Mariko Mine

Comprehensive Clinical Assessment of 740 Cases of Surgically Treated Thyroid Cancer in Children of Belarus

Objective:A retrospective study was designed to evaluate the results of surgical treatment and follow-up data in thyroid cancer patients less than 15 years old at the time of surgery. Summary Background Data:Pediatric thyroid carcinomas have a high rate of lymph nodal and distant metastases. Risk factors for recurrences and postoperative morbidity have not been assessed yet in a representative series. Methods:The group included 740 pediatric patients with thyroid cancer. Total thyroidectomy was performed in 426 (57.6%), lobectomy in 248 (33.5%), subtotal thyroidectomy in 58 (7.8%) cases, and 8 patients (1.1%) underwent partial lobectomy. Results:The mean follow-up period was 115.8 months (range, 1.5–236.4 months). Recurrence was diagnosed in 204 cases (27.6%), including 73 local relapses (9.9%), 90 distant metastases (12.2%), and a combination of local and distant recurrences in 41 (5.5%) patients. Multivariate statistical assessment revealed the following independent parameters significantly associated with the risk of recurrent nodal disease: a young age at diagnosis, multifocal carcinomas, N1 status, and lack of neck lymph node dissection. For lung metastases, the significant risk factors were female gender, young age at diagnosis, and presence of symptoms. The observed 5- and 10-year survival for the entire group was 99.5% and 98.8%, respectively. Postoperative hypoparathyroidism was significantly associated with multifocal tumors, central compartment removal, and ipsilateral dissection. Conclusions:Total thyroidectomy followed by radioiodine therapy is an optimal treatment strategy that makes it possible to achieve a cure in a vast majority of pediatric patients with differentiated thyroid carcinomas. Risk of recurrence is strongly associated with tumor stage, extent of surgery, the young patients age, and presence of symptoms at diagnosis.

Deletions of p15 and/or p16 genes as a poor-prognosis factor in adult T-cell leukemia.

PURPOSE To determine the frequency of the deletions of p15/p16 genes in adult T-cell leukemia (ATL) cells and to evaluate their value in the diagnosis of clinical subtypes of ATL patients and the prediction of their clinical outcome. MATERIALS AND METHODS Peripheral-blood samples from 114 patients with ATL were examined by Southern blot analysis. In five chronic-type patients who showed disease progression to acute type, serial samples also were examined. RESULTS Among 114 patients, 28 (24.6%) showed the deletions of p15 and/or p16 genes. The results were well correlated with the clinical subtypes. Patients with deleted p15 and/or p16 genes had significantly shorter survival times than the patients in whom both genes were preserved (P < .0001). A similar decline in survival time was observed in the analyses within the same subtypes. In multivariate analysis using the Cox proportional hazard model, the deletions of p15 and/or p16 genes emerged as an independent prognostic indicator. Moreover, three of the five chronic-type patients who progressed to acute type lost the p16 gene alone or both the p15 and p16 genes at their exacerbation phase. CONCLUSION The results suggest the following: (1) that the deletions of p15 and/or p16 genes play a key role in the progression of ATL; and (2) that these deletions are reliable prognostic factors that predict shortened survival times.

Clinical and bacteriological characteristics of IMP-type metallo-β-lactamase-producing Pseudomonas aeruginosa

IMP-type metallo-beta-lactamase-producing bacteria have recently emerged worldwide. We conducted a case-control study in which 69 inpatients harboring bla(IMP)-positive Pseudomonas aeruginosa and 247 control subjects with bla(IMP)-negative pathogens were investigated. Prolonged hospitalization, antineoplastic chemotherapy, corticosteroid therapy (P=.001), and indwelling urinary catheters (P=.04) were risk factors for isolation of bla(IMP)-positive pathogens. The predominant source was urine (P=.001). The duration of antibiotic treatment and the total dose (including of carbapenems) were significantly greater among case patients than among control subjects (P<.01). bla(IMP)-positive P. aeruginosa isolates were more frequently resistant to multiple drugs (P=.001) and caused more infections (P=.001) than bla(IMP)-negative pathogens. There were no significant differences in bacteriological outcome (P=.94); however, infection-related death was more frequent among case patients than among control subjects (P=.023). These results suggest that precautionary measures against the spread of bla(IMP)-positive isolates are needed, because, for most of such pathogens, no antibiotic is potent enough to be used as a single agent in treatment of infection.

Apparently Beneficial Effect of Low to Intermediate Doses of A-bomb Radiation on Human Lifespan

Among about 100,000 A-bomb survivors registered at Nagasaki University School of Medicine, 290 male subjects exposed to 50-149 cGy showed significantly lower mortality from non-cancerous diseases than age-matched unexposed males. This was deduced from the fitting of a U-shaped dose-response relationship. Reasons for this effect in males, but not in females, are discussed with reference to selection of individuals and to hormesis.

Characteristics of chemotherapy-induced clinical remission in long survivors with aggressive adult T-cell leukemia/lymphoma

The acute and lymphoma types of adult T-cell leukemia/lymphoma (ATL) usually have a very poor prognosis, although some patients achieve long survival after chemotherapy. A total of 114 patients with these aggressive types of ATL were newly diagnosed at our institution from 1975 to 1989. By multivariate analysis, poor performance status and high serum creatine levels were associated with shortened survival. With combination chemotherapy, 20 patients achieved complete remission (CR), 53 achieved partial remission (PR) and 35 showed no response. Fifteen of the CR or PR patients survived for more than two years and all other patients survived for less than two years. As compared with short survivors (< 2 years) after remission, long survivors (> or = 2 years) after remission had a higher CR/PR ratio, a longer time until remission and a higher doxorubicin dose to achieve remission. Death due to causes other than the primary disease occurred in 18% of short survivors after remission and in 11.2% of nonresponders, but in none of the long survivors. Long survivors with acute ATL included 6 patients with CR and 5 patients with PR. All four lymphoma type ATL long survivors achieved CR. Monoclonal integration of HTLV-I provirus was detected in the peripheral blood mononuclear cells of all 3 PR long survivors with acute ATL studied, but was not detected in all 4 CR cases studied at remission. The minimum CD4/CD8 ratio of peripheral mononuclear cells at remission was < 1.0 in all acute ATL long survivors with CR, and was > 1.0 in all acute ATL long survivors with PR. Three out of six acute ATL long survivors with CR developed suspected viral infection just before achieving CR. Our findings show that in aggressive ATL the characteristics of remission are heterogeneous even among long survivors.

Incidence of intracranial meningiomas in Nagasaki atomic-bomb survivors

Among the Nagasaki atomic‐bomb survivors registered at the Scientific Data Center for Atomic‐Bomb Disaster, Nagasaki University School of Medicine, 45 cases of surgically treated intracranial meningioma were collected from 6 hospitals with departments of neurosurgery in or near Nagasaki City during the period from 1973 to 1992. All 45 patients were over 40 years of age at the time of diagnosis. Subsequently, the 45 cases were statistically analyzed in relationship to the estimated distance from the hypocenter by age, gender, intracranial location, histology and latent period. The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter. The incidence among Nagasaki atomic‐bomb survivors over 40 years of age, especially in those proximally exposed, appears to be increasing, in inverse proportion to the exposure distance, since 1981, 36 years after the explosion of the atomic bomb.

Direct hemoperfusion using immobilized polymyxin B in patients with rapidly progressive interstitial pneumonias: a retrospective study.

Background: Rapidly progressive interstitial pneumonia (IP), including acute exacerbation of IP, has a high mortality rate. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) was recently identified as an effective treatment for sepsis-associated acute respiratory distress syndrome. However, little is known about the effectiveness of PMX-DHP for rapidly progressive IP. Objectives: The present study investigates whether PMX-DHP is safe and effective against rapidly progressive IP. Methods: We retrospectively examined the effects of PMX-DHP in 33 consecutive patients with rapidly progressive IP who were resistant to steroid pulse therapy. Patients were hospitalized at Nagasaki University Hospital between 2006 and 2009. Results: Seventy-two hours after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–153 mm Hg) had significantly improved. One week after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–227 mm Hg), the alveolar-arterial difference of oxygen (median 371–177 mm Hg) and the number of positive criteria for systemic inflammatory response syndrome had significantly improved, despite the ineffectiveness of corticosteroid pulse therapy. The serum level of monocyte chemotactic protein 1 was significantly decreased immediately after PMX-DHP. Conclusions: PMX-DHP was safe and effective in improving oxygenation and systemic inflammatory response syndromein patients with rapidly progressive IP. The beneficialeffects of PMX-DHP may be at least partially due to the inhibition of monocyte activation.

Psychological distress among evacuees of a volcanic eruption in Japan: A follow-up study

Abstract Psychological distress in 248 evacuees from a volcanic eruption was evaluated using a 30‐item General Health Questionnaire (GHQ‐30) at four time points after evacuation: 6 months, 12 months, 24 months and 44 months. The proportion of evacuees with psychological distress (defined as a GHQ score ≥ 8) significantly decreased from 66.1% (6 months) to 45.6% (44 months). The GHQ mean score significantly improved from 12.6 to 8.9. Investigation of each factor on the GHQ showed progressive improvement over time in ‘anxiety, tension and insomnia’ and ‘anergia and social dysfunction’. However, ‘depression’ began to improve only after 44 months and ‘interpersonal dysfunction’ started to worsen after 12 months. The dysfunction in interpersonal relationships continued at 44 months. Examination of the relation between GHQ mean scores and age group showed that recovery from psychological distress was more difficult in middle‐aged and older evacuees than in younger evacuees.

Morphological subtyping of acute myeloid leukemia with maturation (AML-M2): homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of AML-M2 with t(8;21)

Morphologic and cytochemical features of 30 acute myeloid leukemia subtype M2 (AML-M2) patients with t(8;21) were compared with those of 50 AML-M2 patients without t(8;21). It was disclosed that irregular nuclear shape, Auer bodies, and at least 90% myeloperoxidase positivity in blast cells, and pseudo-Pelger-Huët anomaly of the nuclei and homogeneous pink-colored cytoplasm of mature neutrophils were observed in 90–100% of the t(8;21)+ patients. The percentages of patients showing these features were significantly (P < 0.01) lower in the t(8;21)− group. Among these morphological features, homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of t(8;21)+ AML-M2, because it was seen in 90% of the t(8;21)+ patients but in only 2% of the t(8;21)− patients. Conversely, pale-colored cytoplasm without any granules in mature neutrophils or dyserythropoietic features was observed in 84% of the t(8;21)− patients, but in none of the t(8;21)+ patients. These data suggest that it is possible to subtype AML-M2 patients morphologically by the recognition of homogeneous pink-colored or pale-colored cytoplasm of mature neutrophils and dyserythropoietic features. Thus, the morphologic subtyping of AML-M2 can be utilized alone or in combination with chromosomal or molecular subtyping for biological and clinical studies of AML with maturation.

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

BackgroundWe previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection.MethodsWe compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II).ResultsBy a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3).ConclusionsThe modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.