Analysis of a questionnaire on adverse reactions to blood donation in Japan.

In 2007, the Japanese Red Cross Blood Center performed a large-scale questionnaire study of post-donation adverse reactions. The questionnaire was distributed to 98,389 donors, and the answers were returned by 55,231 (56.1%). In total, 2,877 (5.2%) complained of an adverse reaction. Assuming that there were no adverse reactions for the 46,150 donors who did not reply, the rate of adverse reaction can be speculated to be 2.8%. Our study strongly suggests that blood centers have long underestimated the risks of vaso-vagal reactions. Taking at least 6h of careful rest after donation would be a helpful counter measure.

Differential diagnosis of cystic tumors of the pancreas by endoscopic ultrasonography.

BACKGROUND AND STUDY AIMS: Generally, cystic tumors are divided into two categories: neoplastic cystic tumors and non-neoplastic cystic (NNC) tumors. Neoplastic cystic tumors include mucinous cystic neoplasm (MCN), intraductal papillary-mucinous neoplasm (IPMN), and serous cystic neoplasm (SCN). MCNs and IPMNs have the potential to progress to a malignant state, whereas SCNs are known for their almost benign behavior. Thus, in order to make management decisions, it is important to distinguish between potentially malignant (MCN and IPMN), and benign (SCN and NNC) tumors. The aim of this study was to retrospectively investigate the value of endoscopic ultrasonography (EUS) for the differential diagnosis of cystic tumors of the pancreas. PATIENTS AND METHODS: A total of 76 patients with cystic tumors of the pancreas were preoperatively examined by EUS. Eight cases were MCNs, 45 were IPMNs, 13 were SCNs, and 10 were NNC tumors. The EUS findings relevant to distinguishing between potentially malignant and benign were analyzed statistically. RESULTS: All patients with MCNs were female and all these tumors were located in the pancreatic body/tail. IPMN, however, occurred predominantly in men, and in the pancreatic head. Eight of 11 monolocular cystic tumors were NNC in nature. Eleven of 13 SCNs included microcystic areas within the tumors. All MCNs were round in appearance, whereas 93 % of IPMNs were not round in appearance. Mural nodules were present in 25 % of MCN and 38 % of IPMN cases. In univariate analysis, age, tumor size, locularity, the number of cystic formation, cystic component, and appearance were significant variables. In multivariate analysis, locularity and cystic component were important for differential diagnosis of potentially malignant cystic tumors. CONCLUSIONS: The characteristics of cystic tumors of the pancreas revealed by EUS are useful for their differential diagnosis.

Needle-shaped deposits on retinal surface in a case of ocular amyloidosis.

PURPOSE: To report a case in which optical coherence tomography (OCT) showed needle-shaped deposits on the retinal surface oriented toward the vitreous cavity and immunohistochemical findings suggested light chain-related amyloidosis. METHODS: A 59-year-old man with no systemic complications had bilateral neovascular glaucoma and vitreous opacities in the right eye. Vitrectomy was conducted on the right eye and the excised vitreous was examined histopathologically. RESULTS: Glass wool-like opacities were observed during vitrectomy. Postoperative fundus examination of the right eye showed retinal hemorrhage and white deposits around blood vessels and on retinal surface. Fluorescein angiography revealed hyperfluorescence of the optic disc, non-perfusion areas, and vascular focal staining. OCT depicted needle-shaped deposits perpendicular to the retinal surface oriented toward the vitreous. Histologic examination of deposits revealed positive reaction for Congo red stain, and immunohistochemical examination demonstrated positive reactivities for anti-lambda and anti-kappa light chains (precursors of amyloid protein), suggesting a diagnosis of light chain-related amyloidosis. CONCLUSIONS: In this case, OCT showed needle-shaped deposits perpendicular to the retinal surface. Special staining with Congo red revealed the deposit to be amyloid deposition. Immunohistochemical staining suggested light chain-related amyloidosis. Vascular obstructive lesions and neovascular glaucoma secondary to retinal vascular damage in amyloidosis warrant particular attention.

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group.

We evaluated the efficacy of a treatment strategy in which infants with acute lymphoblastic leukemia (ALL) were stratified by their MLL gene status and then assigned to different risk-based therapies. A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and 2001. Those with a rearranged MLL gene (MLL-R, n=80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n=22) were treated with chemotherapy alone. The 5-year event-free survival (EFS) rate for all 102 infants was 50.9% (95% confidence interval, 41.0-60.8%). The most prominent late effect was growth impairment, observed in 58.9% of all evaluable patients in the MLL-R group. This plan of risk-based therapy appears to have improved the overall prognosis for infants with ALL, compared with previously reported results. However, over half the events in patients with MLL rearrangement occurred before the instigation of HSCT, and that HSCT-related toxic events comprised 36.3% (8/22) of post-transplantation events, suggesting that further stratification within the MLL-R group and the development of more effective early-phase intensification chemotherapy will be needed before the full potential of this strategy is realized.

The Leu544Ile polymorphism of the growth hormone receptor gene affects the serum cholesterol levels during GH treatment in children with GH deficiency.

OBJECTIVE: The cellular effects of growth hormone (GH) are mediated by the interaction between GH and the GH receptor (GHR). We investigated the association between polymorphisms in GHR and changes in height standard deviation scores (SDS), and lipid metabolism during GH treatment for GH-deficient children. DESIGN: A 1-year study on growth rate and lipid metabolism under GH treatment. PATIENTS: Eighty-three children (61 boys and 22 girls) with GH deficiency were treated with GH for 1 year after diagnosis. INTERVENTION: The patients were treated with recombinant human GH (0.19 mg/kg/week) for at least 1 year after diagnosis. The growth rates and biochemical parameters for lipid metabolism were measured both before and during treatment. Four single nucleotide polymorphisms (SNPs) in the GHR gene, Cys440Phe, Pro495Thr, Leu544Ile and Pro579Thr, and exon 3 deletion polymorphisms were genotyped by direct sequencing and multiplex PCR. RESULTS: We found no significant association between GHR polymorphisms and changes in height SDS during GH treatment. The total cholesterol levels of the GH-deficient boys with Ile/Ile at codon 544 showed significantly higher cholesterol levels before GH treatment and then maintained high levels during the GH treatment, compared to those with other genotypes. No other polymorphisms seemed to have any apparent effects on lipid metabolism. CONCLUSION: The Leu544Ile polymorphism of the GHR gene is associated with cholesterol levels in boys with GH deficiency.

Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3+, CD4+, T cell receptor (TCR)alphabeta+ or CD8alphaalpha+ cell counts were lower, and CD56+ cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3+ or CD4+ cell counts was slower in patients than in controls. The proportion of CD8alphaalpha+ cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of Valpha24+ cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8alphaalpha+ cells was observed only in patients, and that with Valpha24+ cells was seen only in controls. No gene expression levels of interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome.

FLT3 mutations in normal karyotype acute myeloid leukemia in first complete remission treated with autologous peripheral blood stem cell transplantation.

We retrospectively analysed the significance of FLT3 mutations in patients with acute myeloid leukemia (AML) having a normal karyotype, who were treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation (auto-PBSCT). In all, 34 patients with normal karyotype AML in first complete remission receiving high-dose chemotherapy and auto-PBSCT were analysed based on the presence or absence of FLT3/ITDs and FLT3/D835. They were 16 males and 18 females and with a median age of 41.5 years. FLT3/ITDs were detected in eight of 34 patients (23.5 %), and FLT3 D835 mutations in two of 34 patients (5.9%). White blood cell count (P=0.0087), serum concentration of lactate dehydrogenase (P=0.005), and percentages of peripheral blood (P=0.0131) and bone marrow (BM) blasts (P=0.0312) were significantly higher in patients showing the FLT3 mutations. Overall survival (OS) and disease-free survival (DFS) were similar between patients with or without FLT3 mutations (5 year DFS, 67.5 vs 68.55%, P=0.819; 5 year OS, 64.81 vs 78.88%, P=0.4457, by the log-rank test). FLT3 mutations demonstrate no further prognostic impact in patients with normal karyotype AML in first CR treated with high-dose chemotherapy and auto-PBSCT. Myeloablative chemotherapy supported by auto-PBSCT may overcome any poor prognostic implications of FLT3 mutations.

Risk factors for renal cysts.

OBJECTIVE: To examine the risk factors for renal cysts in a large population-based health survey, as we previously reported that the prevalence of renal cyst increases with age, there is a difference in incidence between the sexes and other studies show an association between renal cysts and hypertension. SUBJECTS AND METHODS: Data were collected on 17 914 individuals who participated in a multiphase health-screening programme at our institution in 2000. Ultrasonography was used for diagnosing renal cysts. Logistic analysis was used to examine various risk factors for renal cyst, including sex, age, serum creatinine, hypertension, hypercholesterolaemia, diabetes mellitus, and smoking habits. Hypertension was defined as a systolic blood pressure of > 140 mmHg, a diastolic blood pressure of > 90 mmHg, or current use of antihypertensive medication. In 45 patients with renal cysts who were followed for a mean (range) of 6 (4-7) years the sequential changes in the size of the cysts and the systolic blood pressure were plotted in relation to age. The relationship of the mean changes in these variables was also examined. RESULTS: The prevalence of renal cysts was 9.9%, ranging from 3.8% for subjects in their third decade to 18.5% in their sixth. Cysts were detected in 13.0% of men and 5.8% of women (P < 0.001). The mean serum creatinine was 83 mg/L in those with cysts and 76 mg/L in those without (P < 0.001); the respective mean systolic blood pressure was 123 and 118 mmHg (P < 0.001). Multivariate logistic regression analysis showed that age (P < 0.001), sex (P < 0.001), hypertension (P = 0.0022) and serum creatinine (P = 0.021) had a significant influence on the occurrence of renal cysts. Enlargement of the cysts was not correlated with the increase in blood pressure. CONCLUSIONS: The risk factors for a renal cyst are age, male gender, renal dysfunction and hypertension. Hypertension might cause renal dysfunction, which leads to the development of renal cysts.

Prognostic significance of metastatic lymph node size in patients with gastric cancer.

BACKGROUND: Patients with gastric cancer that has metastasized to the lymph nodes are a heterogeneous population with a variable prognosis. Stratification of these patients into prognostic groups is necessary for optimal adjuvant therapy. METHODS: The study comprised 715 patients who had undergone curative resection of a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and eosin, and the diameter of the largest metastatic lymph node (MLN) was measured. Patients with metastatic nodes were divided into groups n1 and n2 according to the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank test; patients in group n1 had a MLN size of 7 mm or less and those in group n2 had a MLN of 8 mm or more. RESULTS: Patients were stratified into significant prognostic groups by both the Union International Contra la Cancrum (UICC) node (N) stage and MLN size (n group). The UICC N-stage subcategories were further divided into prognostic groups according to MLN size (n group). On multivariate analysis the MLN size remained independently significant in terms of overall and disease-free survival rates, and the UICC N stage was not significant, independently of the n group. Node-positive patients with fewer than 15 lymph nodes removed at operation could also be stratified into prognostic groups by the n group. Stratification according to the TNM stage and by MLN size was superior to existing UICC TNM staging. CONCLUSION: This new method may help clinicians to design a more appropriate treatment strategy for patients with gastric cancer.

Influence of transplanted dose of CD56+ cells on development of graft-versus-host disease in patients receiving G-CSF-mobilized peripheral blood progenitor cells from HLA-identical sibling donors.

We investigated effects of variations in the cellular composition of G-CSF-mobilized peripheral blood progenitor cell (G-PBPC) allografts on clinical outcomes of allogeneic PBPC transplantation. We retrospectively analyzed transplanted doses of various immunocompetent cells from 27 HLA-identical sibling donors in relation to engraftment, incidence of graft-versus-host disease (GVHD), and survival. Significant variability was documented in both absolute numbers and relative proportions of CD34+, CD2+, CD3+, CD4(high)+, CD4+25+, CD8(high)+, CD19+, CD56+, and CD56+16+ cells contained in these allografts. Stepwise Cox regression analysis revealed that the CD56+ cell dose was significantly inversely correlated with the incidence of GVHD. Thus, there was a significantly higher incidence of grade II acute GVHD in patients receiving a lower CD56+16+ cell dose (hazard ratio (HR) 0.0090; 95% confidence interval (CI), <0.00001-3.38; P=0.031), a higher incidence of chronic GVHD in those receiving allografts with a lower CD56+16+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.0007; P=0.0035), and a higher incidence of extensive chronic GVHD in those receiving allografts with a lower CD56+ to CD34+ ratio (HR <0.00001; 95% CI <0.00001-0.053; P=0.0083). These results suggest that CD56+ cells in G-PBPC allografts from HLA-identical sibling donors may play an important role in preventing the development of GVHD.

Chemical peeling with salicylic acid in polyethylene glycol vehicle suppresses skin tumour development in hairless mice.

BACKGROUND: Chemical peeling with salicylic acid in polyethylene glycol (PEG) vehicle is used clinically to improve the cosmetic appearance of skin that has been damaged by exposure to the sun. It is well known that cancers of the skin such as basal cell carcinoma and squamous cell carcinoma may be induced by the sun. However, the carcinogenic potential of chemical peeling agents has not been studied. OBJECTIVES: To evaluate the effects of chemical peeling with 30% salicylic acid in PEG on skin tumour formation in treated vs. control mice. METHODS: To serve as a model of sun-damaged skin, hairless SKH/hr1 mice were irradiated with ultraviolet (UV) B for 14 weeks, with or without treatment every 2 weeks with 30% salicylic acid in PEG for a total of 18 weeks. RESULTS: Not only was the total number of tumours greatly reduced in the treated vs. the control mice, but skin tumour development was also slower in the treated vs. the control mice. At the final treatment, the fractions of T and B lymphocytes and natural killer cells from spleens of both groups of mice were comparable, and interferon-gamma production did not differ. CONCLUSIONS: Our findings suggest that chemical peeling with salicylic acid in PEG may help to prevent as well as to reduce the number of UVB-induced skin tumours.

Identification of chemotherapeutic refractory cases based on human chorionic gonadotropin values among patients with low-risk persistent trophoblastic disease treated with 8-day methotrexate-folinic acid.

PURPOSE: The aim of the present study was to establish the accurate cutoff points of post-treatment serum beta-hCG values in identifying chemotherapeutic refractory cases among patients with low-risk persistent trophoblastic disease (PTD) treated with 8-day methotrexate-folinic acid as the primary therapy. MATERIALS AND METHODS: The values of serum beta-hCG measured before initiating treatment and weekly thereafter in 26 patients with low-risk PTD undergoing 8-day methotrexate-folinic acid treatment were analyzed. Thereafter, we determined the weekly cutoff points to identify the patient refractory for treatment by means of receiver-operating characteristic (ROC) plots analysis. RESULTS: The values of cutoff points in the pretreatment, the post-treatment 1st, 2nd, 3rd, and 4th week were 18.6, 15.0, 5.4, 3.4, and 2.0 ng/ml, respectively, and the value of accuracy during these weeks was appropriate (> 80%). When using the cutoff points of one and two weeks after initiating treatment, the accuracy in identifying chemotherapeutic refractory patients was 87.5% and 88.0%, respectively, with the highest values exceeding 85%. The sensitivity and specificity at one week were 92.9 and 80.0%, respectively. Similarly, the sensitivity and specificity at two weeks were 93.3 and 80.0%, respectively. CONCLUSION: These results suggest that the cutoff points of one and two weeks after initiating treatment are useful in identifying chemotherapeutic refractory patients among low-risk PTD patients, receiving 8-day methotrexate-folinic acid treatment.

Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction.

Cytomegalovirus (CMV) antigenemia and quantitative real-time polymerase chain reaction (PCR) were compared for monitoring of CMV reactivation after allogeneic stem cell transplantation. The number of CMV antigen-positive cells by the antigenemia assay and the level of CMV DNA by real-time PCR correlated well. The sensitivity and specificity of the antigenemia assay was 55.4% and 95.5%, respectively, using real-time PCR as the reference standard. The probability of positive antigenemia at day 100 was 76.5%, with a median of first detection at day 37 in 51 patients, compared with a positive PCR of 84.3% and day 33, respectively. When HLA-identical sibling donor transplant recipients and other donor transplant recipients were analyzed separately, there was no difference between the two tests. However, temporal patterns of first detection of CMV antigen-positive cells and CMV DNA differed between HLA-identical and alternative recipients; patients without CMV (29%) or with sporadic positive PCR results (14%) were more common in HLA-identical sibling transplants, whereas patients with simultaneous antigenemia and positive PCR occurred more in alternative transplants (48%). Two of 51 patients (4%) developed CMV colitis despite antigenemia-guided prophylaxis, but both were successfully treated with ganciclovir. Although PCR is more sensitive than antigenemia, both tests are useful in the early detection of CMV after allogeneic stem cell transplantation.

Clinicopathological prognostic factors in soft tissue leiomyosarcoma: a multivariate analysis.

AIMS: Prognostic factors affecting survival in cases of leiomyosarcoma of soft parts were investigated in this study. METHODS AND RESULTS: A retrospective study of 267 patients was carried out. This group comprised 142 females (53%) and 125 males (47%), whose ages ranged from 7 to 95 years (median 58 years). One hundred and five cases were superficially situated (arising from the skin or subcutis), while the remaining 162 cases were deeply situated (subfacial). Nineteen were cases of pleomorphic leiomyosarcoma where the diagnosis had been amended from malignant fibrous histiocytoma to leiomyosarcoma whilst under review. Of the 167 patients with follow-up data, 83 died of leiomyosarcoma. In univariate analysis, depth, tumour size (>or=50 mm), mitotic rate of >20 per 10 high-power fields (HPF), tumour necrosis of >50% and a high stage according to the most recent American Joint Committee on Cancer (AJCC) staging for soft tissue sarcoma were found to lessen significantly the rate of survival (log rank test; P < 0.05). However, in multivariate analysis (Cox's proportional hazards model), tumour size and high AJCC stage were the only factors that were correlated independently with decreased survival. CONCLUSIONS: This study indicates that the most reliable prognostic parameters are tumour size and AJCC stage in leiomyosarcoma.

Decreased expression of an ATP-binding cassette transporter, MRP2, in human livers with hepatitis C virus infection.

BACKGROUND/AIMS: To understand hepatic injury during the process of hepatitis viral infection, determination of liver-specific functions at molecular levels is critical. Because the transport of endogenous/exogenous toxic substances is an intrinsically important hepatic function, we examined whether expression of the ATP-binding cassette (ABC) transporter gene was affected in patients with hepatitis viral infection. METHODS: To determine which ABC transporter was expressed differently in patients with hepatic viral infection, we assayed the expression of MDR1, MDR3, MRP1, MRP2, and MRP3 in non-cancerous regions in the liver of 42 patients with hepatic tumors using both quantitative RT-PCR and immunological staining analysis, and compared the hepatic expression levels between patients with hepatitis viral infection and non-infected controls. RESULTS: Of the five ABC transporter genes studied, the mRNAs of MRP2 and MRP3 were highly expressed in the human liver. There was a significant reduction in MRP2 expression to 29% in the virus-infected liver. Treatment of hepatic cells with inflammatory cytokines resulted in decreased mRNA levels of MRP2 and decreased MRP2 promoter activity. CONCLUSIONS: The down-regulation of MRP2 might induce a failure in the transport of various genotoxic substances in the liver with hepatitis virus infection.

Association between birthweight and body mass index at 3 years of age.

BACKGROUND: Obesity in children is one of the risk factors for adulthood obesity, which then leads to the development of chronic diseases such as hypertension, hyperlipidemia and diabetes. In this study, we identified significant factors associating with the body mass index (BMI) at 3 years of age from the perinatal characteristics of children. METHODS: A total of 588 children were included in the study. The BMI at 3 years of age was examined in conjunction with the possible variables such as parents' smoking status during pregnancy, parents' age at birth, gestational age, sibling number and live birth order, sex, birthweight, BMI at 1 month of age, weight gain during the first month of life and feeding method at 1 month of age. RESULTS: Univariate analysis showed that birthweight (P<0.0001), weight gain during the first month of life (P=0.0012) and BMI at 1 month of age (P<0.0001) were significantly associated with the BMI at 3 years of age. Of these factors, birthweight and weight gain during the first month of life were the independent factors correlating with the BMI at 3 years by multivariate analysis (P<0.0001 and P=0.0095, respectively). CONCLUSIONS: Infants with higher birthweight and/or greater weight gain during the first month of life may have a risk of being overweight at 3 years of age.

Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group.

This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population.

Co-stimulatory molecules of CD28, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and the newly identified inducible co-stimulator (ICOS) are expressed on cell surfaces and provide regulatory signals for T-cell activation. Their genes are candidate susceptibility genes for type 1 diabetes because they co-localize to Chromosome 2q33 with the IDDM12 locus. After determining the genomic structure and screening for polymorphisms of the ICOS gene, we performed association studies between newly identified polymorphisms of the ICOS gene, together with known polymorphisms of CD28 and CTLA-4 genes, and type 1 diabetes. The 49A/G dimorphism in exon 1 and the (AT)n in the 3' untranslated region of the CTLA-4 gene were significantly associated with type 1 diabetes. Evaluation of the CTLA-4 49A-3'(AT)n 86-bp haplotype frequency in patients and controls confirmed the results from the analysis of each polymorphic site. Dimorphism in intron 3 of the CD28 gene was associated with type 1 diabetes only in the early-onset group. In contrast, there was no association with the microsatellite polymorphisms in the ICOS gene or dimorphisms in the promotor region of CTLA-4. Of the three genes encoding co-stimulatory molecules, the CTLA-4 gene appears to confer risks for the development of type 1 diabetes.

Quality of life after pylorus-preserving pancreatoduodenectomy.

BACKGROUND: With increasing numbers of long-term survivors after pylorus-preserving pancreatoduodenectomy (PPPD), postoperative quality of life (QOL) has become a great concern. However, few reports are available on data of the postoperative changes in QOL after PPPD. METHODS: A total of 20 patients were studied regarding QOL before and at short term (within 2 months), intermediate term (6 months), and long term (1 year) after PPPD, using a questionnaire. The questionnaire consisted of 13 physical and 10 psychosocial items. The medical records were also reviewed to evaluate objective nutritional status. Factors predicting delayed recovery of QOL were examined at intermediate term by univariate and multivariate analyses. RESULTS: Overall and physical QOL scores returned to the preoperative level at intermediate term after PPPD, showing parallel changes with the objective nutritional status. However, the scores of psychosocial condition, which reflected the patient's mental health, remained low even at long term. QOL scores at intermediate term in patients with pancreatic carcinoma were significantly lower than those with other diseases. Univariate analysis showed that preoperative body weight loss, impaired preoperative pancreatic exocrine function, long operative time, intraoperative radiotherapy, pancreatic carcinoma, and postoperative diarrhea were factors predicting the delayed recovery of QOL. Multivariate analysis revealed that preoperative pancreatic exocrine function significantly affected the delayed recovery of QOL. CONCLUSIONS: Preoperative supplement of pancreatic enzymes together with perioperative mental care would improve QOL at long term after PPPD.