High Tumoral STMN1 Expression Is Associated with Malignant Potential and Poor Prognosis in Patients with Neuroblastoma.

BACKGROUND: Stathmin 1 (STMN1), a marker for immature neurons and tumors, controls microtubule dynamics by destabilizing tubulin. It plays an essential role in cancer progression and indicates poor prognosis in several cancers. This potential protein has not been clarified in clinical patients with neuroblastoma. Therefore, this study aimed to assess the clinical significance and STMN1 function in neuroblastoma with and without MYCN amplification. METHODS: Using immunohistochemical staining, STMN1 expression was examined in 81 neuroblastoma samples. Functional analysis revealed the association among STMN1 suppression, cellular viability, and endogenous or exogenous MYCN expression in neuroblastoma cell lines. RESULT: High levels of STMN1 expression were associated with malignant potential, proliferation potency, and poor prognosis in neuroblastoma. STMN1 expression was an independent prognostic factor in patients with neuroblastoma. Furthermore, STMN1 knockdown inhibited neuroblastoma cell growth regardless of endogenous and exogenous MYCN overexpression. CONCLUSION: Our data suggest that assessing STMN1 expression in neuroblastoma could be a powerful indicator of prognosis and that STMN1 might be a promising therapeutic candidate against refractory neuroblastoma with and without MYCN amplification.

Successful hepatectomy for hepatic abscess with chronic granulomatous disease: a case report.

BACKGROUND: Chronic granulomatous disease (CGD), a rare inherited disorder, is characterized by impaired ability of phagocytic cells to kill certain bacteria and fungi. Although liver abscess is a common manifestation of CGD, its optimal management in these patients is unknown. Here, we present a case of successful hepatectomy for hepatic abscess in a patient with CGD. CASE PRESENTATION: An adolescent patient with previously diagnosed CGD presented to the pediatrics department of our institution with fever. Blood tests showed high concentrations of inflammatory markers. A computed tomography (CT) scan showed a multilocular mass measuring 52 mm × 34 mm in hepatic segment 4 (S4). Blood cultures were negative. Despite administration of antibiotics and γ-globulin, his fever and high concentrations of inflammatory markers persisted and the mass did not change on CT scan images. Because the medications had proved ineffective and percutaneous drainage would have been difficult because of the honeycombing in the abscess, we performed hepatic S4a + S5 anatomic resection and cholecystectomy. Culture of the excised specimen was negative. The patient's postoperative course was uneventful. On day 62, CT showed no abscess around the resection stump. On day 81, he was transferred to undergo bone marrow transplantation. CONCLUSIONS: Surgical treatment for hepatic abscess can be effective when medical treatment has failed.

Histological analysis of appendices removed during interval appendectomy after conservative management of pediatric patients with acute appendicitis with an inflammatory mass or abscess.

BACKGROUND/PURPOSE: To clarify the role of interval appendectomy (IA) in pediatric patients with acute appendicitis with an appendiceal inflammatory mass or abscess, we histologically analyzed the appendices removed during IA. PATIENTS AND METHODS: We treated 355 consecutive pediatric patients with acute appendicitis and reviewed the admission charts of patients who started conservative management (CM). The histology of the appendix removed during IA was also examined. The relationships among the clinical features, appendicolith formation at the time of IA and histological findings were analyzed by stepwise regression analyses. RESULTS: (1) CM was started in 48 patients (13.5 %). Recurrence or a remaining abscess was observed in nine patients (18.8 %). (2) Histopathological changes, particularly foreign body reaction with fibrosis and infiltration of inflammatory cells, were observed in about half of the specimens. (3) In a stepwise regression analysis, the presence of an appendicolith at IA was correlated with an appendicolith at diagnosis, foreign body reaction in the appendix and a decrease in the inflammatory reaction at diagnosis. CONCLUSION: More than half the patients had strong histopathological changes in the appendix, suggesting a high possibility of recurrence. The presence of appendicolith formation at IA, which is a risk factor for recurrence, was influenced by the presence of an appendicolith at diagnosis, foreign body reaction in the appendix and the inflammatory status of patients at diagnosis. These clinical findings are indications for IA.

Outcomes of herniotomy in premature infants: recent 10 year experience.

BACKGROUND: The timing of herniotomy in premature infants is controversial. METHODS: Outcomes of herniotomy in 47 premature infants admitted to the neonatal intensive care unit (NICU) were retrospectively reviewed for preoperative clinical features, respiratory interventions, and anesthetic and surgical complications. The data were compared with those of full-term infants (n = 52). Fourteen of the premature infants underwent herniotomy before NICU discharge and 33 after discharge. The predictive factors for anesthetic and surgical complications were also investigated via multiple regression analysis. RESULTS: Mean post-conceptional age at surgery in premature infants and full-term infants was 47 weeks and 50 weeks, respectively. Mean bodyweight at surgery in those infants was 4087 g and 5454 g, respectively. The rate of incarcerated hernia and emergency surgery was lower in premature infants. Delayed extubation of the tracheal tube after surgery was noted in four premature infants, but not in full-term infants. Two cases of cryptorchidism in premature infants and one recurrence in a full-term infant that required reoperation were noted. On multiple regression analysis no factor (including respiratory interventions) was found to be capable of predicting complications. CONCLUSION: Although no predictive factor for complications was identified, there were some anesthetic and surgical complications in premature infants. If there is no risk of incarceration, herniotomy in premature infants should be performed at a time when the risk of anesthetic complications is decreased. If there is a risk of incarcerated hernia, herniotomy should be performed carefully in order to avoid occurrence of anesthetic and surgical complications.

Increased plasma levels of 8-hydroxydeoxyguanosine are associated with development of colorectal tumors.

Increased oxidative stress is generally thought to be associated with tumorigenesis. In this cross-sectional study, we evaluated plasma 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with colorectal adenoma and cancer, as a surrogate marker of oxidative damage to deoxyribonucleic acid (DNA). We collected blood samples from 58 patients with adenoma, 32 with early cancer, 25 with advanced cancer, and 36 without polyps or cancer (as controls), and measured plasma levels of 8-OHdG by enzyme-linked immunosorbent assay. Univariate analysis by logistic regression showed that an increased level of 8-OHdG was a significant risk for adenoma [odds ratio (OR) 1.393, 95% confidence interval (CI) 1.008-1.926, p = 0.045]. In patients with early cancer, univariate analysis revealed significant differences for age, body mass index (BMI), systolic blood pressure, and 8-OHdG level. Subsequent multivariate analysis revealed that 8-OHdG [OR 1.627, 95% CI 1.079-2.453, p = 0.020] and BMI [OR 1.283, 95% CI 1.038-1.585, p = 0.021] were significant risk factors for early cancer. However, 8-OHdG was not a significant risk factor for advanced cancer. Our results suggest that an increased plasma level of 8-OHdG is associated with development of colorectal adenoma and cancer.

Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer.

AIM: To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced). METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, insulin, total cholesterol, triglyceride, high sensitivity C-reactive protein, insulin like growth factor (IGF)-1, IGF binding protein-3, adiponectin, leptin, and resistin were measured. Each factor level was designated low or high, and the risk of adenoma or cancer was estimated by univariate and multivariate logistic regression analysis. RESULTS: We enrolled 124 male subjects (47 with adenoma, 34 with early cancer, 17 with advanced cancer, and 26 without tumors as controls). In patients with adenoma, high triglyceride and low adiponectin were associated with a significant increase in the odds ratio (OR) by univariate analysis. Only a low adiponectin level was related to increased adenoma risk, with an adjusted OR for low level (< 11 microg/mL) to high (>or=11 microg/mL) of 5.762 (95% confidence interval (CI): 1.683-19.739, P = 0.005). In the patients with early cancer, high body mass index, high triglyceride, and low adiponectin were associated with a significant increase in OR in univariate analysis. In multivariate analysis, only low adiponectin was significantly associated with early cancer, with an adjusted OR of 4.495 (95% CI: 1.090-18.528, P = 0.038). However, in patients with advanced cancer, low adiponectin was not recognized as a significant risk factor for advanced cancer. CONCLUSION: A decreased level of adiponectin is strongly associated with an increased risk of colorectal adenoma and early cancer. These data call for further investigation, including a controlled prospective study.

Biological effect of anaphylatoxin C5a on the generation of anti-inflammatory substances in leukocyte adsorption.

Anaphylatoxins, which are involved in both pro-inflammatory processes and a variety of anti-inflammatory effects, are produced during granulocyte and monocyte adsorptive apheresis. We noticed the anti-inflammatory effects of C5a, the strongest anaphylatoxin, in granulocyte and monocyte adsorptive apheresis. The aim of this study was to investigate the effect of C5a on interleukin-1 receptor antagonist (IL-1ra) and hepatocyte growth factor (HGF) generation in granulocyte and monocyte adsorption. Peripheral blood containing nafamostat mesilate as an endogenous complement activation inhibitor was divided into four groups: (1) no recombinant C5a added, no contact with cellulose acetate (CA) beads (control group); (2) no C5a added, contact with CA beads; (3) C5a added, no contact with CA beads; and (4) C5a added, contact with CA beads. After incubation, IL-1ra and HGF in plasma were measured. IL-1ra was significantly higher in group 3, in which only C5a was added in the absence of CA beads, compared to groups 2 (P < 0.01) and 4 (P < 0.05). HGF was significantly higher only in group 4, in which C5a was added in the presence of CA beads (P < 0.05), but did not increase in the absence of CA beads. C5a can directly induce IL-1ra generation without the granulocyte and monocyte adsorption stimuli to CA beads, but can synergistically induce HGF generation with the adsorption stimuli, indicating C5a has different effects on IL-1ra and HGF generation.

Plasma level of granulocyte-colony stimulating factor during granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis.

BACKGROUND/AIMS: Cytapheresis with extra-corporeal circulation for ulcerative colitis is effective but its mechanisms are still unclear. Granulocytecolony stimulating factor (G-CSF) strongly mobilizes bone marrow-derived cells and serves as antiinflammatory factor. We investigated plasma levels of G-CSF during granulocyte and monocyte adsorptive apheresis (GCAP). METHODOLOGY: Nineteen cases of ulcerative colitis were measured plasma concentration of G-CSF during the first session of GCAP therapy. RESULTS: G-CSF were significantly increased in the column inflow at 30 min compared with the baseline (Wilcoxon test, p < 0.01), and also increased through the column (Wilcoxon test, p < 0.01). The ratio of the increase in the column outflow at 60 min was 1.5-fold compared with the baseline. However, we could not show a significant relation between G-CSF level and clinical efficacy. CONCLUSIONS: This is the first report concerning G-CSF during CAP. G-CSF is increased due to GCAP and appears to be a candidate which should be further investigated.

[Non pulsatile active bleeding from the gastrointestinal mucosa without ulceration during anticoagulation therapy -consideration on bleeding from angiodysplasia during anticoagulation therapy-].

We reported 3 cases of the uncommon type of persistent gastrointestinal bleeding during anticoagulation therapy due to cardiovascular disorders or collagen disease. Endoscopic observation showed non pulsatile active bleeding from apparently normal mucosa, without any ulcer or obvious vascularectasia. The outflow of bleeding was string-like and continuous. Based on previous reports, we considered the possibly of these cases unique bleeding angiodysplasia and angiodysplasia during anticoagulation therapy. The frequency of this type of bleeding may increase, as anticoagulation therapy has become more common. We should pay attention to such lesions when we treat gastrointestinal bleeding.

[A case of primary orbital adenocarcinoma responding to chemoradiation].

Primary orbital adenocarcinoma is very rare. There are not any reports about the treatment of this disease, except for surgery. We experienced a case of primary orbital adenocarcinoma, which we successfully treated by chemoradiation using 5-FU and cisplatin. It is very important to collect and record cases of rare diseases responding to certain chemotherapy regimens.

A multi center study of granulocyte and monocyte adsorption apheresis therapy for ulcerative colitis-clinical efficacy and production of interleukin-1 receptor antagonist.

Granulocyte and monocyte adsorption apheresis (GCAP) is a useful strategy for intractable ulcerative colitis, but its mechanisms of therapy is not fully explained. Previously, depleting activated granulocytes and monocytes (GMs) and modifying product of proinflammatory cytokines had been proposed. In addition, activated GMs are releasing anti-inflammatory cytokines, interleukin-1 receptor antagonist (IL-1ra) that may contribute to the clinical efficacy of GCAP therapy. Hence, to investigate contribution of IL-1ra as well as to confirm clinical efficacy of this therapy based on clinical activity index (CAI), we performed a multicenter study. Twenty-five of 38 (65.8%) patients achieved remission state (CAI < or = 4) and two of 38 (5.3%) revealed clinical improvement. Almost effective cases significantly decreased CAI even at 3rd session of GCAP. Plasma level of IL-1ra from outflow of the GCAP column at 30 min was significantly increased rather than inflow. Median exact elevated level of IL-1ra was 221 pg/ml and median of increasing ratio was 1.6 times. Furthermore, the responsive patients, who well released the IL-1ra at outflow more than 100 pg/ml compared with inflow, tended to show clinical effectiveness. While, the increased ratio of IL-1ra in effective cases did not differ from ineffective cases, and there were no significant relationship with improvement of CAI score. These conflict results suggest that the increase of IL-1ra at outflow is not a direct factor to the clinical improvement, but the induction of clinical improvement is accompanied by the release of IL-1ra. The IL-1ra may be involved in the multiple steps for the improvement induced by GCAP.

Osteonecrosis of the lateral femoral condyle in a patient with ulcerative colitis: report of a case.

Osteonecrosis is a major complication in patients with ulcerative colitis (UC). It appears most commonly in the femoral head, but sometimes occurs in the proximal humerus or femoral condyle. A 27-year-old Japanese woman presented with severe pain in the left knee in 2006. Osteonecrosis was found in the left lateral femoral condyle, and osteochondral autografting was performed. Ten and a half years prior to this episode, at the age of 17 years, she had been diagnosed as having UC, and after 18 months of medication, she had undergone total colectomy. A total prednisolone dose of 3020 mg had been administered before the operation, but the true pathogenesis-i.e. idiopathic or steroid-associated osteonecrosis-had not been determined at that time. The osteonecrosis occurred long after prednisolone therapy had been discontinued, and the total dose of prednisolone was not considered to be unusually high. In this case, osteochondral autografting was ultimately required for treatment of the osteonecrosis. However, conservative therapy is indicated for early-stage cases and should result in a good course. We report this case to draw attention to this relatively rare complication of UC and to facilitate early detection of similar lesions.

Investigation of Musashi-1 expressing cells in the murine model of dextran sodium sulfate-induced colitis.

Musashi-1 (Msi-1), an RNA-binding protein, had been proposed to be a specific marker for neural stem/precursor cells. Msi-1 expressing cells in the intestinal epithelium are also strongly considered as potential stem/precursor cells. To clarify the behavior of those cells in the injury or regeneration phase, we investigated Msi-1 expressing cells of intestinal mucosa in the murine model of dextran sodium sulfate (DSS)-induced colitis. Immunohistochemically, Msi-1-positive cells were found in the area just along the layer of Paneth's cells in the small intestine and in the bottom layer of crypts in the large intestine. During DSS administration, the number of PCNA-positive cells in the large intestine increased markedly. In contrast, the number of Msi-1-positive cells decreased slightly with DSS but returned to normal after DSS administration was stopped. The level of mRNA for Msi-1 was consistent with the result of immunohistochemical examinations. Conclusively, we could describe the behavior of intestinal stem/precursor cells during inflammation using Msi-1.

Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance.

PURPOSE: Colorectal carcinogenesis is thought to be related to abdominal obesity and insulin resistance. To investigate whether visceral fat accumulation contributes to colorectal carcinogenesis, we examined its accumulation and the levels of the adipose tissue-derived hormone adiponectin in Japanese patients with colorectal adenoma. EXPERIMENTAL DESIGN: Fifty-one consecutive Japanese patients ages >/=40 years and with colorectal adenoma were subjected to measurement of visceral fat area by computed tomography scanning and plasma adiponectin concentration. The patients also underwent the 75-g oral glucose tolerance test. Insulin resistance was calculated by the homeostasis metabolic assessment (HOMA-IR) method. The controls were 52 Japanese subjects ages >/=40 years and without colorectal polyp. Cigarette smokers and subjects who consumed alcohol (>/=30 g ethanol/d) were excluded. RESULTS: The patients with colorectal adenoma showed significantly more visceral fat area and significantly less plasma adiponectin concentration in comparison with the controls [odds ratio (OR), 2.19; 95% confidence interval (95% CI), 1.47-3.28; P < 0.001 and OR, 0.24; 95% CI, 0.14-0.41; P < 0.001, respectively] by logistic regression analysis. HOMA-IR index was also associated with colorectal adenoma (OR 2.60; 95% CI, 1.20-5.64; P = 0.040). Visceral fat area and adiponectin were associated with adenoma number (1, 2, >/= 3), the size of the largest adenoma (<10 and >/=10 mm), and adenoma histology (tubular and tubulovillous/villous). CONCLUSIONS: These results suggest an association of visceral fat accumulation and decreased plasma adiponectin concentration with colorectal adenoma in Japanese patients. This study may offer a new insight to understanding the relationship of colorectal carcinogenesis with abdominal obesity and insulin resistance.