More differences between HNPCC-related and sporadic carcinomas from the endometrium as compared to the colon

PURPOSE: Recognition of hereditary nonpolyposis colorectal cancer (HNPCC)-related endometrial carcinoma from sporadic carcinoma by histologic features as compared with colonic cases. STUDY DESIGN: Case-control study. METHODS AND MATERIALS: From the files of the Nijmegen Hereditary Cancer Clinic, HNPCC-related (n = 6) endometrial and colorectal (n = 18) carcinomas were selected. For every HNPCC-related tumor, 2 sporadic control cases were included. The tumors were evaluated for the following 7 pathologic features: tumor differentiation, T-stage, growth pattern, presence of Crohn-like lymphoid reaction, mucinous differentiation, presence of lymphangioinvasive growth, and the amount of tumor-infiltrating lymphocytes. RESULTS: HNPCC-related endometrial carcinomas were significantly more often poorly differentiated (83% versus 27%), more often showed the presence of a Crohn-like lymphoid reaction (100% versus 13%) and lymphangioinvasive growth (67% versus 0%), and high number of tumor-infiltrating lymphocytes were more often present (100% versus 36%) compared with sporadic endometrial carcinomas. The differences between HNPCC and sporadic colorectal cancer specimens were less discriminating. CONCLUSIONS: HNPCC-related endometrial carcinomas are characterized by poor differentiation, more frequent Crohn-like lymphoid reaction, lymphangioinvasive growth and more tumor-infiltrating lymphocytes. These features therefore might form the basis for selecting patients for counseling in a hereditary cancer clinic or testing for microsatellite instability or mutation analysis of mismatch repair genes, especially when they are of relatively young age.     

Achieving K/DOQI laboratory target values for bone and mineral metabolism: an uphill battle

BACKGROUND: The National Kidney Foundation has recently published the Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease (CKD). According to these guidelines, in patients with stage 5 CKD, the adjusted calcium level should be 8.4- 9.5 mg/dl, the serum phosphate should be 3.5-5.5 mg/dl, the calcium phosphorous product should be <55 mg(2)/dl(2) and the intact parathyroid hormone (PTH) level should be 150-300 pg/ml. METHODS: In order to evaluate our ability to meet these targets, we reviewed laboratory parameters of bone and mineral metabolism of 140 patients over a 6-month period in an inner city hemodialysis unit. Serum calcium and phosphate levels were determined using standard assays and PTH levels were determined using the Nichols Intact PTH assay. RESULTS: We found that the levels of serum calcium and serum phosphorus fell within the range recommended by the K/DOQI guidelines 49 and 36% of the time respectively. 57% of the determinations for calcium x phosphorus product were <55 mg(2)/dl(2). PTH levels were within the recommended values in 20% of the determinations. Only 7% of the determinations met all four criteria simultaneously in spite of meeting other K/DOQI targets such as hematocrit and dialysis adequacy. CONCLUSION: These data indicate that current practice for the management of bone and mineral metabolism in hemodialysis falls far short of meeting the K/DOQI guidelines.     

Vitamin D analogs: actions and role in the treatment of secondary hyperparathyroidism

Although calcitriol has been shown to have an important role in the pathogenesis of hyperparathyroidism, its use as a therapeutic agent often has been limited by calcemic and phosphatemic toxicity. Vitamin D analogs and the synthetic prohormones, with the potential to have lesser effects on calcium and phosphorus, have been introduced and shown to be effective therapeutic agents. Paricalcitol is used widely in the United States and may be associated with improved clinical outcomes. Further studies on the effects of these vitamin D sterols on the skeleton and further studies of potential differential effects on calcification processes will be forthcoming, and as the mechanisms of their lesser toxicity become understood, perhaps this will pave the way for a future generation of vitamin D analogs with even greater specificity for the suppression of hyperparathyroidism with lesser toxicity.     

Colour evaluation in scars: tristimulus colorimeter, narrow-band simple reflectance meter or subjective evaluation?

The evaluation of scar colour is, at present, usually limited to an assessment according to a scar assessment scale. Although useful, these assessment scales only evaluate subjectively the degree of scar colour. In this study, the reliability of the subjective assessment of scar colour by observers is compared to the reliability of the measurements of two objective colour measurement instruments. Four independent observers subjectively assessed the vascularisation and pigmentation of 49 scar areas in 20 patients. The degree of vascularisation and pigmentation was scored according to a scale ranging from '1', when it appeared to be like healthy skin, to '10', which corresponds to the worst imaginable outcome of vascularisation or pigmentation. The observers also scored the pigmentation categories of the scar (hypopigmention, hyperpigmention or mixed pigmentation). Finally, each observer measured the scar areas with a tristimulus colorimeter (Minolta Chromameter) and a narrow-band simple reflectance meter (DermaSpectrometer). A single observer could reliably carry out measurements of the DermaSpectrometer and the Minolta Chromameter for the evaluation of scar colour (r = 0.72). The vascularisation of scars could also be assessed reliably with a single observer (r = 0.76) whereas for a reliable assessment of pigmentation at least three observers were necessary (r > or = 0.77). The agreement between the observers for the pigmentation categories also turned out to be unacceptably low (k = 0.349). This study shows that an overall evaluation of scar colour with the DermaSpectrometer and the Minolta Chromameter is more reliable than the evaluation of scar colour with observers. Of both instruments for measuring scar colour, we prefer, because of its feasibility, the DermaSpectrometer.     

Comparison of rocking edge spacing for two common designs of swivel walkers

Two commonly used designs of swivel walker are the Consort 800 and the ORLAU 1000. This paper examines how the footplate rocking edge spacing varies between these two designs and then considers how lateral stability might be influenced if reduced separation is introduced to facilitate ambulation for less able users. In general it is shown that there should be no obstacles to such variation on the part of an orthotist thereby improving access to these devices and function for disabled individuals.     

Significance of the time period between diagnosis of muscle invasion and radical cystectomy with regard to the prognosis of transitional cell carcinoma of the urothelium in the bladder

OBJECTIVE: Standard treatment of muscle-infiltrated transitional cell carcinoma (TCC) of the urothelium consists of radical cystectomy. In some cases there is a delay between the initial diagnosis and a definitive treatment being administered. The objective of this study was to determine the effect of the time window between evidence of muscle invasion and radical cystectomy on the pathological stage and progression-free survival. MATERIAL AND METHODS: Between February 1992 and August 2002, 239 radical cystectomies were carried out as a result of TCC of the bladder. In a total of 189 patients (79%), cystectomy was carried out due to muscle-infiltrated TCC with no evidence of distant metastases (>/=T2, M0). The time between the diagnosis of muscle invasion and cystectomy was determined for all of these patients, who were then divided into two groups on the basis of a 3-month cut-off period. Univariate and multivariate analyses were used to determine the effect of the time period on clinical factors and progression-free survival. RESULTS: The average age of the patients was 63 (range 35-80) years. A median follow-up of 40 months showed a progression-free survival rate of 49% after 5 years. The average time between the diagnosis of muscle invasion and cystectomy was 1.8 (0.3-12.1) months. For a time window of >3 months, 30/42 patients (72%) showed signs of extravesical tumor growth and/or tumor-positive lymph nodes, compared to 89/147 patients (60%) (p = 0.198) for a time window of 3 months between diagnosis of muscle invasion and radical cystectomy were associated with an advanced pathological stage and a poorer progression-free survival. These results underline the need for early cystectomy within the 3-month period between diagnosis of muscle invasion and cystectomy.     

Developing measures of surgeons' equipoise to assess the feasibility of randomized controlled trials in vascular surgery

Background

Equipoise is defined medically as a state of genuine uncertainty about the relative benefits of alternative treatment options. This study investigated individual and collective equipoise among vascular surgeons for controversial clinical questions to assess the feasibility of conducting randomized controlled trials.

Methods

Vascular surgeons throughout Australia and New Zealand received a survey by mail.

Results

Vascular surgeons (n = 146, 77% response fraction) were able to quantify the strength of their treatment preferences and did so differentially between clinical scenarios using a simple scale. Almost one quarter (24%; 95% CI, 18%-32%) were completely undecided about whether carotid endarterectomy or carotid stenting was preferable to treat carotid stenosis in high-risk patients, indicating individual equipoise. In contrast, the vast majority of respondents (89%; 95% CI, 82%-93%) favored carotid endarterectomy over carotid stenting for average-risk patients, suggesting lack of community equipoise for this patient group. Similarly, there was lack of community equipoise for treatments for abdominal aortic aneurysm in high-risk patients with 88% (95% CI, 81%-92%) favoring a minimally invasive approach. Older respondents were consistently less willing to take part in randomized trials, with strength of treatment preference also independently predicting willingness to participate in 4 of 6 trials.

Conclusions

Individual and community equipoise can be measured in a representative sample of surgeons as part of the feasibility assessment for future randomized controlled trials.     

Survival rates after radical cystectomy according to tumor stage of bladder carcinoma at first presentation

INTRODUCTION: The aim of this study was to establish to what extent the survival rates of muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 230 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2002. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n = 41) radical cystectomy was carried out for a superficial bladder carcinoma which had a high likelihood of progressing. Group 2 (n = 57) consisted of patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n = 132) was made up of patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival and overall survival in the three groups were then compared. RESULTS: The average patient age when cystectomy was carried out was 63.9 (35-80) years and the average follow-up period was 38 months. An average of 2.3 (1-16) transurethral tumor resections were carried out before radical cystectomy (median = 1). Progression-free survival and overall survival of all 230 patients was 54 and 50%, respectively, after 5 years. The best result was a 74% progression-free 5-year survival rate with organ-confined lymph node-negative tumors (n = 106) which was statistically significant (p = 0.0004) compared to the progression-free 5-year survival rate of 50% for non-organ-confined, lymph node-negative tumors (n = 64). Lymph node-positive patients achieved a progression-free survival rate of 21% after 5 years regardless of the tumor infiltration. Patients in group 1 achieved a progression-free 5-year survival rate of 77% and an overall survival rate of 63% after 5 years. In group 2 patients achieved a progression-free survival rate of 51% after 5 years and an overall survival rate of 50%. In the case of primary muscle invasion (group 3), progression-free survival and overall survival were 49 and 46%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p > 0.35). However, both groups displayed a significantly poorer progression-free and overall survival rate compared with group 1 (p < 0.01). CONCLUSION: Our results show that superficial bladder carcinoma with tumor progress to muscle invasion does not have a better prognosis after radical cystectomy than initial muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out a cystectomy.