Elevated Preoperative CA19-9 Research Articles

Construction of a nomogram based on clinicopathologic features to predict the likelihood of No. 253 lymph node metastasis in rectal cancer patients.

To explore the high-risk factors for rectal cancer No.253 lymph node metastasis (LNM) and to construct a risk nomogram for the individualized prediction of No.253 LNM. This was a retrospective analysis of 425 patients with rectal cancer who underwent laparoscopic-assisted radical surgery. Independent risk factors for rectal cancer No.253 LNM was identified using multivariate logistic regression analysis, and a risk prediction nomogram was constructed based on the independent risk factors. In addition, the performance of the model was evaluated by discrimination, calibration, and clinical benefit. Multivariate logistic regression analysis showed that No.253 lymphadenectasis on CT (OR 10.697, P < 0.001), preoperative T4-stage (OR 4.431, P = 0.001), undifferentiation (OR 3.753, P = 0.004), and preoperative Ca199 level > 27 U/ml (OR 2.628, P = 0.037) were independent risk factors for No.253 LNM. A nomogram was constructed based on the above four factors. The calibration curve of the nomogram was closer to the ideal diagonal, indicating that the nomogram had a better fitting ability. The area under the ROC curve (AUC) was 0.865, which indicated that the nomogram had high discriminative ability. In addition, decision curve analysis (DCA) showed that the model could show better clinical benefit when the threshold probability was between 1% and 50%. Preoperative No.253 lymphadenectasis on CT, preoperative T4-stage, undifferentiation, and elevated preoperative Ca199 level were found to be independent risk factors for the No.253 LNM. A predictive model based on these risk factors can help surgeons make rational clinical decisions.

Prognostic Value of Systemic Immune-Inflammation Index-Based Nomogram in Patients with Extrahepatic Cholangiocarcinoma Treated by Percutaneous Transhepatic Biliary Stenting Combined with 125I Seed Intracavitary Irradiation.

This study aimed to investigate the prognostic value of systemic immune-inflammation index (SII) in patients with extrahepatic cholangiocarcinoma (EHCC) treated by percutaneous transhepatic biliary stenting (PTBS) combined with 125I seed intracavitary irradiation and further develop a predictive model related to SII. A total of 145 patients with EHCC who received PTBS combined with 125I seed implantation were retrospectively analyzed. The optimal cut-off value of SII was identified by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier curves and Cox regression were applied to estimate the prognostic value of SII and identify other significant factors of overall survival (OS). Additionally, a novel nomogram was constructed. The concordance index (C-index), calibration plots and decision curve analysis were used to evaluate the performance of the nomogram model. The optimal cut-off value for preoperative SII of 890.2 stratified the patients into High-SII (H-SII) and Low-SII (L-SII) groups. Univariate and multivariate analyses demonstrated that SII was an independent factor for OS. We also found that better therapeutic effect could be obtained with combined postoperative chemotherapy (P < 0.001). Moreover, we revealed that elevated preoperative CA19-9 (P = 0.038) and TBIL level (P = 0.024) were reason for poor prognosis of EHCC. A well-discriminated and calibrated nomogram was developed to predict the 1-year and 2-year OS of EHCC (C-index: 0.709). The SII may be a feasible and convenient prognosis predictor for EHCC. The comprehensive nomogram based on SII presented in this study is a promising model for predicting OS in EHCC patients after PTBS combined with 125I seed intracavitary irradiation.

Clinical Significance of Early Recurrence After Curative Resection of Colorectal Cancer.

Although survival in cases with early recurrence after curative resection of colorectal cancer has been persistently poor, the risk factors for early recurrence remain unknown. A total of 1,043 patients with stage I-III colorectal cancer underwent curative resection at Kobe University Hospital between April 2007 and September 2020. Of these, 122 patients developed recurrence: 57 had early recurrence (<1 year after surgery) and 65 patients had late recurrence (≥1 year after surgery). The clinicopathological features were compared between the groups and the risk factors for early recurrence were analyzed. Overall survival both from the date of recurrence and from the date of surgery were significantly worse in the early recurrence group. The proportion of the patients with ≥100 g of intraoperative blood loss, blood transfusion, and postoperative complications were significantly higher in the early recurrence group. R0 resection was achieved more frequently in the late recurrence group. Multivariate analysis revealed that no adjuvant chemotherapy, elevated preoperative CA19-9, blood transfusion, and the occurrence of the postoperative complication were independent risk factors for early recurrence. Early recurrence after curative resection of colorectal cancer was associated with worse overall survival. Adjuvant chemotherapy might be beneficial for patients with risk factors of early recurrence to improve prognosis.

Preoperative serum CA19-9 should be routinely measured in the colorectal patients with preoperative normal serum CEA: a multicenter retrospective cohort study

ObjectiveWhether preoperative serum carbohydrate antigen 19–9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified.MethodsConsecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale.ResultsA total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5–62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724).ConclusionsPreoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Recurrent Intrahepatic Cholangiocarcinoma - Review.

Intrahepatic cholangiocarcinoma (ICC) is the second-most common primary liver malignancy after hepatocellular carcinoma. While surgical resection with negative margin is the only curative treatment, ICC has very high rate of recurrence, up to 60-70% after curative resection. We reviewed the current data available on risk factors for ICC recurrence, recurrence pattern (location and timing), treatment options, and future directions. The risk factors for recurrence include elevated preoperative CA19-9, presence of liver cirrhosis, nodal metastasis, positive margins, and vascular invasion. Understanding different recurrence patterns, timing course, and risk factors for early recurrence is important to tailor postoperative surveillance and select treatment strategies including systemic or locoregional therapy. Re-resection can be considered for a selected patient population at experienced centers, and can yield long-term survival. ICC remains a dismal disease given the high likelihood of recurrence. Advances in our understanding of the genomic landscape of ICC are beginning to identify targetable alterations in ICC in subsets of patients that allow for personalized treatment.

Prognostic Factors and Lymph Node Metastasis Patterns of Primary Duodenal Cancer.

The effectiveness and extent of regional lymph node dissection in primary duodenal cancer (DC) remains unclear. This study aimed to analyze the prognostic factors and lymph node metastasis (LNM) patterns in DC. Fifty-three patients who underwent surgical resection for DC between January 1998 and December 2018 at two institutions were retrospectively analyzed. Univariate and multivariate analyses were performed on the prognostic factors of resected DC. Moreover, the relationships between depth of tumor invasion and incidence of LNM and between tumor location and LNM stations were analyzed. The five-year survival rate of the study population was 68.9%. Multivariate survival analysis demonstrated that histologic grade G2-G4, presence of LNM, pT3-4, and elevated preoperative CA19-9 were the independent poor prognostic factors. No patient with pTis-T2 had LNM. On the other hand, LNM was found in 70% of patients with pT3-4. Among 36 patients who underwent pancreaticoduodenectomy (PD), LNM around the pancreatic head was observed, regardless of the duodenal cancer site, including the duodenal bulb and the third to the fourth portion. Histologic grade G2-G4, presence of LNM, pT3-T4, and elevated preoperative CA19-9 were the independent poor prognostic factors in patients with resected DC. Our results suggested that lymph node dissection could be omitted for DC Tis-T1a. Moreover, based on the high frequency of LNM in T3-4 cases, PD with lymph node dissection in the pancreatic head region was considered necessary for T3-4 DC at any site.

Preoperative risk factors for para-aortic lymph node positivity in pancreatic cancer

PurposeThis study aimed to identify the preoperative risk factors for para-aortic lymph node (PALN) positivity, including micrometastasis, in pancreatic cancer. MethodsMedical records of patients with pancreatic cancer who underwent curative resection were retrospectively reviewed, and the relationships between preoperative risk factors and PALN positivity were identified. Clinicopathological and prognostic factors for overall survival were analyzed. Micrometastasis was investigated by immunohistochemistry. Results400 patients were enrolled. PALN positivity by hematoxylin and eosin staining, micrometastasis, and negative were found in 46 (11%), 32 (8%), and 322 (81%) patients, respectively. The median overall survival times of patients with PALN positivity, including micrometastasis, was 22.5 months. Multivariate logistic regression identified borderline or locally advanced status (p=0.037), elevated preoperative carbohydrate antigen (CA) 19-9 level (p<0.001), larger tumor size ≥30 mm (p=0.001) and larger PALN size ≥10 mm (p=0.019) as independent preoperative risk factors of PALN positivity. Multivariate overall survival analysis demonstrated borderline or locally advanced status (p=0.013), elevated preoperative CA19-9 level (p<0.001) and PALN positivity (p=0.048) were independent poor prognostic factors. ConclusionsBorderline or locally advanced status, elevated preoperative CA19-9 level, and larger tumor and PALN size were risk factors for PALN positivity, and thus, they may contribute to the optimization of preoperative treatments for patients with potential PALN positivity.

Predicting Aborted Hyperthermic Intraperitoneal Chemotherapy (AHIPEC) with Preoperative Tumor and Inflammatory Markers in Potentially Resectable Appendiceal Cancer Patients with Peritoneal Carcinomatosis.

Despite meticulous preoperative diagnostics, aborted hyperthermic intraperitoneal chemotherapy (AHIPEC) is a common, unsuccessful outcome of curative cytoreductive surgery (CRS)/HIPEC. The aim of this study was to evaluate the association between AHIPEC and preoperative risk factors of patients with mucinous appendiceal cancer (AC). A single-institute, case-control study was conducted using a prospective database. Potentially resectable patients with peritoneal carcinomatosis of mucinous AC origin with AHIPEC between October 1994 and February 2019 were identified. Preoperative risk factors were reviewed. Analysis was conducted by tumor grade: low-grade, high-grade, and signet ring cell carcinoma (high-S). All available tumor-type-matched successful CRS/HIPEC controls were obtained from the same database. Univariable and multivariable analyses were performed. Overall, 21, 44, and 15 AHIPEC cases and 153, 133, and 53 tumor-matched controls were identified for low-grade, high-grade, and high-S populations, respectively. Multivariable analysis revealed preoperative cancer antigen (CA)19-9 > 1 upperlimit of normal (ULN) [odds ratio (OR) 6.32; p = 0.014], CA125 > 2 ULN (OR 7.02; p = 0.039), C-reactive protein (CRP) > 2.5mg/L (OR13.7; p = 0.001), and previous HIPEC (OR 7.5; p = 0.031) were significantly associated with AHIPEC in the low-grade population. Preoperative CRP > 2.5mg/L (OR 7.77; p < 0.0001) and previous HIPEC (OR 4.69; p = 0.004) were associated with AHIPEC in a multivariable model for high-grade AC. No single factor showed a significant association with AHIPEC in high-S patients. Risk factors vary for AHIPEC among low-grade, high-grade, and high-S AC histology. Elevated preoperative CA19-9, CA125, CRP, and previous HIPEC should be considered in the selection process for CRS/HIPEC in low-grade AC, as well as elevated CRP and previous HIPEC in high-grade AC, to avoid unnecessary surgery.

Clinical outcome of pancreatic cancer patients with indeterminate pulmonary nodules.

220 Background: Indeterminate pulmonary nodules (IPNs) are often found on staging CT scans for pancreatic cancer and pose a treatment conundrum since resection is contraindicated in metastatic setting. Here we aim to determine the clinical outcome of pancreatic cancer patients with IPNs undergoing curative resection. Methods: Retrospective analysis of 1,182 pancreatic cancer patients in the institutional Oncology Registry between 2007 and 2017 was conducted. Survival probabilities were estimated using the Kaplan-Meier method. Time was calculated from diagnosis to death for overall survival (OS), and from operation to recurrence for recurrence-free survival (RFS). Cox regression models were used to assess the effects of demographic, clinicopathologic, and treatment variables on OS and RFS. Results: IPNs were found in 50 patients undergoing surgery (43 pancreatoduodenectomy, 7 distal pancreatectomy). Negative margins were obtained in 82% of patients. Six and 44 patients had stage 0/I and stage II disease, respectively. Twelve and 35 patients received neoadjuvant and adjuvant therapy, respectively. Over a median follow-up of 20 months from the time of diagnosis, 37 patients (74%) developed local recurrence or distant metastasis in liver (38%), lung (32%), peritoneum (8%), or other sites (8%). Median RFS was 14 months and median OS was 23 months. Tumor size (HR 1.56, CI 1.23-1.98, p &lt; 0.01) and elevated pre-operative CA19-9 (HR 2.51, 1.22 – 5.15, p = 0.01) were associated with lower RFS. Tumor size (HR 1.43, CI 1.10-1.86, p &lt; 0.01) and diabetes (HR 2.05, CI 1.02-4.11, p = 0.04) were associated with lower OS. Patients with lung only recurrence tended to have superior OS relative to other single sites (HR 2.05, CI 0.66-6.33, p = 0.21) or multiple sites (HR 2.30, 0.75-7.50, p = 0.15). Patients with lung only recurrence had a median survival after recurrence of 17.9 months compared to 6.5 months for other single sites or 4.3 months for multiple sites. Conclusions: Only a portion of IPNs develop into true lung metastasis and that isolated lung metastatic recurrence may confer a better survival over metastasis of other sites. Ongoing efforts will identify serum biomarkers to predict recurrence in the hopes of guiding future clinical practice.

Evaluation of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and survival prediction in resectable pancreatic carcinoma

BackgroundWe sought to investigate the efficacy of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and prediction of survival in patients with resectable pancreatic carcinoma (PC).MethodsOne hundred and nineteen patients with resectable PC were enrolled. Serum D-dimer, fibrinogen, and CA19-9 values were analyzed before surgery and at the stages of relapse-free and progression disease.ResultsD-dimer, fibrinogen, and CA19-9 were significantly higher at the active stage of PC than those at the relapse-free stage [1059.2 (1690.1) ng/ml vs 485.18 (289.84) ng/ml, (3.71 ± 0.83) g/l vs (2.75 ± 0.52) g/l, 207.2 (681.8) U/ml vs 24.5 (30) U/ml, respectively, p < 0.01]. Patients with elevated preoperative D-dimer had significantly shorter overall survival (18.9 ± 1.9 months vs 29.2 ± 2.6 months, p < 0.01) and progression-free survival (10.6 ± 1.2 months vs 20.4 ± 2.4 months, p < 0.01) than did those with low D-dimer. The correlation between CA19-9 values and survival depended on the threshold value of CA19-9: when the threshold value was 37 U/ml, there was no correlation between CA19-9 and survival; when the threshold value was 253.8 U/ml (median CA19-9 for the enrolled patients), patients with elevated preoperative CA19-9 had significantly shorter overall survival (19.9 ± 2. 1 months vs 29.0 ± 2. 7 months) and progression-free survival (11.5 ± 1.5 months vs 21.0 ± 2. 6 months) than did the patients with low CA19-9 (p < 0.01); when the threshold value was 1000 U/ml, the overall survival was 15.5 ± 2.3 months vs 28.0 ± 2.0 months and the progression-free survival 8.9 ± 1.9 months vs 19.1 ± 1.9 months (p < 0.01). There was no correlation between fibrinogen and overall survival (25.8 ± 2.1 months vs 21.2 ± 2.9 months; p = 0.096) and progression-free survival (17.8 ± 2.1 months vs 12.7 ± 1.7 months; p = 0.168).ConclusionsFor postoperative monitoring of patients with resectable PC, D-dimer, fibrinogen, and CA19-9 may be used as markers for monitoring disease relapse, but only preoperative D-dimer could predict survival.

Elevated Preoperative Serum CA19‐9 Levels in Patients with Hepatocellular Carcinoma Is Associated with Poor Prognosis after Resection

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status, α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival. A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan-Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival. At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5-5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3-5.4, p = .01). Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.

Elevated baseline CA19-9 levels correlate with adverse prognosis in patients with early- or advanced-stage pancreas cancer

CA19-9 is the most specific biomarker for pancreas cancer. We investigated the prognostic significance of normal (≤ 37 U/mL) versus elevated (>37 U/mL) CA19-9 levels in patients with resected and advanced pancreas cancer. Relevant data were obtained from patients treated for early-stage or advanced pancreatic adenocarcinoma at our institution. Log-rank tests were used to evaluate relationship between CA19-9 and clinical outcomes of interest for both early- and advanced-stage patients. A total of 123 patients were included (Group A: N = 30 stage I/II; Group B: N = 93 stage III/IV). In group A, elevated preoperative CA19-9 was significantly associated with lymph node involvement (p = 0.031), tumor ≥ 3 cm (p = 0.011), and lack of tumor differentiation (p = 0.048). Failure of postoperative CA19-9 to normalize predicted significantly worse DFS (p = 0.021). For group B, elevated baseline CA19-9 was associated with shorter OS on chemotherapy (p = 0.0008) and decline in CA19-9 >25 % with treatment was a significant predictor of improved OS (p = 0.0099). Higher than normal CA19-9 level is an adverse prognostic factor in both early and advanced settings and may prove to be useful in the selection of patients for more aggressive therapy in future trials. CA19-9 level decrease of >25 % predicts improved survival in advanced disease on chemotherapy.

Indicators for surgical resection and intraoperative radiation therapy for pelvic recurrence of colorectal cancer.

We retrospectively analyzed prognostic factors for surgical resection and intraoperative radiation therapy to identify indicators for this treatment strategy. Thirty-nine consecutive patients with locally recurrent colorectal cancer who underwent surgical resection with intraoperative radiation therapy from January 1, 1987, to June 30, 1999, were analyzed. The mean electron energy was 10.5 MeV and the mean intraoperative radiation dose was 22.6 Gy. Kaplan-Meier survival estimates were obtained for the 37 patients who recovered postoperatively. Prognostic factors were analyzed univariately by log-rank test and multivariately by Cox's proportional hazards model. Three-year cumulative survival was 44 percent (standard error = 11) for 26 patients free of unresectable distant metastasis who underwent surgical resection and intraoperative radiation therapy for pelvic recurrence of colorectal cancer, but none of the 11 patients with unresectable distant metastasis survived 3 years. Preoperative prognostic factors which were significant on univariate and multivariate analysis were unresectable distant metastasis (P = 0.001) and elevated preoperative serum CA 19-9 (P = 0.02). Patients with synchronous resection of local recurrence and distant metastasis had a significant survival advantage over those without resection of metastases (P = 0.02). Univariate analysis in a subgroup of 26 patients without unresectable distant metastasis revealed pain (P = 0.0003) to be a useful preoperative prognostic indicator, whereas tumor fixation (P = 0.01) and amount of residual tumor after surgical resection (P = 0.01) were significant intraoperative and postoperative factors, respectively. Fluorouracil-based postoperative systemic chemotherapy produced a significant survival benefit (P = 0.04). Patients with unresectable distant metastasis are not suitable candidates for surgical resection and intraoperative radiation therapy, whereas those with resectable metastasis are potential candidates. Intraoperative radiation therapy may be less useful for patients with pain, elevated preoperative CA19-9, fixed tumors, or gross residual tumor after surgical resection. Multimodal treatment strategies combining preoperative and/or postoperative external beam radiation therapy and intraoperative radiation therapy with fluorouracil-based systemic chemotherapy are recommended for patients with these indicators.