Late-onset peritoneal recurrence of advanced gastric cancer 20 years after primary resection

Late onset of peritoneal recurrence of gastric cancer more than 10 years after surgery is extremely rare, and only three cases have been reported. We present the case of a 61-year-old man who was diagnosed finally with peritoneal recurrence of gastric cancer 20 years after primary curative resection. As a result of small-bowel obstruction caused by peritoneal recurrence, diverting ileostomy with partial ileal resection was performed. The resected specimen revealed tubular adenocarcinoma that resembled the primary gastric cancer. The clinical course after the second operation was unfavorable and systemic chemotherapy had no effect. He died at 62 years of age, 21 years and 7 months after initial gastrectomy. Immunohistochemical analysis using antibodies against proliferating cell nuclear antigen (PCNA), Ki-67, and p53 was performed to investigate the phenotype of primary and recurrence cancer. Protein expression of proliferation markers such as PCNA and Ki-67 was down-regulated, but p53 was overexpressed at the site of recurrence. These data suggest that late peritoneal recurrence has a low proliferation rate and is resistant to chemoradiotherapy. In conclusion, we present late onset of peritoneal recurrence of gastric cancer more than 20 years after primary surgery, and speculate on the mechanism of late-onset recurrence in our case

Uncommon co-localization of pituitary adenoma and parasellar cavernous angioma

We encountered a 49-year-old female presenting with left oculomotor palsy who was found to be co-localized cavernous sinus cavernous angioma (CA) and pituitary adenoma. Although CA originated from parasellar regions are not so rare, on neuroimaging studies, the characteristics of CA may be difficult to differentiate from those of pituitary adenomas. The co-localization of these two tumors was identified by preoperative dynamic MRI study. As intraoperative histological examination confirmed our preoperative diagnosis, we performed biopsy of the CA only to avoid uncontrollable intraoperative hemorrhage. © 2008 Elsevier Ireland Ltd. All rights reserved

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2)

Hospital and clinic cooperation for the treatment of rheumatoid arthritis in Okayama Prefecture, Japan

Objective: To survey the current status and problems of cooperation between clinics and hospitals in Okayama Prefecture, Japan for the treatment of rheumatoid arthritis (RA). 　Methods: We distributed a questionnaire to 300 of the 983 Okayama Prefecture clinics that had either an internal medicine or orthopedic surgery department, from December 2013 to February 2014. The questionnaire covered practice pattern for RA treatment in clinics, current status of the hospital and clinic cooperation, and acceptance of the biologic therapy. 　Results: One hundred clinics responded to the questionnaire. Seventy percent of the clinics reported making referrals to rheumatologists before the initiation of RA treatment, and half of the other 30% of the clinics administered methotrexate as the first-line treatment for RA by their own decision. Sixty-six clinics cooperated with flagship hospitals, conducting medical and laboratory examinations, providing prescriptions, and treating common diseases of patients. These clinics expected the cooperating rheumatologists to follow-up patients every 3 to 6 months and to make the diagnosis, make decisions regarding RA treatment changes, and perform surgery. Seventy-one percent of the clinics responded that cooperation with a hospital is possible even for patients who are administered biologics. As reasons for no cooperation with the flagship hospitals, clinics noted the lack of information about rheumatologists in the area and recent trends in the management of RA. 　Conclusion: The current study reported, for the first time, the actual conditions of management of RA in clinics, as well as future problems of hospital and clinic cooperation in Okayama Prefecture

Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by desiccation and ionizing radiation

Overexpression of a Minimal Domain of Calpastatin Suppresses IL-6 Production and Th17 Development via Reduced NF-κB and Increased STAT5 Signals

Calpain, a calcium-dependent cysteine protease, is reportedly involved in the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In addition, autoantibodies against calpastatin, a natural and specific inhibitor of calpain, are widely observed in RA. We previously reported that E-64-d, a membrane-permeable cysteine protease inhibitor, is effective in treating experimental arthritis. However, the exact role of the calpastatin-calpain balance in primary inflammatory cells remains unclear. Here we investigated the effect of calpain-specific inhibition by overexpressing a minimal functional domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA patients, and fibroblast cell lines. We found that the calpastatin-calpain balance varied during Th1, Th2, and Th17 development, and that overexpression of a minimal domain of calpastatin (by retroviral gene transduction) or the inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th cells and the production of IL-6 by fibroblasts. These suppressions were associated with reductions in RORγt expression and STAT3 phosphorylation. Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS) suppressed Th17 development. We also confirmed that overexpressing a minimal domain of calpastatin suppressed IL-6 by reducing NF-κB signaling via the stabilization of IκBα, without affecting the upstream signal. Moreover, our findings indicated that calpastatin overexpression suppressed IL-17 production by Th cells by up-regulating the STAT5 signal. Finally, overexpression of a minimal domain of calpastatin suppressed IL-6 production efficiently in primary fibroblasts derived from the RA synovium. These findings suggest that inhibiting calpain by overexpressing a minimal domain of calpastatin could coordinately suppress proinflammatory activities, not only those of Th cells but also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate treatment for inflammatory diseases such as RA

Interleukin l(IL-1) and interleukin 2(IL-2) production in patients with chronic renal failure

The mechanism of immune deficiency in patients with chronic renal failure(CRF) was investigated by testing both the ability of monocytes to produce IL-1 and the ability of T cells to produce IL-2.IL-1 production by lipopolysaccharide(LPS)-stimulated monocytes from CRF patients was not less than that of healthy controls. In fact, some patients showed higher values than the normal range(mean±2SD of normal value).IL-2 production by phytohemagglutinin(PHA)-stimulated peripheral blood mononuclear cells(PBMC) from patients on hemodialysis was significantly greater than that of healthy controls and non-hemodialysis patients. To exclude the influence of monocytes, the ability of T cells to produce IL-2 was also examined. IL-2 production by PHA-stimulated T cells was also increased in patients on hemodialysis. There was no correlation between IL-2 production by PHA-stimulated T cells and IL-1 production by LPS-stimulated monocytes. These results indicated that the enhanced IL-2 production by T cells was independent of monocytes.The mean IL-1 activity produced by non-stimulated monocytes was less than lU/ml in all groups. IL-2 production by unstimulated T cells was not observed in any subject. Both the expression of the IL-2 receptor(IL-2R) and that of the transferrin receptor on PBMC were less than 2% at the time cultures were started, or after incubations without stimulation.Thus, the possibility that monocytes and T cells were preactivated could be excluded.There was a significant correlation between IL-2 responsiveness and IL-2R expression on PHA-stimulated PBMC. Both were significantly lower in non-hemodialysis patients than in healthy controls, and gradually improved with the continuation of hemodialysis. One of the causes of immune deficiency, particularly in patients with non-hemodialysis renal failure, might be decreased IL-2 responsiveness based on defective expression of IL-2R

Mortality from cancer and other diseases among radiological technologists in Japan, 1969-1998

第１８回国際疫学会世界疫学会

Research of potential radiation risks in areas with nuclear power plants in Japan: mortality rates from solid cancers and congenital anomalies between 1972- 1977 in 100 selected municipalities

Social concerns for potential radiation risks due to nuclear power plant (NPP) routine operation have challenged us to overcome the inherent limitation of a geographical correlation study. A multi-site study to evaluate health risks in the NPP vicinities for a long time is useful to offer more comprehensive information than a local site study because the radiation dose is very small, at most 10-20 microsievert per year in Japan. Mortality rates from solid cancers and congenital anomalies (age<1 year) between 1972- 1997 in 100 selected Japanese municipalities either with or without a NPP were analyzed using Poisson regression. Excess relative risk (ERR) in all periods and 20 municipalities with a NPP showed a significant negative value (-0.052, P<0.001) for solid cancers and no significant different for congenital anomalies compared with in the remaining 80 control areas. Broadly speaking, the mortality rates from these two causes do not support the social concern about a possibly increased health risks due to radiation from Japanese NPP facilities although several issues remain to be resolved. At present it is not possible in the analysis for us to get an appropriate surrogate score for radiation dose. Further examinations are expected especially for specific site of groups of solid cancers. Our previous report observed a significant small positive ERR (0.228, p=0.0027) for leukemia mortality at old ages, which is due to factors other than radiation. On the other hand, a possible pathogenesis for congenital anomalies is less justified than for solid cancers; no adverse deterministic effects on fetus in the concerned radiation dose range and much less likely adverse genetic efffects than had worried in the past when conducting many tests of nuclear weapons in the atmosphere. Temporal and geographical pattern of these mortality rates throughout Japan will be useful to reduce uncertainty of our findings.12th International Congress of Radiation Researc