Population-based SEER trend analysis of overall and cancer-specific survival in 5138 patients with gastrointestinal stromal tumor

Background: The objective of the present population-based analysis was to assess survival patterns in patients with resected and metastatic GIST. Methods: Patients with histologically proven GIST were extracted from the Surveillance, Epidemiology and End Results (SEER) database from 1998 through 2011. Survival was determined applying Kaplan-Meier-estimates and multivariable Cox-regression analyses. The impact of size and mitotic count on survival was assessed with a generalized receiver-operating characteristic-analysis. Results: Overall, 5138 patients were included. Median age was 62 years (range: 18–101 years), 47.3% were female, 68.8% Caucasians. GIST location was in the stomach in 58.7% and small bowel in 31.2%. Lymph node and distant metastases were found in 5.1 and 18.0%, respectively. For non-metastatic GIST, three-year overall survival increased from 68.5% (95% CI: 58.8–79.8%) in 1998 to 88.6% (95% CI: 85.3–92.0%) in 2008, cancer-specific survival from 75.3% (95% CI: 66.1–85.9%) in 1998 to 92.2% (95% CI: 89.4–95.1%) in 2008. For metastatic GIST, three-year overall survival increased from 15.0% (95% CI: 5.3–42.6%) in 1998 to 54.7% (95% CI: 44.4–67.3%) in 2008, cancer-specific survival from 15.0% (95% CI: 5.3–42.6%) in 1998 to 61.9% (95% CI: 51.4–74.5%) in 2008 (all PTrend < 0.05). Conclusions: This is the first SEER trend analysis assessing outcomes in a large cohort of GIST patients over a 11-year time period. The analysis provides compelling evidence of a statistically significant and clinically relevant increase in overall and cancer-specific survival from 1998 to 2008, both for resected as well as metastatic GIST

Diagnostic accuracy of C-reactive protein and white blood cell counts in the early detection of inflammatory complications after open resection of colorectal cancer: a retrospective study of 1,187 patients

Purpose: Although widely used, there is a lack of evidence concerning the diagnostic accuracy of C-reactive protein (CRP) and white blood cell counts (WBCs) in the postoperative period. The aim of this study was to evaluate the diagnostic accuracy of CRP and WBCs in predicting postoperative inflammatory complications after open resection of colorectal cancer. Methods: In this retrospective study, clinical data and the CRP and WBCs, routinely measured until postoperative day5 (POD 5), were available for 1,187 patients who underwent colorectal cancer surgery between 1997 and 2009. Using the receiver-operating characteristic (ROC) methodology, the diagnostic accuracy was evaluated according to the area under the curve (AUC). Results: Three hundred forty-seven patients (29.2%; 95% CI, 26.7-31.9%) developed various inflammatory complications. Anastomotic leakage occurred in 8.0% (95% CI, 6.1-9.1%) of patients. The CRP level on POD 4 (AUC 0.76; 95% CI, 0.71-0.81) had the highest diagnostic accuracy for the early detection of inflammatory complications. With a cutoff of 123mg/l, the sensitivity was 0.66 (95% CI, 0.56-0.74), and the specificity was 0.77 (95% CI, 0.71-0.82). The diagnostic accuracy of the WBC was significantly lower compared to CRP. Conclusion: Measurement of CRP on POD 4 is recommended to screen for inflammatory complications. CRP values above 123mg/l on POD 4 should raise suspicion of inflammatory complications, although the discriminatory performance was insufficient to provide a single threshold that could be used to correctly predict inflammatory complications in clinical practice. WBC measurement contributes little to the early detection of inflammatory complications. Registered at www.clinicaltrials.gov (NCT01221324

Risk Factors for Anastomotic Leakage after Rectal Cancer Resection and Reconstruction with Colorectostomy. A Retrospective Study with Bootstrap Analysis

Background: This study was designed to apply modern statistical methods to evaluate risk factors for anastomotic leakage after rectal cancer resection in a retrospective cohort of patients who received a colorectostomy. Whereas a diverting stoma and tumor height are considered proven risk factors for anastomotic leakage, a lack of evidence about additional risk factors persists. Methods: In a single-center study, 527 consecutive patients who received a colorectostomy after rectal cancer resection between 1991 and 2008 were retrospectively assessed. In addition to traditional uni- and multivariate regression, locally weighted scatterplot smoothing (LOWESS) regression and bootstrap analysis were applied to increase internal validity. Results: Anastomotic leakage occurred in 70 patients (13.3%; 95% confidence interval (CI), 10.5-16.5%) and mortality was 2.5% (95% CI, 1.4-4.2%). Diverting stoma (odds ratio (OR), 0.4; 95% CI, 0.17-0.61) and tumor height (OR, 0.88; 95% CI, 0.8-0.94) were proven to be protective. Neoadjuvant radiotherapy (OR, 2.15; 95% CI, 1.58-4.24) and intraoperative blood loss (OR, 1.05; 95% CI, 1.02-1.09) had a derogatory effect. Bootstrap analysis identified pre-existing vascular disease (95.5%), more advanced UICC stage III or IV tumors (95.7% or 91.5%, respectively), and intraoperative (96.1%) and postoperative (99.4%) blood substitution as harmful. Both intraoperative and postoperative blood substitution caused a dose-dependent increase in risk. Conclusions: Applying statistical resampling methods identified intraoperative blood loss, blood substitution, vascular disease, and advanced UICC stage as risk factors for anastomotic leakage. Greater distances between the tumor and the anal verge and performance of a diverting stoma were associated with a decreased risk of anastomotic leakag

Diagnostic study and meta-analysis of C-reactive protein as a predictor of postoperative inflammatory complications after gastroesophageal cancer surgery

Purpose: This study assessed the diagnostic accuracy of C-reactive protein (CRP) after gastroesophageal cancer resection for postoperative inflammatory complications (PIC). Methods: The clinical data and CRP values of patients operated on for gastroesophageal cancer surgery between 1997 and 2009 were retrospectively analyzed. The results of this study were compared with published data using a meta-analytic approach for diagnostic outcomes. Results: Of 210 patients included in the study, 59 developed PIC (28.1%; 95% CI: 22.5-34.5%). On the postoperative day (POD) 4 and 7, CRP had the best diagnostic accuracy for PIC (AUC 0.77; 95% CI, 0.64-0.91, AUC 0.81; 95% CI, 0.71-0.91). Using a cut-off value of 141mg/L (95% CI, 131-278mg/L) for CRP on POD 4, the sensitivity was 0.78 (95% CI, 0.55-0.91), the specificity was 0.70 (95% CI, 0.53-0.83) and the NPV was 0.89 (95% CI, 0.77-0.95). The in-hospital mortality rate was 3.3% (95% CI, 1.5-6.9%). In a diagnostic meta-analysis that included two additional studies, CRP had a significant predictive value after POD 3. Conclusion: There is limited evidence for the diagnostic accuracy of CRP levels for PIC after gastroesophageal cancer surgery. CRP levels on POD 4 might be useful to rule out PIC, but its diagnostic accuracy is moderate at best. For clinical routine use CRP levels are clearly not sufficient to predict PIC and have to be interpreted in the context of the whole clinical pictur

C-Reactive Protein 2 Days After Laparoscopic Gastric Bypass Surgery Reliably Indicates Leaks and Moderately Predicts Morbidity

Background: The aim of the present study was to evaluate whether serum C-reactive protein (CRP) is a useful predictor of early post-operative complications, particularly of intestinal leaks after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. Methods: The present study was a retrospective analysis of a prospectively maintained database with 809 patients who underwent LRYGB from 2002 until 2011. For 410 of these patients, at least one CRP measurement within the first seven post-operative days was available. The diagnostic value was determined by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: Forty-nine of 410 patients (12.0%; 95% confidence intervals [95% CI], 9.2-15.5%) developed surgery-related complications. Leaks occurred in 17 patients (4.1%; 95% CI, 2.6-6.5%) at a median of 5days after surgery. CRP levels 2days after surgery showed the highest diagnostic value for post-operative complications (AUC, 0.74; 95% CI, 0.60-0.89). Sensitivity was 0.53 (95% CI, 0.31-0.74) and specificity was 0.91 (95% CI, 0.79-0.96) on day 2 (cutoff level, 229mg/l). The sensitivity for intestinal leaks was 1.00 (95% CI, 0.51-1.00). Conclusion: CRP on post-operative day 2 is a valuable predictor of post-operative complications, in particular intestinal leaks. Radiological imaging studies for intestinal leaks could be restricted to patients with CRP values exceeding 229mg/

Relative survival is an adequate estimate of cancer-specific survival: baseline mortality-adjusted 10-year survival of 771 rectal cancer patients.

BACKGROUND The objective of the present investigation is to assess the baseline mortality-adjusted 10-year survival of rectal cancer patients. METHODS Ten-year survival was analyzed in 771 consecutive American Joint Committee on Cancer (AJCC) stage I-IV rectal cancer patients undergoing open resection between 1991 and 2008 using risk-adjusted Cox proportional hazard regression models adjusting for population-based baseline mortality. RESULTS The median follow-up of patients alive was 8.8 years. The 10-year relative, overall, and cancer-specific survival were 66.5% [95% confidence interval (CI) 61.3-72.1], 48.7% (95% CI 44.9-52.8), and 66.4% (95% CI 62.5-70.5), respectively. In the entire patient sample (stage I-IV) 47.3% and in patients with stage I-III 33.6 % of all deaths were related to rectal cancer during the 10-year period. For patients with AJCC stage I rectal cancer, the 10-year overall survival was 96% and did not significantly differ from an average population after matching for gender, age, and calendar year (p = 0.151). For the more advanced tumor stages, however, survival was significantly impaired (p < 0.001). CONCLUSIONS Retrospective investigations of survival after rectal cancer resection should adjust for baseline mortality because a large fraction of deaths is not cancer related. Stage I rectal cancer patients, compared to patients with more advanced disease stages, have a relative survival close to 100% and can thus be considered cured. Using this relative-survival approach, the real public health burden caused by rectal cancer can reliably be analyzed and reported

Better survival in right-sided versus left-sided stage I - III colon cancer patients

Background: The distinction between right-sided and left-sided colon cancer has recently received considerable attention due to differences regarding underlying genetic mutations. There is an ongoing debate if right- versus left-sided tumor location itself represents an independent prognostic factor. We aimed to investigate this question by using propensity score matching. Methods: Patients with resected, stage I - III colon cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2012). Both univariable and multivariable Cox regression as well as propensity score matching were used. Results: Overall, 91,416 patients (51,937 [56.8%] with right-sided, 39,479 [43.2%] with left-sided colon cancer; median follow-up 38 months) were eligible. In univariable analysis, patients with right-sided cancer had worse overall (hazard ratio [HR] = 1.32, 95% CI:1.29–1.36, P < 0.001) and cancer-specific survival (HR = 1.26, 95% CI:1.21–1.30, P < 0.001) compared to patients with left-sided cancer. After propensity score matching, the prognosis of right-sided carcinomas was better regarding overall (HR = 0.92, 95% CI: 0.89 − 0.94, P < 0.001) and cancer-specific survival (HR = 0.90, 95% CI:0.87 − 0.93, P < 0.001). In stage I and II, the prognosis of right-sided cancer was better for overall (HR = 0.89, 95% CI:0.84–0.94 and HR = 0.85, 95% CI:0.81–0.89) and cancer-specific survival (HR = 0.71, 95% CI:0.64 − 0.79 and HR = 0.75, 95% CI:0.70–0.80). Right- and left-sided colon cancer had a similar prognosis for stage III (overall: HR = 0.99, 95% CI:0.95–1.03 and cancer-specific: HR = 1.04, 95% CI:0.99–1.09). Conclusions: This population-based analysis on stage I - III colon cancer provides evidence that the prognosis of localized right-sided colon cancer is better compared to left-sided colon cancer. This questions the paradigm from previous research claiming a worse survival in right-sided colon cancer patients

Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview

Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with multiple genetic aberrations. Several molecular pathways involved in the regulation of proliferation and cell death are implicated in the hepatocarcinogenesis. The major etiological factors for HCC are both hepatitis B virus (HBV) and hepatitis C virus infection (HCV)

Allogeneic Blood Transfusion Does Not Affect Outcome After Curative Resection for Advanced Cholangiocarcinoma

Purpose: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. Methods: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. Results: Overall, 38 patients (29.7%) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69±0.22 vs. 0.11±0.16, p<0.001). In the unadjusted analysis, blood transfusion was associated with a 105% increased risk of mortality [hazard ratio (HR) 2.05, 95% CI 1.19-3.51, p=0.010]. In the multivariate (HR 1.14, 95% CI 0.52-2.48, p=0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95% CI 0.39-2.62, p=0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95% CI 0.24-1.58, p=0.295), no relevant effect of blood transfusion on disease-free survival was observed. Conclusions: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves