Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer

AIM: To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency, response, outcome, course of carbohydrate antigen 19-9 (CA 19-9)].METHODS: This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with second-line chemotherapy in our center between 2000 and 2008. All patients received first-line chemotherapy with gemcitabine, and prior surgery or radiotherapy was permitted. We analyzed each chemotherapy protocol for second-line treatment, the number of cycles and the type of combination used. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, response rate, grade 3-4 toxicity, dosage modifications and CA 19-9 course.RESULTS: A total of eighty patients (38%) underwent a second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen. Median number of cycles was 4 (range: 1-12) and the median duration of treatment was 2.6 mo (range: 0.3-7.4). The overall disease control rate was 40.0%. The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI: 4.1-6.6) and 3.4 mo (95% CI: 2.4-4.2), respectively. Toxicity was generally acceptable. Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI: 4.5-11.6) vs 5.2 mo (95% CI: 4.0-6.4) for others (P = 0.008).CONCLUSION: A large proportion of patients could benefit from second-line therapy, and CA 19-9 allows efficient treatment monitoring both in first and second-line chemotherapy.     

Analysis of prognostic factors for borderline resectable pancreatic cancer after neoadjuvant chemotherapy: the importance of CA19-9 decrease in patients with elevated pre-chemotherapy CA19-9 levels

BackgroundNeoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel.MethodsFrom 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors.ResultsEighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)].ConclusionIn patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients.     

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase Ⅱ study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m 2 , infused at 10 mg/m 2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reducti     

Impact of gemcitabine on the treatment of metastatic pancreatic cancer

BACKGROUND AND AIM: A previous randomized trial showed gemcitabine was superior to 5-fluorouracil in overall patient survival. However, the incremental improvement in survival was minimal. It is 2.5 years since gemcitabine has become available for the treatment of pancreatic cancer in clinical practice in Japan. The current study was conducted to examine whether treatment outcomes have changed since the introduction of gemcitabine therapy. METHODS: Ninety-one consecutive patients with metastatic pancreatic cancer treated with systemic chemotherapy at the National Cancer Center Hospital East were surveyed. Patients admitted before April 2001 received 5-fluorouracil, and those admitted subsequently received gemcitabine. The patients were divided into the gemcitabine group (n = 50) and the non-gemcitabine group (n = 41), and these groups were compared for five outcomes, objective response rate, non-progressive disease rate, carbohydrate antigen (CA)19-9 response rate, actual survival time, and difference between estimated and observed survivals. The estimated survival time was determined using the prognostic index reported in the previous study. RESULTS: Except for the objective response rate, the four other outcomes in the gemcitabine group were significantly superior to those in the non-gemcitabine group. The frequency of non-progressive disease, CA19-9 response, and favorable prognosis compared with the estimated survival, were 58%, 22%, and 60%, respectively, in the gemcitabine group, and 22%, 6%, 30%, respectively, in the non-gemcitabine group. The median survival time in the gemcitabine and non-gemcitabine group was 5.73 and 2.87 months, respectively. CONCLUSION: It is suggested that there was a definite improvement in pancreatic cancer treatment after gemcitabine was introduced.     

Low efficacy of serum levels of CA 19-9 in prediction of malignant diseases in asymptomatic population in Taiwan

BACKGROUND/AIMS: Serum levels of carbohydrate antigen (CA) 19-9 have long been employed as a biomarker in diagnosing pancreatic cancer in symptomatic patients. We assessed the clinical usefulness of serum CA 19-9 in screening pancreatic cancer and other malignancies in individuals without symptoms. METHODOLOGY: The study enrolled 5,343 consecutive asymptomatic individuals who completed a health check-up comprising serum CA 19-9, chest film, abdominal ultrasonography, esophagogastroduodenoscopy, and colonoscopy or sigmoidoscopy. The sensitivity, specificity and positive predictive rate of CA 19-9 in detecting cancers were analyzed. RESULTS: There were 385 patients (7.2%) with CA 19-9 higher than 37 U/mL. Two patients diagnosed with pancreatic cancer had CA 19-9 levels of 46,885 U/mL and 88.4 U/mL, respectively. Thirteen among 58 patients with other cancers had CA 19-9 levels higher than 37 U/mL. If the cut-off value of CA 19-9 was set at 37 U/mL, the sensitivity and specificity for pancreatic cancer and other cancers were 100% and 92.8%, as well as 22.4% and 92.9%, respectively. However, the positive predictive rates for pancreatic cancer and other cancers were as low as 0.5% and 3.4%, respectively. CONCLUSIONS: Efficacy of CA 19-9 in predicting either pancreatic cancer or other cancers in the asymptomatic population is low.     

胰腺癌患者血清CEMIP、CA19-9和CA242水平变化及其临床意义*

目的 研究胰腺癌患者血清CEMIP、CA19-9和CA242水平变化及其临床意义。方法 2013年4月～2016年8月我院诊治的92例胰腺癌患者、105例胰腺良性疾病患者和选择的83例健康人，采用ELISA法检测血清细胞迁移诱导透明质酸结合蛋白（CEMIP）水平，采用放射免疫法检测血清CA19-9和CA242水平。应用受试者工作特征曲线（ROC）下面积（AUC）评价各指标的诊断效能。采用Kaplan-Meier和Cox风险比例模型行生存分析。采用Logistic回归分析影响术后生存的因素。结果 胰腺癌患者血清CEMIP、CA19-9和CA242水平分别为0.7（0.4，1.0） ng/mL、180.1（89.1，230.3） U/mL和61.7（20.7，93.5）U/mL，均显著高于胰腺良性疾病患者和健康人，差异有统计学意义（P均<0.05）；应用血清CEMIP、CA19-9和CA242联合诊断胰腺癌的AUC为0.966，其诊断效能显著高于任一指标单独诊断；应用血清CEMIP、CA19-9和CA242水平预测胰腺癌患者根治术后1年生存的效能均较高；经Kaplan-Meier和Cox多因素分析，结果表明肿瘤分化程度、血管侵犯、术后化疗、血清CEMIP≥0.7 ng/mL、CA19-9≥90.3 U/mL和CA242≥32.8 U/mL均是影响胰腺癌患者根治术后生存的独立危险因素。结论 检测胰腺癌患者血清CEMIP、CA19-9和CA242水平可有助于对疾病的诊断和预后评估。     

Comparison of tumor marker CA 242 with CA 19-9 and carcinoembryonic antigen (CEA) in pancreatic cancer

BACKGROUND/AIMS: Although there are a variety of tumor markers used for diagnosis of pancreatic carcinoma, the sensitivity and specificity of those markers have not yet reached an ideal level. The aim of this study was to compare the diagnostic value of CA 242 with CA 19-9 and CEA in the patients with pancreatic cancer. METHODOLOGY: Serum CA 242, CA 19-9 and CEA levels were determined in 135 subjects in the following groups: Pancreatic cancer (n = 40), cholangiocellular carcinoma (n = 15), hepatocellular carcinoma (n = 10), cirrhosis (n = 7), chronic active hepatitis (n = 7), choledochal stone (n = 12), chronic pancreatitis (n = 9), acute pancreatitis (n = 6), and healthy controls (n = 29). RESULTS: An elevated serum CA 242 concentration (> 20 U/mL) was found in 30 out of 40 (70%) (mean; 2163 +/- 838 U/mL) patients with pancreas cancer, in 11 out of 15 patients with cholangiocellular carcinoma (93.3%) (mean 916 +/- 529 U/mL), in none of patients with hepatocellular carcinoma and healthy controls. Slightly elevated CA 242 concentration was found in 6 out of 41 patients with benign hepatobiliary and pancreatic disease (range 0.4-97.8 U/mL) (1 acute pancreatitis, 2 chronic pancreatitis, 1 cirrhosis, 2 choledochal stone). Mean serum CA 242, CA 19-9 and CEA levels of the pancreas cancer group were significantly higher than those of the other groups except the cholangiocellular carcinoma group. There was no significant difference between the stage of pancreas cancer regarding mean serum CA 242, CA 19-9 and CEA level. There was positive correlation between serum CA 242 and CA 19-9 level. In the pancreas cancer, the sensitivity of CA 242, CA 19-9 and CEA was 75%, 80%, 40%, respectively and the specificity of those markers was 85.5%, 67.5% and 73%, respectively. CONCLUSIONS: In conclusion, the advantage of CA 242 compared to CA 19-9 is that its specificity is higher than that of CA 19-9 in the diagnosis of pancreas cancer.     

Type 2 diabetes mellitus and CA 19-9 levels

AIM： To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age and gender-matched control subjects.
METHODS： We recorded duration of diabetes and examined fasting glucose levels, HbAlc levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups.
RESULTS： The average CA 19-9 level was 46.0 ± 22.4 U/mL for diabetic patients whereas it was 9.97± 7.1 U/mL for the control group （P 〈 0.001 ）. Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbAlc level （t = 8.8, P 〈 001 ）. Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities.
CONCLUSION： CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cutoff value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.     

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.     

Type 2 diabetes mellitus and CA 19-9 levels

AIM: To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age- and gender-matched control subjects. METHODS: We recorded duration of diabetes and examined fasting glucose levels, HbA1c levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups. RESULTS: The average CA 19-9 level was 46.0 ± 22.4 U/mL for diabetic patients whereas it was 9.97 ± 7.1 U/mL for the control group (P ＜ 0.001 ). Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbA1c level (t = 8.8, P ＜ 001 ). Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities. CONCLUSION: CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cutoff value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.     

Impact of gemcitabine on the treatment of metastatic pancreatic cancer

Background and Aim:  A previous randomized trial showed gemcitabine was superior to 5-fluorouracil in overall patient survival. However, the incremental improvement in survival was minimal. It is 2.5 years since gemcitabine has become available for the treatment of pancreatic cancer in clinical practice in Japan. The current study was conducted to examine whether treatment outcomes have changed since the introduction of gemcitabine therapy.
Methods:  Ninety-one consecutive patients with metastatic pancreatic cancer treated with systemic chemotherapy at the National Cancer Center Hospital East were surveyed. Patients admitted before April 2001 received 5-fluorouracil, and those admitted subsequently received gemcitabine. The patients were divided into the gemcitabine group ( n  = 50) and the non-gemcitabine group ( n  = 41), and these groups were compared for five outcomes, objective response rate, non-progressive disease rate, carbohydrate antigen (CA)19-9 response rate, actual survival time, and difference between estimated and observed survivals. The estimated survival time was determined using the prognostic index reported in the previous study.
Results:  Except for the objective response rate, the four other outcomes in the gemcitabine group were significantly superior to those in the non-gemcitabine group. The frequency of non-progressive disease, CA19-9 response, and favorable prognosis compared with the estimated survival, were 58%, 22%, and 60%, respectively, in the gemcitabine group, and 22%, 6%, 30%, respectively, in the non-gemcitabine group. The median survival time in the gemcitabine and non-gemcitabine group was 5.73 and 2.87 months, respectively.
Conclusion:  It is suggested that there was a definite improvement in pancreatic cancer treatment after gemcitabine was introduced.     

Can preoperative CA19‐9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma?

Background: We aimed to explore the predictive ability of preoperative carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) levels for assessing tumor resectability (R0 resection) in patients with pancreatic adenocarcinoma. Methods: The present study included 72 patients who had been treated surgically for potentially resectable pancreatic adenocarcinoma and 42 patients who had been treated surgically for palliation (bypass surgery) at our institution. Pancreatic adenocarcinoma was histologically confirmed by pathological examination of the resected specimen or, if unresected, by intraoperative biopsy. Results: For resectable disease, the mean and median values of CA19‐9 were significantly lower than for R1/2 or unresectable disease. The best cut‐off points for CEA, CA19‐9, and tumor size to predict resectability were 2.47 ng/mL, 92.77 U/mL and 11.85 cm³, respectively. A CA19‐9 ≥ 92.77 U/mL and both tumor markers no less than the cut‐off levels predicted the possibility of R1/2 or unresectability with 90.6% and 88.6% accuracy, respectively. However, either tumor marker or both tumor markers less than the cut‐off levels predicted the probability of R0 resection only with 27.1% and 40.6% accuracy, respectively. The independent contributing factors to resectability (R0 resection) by multivariate regression analysis were a CA 19‐9 < 92.77 U/mL, a tumor size < 11.85 cm³, and a less advanced AJCC stage. Conclusion: The present study demonstrates that preoperative serum CA19‐9 and CEA levels can be used for the prediction of resectability (R0 resection) in patients with pancreatic adenocarcinoma, which may enable a simple and cost‐effective exclusion of such patients who are unlikely to benefit from surgery.     

Carbohydrate antigen CA 19-9: value in pancreatic pathology

In order to determine the diagnostic usefulness of the dosage of carbohydrate antigen (CA 19-9) serum levels in pancreatic diseases, 38 patients with pancreatic lesions proved at laparotomy were studied. Pancreatic lesions were classified into two groups: a) group I: pancreatic adenocarcinoma (17 cases) b) group II: benign pancreatic diseases (21 cases). CA 19-9 serum levels were statistically higher in patients of the first group (p less than 0.001). All patients except one with CA 19-9 higher than 60 U/ml had pancreatic carcinoma. All patients except two with CA 19-9 less than 60 U/ml had a benign lesion. The sensitivity and specificity of CA 19-9 were 88 and 95 p. 100 respectively. These results show that CA 19-9 dosage is useful in distinguishing between benign and malign lesions of the pancreas.     

Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas

Purose. Determine the safety and efficacy of twice weekly gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with surgically staged, locally advanced pancreatic cancer. Methods. Patients with surgically staged, locally advanced, nonmetastatic adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice weekly (40 mg/m²/d) for 5 wk concurrent with upper abdominal radiation (50.4 Gy in 180 cGy daily fractions over 5.5 wk). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg/m²) weekly for five cycles. Each cycle consisted of 3 wk of treatment followed by 1 wk without treatment. Disease progression and response were assessed at 6- to 8-wk intervals. Results. From February through December 1999, 43 patients were entered into this phase II trial, 39 of whom were evaluable for treatment response. The median age was 59 yr (range: 39–84 yr); there were 18 males (47%) in the study. Grade III and IV hematologic toxicity occurred in 48 and 21% of patients, respectively, and was primarily leukocytopenia and neutropenia. Grade III and IV gastrointestinal toxicities occurred in 31 and 10% of patients, respectively. There was one death attributed to sepsis. The concurrent gemcitabine and radiation portion of the study was completed without treatment interruptions in 56% of patients. The overall median survival was 8.2 mo and the median survival in the 44% of patients demonstrating a sustained CA-19-9 response was 13.5 mo. Only six patients experienced local regional progression as their first site of failure. Two patients (5%) were still alive at 35 and 41 mo posttreatment. Conclusions. These results confirm the feasibility of twice weekly gemcitabine and radiation for the treatment of pancreatic cancer. Although this treatment strategy produced good local regional control, this did not result in a survival advantage. Stratifying patients by performance status and CA-19-9 response in future trials may be of value.     

Gemcitabine treatment in patients with inoperable locally advanced/metastatic pancreatic cancer and prognostic factors

OBJECTIVE: Most patients with pancreatic cancer show an inoperable locally advanced/ metastatic tumour at the time of diagnosis. The present study was aimed at determining the prognostic factors in patients with advanced pancreatic carcinoma treated with gemcitabine. MATERIAL AND METHODS: Sixty-seven unresectable or metastatic pancreatic cancer patients treated with gemcitabine were included in the study and a total of 258 cycles of treatment were applied. RESULTS: The overall response rate was 5%. Thirty-one percent of the patients had stable disease, whereas progressive disease was seen in 49%. Clinical benefit response rate was 15%. The median duration of response was 7.3 months. Median progression-free survival was 3 months, while median overall survival was 9 months. Univariate analysis revealed that worse results were found in patients with performance status (PS) = 2, and in patients with primary tumour location in the body or tail of the pancreas (p<0.05). Multivariate analysis of data revealed that the most important factor was PS of the patient, as the patients with PS = 2 had worse results than the patients with PS = 0-1 (p<0.05). CONCLUSIONS: Low PS is a negative predictive factor for the survival of patients with advanced pancreatic carcinoma treated with gemcitabine.     

Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma

AIM： To evaluate the clinical value of serum CA19-9 levels in predicting the respectability of pancreatic carcinoma according to receiver operating characteristic （ROC） curve analysis.
METHODS： Serum CA19-9 levels were measured in 104 patients with pancreatic cancer which were possible to be resected according to the imaging. ROC curve was plotted for the CA19-9 levels. The point closest to the upper left-hand corner of the graph were chosen as the cut-off point. The sensitivity, specificity, positive and negative predictive values of CA19-9 at this cut-off point were calculated.
RESULTS： Resectable pancreatic cancer was detected in 58 （55.77%） patients and unresectable pancreatic cancer was detected in 46 （44.23%） patients. The area under the ROC curve was 0.918 and 95% CI was 0.843-0.992. The CA19-9 level was 353.15 U/mL, and the sensitivity and specificity of CA19-9 at this cutoff point were 93.1% and 78.3%, respectively. The positive and negative predictive value was 84.38% and 90%, respectively.
CONCLUSION： Preoperative serum CA19-9 level is a useful marker for further evaluating the resectability of pancreatic cancer. Obviously increased serum levels of CA19-9 （〉 353.15 U/mL） can be regarded as an ancillary parameter for unresectable pancreatic cancer.     

Serum tumor markers not useful in screening patients with pancreatic mucinous cystic lesions associated with malignant changes

BACKGROUND: Serum cancer antigen 19-9 (CA19-9) pro-vides additional information about mucinous cystic pancre-atic neoplasm (MPN). This study was undertaken to assess both CA19-9 and carcinoembryonic antigen (CEA) serum concentrations in consecutive patients affected by MPNs and other chronic benign and malignant pancreatic diseases. We also evaluated whether serum CA19-9 and CEA determina-tions provide additional information such as the presence of invasive carcinoma in MPN patients.
METHODS: Serum CA19-9 and CEA from 91 patients with pancreatic diseases were tested by commercially available kits at the time of diagnosis. The upper reference limit of serum CA19-9 was 37 U/mL and that of serum CEA was 3 ng/mL.
RESULTS: Thirty-ifve patients was diagnosed with chronic pancreatitis (CP), 32 with MPN, and 24 with pancreatic ductal adenocarcinoma (PDAC) conifrmed histologically. Surgery was carried out in 5 CP patients, in 10 MPN patients (7 of them had severe dysplasia), and 9 PDAC patients. Serum CA19-9 activity was high in 12 (34.3%) CP patients, in 7 (21.9%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.089). High se-rum CEA concentrations were noted in 6 (17.1%) CP patients, in 6 (18.8%) MPN patients, and in 12 (50.0%) PDAC patients (P=0.010). In the 7 MPN patients associated with histological-ly conifrmed severe dysplasia, 3 (42.9%) patients had elevated serum activity of serum CA19-9, and 2 (28.6%) patients had high levels of CEA.
CONCLUSION: Serum determination of oncological markers is not useful in selecting MPN patients with malignant changes.     

Survival and prognostic factors of unresectable pancreatic cancer

GOALS: The aim of this study was to evaluate the prognostic significance of clinical and laboratory variables, and to investigate survival benefits for different treatment modalities in unresectable pancreatic cancer. BACKGROUND: The majority of pancreatic cancers are found to be unresectable. Therefore, estimations of prognosis and decisions of treatment modalities are important in optimizing the various aspects of care. STUDY: Three hundred and forty unresectable locally advanced, or metastatic pancreatic cancer patients were enrolled from January 1998 to January 2005 at the Seoul National University Hospital. RESULTS: One hundred and five patients received chemotherapy only and 59 patients received concurrent chemoradiotherapy (CCRT). Age, performance status, tumor location, initial CA 19-9 level, American Joint Committee on Cancer stage, and treatment modality (supportive care only, chemotherapy, vs. CCRT) were found to have prognostic significance for overall survival (OS) by univariate analysis, whereas initial CA 19-9 level, stage, and treatment modality were identified as independent prognostic factors by multivariate analysis. In subgroup analysis, stage III patients treated by CCRT (median OS, 10.4 mo) or chemotherapy alone (11.3 mo) showed survival benefit over supportive care (6.4 mo), and stage IV patients treated by chemotherapy alone (6.4 mo) showed survival benefit over supportive care (3.1 mo). CONCLUSIONS: Initial CA 19-9, American Joint Committee on Cancer stage, and treatment modality were independent prognostic factors of OS, and the patients who received chemotherapy or CCRT showed better survival than those who received supportive care only.     

Intensity modulated radiation therapy and chemotherapy for locally advanced pancreatic cancer： Results of feasibility study

AIM: To explore whether intensity modulated radiation therapy (IMRT) in combination with chemotherapy could increase radiation dose to gross tumor volume without severe acute radiation related toxicity by decreasing the dose to the surrounding normal tissue in patients with locally advanced pancreatic cancer. METHODS: Twenty-one patients with locally advanced pancreatic cancer were evaluated in this clinical trial. Patients would receive the dose of IMRT from 21Gy to 30Gy in 7 to 10 fractions within two weeks after conventional radiotherapy of 30Gy in 15 fractions over 3 weeks. The total escalation tumor dose would be 51, 54, 57, 60Gy, respectively. 5-fluororacil (5-FU) or gemcitabine was given concurrently with radiotherapy during the treatment course. RESULTS: Sixteen patients who had completed the radiotherapy plan with doses of 51Gy (3 cases), 54Gy (3 cases), 57Gy (3 cases) and 60Gy (7 cases) were included for evaluation. The median levels of CA19-9 prior to and after radiotherapy were 716 U/ml and 255 U/ml respectively (P<0.001) in 13 patients who demonstrated high levels of CA19-9 before radiotherapy. Fourteen patients who suffered from pain could reduce at least 1/3-1/2 amount of analgesic intake and 5 among these patients got complete relief of pain. Ten patients improved in Karnofsky performance status (KPS). The median follow-up period was 8 months and one-year survival rate was 35%. No patient suffered more than grade III acute toxicities induced by radiotherapy. CONCLUSION: Sixty Gy in 25 fractions over 5 weeks with late course IMRT technique combined with concurrent 5-FU chemotherapy can provide a definitely palliative benefit with tolerable acute radiation related toxicity for patients with advanced pancreatic cancer.     

Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM: To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma (ICC). METHODS: We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003. Of these, 429 (8.1%) patients were diagnosed with ICC, and their clinicopathological, surgical, and survival characteristics were analyzed. RESULTS: Upper abdominal discomfort or pain (65.0%), no symptoms (12.1%), and hypodynamia (8.2%) were the major causes for medical attention. Laboratory tests showed 198 (46.4%) patients were HBsAg positive, 90 (21.3%) had α-fetoprotein > 20 μg/L, 50 (11.9%) carcinoembryonic antigen > 10 μg/L, and 242 (57.5%) carbohydrate antigen 19-9 (CA19-9) > 37 U/mL. Survival data was available for 329 (76.7%) patients and their mean survival time was 12.4 mo. The overall survival of the patients with R0, R1 resection and punching exploration were 18.3, 6.6 and 5.6 mo, respectively. Additionally, CA19-9 > 37 U/mL was associated with lymph node metastases, but inversely associated with cirrhosis. Multivariate analysis indicated that radical resection, lymph node metastases, macroscopic tumor thrombi and size, and CA19-9 were associated with prognosis.CONCLUSION: Surgical radical resection is still the most effective means to cure ICC. Certain laboratory tests (such as CA19-9) can effectively predict the survival of the patients with ICC.