaminated than other parts except digestive tract. Continuous administration of antibiotics, 1g/hr x 4 was most excessive in three methods. The bacteria in the mouth and upper esophagus in operation and those in airway after operation, were not correlated. Furthermore, antibiotics-resistant bacteria which were Pseudomonas, MRSA were found in the airway. These results indicate that nutritional support is important for the host defense system and antibiotics should be administered considering each operative process. And about the postoperative respiratory infection, protection of hospital infection is important.