Independent Predictor Of Better Survival Research Articles

Survival Benefit of Aortic Valve Replacement in Patients With Severe Aortic Regurgitation and Pulmonary Hypertension

Severe pulmonary hypertension occurs in approximately 10% of patients with severe aortic regurgitation (AR). The potential survival benefit of aortic valve replacement (AVR) in these patients is not known, and was analyzed in a large cohort of patients. Our echocardiographic data was screened for severe AR patients with severe pulmonary hypertension defined as pulmonary artery systolic pressure of 60 mm Hg or greater. Chart reviews were performed for clinical, pharmacologic, and surgical details, and survival data were analyzed as a function of AVR. Of the 506 patients with severe AR and measurable pulmonary artery pressures by echocardiography, 83 had severe pulmonary hypertension defined as a pulmonary artery systolic pressure of 60 mm Hg or greater. Severe pulmonary hypertension was associated with lower left ventricular ejection fraction (47% +/- 22% versus 53% +/- 19%, p = 0.006), larger left ventricular size (p = 0.03), and higher grades of mitral regurgitation (2.7 +/- 1.2 versus 1.7 +/- 1.1, p < 0.0001). Of the 83 patients with severe pulmonary hypertension, 32 underwent AVR, which was associated with better survival compared with patients who did not (1-year survival 90% versus 58% and 5-year survival 62% versus 22%, respectively; p = 0.004). After adjusting for comorbidities, AVR remained an independent predictor of better survival (hazard ratio 0.45, 95% confidence interval: 0.22 to 0.92, p = 0.03). This survival benefit of AVR was further supported by propensity score analysis. Severe pulmonary hypertension occurs in approximately 16% of patients with severe AR and is associated with left ventricular enlargement with dysfunction and resultant mitral regurgitation. Aortic valve replacement is associated with an independent survival benefit in these patients.

Effect of Beta-Blocker Therapy on Survival in Patients With Severe Aortic Regurgitation: Results From a Cohort of 756 Patients

We sought to investigate the effect of beta-blocker (BB) therapy on survival in patients with severe aortic regurgitation (AR). Beta-blockers are thought to be contraindicated in patients with AR because a slower heart rate increases the duration of diastole during which AR occurs. But AR also causes neuroendocrine activation similar to a heart failure state for which BBs are potentially beneficial. This is an observational study. Our echocardiographic database was screened for patients with severe AR. Detailed chart reviews were performed for clinical, demographic, and therapeutic data. Mortality data were obtained from the Social Security Death Index and analyzed as a function of BB therapy. Three hundred fifty-five (47%) of the 756 patients with severe AR were on a BB; mean age 61 +/- 18 years and ejection fraction was 54 +/- 19%. Over a mean follow-up of 4.5 years, BB therapy was associated with a higher survival rate (1- and 5-year survival rates of 90% and 70%, respectively) compared with those without (1- and 5-year survival rates of 75% and 55%, respectively) (p = 0.0009). The Cox regression model showed that BB therapy was an independent predictor of better survival after adjusting for age, sex, heart rate, hypertension, coronary artery disease, diabetes mellitus, heart failure, renal insufficiency, ejection fraction, and aortic valve replacement (hazard ratio: 0.74, 95% confidence interval: 0.58 to 0.93, p = 0.01). The survival benefit of BB therapy was further supported by propensity score analysis. This observational study strongly suggests that BB therapy is associated with a survival benefit in patients with severe AR.

The prognostic impact of NF-κB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer

Vimentin, nuclear factor-κB (NF-κB) p105, fascin, E-cadherin, TGF-β, Par6 and atypical PKC are molecular markers that play an important role in cell differentiation. Herein, we investigate their prognostic impact in primary non-small-cell carcinoma (NSCLC). Tumour tissue samples from 335 resected patients with stage I–IIIA were used. Tissue microarrays were constructed from duplicate cores of both neoplastic cells and stromal cells and were immunohistochemically evaluated. In univariate analyses, high tumour epithelial cell expressions of NF-κB p105 (P=0.02) and E-cadherin (P=0.03) were positive prognostic indicators for disease-specific survival (DSS), whereas high tumour epithelial cell expression of vimentin (P=0.001) was a negative prognostic indicator. High expression of NF-κB p105 (P=0.001) and Par6 (P=0.0001) in the stromal compartment correlated with a good prognosis. In multivariate analyses, the tumour epithelial cell expression of NF-κB p105 (P=0.0001) and vimentin (P=0.005) and the stromal cell expression of NF-κB p105 (P=0.007) and Par6 (P=0.0001) were independent prognostic factors for DSS. High expression of NF-κB p105 and low expression of vimentin in tumour epithelial cells are independent predictors of better survival in primary NSCLC. In stromal cells, high expressions of NF-κB p105 and Par6 are both favourable independent prognostic indicators.

Differences in Long-Term Survival in Two Lacunar Stroke Types: A 15-Year Follow-Up Study in 782 Cerebral Infarct Patients

Background: Mortality studies in lacunar (LAC) stroke are scarce and often characterized by short follow-up time, small patient groups and absence of a nonlacunar stroke group for comparison. Besides, there are no separate long-term prognostic data on LAC stroke subtypes. We performed a long-term mortality study in LAC stroke, subtyping two distinct phenotypes and including nonlacunar ischemic stroke for comparison. Methods: We performedcross-sectional follow-up, determining survival status, after a median of 15.0 years, in 333 first-ever atherothrombotic (AT), 184 cardioembolic (CE) and 265 LAC strokes, distinguishing LAC stroke with (type 2) or without (type 1) asymptomatic LAC lesions on CT. Results: End of follow-up mortality (in 30-day survivors) in LAC stroke (76.2%) was significantly lower than in CE (87.1%; OR 0.48, 95% CI 0.27–0.84), but not AT strokes (79.0%; OR 0.85, 95% CI 0.57–1.26), and was significantly lower in LAC type 1 than type 2 strokes (70.9 vs. 87.5%; OR 0.35, 95% CI 0.17–0.73). Kaplan-Meier analysis showed most favorable survival in LAC type 1 stroke. In the Cox regression analyses, LAC type 1 strokeappearedas an independent predictor of better survival versus LAC type 2, versus AT and versus CE strokes. Conclusions: LAC stroke in general cannot be considered a ‘benign’ stroke type: only long-term survival in patients without concomitant asymptomatic LAC lesions is better than in large-vessel stroke. This difference in long-term survival between the two LAC stroke subtypes should be taken into account in prognostic counselling of individual LAC stroke patients.

Predictive value of chemotherapy-induced neutropenia for drug efficacy in advanced gastric carcinoma: Analysis of prospective nationwide survey

15075 Background: Myelosuppression that occurs during chemotherapy has been reported to be a predictor of better survival in patients with breast or lung carcinomas. We evaluated the prognostic implications of chemotherapy-induced neutropenia in advanced gastric cancer. Methods: Data obtained from a prospective nationwide survey of oral fluoropyrimidine S-1, performed in Japan between 1999 and 2000, were reviewed. Advanced gastric cancer patients with both adequate bone marrow function and no prior history of chemotherapy within 6 months before starting S-1 therapy were analyzed (N=1055). Chemotherapy-induced neutropenia was treated as a time-dependent covariate, and the hazard ratios [HRs] of death for experiencing neutropenia, compared with no such toxicity, were estimated using Cox regression model. Results: During treatment with S-1, a total of 293 (28%) patients had grade 1 or higher neutropenia. The adjusted HRs from a multivariate Cox model were 0.72 for patients with grade 1 neutropenia (95% confidence interval [CI] 0.54–0.95; P=0.0189), 0.63 for those with grade 2 neutropenia (95% CI 0.50–0.78; P&lt;0.0001), and 0.71 for those with grade 3–4 neutropenia (95% CI 0.51–0.98; P=0.0388). Conclusions: The results of this study suggest that occurrence of neutropenia during chemotherapy is an independent predictor of better survival for advanced gastric cancer, while the absence of such toxicity indicates that the dosages of drugs are pharmacologically inadequate. Monitoring of neutropenia in patients who receive chemotherapy may contribute to improved drug efficacy and patient survival. No significant financial relationships to disclose.

The Ross Operation — An Evolutionary Tale

The Ross operation has many unique and intricate features, which need to be defi ned and understood if the operation is to achieve its potential. Although the operation was described nearly 35 years ago, it has continued to evolve through gradual understanding of the complex but elegant anatomic and physiological processes involved in execution of the operation as well as adaptation of the pulmonary valve to its new environment, coupled with the application of sophisticated methods of analysing the results of the operation. All of this has resulted in the accumulation of a large amount of knowledge, which strongly suggests that this operation could have an important, unique and wider role to play in the fi eld of valve surgery provided that certain details are adhered to. Some of this knowledge is reviewed in this editorial. Detailed studies of the form and function of the normal aortic valve have shown that this valve performs extremely sophisticated functions which depend largely on the biological properties of the valve at cellular and molecular level 1-4 and are critically dependent on continued viability of the valve. The Ross operation is the only form of valve replacement which guarantees viability of the valve substitute both in the short and long term. We theorise that this should translate into clinical benefi t both in terms of survival and quality of life. Recent studies using microsimulation to compare the pattern of survival of the Ross operation to the general population, have shown similar pattern of survival in the two groups which is signifi cantly better than that observed after aortic valve replacement using other types of substitutes. 5 Excellent postoperative survival after the Ross operation have been described by several authors 6,7 including the article published in the “journal”. 8 Although it could be argued that these fi ndings are due to patient selection, many of the reported series have included a signifi cant number of high-risk patients such as those with active infective endocarditis or redo operations. Furthermore a prospective randomised trial to compare the Ross operation to homograft has shown enhanced survival after the Ross operation 9 confi rming the notion that continued viability of the valve can translate into major clinical benefi t. Further larger prospective randomised trials, possibly multi centre are needed to confi rm or refute these potentially important preliminary observations. Other aspects of the Ross operation which has evolved concern major technical modifi cations and refi nements of the technique of explantation and insertion of the pulmonary autograft to minimise coronary and myocardial injury during explantation and attempt to eliminate the incidence of late dilatation of the autograft while avoiding the use of any foreign prosthetic material such as Tefl on or Dacron strips which could defeat the purpose of the operation. The original Ross operation involved insertion of the autologous pulmonary valve in the subcoronary position using two suture lines. This technique has the theoretical advantage of retaining normal aortic wall around the autograft which is thought to prevent progressive dilatation of the autograft root. This technique however has the potential of distorting the autograft. Although valves inserted by this technique can last for periods of up to 35 years, 10 we have observed calcifi cation in one of the cusps of the autograft which had to be due to abnormal movements of the cusps secondary to distortion. The technique of full aortic (or pulmonary) root replacement was originally introduced to maintain the exact relationship of the semilunar valve mechanism 11 and have been shown to be an independent predictor of better survival and less degeneration following aortic homograft valve replacement. 12 If that technique is used however, we believe that it is essential to use multiple interrupted sutures for the lower suture line with scalloping of the autograft to allow the hinge mechanism to be supported by the native aortic annulus. Another evolutionary point in the Ross operation is the inherent capacity to adapt to the new environment by altering its structure and physical properties. 13 This however, does not occur immediately after the operation and therefore the newly implanted autograft root should not be subjected to pressure higher than 110/80 which could predispose to progressive root dilatation and/or chronic dissection of the arterial wall of the pulmonary autograft root.

Is Hypercapnea a Predictor of Better Survival in the Patients who Underwent Mechanical Ventilation for Chronic Obstructive Pulmonary Disease (COPD)?

BackgroundThere are contradictory reports concerning hypercapnia as a predictor of a better outcome in COPD. This study examined the clinical implications of hypercapnea in COPD patients (M:F = 59:19) who required mechanical ventilation.MethodsThe clinical parameters at the time of MICU admission, the total ventilation time, the APACHE II score and the pulmonary function testing were retrospectively analyzed between the survivors and nonsurvivors.ResultsUnivariate analysis showed that compared with the nonsurvivors, the survivors had lower AaDO2 values (59.8±53.5 vs. 105.0±73.3 mmHg, p=0.000), higher PaCO2 values (64.9±16.0 vs. 48.9±17.8 mmHg, p=0.000), lower APACHE II scores (19.0±3.8 vs. 24.1±5.1, p=0.002), the more frequent application of initial noninvasive positive pressure ventilation (44.0 vs. 14.3%, p=0.008), and a lower combined rate of septic shock (4.0 vs. 39.3%, p=0.000). Multivariate analysis revealed that a lower PaCO2 (OR: 0.94, p=0.008), the presence of septic shock (OR: 10.16, p=0.011), a higher APACHE II score (OR: 1.22, p=0.040) and a longer ventilation time (OR: 1.002, p=0.041) were the risk factors for mortality. A lower PaCO2 was also verified as the predictor for mortality by multivariate analysis when excluding septic shock.ConclusionsHypercapnia at admission is thought to be an independent predictor of better survival for the COPD patients who require mechanical ventilation.

Tumour CEA as predictor of better outcome in squamous cell carcinoma of the lung

High levels of serum carcinoembryonic antigen (S-CEA) are considered a negative prognostic factor in non-small-cell lung cancer (NSCLC), while the prognostic value of tumour CEA (T-CEA) is unknown. We investigated the prognostic role of T-CEA in radically resected early stage NSCLC. We measured preoperative S-CEA levels and T-CEA in 146 patients with stage 1-2 NSCLC, and analysed their influence on survival. In patients positive for T-CEA, 3-year survival was 80%, compared to 65% in T-CEA-negative patients (p=0.03). After stratification by histology, T-CEA positivity was prognostic of better survival in squamous cell carcinoma (SCC) (p=0.024) but not in adenocarcinomas (ADK) (p=0.87). Multiple Cox regression analysis showed that T-CEA positivity was an independent predictor of better survival in patients with early stage NSCLC (p=0.02). In SCC patients, the magnitude of the hazard ratio was confirmed even if the precision of the estimate is decreased (p=0.06). In conclusion, T-CEA expression appears to be an important prognostic factor in early stage SSC of the lung.

Human papillomavirus-31-related types predict better survival in cervical carcinoma.

The aim of the current study was to explore the clinical implications and prognostic value of human papillomavirus (HPV) genotype in cervical carcinomas. A total of 152 patients diagnosed with International Federation of Gynecology and Obstetrics Stage I-IV cervical carcinoma were studied between 1992-1999. HPV DNA status was assessed from paraffin-embedded, formaldehyde-fixed cervical carcinoma specimens by polymerase chain reaction-based methods using E7 type-specific and L1 modified general primers (MY11/GP6+ and GP5+/GP6+). The authors divided the patients into four groups: HPV-16-related, HPV-18-related, HPV-31-related, and HPV-58-related types. The relations with clinicopathologic data and overall survival were evaluated. HPV DNA was detected in 98% of the tumor specimens and 28.9% of the tumor specimens contained multiple HPV types. The HPV-16-related types were detected more often in squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in adenocarcinomas and adenosquamous carcinomas. In addition, Stage I-II diseases were found more frequently in the HPV-16-related group than in the other groups (P = 0.001). Otherwise, no significant correlation between the HPV genotype and other clinicopathologic parameters was found. After a median follow-up of 64.5 months, the 5-year survival rate was 92% in the HPV-31-related group compared with 70% in the HPV-16-related group, 69% in the HPV-18-related group, and 36% in the HPV-58-related group. The survival rates statistically differed among the four groups by log-rank test (P = 0.02). However, the presence of multiple HPV types was not associated with prognosis. After stratifying for clinical stage, multivariate analysis demonstrated that HPV genotype was an independent prognostic factor. Compared with the HPV-16-related group, the long-term mortality rate was 73 % lower in the HPV-31-related group (relative risk, 0.27; 95% confidence interval, 0.09-0.76; P = 0.013). The presence of HPV-31-related types was an independent predictor of better survival in patients with cervical carcinoma. Therefore, HPV genotyping of cervical carcinomas may have profound implications for future patient management.

Prognostic significance of thyroid transcription factor-1 expression in both early-stage conventional adenocarcinoma and bronchioloalveolar carcinoma of the lung

Thyroid transcription factor 1 (TTF-1) is a diagnostic immunohistochemical marker for primary pulmonary neoplasms, but its utility as a prognostic marker is not well established. Surgical specimens from 100 cases of pulmonary adenocarcinoma were retrieved from the hospital computer system, including 50 cases of conventional adenocarcinoma (CA) and 50 cases of bronchioloalveolar adenocarcinoma (BAC) (32 nonmucinous type and 18 mucinous type). Representative sections were immunostained for TTF-1. Positive immunohistochemical study was correlated with other prognostic parameters. In the CA group, strong or moderate TTF-1 expression was seen in 30 of 50 (60%) patients and was associated with significantly better survival compared with those patients having weak staining (7 cases; 14%) or negative staining (13 cases; 26%) ( P <0.01; log-rank test). Spearman and Pearson’s correlation showed no significant correlation between TTF-1 expression and tumor grade, size, recurrence, or vascular invasion; therefore, TTF-1 was considered an independent predictor of survival. In the BAC group, TTF-1 was strongly expressed in 34 of 50 cases (68%) and was negative in 16 of 50 cases (32%), including 14 mucinous BACs. Although TTF-1 immunoreactivity was not statistically associated with good survival in BAC patients, those patients with strong immunohistochemical expression showed a trend toward longer survival. Our results indicate that TTF-1 positivity is an independent predictor of better survival, especially in patients with CA. Mucinous and nonmucinous BACs exhibit disparate staining patterns with TTF-1, with nonmucinous BAC demonstrating greater positivity. Although nonmucinous BAC patients showing strong positive staining had longer survival, the difference was not statistically significant, which is probably related to the overall good survival of patients with early-stage BAC.

Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non-small cell lung cancer: strong thyroid transcription factor-1 expression predicts better survival.

The relationship of thyroid transcription factor-1 (TTF-1) and HER2/neu expression in non-small cell lung cancer (NSCLC) with multiple parameters including survival were examined. Patients with primary NSCLC who had surgical resection and follow-up of at least 5 years were included in the study. There were 57 patients (38 men and 19 women), 44 to 75 years old (median age, 61 years); 28 patients had adenocarcinoma (AD) and 29 had squamous cell carcinoma. Tumors were examined for TTF-1 and HER2/neu expression using formalin-fixed, paraffin-embedded tissue. Clinical and follow-up data were obtained from the hospital records and Cancer Center database. Representative tumor sections were stained using standard immunohistochemical technique and commercial antibodies for TTF-1 (clone 8G7G3/1, Dako) and HER2/neu (polyclonal, Dako). Tumors were graded as negative (<5%), weak positive (5-49%), and strong positive (>50%), based on the percentage of positively stained tumor cells. Statistical analyses were performed using log-rank test, Pearson and Spearman correlations, and Kaplan-Meier survival curves. TTF-1 expression was seen in 45.6% of all tumors (80% of ADs and 14% of squamous cell carcinomas). Eighteen patients with tumors showing strong TTF-1 expression had significantly better survival compared with the 39 patients whose tumors showed negative or weak TTF-1 expression, although many more of the higher stage AD had strong TTF-1 staining than stage I AD. The TTF-1 expression did not correlate with tumor differentiation and was considered an independent predictor of survival. Seventeen of the 18 tumors with strong TTF-1 expression were ADs. Only eight of 57 (17%) tumors showed HER2/neu expression; seven of these eight were ADs. Although HER2/neu expression and survival did not show correlation, the majority of those ADs with weak or strong HER2/neu staining also had strong TTF-1 staining, were mostly stage I tumors. and had overall longer survival. All patients with stage I disease showed better 5-year survival compared with those with stages II and III. Hispanic patients had significantly worse survival compared with Caucasians and African Americans. The results of this study suggest that strong expression of TTF-1 is an independent predictor of better survival and may be a useful prognostic tool for evaluation of patients with NSCLC.

Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy

background Neoadjuvant (primary) chemotherapy is being used increasingly in the treatment of patients with large and locally advanced breast cancer with the aim of reducing the size of the primary tumor and eliminating micrometastatic disease. Response rates to, compliance with, and survival of patients following neoadjuvant chemotherapy have been variable. We report the results of a consecutive series of 77 patients with breast cancer who received neoadjuvant chemotherapy. methods Seventy-seven patients with locally advanced breast cancers were treated with multimodality therapy comprising up to six cycles of chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisolone), radiotherapy, and then surgery. The median follow-up was 54 months. Clinical response rates to therapy and overall survival have been documented. In addition, prognostic factors for survival were identified using the Cox proportional hazards model. results The overall objective response rate of the primary tumor to chemotherapy alone was 87% (25% complete and 62% partial responses, UICC criteria). Following radiotherapy the response rate was 90% (52% complete and 38% partial responses). The overall 5-year survival for all patients was 0.48. However, the probability of survival at 5 years was 0.74 in those with a complete response, and 0.36 if there was a partial clinical response, but no patients who had either stasis of disease or progression survived for 5 years. Independent predictors of better survival that were identified were a complete histopathological response after chemotherapy and radiotherapy, a complete clinical response to chemotherapy, and five or six cycles of chemotherapy versus four or less. conclusions Neoadjuvant chemotherapy in patients with large and locally advanced breast cancers can result in satisfactory local control and overall survival rates, especially in patients with a complete clinical or histopathological response after treatment.