Comparative genomic hybridization analysis of primary colorectal carcinomas and their synchronous metastases

We have analyzed 26 tumors from 12 patients with metastatic colorectal adenocarcinoma by comparative genomic hybridization (CGH). Primary tumors and their lymph node metastases from five Dukes' C patients as well as primary tumors and their liver metastases from seven Dukes' D patients were used to assess the extent of genetic differences between primary and secondary colorectal carcinomas from the same patients, to calculate the degree of clonal divergence and genetic heterogeneity in metastatic colorectal cancer, and to determine the differences in genetic imbalances between Dukes' C and D stage tumors. We show that the same genetic aberrations were frequently found in the primary tumors and their metastases. However, metastases often contained genetic aberrations not found in the corresponding primary tumors. The comparison of Dukes' stages C and D revealed genetic aberrations common to both. However, reduced copy number of chromosome arm 17p (5/5 vs. 0/7; P = 0.001) was significantly associated with Dukes' stage C and lymph node metastases, while increased copy number of chromosome arms 6p (6/7 vs. 0/5; P = 0.007) and 17q (5/7 vs. 0/5; P = 0.027) was associated more with Dukes' stage D and liver metastases. Our results established a repertoire of chromosomal alterations associated with metastatic colorectal cancer and suggest that Dukes' C (lymph node metastasis) tumors are not always simply an earlier stage of Dukes' D (liver metastasis) tumors and, thus, in some instances at least, they are distinct forms of the disease.     

Survivorship and Patient-Reported Outcomes of an Uncemented Vitamin E–Infused Monoblock Acetabular Cup: A Multicenter Prospective Cohort Study

BackgroundAddition of vitamin E to polyethylene is theorized to reduce the potential for oxidative wear in acetabular components. This paper presents a multicenter prospective cohort study that reports on outcomes from use of a Vitamin E–infused highly cross-linked polyethylene acetabular cup.MethodsPatients were recruited across nine medical institutions. Clinical outcome measures recorded were the Harris Hip Score, visual analogue score for pain and satisfaction. Evidence of implant loosening or osteolysis was collected radiologically. Cup survival and reasons for revision in relevant cases were also recorded. Data collection was undertaken preoperatively, at 6-12 weeks, 6 months, 1 year, 2 years, and 5 years. A total of 675 patients were recruited, with 450 cases available at final review. Data regarding cup survival was available to 8 years and 9 months postoperatively.ResultsImprovements in both the Harris Hip Score and visual analogue score for pain and satisfaction were recorded at all time points, with these being maintained through the length of follow-up. In total, 89% of cups were implanted within the Lewinnek safe zone. A lucent line was identified in one case, with no evidence of acetabular osteolysis observed throughout the follow-up period. Cup survival was 98.9% at 8 years and 9 months. No revisions for aseptic loosening were observed.ConclusionsThe use of a vitamin E–infused polyethylene acetabular cup demonstrates reassuring patient-reported outcomes, radiological measures, and cup survival at medium to long-term follow-up.     

Telemedical evaluation of ocular adnexa and anterior segment

PURPOSE: To report the accuracy of telemedical slit-lamp evaluation in examination of ocular adnexa and anterior segment. METHODS: By means of contingency tables, slit-lamp findings by live examination and by real-time telemedicine were compared in 50 eyes of 25 patients. RESULTS: Sensitivity percentages (proportion with findings correctly identified by telemedicine)/specificity percentages (proportion without the finding that was correctly identified by telemedicine) were 100/64 for eyelid mass, 100/85 for conjunctival pigment, 100/100 for posterior synechiae, 80/0 for blepharitis, 83/93 for iridotomy, 70/93 for pinguecula, 75/93 for iris lesions, 56/98 for corneal scar, 0/100 for chamber inflammation, 57/93 for nuclear cataract, and 37/100 for intraocular lens presence. CONCLUSIONS: By means of monocular slit-lamp telemedical evaluation, clinical findings with high contrast cues for color and depth have the highest sensitivity and specificity.     

RKIP regulates CCL5 expression to inhibit breast cancer invasion and metastasis by controlling macrophage infiltration

Accumulating evidence suggests that presence of macrophages in the tumor microenvironment add to the invasive and tumor-promoting hallmarks of cancer cells by secreting angiogenic and growth factors. RKIP is a known metastasis suppressor and interferes with several steps of metastasis. However, the mechanistic underpinnings of its function as a broad metastasis suppressor remain poorly understood. Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis. Using a combination of loss- and gain-of-function approaches, we show that RKIP hinders breast cancer cell invasion by inhibiting expression of the CC chemokine CCL5 in vitro. We also show that the expression levels of RKIP and CCL5 are inversely correlated among clinical human breast cancer samples. Using a mouse allograft breast cancer transplantation model, we highlight that ectopic expression of RKIP significantly decreases tumor vasculature, macrophage infiltration and lung metastases. Mechanistically, we demonstrate that the inhibition of the CCL5 expression is the cause of the observed effects resulting from RKIP expression. Taken together, our results underscore the significance of RKIP as important negative regulator of tumor microenvironment.     

Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status

In this case-control study, our first aim was to evaluate the bone mineral density (BMD) in women with systemic sclerosis (SSc) and its correlates. Secondarily, we aimed to evaluate 25-hydroxyvitamin D3 status and its relationships with disease parameters and BMD. Sixty patients with SSc and 60 age-and gender-matched controls were included in the absence of confounding factors that interfere with bone metabolism. Body mass index, menopausal status, familial history of osteoporosis and/or fractures; personal fracture history; exercise activity and laboratory parameters of bone metabolism were assessed in patients and controls. BMD was measured by using a dual-energy X-ray absorptiometry in lumbar spine (L1-L4) and femoral neck. The 25-hydroxyvitamin D3 was measured in a subgroup of 30 patients and in a subgroup of 30 matched controls. Systemic manifestations of SSc, biological inflammatory parameters, functional disability (scleroderma health assessment questionnaire (S-HAQ)) and immunological status of disease were collected in patients' group. The mean age of patients was 49.44?±?13.07?years versus 49.55?±?12.11 in controls. The mean disease duration was 9.63?±?5.9?years. SSc patients had a significantly earlier age and longer duration of menopause than controls (P?=?0.003). Phosphocalcic metabolism parameters were within normal ranges in both groups. BMD was significantly lower in SSc patients than in controls both in lumbar spine (-2.97?±?0.25 in patients vs. 0.46?±?0.11 in controls) and femoral neck (-1.93?±?0.32 in patients vs. -0.81?±?0.69 in controls) (P?相似文献   

Two-Stage Arthroplasty for Prosthetic Joint Infection : A Systematic Review of Acute Kidney Injury,Systemic Toxicity and Infection Control

Periprosthetic infections of hip and knee joints are now treated by two-stage revision arthroplasty with an infection control rate of 91%. The present systematic review studied the reported incidence of acute kidney injury (AKI) and infection recurrence from January 1989 to June 2012 to assess the risk–benefit ratio of antibiotic spacer use. Ten observational studies (n = 544 patients) with clinical outcomes showed an average incidence of AKI of 4.8%. The average reported persistence or recurrence rate of infection was 11% during a follow-up period that ranged from 13 to 108 months. The risk–benefit ratio presently favors treatment although there appears to be higher complication rates and incidence of AKI than previously reported. Marked heterogeneity in practice and lack of detail in reporting precluded more robust quantitative synthesis. Clinicians need to be aware of the potential risk of AKI, particularly in high-risk patients; practice patterns for the use of antibiotic spacers need to be standardized.     

Chitosan-Gelatin Hydrogel Crosslinked With Oxidized Sucrose for the Ocular Delivery of Timolol Maleate

Ocular hypertension due to increased intraocular pressure is a major risk factor for the development of glaucoma. Rapid clearance and low ocular bioavailability are drawbacks of conventional ocular treatments. This requires frequent and long-term application of antiglaucoma drugs which in turn cause local side effects and are a major cause of therapeutic failure due to loss of persistence in using glaucoma therapy. In this study, a semisynthetic, biocompatible, oxidized sucrose crosslinker was developed and used in the formulation of chitosan-gelatin hydrogel for the sustained release of timolol to control ocular hypertension. The swelling properties of the hydrogel showed a strong relationship with the oxidized sucrose concentration. Mucoadhesive properties of the hydrogel were studied and the in vitro release profiles demonstrated that crosslinking with oxidized sucrose reduced the release rate of the entrapped timolol. The results of both in vitro and in vivo studies supported that the formulated hydrogel maintained the release and in turn the efficacy of timolol for a longer period of time compared to the conventional eye drops. This is expected to reduce the frequency of drug application onto the eye surface and in turn enhances patients’ convenience. In conclusion, the developed formulation represents a promising platform for an effective and compliant treatment of ocular hypertension.     

Cheesy material on macroscopic on-site evaluation after endoscopic ultrasound-guided fine-needle biopsy: Don't miss the tuberculosis

Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is an excellent investigation to diagnose pancreatic lesions and has shown high accuracy for its use in pathologic diagnosis. Recently, macroscopic on-site evaluation (MOSE) performed by an endoscopist was introduced as an alternative to rapid on-site cytologic evaluation to increase the diagnostic yield of EUS-FNB. The MOSE of the biopsy can estimate the adequacy of the sample directly by the macroscopic evaluation of the core tissue obtained from EUS-FNB. Isolated pancreatic tuberculosis is extremely rare and difficult to diagnose because of its non-specific signs and symptoms. Therefore, this challenging diagnosis is based on endoscopy, imaging, and the bacteriological and histological examination of tissue biopsies. This uncommon presentation of tuberculosis can be revealed as pancreatic mass mimicking cancer. EUS-FNB can be very useful in providing a valuable histopathological diagnosis. A calcified lesion with a cheesy core in MOSE must be suggestive of tuberculosis, leading to the request of the GeneXpert, which can detect Mycobacterium tuberculosis deoxyribonucleic acid and resistance to rifampicin. A decent diagnostic strategy is crucial to prevent unnecessary surgical resection and to supply conservative management with antitubercular therapy.