Postoperative Carbohydrate Antigen Research Articles

Assessment of Tumor Markers in Renal Transplant Recipients.

Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its noninvasiveness and convenience. Furthermore, it is known that the excretion and metabolism of some tumor markers are affected by impaired renal function. In the present study, we investigated the effect of improved renal function on pre-and post-transplantation changes in tumor marker levels [carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and prostate-specific antigen (PSA)] in renal transplant recipients. A total of 116 renal transplant recipients, who had not been diagnosed with malignancies between January 2012 and December 2019, were included, and tumor markers were investigated. CEA showed a significant decrease after kidney transplantation, regardless of the dialysis type (3.6→2.6 ng/ml, p<0.001), while other tumor markers showed a significant increase (AFP: 3.6→3.7 ng/ml; CA19-9: 16.2→19.5 U/ml; PSA: 0.95→1.05 ng/ml; all p<0.05). Pre- and postoperative eGFR ratios and postoperative liver function were identified as factors influencing the postoperative CEA and CA19-9 values, while PSA was influenced by the duration of dialysis. No statistically significant factors were found for AFP levels. Caution should be exercised when investigating tumor markers in patients with renal dysfunction, as tumor marker levels may vary depending on the pathophysiology of each patient.

Long-term prognosis of patients with gallbladder carcinoma after curative-intent resection based on changes in the ratio of carbohydrate antigen 19-9 to total bilirubin (CA19-9/TB): a multicenter retrospective cohort study

Background: The prognostic value of carbohydrate antigen 19-9 (CA19-9) is known to be affected by elevated bilirubin levels in patients with gallbladder carcinoma (GBC). The clinical significance of changes in the ratio of CA19-9 levels to total bilirubin (TB) levels in patients with GBC after curative-intent resection remains unknown. The aim of this study was to determine the prognostic value of changes in preoperative and postoperative CA19-9/TB ratio in these patients. Methods: Prospectively colleced data on consecutive patients who underwent curative-intent resection for GBC between January 2015 and December 2020 stored in a multicenter database from 10 hospitals were analysed in this retrospective cohort study. Based on the adjusted CA19-9 defined as the ratio of CA19-9 to TB, and using 2×103 U/µmol as the upper normal value, patients were divided into a normal group (with normal preoperative and postoperative adjusted CA19-9), a normalization group (with abnormal preoperative but normal postoperative adjusted CA19-9), and a non-normalization group (with abnormal postoperative adjusted CA19-9). The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). The log-rank test was used to compare OS and RFS among the groups. The Cox regression model was used to determine factors independently associated with OS and RFS. Results: The normal group (n=179 patients) and the normalization group (n=73 patients) had better OS and RFS than the non-normalization group (n=65 patients) (the 3-year OS rates 72.0%, 58.4% and 24.2%, respectively; the RFS rates 54.5%, 25.5% and 11.8%, respectively; both P&lt;0.001). There were no significant differences between the normal and the normalization groups in OS and RFS (OS, P=0.255; RFS, P=0.130). Cox regression analysis confirmed that the non-normalization group was independently associated with worse OS and RFS. Subgroup analysis revealed that the non-normalization group of patients who received adjuvant therapy had significantly improved OS and RFS as compared to those who did not receive adjuvant therapy (OS, P=0.025; RFS, P=0.003). Conclusions: Patients with GBC who underwent curative-intent surgical resection with postoperative abnormal levels of adjusted CA19-9 (the CA19-9/TB ratio) were associated with poorer long-term survival outcomes. Adjuvant therapy after surgery improved the long-term outcomes of these patients.

Tumor Size Reduction and Serum Carbohydrate Antigen 19-9 Kinetics After Neoadjuvant FOLFIRINOX in Patients With Pancreatic Ductal Adenocarcinoma

BackgroundChanges in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX. MethodsThis was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated. ResultsAmong 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization. ConclusionIn patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival.

ASO Author Reflections: Postoperative Carbohydrate Antigen 19-9 Levels Become a Reliable Biomarker for Establishing Intensity-Stratified Adjuvant Treatments in Pancreatic Ductal Adenocarcinoma.

ASO Author Reflections: Postoperative Carbohydrate Antigen 19-9 Levels Become a Reliable Biomarker for Establishing Intensity-Stratified Adjuvant Treatments in Pancreatic Ductal Adenocarcinoma.

Postoperative Carbohydrate Antigen 19-9 Level as a Good Indicator of Ineffective Response to the Currently Recommended S-1 Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma: A Single-Center, Retrospective Study.

The intensity of adjuvant treatment for pancreatic ductal adenocarcinomas (PDACs) has not been stratified according to the risk after resection. This study was designed to identify patients with PDACs in whom the current S-1 adjuvant treatment is ineffective. This single-center, retrospective study included patients who underwent pancreatectomy for PDACs from 2009 to 2020 at Sendai Open Hospital and were receiving S-1 adjuvant treatment. The independent risk factors for recurrence and survival were determined by using a Cox proportional hazards regression model. The effects of S-1 adjuvant treatment and detailed patterns of recurrence were evaluated in patients with high-risk factors. Overall, 118 patients with PDAC received S-1 adjuvant treatment. Postoperative nonnormalized carbohydrate antigen (CA19-9) was a predictive risk factor for recurrence (p < 0.010; hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.26-6.62) and survival (p = 0.008; HR, 2.25; 95% CI, 1.24-4.11) after S-1 adjuvant treatment. In 24 patients with nonnormalized postoperative CA19-9, S-1 monotherapy was ineffective in preventing recurrence, even during the treatment period, compared with that noted in patients who did not receive adjuvant treatment. The recurrence rate during adjuvant treatment was 41.7%; in all cases, recurrence was caused by distant metastasis. The total recurrence rate was up to 95.8%, and distant recurrence was especially frequent. The current S-1 adjuvant treatment regimen is ineffective for patients with postoperative nonnormalized CA19-9. The postoperative CA19-9 level may be a good indicator for further aggressive treatment. This study may lead to further discussions on intensity stratification of adjuvant treatments for PDAC.

The relationship between serum CA-125 level and recurrence in surgical stage 1 endometrial cancer patients.

The majority of patients diagnosed with early stage endometrial cancer have a favorable prognosis; however, approximately 10-15% experience a recurrence. Therefore, the aim of the present study was to evaluate whether post-operative carbohydrate antigen 125 (CA-125) levels could be used to predict recurrence and recurrence-free survival (RFS) in patients with surgical stage I endometrial cancer. We enrolled a total of 518 patients with stage I endometrial cancer who underwent surgical treatment between January 2010 and March 2019. Serum CA-125 levels were measured prior to surgery, as well as 6-12 months after surgery. Subsequently, the correlations between the CA-125 levels, cancer recurrence, and RFS were analyzed. Although the pre-operative CA-125 level was not associated with the risk of cancer recurrence, the post-operative CA-125 level was found to be the only independent predictor of recurrence in both univariate and multivariate analyses. Additionally, we found that a post-operative CA-125 cut-off value of 13.75 U/mL yielded the best sensitivity and specificity for predicting cancer recurrence. Patients with a post-operative CA-125 level ≥ 13.75 U/mL, and those with a level < 13.75 U/mL, had a median time to recurrence and a 5-year RFS rate of 35.5 vs. 50.5 months and 84.7 vs. 94.4%, respectively. Additionally, post-operative CA-125 levels were not found to be correlated with pre-operative levels. In patients with stage I endometrial cancer, a post-operative CA-125 level ≥13.75 U/mL was found to be significantly correlated with a higher recurrence rate, as well as a shorter RFS. Therefore, obtaining a follow-up CA-125 level within 6-12 months after staging surgery may be a promising noninvasive biomarker for predicting recurrence.

Association of normalization of postoperative carbohydrate antigen 125 levels with treatment failure following uterine artery embolization for adenomyosis.

To investigate the association between carbohydrate antigen 125 (CA125) level and adenomyosis treatment failure (TF) after uterine artery embolization (UAE). We evaluated 224 patients with symptomatic adenomyosis who underwent UAE between January 2016 and December 2020. Improvements in dysmenorrhea and menorrhagia were assessed on the basis of symptom relief criteria. The factors associated with TF were investigated using a multivariate logistic regression model. Patients were analyzed for preoperative CA125 levels, postoperative CA125 levels, and the normalization of postoperative CA125 levels. Long-term symptom relief and quality of life after UAE were compared between the groups. During the 24-month follow-up, 50 patients (22.3%) experienced TF. Compared to patients in the non-TF group, those in the TF group had significantly higher preoperative and postoperative CA125 levels (p < 0.05). Multivariate analysis revealed that failure to normalize postoperative CA125 levels was independently associated with an increased risk of TF (34.7% vs. 8.5%, p < 0.001; hazard ratio 3.953, 95% confidence interval 1.567-9.973, p = 0.004). After a 3-month follow-up period, patients who normalized their CA125 levels were more likely to achieve complete necrosis on magnetic resonance imaging than those who did not (82.1% vs. 56.8%, p < 0.001). Normalization of postoperative CA125 levels was significantly associated with fewer symptoms and better quality of life 12 months after UAE (p < 0.05). Following UAE, normalization of postoperative CA125 levels, rather than absolute values, was the strongest predictive marker of TF.

A nomogram was developed using clinicopathological features to predict postoperative liver metastasis in patients with colorectal cancer.

The objective of this study is to examine the risk factors that contribute to the development of liver metastasis (LM) in patients who have suffered radical resection for colorectal cancer (CRC), and to establish a nomogram model that can be used to predict the occurrence of the LM. The present study enrolled 1377 patients diagnosed with CRC between January 2010 and July 2021. The datasets were allocated to training (n = 965) and validation (n = 412) sets in a randomly stratified manner. The study utilized univariate and multivariate logistic regression analyses to establish a nomogram for predicting LM in patients with CRC. Multivariate analysis revealed that T stage, N stage, number of harvested lymph nodes (LNH), mismatch repair (MMR) status, neutrophil count, monocyte count, postoperative carcinoembryonic antigen (CEA) levels, postoperative cancer antigen 125 (CA125) levels, and postoperative carbohydrate antigen 19-9 (CA19-9) levels were independent predictive factors for LM after radical resection. These factors were then utilized to construct a comprehensive nomogram for predicting LM. The nomogram demonstrated great discrimination, with an area under the curve (AUC) of 0.782 for the training set and 0.768 for the validation set. Additionally, the nomogram exhibited excellent calibration and significant clinical benefit as confirmed by the calibration curves and the decision curve analysis, respectively. This nomogram has the potential to support clinicians in identifying high-risk patients who may develop LM post-surgery. Clinicians can devise personalized treatment and follow-up plans, ultimately leading to an improved prognosis for patients.

Safety and Efficacy of Neoadjuvant SABR in Pancreatic Cancer: Effect of Magnetic Resonance Imaging–Guided Respiratory-Gated Adaptive Radiation Therapy

We aimed to evaluate the safety and efficacy of neoadjuvant SABR using magnetic resonance imaging-guided respiratory-gated adaptive radiation therapy (MRgRg-ART) in pancreatic cancer. We performed a single-institution retrospective review in patients with pancreatic cancer who underwent neoadjuvant SABR followed by surgical resection. After neoadjuvant chemotherapy, those considered resectable by the multidisciplinary team received SABR over 5 consecutive days using MRgRg-ART. Factors associated with severe postoperative complications (Clavien-Dindo grade ≥III) and prognostic factors for overall survival were analyzed. Sixty-two patients were included in the analysis, with a median follow-up of 10.3 months. The median prescribed dose to the planning target volume was 50 Gy. Fifty-two (85.3%) patients underwent R0 resection, and 11 (18.0%) experienced severe postoperative complications. No factors were associated with the incidence of severe postoperative complications. There were 3 cases of locoregional recurrence, resulting in a 12-month local control rate of 93.1%. Elevated postoperative carbohydrate antigen 19-9 was significantly associated with poor overall survival in the multivariate analysis (P=.037). Neoadjuvant SABR with 50 Gy using MRgRg-ART delivered to pancreatic cancer resulted in a notable survival outcome with acceptable toxicities. Further studies are warranted to investigate the long-term effects of this method.

Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. The median recurrence-free survival and overall survival were 30.0 and 90.9months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Carbohydrate Antigen 19-9 Response to Initial Adjuvant Chemotherapy Predicts Survival and Failure Pattern of Resected Pancreatic Adenocarcinoma but Not Which Patients Are Suited for Additional Adjuvant Chemoradiation Therapy: From a Prospective Randomized Study

The predictive value of carbohydrate antigen 19-9 (CA19-9) for adjuvant chemo(radiation) therapy of resected pancreatic adenocarcinoma (PDAC) is undefined. We analyzed CA19-9 levels in patients with resected PDAC in a prospective randomized trial of adjuvant chemotherapy with or without additional chemoradiation therapy (CRT). Patients with postoperative CA19-9 ≤92.5 U/mL and serum bilirubin ≤2 mg/dL were randomized to 2 arms: patients in 1 arm received 6 cycles of gemcitabine, whereas those in the other received 3 cycles of gemcitabine followed by CRT and another 3 cycles of gemcitabine. Serum CA19-9 was measured every 12 weeks. Those who had CA19-9 levels always <3 U/mL were excluded from the exploratory analysis. One hundred forty-seven patients were enrolled in this randomized trial. Twenty-two patients with CA19-9 levels always ≤3 U/mL were excluded from the analysis. For the 125 participants, median overall survival (OS) and recurrence-free survival were 23.1 and 12.1 months, respectively, with no significant differences between the study arms. Postresection CA19-9 levels and, to a lesser extent, CA19-9 change predicted OS (P=.040 and .077, respectively). For the 89 patients who completed the initial 3 cycles of adjuvant gemcitabine, the CA19-9 response was significantly correlated with initial failure over the distant site (P=.023) and OS (P=.0022). Despite a trend of less initial failure over the locoregional area (P=.031), neither postoperative CA19-9 level nor CA19-9 response helped to select patients who might have a survival benefit from additional adjuvant CRT. CA19-9 response to initial adjuvant gemcitabine predicts survival and distant failure of PDAC after resection; however, it cannot select patients suited for additional adjuvant CRT. Monitoring CA19-9 levels during adjuvant therapy for postoperative patients with PDAC may guide therapeutic decisions to prevent distant failure.

The relationship between albumin-bilirubin score and survival in patients operated for pancreatic cancer.

To investigate whether albumin-bilirubin score can be used as a prognostic marker in pancreatic cancer patients post-surgery. The retrospective study was conducted at the Medical Oncology Clinic, Karadeniz Technical University, Trabzon, Turkey, and comprised data from 2010 to 2018 of pancreatic cancer patients who had undergone distal pancreatectomy or pancreaticoduodenectomy and were followed up for 3 years. Preoperative and postoperative serum albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, bilirubin, neutrophil:lymphocyte ratio and platelet:lymphocyte ratio were compared as inflammation markers, while albumin-bilirubin scores were calculated using the equation linear predictor. Data was analysed using SPSS 17. Of the 39 patients, 23(59%) were men and 16(41%) were women. The mean age of the sample was 62.4±10.2 years. No statistically significant changes were observed between preoperative and postoperative albumin-bilirubin scores, carcinoembryonic antigen, neutrophil:lymphocyte ratio and platelet:lymphocyte ratio (p>0.05). Significant decreases were observed in postoperative carbohydrate antigen 19-9, aspartate transaminase and alanine transaminas levels (respectively<0.05). No significant change was determined in postoperative albumin-bilirubin grade distributions compared to preoperative values (p=0.180). Although the rate of recurrence increased in line with preoperative albumin-bilirubin scores, the finding was not statistically significant (p=0.055). Mortality rate increased significantly in line with preoperative albumin-bilirubin scores (p=0.013). The albumin-bilirubin score affected survival in patients with pancreatic cancer, and can be employed as a prognostic factor in this patient group.

Importance of Normalization of Carbohydrate Antigen 19-9 in Patients With Intrahepatic Cholangiocarcinoma.

BackgroundAlthough carbohydrate antigen 19-9 (CA19-9) is an established prognostic marker for intrahepatic cholangiocarcinoma (ICC) patients, the significance of elevated preoperative CA19-9 that normalized after resection remains unknown. This study aimed to investigate whether elevated preoperative CA19-9 that normalized after curative resection had an impact on prognosis among patients with ICC.MethodsPatients who underwent curative resection for stage I to III ICC between 2009 and 2018 were identified. Patients were categorized into three cohorts: normal preoperative CA19-9, elevated preoperative CA19-9 but normalized postoperative CA19-9, and persistently elevated postoperative CA19-9. Overall survival (OS), recurrence-free survival (RFS), and hazard function curves over time were analyzed.ResultsA total of 511 patients (247 [48.3%] male; median age, 58 years) were included. Patients with elevated preoperative CA19-9 (n = 378) were associated with worse RFS and OS than those with normal preoperative CA19-9 (n = 152) (both p < 0.001). Patients with persistently elevated postoperative CA19-9 (n = 254) were correlated with lower RFS and OS than the combined cohorts with normal postoperative CA19-9 (n = 257) (both p < 0.001). The hazard function curves revealed that the risk of recurrence and mortality peaked earlier and higher in the elevated postoperative CA19-9 group than the other 2 groups. Multivariate analyses identified persistently elevated, rather than normalized, postoperative CA19-9 as an independent risk factor for shorter RFS and OS in ICC.ConclusionsElevated preoperative serum CA19-9 that normalizes after curative resection is not an indicator of poor prognosis in ICC. Patients with persistently elevated postoperative CA19-9 are at increased risk of recurrence and death.

Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer.

Simple SummaryMost patients with a pancreatic ductal adenocarcinoma develop a recurrence after surgery. Predictive factors may therefore guide therapeutic decision-making. We aimed to identify perioperative predictors of the early recurrence of pancreatic ductal adenocarcinomas. We found that preoperative (>52 U/mL) and postoperative (>37 U/mL) elevated carbohydrate antigen 19-9 levels as well as a tumor size >3.0 cm were independently associated with an early recurrence after a pancreatectomy. Furthermore, an early recurrence resulted in a more frequent liver metastasis than a late recurrence, suggesting that patients experiencing a recurrence within 12 months had undetectable micrometastases. Further studies are needed to identify new biomarkers for the detection of clinically occult micrometastases during surgery as current preoperative risk factors are inadequate to accurately identify patients susceptible to an early recurrence of pancreatic ductal adenocarcinomas.We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan–Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35–7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67–6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03–3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02–4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.

Predictive value of changes in the level of carbohydrate antigen 19-9 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

The aim of this work was to explore the predictive value of changes in the level of carbohydrate antigen 19-9 (CA19-9) after neoadjuvant chemoradiotherapy (nCRT) and after surgery in patients with locally advanced rectal cancer (LARC). Patients with LARC who underwent nCRT and radical surgery (between 2011 and 2016) were divided into three groups according to pre-nCRT and post-nCRT CA19-9 levels as follows: normal pre-nCRT CA19-9 (normal CA19-9 group), elevated pre-nCRT and normal post-nCRT CA19-9 (normalized group) and elevated pre-nCRT and elevated post-nCRT CA19-9 (nonnormalized group). The pathological nCRT response criteria included ypCR and downstaging (ypStages 0-I). Recurrence-free survival (RFS) and overall survival (OS) were analysed. A total of 721 patients were identified. The normal CA19-9 group was significantly associated with ypCR (n=159) and downstaging (n=347) (P<0.05). The normalized group (n=76) had worse RFS and OS than the normal CA19-9 group (n=622) and better RFS and OS than the nonnormalized group (n=23) (5-year RFS 47.0% vs 66.9% vs 81.5%, P<0.001; 5-year OS 47.0% vs 75.4% vs 85.0%, P<0.001). In multivariate analysis, CA19-9 group and ypTNM stage were independent predictors of RFS and OS. Moreover, for the 23 patients with elevated post-nCRT CA19-9 levels, the RFS and OS of patients with normalized postoperative CA19-9 levels were significantly better than those of patients with elevated postoperative CA19-9 levels (P<0.05). Following nCRT, changes in the CA19-9 level are a strong prognostic marker for long-term survival, and they may be helpful in the selection of patients who prefer more conservative surgery after chemoradiotherapy.

Impact of resection margin status on survival in pancreatic cancer patients after neoadjuvant treatment and pancreatoduodenectomy

BackgroundResection margin status has been recognized as an independent prognostic factor on overall survival in pancreatic cancer patients undergoing surgical resection. However, its impact after neoadjuvant treatment remains uncertain. MethodsWe analyzed 305 patients with resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatoduodenectomy at 3 tertiary referral centers between 2010 and 2017. Positive resection margin was defined as 1 or more cancer cells at any margin. Overall survival was measured from the date of surgery until death or last follow-up. ResultsOne hundred and seventy-eight patients received neoadjuvant chemotherapy and 127 received neoadjuvant chemoradiotherapy. The median overall survival was 29.8 months. The 1-, 3-, and 5-year overall survival rates were 79.2%, 44.0%, and 23.5%, respectively. Negative margin was achieved in 275 (90.2%) patients. Negative margin resection patients had a significantly longer overall survival than positive resection margin patients (31.3 vs 16.3 months, P < .001). In univariate analyses, overall survival was associated with age, margin status, histologic grade, ypT, number of positive lymph nodes, perineural invasion, treatment effect, postoperative carbohydrate antigen 19-9, and adjuvant therapy. Positive margin resection, poorly differentiated carcinoma, treatment effect score of 3, postoperative carbohydrate antigen 19-9 of 37 U/mL or higher, and lack of adjuvant therapy were predictive of poor overall survival in multivariate Cox regression analysis. ConclusionMargin status was an independent predictor of overall survival in patients treated with neoadjuvant therapy and pancreatoduodenectomy, supporting the use of a negative margin resection as a surrogate of adequate oncological resection in this setting. Our findings may also have significant implications for patient stratification in future randomized trials.

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer.

In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the log-rank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.

Prognostic significance of perioperative tumor marker levels in stage II/III gastric cancer.

AIMTo evaluate the prognostic significance of perioperative carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in stage II/III gastric cancer.METHODSFrom a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage II/III gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTSThe prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival. Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSIONThe evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy.

A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma: Implications for AJCC-TNM staging

BackgroundWe evaluated the application of the latest 8th American Joint Committee on Cancer (AJCC) staging system in Chinese patients and determined whether the addition of biologic markers could improve the prediction of postsurgical survival in pancreatic adenocarcinoma (PC). MethodsThis multicenter study involved 1,223 consecutive patients who underwent margin-negative pancreatectomy for PC. A scoring system was devised based on AJCC pathologic parameters and biologic markers and defined using a Cox proportional hazards model. Prognostic accuracies were evaluated by concordance index (C-index) and Akaike information criterion (AIC). ResultsThe 8th edition AJCC staging system had a better survival distribution of PC with different stages and a similar C-index (0.62 in the training cohort, 0.60 in the validation cohort) than the 7th edition (0.59 in the training cohort, 0.58 in the validation cohort). Nevertheless, survival of resected patients with stage IIA or IIB disease was indistinguishable. Incorporation of postoperative carbohydrate antigen 19-9 (CA19-9) levels and tumor grade into the 8th edition AJCC staging system generated a scoring system with better predictive accuracy for overall survival (OS) (C-index of 0.73 and AIC of 4301.05 in the training cohort, C-index of 0.71 and AIC of 3309.23 in the validation cohort). More importantly, patients with median or higher scores experienced OS benefits from adjuvant chemotherapy. ConclusionPostoperative CA19-9 levels and tumor grade are two well-known PC biologic markers that could be incorporated into a standard AJCC staging system to refine risk stratification and predict OS benefit from adjuvant chemotherapy in resected PC.

Comparison of the prognostic impact of pre- and post-operative CA19-9, SPan-1, and DUPAN-II levels in patients with pancreatic carcinoma

BackgroundAlthough serum carbohydrate antigen 19-9 (CA19-9), s-pancreas antigen-1 (SPan-1), and duke pancreatic monoclonal antigen type 2 (DUPAN-II) are commonly utilized tumor markers in pancreatic ductal adenocarcinoma (PDAC), it is still unclear which is the most useful for predicting prognosis after surgical resection. Here, we aimed to compare the prognostic impact of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC. MethodsPre-operative CA19-9, SPan-1, and DUPAN-II levels were analyzed to compare their prognostic values for resectable PDAC in 198 patients whose pre-operative tumor markers were available. The relationships of clinicopathological factors, including pre- and postoperative CA19-9, SPan-1, and DUPAN-II levels, with overall survival (OS) were analyzed using univariate and multivariate analyses in 149 patients for whom both pre- and postoperative tumor markers were available. ResultsElevated pre-operative CA19-9 (≥37 U/mL), SPan-1 (≥30 U/mL), and DUPAN-II (≥150 U/mL) levels were found in 113 (60%), 96 (51%), and 82 (43%) patients, respectively. In multivariate analysis, absence of adjuvant chemotherapy (hazard ratio [HR], 4.17; p = 0.001), R1 resection (HR, 1.90; p = 0.03), higher histological grade (HR, 1.99; p = 0.02), advanced UICC T factor (HR, N/A; p = 0.04) and elevated postoperative CA19-9 (HR, 3.39; p = 0.009) were identified as independent predictors for worse OS. ConclusionWhen the prognostic impacts of pre- and post-operative serum CA19-9, SPan-1, and DUPAN-II levels in patients with resectable PDAC were compared, elevated postoperative CA19-9 was the strongest predictive marker of poor survival in the pre- and post-operative period.