Self-Expanding Metal Stents for Biliary Drainage in Patients with Resectable Pancreatic Cancer: Single-Center Experience with 79 Cases

Background and Aims

To study pre-operative and peri-operative course and outcome on follow up after pancreaticoduodenenctomy (PD) for resectable pancreatic cancer amongst patients receiving self-expanding metal stents (SEMS).

Methods

Medical charts of consecutively reviewed patients (2005?C2009) with resectable pancreatic cancer and SEMS placement before PD at the MD Anderson Cancer Center (MDACC) were studied.

Results

Seventy-nine patients (mean age, 68 ± 9 years; 54% males) undergoing PD after SEMS placement were analyzed. Of these, 70% (55/79) had come with previous plastic stents placed within a median of 29 (5?C216) days because of presentation and most (95%) underwent neoadjuvant chemoradiation after SEMS placement. The median interval between SEMS placement and PD was 120 (range 28?C306) days. There were no technical difficulties during PD. The resected tumor was stage T3 in 72 patients, positive node in 44, lymphovascular invasion in 47, and perineural invasion in 62. Within 30 days after surgery, 26 (33%) patients developed complications requiring intervention, but none died. During a median follow-up of 349 (14?C1,508) days after surgery, 32 (41%) patients developed metastatic disease, and 20 (25%) died; median survival was approximately 3 years. Development of metastatic disease during follow-up independently predicted survival with hazard ratio of 16 (95% CI: 4?C68; P = 0.0001).

Conclusions

Contrary to the tendency of avoiding the use of metal stents for biliary decompression amongst patients with resectable pancreatic cancer, our study demonstrated that SEMS did not adversely affect surgical technique, postoperative course, or long-term outcome. Therefore, metal stents should be considered for patients with resectable pancreatic cancer who will undergo preoperative chemoradiation.     

Tumor suppressor death-associated protein kinase is required for full IL-1β production

Interleukin-1β (IL-1β) is critical for inflammation and control of infection. The production of IL-1β depends on expression of pro-IL-1β and inflammasome component induced by inflammatory stimuli, followed by assembly of inflammasome to generate caspase-1 for cleavage of pro-IL-1β. Here we show that tumor suppressor death-associated protein kinase (DAPK) deficiency impaired IL-1β production in macrophages. Generation of tumor necrosis factor-α in macrophages, in contrast, was not affected by DAPK knockout. Two tiers of defects in IL-1β generation were found in DAPK-deficient macrophages: decreased pro-IL-1β induction by some stimuli and reduced caspase-1 activation by all inflammatory stimuli examined. With a normal NLRP3 induction in DAPK-deficient macrophages, the diminished caspase-1 generation is attributed to impaired inflammasome assembly. There is a direct binding of DAPK to NLRP3, suggesting an involvement of DAPK in inflammasome formation. We further illustrated that the formation of NLRP3 inflammasome in situ induced by inflammatory signals was impaired by DAPK deficiency. Taken together, our results identify DAPK as a molecule required for full production of IL-1β and functional assembly of the NLRP3 inflammasome. In addition, DAPK knockout reduced uric acid crystal-triggered peritonitis, suggesting that DAPK may serve as a target in the treatment of IL-1β-associated autoinflammatory diseases.     

Does Hospice Improve Quality of Care for Persons Dying from Dementia?

OBJECTIVES: To examine the effectiveness of hospice services for persons dying from dementia from the perspective of bereaved family members. DESIGN: Mortality follow‐back survey. SETTING: Death certificates were drawn from five states (AL, FL, TX, MA, and MN). PARTICIPANTS: Bereaved family members listed as the next of kin on death certificates when dementia was listed as the cause of death. MEASUREMENTS: Ratings of the quality of end‐of‐life care, perceptions of unmet needs, and opportunities to improve end‐of‐life care. Two questions were also asked about the peacefulness of dying and quality of dying. RESULTS: Of 538 respondents, 260 (48.3%) received hospice services. Family members of decedents who received hospice services reported fewer unmet needs and concerns with quality of care (adjusted odds ratio (AOR)=0.49, 95% confidence interval (CI)=0.33–0.74) and a higher rating of the quality of care (AOR=2.0, 95% CI=1.53–2.72). They also noted better quality of dying than those without hospice services. CONCLUSION: Bereaved family members of people with dementia who received hospice reported higher perceptions of the quality of care and quality of dying.     

High glucose impairs EDHF-mediated dilation of coronary arterioles via reduced cytochrome P450 activity

Endothelium-derived hyperpolarizing factor (EDHF) is an important vasodilator that regulates the vasomotor function. However, it remains unclear whether diabetes/hyperglycemia-induced vascular impairments extend to the EDHF. The present study aims to determine the effect of high glucose (HG) on EDHF-mediated arteriolar dilation and the underlying mechanism. Porcine coronary arterioles were isolated and pressurized for vasomotor study. Cultured porcine coronary artery endothelial cells (ECs) were used for molecular and biochemical analysis. Our results demonstrate that bradykinin (BK)-simulated arteriolar dilation is mediated by nitric oxide (NO) and EDHF pathways. Direct incubation of HG impaired vasodilation to BK but not to sodium nitroprusside (endothelium-independent vasodilator). In the presence of inhibitors of endothelial NO synthase (eNOS) and cyclooxygenase, the EDHF-mediated dilation was reduced by HG incubation. The inhibitory effect of HG was prevented by treating the vessels with superoxide scavenger Tempol. In cultured coronary endothelial cells, HG reduced endothelial epoxyeicosatrienoic acid (EET) production as well as cytochrome P450 epoxygenase (CYP) activity. Furthermore, the superoxide production was elevated in ECs after HG incubation. Pretreatment with Tempol before HG incubation prevented the increase of cellular superoxide and abolished the decrease of CYP activity. Collectively, our results suggest that, in addition to NO-mediated pathway, HG impairs the EET/EDHF-mediated vasodilation in coronary arterioles via the elevated level of superoxide leading to inhibition of CYP activity in coronary ECs.     

Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves' hyperthyroidism

OBJECTIVE: The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves' hyperthyroidism. BACKGROUND: Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hormones and thyrotropin receptor antibodies (TRAb) levels. METHODS: Thirty patients with newly diagnosed Graves' hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS: There was no significant difference in baseline thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION: During the 12-week treatment of Graves' hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves' hyperthyroidism.     

Left atrial parameters in the estimation of left ventricular filling pressure and prognosis in patients with acute coronary syndrome

Because left atrial (LA) volume plays a critical role in determining cardiovascular outcomes, it was hypothesized that this might be related to the distensibility of the left atrium and how this relates to left ventricular filling pressure (LVFP). Echocardiographic estimates of LVFP were compared to cardiac catheterization measurements in 521 consecutive patients with acute myocardial infarction and correlated with short- and long-term outcomes. Receiver-operating characteristic curve analysis was performed to investigate the sensitivity and specificity of echocardiographic parameters for predicting elevated LVFP (> 15 mm Hg). LA distensibility was calculated as (maximal volume - minimal volume) × 100%/minimal volume(.) and was found to be logarithmically associated with LVFP (p < 0.0001). LA distensibility was superior to mitral E/annular Em for identifying increased LVFP (area under the receiver-operating characteristic curve 0.92 vs 0.78). A total of 44 patients died during hospitalization, and 89 patients had died or experienced heart failure requiring rehospitalization at 12-month follow-up. In a multivariate Cox regression model, LA distensibility was an independent predictor of in-hospital mortality (hazard ratio 2.373 for LA distensibility ≤ 60%, p = 0.026), while LA volume was an independent prognostic factor of 1-year death or heart failure (hazard ratio 2.266 for LA volume ≥ 34 ml/m2, p = 0.007). In conclusion, LA distensibility accurately identifies patients with increased LVFP after acute myocardial infarction and is an independent predictor of in-hospital mortality.     

增殖抑制基因单核苷酸多态性与原发性高血压的相关性

目的 探讨增殖抑制基因第二内含子7个单核苷酸多态性位点与原发性高血压的相关性.方法 筛选正常血压人群500名和原发性高血压患者930名,提取血中白细胞基因组DNA后设计特定的单核苷酸多态性引物进行定量多聚酶链反应,通过荧光定量方法确定该基因是否存在着某种特定的多态性位点.结果 7个不同的单核苷酸多态性中有3种即rs873457、rs2336384和rs4846085的基因型频率在正常血压组和原发性高血压组之间存在明显的差别(P<0.05),分别为TT:TC:CC=21.8%:46.6%:31.6%/22.5%:53.0%:24.5%、CC:CA:AA=21.8%:46.8%:31.4%/22.8%:52.6%:24.6%及TT:TC:CC=22.6%:46.4%:31.0%/23.4%:51.8%:24.7%,等位基因频率在正常血压组与原发性高血压组之间也存在明显差别(P<0.05),分别为T:C=45.1%:51.0%/49.0%:51.0%、C:A=45.2%:54.8%/49.1%:50.9%及T:C=45.8%:54.2%/49.1%:50.6%,其余4个单核苷酸多态性位点在正常血压组和原发性高血压组之间不存在明显的差别.对不同性别进行分析后发现在男性正常血压组与原发性高血压组的7个单核苷酸多态性位点之间均存在着明显的差别(P<0.05或P<0.01),而在女性正常血压组与原发性高血压组之间没有明显差别(P>0.05).相关性分析发现体质指数、年龄和基因型与血压之间存在着明显的相关性 (P<0.05).在进行了年龄和性别调整后,回归分析发现体质指数和rs873457与血压密切相关.单倍体型分析发现C-G-A-A-A-C-C(以 rs873457、rs2336384、rs1474868、rs4846065、rs4240897、rsrs2236055和 rs873458为序)无论在总体人群、男性还是女性人群中,均存在着明显的差别(P<0.01).结论 增殖抑制基因的基因多态性与高血压尤其是男性高血压之间存在着明显的差别.     

Acquirement and disappearance of HBsAg and anti‐HCV in an aged population: a follow‐up study in an endemic township

Background: HBsAg and anti‐hepatitis C virus (anti‐HCV) are stable markers and widely used. The seroconversion and seroclearance of HBsAg and anti‐HCV are important for disease control and prognosis of diseases. Aims: To investigate acquirement and disappearance of HBsAg and anti‐HCV in an endemic area. Methods: Seven years after a community screening, 1002 of 2909 residents of Tzukuan Township were recruited. HBsAg, anti‐HCV and alanine transaminase (ALT) were checked in all who participated and hepatitis B virus (HBV) DNA, anti‐HBs, anti‐HBc, HCV RNA, anti‐HDV and upper abdominal ultrasonography were studied in different groups. Results: There were 461 male and 541 female residents with a mean age of 66.7±8.6 years. No new HBsAg carrier was noted and the HBsAg clearance rate was 1.58% per year. One of the 17 cases with HBsAg clearance had positive HBV DNA, three had ALT elevation, two had cirrhosis and seven had anti‐HBs seroconversion. Quantitative of HBsAg and HBV DNA were concordant and 78.1% subjects had low levels of titration. Anti‐HBc alone contributed to 32.1% and was prominent in old age and the anti‐HCV‐positive group. The anti‐HCV seroconversion rate was only 0.74% per year and household transmission was the only risk factor. Only 37.5% of cases with anti‐HCV seroconversion had HCV viraemia and the anti‐HCV seroreversion rate was 0.63% per year. The anti‐HDV seroconversion rate was 0.72% per year and no subject showed anti‐HDV clearance. Conclusions: Much higher rates of HBsAg seroclearance, anti‐HCV seroreversion and anti‐HBc alone were noted in this endemic area and no subject showed anti‐HDV clearance.     

Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan

Few studies have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.91 years of follow-up, there were 18 cases of ICC and 192 cases of NHL, including 99 cases of diffuse large B-cell lymphoma (DLBCL). Incidence rates of ICC were 0.09 and 0.43 per 100,000 person-years, respectively, among women who were hepatitis B surface antigen (HBsAg)-seronegative and HBsAg-seropositive, showing an age-adjusted hazard ratio (HR(adj) ) (95% confidence interval [CI]) of 4.80 (1.88-12.20). The incidence rates of NHL overall for HBsAg-seronegative and HBsAg-seropositive women were 1.23 and 3.18 per 100,000 person-years, respectively, with an HR(adj) (95% CI) of 2.63 (1.95-3.54). Among NHL subtypes, HBsAg-seropositive women had an increased risk of DLBCL compared with those who were HBsAg-seronegative (incidence rates: 1.81 and 0.60 per 100,000 person-years, respectively; HR(adj) [95% CI]: 3.09 [2.06-4.64]). The significantly increased risk was not observed for other specific subtypes of NHL. CONCLUSIONS: Chronic HBV infection was associated with an increased risk of ICC and DLBCL in women. Our data suggested a possible etiological role of HBV in the development of ICC and specific subtypes of NHL.