Satoshi Kondo

Extended thymectomy for myasthenia gravis patients: a 20-year review.

BACKGROUNDnSince 1973 we have performed extended thymectomy for myasthenia gravis because of the presence of thymic tissue in the anterior mediastinal fatty tissue. Follow-up results were reviewed and influencing factors were investigated.nnnMETHODSnThree hundred seventy-five patients with myasthenia gravis (286 nonthymomatous and 89 thymomatous) who have undergone extended thymectomies were reviewed. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Evaluation was performed at 3 and 6 months, and at 1, 3, 5, 10, 15, and 20 years. The effectiveness of the operation was estimated by the remission rate (RR = A/Total number of patients evaluated) and the palliation rate (PR = A + B/Total number of patients evaluated) at each point.nnnRESULTSnRemission rates of the nonthymomatous patients were 15.2% (3 months), 15.9% (6 months), 22.4% (1 year), 36.9% (3 years), 45.8% (5 years), 55.7% (10 years), 67.2% (15 years), and 50.0% (20 years). Remission rates in the thymomatous patients were 13.6% (3 months), 17.5% (6 months), 27.5% (1 year), 32.4% (3 years), 23.0% (5 years), 30.0% (10 years), 31.8% (15 years), and 37.5% (20 years). Absence of thymoma, younger age, and short duration of the disease were favorable prognostic factors. Thymectomy was effective also in patients with ocular myasthenia gravis. Preoperative steroid administration did not improve the outcome.nnnCONCLUSIONSnExtended thymectomy is an excellent operative procedure for myasthenia gravis in both nonthymomatous and thymomatous patients.

Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT

BackgroundIn the recent years, surgical resection with pre- and/or postoperative chemotherapy has markedly improved the survival rate of hepatoblastoma patients. We herein report the results of patients treated with the current protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2.MethodsA total of 279 patients with malignant liver tumor were enrolled in JPLT-2. Data from 212 hepatoblastoma cases were analyzed. PRETEXT I patients were treated with primary resection followed by low doses of cisplatin–pirarubicin (tetrahydropyranyl-adriamycin). Otherwise, patients received preoperative cisplatin–pirarubicin (CITA), followed by surgery and postoperative chemotherapy. Ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC) were given as a salvage treatment. High-dose chemotherapy with hematopoietic stem cell transplantation (SCT) was reserved for patients with metastatic diseases.ResultsThe 5-year overall survival rate (OS) in non-metastatic cases was 100% for PRETEXT I, 87.1% for PRETEXT II, 89.7% for PRETEXT III, and 78.3% for PRETEXT IV. The 5-year OS in metastatic cases was 43.9%. The outcome in non-metastatic PRETEXT IV cases was markedly improved, while the results of metastatic tumors remained poor.ConclusionsJPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases.

Effectiveness of screening for neuroblastoma at 6 months of age: a retrospective population-based cohort study

BACKGROUNDnIn Japan, a nationwide programme between 1984 and 2003 screened all infants for urinary catecholamine metabolites as a marker for neuroblastoma. Before 1989, this was done by qualitative spot tests for vanillylmandelic acid in urine, and subsequently by quantitative assay with high-performance liquid chromatography (HPLC). However, the Japanese government stopped the mass-screening programme in 2003, after reports that it did not reduce mortality due to neuroblastoma. We aimed to assess the effectiveness of the programme, by comparing the rates of incidence and mortality from neuroblastomas diagnosed before 6 years of age in three cohorts.nnnMETHODSnWe did a retrospective population-based cohort study on all children born between 1980 and 1998, except for a 2-year period from 1984. We divided these 22,289,695 children into three cohorts: children born before screening in 1980-83 (n=6,130,423); those born during qualitative screening in 1986-89 (n=5,290,412); and those born during quantitative screening 1990-98 (n=10,868,860). We used databases from hospitals, screening centres, and national cancer registries. Cases of neuroblastoma were followed up for a mean of 78.7 months.nnnFINDINGSn21.56 cases of neuroblastoma per 100,000 births over 72 months were identified in the qualitatively screened group (relative risk [RR] 1.87, 95% CI 1.66-2.10), and 29.80 cases per 100,000 births over 72 months in the quantitatively screened group (RR 2.58, 2.33-2.86). The cumulative incidence of neuroblastoma in the prescreening cohort (11.56 cases per 100,000 births over 72 months) was lower than that in other cohorts (p<0.0001 for all comparisons), but more neuroblastomas were diagnosed after 24 months of age in this cohort (p=0.0002 for qualitative screening vs prescreening, p<0.0001 for quantitative screening vs prescreening). Cumulative mortality was lower in the qualitative screening (3.90 cases per 100,000 livebirths over 72 months) and quantitative screening cohorts (2.83 cases) than in the prescreening cohort (5.38 cases). Compared with the prescreening cohort, the relative risk of mortality was 0.73 (95% CI 0.58-0.90) for qualitative screening, and 0.53 (0.42-0.63) for quantitative screening. Mortality rates for both the qualitative and quantitative screening groups were lower than were those for the prescreening cohort (p=0.0041 for prescreening vs qualitative screening, p<0.0001 for prescreening vs quantitative screening).nnnINTERPRETATIONnMore infantile neuroblastomas were recorded in children who were screened for neuroblastoma at 6 months of age than in those who were not. The mortality rate from neuroblastoma in children who were screened at 6 months was lower than that in the prescreening cohort, especially in children screened by quantitative HPLC. Any new screening programme should aim to decrease mortality, but also to minimise overdiagnosis of tumours with favourable prognoses (eg, by screening children at 18 months).

Pediatric and adult tracheobronchomalacia.

Twelve cases of tracheobronchomalacia (TBM) cases were reviewed: five were pediatric, and seven were adult, two of which were due to relapsing polychondritis (RPC). In pediatric TBM, the malacic segments were short. Resection of the malacic segment in one case and laryngotracheoplasty with autologous costal cartilage in one case were unsuccessful. However, aortopexy gained good results. Two cases managed conservatively experienced gradual improvement of their symptoms. In adult TBM, plication of pars membranacea was not effective in one case. The insertion of a stent was minimally effective in one case, and distinctly in one polychondritic case. The other four cases managed conservatively have deteriorated gradually. From these findings, a new classification system is proposed.

Expression of the prothymosin α mRNA correlated with that of N-myc in neuroblastoma

Abstract Neuroblastoma is the most common malignant solid cancers in early childhood. Overexpression of the proto-oncogene, N-myc, has been reported to be correlated with more malignant course of the disease. Prothymosin α, a cellular proliferation-associated gene, is reported to be a target of myc and elevated in several malignant cells and tissues. Expression of prothymosin α and N-myc messenger RNAs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) assay in 18 tumor samples from neuroblastoma using LightCycler. The data was analyzed in reference to clinicopathological factors. There was a tendency that higher prothymosin α transcripts levels in the tumor samples from younger patients ( 1 year.) ( P =0.0845). There was no relationship between prothymosin α gene expression and gender ( P =0.3029), mass screening case or not ( P =0.3007), or stage. The prothymosin α mRNA expression levels were correlated with N-myc mRNA levels ( P =0.006). Thus we suggest that prothymosin α plays an active role as a target of N-myc in neuroblastoma.

A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT)

IntroductionThe Japanese Study Group for Pediatric Liver Tumor (JPLT) has conducted cooperative treatment studies on hepatoblastoma (HBL) since 1991. The JPLT2 protocol was launched in 1999 to evaluate the efficacy of cisplatin/pirarubicin (CITA) under risk stratification. European and North American groups showed the improvement of HBL patients by pre- and postoperative chemotherapeutic regimens. Therefore, we evaluated the results of JPLT study and considered the future aspect of JPLT.MethodsA total of 389 children with malignant hepatic tumors were enrolled in JPLT-2 until 2010. Data from 331 HBL cases were analyzed.Results and dicussionOf the 331 patients enrolled, their 5-year overall survival and event-free survival rates were 83.3 and 68.0xa0%, respectively. While outcomes of standard-risk cases (tumors involving 3 or fewer sectors of the liver) were excellent, those of high-risk cases (tumors involving 4 sectors of the liver or with distant metastases) remained poor. For 26 high-risk or relapse/refractory HBL cases, high-dose chemotherapy (HDC) with stem cell transplantation (SCT) was carried out. Among them, 6 of 12 relapse or refractory cases died. Compared with other regimens, the CITA regimen achieved similar or superior rates of survival among children with standard-risk HBL, while HDC with SCT was not effective in patients with high-risk HBL. Presently, a global Children’s Hepatic Tumor International Consortium (CHIC) project is ongoing, with a focus on international cooperation and risk stratification in the field of rare liver cancers in children. More promising strategies, including liver transplantation and new targeting drugs under global risk stratification, are being proposed.

Evaluating patients’ outcome post-Kasai operation: a 19-year experience with modification of the hepatic portoenterostomy and applying a novel steroid therapy regimen

BackgroundWe reported a modification of the hepatic portoenterostomy (HPE) for biliary atresia with favorable results. HPE is associated with a risk of hepatic impairment, so we adopted a novel steroid therapy regimen well suited to our procedure. This paper reports the results of our experience.Patients and methodsBetween 1991 and 2009, 53 patients (18 boys, 35 girls) underwent modified HPE with novel steroid therapy, which consisted of administering hydrocortisone immediately after surgery, followed by intravenous administration of prednisolone. The number of patients who became normal total bilirubin (TB) levels, frequency of early onset cholangitis and other postoperative complications, and outcomes were retrospectively studied.ResultsThe TB levels in 43 of the 53 patients became normal. Cholangitis was observed in seven, but all of them recovered. Other postoperative complications were noted in eight, but with no fatal cases. Of the 11 patients who underwent living-donor liver transplantation, 3 died after the transplant. Of the 53 patients, 39 are alive without liver transplantation and 34 have normal TB (range of observation period: 18xa0years and 9–2xa0months).ConclusionsThe novel steroid regimen may have contributed to the outcome and appears to be well suited to the modified HPE.

Novel adaptor protein Shf interacts with ALK receptor and negatively regulates its downstream signals in neuroblastoma

Our neuroblastoma cDNA project previously identified Src homology 2 domain containing F (Shf) as one of the genes expressed at high levels in favorable neuroblastoma. Shf is an adaptor protein containing four putative tyrosine phosphorylation sites and an SH2 domain. In this study, we found that Shf interacted with anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase in neuroblastoma. Real‐time PCR analysis showed that Shf mRNA is highly expressed in non‐metastatic neuroblastomas compared to metastatic tumor samples (P < 0.030, n = 106). Interestingly, patients showing high ALK and low Shf mRNA expressions showed poor prognosis, whereas low ALK and high Shf expressions were related to better prognosis (P < 0.023, n = 38). Overexpression of ALK and siRNA‐mediated knockdown of Shf yielded similar results, such as an increase in cellular growth and phosphorylation of ALK, in addition to Erk1/2 and signal transducer and activator of transcription 3 (STAT3) that are downstream signals of the ALK‐initiated phospho‐transduction pathway. Knockdown of Shf also increased the cellular mobility and invasive capability of neuroblastoma cells. These results suggest that Shf interacts with ALK and negatively regulates the ALK‐initiated signal transduction pathway in neuroblastoma. We thus propose that Shf inhibits phospho‐transduction signals mediated by ALK, which is one of the major key players on neuroblastoma development, resulting in better prognosis of the tumor.

Left diaphragmatic hernia complicated by perforation of an intrathoracic gastric ulcer into the aorta: report of a case.

Abstract: We describe herein a rare but fatal complication of diaphragmatic hernia that occurred in a 51-year-old man 3 years after his diaphragm had been repaired by a polytetrafluoroethylene sheet following resection during pleuropneumonectomy for a left pleural mesothelioma. He was admitted to our hospital in shock status, and was found to have massive bleeding from the nasogastric tube. An emergency operation revealed that an ulcer of the stomach, which had been displaced into the left thorax, had perforated directly into the descending aorta.

Esophageal tracheobronchoplasty for diseases of the central airway.

Three infants with congenital tracheal stenosis and three adults with various diseases of the central airway underwent esophageal tracheobronchoplasty to repair long-segment stenoses and defects. The primary operative goal was enlargement of the stenosis (n = 4), repair of the defect (n = 1), or both (n = 1). Cardiopulmonary support was required in two cases. All three infants were operated on for generalized congenital tracheal stenoses. There was one postoperative death on the fifth day. Another infant died of pneumonia 3 months after operation. Tracheal patency was excellent in two infants. One infant is well without symptoms 6 years after the operation, although balloon dilation was required three times during the first postoperative year. In the three adult patients, the primary diseases were congenital tracheal stenosis, iatrogenic injury associated with relapsing polychondritis, and malignant mediastinal tumor involving the trachea. All lesions involved both the trachea and main stem bronchi. Postoperative airway patency was excellent in all three adults, although expandable metallic stents had to be inserted in one patient. Postoperative pulmonary function was improved, particularly forced expiratory volume in 1 second and peak expiratory flow rate. Although the postoperative mortality rate was still high, especially among the infants, and prolonged postoperative ventilatory support was required for five of the six patients, long-term patency and postoperative pulmonary functional improvement are encouraging.