Tumor-Associated Carbohydrate Antigen 19-9 (CA 19-9), a Promising Target for Antibody-Based Detection, Diagnosis, and Immunotherapy of Cancer.

Carbohydrate antigen 19-9 (CA 19-9) also known as sialyl Lewis A is a tetrasaccharide overexpressed on a wide range of cancerous cells, which has been detected at elevated levels in sera of patients with various types of malignancies, most prominently pancreatic ductal adenocarcinoma. After its identification in 1979, multiple studies have highlighted the significant roles of CA 19-9 in cancer progression, including facilitating extravasation and eventually metastases, proliferation of cancer cells, and suppression of the immune system. Therefore, CA 19-9 has been considered an attractive target for cancer diagnosis, prognosis, and therapy. This review discusses the synthesis of CA 19-9 antigen, elicitation of antibodies through vaccination, development of anti-CA 19-9 monoclonal antibodies, and their applications as imaging tracers and therapeutics for a variety of CA 19-9-positive cancer.

Clinical outcomes and risk stratification in unresectable biliary tract cancers undergoing radiation therapy.

BACKGROUND: Biliary tract cancers (BTC) are rare and aggressive malignancies originating from intrahepatic and extrahepatic bile ducts and the gallbladder. Surgery is the only curative option, but due to late-stage diagnosis, is frequently not feasible, leaving chemotherapy as the primary treatment. Radiotherapy (RT) can be an effective alternative for patients with unresectable, non-metastatic BTC despite the generally poor prognosis and significant variability. To help manage patients with unresectable BTC who receive RT, we aimed to identify prognostic markers that could aid in predicting overall survival (OS). METHODS: A retrospective cohort study was conducted at the University of Pennsylvania, involving seventy-eight patients with unresectable BTC treated with definitive intent RT. Comprehensive demographic, clinical, and treatment-related data were extracted from the electronic medical records. Univariate and multivariate Cox regressions were employed to identify predictors of OS after RT. A biomarker model was developed for refined survival prediction. RESULTS: The cohort primarily comprised patients with good performance status without significant hepatic dysfunction at presentation. The predominant treatment approach involved hypofractionated RT or concurrent 5FU-based chemoRT. Median OS after RT was 12.3 months, and 20 patients (15.6%) experienced local progression with a median time of 30.1 months. Univariate and multivariate analyses identified CA19-9 (above median) and higher albumin-bilirubin (ALBI) grades at presentation as significant predictors of poor OS. Median OS after RT was 24 months for patients with no risk factors and 6.3 months for those with both. CONCLUSIONS: Our study demonstrates generally poor but significantly heterogeneous OS in patients with unresectable BTC treated with RT. We have developed a biomarker model based on CA19-9 and ALBI grade at presentation that can distinguish sub-populations with markedly diverse prognoses. This model can aid the clinical management of this challenging disease.

First-line Chemotherapy in Combination With Oral Recombinant Methioninase and a Low-methionine Diet for a Stage IV Inoperable Pancreatic-Cancer Patient Resulted in 40% Tumor Reduction and an 86% CA19-9 Biomarker Decrease.

BACKGROUND/AIM: Pancreatic cancer has a very poor prognosis with a 5-year survival rate of less than 5% among patients with distant metastasis, a figure that has not improved over many decades. Only 10 to 20% patients are candidates for curative surgery at presentation due to the aggressive nature and asymptomatic progression of pancreatic cancer. Although first-line chemotherapy, such as FOLFIRINOX and gemcitabine + nab paclitaxel, improved the median survival from 8.5 to 11.1 months, more effective treatments are immediately needed. The aim of the present study was to evaluate the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet combined with first-line chemotherapy on a patient with stage IV metastatic pancreatic cancer. CASE REPORT: A 63-year-old female was diagnosed with metastatic pancreatic cancer in October 2023. The patient started FOLFIRINOX as first-line chemotherapy in combination with methionine restriction, which comprised o-rMETase 250 units twice a day and a low-methionine diet. The patient was monitored using computed tomography and CA19-9 blood tests. After five months from the start of combination therapy, the size of the primary tumor decreased by 40% along with liver-metastasis regression. The CA19-9 blood marker decreased by 86%. The patient sustains a high performance status and continues the combination therapy without severe side effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer.

Ruptured large hepatic cyst with elevated serum and ascites CA19-9 level.

Tumor markers such as carbohydrate antigen 19-9 (CA19-9) are generally useful in ruling out malignancy of hepatic cysts. The patient was a 72-year-old man who had a ruptured liver cyst in the right liver, which had been noted since he was 67 years old at another hospital. The initial laboratory tests demonstrated elevated CA19-9 (193 784.3 U/mL). We made the diagnosis with a simple ruptured liver cyst from magnetic resonance imaging and cytological examination of ascites, and laparoscopic fenestration with drainage of the abdominal fluid was performed. Pathological diagnosis of the resected wall cyst was non-parasitic simple hepatic cyst with acute inflammation and hemorrhage. The patient's serum levels of CA19-9 were 164.0 U/mL on postoperative day 23. The follow-up abdominal computed tomography scan performed 2 months later did not any finding of tumor.

Analytical interference in CA 19-9 immunoassay generates false-positive results in a young woman with a low-grade appendiceal tumor: An educational case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for the follow-up of patients with pancreatic cancer and other digestive neoplasia. This case report describes a discrepancy between the results of serum CA 19-9 analyses using the Alinity analytical platform (Abbott™) and two other techniques, Kryptor Gold (ThermoFisher Scientific™) and Cobas E411 (Roche™), in the context of a young woman with appendiceal mucocele. In this context, when the serum concentration of CA 19-9 is high, it may raise concerns about potential malignancy or rupture of the mucocele that may lead to tumoral dissemination in the abdominal cavity. In the present case, we observed with Alinity a false elevation in CA 19-9 concentration at 190 kU/L (normal range < 37 kU/L) before appendix resection that continued to increase until reaching 619 kU/L six months after surgery. This situation led to unnecessary additional tests, increased hospitalization time and stress for the patient who also had to interrupt her medically assisted reproduction project. We solved this case using new measurements in CA 19-9 concentration with two other techniques, Kryptor Gold and Cobas E411, and we identified an analytical interference caused by the presence of heterophile antibodies. In all cases, abnormal result initially obtained with Alinity was found below normal range not only with the two other techniques but also with Alinity after a neutralisation step by using Heterophile Blocking Tubes (Scantibodies Laboratory™). Analytical interferences in medical tests can lead to inappropriate medical care. It is an important issue requiring a continuing training of biologists who must be aware of these problems, which are recurring concerns and are not always easy to identify in laboratories of medical biology, in particular when immunoassays are used. This case report also provides an opportunity to do a brief review of the literature and to remind some recommendations and actions to take into consideration in the presence of discrepancies between the clinic and the biology, in particular, one of them is to measure the biological analyte with a different technique. Moreover, the use of Heterophile Blocking Tubes neutralizing specifically the heterophile antibodies may be useful. In all cases, dialogue between clinicians and biologists remains essential.

MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients.

Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.

Abrupt elevation of tumor marker levels in a huge splenic epidermoid cyst, a case report.

Epidermoid cyst of the spleen is a rare disease, and relatively few cases were reported by literatures. Most published case reports provided inadequate information on the impact of splenic epidermoid cyst on tumor markers. A 32-year-old woman with a giant splenic epidermoid cyst was reported, for whom the serum concentration of a collection of tumor markers (CA19-9, CEA, CA125, CA242, and CA50) increased abruptly accompanied by left upper abdominal pain for 5 days. After comprehensive preoperative examination and multidisciplinary team discussion, we ruled out any concurrent malignancy and a laparoscopic total splenectomy was performed, during which the splenic cyst spontaneously ruptured unexpectedly. After surgery, the elevated serum tumor marker levels decreased sharply until reaching normal range 3 months later. Learning from the case, we conclude that interval monitoring of serum tumor markers is of critical value for patients with splenic epidermoid cyst. Abrupt elevation of tumor marker levels and abdominal pain may serve as signs of cyst rupture, which is strongly indicative of surgical intervention as soon as possible. Total removal of the splenic cyst is strongly suggested considering the recurrence and malignant potential of the splenic epidermoid cyst.

Prognostic Strength of CA 19-9, Demographic Parameters, and Maximum Standardized Uptake Value of Baseline 18F-FDG PET/CT in Treatment-naïve Patients with Pancreatic Carcinoma.

Aim and Background: The aim of this study was to evaluate the prognostic value of imaging-based variables and tumor marker in predicting the progression-free survival (PFS) in treatment-naïve pancreatic cancer (PC) using baseline 18-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT). Materials and Methods: This retro-prospective study was conducted at PET/CT imaging facility of JCIA health-care facility of Pakistan. Total 68 patients with PCs were retrospectively included who had 18FDG PET/CT for staging from March 2017 to December 2020. Thirty-two patients had unresectable Stage IV disease on baseline imaging while the remaining 36 underwent Whipple's procedure and both categories were followed by chemotherapy with/without immunotherapy. These patients were followed for a median period of 18 months (1-62 months) for PFS. Logistic regression analysis and receiver operating characteristic (ROC) analysis were used for independent predictors of patients' demographics, tumor characteristics, CA 19-9, and maximum standardized uptake value (SUVmax) in PFS. Kaplan-Meier's survival curves were analyzed to measure PFS using ROC-derived significant cutoff values of CA 19-9 and SUVmax. Results: Median PFS was 18 months (11-45) with 60% (41/68) patients were either died or labelled having metabolic progressive disease (MPD. Using logistic regression analysis, significant correlations were found for Stage IV disease and pancreatic body/tail tumor with disease progression (odd ratio: 7.535 and 4.803, respectively; P < 0.05). Gender, obesity, histological tumor type, and 18FDG-avid regional nodes did not show a significant impact on PFS. On ROC analysis, SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS (area under the curve: 0.827 and 0.911, respectively; P < 0.0001) and no association of age and primary tumor size in PFS. Significantly, shorter PFS was found using ROC-derived cutoff values of SUVmax >5.3 versus ≤5.3 of primary tumor (mean and 95% confidence interval [CI]: 16.7 vs. 48.5 and 10-23 vs. 41-56; log-rank = 25.014; P < 0.0001) and baseline CA 19-9 >197 versus ≤197 U/ml (mean and 95% CI: 11.8 vs. 46.9 and 7-16 vs. 39-55; log-rank = 38.217; P < 0.0001). Conclusion: SUVmax >5.3 of primary tumor and baseline CA 19-9 >197 U/ml were found to have a significant negative correlation with PFS in treatment-naïve PC patients. Among demographics, only Stage IV disease and pancreatic tail and body tumors were found to have a negative association with disease progression.

Benign Etiology for High-Risk Intraductal Papillary Mucinous Neoplasm: A Case Report and Literature Review.

Intraductal papillary mucinous neoplasms are relatively common and entail a variable risk of malignant potential. The Fukuoka guidelines present criteria for the risk of malignant transformation and are used for risk stratification and treatment decision-making. However, these guidelines entail some fallibility with limited sensitivity and specificity. In this case, we present an individual who had many of the hallmarks of malignant transformation but was found to have no evidence of malignancy or high-grade dysplasia. We discuss the suspected etiology of this individual's condition and how it might arise in others, as well as a brief review of the literature on risk factors in intraductal papillary mucinous neoplasms.

Longitudinal evaluation of external quality assessment results for CA 15-3, CA 19-9, and CA 125.

Background: Tumor markers are established laboratory tools that help to diagnose, estimate prognosis, and monitor the course of cancer. For meaningful decision-making in patient care, it is essential that methods and analytical platforms demonstrate high sensitivity, specificity, precision, and comparability. Regular participation at external quality assessment (EQA) schemes is mandatory for laboratories. Here, a longitudinal evaluation of EQA data was performed to assess the performance of tumor marker assays over time. Methods: Longitudinal data of the cancer antigens (CA) 15-3 (n = 5,492), CA 19-9 (n = 6,802), and CA 125 (n = 5,362) from 14 INSTAND EQAs conducted between 2019 and 2023 were evaluated. A median of 197, 244 and 191 laboratories participated at the EQAs for CA 15-3, CA 19-9 and CA 125, respectively. Data evaluation encompasses intra- and inter-manufacturer specific variations over time, assay precision, and adherence to the EQA limits of ±24% for CA 15-3, ±27% for CA 19-9 and ±36% for CA 125. Results: The study showed median manufacturer-dependent differences of up to 107% for CA 15-3, 99% for CA 125, and even 549% for CA 19-9 between the highest and the lowest methods over the studied period. Regarding the normalized median of all methods, the values of the most deviant methods were 0.42 for CA 15-3, 7.61 for CA 19-9, and 1.82 for CA 125. Intra-manufacturer variability was generally low, with median coefficients of variation (CV) below 10%. As the methods were evaluated according to method-specific consensus values, most participants passed the EQAs within the acceptance criteria. When the criteria were consistently set at 24%, the central 90% of participants passed the EQAs in 78.6%-100% for CA 15-3 (with exception of AX), 89.3%-100% for CA 125, and 64.3%-100% for CA 19-9. Conclusion: While intra-method precision of most analytical platforms is acceptable for all three tumor markers, considerable inter-method variability was observed over the whole studied period demonstrating the necessity for better standardization and harmonization of the methods, development of international reference materials, and comprehensive commutability studies with patient samples.

Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities.

Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.

Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms: Small nuances between guidelines lead to vastly different results.

Backgrounds/Aims: The guidelines regarding the management of intraductal papillary mucinous neoplasms (IPMNs) all have slightly different surgical indications for high-risk lesions. We aim to retrospectively compare the accuracy of four guidelines in recommending surgery for high-risk IPMNs, and assess the accuracy of elevated CA-19-9 levels and imaging characteristics of IPMNs considered high-risk in predicting malignancy or high-grade dysplasia (HGD). Methods: The final histopathological diagnosis of surgically resected high-risk IPMNs during 2013-2020 were compared to preoperative surgical indications, as enumerated in four guidelines: the 2015 American Gastroenterological Association (AGA), 2017 International Consensus, 2018 European Study Group, and 2018 American College of Gastroenterology (ACG). Surgery was considered "justified" if histopathology of the surgical specimen showed HGD/malignancy, or there was postoperative symptomatic improvement. Results: Surgery was postoperatively justified in 26/65 (40.0%) cases. All IPMNs with HGD/malignancy were detected by the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines. The combined ("high-risk stigmata" and "worrisome features") 2017 International guideline missed 1/19 (5.3%) IPMNs with HGD/malignancy. The 2015 AGA guideline missed the most cases (11/19, 57.9%) of IPMNs with HGD/malignancy. We found the features most-associated with HGD/malignancy were pancreatic ductal dilation, and elevated CA-19-9 levels. Conclusions: Following the 2015 AGA guideline results in the highest rate of missed HGD/malignancy, but the lowest rate of operating on IPMNs without these features; meanwhile, the 2018 ACG and the combined (absolute and relative criteria) 2018 European guidelines result in more operations for IPMNs without HGD/malignancy, but the lowest rates of missed HGD/malignancy in IPMNs.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Availability of Serum Levels of Carbohydrate Antigen 19-9 (CA19-9) as a Surrogate Tumor Marker for Papillary Thyroid Carcinoma.

Introduction: Thyroglobulin (Tg) is a very sensitive and specific marker in patients who have undergone total thyroidectomy for papillary thyroid carcinoma (PTC). However, the presence of a Tg antibody (TgAb) interferes with Tg immunometric assays, making Tg levels unreliable indicators. There are currently no other tumor markers to monitor in patients with PTC whose serum is TgAb-positive. Thus, we investigated whether carbohydrate antigen 19-9 (CA19-9) can be used as a tumor marker for PTC. Methods: We retrospectively analyzed 196 consecutive patients with PTC (maximum diameter ≥ 2 cm). The serum CA19-9 and Tg values of each patient were obtained before and 0.5-1 month postsurgery. Immunohistochemical staining for PTC was performed using an antibody against CA19-9. Results: High pre-surgery serum levels of CA19-9 were observed in 6.1% of the patients. Postsurgery, serum CA19-9 levels in all 196 patients decreased considerably and were within the normal range. CA19-9 expression was detected in 28 of 62 PTCs (45.2%) and was detected at various degrees and ranges in conventional PTC histology. Conclusions: Although further studies with longer follow-ups are necessary, serum CA19-9 levels may serve as a surrogate tumor marker for PTC in place of serum Tg levels sin some patients.

Carbohydrate Antigen (CA 19-9) Surge: Unraveling the Enigma of Elevated Levels in the Setting of Benign Etiologies.

Carbohydrate antigen 19-9 (CA 19-9) is widely recognized as a tumor marker primarily associated with pancreatic cancer. However, its elevation in benign pancreaticobiliary conditions complicates its diagnostic utility. We present the case of a 39-year-old male with no significant medical history who presented with symptoms of abdominal pain, nausea, vomiting, and diarrhea. The initial diagnosis suggested viral enteritis, but the subsequent worsening of symptoms led to further investigation. Elevated white blood cell counts, bilirubin levels, and liver function tests prompted magnetic resonance cholangiopancreatography (MRCP), which revealed dilated bile ducts and acute cholecystitis. Following endoscopic retrograde cholangiopancreatography (ERCP), significant hemobilia was observed, raising suspicions of cholangiocarcinoma. Despite extensive investigations, including CT angiography, MRCP, and repeat ERCPs, no malignancy was detected. Remarkably, the CA 19-9 level was elevated to 904 U/mL after the initial ERCP and uptrended to 7380 U/mL. These levels, however, normalized to 13 U/mL within two weeks of discharge. While CA 19-9 is a valuable marker in the diagnosis of pancreatic cancer, its elevation in benign pancreaticobiliary conditions necessitates cautious interpretation. In our case, choledocolithasis, cholangitis, and biliary manipulation appeared to have contributed to a transiently elevated CA 19-9. Clinicians must consider the entire clinical context when evaluating elevated CA 19-9 levels to avoid misdiagnosis and ensure appropriate patient management.

Preoperative CA19­9 level and dual time point FDG­PET/CT as strong biological indicators of borderline resectability in pancreatic cancer: A retrospective study.

Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability.

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug.

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

The Usefulness of Vitamin K-Dependent Proteins in the Diagnosis of Colorectal Carcinoma.

Colorectal cancer (CRC) is one of the most common neoplasms in developed countries, with increasing incidence and mortality, even in young people. A variety of serum markers have been associated with CRC (CEA, CA 19-9), but neither should be used as a screening tool for the diagnosis or evolution staging of CRC. The sensitivity and specificity of these markers are not as good as is required, so new ones need to be found. Matrix Gla protein and PIVKA II are involved in carcinogenesis, but few studies have evaluated their usefulness in predicting the presence and severity of CRC. Two hundred patients were divided into three groups: 80 patients were included in the control group; 80 with CRC and without hepatic metastasis were included in Group 1; 40 patients with CRC and hepatic metastasis were included in Group 2. Vitamin K-dependent proteins (VKDPs) levels in plasma were determined. Patients with CRC without methastasis (Group 1) and CRC patients with methastasis (Group 2) presented significantly higher values of CEA, CA 19-9, PIVKA II (310.05 ± 38.22 vs. 430.13 ± 122.13 vs. 20.23 ± 10.90), and ucMGP (14,300.00 ± 2387.02 vs. 13,410.52 ± 2243.16 vs. 1780.31 ± 864.70) compared to control group (Group 0). Interestingly, Group 1 presented the greatest PIVKA II values. Out of all the markers, significant differences between the histological subgroups were found only for ucMGP, but only in non-metastatic CRC. Studying the discrimination capacity between the patients with CRC vs. those without, no significant differences were found between the classical tumor markers and the VKDP AUROC curves (PIVKA II and ucMGP AUROCs = 1). For the metastatic stage, the sensitivity and specificity of the VKDPs were lower in comparison with those of CA 19-9 and CEA, respectively (PIVKA II AUROC = 0.789, ucMGP AUROC = 0.608). The serum levels of these VKDPs are significantly altered in patients with colorectal carcinoma; it is possible to find additional value of these in the early stages of the disease.

The role of biomarkers in the early detection of pancreatic cancer.

Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is recommended only for individuals who meet familial/genetic risk criteria. To improve upon current approaches to pancreatic cancer early detection and to expand access, more accurate, inexpensive, and safe biomarkers are needed, but finding them has remained elusive. Newer approaches to early detection, such as using gene tests to personalize biomarker interpretation, and the increasing application of artificial intelligence approaches to integrate complex biomarker data, offer promise that clinically useful biomarkers for early pancreatic cancer detection are on the horizon.

A Case of Cholecystitis Camouflaging Cholangiocarcinoma.

Cholangiocarcinoma is a malignancy that is hard to detect and resect, due mostly to its location as well as a lack of current screening tests. When found, it is often in the advanced stage as patients are usually asymptomatic during the early course of the disease; the overall prognosis is modest in patients diagnosed at this stage. Here, we discuss the case of a 48-year-old female with no significant past medical history or family history who presented to our hospital with symptoms of acute cholecystitis with a supporting ultrasound. She proceeded to get a laparoscopic cholecystectomy for the same, but an ensuing workup and pathology revealed advanced-stage cholangiocarcinoma. The patient ultimately opted for palliative care given her poor prognosis.