Abstract Background Recent evidence indicates that tumor progression involves factors of systemic inflammation, such as platelets and lymphocytes. In this study, we investigated the prognostic ...relevance of the preoperative platelet to lymphocyte (P/L) ratio on time to recurrence (TTR) and overall survival (OS) in patients with stage II and III colon cancer (CC) who underwent curative resection. Methods In this retrospective study, 372 CC patients were included. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS. Results In univariate analysis, the elevated P/L ratio was significantly associated with decreased TTR (HR = 1.60, 95% CI = 1.02 to 2.51, P = .040) and remained significant in multivariate analysis (HR = 1.65, 95% CI = 1.05 to 2.58, P = .030), where HR and CI represent Hazard ratio and confidence interval, respectively. Patients with elevated P/L ratio showed a median TTR of 116 months. In contrast, patients with low P/L ratio had a median TTR of 132 months. In OS analysis, the elevated P/L ratio showed a trend toward decreased OS in univariate analysis (HR = 1.54, 95% CI = .95 to 2.48, P = .079). Conclusion In this study, we identified the preoperative P/L ratio as a prognostic marker for TTR in stage II and III CC patients.
Resection of colorectal liver metastases (CLM) in selected patients has evolved as the standard of care during the last 20 years. In the absence of prospective randomized clinical trials, a survival ...benefit has been deduced relative to historical controls based on actuarial data. There is now sufficient follow-up on a significant number of patients to address the curative intent of resecting CLM.
Retrospective review of a prospectively maintained database was performed on patients who underwent resection of CLM from 1985 to 1994. Postoperative deaths were excluded. Disease-specific survival (DSS) was calculated from the time of hepatectomy using the Kaplan-Meier method.
There were 612 consecutive patients identified with 10-year follow-up. Median DSS was 44 months. There were 102 actual 10-year survivors. Ninety-nine (97%) of the 102 were disease free at last follow-up. Only one patient experienced a disease-specific death after 10 years of survival. In contrast, 34% of the 5-year survivors suffered a cancer-related death. Previously identified poor prognostic factors found among the 102 actual 10-year survivors included 7% synchronous disease, 36% disease-free interval less than 12 months, 25% bilobar metastases, 50% node-positive primary, 39% more than one metastasis, and 35% tumor size more than 5 cm.
Patients who survive 10 years appear to be cured of their disease, whereas approximately one third of actual 5-year survivors succumb to a cancer-related death. In well-selected patients, there is at least a one in six chance of cure after hepatectomy for CLM. The presence of poor prognostic factors does not preclude the possibility of long-term survival and cure.
Summary The prognostic significance of tumor necrosis in colorectal cancer is unclear. Our study aimed to analyze the prognostic value of tumor necrosis with respect to progression-free and ...cancer-specific survival and to relate findings to expression of proteins involved in the control of cancer cell death, such as p53 and bcl-2. A total of 381 colorectal cancer specimens were retrospectively reevaluated. The extent of tumor necrosis was semiquantitatively assessed and recorded as either absent, focal (≤10% of the tumor area), moderate (10%-30%), or extensive (≥30%). Expression of p53 and bcl-2 was assessed immunohistochemically and recorded as either positive (using a cutoff value of 10%) or negative. In addition, mismatch repair protein status was assessed by immunohistochemistry using antibodies directed against hMLH1, hMSH2, and hMSH6. Tumor necrosis was observed in 365 (96%) cases, with 180 (47%) tumors showing focal necrosis, 119 (31%) moderate necrosis, and 66 (17%) extensive necrosis, respectively. Extent of necrosis was significantly associated with high T classification ( P < .001), high N classification ( P = .005), high International Union Against Cancer stage ( P < .001), poor tumor differentiation ( P < .001), large tumor size ( P < .001), and blood vessel invasion ( P = .01). No association of tumor necrosis with expression of p53, bcl-2, and mismatch repair protein status was observed. Tumor necrosis proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. In conclusion, tumor necrosis showed significant impact on prognosis of colorectal cancer patients. Its presence is readily assessable in hematoxylin and eosin–stained sections and should therefore routinely be commented upon in the pathology report.
Mucin glycoprotein expression can be altered during the carcinogenic process. The impact on the prognosis of patients with colorectal cancer (CRC) is controversial. We analyzed tumors from 381 ...patients for MUC1, MUC2, MUC5AC, and MUC6 expression by immunohistochemical staining, using tissue microarrays. Progression-free and cancer-specific survival were determined using the Kaplan-Meier method. Expression of intestinal mucin MUC2 was lost in 85 (23 %) CRCs, and patients with MUC6-negative tumors showed shorter progression-free survival (PFS,
p
= 0.043). Gastric mucins MUC5AC and MUC6 showed high (>50 %) aberrant expression in 28 (8 %) and 9 (2 %) cases, respectively. High expression of MUC5AC was associated with longer PFS (
p
= 0.055). High expression of MUC6 was associated with 100 % PFS (
p
= 0.024) and longer cancer-specific survival (CSS,
p
= 0.043). MUC1 was expressed in 238 (64 %) tumors and had no impact on outcome. When analysis was restricted to stages II and III, loss of MUC2 was associated with adverse outcome. Overexpression of both MUC5AC and MUC6 significantly predicted favorable PFS and CSS. In conclusion, loss of MUC2 expression proved to be a predictor of adverse outcome, while the gain of aberrant expression of MUC5AC and particularly of MUC6 was associated with favorable outcome in CRC, notably in intermediate stages II and III.
SOX9 has been previously shown to be involved in hepatocellular carcinoma (HCC) and other types of cancer. However, prognostic studies so far involved rather small cohorts or lack external validation ...and experimental data. In this study, we firstly determined the histological expression pattern of SOX9 in human HCC by immunohistochemistry (n = 84) and evaluated its prognostic value. External cohorts of publicly available datasets were used to validate its prognostic relevance in HCC (n = 359) and other types of cancer including breast (n = 3951), ovarian (n = 1306), lung (n = 1926) and gastric cancer (n = 876). Functional SOX9 knock-down studies using siRNA and cancer stem cell models were generated in a panel of liver and breast cancer cell lines. High level of SOX9 was associated with poor survival even after adjustment for other prognostic factors in multivariate analysis (HR = 2.103, 95%CI = 1.064 to 4.156, p = 0.021). SOX9 prevailed a poor prognostic factor in all cancer validation cohorts (p<0.05). Reduced SOX9 expression by siRNA decreased the growth of liver cancer cells (p<0.05). SOX9 expression was associated with stem cell features in all tested cell lines (p<0.05). In conclusion, this study demonstrated in a large number of patients from multiple cohorts that high levels of SOX9 are a consistent negative prognostic factor.
Background
Despite improvements in surgery and chemotherapy, most patients develop recurrence after hepatectomy for metastatic colorectal cancer. Data are lacking on the effect of these patterns on ...outcome.
Methods
A retrospective review of a prospectively maintained hepatobiliary database was performed. Pattern and timing of recurrence and outcome after recurrence were analyzed. Univariate and multivariate analyses of factors associated with outcome after recurrence were carried out.
Results
From January 1997 through May 2003, a total of 733 patients underwent hepatectomy for colorectal metastases. Of these, 637 patients (87%) were included in the analysis, and in 393 patients (62%), recurrence was documented at the time of last follow-up. Initial recurrence patterns included the following: liver only in 120 patients (31%), lung only in 107 (27%), other single sites in 49 (12%), and multiple sites in 117 (30%). Recurrence occurred within 2 years of hepatectomy in 75% of patients and after 3 years in 11%. Margins at hepatectomy, recurrence pattern, resected recurrence, and disease-free interval from time of colectomy to hepatic metastasis and from time of hepatectomy to recurrence were independently associated with survival as measured from the time of recurrence. Recurrence in the lung, resected recurrence, and time to recurrence after hepatectomy were associated with prolonged survival as measured from the time of hepatectomy and the time of recurrence.
Conclusions
The timing and pattern of recurrence after hepatic resection for metastatic colorectal cancer are important predictors of long-term survival.
Gastrointestinal complications following on-pump cardiac surgery are orphan but serious risk factors for postoperative morbidity and mortality. We aimed to assess incidence, perioperative risk ...factors, treatment modalities and outcomes.
A university medical center audit comprised 4883 consecutive patients (median age 69 interquartile range IQR 60-76 years, 33% female, median logistic EuroScore 5 IQR 3-11) undergoing all types of cardiac surgery including surgery on the thoracic aorta; patients undergoing repair of congenital heart disease, implantation of assist devices or cardiac transplantation were excluded. Coronary artery disease was the leading indication for on-pump cardiac surgery (60%), patients undergoing cardiac surgery under urgency or emergency setting were included in analysis. We identified a total of 142 patients with gastrointestinal complications. To identify intra- and postoperative predictors for gastrointestinal complications, we applied a 1:1 propensity score matching procedure based on a logistic regression model.
Overall, 30-day mortality for the entire cohort was 5.4%; the incidence of gastrointestinal complications was 2.9% and median time to complication 8 days (IQR 4-12). Acute pancreatitis (n = 41), paralytic ileus (n = 14) and acute cholecystitis (n = 18) were the leading pathologies. Mesenteric ischemia and gastrointestinal bleeding accounted for 16 vs. 18 cases, respectively. While 72 patients (51%) could be managed conservatively, 27 patients required endoscopic/radiological (19%) or surgical intervention (43/142 patients, 30%); overall 30-day mortality was 12.1% (p<0.001). Propensity score matching identified prolonged skin-to-skin times (p = 0.026; Odds Ratio OR 1.003, 95% Confidence Interval CI 1.000-1.007) and extended on-pump periods (p = 0.010; OR 1.006, 95%CI 1.001-1.011) as significant perioperative risk factors.
Prolonged skin-to-skin times and extended on-pump periods are important perioperative risk factors regardless of preoperative risk factors.
With growing evidence on the role of inflammation in cancer biology, the presence of a systemic inflammatory response has been postulated as having prognostic significance in a wide range of cancer ...types. The derived neutrophil to lymphocyte ratio (dNLR), which represents an easily determinable potential prognostic marker in daily practise and clinical trials, has never been externally validated in pancreatic cancer (PC) patients.
Data from 474 consecutive PC patients, treated between 2004 and 2012 at a single centre, were evaluated retrospectively. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. To evaluate the prognostic relevance of dNLR, univariate and multivariate Cox regression models were applied.
We calculated by ROC analysis a cut-off value of 2.3 for the dNLR to be ideal to discriminate between patients' survival in the whole cohort. Kaplan-Meier curve reveals a dNLR≥2.3 as a factor for decreased CSS in PC patients (p<0.001, log-rank test). An independent significant association between high dNLR≥2.3 and poor clinical outcome in multivariate analysis (HR = 1.24, CI95% = 1.01-1.51, p = 0.041) was identified.
In the present study we confirmed elevated pre-treatment dNLR as an independent prognostic factor for clinical outcome in PC patients. Our data encourage independent replication in other series and settings of this easily available parameter as well as stratified analysis according to tumor resectability.
Introduction:
Postoperative pancreatic fistula (POPF) is the most dreaded complication after distal pancreatectomy (DP). This multicenter randomized trial evaluated the efficacy, safety, and ...tolerance of Hemopatch in preventing clinically relevant (grades B/C according to the ISGPS classification) POPF after DP.
Material and methods:
After stump closure, patients were randomized to affix Hemopatch to the stump or not. Statistical significance was set at 0.025. Clinical significance was defined as the number of patients needed to treat (NNT) to avoid 1 B/C POPF.
Results:
Of 631 eligible patients, 360 were randomized and 315 analyzed per protocol (155 in the standard closure group; 160 in the Hemopatch group). The rates of B/C POPF (the primary endpoint) were 23.2% and 16.3% (
P
= 0.120), while the number of patients with 1 or more complications (including patients with B/C POPF) was 34.8% and 24.4% (
P
= 0.049) in the standard and Hemopatch groups, respectively. In patients with hand-sewn stump and main duct closure, the rates were 26.2% versus 10.0% (
P
= 0.014) and 23.3% versus 7.7% (
P
= 0.015) in the standard and Hemopatch groups, respectively. The NNT in these 2 subgroups was 6 and 6.4, respectively.
Conclusion:
The results of the first randomized trial evaluating Hemopatch-reinforced pancreatic stump after DP to prevent type B/C POPF do not allow us to conclude that the risk of B/C POPF was lower. Based on the NNT, however, routine use of Hemopatch after DP may result in fewer complications (including POPF) overall, especially in cases with hand-sewn closure of the pancreatic stump or main pancreatic duct.
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