HGF 基因修饰的间充质干细胞对犬后肢缺血后股神经的保护作用简

目的观察携带人肝细胞生长因子基因的重组腺病毒（Ad—HGF）修饰的骨髓间充质干细胞（Msc）对犬后肢缺血后神经组织病理学的影响。方法18只犬随机分为Ad—HGF—MSC处理组、模型对照组和正常对照组,每组6只。将Ad—HGF—MSC处理组和模型对照组犬麻醉后,全结扎左后肢股动脉制作犬左后肢缺血模型,体外分离、培养犬骨髓MSC,转染Ad—HGF,并将含Ad-HGF—MSC的细胞悬液对Ad—HGF—MSC处理组犬病肢行多点肌肉注射,模型对照组犬注射等量的PBS缓冲液,正常对照组不进行任何处理。90d后,取组织标本,常规组织病理切片染色,光学显微镜下观察。结果12只犬均建模成功。模型对照组犬病侧股神经至肌束间的细小神经均发生显著退行性变,累及轴突、髓鞘和施旺细胞核。而Ad—HGF—MSC处理组犬的各级神经病变不明显,部分甚至与正常对照组无差别。结论Ad—HGF—MSC局部注射可减轻或阻遏犬后肢缺血后股神经组织损伤,具有一定的神经组织保护作用。     

Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

CD151 Overexpression is Associated with Poor Prognosis in Patients with pT3 Gastric Cancer

Introduction

CD151, a transmembrane protein of the tetraspanin family, is implicated in the regulation of cell-substrate adhesion and cell migration. Overexpression of CD151 has been reported in several cancers and controls MET-dependent neoplastic growth by enhancing receptor signaling. However, association of CD151 overexpression with MET or tumor progression has not been reported in gastric cancer.

Materials and Methods

We conducted immunohistochemical analysis of CD151 overexpression in 491 pT3 gastric carcinomas and analyzed the relationship with MET overexpression and prognostic significance.

Results

CD151 was highly expressed in 119 gastric carcinomas (24.2 %) and was significantly associated with higher pN stages. Patients with CD151-positive gastric cancer showed shorter overall (p = 0.003) and disease-free survival (p = 0.001) compared with patients with CD151-negative gastric carcinoma. CD151 overexpression was an independent prognostic factor for overall survival [hazard ration (HR) 1.335; 95 % CI 1.005–1.775; p = 0.046] and disease-free survival (HR 1.903; 95 % CI 1.348–2.685; p < 0.001). Co-overexpression of CD151 and MET was observed in 30 (6.1 %) gastric cancers and was more frequent in advanced pN stages than in other groups. Moreover, co-overexpression of CD151 and MET was a strong independent prognostic factor for overall survival (HR 3.163; 95 % CI 1.958–5.108; p < 0.001) and disease-free survival (HR 3.834; 95 % CI 2.145–6.852; p < 0.001).

Conclusion

CD151 overexpression is an independent prognostic factor and could be a potential molecular therapeutic target in patients with advanced gastric cancers. Further studies are needed to establish the biological significance of CD151/MET co-overexpression and the potential of targeting both molecules as a therapeutic strategy.     

Underutilization of local salvage therapy after radiation therapy for prostate cancer

ObjectiveTo evaluate the rates at which patients are offered and receive local salvage therapy (LST) after failure of primary radiotherapy for localized prostate cancer, as it is the only potentially curative treatment for localized recurrence but appears to be underutilized when compared with androgen-deprivation therapy (ADT) or observation.Materials and methodsPatients with localized prostate cancer who received primary radiotherapy with curative intent between 1999 and 2000 were identified in the British Columbia Tumour Registry. Exclusion criteria included patient age >72 years, prostate-specific antigen>40 ng/ml, and clinical stage T4 at diagnosis. Data on clinicopathologic features, primary therapy, prostate-specific antigen kinetics, and salvage therapy were collected retrospectively. Radiation failure was defined as biochemical recurrence according to the Phoenix criteria or by initiation of salvage therapy.ResultsOf 1,782 patients treated in the study period, 1,067 met inclusion criteria. Of these, 257 failed radiation therapy. Radiation therapy failure was managed with observation (>12 mo) in 126 patients and ADT in 119. Of the observed patients, 66 subsequently received ADT. Five patients (1.8%) received LST (3 radical prostatectomy and 2 brachytherapy).ConclusionsOnly 2% of patients relapsing after radiation therapy for localized prostate cancer received LST. Although the benefits of LST are unproven, these findings reveal a possible underutilization of LST and indicate a need for enhanced collaboration between specialties to optimize care of this challenging cohort.     

Pancreatic Atrophy Relative to External Versus Internal Drainage of the Pancreatic Duct After Pylorus-Preserving Pancreaticoduodenectomy

Background

Atrophy of the pancreatic parenchyma, which occurs frequently after pylorus-preserving pancreaticoduodenectomy (PPPD), is often associated with pancreatic exocrine insufficiency. Many surgeons prefer to insert a drainage tube into the remnant pancreatic duct primarily to prevent pancreatic leakage at the pancreaticojejunostomy (PJ) after PPPD. Drainage methods vary widely but can be roughly classified as internal or external drainage. This study intended to evaluate their effects on pancreatic parenchymal atrophy following PPPD.

Methods

Fifty-seven patients who underwent PPPD were retrospectively divided into two groups, 28 who underwent external and 29 who underwent internal pancreatic drainage. External drainage tubes were removed 4 weeks after PPPD. The volume of the pancreatic parenchyma was serially measured on abdominal computed tomography (CT) scans before PPPD, as well as 7 days and 3, 6, and 12 months after surgery. Degree of pancreatic parenchymal atrophy was determined by calculating pancreatic volume relative to that on day 7.

Results

Univariate analysis showed that patient sex, age, body mass index, concurrent pancreatitis, pathology, and types of PJ did not significantly affect changes in pancreatic volume following PPPD. The degree of pancreatic volume atrophy did not differ significantly in the external and internal drainage groups. No patient in the external drainage group experienced drainage-related surgical complications. The incidence of PJ leak was comparable in the two groups. Postoperative pancreatic atrophy did not induce new-onset diabetes mellitus at 1 year.

Conclusions

Both external and internal pancreatic drainage methods showed similar atrophy rate of the pancreatic parenchyma following PPPD.