Genetic aberrations of NAT2 and chromosome 8: their association with progression in transitional cell carcinoma of the urinary bladder

INTRODUCTION/OBJECTIVE: N-acetyltransferase 2 (NAT2), mapped to 8p22, is a polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of 8p22 is associated with an increased risk of bladder cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to determine if NAT2 alterations increase the risk of progression. MATERIALS AND METHODS: Thirty-seven sequential carcinomas from 19 patients were assessed using fluorescence in situ hybridization. RESULTS: Five carcinomas showed loss of NAT2; 4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%) primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally invasive tumours with polysomy 8 were from patients who subsequently developed disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number. Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and disease progression (p = 0.03). CONCLUSION: Whilst there does not appear to be an association between loss of NAT2 and risk of progression in transitional cell carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on this chromosome significantly influence disease progression.     

CD103+ CTL accumulate within the graft epithelium during clinical renal allograft rejection.

BACKGROUND: We have previously reported that activated CD8+TCRalphabeta+ cells that express high levels of the beta7 integrin CD103 (formerly alphaE, MLA) are present at the graft site during clinical renal allograft rejection. This observation potentially provides new insight into the mechanisms underlying renal allograft destruction because the ligand of CD103 is the epithelial cell-specific molecule E-cadherin, which is known to be expressed by critical graft functional elements such as the renal tubular epithelium. We herein used combined fluorescence-activated cell sorter (FACS) and immunohistochemical (IHC) analyses of transplant nephrectomy (TN) specimens to demonstrate that CD103+ cytolytic T lymphocytes (CTLs) specifically home to the graft epithelium during rejection episodes. METHODS: Serial sections of TN specimens undergoing histologically confirmed cellular rejection (n=7) were stained with anti-CD8 or anti-CD103 and were scored for the presence of positively stained cells within the tubular basement membrane. Freshly isolated graft-infiltrating lymphocytes were subjected to three-color FACS analyses to define the extended phenotypic characteristics of CD103+ cells detected by IHC. RESULTS: CD103+ cells in all specimens were biased towards an intratubular localization. On average, the percentage of CD103+ cells with an intraepithelial localization was 52.2+/-13.1 compared to 12.0+/-3.5 for pan CD8+ cells (mean+/-SE, n=5). FACS analyses confirmed that CD103+ cells detected by IHC exhibited the salient characteristics of CD8+ CTLs (large CD8+TCRalphabeta+CD62L-CD11a(hi)perforin+). The CD103- subset of graft-infiltrating CD8 cells also exhibited a CTL phenotype, but these were predominantly restricted to the graft interstitium. CONCLUSIONS: These data implicate CD103 as a homing receptor that targets graft-infiltrating CD8+ CTLs to the graft epithelium. Given the strong association of tubulitis with clinical rejection, these data are consistent with a role for the CD103+ CTL subset as an effector mechanism in renal allograft destruction.     

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

Background

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival.

Methods

A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan–Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival.

Results

At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5–5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3–5.4, p = .01).

Conclusions

Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.     

Algorithm for Total Face and Multiorgan Procurement From a Brain‐Dead Donor

Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time–intensive, “simultaneous–start” procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain–dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO₂ remained normal. All organs had good postoperative function. We propose an algorithm that allows “face first, concurrent completion” recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.     

Pilot study of a web-based antibiotic decision management guide

BACKGROUND: Use of electronic medical information resources by health-care professionals is increasing. Portable handheld computers have facilitated access to medical knowledge at the point of patient care. Little is known about the impact of mobile medical information tools on physician learning or improvement in decision-making. STUDY DESIGN: A 6-month prospective, randomized pilot study of 12 first-year trauma and critical care Fellows at the R Adams Cowley Shock Trauma Center was conducted from November 1, 2001 to May 31, 2002 at the University of Maryland. Six Fellows were randomized to use the Johns Hopkins Antibiotic Guide (JHABX) on the RIM Blackberry personal digital assistant (PDA) for 6 months of their clinical rotation. Six Fellows were randomized to the non-PDA-use arm. Three-month and 6-month examination raw scores on knowledge of infectious diseases management among Blackberry PDA users versus non-PDA users were obtained. Measurement of antibiotic decision accuracy by diagnosis at 3 and 6 months among Fellows randomized to use the JHABX on the RIM Blackberry PDA was also evaluated. RESULTS: PDA group demonstrated a considerable improvement in test scores over the 3-month time interval, compared with their baseline score (40.8 +/- 2.3 versus 34.3 +/- 4.6, p < 0.05) and compared with the non-PDA group (40.8 +/- 2.3 versus 36.8 +/- 3.3, p < 0.01). Improvement became even more notable at the 6-month interval again, compared with themselves (43.8 +/- 4.5 versus 34.3, p < 0.001) and the non-PDA group (43.8 +/- 4.5 versus 38.1 +/- 5.1, p < 0.001). There was no notable improvement in test scores at 3 months or 6 months in the control group. Overall antibiotic decision accuracy substantially improved from 66% during the initial 3-month period to 86.6% during the second 3-month period (p = 0.005) among users of the JHABX. This was most evident in respiratory, blood, and skin and soft tissue infections. CONCLUSIONS: Web-based handheld technology is highly effective for supplying information to support infectious disease clinical practice. In a hospital intensive care setting, results of this study demonstrate that resident physician knowledge and antibiotic decision selection accuracy improved among Fellows using the JHABX. Reasons for this difference can be multifold and not thoroughly evaluated from this small pilot study. Future studies on the impact of point-of-care technology on patient outcomes are warranted.     

Life-threatening intrathoracic complications during treatment with extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) has been successful (greater than 80% survival) in 35 centers in greater than 900 newborns with severe respiratory failure having an estimated mortality of greater than 80% on conventional management. During the last 3 years we have treated 79 newborns with 74 survivors (94%). Their diagnoses included meconium aspiration, persistent fetal circulation, respiratory distress syndrome, congenital diaphragmatic hernia, and sepsis. Seven patients (9%) had life-threatening intrathoracic complications requiring emergent intervention while on ECMO: tension hemothorax (3), tension pneumothorax (2), and pericardial tamponade (2). Pericardial tamponade and tension hemothorax and pneumothorax show a similar pathophysiology of increasing intrapericardial pressure and decreasing venous return. Perfusion is initially maintained by the nonpulsatile flow of the ECMO circuit before further decrease in venous return results in decreasing ECMO flow and progressive hemodynamic deterioration. Each of the seven patients demonstrated a clinical triad that includes increasing PaO2 and decreasing peripheral perfusion (as evidenced by decreasing pulse pressure and decreasing SvO2) followed by decreasing ECMO flow with progressive deterioration. The diagnoses were confirmed by transillumination, chest x-ray, or cardiac echocardiogram. Initial emergent placement of a percutaneous drainage catheter was temporizing in all seven cases. However, four patients required emergent thoracotomy for definitive treatment while still on ECMO. All seven patients were weaned from ECMO and are short-term survivors (6 months to 3.5 years). As use of ECMO for newborn severe respiratory failure increases, responsible physicians must be familiar with life-threatening intrathoracic complications and appropriate treatment strategies.     

Multiple aneurysms in Beh?et's disease

Beh?et's disease is characterized by recurrent ulcers of the mouth and genitalia and relapsing iritis. It is now recognized as a chronic multisystem disease affecting the skin, mucous membranes, eye, joints, central nervous system, and blood vessels. One of the known vascular complications of Beh?et's disease is aneurysm formation or venous thrombosis. The two patients with Beh?et's disease in this report developed multiple aneurysms over a short time span. Vascular surgeons dealing with young adults with peripheral aneurysms must be aware of this uncommon yet challenging clinical entity.     

Serial measurement of lymphocytotoxic antibody and response to nonmatched platelet transfusions in alloimmunized patients

Serial evaluations of lymphocytotoxic antibody (LCTAb) and responsiveness to random donor platelet transfusion were reviewed in 234 patients who had developed LCTAb at some time during their treatment course. Seventy (30%) of these patients had significant falls in antibody levels. In 44 patients these declines occurred after further antigenic exposure was reduced either because no transfusions were administered or only histocompatible platelets were transfused. Forty patients with declines in LCTAb levels who were previously refractory to platelet transfusion were rechallenged with random donor platelets. Thirty-four of 35 clinically evaluable patients had good responses to these unmatched transfusions for 2 weeks to 36 months, and in 21 patients antibody did not return despite repeated transfusions. Thus, serial LCTAb measurements are helpful in the management of alloimmunized patients. Many patients will have decreases or a loss of LCTAb, either permanently or transiently, and can be successfully supported with more easily available unmatched random donor platelet transfusions.     

脑卒中患者对负性情绪及心理治疗认知状况的调查

目的：调查甘肃省脑卒中患者对负性情绪是否影响肢体功能以及心理治疗的认知。方法：采用问卷调查方式,对甘肃省10家不同级别的省市县级医院神经内、外科2010年收治的脑卒中住院患者1 100例进行调查。结果：负性情绪对肢体功能恢复的影响占69.80%,脑卒中后心理治疗的需要占76.99%。结论：负性情绪对脑卒中患者肢体功能恢复有影响,并且非常需要心理治疗。