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PubMed1995

The use of digital image analysis of chromatin texture in Feulgen-stained nuclei to predict recurrence of low grade superficial transitional cell carcinoma of the bladder.

BACKGROUND: Identifying a marker enabling prediction of recurrence in the group of superficial transitional cell carcinomas (sTCCs) of the bladder remains an important challenge today. This report quantitatively describes chromatin patterns with respect to such sTCC recurrence. MATERIALS AND METHODS: Twenty-nine patients with sTCCs who did not exhibit tumor recurrence within a minimum of 24 months were compared with 21 patients with sTCCs who exhibited tumor recurrence two or three times in a 24-month period, for a total of 74 sTCCs. Quantitative chromatin pattern description was performed by the digital cell image analyses of Feulgen-stained nuclei. Six morphonuclear parameters were thus described and subsequently used to determine a score, allowing biological behavior of sTCCs to be described, i.e., recurrence versus non-recurrence in one calculation step. DNA ploidy level was also determined in each sTCC by assessing its DNA histogram type. RESULTS: Of 32 patients with Grade 1 pathologically classified pTa/pT1 tumors, DNA ploidy level determination permitted correct prediction of tumor nonrecurrence or recurrence of 13 (41%), whereas determination of the score values enabled prediction of nonrecurrence or recurrence of 25 (78%). Combining DNA ploidy level data and the score values enabled recurrence or nonrecurrence to be predicted for 29/32 of the patients (91%). CONCLUSIONS: The quantitative description of chromatin patterns by digital cell image analysis of Feulgen-stained nuclei can provide helpful information, in addition to DNA ploidy level determination, in predicting tumor recurrence of low grade superficial transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗

PubMed2002

Expression of E-cadherin in prostate cancer in formalin-fixed, paraffin-embedded tissues: correlation with pathological features.

AIMS: E-cadherin has been studied recently as a potential marker for tumour progression. The present study aimed to assess the expression of E-cadherin in formalin-fixed and paraffin-embedded radical prostatectomy specimens and to compare its expression with the pathological stage and Gleason score. METHODS: This study comprised a total of 58 men who were selected on the basis of the negative surgical margins of surgical specimens from radical retropubic prostatectomies and concomitant pelvic lymph node dissections. Indirect immunoperoxidase staining was performed as described previously using HECD-1 monoclonal antibody with the retrieval of antigen by treatment of the paraffin-embedded tissue with microwaves in citrate buffer. RESULTS: Aberrant staining patterns of E-cadherin were observed in 18 (64%) and in 25 (83%) of cases with pathological stages pT2 and pT3a, respectively (P>0.05). Immunohistochemical examination also revealed aberrant staining patterns of E-cadherin in 16 (89%) of specimens with Gleason score > or =7 and in 27 (68%) of specimens with Gleason score <7 (P>0.05). Biochemical recurrence was identified in three (5%) patients and immunohistochemical examination of their specimens revealed aberrant staining patterns of E-cadherin molecule in all of them. CONCLUSION: Our preliminary results indicate that, even though we could not demonstrate any significant correlation between E-cadherin staining pattern and tumour invasion and Gleason scores, aberrant staining patterns of E-cadherin may be a significant predictor for disease recurrence following radical prostatectomies if supported by large scale studies.

Adenocarcinoma↗

PubMed1997

New concepts in understanding evolution of desmoid tumors: MR imaging of 30 lesions.

The objective of this study was to evaluate the appearance and the natural evolution of desmoid tumors on MR imaging, given histologic correlation. The MR images of 30 desmoids (20 primary and 10 recurrent) in 26 patients were scored for a multiplicity of morphological parameters, signal intensity (SI) on different pulse sequences, and behavior after contrast administration. Natural evolution was evaluated in 2 primary and 3 recurrent lesions, and correlated with evolution on histologic specimens. Desmoid tumors are mostly found in muscles of shoulder and hip girdle and are often fusiform with partially ill-defined margins. Rare subcutaneous desmoids have a more stellar morphology. Variable amounts of low-SI areas are present on all sequences. On T1-weighted images (T1-WI), most lesions are near homogeneous and isointense to muscle, whereas on T2-WI they are more heterogeneous with an overall SI equal to or slightly lower than fat. Histologic correlation reveals that SI on T2-WI cannot be explained solely by cellularity. After initial growth, spontaneous evolution of desmoids is characterized by shrinking and an increase in low-SI areas on T2-WI. While distal lesions shrink, the more recent lesions in asynchronous multicentric desmoids have a tendency to develop proximally in the same limb, and should not be confused with recurrences. Fast growth, extracompartmental spread, and bone involvement are often seen in recurrences. Follow-up MR imaging of desmoids indicates natural regression of desmoids and more aggressive behavior of recurrences, which may justify a more conservative therapeutic approach.

Adolescent↗

PubMed1996

MIB-1 immunostaining and DNA flow cytometry in meningiomas.

The correlation between S- and G2/M-phase fractions and MIB-1 index in meningiomas was investigated. Flow cytometric analyses were performed on cell suspensions from 81 samples of paraffin-embedded tissue from 29 patients with a total of 28 meningiomas and 1 hemangiopericytoma using the modified Hedley's method. Sections from the paraffin-embedded tissues were stained with anti-MIB-1 monoclonal antibody after microwave oven processing. Five hundreds cells were scored. Correlations between data were estimated using linear regression. DNA aneuploidy was present in 4/29 tumors. Mean S- and G2/M-phase fractions in the 25 nonrecurrent tumors were 1.77 and 4.76%, and in the recurrent tumors were 2.41 and 5.81%, respectively. The proliferative index (PI = S + G2/M fraction) was 6.52% in the nonrecurrent tumors and 8.29% in the recurrent tumors. The mean MIB-1 score in the nonrecurrent tumors was 1.25% and in the recurrent tumors was 2.69%. There was a linear correlation between percentage of S-phase fraction or PI and the MIB-1 score. Both methods are useful to assess the proliferative activity in meningioma.

Antibodies, Monoclonal↗

PubMed2002

Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer.

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA < or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r(2)=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r(2) =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.

Aged↗

PubMed1989

Determinants of early recurrence of cerebral infarction. The Stroke Data Bank.

We studied 1,273 patients with ischemic cerebral infarction who were entered into the Stroke Data Bank, a prospective, observational study involving four university hospitals and the Biometry and Field Studies Branch of the National Institute of Neurological Disorders and Stroke. Forty patients had noniatrogenic recurrent stroke within 30 days after the index cerebral infarction. Using life tables, the 30-day cumulative +/- SE risk of early recurrence for all infarctions was 3.3 +/- 0.4%. The risk of early recurrence was greatest for atherothrombotic infarction (7.9 +/- 2.2%, eight of 113 patients) and least for lacunar infarction (2.2 +/- 1.2%, eight of 337 patients). Both cardioembolic infarction (4.3 +/- 0.9%, 10 of 246 patients) and infarction of undetermined cause (3.0 +/- 0.5%, 14 of 508 patients) had intermediate risks. History of hypertension and diabetes mellitus, as well as diastolic hypertension and elevated blood sugar concentration at admission, were associated with early recurrence. Logistic regression analysis estimated the risk of early recurrence to be 8.56% in those with coexisting hypertension and a glucose concentration of 300 mg/dl versus 0.77% in the absence of these two abnormalities. Early recurrence was associated with longer median duration of initial hospital stay (27 vs. 14 days) and a higher 30-day case-fatality rate (20% vs. 7.4%). Increased weakness scores were associated with early recurrent stroke. Identification of the determinants of early recurrent stroke may lead to better secondary prevention and may help select high-risk patients for further study.

Academic Medical Centers↗

PubMed2004

Role of cytokine gene polymorphism and hepatic transforming growth factor beta1 expression in recurrent hepatitis C after liver transplantation.

Recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT) is nearly universal. Cytokines play an important role in the immune response to viral infection, and cytokine gene polymorphism affects the overall expression and secretion of cytokines. The objective of this study was to define the relationship between cytokine polymorphism and recurrent hepatitis C after OLT. Blood samples were collected from 36 patients at a mean of 44.6+/-30.4 months after OLT for chronic HCV infection. DNA was extracted from peripheral blood mononuclear cells, and polymerase chain reaction-sequence specific primers (PCR-SSP) analysis was performed on promoter sequences of transforming growth factor beta1 (TGF-beta1), interleukin 6 (IL-6) interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). Liver biopsies performed at diagnosis of recurrent disease were graded with the Knodell score, and hepatic TGF-beta1 expression was determined semiquantitatively by immunohistochemistry. The gene polymorphism of TGF-beta1 was correlated with its expression on hepatocytes and sinusoids. Polymorphism in all studied cytokine genes was correlated with recurrence, and interval to recurrence (>12 or < or =12 months post-OLT), and clinical (ascites, Child-Pugh score and death), biochemical parameters of recurrent HCV (serum alanine aminotransferase (ALT)), INR, albumin, bilirubin), and virological parameters (HCV genotype and load). Biopsies revealed recurrent HCV in 31 patients (86.1%); in 21 (67.7%), the interval to recurrence was 12 months. There was a statistically significant correlation between TGF-beta1 gene polymorphism, i.e., the genetic ability to produce high levels of TGF-beta1, and the intensity of TGF-beta1 staining on hepatocytes (p=0.003) and sinusoids (p=0.003), and the degree of fibrosis (p=0.02). A borderline correlation was found with the presence of ascites (p=0.007), but not with Child-Pugh score, synthetic liver function tests or HCV genotype and load. The genetic ability to produce low levels of IFN-gamma was correlated with recurrent disease (p=0.015). No such correlation was found for TGF-beta1 gene polymorphism. In conclusion, polymorphism in the TGF-beta1 gene correlates with its in situ hepatic expression in patients with recurrent HCV after liver transplantation. INF-gamma, but not TGF-beta1 gene polymorphism, correlates with early recurrent hepatitis C after transplantation. These findings might help to design preemptive prevention therapy in selected patients at risk.

Cohort Studies↗

PubMed2006

Characterization of ZAG protein expression in prostate cancer using a semi-automated microscope system.

OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is known to stimulate lipid degradation in adipocytes. The aim of this study was to determine how ZAG protein expression is associated with prostate cancer (PCa). MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227 PCa tissue microarray cases. ZAG protein expression was assessed using a semi-automated cellular image analysis system. RESULTS: ZAG expression was associated with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely associated with Gleason score on pathology (P = 0.01). ZAG intensity was predictive of biochemical recurrence (P = 0.002). On multivariate analysis including pT2 patients, the predictive factors of biochemical recurrence were ZAG expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa using a semi-automated system. ZAG expression level found to have an independent prognostic value for pT2 patients.

Adipokines↗

PubMed1993

Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer.

The ultimate goal of prognostic assessment is optimization of individual counseling. Often, however, studies on prognostic factors focus on discriminating between high risk and low risk subgroups without considering the relevance of 1 or more factors for predicting disease outcome in individual patients. We quantified the accuracy of prediction of future recurrences and disease progression in individual patients with primary superficial bladder cancer. The study cohort consisted of 1,674 patients who were followed prospectively between 1983 and 1991 in the Netherlands. By analyzing half of the patients with proportional hazards regression, we computed relative risks of recurrence and progression. A prognostic index score based on these relative risks was then applied to the other half of the patients to determine whether group outcome could be predicted accurately. To assess the accuracy of prediction in individuals we used a method similar to the construction of receiver operating characteristic curves in diagnostic test assessment. The 3-year risk of first recurrence was 55% (95% confidence interval 51 to 59%). The 3-year risk of first progressive disease was 10% (95% confidence interval 8 to 12%). For the risk of first recurrence, tumor stage, tumor extent and multicentricity had statistically significant prognostic ability. Prognostic factors for the risk of disease progression were tumor stage, grade, multicentricity and the result of random biopsies from cystoscopically normal-appearing urothelium. For patients with a prognostic index score that suggested a low risk for recurrent and progressive disease the predicted 3-year risk of first recurrence was still 44% but the predicted 3-year risk of progression was only 3%. For patients with a prognostic index score that suggested a high risk the predicted risks were 74% and 22%, respectively. These predicted risks appeared to be fairly accurate when applied to the other half of our case series. However, in any 2 patients chosen at random the chance that the patient with the worst predicted prognosis would have a shorter recurrence-free and progression-free followup was calculated to be only 58% and 67%, respectively. Although the available prognostic factors in superficial bladder cancer may be useful to identify high risk and low risk subgroups, predictability in individuals is highly inaccurate. More relevant prognostic factors are needed to decrease current overtreatment and undertreatment rates, and to improve the followup policy.

Adult↗

PubMed2002

Scores for post-myocardial infarction risk stratification in the community.

BACKGROUND: Several scores, most of which were derived from clinical trials, have been proposed for stratifying risk after myocardial infarctions (MIs). Little is known about their generalizability to the community, their respective advantages, and whether the ejection fraction (EF) adds prognostic information to the scores. The purpose of this study is to evaluate the Thrombolysis in Myocardial Infarction (TIMI) and Predicting Risk of Death in Cardiac Disease Tool (PREDICT) scores in a geographically defined MI cohort and determine the incremental value of EF for risk stratification. METHODS AND RESULTS: MIs occurring in Olmsted County were validated with the use of standardized criteria and stratified with the ECG into ST-segment elevation (STEMI) and non-ST-segment elevation (NSTEMI) MI. Logistic regression examined the discriminant accuracy of the TIMI and PREDICT scores to predict death and recurrent MI and assessed the incremental value of the EF. After 6.3+/-4.7 years, survival was similar for the 562 STEMIs and 717 NSTEMIs. The discriminant accuracy of the TIMI score was good in STEMI but only fair in NSTEMI. Across time and end points, irrespective of reperfusion therapy, the discriminant accuracy of the PREDICT score was consistently superior to that of the TIMI scores, largely because PREDICT includes comorbidity; EF provided incremental information over that provided by the scores and comorbidity. CONCLUSION: In the community, comorbidity and EF convey important prognostic information and should be included in approaches for stratifying risk after MI.

Aged↗

PubMed2005

Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo.

BACKGROUND: Intranasal corticosteroids used with antibiotics are known to improve rhinosinusitis symptoms compared with antibiotic therapy alone. However, the efficacy of intranasal corticosteroid monotherapy for acute, uncomplicated rhinosinusitis is not established. OBJECTIVES: To evaluate efficacy and safety of mometasone furoate nasal spray (MFNS) versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis. METHODS: In this double-blind, double-dummy trial, subjects (> or =12 years; N = 981) were randomized to MFNS 200 microg once daily or twice daily for 15 days, amoxicillin 500 mg 3 times daily for 10 days, or respective placebo. Follow-up was 14 days. The primary efficacy endpoint was mean am/pm major symptom score over the treatment phase. Secondary efficacy endpoints included total symptom score. Safety assessments included disease recurrence during follow-up and adverse event monitoring. RESULTS: Mometasone furoate nasal spray 200 microg twice daily was significantly superior to placebo (P < .001) and amoxicillin (P = .002) at improving major symptom score. Starting on day 2, MFNS 200 microg twice daily improved total symptom score throughout treatment versus amoxicillin (P = .012) and placebo (P < .001). Global response to treatment was significantly greater with MFNS 200 microg twice daily versus amoxicillin (P = .013) and placebo (P = .001). Although significantly superior to placebo, MFNS 200 microg once daily was not superior to amoxicillin for the primary or secondary efficacy endpoints. All treatments were well tolerated with a similar incidence of adverse events. CONCLUSION: In patients with acute, uncomplicated rhinosinusitis, MFNS 200 microg twice daily produced significant symptom improvements versus amoxicillin and placebo, without predisposing the patient to disease recurrence or bacterial infection.

Acute Disease↗

PubMed2005

Reirradiation alternating with docetaxel and cisplatin in inoperable recurrence of head-and-neck cancer: a prospective phase I/II trial.

PURPOSE: Inoperable locoregional recurrences of head-and-neck cancer in a previously irradiated volume represent a therapeutic dilemma. Chemotherapy alone has no curative potential, whereas reirradiation and concurrent chemoradiation can salvage a small fraction of patients. Mucosal toxicity of concurrent chemoradiation requires substantial dose reduction of chemotherapy. Alternating chemoradiation offers the chance to give both full-dose chemotherapy and radiotherapy. The latter may provide a particular advantage for recurrent, potentially radiation resistant tumors. The feasibility and efficacy of a full-dose docetaxel containing alternating chemoradiation schedule was tested. PATIENTS AND METHODS: Twenty-seven patients (Karnofsky performance status score >/=70%) with histologically proven recurrent squamous cell cancer that occurred >/= 6 months in a previously irradiated area (>/= 60 Gy) were considered unresectable and unsuitable for brachytherapy. Alternating chemoradiation consisted of 3 cycles of docetaxel 60 mg/m(2) d1 and cisplatin 15 mg/m(2) d2-5, q d22, and involved field radiotherapy 2.0 Gy every day d8-12, d15-19, d29-33, and d36-40 (40.0 Gy total dose). Dose reduction of docetaxel to 50 mg/m(2) was necessary, because of hematologic toxicity in the first 12 patients. RESULTS: Alternating chemoreirradiation was applied as planned in 12 of 27 patients, with reirradiation completed per protocol in 81%. Overall, patients received 83% of the intended dose of docetaxel and 73% of cisplatin. Third-degree common toxicity criteria mucositis occurred in 15%, leukopenia of >/= third degree by common toxicity criteria in 37%, and 3 early deaths were observed. Median time to follow-up, time to local progression, median survival, and 3-year survival rates were 42 months, 10 months, 10 months, and 18%, respectively. CONCLUSIONS: Alternating chemoreirradiation in recurrences of head-and-neck cancer resulted in 80% overall response with acceptable toxicity. A significant minority of patients had durable tumor control with a chance of long-term survival.

Adult↗

PubMed1999

The development of a prognostic score for patients with parotid carcinoma.

BACKGROUND: Understanding of prognostic factors in parotid carcinoma has grown considerably. In particular, clinical tumor staging and histologic classification have been found to be prognostically important. Univariate and multivariate analyses have indicated that other variables, such as age, pain, skin invasion, and facial nerve impairment, are important predictors as well. In an actual patient, some of these factors are present and others are absent. However, a clinical tool incorporating this information, resulting in an individualized prognosis based on the combined effects of present adverse prognostic factors, has never been devised. METHODS: Of a cohort of 168 patients, 151 were evaluated to assess the prognostic value of clinical and pathologic factors in a multivariate proportional hazards analysis. Follow-up ranged from 1 to 278 months (median, 37 months). The end point was tumor recurrence. Identified prognostic factors and their hazard ratios were combined into prognostic scores. RESULTS: Clinical T classification, clinical N classification, pain, age at diagnosis, skin invasion, facial nerve dysfunction, perineural growth, and positive surgical margins acted as major factors predicting recurrence. A prognostic score (PS), generated by the weighted combination of the factors present in the individual patient, placed the patient in one of four subgroups with markedly different prognoses. In the subgroups based on the preoperative prognostic score, 5-year recurrence free percentages ranged from 92% (in the group PS1=1) to 23% (in PS1=4). In the subgroups based on the postoperative prognostic score, which took into account the histologic details of the resected specimen, 5-year recurrence free percentages ranged from 95% (in the group PS2=1) to 42% (in PS2=4). CONCLUSIONS: The proposed subgrouping, which is based on the combined effects of key prognostic preoperative and postoperative factors, provides a practical prognostic grouping system for the clinician treating patients with parotid carcinoma.

Adolescent↗

PubMed1997

Disease recurrence and progression in untreated pathologic stage T3 prostate cancer: selecting the patient for adjuvant therapy.

PURPOSE: Optimal management of pathologic T3 prostate cancer is poorly defined. We conducted a prospective study of untreated pT3 patients to improve understanding of the natural history of this disease and to identify clinical parameters useful in patient selection for adjuvant therapy. MATERIALS AND METHODS: Of 583 consecutive patients with clinical stage T1 to 2 disease managed by total prostatectomy, 206 had pT3 disease. Excluding patients requesting immediate adjuvant treatment or neoadjuvant therapy, 156 subjects were eligible for the study, including 34 with pT3a, 80 pT3b, 22 pT3c, and 20 pT3N+ disease. Patients were followed for prostate-specific antigen (PSA) recurrence of greater than 0.2 ng./ml. and biopsy proved local or distant tumor progression demonstrated by imaging studies. RESULTS: After a median of 45 months, PSA recurrence was seen in 29.4% of pT3a (10/34), 30% of pT3b (24/80), 27.3% of pT3c (6/22), and 80% of pT3N+ (16/20 cases). Local or distant progression was seen in 2.9% of pT3a (1), 6.2% of pT3b (5), 9.1% of pT3c (2), and 55% of pT3N+ (11 cases). Recurrence and progression correlated with the number of surgical margins involved by tumor, pathological Gleason score and baseline pre-prostatectomy PSA levels. PSA recurrence was seen in 20.8% (10/48) patients with 1 surgical margin involved, 40.9% (9/22) with 2 margins involved and 50% (5/10) with 3 or more margins involved. PSA recurrence was 20.3% (14/69) with Gleason scores of less than 7, 33.9% (19/56) with a score of 7 and 74.2% (23/31) with scores of greater than 7. Pre-prostatectomy PSA levels less than 10 ng./ml. were associated with a PSA recurrence of 17.3% (14/81) and 45.4% (25/55), with levels greater than 10 ng./ml. Selecting patients for high or low risk based upon the results of these parameters allowed accurate prediction of PSA recurrence; 8.5% (4/47) for low risk patients and 44.8% (30/67) for high risk. Tumor progression was seen in no low risk patient and in 9% (6) with high risk. The difference between the 2 risk groups was highly significant (p <0.0001). CONCLUSIONS: The majority of patients with pT3 prostate cancer will not experience recurrent disease for many years if ever. Immediate use of adjuvant treatment should be reserved for those patients with a high risk of recurrent disease.

Disease Progression↗

PubMed2004

Validation of the Kattan preoperative nomogram for prostate cancer recurrence using a community based cohort: results from cancer of the prostate strategic urological research endeavor (capsure).

PURPOSE: The Kattan preoperative nomogram combines preoperative prostate specific antigen (PSA), biopsy Gleason grade and clinical stage to estimate disease recurrence after radical prostatectomy. Several studies using patient data from academic centers have validated the nomogram. We assessed the performance of the Kattan nomogram using the Cancer of the Prostate Strategic Urological Research Endeavor database, a national, largely community based observational disease registry. MATERIALS AND METHODS: From the Cancer of the Prostate Strategic Urological Research Endeavor database we identified 1701 men with clinically localized prostate cancer undergoing radical prostatectomy with sufficient pretreatment information and PSA followup after surgery. Disease recurrence was defined as 2 consecutive PSA values 0.2 ng/ml or greater, or a second cancer treatment more than 6 months after prostatectomy. A concordance index was used to evaluate the performance of the nomogram compared to observed 5-year recurrence-free survival (Kaplan-Meier). Kattan nomogram scores were calculated for each patient and stratified into 6 groups for analysis. RESULTS: In our cohort of 1701 men 413 (24%) had evidence of disease recurrence. Median followup in these patients was 2.3 years. Kattan nomogram scores were 17% to 99% (mean 79%). The overall concordance index was 0.68. Varying the definition of recurrent disease and excluding patients with imputed data did not substantially alter nomogram performance (concordance index 0.65 to 0.70). The Kattan nomogram tended to overestimate 5-year freedom from recurrence in patients with scores of 65% and higher. CONCLUSIONS: We noted the reasonable performance of the Kattan nomogram for predicting cancer outcomes after radical prostatectomy using a community based population. Although concordance is lower than in previous validation studies and the nomogram overestimates recurrence-free survival in patients at lower risk, the model is fairly robust and it provides important information when counseling patients regarding treatment options in the community setting. Further refinements in pretreatment estimation of disease-free survival and ultimately overall survival are needed.

Cohort Studies↗

PubMed2006

[Long-term follow-up results of synovectomy for rheumatoid knee].

OBJECTIVE: To continuously observe the long-term effects of synovectomy for improving joint damage and quality-of-life in patients with the rheumatoid knee. METHODS: Twenty-one consecutive patients with rheumatoid arthritis (RA) involving 24 knees underwent open synovectomy from November 1988 to January 1997 between November 1988 and January 1997. The changes in radiographic damage were assessed with Larsen score on plain films before and 6 months after surgery with subsequent annual assessment for 8 years, and the functional recovery of the patients was also evaluated with Health Assessment Questionnaire (HAQ) at the same time. RESULTS: The radiographic joint damage and juxta-articular osteoporosis or bone erosion was ameliorated after surgery in all the patients. Larsen score began to decrease 6 months after the operation, and the best effects were achieved at one year and maintained for at least 5 years after the operation, but then followed by recurrence of joint lesions. HAQ scores were improved after the surgery with the best effects observed 6 months after the operation lasting for over 2 years. HAQ score gradually decreased 4 years after the operation till reaching the preoperative scores. CONCLUSION: Synovectomy in the patients with rheumatoid knee not only reverses progressive joint damage, but also improves juxta-articular bone erosions and the patients' quality of life. However, radiographic joint damage and functional deterioration may recur due to hyperplasia of the inflammatory synovium in the long term after operation, suggesting that the inflammatory synovium participates in local joint damage with bone erosions and systemic pathologic process of RA.

Adult↗

PubMed2002

Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study.

PURPOSE: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new-onset seizures. METHODS: Subjects were 224 children with new-onset seizures (aged 4-14 years) and 159 siblings (4-18 years). Caregiver's ratings of the behavior were collected 4 times: at baseline, and at 6, 12, and 24 months. During the 2-year period, 163 (73%) children had at least one additional seizure, and 61 (27%) had none. Data were analyzed by using repeated measures analysis of variance both with and without covariates [site, age, gender, race, caregiver education (years), and seizure medications]. RESULTS: On average, children had higher CBCL Total and Internalizing Behavior Problems scores across all times when experiencing recurrent seizures than when not experiencing recurrent seizures (Total Problems, p = 0.041, controlling for demographics and seizure medications). Siblings had significantly lower Total and Internalizing Problems scores than both children experiencing (Total Problems adjusting for covariates, p = 0.0001) and not experiencing recurrent seizures (p = 0.0004). Externalizing Problems scores were not significantly different among children with recurring seizures, children without recurring seizures, and siblings. CONCLUSIONS: Recurrent seizures significantly predicted behavior problems very early in the course of a seizure condition, even when key child, demographic, and seizure variables were controlled. Explanations for these findings include the possibilities that both seizures and behavior problems are caused by an underlying neurological disorder, that seizures per se disrupt behavior, or that children have negative psychological responses to seizure activity.

Adolescent↗

PubMed2005

Controlled, randomized trial of island flap anoplasty for treatment of trans-sphincteric fistula-in-ano: early results.

Treatment of trans-sphincteric fistula is usually a compromise between recurrence and incontinence. Dermal island flap anoplasty has been found to be useful in the treatment of these fistulas. We performed a randomized trial to compare dermal island flap anoplasty with conventional treatment for trans-sphincteric fistula-in-ano. Seventy nine patients with fistula-in-ano were recruited; twenty patients with trans-sphincteric fistula confirmed by endoanal ultrasound were prospectively randomized to receive either dermal island flap anoplasty (IFA) or conventional treatment (CVN) for trans-sphincteric fistula-inano. Conventional treatment consisted of lay open fistulotomy or seton insertion if deemed unsuitable for fistulotomy. Dermal island flap anoplasty involved a cutaneous advancement flap into the rectum. Pain scores, fecal incontinence scores, operative complications, wound healing and recurrence rates were charted. Two patients in the CVN group required seton insertions, which were still intact at the 9-month follow-up. Two patients with similar high trans-sphincteric fistula in the IFA group avoided having a long-term seton. There were no differences in the postoperative pain score, incontinence score, complications, wound healing and recurrence rates between the two groups. IFA is a safe and useful method for treating transsphincteric fistula. It can be considered when a suprasphincteric extension is suspected, thus avoiding risk of incontinence or the discomfort of a long-term seton.

Adult↗