High CA19-9 level in resectable pancreatic cancer is a potential indication of neoadjuvant treatment

BackgroundPrevious studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC.MethodsWe retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR).ResultsOverall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group.ConclusionsIt is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.     

Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer

Objectives

The purpose of this study was to determine the relationship between carbohydrate antigen (CA) 19-9 levels and outcome in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy (NT).

Methods

This study included all patients with borderline resectable pancreatic cancer, a serum CA 19-9 level of ≥40 U/ml and bilirubin of ≤2 mg/dl, in whom NT was initiated at one institution between 2001 and 2010. The study evaluated the associations between pre- and post-NT CA 19-9, resection and overall survival.

Results

Among 141 eligible patients, CA 19-9 declined during NT in 116. Following NT, 84 of 141 (60%) patients underwent resection. For post-NT resection, the positive predictive value of a decline and the negative predictive value of an increase in CA 19-9 were 70% and 88%, respectively. The normalization of CA 19-9 (post-NT <40 U/ml) was associated with longer median overall survival among both non-resected (15 months versus 11 months; P = 0.022) and resected (38 months versus 26 months; P = 0.020) patients. Factors independently associated with shorter overall survival were no resection [hazard ratio (HR) 3.86, P < 0.001] and failure to normalize CA 19-9 (HR 2.13, P = 0.001).

Conclusions

The serum CA 19-9 level represents a dynamic preoperative marker of tumour biology and response to NT, and provides prognostic information in both non-resected and resected patients with borderline resectable pancreatic cancer.     

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.     

Preoperative CA 125 is significant indicator of curative resection in gastric cancer patients

AIM: To investigate the correlation among tumor markers, curative resection, and recurrence in gastric cancer.METHODS: The patients with preoperative tumormakers [Carcinoembryonic antigen, Carbohydrate antigen(CA) 19-9, and CA 125] and elective gastrectomy between January 2000 and December 2009 at Chungbuk National University Hospital were enrolled in this study. We analyzed the relationship among the tumor makers, curative resection and recurrence, retrospectively.RESULTS: Among the 679 patients with gastric cancer, curative resection was 93.6%(n = 636) and noncurative resection was 6.4%(n = 43). The independent risk factors for the non-curative resection were tumor location and the positivity of preoperative serum CA 19-9 and CA 125 levels. After curative resection, the independent prognostic risk factors for recurrence in curative resection were gender, stage, and preoperative increased serum CA 125 level(HR = 2.431, P =0.020), in a multivariate analysis. CONCLUSION: Preoperative CA 125 is a useful predictive biomarker for curative resection and prognostic biomarker for recurrence in gastric cancer patients.     

Is jaundice a cause of error in the interpretation of CA 19-9 blood levels?

Serum CA 19-9 has been proposed as a tumour marker for pancreatic cancer (PC). However, false positive results are seen in sera of patients with benign jaundice. The CA 19-9 assay was performed by a solid state radioimmunoassay in 86 icteric patients (total bilirubin greater than 2 mg/dl). 24/86 had PC (12 men, 12 women, mean age 74 years) and 62/86 had benign jaundice (29 men, 33 women, mean age 56 years; cirrhosis: n = 20, angiocholitis: n = 21, hepatitis: n = 21). At a cut-off level of 60 U./ml, for detecting icteric PC, sensitivity was 83%, and specificity was 79%. At 120 U./ml, sensitivity was 79%, but specificity was increased to 92%. We conclude that 21% of patients with benign jaundice had a CA 19-9 level greater than 60 U./ml, and using a CA 19-9 level of 120 U./ml, the specificity of the test to detect icteric PC was increased, with little decrease in the sensitivity.     

CEA and CA 19-9 as prognostic indexes in colorectal cancer.

Carcinoembryonic Antigen (CEA) and CA 19-9 are tumor markers expressed by colorectal cancers (CR), particularly in advanced cases. The aim of this study was to evaluate the prognostic value of pre-operative elevated CEA and/or CA 19-9 levels for patients with CR. Blood samples were collected from 74 patients. CEA and CA 19-9 were determined by ELISA (normal range: 0-3 ng/ml for CEA and 0-37 U/ml for CA 19-9). All patients were followed-up for at least 30 months or until death. At the time of diagnosis, 42% of the patients had elevated serum levels of CEA and 35% of CA 19-9. Relapse was observed in 33 patients, 73% of whom had elevated CEA and/or CA 19-9 levels. Among patients without relapse, 68% and 73% had normal values of CEA and CA 19-9, respectively. Ninety-three percent of patients, who had CR recurrence during the first year, had an elevated CEA and/or CA 19-9 level, while 67% of the patients with CR after 1 year, had normal tumor markers. Elevated pre-operative serum CEA and CA 19-9 levels were each predictive of increased cancer mortality (p = 0.001 for CEA, p = 0.01 for CA 19-9). Raised CEA and CA 19-9 levels identify patients at high risk for CR and death and may be useful in selecting patients for adjuvant therapy.     

Prognostic value of CA 19-9, CEA, CRP, LDH and bilirubin levels in locally advanced and metastatic pancreatic cancer: results from a multicenter, pooled analysis of patients receiving palliative chemotherapy

Purpose

CA 19-9 is the only established tumor marker in pancreatic cancer (PC); the prognostic role of other serum markers like CEA, CRP, LDH or bilirubin has not yet been defined.

Methods

We pooled pre-treatment data on CA 19-9, CEA, CRP, LDH and bilirubin levels from two German multicenter randomized phase II trials together with prospective patient data from one high-volume German Cancer Center. Marker levels were assessed locally before the start of palliative first-line therapy for advanced PC and serially during treatment (for CA 19-9 only). Clinical and biomarker data (overall 12 variables) were correlated with the efficacy endpoints time-to-progression (TTP) and overall survival (OS) by using uni- and multivariate Cox models.

Results

Data from 291 patients were included in this pooled analysis; 253 patients (87 %) received treatment within prospective clinical trials. Median TTP in the study cohort was 5.1 months and median OS 9.0 months. In univariate analysis, pre-treatment CA 19-9 (HR 1.55), LDH (HR 2.04) and CEA (HR 1.89) levels were significantly associated with TTP. Regarding OS, baseline CA 19-9 (HR 1.46), LDH (HR 2.07), CRP (HR 1.69) and bilirubin (HR 1.62) were significant prognostic factors. Within multivariate analyses, pre-treatment log [CA 19-9] (as continuous variable for TTP) and log [bilirubin] as well as log [CRP] (for OS) had an independent prognostic value. A CA 19-9 decline of ≥25 % during the first two chemotherapy cycles was predictive for TTP and OS, independent of the applied CA 19-9 assay.

Conclusion

Baseline CA 19-9 and CA 19-9 kinetics during first-line chemotherapy are prognostic in advanced PC. Besides that finding other serum markers like CRP, LDH and bilirubin can also provide prognostic information on TTP and OS.     

Clinical importance of preoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels in gastric cancer

Although serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are commonly measured before surgery for gastric carcinoma, this clinical significance is not fully understood. We evaluated a total of 549 patients with gastric cancer who underwent gastrectomy. Levels of CEA and CA19-9 were measured preoperatively in all patients. We retrospectively analyzed correlations between CEA or CA19-9 and clinicopathologic features, and estimated the prognostic utility of the tumor markers by analyzing clinicopathologic characteristics of the carcinoma as a function of seropositivity or negativity of the antigens in combination or by raising the levels. The positivity rates of CEA (> or =5 ng/mL) and CA19-9 (> or =37 U/mL) were 19.5% and 18%, respectively. Serum CEA and CA19-9 positivity significantly correlated with depth of invasion, hepatic metastasis, and curativity. Forty-nine patients positive for both CEA and CA19-9 had significantly higher frequencies of lymph node metastasis, deeper invasion by the tumor, lower rates of curative resection (p < 0.01), and higher rates of hepatic metastasis (p < 0.05) than 377 patients with normal levels of CEA and CA19-9. Surgical outcomes of patients who were CEA- and CA19-9-positive were poorer than those of patients with normal CEA and CA19-9 levels (p < 0.01). Significant correlation was found between serum CEA and CA19-9 level (p < 0.001, r = 0.24). Doubling the threshold level of serum positivity to 10 ng/mL (CEA) and 74 U/mL (CA19-9) improved the prognostic value of these factors. However, multivariate analysis using Cox's hazards model revealed that only CEA positivity using the doubled threshold value (10 ng/mL) (p = 0.04, hazard ratio = 1.7), nodal involvement (p = 0.01, hazard ratio = 1.9), and depth of invasion (p = 0.02 hazard ratio = 1.5) significantly predicted prognosis. Carcinoembryonic antigen positivity using the doubled threshold level (10 ng/mL) was an important prognostic factor in patients with gastric cancer.     

Colorectal carcinoma liver metastases: clinical significance of preoperative measurement of serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels

The clinical significance of preoperative levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) was evaluated in patients with colorectal carcinoma liver metastases. Preoperative serum CEA and CA 19-9 levels, the number and size of liver metastases, and survival data were analyzed retrospectively in 73 patients. Using the cutoff level of 5 ng/ml for CEA and 37 U/ml for CA 19-9, the positivity of these for detecting metastatic deposits were 81% and 56%, respectively. CEA level was correlated with the number (P = 0.0081) and size (P = 0.013) of liver metastases among patients with positive CEA level, while CA 19-9 level was correlated only with the number of liver metastases (P = 0.0072) among those with positive CA 19-9 level. In the overall series, preoperative CEA and CA 19-9 levels were correlated significantly with survival only at higher cutoff levels. In 46 patients undergoing curative hepatectomy, however, these levels were not correlated with survival, even at higher cutoff levels. In conclusion, the CEA level is closely associated with the extent of liver metastases, while the CA 19-9 level may reflect multiplicity of hepatic deposits. Preoperative measurement of serum CEA and CA 19-9 levels appears to be of some prognostic value.     

Assay of serum elastase 1 in adenocarcinoma of the pancreas: diagnostic value, compared and combined study with serum CEA and CA 19-9

Serum elastase 1, CEA and, CA 19-9 titers were determined by radioimmunoassay in 113 patients with benign non pancreatic digestive disease, 88 patients with non pancreatic carcinoma, 25 patients with chronic pancreatitis and 40 patients with pancreatic carcinoma (of whom 34 were classified according to Fortner's staging classification), respectively: a) to evaluate the diagnostic value of elastase in pancreatic carcinoma, b) to compare and to study the value of its association with CEA and CA 19-9 for earlier detection of this type of cancer. The specificity of serum elastase (greater than 500 ng/dl) was greater than that of CA 19-9 (greater than 37 U/ml), (93.3 p. 100 vs 64.6 p. 100, p less than 0.01), but its sensitivity was significantly lower than that of CA 19-9 (27.5 p. 100 vs 82.5 p. 100; p less than 0.001). The sensitivity of CA 19-9 (greater than 37 U/ml) and/or elastase (greater than 500 ng/dl) was 85.2 p. 100 (greater, but not significantly, than CA 19-9 alone) and 91.6 p. 100 in Fortner stage I or II tumors (greater, but not significantly, than Fortner stage III tumors which were at 83.6 p. 100). The specificity of the combined test was 62 p. 100, lower (but not significantly) than CA 19-9 alone. As serum CEA (greater than 5 ng/ml) alone and in association with CA 19-9 was disappointing, it might be replaced by the elastase assay. The combined CA 19-9-elastase assay coupled with morphologic investigations could represent an attractive approach for earlier detection of this cancer.     

Difference in prognostic value between sialyl Lewis(a) and sialyl Lewis(x) antigen levels in the preoperative serum of gastric cancer patients

Sialyl Lewis(a) (CA19-9) and sialyl Lewis(x) antigens (SLX) may play a role in tumor metastasis by serving as functional ligands in the cell adhesion system. The authors examined preoperative serum levels of CA19-9 and SLX in 218 patients who underwent resection for gastric cancer to determine their prognostic value. The patients were divided into two groups, termed the low and high antigen groups, based on a value selected as a diagnostic cutoff. Correlation between the antigen serum levels, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. The disease-specific interval for high CA19-9 and SLX groups was significantly shorter than that of their respective low groups (p = 0.0024 and p < 0.0001, respectively). Patients with stage III/IV tumors who had high serum SLX levels had shorter disease-specific intervals than those with low serum levels (p = 0.0017). A Cox's regression analysis revealed a high serum SLX level as an independent factor for worse outcome. In addition, logistic regression analysis revealed that a high serum SLX level was an independent predictor for liver metastasis. In conclusion, an elevated preoperative serum SLX level was a predictor for poor outcome after resection for gastric cancer, whereas CA19-9 was not.     

Biological and conditional factors should be included when defining criteria for resectability for patients with pancreatic cancer

BackgroundThis study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines.Methods369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified.ResultsBased on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status ≥2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 ≥ 500 U/ml was not (HR: 1.23, P = 0.190).ConclusionThe IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria.     

Preoperative Serum CA125 Levels Predict the Prognosis in Hyperbilirubinemia Patients With Resectable Pancreatic Ductal Adenocarcinoma

Serum carbohydrate antigen 19-9 (CA19-9) is widely used to predict the prognosis for pancreatic ductal adenocarcinoma (PDAC). However, hyperbilirubinemia and the CA19-9 nonsecretor phenotype restrict the usage of serum CA19-9 alone. The goal of this study was to confirm the prognostic role of preoperative serum CA125 in PDAC, especially in patients with jaundice.A total of 211 patients with resected PDAC were eligible for this retrospective study, and were classified into 2 groups based on serum bilirubin levels. The prognostic significance of all clinicopathologic factors was evaluated by univariate and multivariate analyses, and the performance of each factor in predicting overall survival (OS) and recurrence-free survival (RFS) was compared.High preoperative CA125, high TNM stage, and lymph node metastasis were independent risk predictors for OS and RFS in all patients and the 2 subgroups, but high CA19-9 was only significant when considering all patients and those with nonelevated bilirubin. Using time-dependent receiver-operating characteristic analysis, better predictive performance for OS and RFS was observed for serum CA19-9 as compared to serum CA125 in these patients.High serum CA125 can independently predict poor prognosis. Importantly, in PDAC patients with hyperbilirubinemia, preoperative serum CA125 can predict the prognosis, whereas CA19-9 cannot. Preoperative CA19-9 had better predictive performance for survival than CA125, and the performance of CA19-9 did not decline between all patients and those with nonelevated bilirubin, but was significantly affected by hyperbilirubinemia.     

Prognostic Factors for Patients with Borderline Resectable or Locally Advanced Pancreatic Cancer Receiving Neoadjuvant FOLFIRINOX

Background/AimsThere has been growing evidence on the utility of neoadjuvant FOLFIRINOX in borderline resectable (BR) or locally advanced (LA) pancreatic cancer. However, factors predicting survival in these patients remain to be identified, and we aimed to identify these prognostic factors.MethodsBetween January 2013 and April 2017, patients with BR or LA pancreatic cancer who received FOLFIRINOX as their initial treatment were identified. Demographic data and clinical outcomes, including the chemotherapy response, conversion to resection, and survival, were reviewed.ResultsA total of 117 patients with BR (n=39) or LA (n=78) pancreatic cancer were included. Of these patients, 29 (24.8%) underwent curative surgery, and R0 resection was achieved in 21 patients (72.4%). The median progression-free survival and overall survival time of all patients were 11.6 and 19.0 months, respectively. In resected patients, the median relapse-free survival and overall survival times were 14.8 and 28.6 months, respectively. In the multivariate Cox model, the lowest level of serum carbohydrate antigen 19-9 (CA 19-9) and resection after FOLFIRINOX were independent factors for improved overall survival. In the subgroup analysis of patients with initial ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images, the maximum standardized uptake value (SUVmax) of the pancreatic mass was also shown as an independent factor for improved overall survival.ConclusionsIn patients with BR or LA pancreatic cancer, FOLFIRINOX is a valuable neoadjuvant treatment that enables curative surgery in approximately one-quarter of patients and significantly improves overall survival. In these patients, the prognosis can be estimated using the lowest level of serum CA 19-9, operative status, and initial FDG-PET SUVmax.     

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study

Background/ObjectiveThe benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.MethodsPatients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.Results214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3–4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997–3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904–3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151–0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.ConclusionAdjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.     

An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN

BackgroundCurrent guidelines for IPMN include an elevated serum carbohydrate antigen (CA) 19-9 among the worrisome features. However, the correlation of CA 19-9 with histological malignant features and survival is unclear. Serum CEA is also currently used for preoperative management of IPMN, although its measurement is not evidence-based. Accordingly, we aimed to assess the role of these tumor markers as predictors of malignancy in IPMN.MethodsIPMN resected between 1998 and 2018 at Massachusetts General Hospital were analyzed. Clinical, pathological and survival data were collected and compared to preoperative levels of CA 19-9 and CEA. Receiver operating characteristic (ROC) and Cox regression analyses were performed considering cut-offs of 37 U/ml (CA 19-9) and 5 μg/l (CEA).ResultsAnalysis of 594 patients showed that preoperative CA 19-9 levels > 37 U/ml (n = 128) were associated with an increased likelihood of invasive carcinoma when compared to normal levels (45.3% vs. 18.0%, P < 0.001), while there was no difference with respect to high-grade dysplasia (32.9% vs 31.9%, P = 0.88). The proportion of concurrent pancreatic cancer was higher in patients with CA 19-9 > 37 U/ml (17.2% vs 4.9%, P < 0.001). An elevated CA 19-9 was also associated with worse overall and disease-free survival (HR = 1.943, P = 0.007 and HR = 2.484, P < 0.001 respectively). CEA levels did not correlate with malignancy.ConclusionIn patients with IPMN, serum CA19-9 > 37 U/ml is associated with invasive IPMN and concurrent pancreatic cancer as well as worse survival, but not with high-grade dysplasia. Serum CEA appears to have minimal utility in the management of these patients.     

Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery

Background We performed hepatectomy without lymph node (LN) dissection for intrahepatic cholangiocarcinoma (ICC) limited to the peripheral region of the liver, and hepatectomy with extrahepatic bile duct resection and regional LN dissection for any types of ICC extending to the hepatic hilum. Surgical outcomes were evaluated to elucidate the prognostic factors that influence patient survival with respect to intrahepatic recurrence. Methods Forty-one patients underwent resection of ICC with no macroscopic evidence of residual cancer. Results Significant risk factors for poorer survival included preoperative jaundice (P = 0.0115), serum CA19-9 levels >37 U/ml (P = 0.0089), tumor diameter >4.5 cm (P = 0.017), ICC extending to the hepatic hilum (P = 0.0065), mass-forming with periductal-infiltrating type (P = 0.003), poorly differentiated adenocarcinoma, portal vein involvement (P = 0.0785), LN metastasis at initial hepatectomy (P < 0.0001), and positive surgical margin (P = 0.023). Intrahepatic recurrence, which was the predominant manner of recurrence, was detected in 20 patients (74.1%). Patients with intrahepatic recurrence had a significantly high incidence of high serum CA19-9 levels (>37 U/ml; P = 0.0006), preoperative jaundice (P = 0.0262), ICC extended to the hepatic hilum (P = 0.0349), large tumors (>4.5 cm; P = 0.0351), portal vein involvement (P = 0.0423), and LN metastasis at initial hepatectomy (P = 0.009) compared with disease-free patients. The multiple logistic regression analysis revealed that preoperative CA19-9 elevation and obstructive jaundice influenced intrahepatic recurrence of ICC. Conclusions Although LN metastasis is a significant prognostic factor, the most obvious recurrence pattern after surgery was intrahepatic recurrence, which could be predicted preoperatively by a combination of elevated serum CA19-9 levels and manifestation of obstructive jaundice.     

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms

ObjectivesHigh-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs.MethodsSeventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan–Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses.ResultsSerum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs.ConclusionsSerum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.     

Resectability and prognostic factors after resection of hilar cholangiocarcinoma

BACKGROUND/AIMS: Hilar cholangiocarcinoma, still a challenging problem for surgeons and resectional surgery, is the treatment of choice for long-term survival. In this study we tried to evaluate different prognostic factors after resection. METHODOLOGY: From January 1995 to October 2004, 440 patients with hilar cholangiocarcinoma were admitted to the Gastroenterology Surgical Center, Mansoura University, Egypt. Of these patients 73 underwent potentially curative resection giving respectability rate of 17%, and the remaining 367 patients underwent non-surgical treatment because of advanced disease, advanced cirrhosis and poor general condition. Of the 73 patients, 35 (48%) underwent localized hepatic resection and 38 (52%) patients underwent major hepatic resection. Various prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: Hospital mortality occurred in 8 (11%) patients. The most common postoperative complications were: bile leak, liver cell failure and wound infection 23.2%, 17.8% and 9.5% respectively. The survival rates at 1, 2, 3, 4, and 5 years were 79%, 32.6, 18.5, 137% and 13% respectively. The result of univariate analysis revealed that radicality of resection, lymph nodes status, tumor differentiation, modified Bismuth staging, underlying liver pathology, HCV viral infection, blood transfusion, preoperative serum bilirubin <10mg and CA19-9 are dependent prognostic factors. By multivariate Cox analysis radicality of resection, lymph nodes status, serum bilirubin below 10mg/dL level of CA19-9 and hepatitis viral infection were independent predictor factors. CONCLUSIONS: From this study we found that aggressive surgical procedure to obtain curative resection with preoperative serum bilirubin below 10mg and HCV infective negative especially in noncirrhotic liver may bring a better prognosis in hilar cholangiocarcinoma.     

Adjusting CA19-9 values to predict malignancy in obstructive jaundice: influence of bilirubin and C-reactive protein

AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ).METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment.RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively.CONCLUSION: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.