High CA19-9 Level Research Articles

The platelet pannexin 1-IL-1β axis orchestrates pancreatic ductal adenocarcinoma invasion and metastasis.

We aimed to investigate the protumor mechanisms of platelets in pancreatic ductal adenocarcinoma (PDAC). Serum samples were collected from 656 PDAC patients and 3105 healthy people, and a Panx1 knockout tumor model and an adoptive platelet transfusion mouse model were established. We showed that the blood platelet counts were not significantly different between stage III/IV and stage I/II patients, while the number of the CD41+/CD62P+ platelets was significantly elevated in stage III/IV patients, indicating that CD41+/CD62P+ platelets are associated with a poor prognosis. Further analysis showed that a high level of CD41+/CD62P+ platelets was significantly correlated with microvascular invasion (P = 0.002), advanced 8th edition AJCC stage (P < 0.001), and a high CA19-9 level (P = 0.027) and independently predicted a poor prognosis for resectable I/II PDAC. Furthermore, we found significantly higher Panx1 expression in CD41+/CD62P+ platelets than in CD41+/CD62P- platelets in PDAC patients. Mechanistically, Panx1 was able to enhance IL-1β secretion in CD41+/CD62P+ platelets by phosphorylating p38 MAPK and consequently promoted the invasion and metastasis of PDAC cells. Finally, we synthesized a novel compound named PC63435 by the ligation of carbenoxolone (a Panx1 inhibitor) and PSGL-1 (a CD62P ligand). PC63435 specifically bound to CD41+/CD62P+ platelets, then blocked the Panx1/IL-1β pathway and reduced the proportion of CD41+/CD62P+ platelets, which suppressed PDAC tumor invasion and metastasis in vivo. These results demonstrated that the Panx1/IL-1β axis in CD41+/CD62P+ platelets enhanced PDAC cell malignancy and that this axis may be a promising target for PDAC therapy.

Evaluation of Ki-67 staining index and BRAF mutation in women diagnosed with advanced endometriosis

Introduction: Recent studies have proposed that advanced endometriosis might harbor histopathological, molecular, and genetic properties of malignant lesion. Thus we aimed to investigate the presence of Ki-67 staining index (KSI) and BRAF mutation in patients with and without recurrent endometriosis of stage III and IV. Materials and methods: Cross sectional study on 50 consecutive patients with endometriosis of stage III and IV was performed. Tissue specimens collected during laparoscopic surgery were used for the evaluation of presence of KSI and BRAF mutation. Also, serum levels of tumor markers including CA-125, CA19-9, AMH and αFP were gathered. Results: The mean ± SD of KSI was 12.18 ± 16.58. Forty-one out of 50 (82%) patients had a non-recurrent disease. KSI ⩾ 10% was found in 20 patients (40%). Furthermore, 29 patients (58%) and 13 patients (26%) had high levels of CA-125 and CA19-9, respectively. No evidence of significant correlation was observed between the KSI and CA-125 and CA19-9 (all p values &gt; 0.05). However, a positive correlation was observed between CA-125 and CA19-9 ( r = 0.55, p-value = 0.02). KSI level was insignificantly lower in recurrent patients compared with non-recurrent patients (9.78 ± 6.24 vs 12.71 ± 18.09, p-value = 0.33). Other tumor markers did not show any statistically significant difference (all p values &gt; 0.05). None of the participants had BRAF V600E mutation. Conclusion: Endometriosis manifests malignant behavioral of rapid proliferation but the exact genetic alteration causing this phenomenon is not understood.

Recurrent embolic stroke associated with adenomyosis: A single case report and literature review.

Uterine adenomyosis is a benign disorder in which endometrial glands and stroma are present within the myometrium. There have been several case reports of cerebral infarction associated with adenomyosis, but their clinical characteristics, optimal treatment, and prognosis have not been systematically reviewed. A case of cerebral infarction with adenomyosis is reported, and a comprehensive systematic literature search using the PubMed database was conducted. A 42-year-old woman, previously diagnosed with adenomyosis, developed multiple cerebral infarctions during menstruation. Her CA125 level was 293 U/mL, and treatment with edoxaban 30mg was started. Seven days after hospital discharge, she had her subsequent menstrual period and then developed a recurrent stroke. Her CA125 level was 743 U/mL on readmission. A hysterectomy was performed, and the patient has had no further stroke recurrence. A systematic review identified 19 cases with cerebral infarction associated with adenomyosis, including the present case. The patients' clinical characteristics included young age (44.7 ± 6.2years), stroke development during menstruation (85%), multiple infarctions affecting ≥ 3 vessel territories (39%), and high levels of CA125 and D-dimer (810.6 ± 888.4 U/mL, and 10.3 ± 18.6μg/mL, respectively). Antithrombotic therapy was given to 14 patients, but recurrent stroke occurred in 5 (36%) patients. Hysterectomy was conducted in 5 and 4 patients with initial and recurrent stokes, respectively, and there were no further recurrences thereafter. Cerebral infarction associated with adenomyosis has specific clinical characteristics. Antithrombotic therapy was insufficient, and hysterectomy should particularly be considered in cases of recurrent stroke.

Complete resection of an intrapericardial bronchogenic cyst with median sternotomy showing high CA19-9 level fluid sampling by EBUS-TBNA: a case report

BackgroundAn intrapericardial bronchogenic cyst (IBC) is rare and compresses the surrounding organs, causing symptoms. Resection of an IBC leads to an improvement in symptoms. We completely resected an IBC by performing median sternotomy and the symptom improved, and we described the clinical course.Case presentationA 48-year-old man with palpitation and chest discomfort was referred to our institution. Chest computed tomography (CT) revealed a 42 × 35 × 32-mm cystic mass attached to the right pulmonary artery and right bronchus. Chest CT also revealed that this cystic mass compressed the superior vena cava, right superior pulmonary vein, and left atrium. Endobronchial ultrasonography transbronchial needle aspiration (EBUS-TBNA) revealed a mucinous fluid with high CA19-9 level (> 12,000 U/mL). We performed complete resection of the IBC that firmly adhered to the superior pulmonary vein and left atrium with cardiopulmonary bypass (CPB) using median sternotomy. The postoperative course was uneventful, and the patient was discharged on postoperative day 16 without major complications. The cystic mass was diagnosed as an IBC. He has been well without symptom of chest discomfort and any signs of recurrence for 18 months postoperatively.ConclusionsFor complete resection of an IBC, CPB needs to be anticipated for difficulty in predicting firm adhesion to the heart and great vessels. Measuring the CA19-9 level in the sampling fluid with EBUS-TBNA can be useful for the preoperative IBC diagnosis.

Prognostic significance of serum CA125 in the overall management for patients with gastrointestinal stromal tumors

BackgroundCarbohydrate antigen 125 (CA125) is elevated as a tumor marker in many carcinomas, but its association with gastrointestinal stromal tumor (GIST) has received less attention. This study intends to evaluate whether CA125 level can predict tumor progression and overall survival (OS) of GIST patients.MethodsWe retrospectively analyzed the clinical data and follow-up records of GIST patients who underwent surgical resection in Nanjing Drum Tower Hospital from August 2010 to December 2020. All patients were classified according to serum CA125 level. The relationship between CA125 and clinical outcomes was then examined.ResultsA total of 406 GIST patients were enrolled in this study, among which 46 patients had preoperative elevated serum CA125 level and 13 patients with high CA125 level both preoperative and postoperative were observed. Preoperative CA125 concentration was significantly related to rupture status, resection style, tumor site, tumor size, mitotic index, NIH risk grade and c-kit exons. According to Kaplan–Meier curve analysis, high expression of postoperative CA125 was significantly correlated with worse progression-free survival (PFS) and OS among patients with preoperative elevated CA125 level. Ultimately, Cox proportional regression model analysis revealed that increase of preoperative and concurrent postoperative CA125 concentration was an independent predictive factor for PFS.ConclusionsThe concurrent abnormality of serum CA125 before and after operation was an independent risk factor for GIST progression, suggesting its significance as a serum biomarker in the overall management of GIST patients.

High level of tumor marker CA19-9 returned to normal after cholecystectomy in calculous cholecystitis patients

Background High serum CA19-9 is usually caused by pancreaticobiliary malignancies, but it has also been found in a tiny minority of calculous cholecystitis patients. Aims To clarify the relationship between calculous cholecystitis and serum CA19-9. Methods Clinical data of calculous cholecystitis patients with high serum CA19-9 (high group, n = 20) and normal serum CA19-9 (normal group, n = 40) who underwent cholecystectomy were analyzed. Serum CA19-9 of high group were followed-up and gallbladder specimens were analyzed by immunohistochemistry. Results Serum CA19-9 in the high group ranged from 105 to 1635 U/ml, of which 30% exceeded 1000 U/ml. Follow-up results showed that 20 patient’s serum CA19-9 returned to normal after cholecystectomy, including 4 closely followed-up patients whose serum CA19-9 recovered within one month. Immunohistochemical results revealed that CA19-9 was mildly positive only in mucosal epithelial cells in the normal group, but positive in mucosal epithelial cells, vascular endothelial cells, and intercellular substances in the high group, accounting for high serum CA19-9. Conclusion Serum CA19-9 is proved to be associated with calculous cholecystitis for the first time, so that clinicians should consider calculous cholecystitis associated CA19-9 elevation in the clinic practice besides other CA19-9 related diseases.

A Very High Ca-125 Level Is Not Always Malignant: A Case-Based Experience From Tuberculosis Patient

CA-125 is a serum marker that is raised in various malignant and non- malignant conditions, but a very high rise (&gt;1000 U/mL) almost always suggests ovarian malignancy. Here we report a rare case of tuberculous peritonitis in a 58-year-old woman who presented with gradually progressive abdominal distension and weight loss, and her CA-125 level was &gt;1000 U/mL. Initially suspecting this as a case of ovarian malignancy, ascitic fluid study to detect malignant cells and a contrast CT scan of the abdomen was done, but the results didn’t suggest any malignancy. Finally, diagnostic laparoscopy was done and tuberculous peritonitis was diagnosed by peritoneal biopsy and histopathology. This case is an excellent example showcasing the importance of tissue diagnosis over indirect supportive tests, and it also suggests that clinical suspicion of tuberculosis in an endemic zone should always be there even if the patient has very high CA-125 level. Bangladesh J Medicine 2022; 33: 49-51

Sarcopenia in patients with pancreatic cancer, an independant prognostic factor

Pancreatic cancer is despite modern diagnostic tools and treatment regimen associated with poor outcome. Many patients show cachexia and sarcopenia. In a retrospective analysis the SMI (cm²/m²) was measured by determining the skelettal muscle area in a computed tomography image at lumbar vertebrae 3. Further clinical parameters were measured to determine the outcome. The mean survival after diagnosis in the population with sarcopenia was significantly lower (14,4 vs 17,7 months, p=0,046). Significantly shorter survival was also seen for higher age (p=0,006), no tumor resection (p=0,004), metastases (p=0,002) and high CA19-9 level (p=0,002) CONCLUSION: Sarcopenia is an indipendant prognostic factor in patients with pancreatic cancer. SMI should be measured clinical practice and further studies are necessary to asses a potential therapeutic strategy.

Diagnosis challenges of a patient with peritoneal tuberculosis masquerading as ovarian malignancy: a case report

Background: Peritoneal tuberculosis (PTB) could mimic advanced ovarian cancer cases, making its diagnosis challenging. Comprehensive and conscientious examinations for diagnosis are needed to differentiate such cases to avoid inappropriate treatment. We report a problematic diagnosis of PTB that mimic ovarian malignancy. Case Presentation: A 20-year-old female patient with history of multiple rehospitalizations, presented with complaints of abdominal pain, nausea/vomiting, low-grade fever, and weight loss in the last five months. In the first admission, patient was suspected with malignant ovarian cyst due to clinical features of malignancy with normal chest X-ray, abdominal USG suggested ovarian cyst in both ovaries, high levels of Ca125. However abdominal CT-scan showed thickening in peritoneum which suggested PTB. The patient was planned for urgent laparotomy while waiting for GenExpert result. On the second admission, patient presented with recurrent abdominal pain, GenExpert sputum and stool showed negative result, and planned for surgery but the patient refused. On the last admission, patient diagnosed with impending bowel obstruction and underwent abdominal CT-scan with contrast showed diffuse multiloculated cystic lesion in cavum pelvic and multiple prominent mesenteric lymph nodes that suggested abdominal TB with abscess in cavum pelvic. Exploratory laparotomy revealed conglomeration, pus and tubercles in the peritoneum. A TB was confirmed based on pathology and microbiology examination from tissue biopsy and pus. Conclusion: We reported patients with PTB with unspecific clinical symptoms which suspected as ovarian malignancy. This study highlights the challenges in diagnosing PTB and therefore PTB could be considered a differential diagnosis in patients suspected of ovarian malignancy in the TB endemic countries.

Clinical Significance of Methyltransferase-like 16 Expression in Epithelial Ovarian Cancer.

To detect methyltransferase-like (METTL) 16 expression in epithelial ovarian cancer (EOC) by immunohistochemistry (IHC), and its relationship with clinicohistopathological parameters and prognosis. Observational study. Department of Gynaecology and Pathology, The First Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), from February to June 2022. METTL16 expression in 115 EOC patients was evaluated by IHC. According to the immunoreactive score (IRS), scores <6 represented low expressions and ≥6 high expressions. Clinicopathologic data and follow-up information were collected for statistical evaluation. METTL16 expression decreased in EOC (p = 0.001) and affected the poor prognosis of EOC patients. Low METTL16 patients expression had significantly higher frequencies of advanced FIGO stage, low grade, more lymph node metastasis, high CA125 levels, bilateral disease, distant metastasis, and high frequency of neural/vascular invasion compared to high METTL16 patients (p ≤0.001, <0.001, <0.001, 0.017, 0.027, <0.001, and 0.010, respectively). The survival analysis showed that the overall survival (p <0.0001) as well as the disease-free survival (p <0.0001) were remarkably shorter in low METTL16 patients compared to high METTL16 patients, suggesting worse survival. There was a clear association between the expression of METTL16, poor prognostic factors, and lower survival of EOC patients, suggesting that it might exert a vital effect on the malignant progression / prognosis of EOC. Epithelial ovarian cancer (EOC), METTL16, Immunohistochemistry, Prognosis.

Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma.

As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p<0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p<0.05). The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.

Abstract PR014: Evaluating circulating tumor DNA by targeted next generation sequencing as a biomarker in the treatment of localized pancreatic cancer

Abstract Introduction: The utility of circulating tumor DNA (ctDNA) as a biomarker in localized pancreatic ductal adenocarcinoma (PDAC) remains unclear. We aimed to characterize the detection of ctDNA by targeted next-generation sequencing (NGS) during treatment for localized PDAC and to evaluate the clinical implication of detection. Methods: Patients with localized PDAC were enrolled in a prospective study at Northwestern Medicine Cancer Centers between September 2020 and May 2022. During treatment, blood was drawn for targeted NGS ctDNA assessment utilizing the Tempus xF 105 gene panel assay. Three timepoints during the course of treatment were evaluated: at diagnosis prior to treatment, after neoadjuvant chemotherapy (NAC), and after local therapy, which included surgery with or without radiotherapy, or radiotherapy alone. The effect of NAC and local therapy on ctDNA mutational status and its relationship with serum CA19-9 was analyzed. Results: 32 patients who underwent NAC were included in the analysis. 66% of patients received FOLFIRINOX and 34% received Gemcitabine/nab-paclitaxel. The mean length of NAC was 3.1 months. TP53 mutations were the most common mutation detected by targeted NGS (41%), followed by KRAS (G12D/V/R, 13%) and ATM mutations (13%). In 24 patients assessed prior to treatment, 10 (42%) were found to have detectable ctDNA. 11 of 32 (34%) patients had detectable ctDNA following completion of NAC. 22 patients underwent surgery, of which 6 (27%) had detectable ctDNA following NAC and surgery. Of the 10 patients who had detectable ctDNA prior to treatment, 4 (40%) cleared ctDNA after treatment. Patients with detectable ctDNA prior to treatment had higher CA19-9 levels following NAC compared with those with undetectable ctDNA prior to treatment (1244.83 U/ml vs 60.42 U/ml, p = 0.0299). Following NAC, patients with detectable ctDNA had higher CA19-9 levels than those with undetectable ctDNA after NAC (1121.05 U/ml vs 58.89 U/ml, p = 0.0231). 6 of 32 (19%) patients were found to have unresectable disease following NAC and underwent definitive radiotherapy for local control; none of these patients had ctDNA clearance. Conclusion: This is the first reported study demonstrating the value of targeted NGS as a biomarker in the treatment of localized pancreatic cancer. Treatment led to clearance of detectable ctDNA, although the effect was not seen in all patients. Patients with detectable ctDNA prior to treatment had higher levels of CA19-9 following NAC, suggesting that pre-therapy detection may be a predictor of poor serum CA19-9 response after NAC. Given that after NAC, patients with detectable ctDNA had significantly higher serum CA19-9 levels, ctDNA assessment by targeted NGS may be an additional biomarker of treatment response. Taken together, ctDNA detected by targeted NGS is a potential biomarker of treatment response in localized PDAC. Citation Format: Dhavan Shah, Amy Wells, Kevin Dawravoo, John Abad, Arlene D'Souza, Grace Suh, Robert Bayer, Sohail Chaudhry, David Bentrem, Akhil Chawla. Evaluating circulating tumor DNA by targeted next generation sequencing as a biomarker in the treatment of localized pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR014.

Preoperative serum CA19-9 predicts postoperative pancreatic fistula in PDAC patients: retrospective analysis at a single institution

BackgroundPostoperative pancreatic fistula (POPF) is a critical complication of pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC). Recent papers reported that serum carbohydrate antigen (CA)19-9 levels predicted long-term prognosis. We investigated whether preoperative serum CA19-9 levels were associated with POPF in PDAC patients.MethodsThis cohort study was conducted at a single institution retrospectively. Clinicopathologic features were determined using medical records.ResultsAmong of 196 consecutive patients who underwent pancreatectomy against PDAC, 180 patients whose CA19-9 levels were above the measurement sensitivity, were registered in this study. The patients consisted of 122 patients who underwent pancreaticoduodenectomy and 58 patients who underwent distal pancreatectomy. Several clinicopathological factors, including CA 19-9 level, as well as surgical factors were determined retrospectively based on the medical records. Patients with high CA19-9 levels had a significantly higher incidence of POPF than those with low levels (43.9 vs. 13.0%, P < 0.0001). The receiver operating characteristic curves calculated that the cutoff CA19-9 value to predict POPF was 428 U/mL. CA19-9, BMI, curability, and histology were statistically significant risk factors for POPF by univariate analysis. Multivariate analysis showed that CA19-9 and BMI levels were statistically significant independent risk factors for POPF. CA19-9 levels were correlated with both histology and curability. Disease free survival and overall survival of patients with higher levels of CA19-9 were significantly shorter than that of patients with lower levels of preoperative serum CA19-9.ConclusionsIn patients undergoing pancreatectomy for PDAC, higher preoperative CA19-9 levels are a significant predictor for POPF.

Benign Diseases Masquerading as Cholangiocarcinoma: Can we Differentiate before Surgery?

Background: Cholangiocarcinoma (CCA) is a potentially lethal disease that requires surgical treatment. There are many benign conditions, those that do not require surgical treatment, displaying imaging characteristics that resemble CCA, leading to therapeutic misadventures. This study aimed to evaluate the proportion of benign conditions that underwent hepatic resection for presumed CCA, and explore the differences between the characteristics of these two entities stratified by primary imaging features of the lesions. Methods: This retrospective study ran between January 2004 and December 2011. We reviewed the pathological records of all 1,402 patients who underwent curative-intent hepatic resection for preoperatively diagnosed CCA. All clinical and pathological parameters were analyzed. Results: The proportion of benign conditions that underwent hepatic resection was 3.78% (53/1,402). For mass-forming lesions, CCA was associated with higher age, alkaline phosphatase, tumor markers, neutrophil to lymphocyte ratio, and mass size. The patients with mass-forming benign conditions were more associated with diabetes mellitus. For lesions with bile duct dilatation, intraductal tumor, including CCA, had higher CA19-9 level and NLR with statistical significance. For cystic lesions, biliary cystic neoplasm had statistical significance in the rate of abdominal pain. Conclusions: The proportion of hepatic resection for benign conditions was quite low. There were many characteristic differences used to differentiate benign mass-forming conditions from CCA, whereas only few markers in the setting of cystic lesions and biliary dilatation. We recommend performing standard hepatic resection in every case, regardless of the type of imaging features, if the lesion has a chance of being CCA.

Validation of a genotype-based algorithm that identifies individuals with low, intermediate, and high serum CA19-9 levels in cancer-free individuals and in patients with colorectal cancer

BackgroundSerum levels of Carbohydrate antigen CA19-9 are determined by the genotype of fucosyltransferases 2 and 3. To validate, possibly modify, and improve a grouping algorithm based on these genotypes.MethodsCA19-9 levels genotypes and of fucosyltransferase 2 and 3 were analyzed in cancer-free and colorectal cancer patients. Patients were assigned to groups with low (group A), intermediate (B), or high (C) CA19-9 biosynthetic activity based on a previously developed grouping algorithm based on genotype of fucosyltransferases 2 and 3.ResultsThree hundred thirty-eight patients were included (n=177 cancer-free). Of cancer-free patients 7.9%, 75.7%, and 16.4% were assigned to groups A, B, and C, respectively. In colorectal cancer patients it 7.5%, 77.0%, and 15.5%, respectively. There were significant differences between median CA19-9 levels in the three groups (P<0.001) in both cohorts. The T59G single-nucleotid polymorphism in fucosyltransferase 3 had a significant influence on CA19-9 levels in cancer-free group B patients, which led to establishment of subgroups B1 and B2. However, no difference in CA19-9 levels between these subgroups was found in colorectal cancer patients. A receiver-operating characteristic showed similar areas under the curve for original group B as well as for subgroups B1 and B2.ConclusionsThe grouping algorithm based on genotype of fucosyltransferases 2 and 3, which defines groups with distinct CA19-9 serum levels, was validated in cancer-free patients and in colorectal cancer patients. No clinically relevant improvement to the grouping algorithm was identified.

Association of carbohydrate 125 antigen with sepsis mortality in critical patients

IntroductionThe increased synthesis of CA125 in mesothelial cells is connected with pathophysiological processes, also present in sepsis, that link inflammation with systemic congestion. We propose to evaluate serum levels of this biomarker in patients with sepsis and to study its association with the severity and evolution of the disease. MethodsLongitudinal retrospective observational study, which included 126 patients admitted to an Intensive Care Unit with sepsis criteria. The main variables analyzed were: CA125 values for 7 days, the variation of its levels according to the source of infection (abdominal, pulmonary, nephrourinary and others), sepsis, septic shock, APACHE-II score and mortality. ResultsCA125 levels remained elevated throughout the study period. The abdominal focus presented higher mean levels of CA125 (62 ± 55.5 U/mL; P = 0.001) and were higher in non-survivors (77.2 U/mL; interquartile range 35.9−118.5; P = 0.0273). CA125 levels > 35 U/mL throughout the weal had an independently effect on the evolution (relative risk [RR] 3.1; 95% confidence interval [CI] 1.6–6.2; P = 0.001) and the elevated mean value of CA125 was also associated with mortality (RR 1.004; 95% CI 1.001–1.005; P = 0.0001). ConclusionsSeptic patients presented high levels of CA125 on the study days, being higher in abdominal infections. In our study, serial determination of CA125 is a prognostic marker of mortality independent of age, origin of infection or severity.

Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections.

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be downregulated in CRC patients with liver metastases compared to those without (P = 0.025, fold change [FC] = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival (OS) time (33.3 months versus 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced tumor node metastasis staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by ExomiR-150. Target-prediction assessment and dual-luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.

Extremely high serum CA19-9 level along with elevated D-dimer in assisting detection of ruptured ovarian endometriosis

Background To clarify clinical importance of serum CA19-9, CA-125, and plasma D-dimer (D-D) levels in detecting spontaneously ruptured ovarian endometriosis (OE). Materials and Methods We retrospectively examined 173 patients with endometriosis out of 735 cases of OE between 2013 and 2019. Among these, 21 cases were diagnosed as “spontaneously ruptured” after surgery, while the remaining cases were unruptured. Venous blood was collected pre-operatively to detect CA19-9, CA-125, and D-D levels. A receiver operating characteristic curve analysis was applied to test clinical value of each marker. Results Among the 21 patients with ruptured OE, 16 had a history of pelvic cysts, 19 claimed sudden onsets of lower abdominal pain, and fluid accumulation were detected in cul-de-sac in only six participants by ultrasound. For serological investigation, both CA19-9 and D-D were significantly elevated in the ruptured OE group (343.09 ± 367.67 U/ml vs. 36.84 ± 40.01 U/ml, 3.39 ± 4.90 mg/L vs. 0.43 ± 0.29 mg/L, both p < .0001). The area under curve (AUC) value for the combination of CA19-9 and D-D was 0.975 (95% CI, 0.939 − 0.993), with specificity of 96.69%, and sensitivity of 85.71%. The combination of CA-125, CA19-9 and D-D showed the highest AUC value that up to 0.976 (95% CI, 0.940–0.993), with sensitivity of 95.24%, and specificity of 87.50%. Conclusion The combination of CA19-9 and D-D can be chosen as an effective and economical indicators to identify patients with spontaneously ruptured OE in pre-operation assessment. However, from the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice. Key messages Taking into account the economic effect, the combination of CA19-9 and D-D can be chosen as an effective indicators to identify patients with spontaneously ruptured OE in pre-operation assessment. From the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice to identify patients with spontaneously ruptured OE.

Molecular genetic characteristics of colorectal cancer depending on the status of microsatellite instability

Introduction. The emergence of new markers that determine the choice of therapy for metastatic colorectal cancer (CRC) has led to an increase in overall survival. The optimal treatment tactics now take into account both clinical and molecular-genetic characteristics of the tumor.Aim. Investigation of the features of the KRAS, NRAS and BRAF mutations and amplification of the HER2 gene depending on microsatellite instability (MSI) in CRC.Materials and methods. The study included 400 patients with CRC. MSI, BRAF V600E mutation, mutations in the KRAS and NRAS genes was identified to them. MSI was determined by fragment analysis, and mutations in the KRAS, NRAS, BRAF genes by realtime PCR. HER2 amplification was determined in 100 patients with a negative RAS/BRAF. NTRK translocations were determined in all patients with MSI. Data on preoperative levels of CEA and CA19-9 were obtained from 185 patients.Results and discussion. The prevalence of MSI was 6.8%. The prevalence of KRAS, NRAS, BRAF mutations in CRC with MSI was 66.7%, and in CRC with MSS - 52.3%. In patients with MSI, the level of CEA was lower than in MSS (p = 0.0061). The overall prevalence of KRAS and NRAS mutations was 45% and 2.5%. The overall prevalence of the BRAF V600E mutation was 5.8% and was more common in MSI-positive tumors (p &lt; 0.0001). Regardless of MSI, BRAF-positive tumors were characterized by right-sided localization (p &lt; 0.0001), category T3-4 (p = 0.013), lymph node involvement (p = 0.004), carcinomatosis (p = 0.046), high levels of CA19-9 (p = 0.014). HER2 amplification was found in 7% of wild-type RAS/BRAF cases and was associated with rectal cancer (p = 0.044), category T3-4 (p = 0.041), and distant metastases (p = 0.038). HER2 amplifications and NTRK translocations were not detected in cases with MSI.Conclusion. MSI-positive CRC had a higher prevalence of mutations in major genes. CRC with the BRAF V600E mutation and HER2 amplification had aggressive clinical and morphological parameters.

The prognostic value of stromal tumor-infiltrating lymphocytes in intrahepatic cholangiocarcinoma: a population-based study

Objective We assess the predictive value impacted by tumor-infiltrating lymphocytes (TILs) for overall survival (OS) and progression-free survival (PFS) in patients with intrahepatic cholangiocarcinoma (ICC) undergoing complete resection. Methods Sixty-eight patients with resectable ICC were included in this study. We studied stromal TIL density and scored it by staining sections from surgically resected ICC patients with hematoxylin and eosin (HE). The clinical data and prognosis of patients with ICC were obtained by searching clinical and follow-up records. Results A stromal TIL negative status was a predictor of poor OS (HR = 0.41, 95% CI 0.20–0.83, p = .01) and poor PFS (HR = 0.47, 95% CI 0.23–0.97, p = .04) independently. Low stromal TIL density was associated with high levels of CA125 (p = .03) and CA19-9 (p < .01). The high level of CA19-9 (p = .05), high differentiation (p = .02), a large diameter (p = .05), a positive bile duct/vascular cancer embolus (p = .03) and positive satellite nodules (p = .02) were tendencies to develop tumors for patients with a negative status of stromal TIL. Conclusion Our data prompt for the prediction of the PFS and OS of patients with ICC after complete resection, stromal TILs play an important role.