CA125 Levels Research Articles

Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and efficacy of phase 1b/2 study (RAMP 205).

4140 Background: More than 90% of pancreatic ductal adenocarcinomas (PDAC) harbor an activating KRASmutation .Avutometinib (avuto) is an oral RAF/MEK clamp. Defactinib (defact) is an oral selective FAK inhibitor. Avuto/defact combined with gemcitabine/paclitaxel have shown synergistic antitumor activity in preclinical PDAC models. RAMP 205 (NCT05669482) is a Phase 1b/2 study assessing the safety and efficacy of avuto/defact + gemcitabine/nab-paclitaxel (GnP) in first-line metastatic PDAC. Methods: Eligible patients (pts) were enrolled and treated in 3+3 cohorts with escalating doses of avuto orally (PO) twice weekly (BIW) and defact PO twice daily (BID), both 3 out of 4 weeks, in combination with GnP dosed intravenously (IV) on a D1, D8, D15 or D1, D15 (modified) 4wk schedule (Table 1). Key eligibility criteria include histologically confirmed newly diagnosed metastatic PDAC with measurable disease, ECOG performance status (PS) ≤1, adequate organ function, and no prior treatment. Results: At the 24Jan2024 data cutoff, 18 pts were enrolled, 44% were male, 65 y median age, and 61% ECOG PS 1. Pts were enrolled to DL-1 (n=3), DL1 (n=6), DL1a (n=6), and DL2a (n=3). No dose-limiting toxicities (DLTs) were reported and the majority of treatment related adverse events (TRAEs) were mild to moderate. The most frequently reported TRAEs of any grade in the safety population (N=18) were nausea (50%), alopecia (44%), fatigue (39%), maculo-papular rash (33%), and peripheral edema (28%). The most common grade ≥3 TRAEs included alanine aminotransferase increase (17%), neutropenia (17%), peripheral edema (11%), anemia (11%), and sepsis (11%). Four patients experienced serious AEs (SAEs). Grade ≥3 treatment emergent SAEs included pulmonary embolism (n=2; unrelated), sepsis (n=2), febrile neutropenia (n=1; did not meet DLT criteria), and neutropenia (n=1). One patient discontinued treatment due to TRAE (febrile neutropenia and blood bilirubin increased). All efficacy evaluable pts (n=8) experienced a reduction in target lesions (100% disease control rate) and partial responses were observed in 6/8 (75%), 3 being confirmed at data cutoff. All efficacy evaluable pts with an elevated CA19-9 at baseline (n=7) had a ≥60% CA19-9 reduction from baseline. Conclusions: Avuto/defact and GnP are combinable and show notable preliminary efficacy in first-line metastatic PDAC based on RECIST v.1.1 criteria and CA19-9 levels. No DLTs were reported across the 4 dosing cohorts/schedules and safety signals were consistent with previous clinical data. Updated safety and efficacy will be reported. Clinical trial information: NCT05669482 . [Table: see text]

Thioredoxin 1 in blood as a monitoring biomarker for patients with breast cancer post-treatment.

e15041 Background: The spatial and temporal heterogeneity of tumors in breast cancer pose challenges in precision oncology. Although breast imaging during screening has increased tumor detection and reduced mortality rates, it is limited in tracking minimal residual disease after surgery. Consequently, there is a need for liquid biopsy with easy longitudinal sampling to track real-time changes in tumor characteristics during treatment. Existing biomarkers (CA15-3 and CEA) for post-treatment monitoring are unsatisfactory. This study explores the clinical validity and stability of thioredoxin1 (Trx1) in a 54-month longitudinal study, reflecting tumor characteristics during treatment. Methods: Approved by IRB from Chungnam National University Hospital (IRB: 2021-02-003). Fourteen out of the initial 20 BC patients were finally enrolled because pre-surgery samples for the 6 patients excluded were missing. A total of 116 sera were collected before and after surgery at intervals from 6 to 54 months. After isolating the serum, an immunoassay was performed to measure the level of serum Trx1 using the DxMe® BC kit (E&S Healthcare). CA15-3 and CEA levels were measured in paired samples and collected from medical records. The results were retrospectively analyzed along with clinical information, and the profile of Trx1 level change was analyzed for each individual. Results: The blood Trx1 levels in pre-operation BC patients were 20.68±4.44 U/ml (±SD). From 6 months’ post-operation to the 54th month, blood Trx1 levels in patients were consistently low, averaging 5.43±3.34 U/ml (p < 0.0001 compared to pre-op). In contrast, levels of CEA and CA15-3 did not change significantly before and after surgery. The pre-op and post-op AUC for Trx1, CA15-3, and CEA were 0.998 (95% CI: 0.941 to 1.000), 0.599 (95% CI: 0.482 to 0.709), and 0.550 (95% CI: 0.433 to 0.663), respectively. There was no significant difference in the decreasing profile of Trx1 levels over 54 months between different treatment methods. While existing a microscopic difference according to BC characteristics, all post-op values were already below the cut-off value. Regardless of treatment, Trx1 levels decreased to those of normal healthy women after surgery. There were no recurring cases to compare over 54 months. Conclusions: The results of this 54-month post-operation tracking observation revealed a rapid decrease in Trx1 levels in the blood after surgery, which remained consistently downregulated without a statistical association with pathological findings. This suggests that Trx1 is related to the presence of tumor masses rather than the pathological characteristics of the tumor. It is likely that if any treatment causes the removal and suppression of BC, the level of Trx1 is kept low. Besides its already reported ability to detect BC in blood, Trx1 levels have the potential to serve as a monitoring biomarker in the management of BC patients after treatment.

Study on the efficacy and toxicity of pamiparib combined with tamoxifen in the treatment of patients with epithelial ovarian cancer with biochemical recurrence during first-line PARPi maintenance therapy.

TPS5621 Background: A high proportion of ovarian cancer patients tend to have elevated CA-125 1-6 months before imaging recurrence. The time between biochemical recurrence (i.e., only elevated CA-125 without imaging finding or clinical symptoms) to imaging recurrence can be considered a "window period", and if the “window period” can be extended, it may convert platinum-resistant relapsed patients to platinum-sensitive patients, and ultimately improving patient outcomes. The timing of treatment for the biochemical recurrent patients has been controversial. Tamoxifen, an anti-estrogenic drug, is considered an effective option for these patients. Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. According to OReO study(NCT03106987), the "PARPi after PARPi" strategy is effective in recurrent ovarian cancer patients previously treated with a PARP inhibitor. Therefore, we aim to further explore the use of PARP inhibitors in maintenance therapy for patients with ovarian cancer. Methods: This study (NCT05669768) will evaluate the efficacy and toxicity of pamiparib and tamoxifen in ovarian cancer patients with biochemical recurrence during first-line PARPi maintenance therapy. The included ovarian cancer patients are required to achieve No Evidence of Disease (NED) or demonstrated a response following platinum-based chemotherapy, with normalized CA-125 levels. First-line maintenance treatment with a PARP inhibitor is mandatory, with a minimum interval of ≥6 months to biochemical recurrence. The trial design is interventional, employing a Simon two-stage design to estimate sample size. The primary outcome of the study is the CA-125 response rate, which was assessed according to the GCIG criteria.1 The secondary outcome was Time to First Subsequent Therapy (TFST). Patients undergo regular assessments for tumor markers and imaging throughout treatment. If persistent elevation of tumor markers or the detection of recurrent lesions or distant metastases is observed, the patient is promptly removed from the study group. Standardized antitumor therapy is then initiated based on the patient's condition. The total planned enrollment is 46 participants, utilizing a single-group assignment and an open-label design. 1 of planned 12 patients for the first stage of accrual have been enrolled. Reference: 1. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419-423. Clinical trial information: NCT05669768 .

Phase II study of pirfenidone combined with nab-paclitaxel and gemcitabine for patients with metastatic pancreatic cancer.

4152 Background: Pancreatic cancer is a disastrous malignancy characterized by the dense fibrous stroma, elevating interstitial pressure and impairing perfusion of chemotherapeutics. Pirfenidone (PFD) is an oral antifibrotic agent, which might reduce the degree of fibrosis of pancreatic cancer and increase drug delivery. Thus, we aimed to evaluate the efficacy and safety of pirfenidone (PFD) plus nab-paclitaxel and gemcitabine (AG) for patients with metastatic pancreatic cancer. Methods: In this two-stage single-arm phase II trial, treatment-naïve patients with metastatic pancreatic cancer received oral PFD, 200 mg three times daily in the first week and 400 mg three times daily thereafter, in combination with intravenously administered gemcitabine 1000 mg/m2 and nab-paclitaxel 120 mg/m2 on days 1,8 of each 21-day cycle. The primary endpoint was overall response rate (ORR). A total of 33 patients were required based on the assumption of an expected ORR of 45%, with an α-error of 5% (one-sided) and a β-error of 20%. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: We enrolled 33 patients from October 2020 to February 2023, with median age of 61years (IQR 53-65), 21(63.6%) male and 12(36.4%) female. Metastatic sites included the liver (32cases), lung(7cases) and peritoneum (11cases). The last one patient was enrolled on February 24, 2023 and the deadline of follow up was Jan 25, 2024, with only one was unevaluable. The ORR was 50.0% (95% CI 33.6%-66.4%) and the DCR was 93.8%(95%CI 79.9%-98.9%). The median PFS was 4.9 months (95% CI 3.9-5.9) and the median OS was 9.1 months (95% CI 7.8-10.4). Among all cases of 25 with elevated CA19-9 at diagnosis, 56% patients experienced a decrease in CA19-9 levels of more than 50%. Grade 3-4 toxicities were observed in 11 (34.4%) patients, with leukopenia (7[21.9%]), anemia (5[15.6%]) and elevated AST level (4[12.5%]). No treatment-related deaths occurred. Conclusions: Adding PFD to AG showed promising ORR and DCR and an acceptable adverse event in patients with metastatic pancreatic cancer. Clinical trial information: ChiCTR2000034397.

Adjuvant S-1 vs. observation for resected biliary tract cancer: 5-year follow-up of the JCOG1202/ASCOT.

4119 Background: S-1, an oral fluoropyrimidine derivative, demonstrated significant improvement in overall survival (OS) over observation in patients with curatively resected biliary tract cancer (BTC) (hazard ratio [HR] 0.694, p=0.008; the 3-year OS, 67.6% vs. 77.1%, Lancet 2023). We present updated efficacy data based on a 5-year follow-up of JCOG1202/ASCOT. Methods: Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone R0/R1 resection were randomly assigned (1:1) to undergo observation or to receive S-1 (at the dose of 40 mg/m2 twice daily for 4 weeks, followed by 2 weeks of rest, for 4 cycles). The primary endpoint was OS, and the secondary endpoints were relapse-free survival (RFS), adverse events, and proportion of treatment completion. Results: From September 2013 to June 2018, a total of 440 patients (observation, n=222; adjuvant S-1, n=218) were enrolled. The final data cutoff date was June 23, 2023, and the median follow-up duration was 61.5 months. Of all the randomized patients, 215 (48.4%) had died (118 [53.2%] in the observation group; 97 [44.5%] in the S-1 group). The 5-year OS was 52.2% in the observation group and 64.1% in the S-1 group (stratified HR 0.723, 95% confidence interval [CI], 0.551-0.948; one-sided p=0.019). Of the 440 patients, 239 (54.3%) had RFS event (127 [57.2%] in the observation group; 112 [51.4%] in the S-1 group). The 5-year RFS was 45.9% in the observation group and 53.6% in the S-1 group (unstratified HR 0.797, 95% CI 0.618-1.028, stratified HR 0.761, 95% CI 0.589-0.984 in the sensitivity analysis). Most prespecified subgroup analyses (age, primary site, stage, lymph node metastases, types of resections, and serum CA19-9 levels) revealed favorable OS and RFS for the S-1 group. Conclusions: Adjuvant S-1 therapy maintained its survival benefit in a 5-year long-term follow-up, with clinically meaningful improvement in RFS, suggesting that it could be a standard of care for BTC. Clinical trial information: UMIN000011688.

Penpulimab combined with anlotinib and nab-paclitaxel plus gemcitabine (PAAG) as first-line treatment for metastatic pancreatic cancer: A prospective, multicenter, single-arm, phase 2 study.

4135 Background: Chemotherapy currently serves as the cornerstone for treating metastatic pancreatic cancer (mPC). Nevertheless, the survival of patients with mPC remains poor. Besides, the efficacy of single-agent immune checkpoint inhibitors or antiangiogenesis in the treatment of mPC is not satisfying. Therefore, it is important to explore combination therapy options for patients with mPC. This trial was conducted to evaluate the effectiveness and safety of penpulimab combined with anlotinib and nab-paclitaxel plus gemcitabine (PAAG) for mPC. Methods: This was a prospective, multicenter, single-arm phase II trial. Eligible pts were those who aged over 18 years, histologically or cytologically confirmed PC, have not received treatment before and radiographically showed distant metastases and measurable lesions. Patients received penpulimab (200mg, IV, D1) and Anlotinib (12mg, P.O, QD, D1-14), in addition to nab-paclitaxel (125mg/m2, I.V, D1,8) and gemcitabine (1.0g/m2, I.V, D1,8), administered over a 21-day treatment cycle. The primary endpoint was objective response rate (ORR) and disease control rate (DCR). Secondary end points included Progression-free Survival (PFS), overall survival (OS) and safety. Immune microenvironmental features of baseline were analyzed as exploratory results (NCT05493995). Results: 66 pts were enrolled and received PAAG therapy, and the last follow-up time was December 31, 2023. All pts were eligible for response evaluation. The ORR was recorded at 50% (33/66) (95% CI, 37.4%-62.6%), with 33 pts achieving partial response. The DCR was 95.5% (63/66) (95% CI, 87.3%-99.1%). With median follow-up duration of 12.8 months, median PFS was 8.8 months (95% CI, 8.1–11.3) and median OS was 13.7 months (95% CI, 12.4-not reached). The most common TRAEs were anaemia, leukocytopenia, fatigue and rash. Grade 3 TRAEs were reported in 36.4% pts (24/66). In exploratory analysis, higher T cell recruiting score and lower baseline serum CA72-4 level were detected in PR pts compared with SD/PD pts. Furthermore, the B cell, NK CD56dim cell and Th9 cell scores were up-regulated in PFS-long pts. Conclusions: PAAG regimen as first-line treatment was demonstrated to be tolerable, with promising anti-tumor activity in mPC. The identified biomolecular markers revealed potential to guide precision treatment of PAAG for mPC. Clinical trial information: NCT05493995 .

Clinical value of serum tumor markers in assessing the efficacy of neoadjuvant chemotherapy in advanced ovarian cancer: single-center prospective clinical study.

This study aimed to assess the clinical importance of various biomarkers, including NLR, CEA, CA199, CA125, CA153, and HE4, through dynamic testing to evaluate the effectiveness of neoadjuvant chemotherapy (NACT) for individuals facing advanced ovarian cancer. This provides valuable information for tailoring treatment plans to individual patients, thereby leading to a more personalized and effective management of individuals facing ovarian cancer. The levels of NLR, CA125, CA199, CEA, CA153, and HE4 were detected before chemotherapy and after 3 courses of chemotherapy. Patients were categorized into ineffective and effective groups according to the effectiveness of NACT. To evaluate the factors influencing NACT's effectiveness in individuals facing advanced ovarian cancer, receiver operating characteristic (ROC) curves, predictive modeling, and multifactorial regression analysis were employed. In the effective group, the patients' age, maximum tumor diameter, and CEA and HE4 levels of the patients were significantly higher compared to those in the ineffective group (P <.05). Additionally, the difference in HE4 levels before and after treatment between the effective and ineffective groups was statistically significant (P<.05). Multifactorial analysis showed that age and maximum tumor diameter were independent risk factors impacting the effectiveness of NACT in individuals facing advanced ovarian cancer (P<.05). The ROC curve for predicting the effectiveness of NACT in individuals facing advanced ovarian cancer showed a sensitivity of 93.3% for NLR and a specificity of 92.3% for CA199. HE4 emerged as the most reliable predictor, demonstrating a specificity of 84.6% and a sensitivity of 75.3%. The area under the curve of the combined CA125 and HE4 assays for predicting the ineffectiveness of NACT in individuals facing advanced ovarian cancer was 0.825, showcasing a specificity of 74.2% and a sensitivity of 84.6%. The predictive capacity for the effectiveness of NACT in individuals facing advanced ovarian cancer is notably high when considering the sensitivity of NLR and the specificity of CA199. Additionally, the combination of CA125 and HE4 assays can obtain a better predictive effect, which can accurately select patients suitable for NACT, determine the appropriate timing of the interval debulking surgery (IDS) surgery, and achieve a satisfactory tumor reduction effect.

Surgical treatment for pulmonary metastasis from ovarian cancer: a retrospective case series

BackgroundDistant metastases of ovarian cancer are rarely detected alone. The effectiveness of surgical intervention for pulmonary metastases from ovarian cancer remains uncertain. This study aimed to investigate the clinicopathologic characteristics and outcomes of patients undergoing resection for pulmonary metastasis from ovarian cancer.Case presentationThe clinicopathologic characteristics and outcomes of radical surgery for pulmonary metastasis from ovarian cancer were investigated. Out of 537 patients who underwent pulmonary metastasis resection at two affiliated hospitals between 2010 and 2021, four (0.74%) patients who underwent radical surgery for pulmonary metastasis from ovarian cancer were included. The patients were aged 67, 47, 21, and 59 years; the intervals from primary surgery to detection of pulmonary metastasis from ovarian cancer were 94, 21, 36, and 50 months; and the overall survival times after pulmonary metastasectomy were 53, 50, 94, and 34 months, respectively. Three of the four patients experienced recurrence after pulmonary metastasectomy. Further, preoperative carbohydrate antigen (CA) 125 levels were normal in two surviving patients and elevated in the two deceased patients.ConclusionIn this study, three of the four patients experienced recurrence after pulmonary metastasectomy, but all patients survived for > 30 months after surgery. Patients with ovarian cancer and elevated CA125 levels may not be optimal candidates for pulmonary metastasectomy. To establish appropriate criteria for pulmonary metastasectomy in patients with ovarian cancer, further research on a larger patient cohort is warranted.

The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis

Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.

Clinicopathological analysis of giant ovarian tumors

ObjectiveThis study aims to analyze giant ovarian tumors' clinical and pathological characteristics. Material and MethodsThis was an analytical observational study. Medical records of all patients with giant ovarian tumors who underwent surgery between January 2020 and June 2022 at Dr. Soetomo Academic Hospital, Surabaya, Indonesia, were analyzed. ResultsWe analyzed 63 patients with ovarian tumors measuring > 20 cm who underwent surgery at Dr. Soetomo Academic Hospital, Surabaya, Indonesia. The mean tumor size was 25.9 cm (largest size was 41 cm). There was no significant difference in tumor size between benign and malignant giant ovarian tumors (p = 0.261). Based on histopathological results, 66.67 % of giant ovarian tumors were malignant, 26.98 % were benign, and 6.35 % were borderline. Among the malignant tumors, the epithelial type accounted for 69 % of cases. Most giant ovarian tumors originated in the left adnexa (68.25 %). There was no significant difference in patient age (p = 0.511), tumor size (p = 0.168), malignancy (p = 0.303), and histopathological type (p = 0.232) regardless of adnexal side. CA125 levels did not differ significantly between malignant and benign giant ovarian tumors (p = 0.604). There was no correlation between malignant ovarian tumor size and CA125 levels, while there was a significant difference between CA125 levels and the adnexal side (p = 0.010). ConclusionsMost giant ovarian tumors were malignant, diagnosed at an early stage, and predominantly epithelial type. CA125 levels did not correlate with the size of malignant ovarian tumors. Most giant ovarian tumors originate in the left adnexa.

Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials.

CT041 is a chimeric antigen receptor (CAR)-modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC). These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity. The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients. In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.

Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Extremely high levels of CA199 antigen in borderline mucinous ovarian cystadenoma.

SynopsisA case report on a patient with a mucinous borderline ovarian cystadenoma with extremely elevated CA199 levels.

Clinical profiling of patients admitted with acute heart failure: a comprehensive survival analysis.

In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival analysis. A retrospective study was conducted on patients consecutively admitted for HF from 2018 to 2023. Patients who died during admission were excluded (final number 1,668). Four clinical types of HF were defined: low cardiac output (n:83), pulmonary congestion (n:1,044), mixed congestion (n:353), and systemic congestion (n:188). The low output group showed a higher prevalence of reduced left ventricular ejection fraction (93%) and increased biventricular diameters (p < 0.01). The systemic congestion group exhibited a greater presence of tricuspid regurgitation with dilatation and right ventricular dysfunction (p:0.0001), worse renal function, and higher uric acid and CA125 levels (p:0.0001). Diuretics were more commonly used in the mixed and, especially, systemic congestion groups (p:0.0001). The probability of overall survival at 5 years was 49%, with higher survival in pulmonary congestion and lower in systemic congestion (p:0.002). Differences were also found in survival at 1 month and 1 year (p:0.0001). Mortality in acute HF is high. Four phenotypic profiles of decompensation differ clinically, with distinct characteristics and varying prognosis in the short, medium, and long term.

Predictive value of preoperative CT enhancement rate and CT perfusion parameters in colorectal cancer

BackgroundAngiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers.MethodsThis retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers.ResultsCER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 − 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05).ConclusionsSome single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.

TSR2 overexpression inhibits proliferation and invasion of gastric cancer cells by downregulating the PI3K/AKT signaling pathway

To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism. We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2. In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown, the changes in cell proliferation, invasion, and migration were assessed with CCK-8 and Transwell assays, and the expressions of p-PI3K and p-AKT were detected using Western blotting. TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (P < 0.05). A low TSR2 expression, CEA≥5 μg/L, CA19-9≥37 kU/L, T3-T4 stages, and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery (P < 0.05), and a high TSR2 expression was associated with a higher 5-year survival rate of the patients (P < 0.001). Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway. MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation, migration, and invasion capacities (P < 0.05), while TSR2 knockdown produced the opposite effects (P < 0.05). Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT, and TSR2 knockdown caused the opposite changes in MGC-803 cells (P < 0.05). TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients' prognosis, and its overexpression inhibits gastric cancer cell proliferation, invasion, and migration possibly by downregulating the PI3K/AKT pathway.

High expression of ATP5A1 in gastric carcinoma is correlated with a poor prognosis and enhanced glucose metabolism in tumor cells

To analyze the expression level of ATP5A1 in gastric carcinoma and its influence on the prognosis of the patients and glucose metabolism in the tumor cells. We retrospectively analyzed the data of 115 patients undergoing radical resection of gastric carcinoma in our hospital from February, 2013 to November, 2016. ATP5A1 expression in the surgical specimens were detected using immunohistochemistry, and the long-term prognosis of the patients with high (n=58) and low ATP5A1 expression (n=57) were analyzed. In gastric carcinoma MGC803 cells, the effects of lentivirus-mediated ATP5A1 knockdown or overexpression on glucose metabolism were investigated. We also observed the growth and glucose metabolism of xenografts derived from MGC803 cells with ATP5A1 knockdown or overexpression in nude mice. ATP5A1 was significantly overexpressed in gastric carcinoma tissues in close correlation with blood CEA and CA19-9 levels, pathological grade, T stage and N stage (P < 0.05). ATP5A1 overexpression was an independent risk factor for a significantly lowered 5-year survival rate of patients with gastric carcinoma (P < 0.05). ROC curve analysis demonstrated the predictive value of high ATP5A1 expression for the patients'prognosis (P < 0.001). In MGC803 cells, ATP5A1 overexpression significantly upregulated cellular glucose uptake and lactate production and increased the protein levels of HK2, PFK1, and LDHA (P < 0.05), while ATP5A1 knockdown produced the opposite changes (P < 0.05). In the tumor-bearing mice, overexpression of ATP5A1 increased glucose metabolism of the tumor cells and promoted tumor growth (P < 0.05). Overexpression of ATP5A1 promoted the expressions of p-JNK and p-JUN in MGC803 cells (P < 0.05), and the JNK inhibitor SP600125 significantly inhibited the enhancement of cellular glucose metabolism induced by ATP5A1 overexpression (P < 0.05). High ATP5A1 expression in gastric cancer is associated a poor long-term prognosis of the patients, and its effect is mediated at least partly by promoting glucose metabolism of the cells through the JNK/JUN pathway.

The Value of Clinical Characteristics and Hematological Parameters for Prognostic Assessment of Pancreatic Cancer Patients Undergoing Radical Resection

To explore the relationship between baseline clinical characteristics and hematological parameters of patients undergoing radical resection for pancreatic ductal adenocarcinoma (PDAC) and their prognosis, and to provide references for stratifying the patients' clinical risks. We retrospectively collected clinical data from 445 patients who underwent radical surgical treatment for PDAC at West China Hospital, Sichuan University between January 2010 and February 2019. Then, we conducted retrospective clinical analysis with the collected data. Data on patients' basic clinical characteristics, routine blood test results, and tumor indicators were collected to explore their effects on the postoperative overall survival (OS) of PDAC patients. Cox proportional hazards regression was used to identify factors affecting OS. Statistical analysis was performed using the SPSS 23.0 software package. The postoperative median overall survival (mOS) was 17.0 months (95% CI: 15.0-19.0). The 1, 2, 3, 4, and 5-year survival rates of the patients included in the study were 60.6%, 33.4%, 19.1%, 12.7%, and 9.6%, respectively. The multivariate Cox proportional hazards model analysis demonstrated that a number of factors independently affect postoperative survival in PDAC patients. These factors include tumor location (hazards ratio [HR]=1.574, 95% CI: 1.233-2.011), degree of tumor cell differentiation (HR=0.687, 95% CI: 0.542-0.870), presence of neural invasion (HR=0.686, 95% CI: 0.538-0.876), TNM staging (HR=1.572, 95% CI: 1.252-1.974), postoperative adjuvant therapy (HR=1.799, 95% CI: 1.390-2.328), preoperative drinking history (HR=0.744, 95% CI: 0.588-0.943), and high serum CA199 levels prior to the surgery (HR=0.742, 95% CI: 0.563-0.977). In PDAC patients, having tumors located in the head of the pancreas, moderate and high degrees of differentiated, being free from local neurovascular invasion, being in TNM stage Ⅰ, undergoing postoperative adjuvant therapy, no history of alcohol consumption prior to the surgery, and preoperative serum CA199 being less than or equal to 37 U/mL are significantly associated with a better prognosis.

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.

Diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging parameters and serum tumor markers in rectal carcinoma prognosis.

Rectal carcinoma (RC), one of the most common malignancies globally, presents an increasing incidence and mortality year by year, especially among young people, which seriously affects the prognosis and quality of life of patients. At present, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC. However, the accuracy of these evaluation modalities still needs further research. This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC. To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers (TMs) in assessing pathological processes and prognosis of RC patients. A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022. Patients were categorized into stages T1, T2, T3, and T4, depending on their T stage and differentiation degree. In addition, they were assigned to low (L group) and moderate-high differentiation (M + H group) groups based on their differentiation degree. The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared. In addition, the value of DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) in assessing the differentiation and T staging of RC patients was discussed. Furthermore, the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed. Ktrans, Ve, CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M + H Group, respectively (P < 0.05). The areas under the curve (AUCs) of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages, respectively, and 0.672 and 0.725 in diagnosing moderate-high and low differentiation, respectively. The AUC of DCE-MRI parameters (Ktrans + Ve) in the diagnosis of high and low stages was 0.742, and the AUC in diagnosing moderate-high and low differentiation was 0.769. The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages, respectively, and 0.834 and 0.796 in diagnosing moderate-high and low differentiation, respectively. Then, we combined DCE-MRI (Ktrans + Ve) parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation. According to the Delong test, the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree (P < 0.001). The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice. Moreover, the combined evaluation of the above indices has a better effect and more obvious clinical value, providing important guiding importance for clinical condition judgment and treatment selection.