Utility of tumor markers in determining resectability of pancreatic cancer

HYPOTHESIS: Despite advances in preoperative radiologic imaging, a significant fraction of potentially resectable pancreatic cancers are found to be unresectable at laparotomy. We tested the hypothesis that preoperative serum levels of CA19-9 (cancer antigen) and carcinoembryonic antigen will identify patients with unresectable pancreatic cancer despite radiologic staging demonstrating resectable disease. DESIGN AND SETTING: Academic tertiary care referral center. PATIENTS: From March 1, 1996, to July 31, 2002, 125 patients were identified who underwent surgical exploration for potentially resectable pancreatic cancer based on a preoperative computed tomographic scan; in 89 of them a preoperative tumor marker had been measured. MAIN OUTCOME MEASURES: Preoperative tumor markers (CA19-9 and carcinoembryonic antigen) were correlated with extent of disease at exploration. As CA19-9 is excreted in the biliary system, CA19-9 adjusted for the degree of hyperbilirubinemia was determined and analyzed. RESULTS: Of the 89 patients, 40 (45%) had localized disease and underwent resection, 25 (28%) had locally advanced (unresectable) disease, and 24 (27%) had metastatic disease. The mean adjusted CA19-9 level was significantly lower in those with localized disease than those with locally advanced (63 vs 592; P =.003) or metastatic (63 vs 1387; P<.001) disease. When a threshold adjusted CA19-9 level of 150 was used, the positive predictive value for determination of unresectable disease was 88%. Carcinoembryonic antigen level was not correlated with extent of disease. CONCLUSIONS: Among the patients with resectable pancreatic cancer based on preoperative imaging studies, those with abnormally high serum levels of CA19-9 may have unresectable disease. These patients may benefit from additional staging modalities such as diagnostic laparoscopy to avoid unnecessary laparotomy.     

CA 19-9 levels predict results of staging laparoscopy in pancreatic cancer

Laparoscopy has emerged as an important staging procedure for determining resectability of pancreatic cancer. However, a small fraction of patients with pancreatic cancer benefit from its use and therefore the routine application of laparoscopy remains controversial. We hypothesized that serum CA 19-9 levels may identify patients who will or will not benefit by laparoscopy. We retrospectively reviewed our database of 63 patients with pancreatic adenocarcinoma who underwent staging laparoscopy and correlated findings with CA 19-9 levels. Overall, laparoscopy identified metastatic disease in 12 patients (19%). None of those required any further operation. The resectability rate (patients who underwent resection after laparoscopy) was 73.5%. There was one false-negative laparoscopy (1.6%). Patients with higher CA 19-9 levels had significant higher odds of having metastasis identified by laparoscopy (odds ratio, 1.83; 95% confidence interval, 1.03-3.24; P = .04). There was no patient with CA 19-9 levels below 100 U/ml in whom metastatic disease was identified during laparoscopy: 18 patients (28.6%) with CA 19-9 levels below this cutoff point had negative laparoscopy and could have avoided the procedure had this cutoff been used for screening. This would have increased the laparoscopy yield to 26.7%. In patients with adenocarcinoma of the pancreas, low CA 19-9 levels predict low probability of metastatic disease; in those patients, laparoscopy can be spared. On the contrary, patients with elevated CA 19-9 have an increased probability of metastatic disease, and these patients may benefit from diagnostic laparoscopy. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, IL, May 14–18, 2005 (poster presentation).     

Prognostic significance of serum CA19-9 levels in resected pancreatic cancer

Twenty-eight patients with histologically proven pancreatic adenocarcinoma were investigated to evaluate the utility of serum CA19-9 levels as a prognostic indicator after pancreatic resection. Three patients were excluded from the study because their serum CA19-9 levels remained normal throughout the course of the disease. Of the remaining 25 patients, those with preoperative serum CA19-9 levels 200U/ml had a better prognosis than those with serum CA19-9 levels >200 U/ml; however, the difference between the two groups was not significant (P=0.13). Serum CA19-9 levels 30 days after pancreatic resection were normalized (37 U/ml) in 11 patients (group A), and the survival rate of this group was significantly higher than that of the group of patients with persistently elevated CA19-9 levels (>37 U/ml) (group B) (P<0.005). Other factors i.e., preoperative CA19-9 values, tumor size, lymph node metastasis, histology, and stage classification showed no significant differences between group A and group B. Univariate analysis of the findings for the 25 patients showed that the stage classification and postoperative CA19-9 levels were of prognostic significance for prolonged survival. Other factors, i.e., gender, age, histology, preoperative CA19-9 levels, location of the tumor, and mode of operation, had no significance as prognostic indicators. Multivariate analysis showed that postoperative CA19-9 level was the only significant independent predictor of poor survival. Postoperative serum CA19-9 level appears to be useful as a prognostic indicator after resection of pancreatic cancer.     

Surrogate Markers of Resectability in Patients Undergoing Exploration of Potentially Resectable Pancreatic Adenocarcinoma

Despite extensive preoperative staging, a significant number of pancreatic cancers are unresectable at surgical exploration. Patients undergoing pancreatic exploration with a view to resection were studied and comparisons are then made between those undergoing resection and a bypass procedure to identify surrogate markers of unresectability. One hundred thirteen consecutive patients underwent pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass procedure. Student’s t test, receiver operator characteristics (ROC) and logistic regression were used to compare the predictive value of preoperative patient variables collected retrospectively. The bypass group had a significantly higher median CA19.9 than the resection group (P = 0.003). Platelet count and neutrophil–lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P = 0.026, respectively). ROC analysis indicated that age ≤65, platelet count >297 × 10⁹/l, CA19.9 ≤473 Ku/l, and CA19.9–bilirubin ratio were predictive variables for resectable disease. NLR and CA19.9–bilirubin ratio had specificity values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9 was found to be an independent risk factor for unresectable disease (P = 0.031). A significant proportion of patients with HOP adenocarcinoma are understaged preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and CA19.9–bilirubin ratio may be used as additional discriminators of resectability particularly for high-risk patients.     

Undetectable Preoperative Levels of Serum CA 19-9 Correlate with Improved Survival for Patients with Resectable Pancreatic Adenocarcinoma

Background: Serum levels of CA19-9 have been shown to correlate with both recurrence and survival in patients with pancreatic cancer. However, little is known about the prognosis for patients with undetectable levels of serum CA19-9.Methods :One hundred twenty-nine patients with pancreatic cancer who underwent preoperative assessment of serum CA19-9 followed by resection with curative intent between 1990 and 2002 were retrospectively analyzed. Data collected included preoperative serum CA19-9 level (U/mL), age, pathologic staging, and survival. Data were analyzed with the SAS system according to four distinct preoperative serum CA19-9 levels: undetectable, normal (<37), 38–200, and 200 U/mL.Results: Serum CA19-9 levels ranged from undetectable to 16,300 U/mL. Stage III/IV disease accounted for 86%, 67%, 59%, and 53% of patients in the four CA19-9 groups. The overall median and 5-year survivals were 19 months and 11%, respectively. Survival was similar between nonsecretors and those with normal CA 19-9 levels. However, both groups had statistically significant prolonged survival compared with the two groups with elevated CA 19-9 levels (P = .003). The only factors that were significant on univariate and multivariate analysis for overall survival were lymph node positivity (P = .015 and .002) and CA 19-9 grouping (P = .003 and P < .0001). Although this group of patients presented with predominately advanced-stage disease, their overall survival was superior.Conclusions: These findings suggest that patients who present with undetectable preoperative CA19-9 levels and potentially resectable pancreatic cancer, regardless of advanced stage, should be considered candidates for aggressive therapy.the 56th Annual Cancer Symposium of the Society of Surgical Oncology, Los Angeles, California, March 5–9, 2003.     

Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas

Background: CA 19-9 levels are useful for the diagnosis of patients with pancreatic adenocarcinoma. However, interest has recently turned toward its use as a prognostic indicator. The purpose of this study is to determine whether postoperative CA 19-9 levels predict disease-free survival (DFS) and median survival (MS) in patients after resection. Methods: Between 1988 and 1996, 40 patients underwent resection for pancreatic adenocarcinoma and were evaluated with postoperative CA 19-9 assays. Eight patients had low preoperative levels of CA 19-9 (<2) and were excluded. Results: CA 19-9 levels are good predictors of DFS and MS. Patients whose postoperative CA 19-9 values normalized by 3 to 6 months (<37 U/ml) had longer DFS (24 vs. 10 months,p<0.04) and MS (34 vs. 13 months,p<0.04). Patients with postoperative CA 19-9 values less than 180 U/ml at 1 to 3 months had a similar DFS (19 vs. 5 months,p<0.0009) and MS (34 vs. 13 months,p<0.0001) compared to patients with normal values at 3 to 6 months. Conclusions: Postoperative measurements of CA 19-9 were the best predictors of DFS and MS. Values<180 U/ml at 3 months were as predictive as normal values by 3 to 6 months postoperatively. Consequently, CA 19-9 levels should be obtained for use as a stratification parameter in phase III trials.Presented at a plenary session for 50th Annual Cancer Symposium, The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

CA19-9 in Potentially Resectable Pancreatic Cancer: Perspective to Adjust Surgical and Perioperative Therapy

Purpose

In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences.

Methods

Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels.

Results

The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135).

Conclusions

In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.     

CA 19-9 Velocity Predicts Disease-Free Survival and Overall Survival After Pancreatectomy of Curative Intent

Introduction  This study was undertaken to correlate serum CA 19-9 levels and CA 19-9 velocity with disease-free and overall survival after pancreatectomy for adenocarcinoma. Methods  From 1997 to 2002, 96 patients underwent pancreatectomy without adjuvant chemotherapy as the control arm of a large randomized prospective adjuvant therapy trial. After resection, CA 19-9 levels were drawn at baseline, 4 weeks, and 12-week intervals thereafter. CA 19-9 velocity denotes rate of change in CA 19-9 levels over a 4-week period. Postoperative baseline CA 19-9 levels and CA 19-9 velocity were correlated with disease-free and overall survival. Data are presented as median (mean ± SD). Results  Disease-free survival was 7 months (14 ± 13.7), and overall survival was 12 months (19 ± 14.3) with 24 (25%) patients alive at 41 months (39 ± 7.8). Baseline CA 19-9 levels and CA 19-9 velocity predicted disease-free (p < 0.01) and overall survival (p < 0.01). CA 19-9 velocity was a better predictor of overall survival than baseline CA 19-9 (p < 0.001). CA 19-9 velocity at disease progression was 131 U/ml/4-weeks (1,684 ± 4,474.8) vs. 1 U/ml/4-weeks (1 ± 3.8) at 22 months for patients without disease progression (p < 0.001). Conclusions  CA 19-9 velocity predicts imminent disease progression after resection of pancreatic adenocarcinoma and is a better predictor of overall survival than baseline CA 19-9 levels. CA 19-9 velocity is a reliable and relatively inexpensive means of monitoring patients after resection of pancreatic cancer and should be considered in all patients enrolled in clinical trials as well as patients receiving adjuvant therapy.     

Serum CA19-9 measurement increases the effectiveness of staging laparoscopy in patients with suspected pancreatic malignancy

BACKGROUND/AIMS: Staging laparoscopy for suspected pancreatic neoplasia is not widely accepted due to its low yield. The aim of this study was to determine if serum carbohydrate antigen (CA19-9) levels could be used to improve the selection of patients for staging laparoscopy. METHODS: The data from a prospectively collected database (1997-2004) with 159 patients who had computed tomography-predicted resectable disease and who had undergone laparoscopic staging were analysed to determine if a low preoperative CA19-9 level (< or =150 kU/l, or < or =300 kU/l with a bilirubin >35 micromol/l) identified patients in whom laparoscopy was not useful. Results: The CA19-9 level was >150 kU/l in 96 patients of whom 75 (78%) were considered resectable following laparoscopic assessment. There were 63 patients with a CA19-9 < or =150 kU/l of whom 60 (95%) were considered resectable following laparoscopic assessment. The sensitivity, specificity, positive predictive value and negative predictive value for CA19-9 < or =150 kU/l in predicting that laparoscopic assessment would judge patients as resectable were 44, 88, 95 and 22%, respectively. A cut-off level of < or =300 kU/l in patients with a bilirubin >35 micromol/l produced values of 30, 94, 94 and 28%, respectively. By using CA19-9 < or =150 kU/l, laparoscopy could have been avoided in 40% of patients, increased to 55% of patients with adjustment for the presence of jaundice; concomitantly, the yield from laparoscopy would have been increased from 15 to 22 and 25%, respectively. Conclusion: Use of serum CA19-9 levels would increase the efficiency of laparoscopic staging in patients with suspected pancreatic malignancy.     

CA19-9对胰腺癌手术可切除性的预测价值

目的探讨肿瘤标志物CA19-9等对胰腺癌手术可切除性的术前预测价值。方法回顾性分析病理证实的胰腺癌手术病人221例,据手术方式分为根治性胰十二指肠切除术组（PD）和姑息性手术组;将有术前血清CA19-9检测结果的病人分为CA19—9正常、轻度升高和异常升高组,根据术中情况进行TNM分期。结果CA19—9升高率在PD组为64．41％,在姑息组为79．45％。所有胰腺癌病人CA19—9异常升高率为82．86％;PD组CA19—9水平显著性低于胰腺癌不能切除组（P=0．035）。结论不能行根治性切除的胰腺癌病人血清CA19-9水平显著的高于能行根治性手术的病人,血清CA19-9〉1000u／ml可做为判定胰腺癌难以行根治性手术切除的参考指标。联合检测肿瘤标志物无助于早期诊断和预测胰腺癌的可切除性。     

用于胰头癌可切除性判断的术前血清标志物筛选

目的:探讨术前血清肿瘤标记物糖类抗原(CA19-9、CA50、CA242、CA125)和癌胚抗原(CEA)水平对胰头癌可切除性评估的临床价值。方法:回顾性分析2014年1月—2015年12月收治的104例胰头癌患者的临床资料,筛选与胰头癌可切除性相关的血清肿瘤标记物,并采用受试者工作特性曲线(ROC)与曲线下面积(AUC)分析其对胰头癌可切除性的预测价值。结果:104例患者均行手术探查,其中可切除54例(可切除组),不可切除50例(不可切除组)。两组术前血清CA50和CEA水平差异无统计学意义(均P0.05),而不可切除组CA19-9、CA242和CA125水平明显高于可切除组(317.99k U/Lvs.152.98k U/L;67.81k U/Lvs.39.36k U/L;71.53k U/Lvs.29.22k U/L,均P0.05)。ROC分析得出CA19-9和CA125对胰头癌可切除性均具有判断价值,其最佳截断点分别为236.13k U/L和16.44k U/L,AUC值分别为0.667和0.678(均P0.05),而单项检测CA242对胰头癌可切除性诊断无明显判别价值(AUC=0.609,P=0.085)。CA19-9、CA125联合诊断对胰头癌可切除性诊断的灵敏度和特异性提高。结论:术前检测血清CA19-9和CA125水平可作为辅助指标应用于胰头癌的可切除性评估,两者联合检测更能提高灵敏度和特异性。     

Biliary Ca 19-9 values correlate with the risk of hepatic metastases in patients with adenocarcinoma of the pancreas

Serum values of the tumor-associated antigen CA 19-9 are useful as an independent predictor of survival in patients with adenocarcinoma of the pancreas. However, the utility of biliary CA 19-9 values is unknown. This study was undertaken to determine whether biliary CA 19-9 levels are predictive of hepatic metastases. Between 1991 and 1996, thirty-eight patients treated for adenocarcinoma of the pancreas were evaluated using a biliary CA 19-9 assay. Bile was obtained from percutaneous stents placed during the perioperative period. Five of the 38 patients had low serum levels of CA 19-9 (<2 U/ml) and were excluded from the study. Twenty-seven (80%) of the 33 patients developed distant metastases: five pulmonary, five peritoneal, and 17 hepatic. Liver metastases were discovered initially in 10 and after resection of the primary tumor in seven (median interval 10 months). Biliary CA 19-9 values were significandy higher in patients with hepatic metastases (median 267,400 U/ml; range 34,379 to 5,000,000 U/ml) compared to patients without metastatic disease (median 34,103 U/ml; range 6,620 to 239,880 U/ml; P <0.006). Patients with hepatic, peritoneal, and pulmonary metastases had median survivals of 8, 14, and 35 months, respectively (P <0.0041). All patients without metastatic disease are alive (median follow-up 13 months). Biliary CA 19-9 values are associated with a stepwise increase in the risk of developing metastatic disease. Patients with biliary CA 19-9 levels greater than 149,490 U/ml have an increased risk of developing recurrent disease in the liver and may warrant further hepatic evaluation or therapy. Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997.     

Prognostic Impact of Perioperative Serum CA 19-9 Levels in Patients with Resectable Pancreatic Cancer

Background

Pancreatic cancer is one of the most deadly cancers, and serum carbohydrate antigen 19-9 (CA19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The purpose of this study was to determine which prognostic factor (preoperative or postoperative serum CA19-9 level) is more useful.

Methods

Pre- and postoperative serum CA19-9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009, and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods.

Results

In univariate analysis, tumor location (P = 0.019), postoperative adjuvant chemotherapy (P < 0.001), residual tumor factor status (P < 0.001), UICC pT stage (P = 0.004), lymph node metastasis (P = 0.015), and UICC final stage (P = 0.015) were significantly associated with overall survival. Differences in overall survival were significant between groups divided on the basis of four postoperative CA19-9 cutoff values (37, 100, 200, and 500 U/ml) but not significant between groups divided on the basis of the same four preoperative CA19-9 cutoff values. Pre- to postoperative increase in CA19-9 level also was significantly associated with poor prognosis. In multivariate analysis, postoperative adjuvant chemotherapy (hazard ratio, 1.59; P = 0.004) and postoperative CA19-9 cutoff value of 37 U/ml (HR, 1.64; P = 0.004) remained independent predictors of prognosis.

Conclusions

Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level.     

Serum CA 19-9 as a Marker of Resectability and Survival in Patients with Potentially Resectable Pancreatic Cancer Treated with Neoadjuvant Chemoradiation

Purpose

The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.

Patients and Methods

We analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level.

Results

We enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74).

Conclusions

Although the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.     

Preoperative Serum CA19-9 and Dissected Peripancreatic Tissue Margin as Determiners of Long-Term Survival in Pancreatic Cancer

Background  Pancreatic cancer, a particularly deadly form of malignancy, has increased in the last decade worldwide. The purpose of this study is to identify markers for determining and identifying possible long-term survivors in cases of advanced pancreatic cancer. Patients and methods  117 patients with pancreatic ductal carcinoma, including 89 with invasive tubular adenocarcinoma of the pancreas, Japan Pancreas Society (JPS) stage III–IVb patients, who underwent tumor resection between 1986 and 2006. Results  Univariate prognostic analyses of the 5-year disease-specific survival (DSS) revealed that JPS stage (P < 0.0001), preoperative serum carbohydrate antigen 19-9 (CA19-9) level (preCA19-9; P < 0.0001), dissected peripancreatic tissue margin (DPM; P < 0.0001), residual tumor (R factor; P = 0.0007), lymph node metastasis density over 10% (ND10; P = 0.006), volume of the stromal connective tissue (stroma factor; P = 0.008), growth pattern (P = 0.01), and histology (P = 0.03) were all significantly associated with poor outcome in advanced pancreatic cancer. Multivariate logistic analysis confirmed that preCA19-9 [P = 0.0006, relative risk (RR) = 2.16] and DPM (P = 0.04, RR = 1.62) were prognostic factors that remained, independent of JPS stage (P = 0.001). The higher preCA19-9 was, the worse the prognosis was. Astonishingly, among JPS stage III cases, 76.9% of the patients with preCA19-9 below 37 U/ml survived more than 5 years. This, combined with an analysis of DPM, allowed us to identify those with the potentiality for long-term survival. Conclusion  Our results reveal for the first time that it is possible with JPS stage III–IVb invasive tubular adenocarcinomas of the pancreas to differentiate prognostic groups and potential survival rates, like with other cancers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Prognosis of Resected Ampullary Adenocarcinoma by Preoperative Serum CA19-9 Levels and Platelet-Lymphocyte Ratio

Background  The objective of this study was to evaluate whether preoperative CA19-9 levels and the platelet–lymphocyte ratio (PLR) might reflect prognostic indices for resected ampullary adenocarcinoma. Materials and Methods  Data were collected prospectively over a 10-year period for consecutive patients undergoing pancreatoduodenectomy for malignancy. Results  Both preoperative PLR and CA19-9 results were available in 52 cases of resected ampullary adenocarcinoma. Preoperative CA19-9 levels of ≤150 kU/l (or ≤300 kU/l in the presence of bilirubin levels >35 μmol/l) and a PLR of ≤160 were found to represent the optimal cut-off values to risk stratify patients. If both levels were elevated (n = 8), patients had a median overall survival of 10.1 months. If either CA19-9 or PLR were elevated individually (n = 23), patients had a median survival of 25.2 months. For cases where both levels were less than the cut-off values (n = 21), the median overall survival time was not reached but was greater than 60 months (log rank, p < 0.001). This preoperative risk stratification was found to remain a significant independent predictor of survival on multivariate analysis (Cox, p = 0.001) alongside resection margin status (p = 0.002) and tumor size (p = 0.051). Conclusions  Preoperative CA19-9 and PLR both merit further evaluation as prognostic indices in resected ampullary adenocarcinoma.     

The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer

BACKGROUND: Despite the usefulness of CA 19-9 in the diagnosis and prognosis of pancreatic cancer, cholestasis can falsely elevate CA 19-9 levels, which contributes to limited clinical utility in patients with biliary obstruction. This study was designed to evaluate the usefulness of adjusted preoperative CA 19-9 levels in predicting a prognosis of pancreatic cancer. METHODS: The available medical records of patients with resected pancreatic cancer from January 1990 to June 2005 were retrospectively viewed at Yonsei Medical Center, Seoul, Korea. The adjusted CA 19-9 value was obtained by dividing the serum CA 19-9 level by the values of serum bilirubin in case of bilirubin greater, similar 2 mg/dL. Disease-free survival was evaluated according to the adjusted preoperative CA 19-9 value. RESULTS: Sixty-one patients were investigated. Their adjusted preoperative CA 19-9 values were significantly different from the actual baseline CA 19-9 value (129.4 +/- 225.2 U/mL, versus 442.1 +/- 645.5 U/mL, P < 0.0001). On univariate analysis, peripancreatic microscopic invasion (P = 0.0142), lymphovascular invasion (P = 0.0038), and adjusted preoperative CA 19-9 > or = 50 U/mL (P = 0.0049) were predictive factors for cancer recurrence after curative resection. Adjusted preoperative CA 19-9 > or = 50 U/mL (Exp (B) = 2.097, P = 0.027) was an independent predictive factor in multivariate analysis. CONCLUSIONS: The adjusted preoperative CA 19-9 value can predict the risk of recurrence after curative resection of pancreatic cancer. Interpreting the preoperative CA 19-9 value adjusted to the serum bilirubin values seems to be more reasonable in evaluating prognosis of pancreatic cancer.     

CA125 is Superior to CA19-9 in Predicting the Resectability of Pancreatic Cancer

Background

Although carbohydrate antigen 19-9 (CA19-9) has been reported as a biomarker to predict the resectability of pancreatic cancer, several limitations have restricted its clinical use.

Methods

The potential of several serum tumor markers (CA19-9, CA125, CA50, CA242, CA724, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP)) to predict the resectability of pancreatic cancer was evaluated by receiver operating characteristic (ROC) analysis in a series of 212 patients with proven pancreatic cancer.

Results

Compared with other tumor markers including CA19-9, CA125 has a superior predictive value (CA19-9, ROC area 0.66, cutoff value 289.40 U/mL; CA125, ROC area 0.81, cutoff value 19.70 U/mL). In addition, for patients with unresectable diseases misjudged by CT as resectable, the percentage of CA125 over selected cutoff value was higher than that of CA19-9 (CA19-9, 70.27 %; CA125, 81.08 %).

Conclusion

CA125 is superior to CA19-9 in predicting the resectability of pancreatic cancer. Aberrant high levels of CA125 may indicate unresectable pancreatic cancer.     

Preoperative prediction of complete resection in pancreatic cancer

BACKGROUND: Accurate preoperative staging is essential in pancreatic cancer to select the 15% of patients who can benefit from surgery and avoid surgery in the 85% with advanced disease. With improvements in computed tomography (CT) scanning, the value of routine laparoscopy for preoperative staging of pancreatic cancer has been questioned because it changes the preoperative plan in less than 20% of unselected cases. METHODS: We retrospectively reviewed our experience with preoperative staging in 88 consecutive patients with pancreatic cancer. All patients had preoperative CT scans, and selective criteria were used to determine which patients would also undergo preoperative staging laparoscopy. Patients were categorized preoperatively as resectable or not resectable (locally advanced or metastatic). Medical records, operative, and pathology reports were reviewed to determine the accuracy of preoperative predictions. RESULTS: Thirty patients were deemed resectable based on CT alone and 27 (90%) were resected (25 R0, 2 R1). Two (7%) had metastatic disease discovered at laparotomy and one (3%) had a R2 resection. Only 19 patients (39%) of 49 patients deemed resectable by CT met our selective criteria for preoperative staging laparoscopy. Laparoscopy changed the treatment plan in 11 (58%) of these patients. Eight were still deemed resectable after staging laparoscopy and 7 (88%) were resected (6 R0, 1 R1). One patient (12%) had metastatic disease diagnosed at laparotomy. If selective staging laparoscopy were eliminated from our algorithm, 49 patients would have been deemed potentially resectable based on CT alone, 34 (69%) would have been found to be resectable at laparotomy (31 R0, 3 R1), and 15 (31%) would have been found to be unresectable at laparotomy (positive predictive value of 69%). The addition of selective staging laparoscopy avoided unnecessary laparotomy in 11 patients and increased the positive predictive value to (34/38) 89%. CONCLUSION: Selective use of laparoscopy increases the positive predictive value of preoperative staging in pancreatic cancer and avoids unnecessary laparoscopy in the majority of patients.     

Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels for the evaluation of curability and resectability in patients with pancreatic adenocarcinoma

Background Purpose Although carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are the most studied serum tumor markers that have been evaluated for diagnosis and prognosis in patients with pancreatic cancer, little is known of the value of these markers for the prediction of curability and resectability. Methods We retrospectively reviewed preoperative serum levels of CEA and CA 19-9 in 244 consecutive patients with pancreatic operations. Results Although 159 pancreatic operations seemed “resectable”, 93 of them were judged curative (R0) and the other 66 turned out to be noncurative (R1/2). The remaining 85 failed resection because of unexpected metastasis or locally advanced disease (LD), which was unresectable compared with levels in those patients without liver metastasis or LD. CEA levels were significantly higher in patients with liver metastasis and LD, while CA 19-9 levels were correlated with liver and peritoneal metastases. When both markers were negative, curative (R0) and respectable (R0 + R1/2) operation were performed in 70% and 85% of patients, respectively. Logistic regression analysis indicated that under conditions where both CEA and CA 19-9 were negative, the odds ratios for curative and respectable operations were 4.43 and 3.58, respectively. Conclusions Our data suggest that combined preoperative CEA and CA 19-9 levels are suitable for assessing expected curability and resectability in patients with pancreatic cancer.