Significant Predictors Of Poor Survival Research Articles

Should we operate on microscopic N2 non-small cell lung cancer?

Traditionally non-small cell lung cancer (NSCLC) stage N2 is considered as a contraindication for curative resection. We investigated the outcome of patients with microscopic N2 disease, who underwent potentially curative resections. The independent effects of lobectomy vs. pneumonectomy, histology subtype, body mass index (BMI), sex, and PET-scanning were investigated. An N2 survival risk score was calculated and correlated with survival. Benchmarking revealed no discrepancies in our stage-specific survival data against the seventh edition of the International Association for the Study of Lung Cancer (IASLC) results. Of 1999 lung resections for primary lung cancer, 146 were pathologically staged as N2. Patients with resected microscopic N2 disease had a five-year survival equivalent to stage T3N1, P=0.39. Univariate analysis suggested pneumonectomy and T stage 3 as significant predictors of poor survival. Cox multivariate regression analysis revealed that age, BMI>30kg/m(2), pneumonectomy, squamous type and positron emission tomography (PET)-scan all had a significant effect on survival, P<0.05. A low N2 survival risk score was associated with increased survival, P=0.001. Resecting microscopic N2 disease in NSCLC may be appropriate in some patients. An N2 survival scoring system may help select patients for surgery, and help evaluate adjuvant and neoadjuvant publications with regard to microscopic N2 disease.

The Prognostic Factors That Influence Long-Term Survival in Acute Large Cerebral Infarction

We retrospectively evaluated the prognostic factors that can influence long-term survival in patients who suffered acute large cerebral infarction. Between June 2003 and October 2008, a total of 178 patients were diagnosed with a large cerebral infarction, and, among them, 122 patients were alive one month after the onset of stroke. We investigated the multiple factors that might have influenced the life expectancies of these 122 patients. The mean age of the patients was 70±13.4 years and the mean survival was 41.7±2.8 months. The mean survival of the poor functional outcome group (mRS≥4) was 33.9±3.3 months, whereas that of the good functional outcome group (mRS≤3) was 58.6±2.6 months (p value =0.000). The mean survival of the older patients (≥70 years) was 29.7±3.4 months, whereas that of the younger patients (<70 years) was much better as 58.9±3.2 months (p value=0.000). Involvement of ACA or PCA territory in MCA infarction is also a poor prognostic factor (p value=0.021). But, other factors that are also known as significant predictors of poor survival (male gender, hypertension, heart failure, atrial fibrillation, diabetes mellitus, a previous history of stroke, smoking, and dyslipidemia) did not significantly influence the mean survival time in the current study. Age (older versus younger than 70 years old) and functional outcome at one month could be critical prognostic factors for survival after acute large cerebral infarction. Involvement of ACA or PCA territory is also an important poor prognostic factor in patients with MCA territorial infarction.

The initial development and assessment of an automatic alert warning of acute kidney injury

Acute kidney injury (AKI) recognition by clinicians has been shown to be suboptimal. Little work has focused on the use of an automated warning of a rise in a patient's creatinine, indicating AKI. Over 3 months in 2008 we ran a prospective observational study of 'alerts' sent by our Integrated Clinical Environment pathology system, identifying all patients with a ≥ 75% rise in their creatinine from its previous value. Information was collected on subsequent renal function, comorbidities and other potential predictors of survival. In the 3-month period 463 adults with a first episode of AKI were identified by an alert; 87% were hospital inpatients. Median follow-up was 404 days. In-hospital mortality was 36% for those who were admitted. After performing Weibull survival analysis, significant predictors of poorer survival were the presence of metastatic, haematological or lower risk malignancy, a residential or nursing home address and higher age, number of non-malignant comorbidities or C-reactive protein level. Predictors of better survival were higher serum albumin level or nadir GFR during the episode and Indian subcontinent ethnicity. A receiver-operator curve for a prognostic score developed from the analysis showed an area under the curve of 0.84. The alerts identified a group of AKI patients who are at moderately high risk of death. The prognostic score using a combination of covariates shows early promise. Both the alerts and the score warrant further development as tools for earlier intervention in AKI.

Renal function and mortality following cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) improves outcomes in heart failure, yet selection of patients likely to have survival benefit is problematic. Chronic kidney disease (CKD) is an important determinant of mortality in patients with congestive heart failure therefore we sought to determine the impact of CKD on mortality benefit after CRT. All CRT device implantations in patients not on dialysis at Mayo Clinic between January 1999 and December 2005 were included. Of 482 patients, 342 (71%) had CKD (defined as a glomerular filtration rate (GFR) of ≤60 mL/min/1.73 m(2)) at the time of device implantation. Patients with CKD were older (71 ± 10 vs. 63 ± 14 years, P < 0.01) than patients without CKD, and more often anaemic (12.70 ± 1.73 vs. 13.24 mg/L, P < 0.01), with similar ejection fraction (22 ± 8 vs. 23 ± 8%, P = 0.32). Survival was superior in patients with normal or mild renal dysfunction compared with patients with CKD (72 vs. 57% at 3 years, P < 0.01). After multivariate analysis, CKD remained a significant predictor of poor survival following CRT. Chronic kidney disease is common in patients undergoing CRT and associated with a higher mortality and should be considered when evaluating patients for CRT.

Pneumothorax and idiopathic pulmonary fibrosis

We evaluated the relation between the severity of idiopathic pulmonary fibrosis (IPF) and the incidence of pneumothorax on computed tomography (CT) images. In this retrospective study, we evaluated the presence of pneumothorax in 56 consecutive patients who died of IPF from the initial CT to death. We quantitatively analyzed a total of 207 CT images and measured the volume of the normal pattern (N-pattern) and each lesion pattern on the initial CT and their serial changes. The effects of pneumothorax and clinical and CT features on survival were evaluated using Cox regression analysis. Pneumothorax occurred in 17 of 56 patients. Comparison of the pneumothorax (+) and (-) groups showed the initial vital capacity (VC) was lower (P = 0.005) and the follow-up period was shorter (P = 0.03) in the former group. The decrease in the N-pattern volume in the pneumothorax(+) group was significantly faster than in the pneumothorax(-) group (P = 0.013). Cox regression analyses identified a rapid decrease in N-pattern volume (P = 0.008) and a rapid decrease in VC (P = 0.002), but not pneumothorax, as significant predictors of poor survival. Pneumothorax in IPF patients is associated with lower VC and rapid deterioration of CT findings. The findings suggest that pneumothorax is a complication of advanced IPF.

Molecular typing of epithelial ovarian carcinomas using inflammatory markers

Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P = .0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P = .029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P = .005). The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy.

Acute exacerbation of idiopathic pulmonary fibrosis: incidence, risk factors and outcome

Although acute exacerbation of idiopathic pulmonary fibrosis (IPF) has become well recognised, the reported incidence and outcomes are highly variable, and risk factors are unknown. The aim of this study was to estimate the incidence, risk factors and impact of acute exacerbations, and other known causes of rapid deterioration. This was a retrospective review of 461 patients with IPF (269 cases were biopsy-proven). The median follow-up period was 22.9 months. Rapid deterioration requiring hospitalisation occurred in 163 (35.4%) patients, with multiple episodes in 42 patients. Acute exacerbation was the most frequent cause (55.2%), followed by infection. The 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low forced vital capacity (FVC) were significant risk factors. The in-hospital mortality rate was 50.0%, and the 1- and 5-yr survival rates from the initial diagnosis were 56.2 and 18.4%, respectively. Acute exacerbation was a significant predictor of poor survival after the initial diagnosis, along with increased age, low FVC and diffusing capacity of the lung for carbon monoxide, and steroid use with or without cytotoxic therapy. 1- and 3-yr incidences of acute exacerbation were 14.2 and 20.7%, respectively. Never having smoked and low FVC were risk factors. Acute exacerbation had a serious impact on the overall survival of the patients with IPF.

Do all patients with carcinoma of the esophagus benefit from treatment at teaching facilities?

We sought to determine whether patients with esophageal carcinoma benefit from regionalization of care. The Florida Cancer Data System (FCDS) and the Agency for Health Care Administration data sets (1998-2002) were merged and queried. A total of 5,041 patients (87.6% Caucasian vs. 11.1% African American (AA)) demonstrated a median survival time of 9.8 months overall and 23.4 months following surgical resection (P < 0.001). Adenocarcinoma arose predominantly in Caucasian patients (98.1%). Patients with adenocarcinoma (n = 2,248) derived a treatment benefit at a TF (HR = 1.35, P = 0.003), including an improved 90-day mortality following surgery (2.1% vs. 4.0%, P < 0.001). Squamous cell carcinoma (SCC) arose predominantly in AA patients (91.6%). No overall survival benefit at TF was observed (HR = 1.01, P = 0.915), however a trend for reduced 90-day surgical mortality was observed at TF (1.9% vs. 5.2%, P = 0.062). Multivariate analysis for adenocarcinoma demonstrates that poverty, lack of chemotherapy or surgery, and failure to provide treatment at a TF are independent predictors of worse survival. For SCC patients, AA race was a significant predictor of poorer survival while TF and poverty level were not. These data suggest no benefit from potential regionalized care for patients with squamous histology, which disproportionately affects AA.

Genomic Changes in Chromosomes 10, 16, and X in Malignant Peripheral Nerve Sheath Tumors Identify a High-Risk Patient Group

The purpose of this study was to identify genetic aberrations contributing to clinical aggressiveness of malignant peripheral nerve sheath tumors (MPNSTs). Samples from 48 MPNSTs and 10 neurofibromas were collected from 51 patients with (n = 31) or without (n = 20) neurofibromatosis type 1 (NF1). Genome-wide DNA copy number changes were assessed by chromosomal and array-based comparative genomic hybridization (CGH) and examined for prognostic significance. For a subset of 20 samples, RNA microarray data were integrated with the genome data to identify potential target genes. Forty-four (92%) MPNSTs displayed DNA copy number changes (median, 18 changes per tumor; range, 2 to 35 changes). Known frequent chromosomal gains at chromosome arms 8q (69%), 17q (67%), and 7p (52%) and losses from 9p (50%), 11q (48%), and 17p (44%) were confirmed. Additionally, gains at 16p or losses from 10q or Xq identified a high-risk group with only 11% 10-year disease-specific survival (P = .00005). Multivariate analyses including NF1 status, tumor location, size, grade, sex, complete remission, and initial metastatic status showed that the genomic high-risk group was the most significant predictor of poor survival. Several genes whose expression was affected by the DNA copy number aberrations were identified. The presence of specific genetic aberrations was strongly associated with poor survival independent of known clinical risk factors. Conversely, within the total patient cohort with 34% 10-year disease-specific survival, a low-risk group was identified: without changes at chromosomes 10q, 16p, or Xq in their MPNSTs, the patients had 74% 10-year survival.

Factors influencing survival of patients with cancer of the pancreatic head after resection

The aim of this cohort study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. patients with pancreatic head cancer undergoing curative resection (R0) between 1997 and 2002 were included in this study. Univariate and multivariate analyses were performed to examine factors affecting clinical outcome and recurrence of the cancer. Surgical procedures consisted of 58 (43.3%) extended pancreaticoduodenectomies (EPD), 47 (35.1%) pancreaticoduodenectomies (PD) and 29 (21.6%) pylorus-preserving pancreaticoduodenectomies (PPPD). The results showed that 81.3% (109/134) of patients had a recurrence during the study period, mainly retroperitoneal combined with distant metastasis (53.7%). The median postoperative survival time was 24.7 months. The 1-, 3- and 5-year overall survival rates for the study population were 67.1%, 38.5% and 17.6%, respectively. Univariate analysis showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion, and CA19-9 level were all significant predictors for poor survival. Multivariate analysis also showed that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion were all significant predictors for poor survival. Our results suggest that preoperative abdominal and/or back pain, tumor size > 2 cm, lymph node involvement and vascular invasion are significant predictors for poor survival in patients with pancreatic head cancer.

Trimodality Therapy With Induction Chemotherapy Followed by Extrapleural Pneumonectomy and Adjuvant High-Dose Hemithoracic Radiation for Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) remains associated with poor outcome. We examined the results of trimodality therapy with cisplatin-based chemotherapy followed by extrapleural pneumonectomy (EPP) and adjuvant high-dose (50 to 60 Gy) hemithoracic radiation therapy for MPM. We conducted a retrospective review of all patients prospectively evaluated for trimodality therapy protocol between January 2001 and December 2007 in our institution. A total of 60 patients were suitable candidates. Histology was epithelioid (n = 44) or biphasic (n = 16). Chemotherapy regimens included cisplatin/vinorelbine (n = 26), cisplatin/pemetrexed (n = 24), cisplatin/raltitrexed (n = 6), or cisplatin/gemcitabine (n = 4). EPP was performed in 45 patients, and hemithoracic radiation therapy to at least 50 Gy was administered postoperatively to 30 patients. Completion of the trimodality therapy in the absence of mediastinal node involvement was associated with the best survival (median survival of 59 months v <or= 14 months in the remaining patients, P = .0003). The type of induction chemotherapy had no significant impact on survival. Pathologic nodal status remained a significant predictor of poor survival despite completion of the trimodality therapy. After completion of the protocol, the 5-year disease-free survival was 53% for patients with N0 disease, reaching 75% in patients with ypT1-2N0 and 45% in patients with ypT3-4N0. This large, single-center experience with induction chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation for MPM shows that half of the patients are able to complete this protocol. The results are encouraging for patients with N0 disease. However, N2 disease remains a major factor impacting on survival, despite completion of the entire trimodality regimen.

Gastrin‐releasing peptide: Different forms, different functions

All forms of the neuropeptide gastrin-releasing peptide (GRP) are derived from the precursor proGRP1-125. Amidated GRP18-27, which together with amidated GRP1-27 was long thought to be the only biologically relevant product of the GRP gene, is involved in a multitude of physiological functions and acts as a mitogen, morphogen, and proangiogenic factor in certain cancers. Recently, GRP has been implicated in several psychiatric conditions, in the maintenance of circadian rhythm, in spinal transmission of the itch sensation, and in inflammation and wound repair. The actions of GRP are mediated by the GRP receptor. Over the last decade, nonamidated peptides derived from proGRP, such as the glycine-extended form GRP18-28 and recombinant and synthetic fragments from proGRP31-125, have been shown to be biologically active in a range of tissues and in cancer cell lines. While GRP18-28 acts via the GRP receptor, the identity of the receptor for proGRP31-125 and its fragments has not yet been established. Nonamidated fragments are also present in normal tissues and in various cancers. In fact, proGRP31-98 is the most sensitive serum biomarker in patients with small cell lung cancer and is a significant predictor of poor survival in patients with advanced prostate cancer.

Pulmonary Atresia With Ventricular Septal Defects and Major Aortopulmonary Collateral Arteries 18-Year Clinical Experience and Angiographic Follow-up of Major Aortopulmonary Collateral Arteries

There is no consensus on the long-term outcome after unifocalization in patients undergoing surgery for pulmonary atresia with ventricular septal defects (VSD) and major aortopulmonary collateral arteries (MAPCAs). From 1988 to 2006, 40 patients (median age 8.5 months) underwent surgery for pulmonary atresia, VSD, and MAPCAs. The hospital mortality rate for the preparatory procedures was 1.2%; 17 patients had a complete repair (CR) at a median age of 3 years. Patients with a pulmonary artery index greater than 100 mm(2)/m(2) had a higher likelihood of CR. The overall survival rate 15 years after first operation in the CR group was 87.5%. Cox analysis demonstrated that increased number of MAPCAs (P=0.019, HR=1.666) was a significant predictor of poor survival, and CR (P=0.025, HR=0.141) was a significant predictor of favorable prognosis. On angiography, serial measurements of MAPCAs showed a significant decrease in size (from 5.2+/-2.9 to 4.1+/-2.9 mm after a mean of 20 months) (P<0.0001). Long-term survival into adulthood can be achieved with an integrated approach. Late survival depends on the number of MAPCAs, and CR. Growth potential of unifocalized MAPCAs was not definite.

Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi‐center study

The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment. From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child-Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log-rank test and multivariate analysis with the Cox proportional hazards model. On univariate analysis, advanced Child-Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (</=70), large tumor (>30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child-Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence. Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.

Prospective study of combined treatment with interferon‐alpha and active vitamin D3 for Japanese patients with metastatic renal cell carcinoma

To assess the safety and efficacy of combined therapy with interferon-alpha (INF-alpha) and active vitamin D(3) for metastatic renal cell carcinoma (RCC). Sixteen patients with metastatic RCC were enrolled in this prospective study. All received oral alfacalcidol (1 microg once daily) and INF-alpha (Sumiferon; 3 million units, three times a week). The primary endpoint was the response rate (defined as complete + partial remission). Secondary endpoints were cancer-specific survival and toxicity. The median follow-up period was 17 months (range: 5-49 months). The median age of the patients was 68 years (range: 41-73 years). The sites of metastases were: lung in 13 patients, bone in one, lung and bone in one, and lung, bone, and lymph nodes in one. Four patients (25%) had a partial response (PR), 10 patients (62.5%) showed no change (NC), and two patients (12.5%) had progressive disease (PD). The median cancer-specific survival time was 45 months. One patient had to discontinue vitamin D(3) because of hypercalcemia. Kaplan-Meier survival analysis revealed that metastasis at the time of initial diagnosis and older than average age were significant predictors of poor survival (P < 0.05). Combined treatment with INF-alpha and active vitamin D(3) has shown to be safe and effective for metastatic RCC patients.

Patient Education Level As a Predictor of Survival In Lung Cancer Clinical Trials

To investigate the effect of socioeconomic status, as measured by education, on the survival of 1,577 lung cancer patients treated on 11 studies conducted by the Cancer and Leukemia Group B. Sociodemographic data, including education, was reported by the patient at the time of clinical trial accrual. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival after adjustment for known prognostic factors. The patient population included 1,177 patients diagnosed with non-small-cell lung cancer (NSCLC; stage III or IV) and 400 patients diagnosed with small-cell lung cancer (SCLC; extensive or limited). Patients with less than an eighth grade education (13% of patients) were significantly more likely to be male, nonwhite, and older; have a performance status (PS) of 1 or 2; and have chest pain. Significant predictors of poor survival in the final model included male sex, PS of 1 or 2, dyspnea, weight loss, liver or bone metastases, unmarried, presence of adrenal metastases and high alkaline phosphatase levels among patients with NSCLC, and high WBC levels among patients with advanced disease. Education was not predictive of survival. The physical condition of patients with low education who enroll onto clinical trials is worse than patients with higher education. Once enrolled onto a clinical trial, education does not affect the survival of patients with SCLC or stage III or IV NSCLC. The standardization of treatment and follow-up within a clinical trial, regardless of education, is one possible explanation for this lack of effect.

Long-Term Follow-Up of Patients Who Experienced Graft Failure Postallogeneic Progenitor Cell Transplantation. Results of a Single Institution Analysis

The long-term outcome of graft failure after allogeneic stem cell transplantation (SCT) has not been well described. To fill this knowledge gap we performed a retrospective analysis of patients with graft failure over a 10-year time period in a single institution. Cases were included for analysis if they had failed to achieve an absolute neutrophil count (ANC) of 500/μL or more by 28 days post-SCT or 42 days after cord blood transplantation (primary graft failure); had a decrease in their ANC to <500/mL for 3 consecutive days after having achieved neutrophil engraftment (secondary graft failure); or failed to have evidence of at least 5% or more donor cell engraftment (primary graft failure with autologous reconstitution). Among 1726 patients who underwent allografts from January 1, 1990, through December 31, 2000, we identified 68 patients with graft failure. The 1-, 2-, and 5-year overall survival (OS) for all patients was 31%, 24%, and 15%. A diagnosis of acute leukemia was a significant predictor for poor survival on multivariate analysis. We conclude that graft failure is an uncommon complication postallogeneic SCT, and is associated with poor outcomes. Collection of autologous stem cells prior to high-risk allografting can salvage a fraction of patients and lead to prolonged survivals.

Clinical Significance of Insulin-Like Growth Factor Type 1 Receptor and Epidermal Growth Factor Receptor in Patients with Advanced Gastric Cancer

Objective: To better understand the clinical implications of insulin-like growth factor type 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and HER2 expressions in gastric cancer (GC). Methods: The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital. Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of IGF-1R, EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors. Results: In univariate analysis of the study group as a whole, patients with low expression of both IGF-1R and EGFR (n = 13) had a significantly longer overall survival than the other patients (n = 51; median, 24.6 vs. 12.8 months; log-rank p = 0.013). Multivariate survival analysis demonstrated that high EGFR expression [hazard ratio, HR: 2.94 (95% confidence interval, CI: 1.40–6.17), p = 0.004] and poor performance status [HR: 1.96 (95% CI: 1.12–3.42), p = 0.018] were significant predictors of poor survival. In patients given first-line S-1 monotherapy (n = 29), low IGF-1R (p = 0.002) and low EGFR (p = 0.035) gene expression correlated with a better response, without a significant prolongation of survival. Conclusion: Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC.

Impact of Insulin-Like Growth Factor Type 1 Receptor, Epidermal Growth Factor Receptor, and HER2 Expressions on Outcomes of Patients with Gastric Cancer

Expression levels of insulin-like growth factor type 1 receptor (IGF-IR), epidermal growth factor receptor (EGFR), and HER2 expressions have been linked to clinical outcomes in several solid tumors. However, the clinical significance of these biomarkers in gastric cancer (GC) remains unclear. This study was designed to delineate the clinical implications of these three biomarkers in GC. The study group comprised 87 patients who underwent gastrectomy at National Cancer Center Hospital and subsequently received chemotherapy for recurrent or residual tumors. Using immunohistochemical techniques, we analyzed the expressions of IGF-IR, EGFR, and HER2 on formalin-fixed paraffin-embedded specimens of surgically removed primary tumors. IGF-IR expression (defined as >10% membranous staining) was found in 67 tumors (77%), EGFR expression in 55 (63%), and HER2 expression in 16 (18%). Positive coexpression of IGF-IR and EGFR was found in 48 tumors (55%), that of IGF-IR and HER2 in 16 (18%), and that of EGFR and HER2 in 13 (15%). Multivariate survival analysis showed that IGF-IR-positive expression [hazard ratio (HR) 2.14, 95% confidence interval (95% CI) 1.20-3.82; P = 0.01], performance status 1 or 2 (HR 1.83, 95% CI 1.15-2.91; P = 0.01), and diffuse type tumors (HR 1.71; 95% CI 1.08-2.70; P = 0.02) were significant predictors of poor survival. IGF-IR expression in surgical GC specimens, poor performance status, and diffuse type tumors are significant predictors of poor outcomes in patients with GC. Our data suggest that anti-IGF-IR strategies may prove valuable in such patients.

Prosthesis–patient mismatch affects long-term survival after mechanical valve replacement

We sought to examine the relationship between the degree of prosthesis-patient mismatch and long-term survival after mechanical aortic valve replacement. Prospectively collected long-term follow-up data from 469 consecutive patients who underwent aortic valve replacement between 1995 and 1998 were reviewed. The indexed effective orifice area was derived from the reference normal values of effective orifice area divided by the patient's body surface area. Outcome was stratified according to the severity of prosthesis-patient mismatch: moderate mismatch was defined as 0.65 to 0.85 cm(2)/m(2) and severe mismatch as less than 0.65 cm(2)/m(2). The Cox proportional-hazards model with propensity score adjustment was used to adjust for the observed differences in baseline characteristics between the mismatch groups. The degree of prosthesis-patient mismatch was minimal in 57% of patients, moderate in 39%, and severe in 4%. Predictors of clinically significant mismatch included small aortic valve sizes (19 and 21 mm), obesity, age greater than 65 years, and class III or IV heart failure. During a median follow-up period of approximately 7.9 years, overall survival was 77% in patients with minimal mismatch, 63% in those with moderate mismatch, and only 47% in those with severe mismatch (P < .001). Moderate or severe mismatch was a significant predictor of poorer survival (hazard ratio, 1.6; 95% confidence interval, 1.4-2.3; P < .01), even after adjustment for all significant clinical predictors (ie, propensity score; hazard ratio, 1.2; 95% confidence interval, 1.0-1.5; P = .05). In a large aortic valve surgery population, prosthesis-patient mismatch occurred in 43% of patients, and those with significant mismatch had worse long-term outcomes than those with minimal mismatch.