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Background: Purpose of this study was to analyze whether preoperative maximum standardized uptake value (SUVmax) and carbohydrate antigen 19-9 (CA19-9) levels might provide prognostic information in Chinese patients with pancreatic duct adenocarcinoma (PDAC) after pancreaticoduodenectomy (PD).Methods: Standard PD was performed on 109 patients with PDAC by the same operative team, and all patients received preoperative positron emission tomography/computed tomography examination and blood test.Results: Patients had a mean age of 59 ± 9.35 years. Females accounted for 38.5%. Mean levels of SUVmax, carcino-embryonic antigen (CEA) and CA19-9 were 5.70 ± 2.76, 3.95 ± 4.16ng/mL and 321.62 ± 780.71kU/L. In univariate Logistic regression analysis, preoperative SUVmax, CEA and CA19-9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to AJCC stages. Multivariate Logistic regression analysis showed that preoperative SUVmax and CA19-9 levels (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with AJCC stages. Mean overall survival (OS) was 21 ± 14.50 months. In univariate Cox regression analysis, age, SUVmax, CEA and CA19-9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly related to OS. Multivariate Cox regression analysis showed that age, SUVmax and CA19-9 levels before operation (p < 0.05 for all) rather than other preoperative variables (p > 0.05 for all) were significantly associated with OS.Conclusions: This study demonstrated that preoperative SUVmax and CA19-9 levels independently predicted pathological stages and OS of patients with PDAC after PD. These preoperative variables might have significant prognostic implication in patients with PDAC after PD. Patients with abnormal SUVmax and CA19-9 levels should be paid special attention to in operative strategy and perioperative management. [ABSTRACT FROM AUTHOR]

Background: We developed a prognostic model to evaluate the overall survival (OS) and progression-free survival (PFS) of patients with unresectable hepatocellular carcinoma (u-HCC) treated with Hepatic arterial infusion chemotherapy of infusion oxaliplatin, fluorouracil and leucovorin (FOLFOX-HAIC). Methods: This model was based on a retrospective study of u-HCC patients treated with the FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 23–46 h, once every 3–4 weeks). We divided the patients into a training cohort and a validation cohort, used LASSO regression construct prognostic models, predict patient’s OS and PFS based on nomograms of models. Patients were divided into high-risk, medium-risk, and low-risk groups according to their respective model risk scores. Kaplan-Meier survival analysis was used to assess the survival time between the three patient cohorts. Results: A total of 333 patients were enrolled in the study and divided into a training cohort and a verification cohort at a ratio of 7:3 (233 in the training cohort and 100 in the validation cohort). The prognostic model we established contained nine prognostic variables. The results of concordance index (C-index) of the OS and PFS prognostic model was 0.75 and 0.71, respectively, higher than that of the TNM staging (0.57 and 0.55, p < 0.001), time-dependent ROC (td-ROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) also showed that the model was better than the TNM staging for u-HCC predicting OS and PFS. Subsequently, the model was used to develop a nomogram to predict the individualized prognosis of patients with u-HCC treated with the FOLFOX-HAIC, with a higher net benefit than the TMN staging. According to the risk score, patients were divided into a low-risk group (risk score ≤ 0.458), the medium-risk group (risk score: 0.458–0.799) and the high-risk group (risk score > 0.799). There were significant differences in the OS and PFS between the three groups. Conclusions: The model developed by our team enables risk stratification and personalized prognosis assessment for u-HCC patients undergoing FOLFOX-HAIC treatment, exhibiting superior predictive accuracy and discriminative capability compared to TNM staging. [ABSTRACT FROM AUTHOR]

Objective: This investigation attempted to examine the effectiveness of CT-derived peritumoral and intratumoral radiomics in forecasting microsatellite instability (MSI) status preoperatively among gastric cancer (GC) patients. Methods: A retrospective analysis was performed on GC patients from February 2019 to December 2023 across three healthcare institutions. 364 patients (including 41 microsatellite instability-high (MSI-H) and 323 microsatellite instability-low/stable (MSI-L/S)) were stratified into a training set (n = 202), an internal validation set (n = 84), and an external validation set (n = 78). Radiomics features were obtained from both the intratumoral region (IR) and the intratumoral plus 3-mm peritumoral region (IPR) on preoperative contrast-enhanced CT images. After standardizing and reducing the dimensionality of these features, six radiomic models were constructed utilizing three machine learning techniques: Support Vector Machine (SVM), Linear Support Vector Classification (LinearSVC), and Logistic Regression (LR). The optimal model was determined by evaluating the Receiver Operating Characteristic (ROC) curve's Area Under the Curve (AUC), and the radiomics score (Radscore) was computed. A clinical model was developed using clinical characteristics and CT semantic features, with the Radscore integrated to create a combined model. Used ROC curves, calibration plots, and Decision Curve Analysis (DCA) to assess the performance of radiomics, clinical, and combined models. Results: The LinearSVC model using the IPR achieved the highest AUC of 0.802 in the external validation set. The combined model yielded superior AUCs in internal and external validation sets (0.891 and 0.856) in comparison to clinical model [(0.724, P = 0.193) and (0.655, P = 0.072)] and radiomics model [(0.826, P = 0.160) and (0.802, P = 0.068)]. Furthermore, results from calibration and DCA underscored the model's suitability and clinical relevance. Conclusion: The combined model, which integrates IPR radiomics with clinical characteristics, accurately predicts MSI status and supports the development of personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: To construct a CT-based radiomics nomogram, enabling the estimation of overall survival (OS) in small cell lung cancer (SCLC) patients and facilitating the identification of prophylactic cranial irradiation (PCI) beneficiaries through risk stratification using the radiomics score (RS). Methods: A retrospective recruitment of 375 patients with pathologically confirmed SCLC was conducted across three medical centers, followed by their division into different cohorts. To generate the RS, a series of analyses were performed, including Pearson correlation analysis, univariate Cox analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Subsequently, patients were stratified into either the low RS or high RS group, determined by identifying the optimal RS cutoff value. Subsequently, a radiomics nomogram was constructed using the RS, followed by assessments of its discrimination, calibration, clinical utility and reclassification. Moreover, we evaluated the potential benefits of PCI following stratification by RS. Results: For the internal and external validation cohorts, the radiomics nomogram (concordance index [C-index]: 0.770, 0.763) outperformed clinical nomogram (C-index: 0.625, 0.570) in predicting OS. Besides, patients with high RS had survival benefit from PCI in both the limited and extensive stage (hazard ratio [HR]: 0.304, 95% confidence interval [CI]: 0.087–1.065, P = 0.003; HR: 0.481, 95% CI: 0.270–0.860, P = 0.019, respectively), while no significant association were observed in patients with low RS. Conclusion: A radiomics nomogram based on CT shows potential in predicting OS for individuals with SCLC. The RS could assist in tailoring treatment plans to identify patients likely to benefit from PCI. [ABSTRACT FROM AUTHOR]

Purpose: Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. Patients and methods: Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. Results: Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. Conclusions: Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA. [ABSTRACT FROM AUTHOR]

Background: The primary aim of this study was to evaluate the safety of a novel dendritic cell (DC) vaccine pulsed with survivin and MUC1, silenced with suppressor of cytokine signaling 1 (SOCS1), and immune stimulated with flagellin for patients with stage I to IIIA non-small cell lung cancer (NSCLC) in a phase I open-label, uncontrolled, and dose-escalation trial. Moreover, we evaluate the potential efficacy of this modified DC vaccine as secondary aim.Methods: The patients were treated with the vaccine at 1 × 106, 1 × 107and the maximum dose 8 × 107 at day 7, 14, and 21 after characterization of the vaccine phenotype by flow cytometry. The safety of the vaccine was assessed by adverse events, and the efficacy by the levels of several specific tumor markers and the patient quality of life.Results: The vaccine was well tolerated without dose-limiting toxicity even at higher doses. The most common adverse event reported was just grade 1 flu-like symptoms without unanticipated or serious adverse event. A significant decrease in CD3 + CD4 + CD25 + Foxp3+ T regulatory (Treg) cell number and increase in TNF-α and IL-6 were observed in two patients. Two patients showed 15% and 64% decrease in carcino-embryonic antigen and CYFRA21, respectively. The vaccination with the maximum dose significantly improved the patients'quality of life when administered at the highest dose. More importantly, in the long-term follow-up until February 17, 2017, 1 patient had no recurrence, 1 patients had a progressive disease (PD), and 1 patient was died in the low dose group. In the middle dose group, all 3 patients had no recurrence. In the high dose group, 1 patient was died, 1 patient had a PD, and the other 7 patients had no recurrence.Conclusions: We provide preliminary data on the safety and efficacy profile of a novel vaccine against non-small cell lung cancer, which was reasonably well tolerated, induced modest antitumor activity without dose-limiting toxicity, and improved patients' quality of life. Further more, the vaccine maybe a very efficacious treatment for patients with resected NSCLC to prevent recurrence. Our findings on the safety and efficacy of the vaccine in this phase I trial warrant future phase II/III clinical trial. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is the third most commonly diagnosed malignancy and the fourth leading cause of cancer-related death globally. It is the second most common cancer among both males and females in Malaysia. The economic burden of colorectal cancer is likely to increase over time owing to its current trend and aging population. Cancer survival analysis is an essential indicator for early detection and improvement in cancer treatment. However, there was a scarcity of studies concerning survival of colorectal cancer patients as well as its predictors. Therefore, we aimed to determine the 1-, 3- and 5-year survival rates, compare survival rates among ethnic groups and determine the predictors of survival among colorectal cancer patients.Methods: This was an ambidirectional cohort study conducted at the University Malaya Medical Centre (UMMC) in Kuala Lumpur, Malaysia. All Malaysian citizens or permanent residents with histologically confirmed diagnosis of colorectal cancer seen at UMMC from 1 January 2001 to 31 December 2010 were included in the study. Demographic and clinical characteristics were extracted from the medical records. Patients were followed-up until death or censored at the end of the study (31st December 2010). Censored patients' vital status (whether alive or dead) were cross checked with the National Registration Department. Survival analyses at 1-, 3- and 5-year intervals were performed using the Kaplan-Meier method. Log-rank test was used to compare the survival rates, while Cox proportional hazard regression analysis was carried out to determine the predictors of 5-year colorectal cancer survival.Results: Among 1212 patients, the median survival for colorectal, colon and rectal cancers were 42.0, 42.0 and 41.0 months respectively; while the 1-, 3-, and 5-year relative survival rates ranged from 73.8 to 76.0%, 52.1 to 53.7% and 40.4 to 45.4% respectively. The Chinese patients had the lowest 5-year survival compared to Malay and Indian patients. Based on the 814 patients with data on their Duke's staging, independent predictors of poor colorectal cancer (5-year) survival were male sex (Hazard Ratio [HR]: 1.41; 95% CI: 1.12, 1.76), Chinese ethnicity (HR: 1.41; 95% CI: 1.07,1.85), elevated (≥ 5.1 ng/ml) pre-operative carcino-embryonic antigen (CEA) level (HR: 2.13; 95% CI: 1.60, 2.83), Duke's stage C (HR: 1.68; 95% CI: 1.28, 2.21), Duke's stage D (HR: 4.61; 95% CI: 3.39, 6.28) and emergency surgery (HR: 1.52; 95% CI: 1.07, 2.15).Conclusions: The survival rates of colorectal cancer among our patients were comparable with those of some Asian countries but lower than those found in more developed countries. Males and patients from the Chinese ethnic group had lower survival rates compared to their counterparts. More advanced staging and late presentation were important predictors of colorectal cancer survival. Health education programs targeting high risk groups and emphasizing the importance of screening and early diagnosis, as well as the recognition of symptoms and risk factors should be implemented. A nationwide colorectal cancer screening program should be designed and implemented to increase early detection and improve survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory factors play an important role in the onset and progression of colorectal cancer (CRC). This study aimed to develop and validate a novel scoring system that utilizes specific inflammatory factor indicators to predict intestinal obstruction in CRC patients. Methods: This study conducted a retrospective analysis of 1,470 CRC patients who underwent surgical resection between January 2013 and July 2018. These patients were randomly allocated to the training group (n = 1060) and the validation group (n = 410). Univariate and multivariate logistic regression analyses were performed to identify independent predictive factors for intestinal obstruction. The CRC peculiar inflammation score (CPIS), comprising lymphocyte-to-monocyte ratio (LMR), prognostic nutrition index (PNI), and alanine transaminase-to-lymphocyte ratio index (ALRI) scores, was significantly associated with the occurrence of intestinal obstruction. A nomogram combining CPIS with other clinical features was developed to predict this occurrence. Model accuracy was assessed by determining the area under the receiver operating characteristic (ROC) curve (AUC). Results: The CPIS generated by multi-factor logistic regression was as follows: − 1.576 × LMR − 0.067 × PNI + 0.018 × ALRI. Using CPIS cutoff values of 50% (− 7.188) and 85% (− 6.144), three predictive groups were established. Patients with a high CPIS had a significantly higher risk of intestinal obstruction than those with a low CPIS (odds ratio [OR]: 10.0, confidence interval [CI]: 5.85–17.08, P < 0.001). The predictive nomogram demonstrated good calibration and discrimination abilities. The AUC of the ROC curve for the obstruction nomogram was 0.813 (95% CI: 0.777–0.850) in the training set and 0.806 (95% CI: 0.752–0.860) in the validation set. The calibration curve exhibited neither bias nor high credibility. Decision curve analysis indicated the utility of this predictive model. Conclusion: CRC-associated intestinal obstruction is closely linked to inflammatory markers in patients. CPIS is a CRC-specific inflammatory predictive score based on a combination of inflammatory-related indicators. A high CPIS serves as a strong indicator of intestinal obstruction. Its integration with other clinical factors and preoperative inflammatory-specific indicators significantly enhances the diagnosis and treatment of CRC patients with intestinal obstruction. [ABSTRACT FROM AUTHOR]

Background: At present, conventional endoscopy and chromoendoscopy using indigo carmine (IC) is a very useful method to determine the demarcation line (DL) of early gastric cancer lesions, but it is not suitable for all lesions. Aims: This study aimed to determine the applicable conditions for IC chromoendoscopy. Methods: We retrospectively evaluated 187 lesions in 181 patients who had an endoscopic diagnosis of EGC and were treated with endoscopic submucosal dissection (ESD). According to the existence of the DL between the lesion mucosa and normal mucosa with IC chromoendoscopy, the lesions were divided into two groups: clear group and unclear group. Clinicopathological characteristics were evaluated in each group. From January 2022 to March 2023, the postoperative pathological sections of 19 lesions (81 slices) in the clear group and 19 lesions (80 slices) in unclear group were scanned with high definition, and the crypt structure between the two groups was evaluated. Results: There was no significant difference in clinical factors between the clear group and unclear group. There were significant differences in crypt area, crypt length, and crypt opening diameter between the two groups. In the clear group, there were significant differences in crypt area, crypt length, and crypt opening diameter between the normal area and cancer area, but there was no significant difference in the unclear group. Conclusions: The margins of lesions with fused or absent crypt structures, a small crypt area, a short crypt length, and a short crypt opening diameter can be easily determined with IC chromoendoscopy. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the correlation between spleen density and the prognostic outcomes of patients who underwent curative resection for colorectal cancer (CRC). Methods: The clinical data of patients who were diagnosed with CRC and underwent radical resection were retrospectively analyzed. Spleen density was determined using computed tomography. Analysis of spleen density in relation to overall survival (OS) and disease-free survival (DFS) utilizing the Kaplan–Meier method. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors, and a nomogram was constructed to predict OS and DFS. Moreover, internally validated using a bootstrap resamplling method. Results: Two hundred twelve patients were included, of whom 23 (10.85%) were defined as having a diffuse reduction of spleen density (DROSD) based on diagnostic cutoff values (spleen density≦37.00HU). Kaplan–Meier analysis indicated that patients with DROSD had worse OS and DFS than those non-DROSD (P < 0.05). Multivariate Cox regression analysis revealed that DROSD, carbohydrate antigen 199 (CA199) > 37 U/mL, tumor node metastasis (TNM) stage III-IV, laparoscopy-assisted operation and American Society of Anesthesiology (ASA) score were independent risk factors for 3-year DFS. DROSD, CA199 > 37 U/mL, TNM stage III-IV, hypoalbuminemia, laparoscopy-assisted operation and ASA score were chosen as predictors of for 3-year OS. Nomograms showed satisfactory accuracy in predicting OS and DFS using calibration curves, decision curve analysis and bootstrap resamplling method. Conclusion: Patients with DROSD who underwent curative resection have worse 3-year DFS and OS. The nomogram demonstrated good performance, particularly in predicting 3-year DFS with a net clinical benefit superior to well-established risk calculator. [ABSTRACT FROM AUTHOR]

Background: There is an insufficient number of reliable prognostic and response predictive biomarkers in colorectal cancer (CRC) management. In a previous study, we found that high tumour tissue expression of tumourassociated trypsin inhibitor (TATI) correlated with liver metastasis and an impaired prognosis in CRC. The aim of this study was to investigate the prognostic validity of serum TATI (s-TATI) in CRC. We further assessed the prognostic value of carcino-embryonic antigen in serum (s-CEA) and the interrelationship between s-TATI and TATI in tissue (t-TATI). Methods: Using an immunofluorometric assay, s-TATI levels were analysed in 334 preoperatively collected serum samples from patients with CRC. Spearman's Rho and Chi-square test were used for analysis of correlations between s-TATI and clinicopathological parameters, s-CEA and t-TATI. Kaplan-Meier analysis and Cox uni- and multivariate regression analysis were used to estimate disease free survival (DFS) and overall survival (OS) according to quartiles of s-TATI and cut-offs derived from ROC-analysis of s-TATI and s-CEA. Results: Increased levels of s-TATI were associated with a reduced DFS (HR = 2.00; 95% CI 1.40-2.84, P < 0.001) and OS (HR = 2.40; 95% CI 1.74-3.33, P < 0.001). (HR = 2.89; 95% CI 1.96-4.25). This association remained significant in multivariate analysis. The association for OS remained significant in multivariate analysis (HR = 1.51; 95% CI 1.03- 2.22, P = 0.034 for DFS and HR = 1.78; 95% CI 1.25-2.53, P = 0.001 for OS). There was no significant association between s-TATI and t-TATI. The prognostic value of s-CEA was also evident, but somewhat weaker than for s-TATI. Conclusions: High preoperative s-TATI levels predict a poor prognosis in patients with CRC, and the prognostic value is independent of established prognostic parameters and t-TATI expression. These data suggest that s-TATI might be a useful marker for prognostic stratification in CRC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is among the most frequently diagnosed cancers. Approximately 20–30% of stage I-III CRC patients develop a recurrent tumour or metastases after curative surgical resection. Post-operative follow-up is indicated for the first five years after curative surgical resection. As intensified follow-up after curative surgical resection has shown no effect on survival, patient organisations and policy makers have advocated for a more patient-centred approach to follow-up. The objective of this study is to successfully implement patient-led, home-based follow-up (PHFU) in six hospitals in The Netherlands, with as ultimate aim to come to a recommendation for a patient-centred follow-up schedule for stage I-III CRC patients treated with surgical resection with curative intent. Methods: This study is designed as a stepped-wedge cluster-randomised trial (SW-CRT) in six participating centres. During the trial, three centres will implement PHFU after six months; the other three centres will implement PHFU after 12 months of inclusion in the control group. Eligible patients are those with pT2-4N0M0 or pT1-4N1-2M0 CRC, who are 18 years or older and have been free of disease for 12 months after curative surgical resection. The studied intervention is PHFU, starting 12 months after curative resection. The in-hospital, standard-of-care follow-up currently implemented in the participating centres functions as the comparator. The proportion of patients who had contact with the hospital regarding CRC follow-up between 12–24 months after curative surgical resection is the primary endpoint of this study. Quality of life, fear of cancer recurrence, patient satisfaction, cost-effectiveness and survival are the secondary endpoints. Discussion: The results of this study will provide evidence on whether nationwide implementation of PHFU for CRC in The Netherlands will be successful in reducing contact between patient and health care provider. Comparison of PROMs between in-hospital follow-up and PHFU will be provided. Moreover, the cost-effectiveness of PHFU will be assessed. Trial registration: Dutch Trail Register (NTR): NL9266 (Registered on January 1st, 2021). [ABSTRACT FROM AUTHOR]

Background: Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC.Methods: Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence.Results: The median value of Ca19-9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8).Conclusions: Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence. [ABSTRACT FROM AUTHOR]

Background: Breast cancer has become the most common malignant tumour worldwide. Distant metastasis is one of the leading causes of breast cancer-related death. To verify the performance of clinicomics-guided distant metastasis risk prediction for breast cancer via artificial intelligence and to investigate the accuracy of the created prediction models for metachronous distant metastasis, bone metastasis and visceral metastasis. Methods: We retrospectively enrolled 6703 breast cancer patients from 2011 to 2016 in our hospital. The figures of magnetic resonance imaging scanning and ultrasound were collected, and the figures features of distant metastasis in breast cancer were detected. Clinicomics-guided nomogram was proven to be with significant better ability on distant metastasis prediction than the nomogram constructed by only clinical or radiographic data. Results: Three clinicomics-guided prediction nomograms on distant metastasis, bone metastasis and visceral metastasis were created and validated. These models can potentially guide metachronous distant metastasis screening and lead to the implementation of individualized prophylactic therapy for breast cancer patients. Conclusion: Our study is the first study to make cliniomics a reality. Such cliniomics strategy possesses the development potential in artificial intelligence medicine. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the diagnostic value of serum oligosaccharide chain (G-test), alpha-fetoprotein (AFP) and aspartic aminotransferase to alanine aminotransferase ratios (AAR), both alone and in combination, for predicting hepatocellular carcinoma (HCC) onset.Methods: Between Januarys 2020-2022, 152 subjects admitted to the First Affiliated Hospital of Nanchang University was enrolled in this study, of which 77 had HCC, 18 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 20 were healthy. Data for patient characteristics were collected, and differences between groups were analyzed by either Mann-Whitney U or χ2 tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of AFP, G-test, and AAR for HCC.Results: G-test, AFP, and AAR were all found to have close correlations with HCC among the different patient groups, with G-test being the most predictive for HCC among healthy and CL patients, as represented by respective areas under the curve (AUC) of 0.953 and 0.792 (P < 0.001). By contrast, AAR had the greatest diagnostic ability for HCC among CH patients (AUC = 0.850; P < 0.001). However, the combination of all 3 biomarkers obtained the most optimal results for predicting HCC onset, in terms of predictive capability for all 3 non-HCC patient groups, yielding AUCs of 0.958, 0.898, and 0.808 (P < 0.001) for, respectively, healthy, CH, and LC patients. Additionally, AFP had higher specificity, but lower sensitivity, with increased threshold values, as the recommended threshold of AFP ≥ 400 ng/mL yielded a missed diagnosis rate of 72.7%. For AFP-negative HCC (AFP-NHCC) patients, G-test alone had the greatest diagnostic capability (AUC = 0.855; P < 0.001), sensitivity (83.8%), and specificity (87.5%).Conclusion: G-test has the greatest diagnostic capability for HCC and AFP-NHCC, with high sensitivity and specificity, among healthy and LC patients. However, AAR had the highest diagnostic capability and sensitivity for HCC in CH. Overall, though, the combination of G-test, AFP and AAR provided the most optimal outcomes for predicting HCC onset, no matter the patient pre-conditions. [ABSTRACT FROM AUTHOR]

Background: Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated.Methods: In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells.Results: The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis.Conclusions: In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis. [ABSTRACT FROM AUTHOR]

Background: For colorectal cancer, preoperative (neoadjuvant) chemotherapy is more effective than postoperative chemotherapy because it not only eradicates micrometastases more effectively but also reduces the risk of incomplete intraoperative resection and tumor cell shedding. For the treatment of acute left-sided malignant colorectal obstruction, colorectal stents as well as stoma are being used to relieve the obstructive colorectal cancer, and as a bridge to surgery, allowing easy mobilization and resection of the colon. Neoadjuvant chemotherapy combined with self-expandable metal stents (SEMS) or neoadjuvant chemotherapy combined with decompressing stoma (DS) can be used as a bridge to elective surgery (BTS) as an alternative to emergency surgery in patients with acute left-sided malignant colorectal obstruction, but its benefit is uncertain. The purpose of this study was to evaluate the safety and feasibility of neoadjuvant chemotherapy as a bridge to surgery in the treatment of acute left-sided malignant colorectal obstruction.Methods: Data from patients who were admitted with acute left-sided malignant colorectal obstruction between January 2012 and December 2020 were retrospectively reviewed, and patients with gastrointestinal perforation or peritonitis were excluded. We performed one-to-two propensity score matching to compare the stoma requirement, postoperative complications, and other short-term oncological outcomes between the neoadjuvant chemotherapy group and surgery group.Results: There were no differences in intraoperative blood loss, operative time, one-year postoperative mortality, and postoperative tumor markers between the two groups. The 1-year recurrence-free survival (RFS) rates of neoadjuvant chemotherapy group and surgery group were 96.8 and 91.3% (p = 0.562). The neoadjuvant chemotherapy group was able to reduce stoma rate 1 year after surgery (p = 0.047). Besides, the neoadjuvant group significantly reduced postoperative bowel function time (p < 0.001), postoperative hospital stay (p < 0.001), total hospital stay (p = 0.002), postoperative complications (p = 0.017), reduction in need to stay in the intensive care unit (ICU) (p = 0.042).Conclusions: Neoadjuvant chemotherapy as a bridge to elective surgery in patients with acute left-sided malignant colorectal obstruction is safe and has many advantages. Prospective multicenter studies with large samples are needed to further evaluate the feasibility of neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19–9 (CA19–9) and carcinoma embryonic antigen (CEA) in patients with GBC. Methods Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19–9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence. Results The median value of Ca19–9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8). Conclusions Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19–9 was better than CEA in prediction of tumor burden and in predicting recurrence.

Background: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers.Methods: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci.Results: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037.Conclusion: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China. [ABSTRACT FROM AUTHOR]

Background: The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC.Methods: Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated.Results: High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort.Conclusion: ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq. [ABSTRACT FROM AUTHOR]

Background: Microparticles (MPs) are extracellular vesicles that are associated with cancer development and progression. Advanced non-small cell lung cancer (NSCLC) still shows disease progression after multiple lines of treatment. Therefore, the objective of this study was to explore the correlation between circulating MPs and disease progression in advanced NSCLC, and to find a new method for concise and rapid determination of disease progression.Methods: Patients with advanced NSCLC admitted to hospital between October 2019 and October 2020 were included and divided into objective remission (OR) and progressive disease (PD) groups. The morphology of MPs was observed using transmission electron microscopy. The circulating total MPs, neutrophil MPs (NMPs), and platelet MPs (PMPs) before and after treatment were detected by flow cytometry, and a predictive model for disease progression in advanced NSCLC was developed.Results: Eighty-six patients were included; 60 in the OR group and 26 in the PD group. There was no significant difference in total MPs, NMPs, or PMPs at baseline between the two groups. After treatment, total MPs, NMPs, and PMPs were significantly higher in the PD than those in the OR group. Multivariate regression analysis showed that post-treatment NMPs≥160 events/μL(OR,3.748;95%CI,1.147-12.253,p = 0.029), PMPs≥80 events/μL(OR,10.968;95%CI,2.973-40.462,p < 0.0001) and neutrophil/lymphocyte ratio (NLR) ≥3.3 (OR,4.929;95%CI,1.483-16.375,p = 0.009) were independently associated with progression of advanced NSCLC. Post-treatment NMPs and PMPs combined with NLR were used to build a predictive model for progression of advanced NSCLC. The area under the curve was 0.825 (95%CI,0.715-0.934, p < 0.0001), optimal cut-off value was 16, sensitivity was 80.8%, and specificity was 88.3%.Conclusion: NMPs and PMPs are associated with progression of advanced NSCLC. The predictive model for progression of advanced NSCLC, established combining NMPs, PMPs, and NLR, can screen out 80.8% of patients with PD. This is helpful for real-time accurate, concise and rapid assessment of disease progression and timely adjustment of drug therapy.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020223 . Registered 20 December 2018, http://www.chictr.org.cn/index.aspx . [ABSTRACT FROM AUTHOR]

Background: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.Methods: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.Results: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported.Conclusion: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.Trial Registration: PROSPERO registration number: CRD42019125245 . [ABSTRACT FROM AUTHOR]

Background: The clinical staging systems for adenocarcinoma of the esophagogastric junction (AEG) are controversial. We aimed to propose a prognostic nomogram based on real-world data for predicting survival of Siewert type II/III AEG patients after surgery.Methods: A total of 396 patients with Siewert type II/III AEG diagnosed and treated at the Center for Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, from June 2009 to June 2017 were enrolled. The original data of 29 variables were exported from the electronic medical records system. The nomogram was established based on multivariate Cox regression coefficients, and its performance was measured using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curve analysis and calibration curve.Results: A nomogram was constructed based on nine variables. The C-index for overall survival (OS) prediction was 0.76 (95% CI, 0.72 to 0.80) in the training cohort, in the validation-1 cohort was 0.79 (95% CI, 0.72 to 0.86), and 0.73 (95% CI, 0.67 to 0.80) in the validation-2 cohort. Time-dependent ROC curves and calibration curves in all three cohorts showed good prognostic predictive accuracy. We further proved the superiority of the nomogram in predictive accuracy for OS to pathological TNM (pTNM) staging system and other independent prognostic factors. Kaplan-Meier survival curves demonstrated the pTNM stage, grade of differentiation, positive lymph node, log odds of positive lymph node and organ invasion were prognostic factors with good discriminative ability.Conclusion: The established nomogram demonstrated a more precise prognostic prediction for patients with Siewert type II/III AEG. [ABSTRACT FROM AUTHOR]

Background: Inositol polyphosphate 4-phosphatase type II (INPP4B) is a negative regulator of the PI3K-Akt signalling pathway and plays a contradictory role in different types of cancers. However, the its biological role played by INPP4B in human gallbladder cancer (GBC) has not been elucidated. In this study, we investigated the expression, clinical significance and biological function of INPP4B in GBC patients and cell lines.Methods: The INPP4B protein expression levels in gallbladder cancer tissues and normal gallbladder tissues were detected by immunohistochemistry, and the clinical significance of INPP4B was analysed. Knockdown and overexpression of INPP4B in GBC-SD and SGC-996 cells followed by cell proliferation, clonogenic, apoptosis detection, scratch wound-healing and transwell assays were used to identify INPP4B function in vitro.Results: INPP4B was up-regulated in human GBC tissues compared with normal gallbladder tissues and was related to histopathological differentiation (p = 0.026). Here, we observed that INPP4B was highly expressed in high-moderately differentiated tumours compared with low-undifferentiated tumours (p = 0.022). Additionally, we found that INPP4B expression was not associated with overall survival of GBC patients (p = 0.071) and was not an independent prognostic factor. Furthermore, when we stratified the relationship between INPP4B expression and the prognosis of GBC based on histopathological differentiation, we found that INPP4B played a contradictory role in GBC progression depending on the degree of differentiation. In addition, INPP4B knockdown inhibited the proliferation, colony formation, migration and invasion in GBC cells, while INPP4B overexpression had the opposite effects in vitro, which indicates its role as an oncoprotein.Conclusions: These findings suggested that INPP4B may play a dual role in the prognosis of GBC depending on the degree of differentiation and that INPP4B might act as an oncogene in gallbladder cancer cells. [ABSTRACT FROM AUTHOR]

Background: Although criteria for liver transplantation, such as the Milan criteria and Hangzhou experiences, have become popular, criteria to guide adjuvant therapy for patients with hepatocellular carcinoma after liver transplantation are lacking.Methods: We collected data from all consecutive patients from 2012 to 2019 at three liver transplantation centers in China retrospectively. Univariate and multivariate analyses were used to analyze preoperative parameters, such as demographic and clinical data. Using data obtained in our center, calibration curves and the concordance Harrell's C-indices were used to establish the final model. The validation cohort comprised the patients from the other centers.Results: Data from 233 patients were used to construct the nomogram. The validation cohort comprised 36 patients. Independent predictors of overall survival (OS) were identified as HbeAg positive (P = 0.044), blood-type compatibility unmatched (P = 0.034), liver transplantation criteria (P = 0.003), and high MELD score (P = 0.037). For the validation cohort, to predict OS, the C-index of the nomogram was 0.874. Based on the model, patients could be assigned into low-risk (≥ 50%), intermediate-risk (30-50%), and high-risk (≤ 30%) groups to guide adjuvant therapy after surgery and to facilitate personalized management.Conclusions: The OS in patients with hepatocellular carcinoma after liver transplantation could be accurately predicted using the developed nomogram. [ABSTRACT FROM AUTHOR]

Background: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC.Methods: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort.Results: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively.Conclusions: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background The incidence and survival rates for colorectal cancer in Australia are among the highest in the world. With population growth and ageing there are increasing numbers of colorectal cancer survivors in the community, yet little is known of their ongoing follow up and survivorship care experiences. This study investigated patterns and predictors of follow up and survivorship care received and recommended for adults with colorectal cancer in New South Wales (NSW), Australia. Methods Cross-sectional analysis within the NSW Bowel Cancer Care Survey, a population-based cohort of adults diagnosed with colorectal cancer between April 2012 and May 2013 in NSW. One year after diagnosis, participants completed a study specific questionnaire about their follow up and survivorship care experience and plans. Logistic regression was used to identify independent predictors of guideline-recommended care. Results Of 1007 eligible people, 560 (56%) participated in the NSW Bowel Cancer Care Survey with 483 (86% of study participants, 48% of invited sample) completing the survivorship survey. Among these 483 participants, only 110 (23%, 95% Confidence Interval CI 19–27%) had received a written follow up plan, with this more common among migrants, non-urban dwellers and those with little experience of the health system. Of 379 (78%) people treated with curative intent, most were receiving ongoing colorectal cancer follow up from multiple providers with 28% (23–32%) attending three or more different doctors. However, less than half had received guideline-recommended follow-up colonoscopy (46%, CI 41–51%) or carcino-embryonic antigen assay (35%, CI 30–40%). Socio-economic advantage was associated with receipt of guideline-recommended care. While participants reported high interest in improving general health and lifestyle since their cancer diagnosis, few had received advice about screening for other cancers (24%, CI 19–28%) or assistance with lifestyle modification (30%, CI 26–34%). Less than half (47%, CI 43–52%) had discussed their family’s risk of cancer with a doctor since their diagnosis. Conclusions Survivorship care was highly variable, with evident socioeconomic disparities and missed opportunities for health promotion.

Background: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues. ROR1 was shown to inhibit apoptosis, potentiate EGFR signaling and reported to be overexpressed and associated with poor prognosis in several tumor models. This study aimed to assess the expression of ROR1 in lung adenocarcinoma (AC) patients. Methods: We analyzed ROR1 expression by quantitative real-time PCR (qRT-PCR) in 56 histologically confirmed lung AC, stage I to IV, in addition we evaluated its association with TTF-1 (thyroid transcription factor-1) expression and the main molecular alterations involved in lung cancerogenesis. Results: ROR1 overexpression was observed in 28.6% of the entire cohort, using a cut-off of 1, or in 51.8% of the cases using the median value as threshold. Among patients without any genetic alteration, ROR1 overexpression was observed in 34.8% considering a cut-off of 1 and 52.2% considering the median value. The distribution of ROR1 was homogeneous among the different molecular categories: we found no association of ROR1 expression and the presence of gene mutations/rearrangements or the expression of TTF-1. Conclusions: ROR1 overexpression could constitute a potential therapeutic target because altered in a consistent number of lung AC, especially in cases without druggable genetic alterations. ROR1 expression is independent of classical lung cancer molecular alterations and not correlated, in a Caucasian cohort, to TTF-1 expression. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.Methods: In this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.Results: A total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769-4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545-1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686-6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06).Conclusions: The present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC. [ABSTRACT FROM AUTHOR]

Background: The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined.Methods: Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods.Results: A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99-100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent.Conclusions: Dutch colorectal surgeons' adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC. [ABSTRACT FROM AUTHOR]

Background: Myxofibrosarcoma (MFS) is most often found on the limbs of aged male people, but extremely uncommon in the liver.Case Presentation: A 52-year-old female patient with a liver mass was diagnosed as a primary MFS. It had no obvious abdominal symptoms, and the tumor was resected with an extended margin. Three years after the surgery, the patient was readmitted for peritoneal metastasis and passed away 4 months later. The tumor has a benign presentation, but malignant outcome.Conclusions: Comprehensive radiological inspection, intensive preoperative evaluation, careful design of operating procedures, wide margin resection, consecutive treatment, and strict periodical follow-ups should be taken to ensure a better prognosis of this kind of neoplastic disease. [ABSTRACT FROM AUTHOR]

Background: The incidence and survival rates for colorectal cancer in Australia are among the highest in the world. With population growth and ageing there are increasing numbers of colorectal cancer survivors in the community, yet little is known of their ongoing follow up and survivorship care experiences. This study investigated patterns and predictors of follow up and survivorship care received and recommended for adults with colorectal cancer in New South Wales (NSW), Australia.Methods: Cross-sectional analysis within the NSW Bowel Cancer Care Survey, a population-based cohort of adults diagnosed with colorectal cancer between April 2012 and May 2013 in NSW. One year after diagnosis, participants completed a study specific questionnaire about their follow up and survivorship care experience and plans. Logistic regression was used to identify independent predictors of guideline-recommended care.Results: Of 1007 eligible people, 560 (56%) participated in the NSW Bowel Cancer Care Survey with 483 (86% of study participants, 48% of invited sample) completing the survivorship survey. Among these 483 participants, only 110 (23%, 95% Confidence Interval CI 19-27%) had received a written follow up plan, with this more common among migrants, non-urban dwellers and those with little experience of the health system. Of 379 (78%) people treated with curative intent, most were receiving ongoing colorectal cancer follow up from multiple providers with 28% (23-32%) attending three or more different doctors. However, less than half had received guideline-recommended follow-up colonoscopy (46%, CI 41-51%) or carcino-embryonic antigen assay (35%, CI 30-40%). Socio-economic advantage was associated with receipt of guideline-recommended care. While participants reported high interest in improving general health and lifestyle since their cancer diagnosis, few had received advice about screening for other cancers (24%, CI 19-28%) or assistance with lifestyle modification (30%, CI 26-34%). Less than half (47%, CI 43-52%) had discussed their family's risk of cancer with a doctor since their diagnosis.Conclusions: Survivorship care was highly variable, with evident socioeconomic disparities and missed opportunities for health promotion. [ABSTRACT FROM AUTHOR]

Background: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been emerged as the standard selection in non-small cell lung cancer (NSCLC) patients with EGFR sensitive mutations. However, primary or acquired resistance to EGFR-TKIs seems inevitable, especially to third-generation TKIs, which has appeared absence of effective solutions so far.Case Presentation: Here we reported a NSCLC patient with EGFR sensitive mutation of deletion within EGFR exon 19, who had been resistant to icotinib and AZD9291 successively after a period of 18 months response duration. Next-generation sequencing (NGS) technique using plasma sample suggested an acquired EGFR Leu792H mutation, rather than C797S one. Interestingly, the patient obtained another 8 months of disease-free duration with symptoms greatly relieved after repeating icotinib administration. The overall survival of the patient has been thirty-six months and still in the extension.Conclusion: The presentation of the case may provide some selective therapeutic thoughts for NSCLC patients with acquired EGFR Leu792H mutation suffering resistance to the third-generation TKIs. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence indicates that cetuximab (CET) combined with chemoradiotherapy may be effective for patients with esophageal cancer. However, the recent results are still contradictory and no consensus has yet been reached on this issue. To evaluate the clinical effects and safety of CET, we conducted an updated meta-analysis by retrieving published data up to June 2018.Methods: A comprehensive literature search was performed in several electronic databases, including PubMed, Embase, the Cochrane Library, CNKI database and Chinese Biomedicine Database using subject terms and free terms. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the efficiency and safety of CET.Results: This meta-analysis included 10 randomized controlled trials (RCTs). Five RCTs reported localized esophageal cancer and other five RCTs reported metastatic esophageal cancer. For these patients with localized esophageal cancer, CET could not significantly improve the response rate, overall survival and progression-free survival (PFS, 1-5 years). But CET treatment might increase the incidences of diarrhea (OR = 2.07; CI = 1.01-4.25) and rash (OR = 16.91; CI = 3.20-89.42). For other patients with metastatic esophageal cancer, the addition of CET significantly increased the response rate (OR = 3.34; CI = 1.90-5.88), disease control rate (OR = 2.92; CI = 1.49-5.71) and 2-year overall survival (OR = 2.78; CI = 1.20-6.46) compared with the control group. However, CET could not improve the 1-year overall survival and might make patients with metastatic esophageal cancer more susceptible to rash (OR = 5.50; CI = 2.14-14.14). No significant differences in other adverse effects were found between the two groups.Conclusions: Our findings suggested that adding CET to multimodal therapy significantly improved response rate and disease control rate for patients with metastatic esophageal cancer rather than patients with localized esophageal cancer. CET might be a safe therapeutic choice, but CET failed to significantly improve the overall survival and PFS for patients with localized or metastatic esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133+ cells and their sensitivity to pharmacological inhibition.Methods: GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a cancer stem cell marker. Cell proliferation was determined using the WST-1 assay. An intracranial mouse model and bioluminescence imaging were used to assess the effects of drugs on tumor growth in vivo.Results: CD133+ cells expressed stem cell markers and exhibited self-renewal and enhanced tumor formation. Minocycline (Mino) was more effective in reducing the survival rate of CD133+ cells, whereas CD133- cells were more sensitive to inhibition by the signal transducer and activator of transcription 3 (STAT3) inhibitor. Inhibition of STAT3 decreased the expression of CD133+ stem cell markers. The combination of Mino and STAT3 inhibitor synergistically reduced the cell viability of glioma cells. Furthermore, this combination synergistically suppressed tumor growth in nude mice.Conclusion: The results suggest that concurrent targeting of different subpopulations of glioblastoma cells may be an effective therapeutic strategy for patients with malignant glioma. [ABSTRACT FROM AUTHOR]

Background: Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ with respect to their biology and genomic patterns, but inflammatory index variation did not fully investigate. This study aimed to examine the difference of inflammatory indexes and its value between RCC and LCC.Methods: The differences of common clinicopathologic factors, inflammatory indexes including PLR (Platelet lymphocyte ratio) between LCC and RCC were analyzed in the training cohort with logistic regression model, subsequently, confirmed in validation cohort. Kaplan-Meier analysis was applied for the analysis of the survival difference distinguished by the PLR and the Nonparametric Test was adopted to demonstrate the difference of PLR variation with the standard TNM classification between RCC and LCC.Results: A total of 1846 CRC patients entered the study, 744 (40.3%) patients were RCC, 1102 (59.7%) were LCC. The patients' number in both cohorts was 923. It was found that LCC patients in the training cohort significantly to be with higher CEA, adenocarcinoma, early UICC/AJCC stage, p-MMR (mismatch-repair proficient), and lower PLR, and the later four features were confirm in validation cohort. Higher PLR, the unique inflammatory index, was significantly associated with poorer OS in LCC cohort (P = 0.002) and was elevated with the TNM stage in the LCC patients (P < 0.001), however, the two relationships did not sustain in RCC patients.Conclusion: Expect the classical characteristics, PLR, an inexpensive and easily assessable inflammatory index was found first time to be significant differ between LCC and RCC. Further, elevated PLR associated with poor OS (overall survival) in the LCC and more common in advanced TNM stage. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds.Methods: Breast cancer tissue sections were minced and cultured in media for several weeks. KAIMRC1 cells were successfully isolated from one of the primary breast tumor tissue cultures without any enzymatic digestion. To study the growth characteristics of the cells, wound healing assay, clonogenic assay, cell proliferation assays and live cell time-lapse microscopy was performed. Karyotyping, Immunophenotyping and molecular pathway specific compound treatment was also performed. A selective breast cancer gene expression panel was used to identify genes involved in the signal transduction dysregulation and malfunction of normal biological processes during breast carcinogenesis.Results: These cells are ER/PR-positive and HER2-negative. The epithelial nature of these cells was confirmed by flow cytometry analysis using epithelial cell markers. They are cuboidal in shape and relatively smaller in size as compared to established cell lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell culture conditions these cells showed the capability of growing both in monolayer as well as in 3-D conformation. They showed a doubling time in vitro of approximately 24 h. They exhibit a modal karyotype of 58-63,X with abnormalities in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7 cell lines.Conclusions: In conclusion we have isolated and characterized a new naturally immortalized breast cell line, KAIMRC1 with a potential to play a key role in opening up novel avenues towards the understanding of breast carcinoma. [ABSTRACT FROM AUTHOR]

Background: The levels of liver function tests (LFTs) are often used to assess liver injury and non-liver disease-related mortality. In our study, the relationship between pretreatment serum LFTs and overall survival (OS) was evaluated in esophageal squamous cell carcinoma (ESCC) patients.Methods: Our purpose was to investigate the prognostic value of the preoperative alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and gamma glutamyltransferase (GGT) in ESCC patients. A retrospective study was performed in 447 patients with ESCC, and follow-up period was at least 60 months until death. The prognostic significance of serum LFTs were determined by univariate and multivariate Cox hazard models.Results: LFTs including ALT, AST, LSR, GGT, TBA and LDH were analyzed. Serum LSR (HR: 0.592, 95% CI = 0.457-0.768, p < 0.001 and GGT (HR: 1.507, 95% CI = 1.163-1.953, p = 0.002) levels were indicated as significant predictors of OS. The 5-year OS among patients with higher LSR levels was longer compared with those patients with decreased LSR levels, not only in the whole cohort but also in the subgroups stratified by pathological stage (T1-T2 subgroup, T3-T4 subgroup, N0 subgroup and M0 subgroup). We also found that patients with a higher GGT might predict worse OS than patients with a normal GGT, not only in the whole cohort but also in the subgroups stratified by pathological stage (T3-T4 subgroup and N1-N2 subgroup).Conclusions: Both increased levels of LSR and decreased levels of GGT might predict shorter overall survival in ESCC patients. Our findings suggest that serum LSR and GGT levels could be used as a key predictor of survival in patients with ESCC. [ABSTRACT FROM AUTHOR]

Background: The identification of four Consensus Molecular Subtypes (CMS1-4) of colorectal cancer forms a new paradigm for the design and evaluation of subtype-directed therapeutic strategies. The most aggressive subtype - CMS4 - has the highest chance of disease recurrence. Novel adjuvant therapies for patients with CMS4 tumours are therefore urgently needed. CMS4 tumours are characterized by expression of mesenchymal and stem-like genes. Previous pre-clinical work has shown that targeting Platelet-Derived Growth Factor Receptors (PDGFRs) and the related KIT receptor with imatinib is potentially effective against mesenchymal-type colon cancer. In the present study we aim to provide proof for the concept that imatinib can reduce the aggressive phenotype of primary CMS4 colon cancer.Methods: Tumour biopsies from patients with newly diagnosed stage I-III colon cancer will be analysed with a novel RT-qPCR test to pre-select patients with CMS4 tumours. Selected patients (n = 27) will receive treatment with imatinib (400 mg per day) starting two weeks prior to planned tumour resection. To assess treatment-induced changes in the aggressive CMS4 phenotype, RNA sequencing will be performed on pre- and post-treatment tissue samples.Discussion: The development of effective adjuvant therapy for primary colon cancer is hindered by multiple factors. First, new drugs that may have value in the prevention of (early) distant recurrence are almost always first tested in patients with heavily pre-treated metastatic disease. Second, measuring on-target drug effects and biological consequences in tumour tissue is not commonly a part of the study design. Third, due to the lack of patient selection tools, clinical trials in the adjuvant setting require large patient populations. Finally, the evaluation of recurrence-prevention requires a long-term follow-up. In the ImPACCT trial these issues are addressed by including newly diagnosed pre-selected patients with CMS4 tumours prior to primary tumour resection, rather than non-selected patients with late-stage disease. By making use of the pre-operative window period, the biological effect of imatinib treatment on CMS4 tumours can be rapidly assessed. Delivering proof-of-concept for drug action in early stage disease should form the basis for the design of future trials with subtype-targeted therapies in colon cancer patients.Trial Registration: ClinicalTrials.gov: NCT02685046 . Registration date: February 9, 2016. [ABSTRACT FROM AUTHOR]

Background: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.Methods: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.Results: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036).Conclusions: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients.Methods: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients.Results: In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs.Conclusions: Plasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to review our results for pancreatic resection in patients with intraductal papillary mucinous neoplasm (IPMN) with and without associated carcinoma. Methods: A total of 54 patients undergoing pancreatic resection for IPMN in a single university surgical center (Medical University of Graz) were reviewed retrospectively. Their survival rates were compared to those of patients with pancreatic ductal adenocarcinoma. Results: Twenty-four patients exhibit non-invasive IPMN and thirty patients invasive IPMN with associated carcinoma. The mean age is 67 (+/-11) years, 43 % female. Surgical strategies include classical or pylorus-preserving Whipple procedure (n =30), distal (n = 13) or total pancreatectomy (n = 11), and additional portal venous resection in three patients (n= 3). Median intensive care stay is three days (range 1 - 87), median in hospital stay is 23 days (range 7 - 87). Thirty-day mortality is 3.7 %. Median follow up is 42 months (range 0 - 127). One-, five- and ten-year overall actuarial survival is 87 %; 84 % and 51 % respectively. Median overall survival is 120 months. Patients with non-invasive IPMN have significantly better survival than patients with invasive IPMN and IPMN-associated carcinoma (p < 0.008). In the subgroup of invasive IPMN with associated carcinoma, a positive nodal state, perineural invasion as well as lymphovascular infiltration are associated with poor outcome (p < 0.0001; <0.0001 and =0.001, respectively). Elevated CA 19-9(>37 U/l) as well as elevated lipase (>60 U/l) serum levels are associated with unfavorable outcome (p = 0.009 and 0.018; respectively). Patients operated for pancreatic ductal adenocarcinoma show significantly shorter long-term survival than patients with IPMN associated carcinoma (p = 0.001). Conclusions: Long-term outcome after pancreatic resection for non-invasive IPMN is excellent. Outcome after resection for invasive IPMN with invasive carcinoma is significantly better than for pancreatic ductal adenocarcinoma. In low- and intermediate risk IPMN with no clear indication for immediate surgical resection, a watchful waiting strategy should be evaluated carefully against surgical treatment individually for each patient. [ABSTRACT FROM AUTHOR]

Background: Noninvasive prognostic tools for esophageal squamous cell carcinoma (ESCC) are urgently needed. Serum lipids and lipoproteins are used for the prognosis of certain diseases; however, the prognostic value of serum apolipoprotein A-I (ApoA-I) in ESCC has not been described.Methods: Pre-treatment serum lipids and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) were analyzed retrospectively and compared between 210 patients with ESCC and 219 healthy controls. The prognostic significance of serum lipids and lipoproteins was determined by univariate and multivariate Cox hazard models in ESCC.Results: Clinical characteristics (age, sex, pT status, pN status, pM status, pTNM status, histological differentiation or alcohol index) had no influence on baseline ApoA-I level. Serum ApoA-I, HDL-C, LDL-C, and TC levels were significantly lower and Apo-B was significantly higher in ESCC patients than in normal controls. On univariate analysis, ApoA-I, alcohol index, pT status, pN status and pTNM status were associated with significantly poor survival, and ApoA-I (p = 0.039), alcohol index (p = 0.037) and pTNM status (p = 0.000) were identified as prognostic factors associated with shorter survival in the multivariate analysis.Conclusions: Overall survival was shorter in ESCC patients with decreased pre-treatment ApoA-I levels. Our findings suggest that serum ApoA-I level should be evaluated as a predictor of survival in patients with ESCC. [ABSTRACT FROM AUTHOR]

Background: In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients.Methods: We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization.Results: Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001).Conclusion: Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of lactate dehydrogenase levels in the prognosis of colorectal cancer patients has been assessed for years, although the results remain controversial and heterogeneous. Thus, we comprehensively reviewed the evidence from studies that evaluated lactate dehydrogenase levels in colorectal cancer patients to determine their effect.Methods: The following databases were searched in September 2014 to identify studies that evaluated the prognostic value of lactate dehydrogenase levels in colorectal cancer: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted hazard ratios (HRs) and the associated 95% confidence intervals (CIs) from the identified studies, and performed random-effects model meta-analyses on the overall survival (OS) and progression-free survival (PFS). Thirty-two studies with a cumulative sample size of 8,261 patients were included in our analysis.Results: Our meta-analyses revealed that high levels of lactate dehydrogenase were associated with poor OS (HR, 1.75; 95% CI, 1.52-2.02) in colorectal cancer patients. However, this effect was not obvious in the OS of non-metastatic colorectal cancer patients (HR, 1.21; 95% CI, 0.79-1.86). The prognostic value of lactate dehydrogenase levels on PFS was also not confirmed (HR, 1.36; 95% CI, 0.98-1.87). Subgroup analyses revealed that the prognostic significance of lactate dehydrogenase was independent of study location, patient age, number of patients, metastasis, chemotherapy with anti-angiogenesis drugs, study type, or risk of bias.Conclusions: Our results indicate that high lactate dehydrogenase levels are associated with poor OS among colorectal cancer patients, although these levels are not significant predictors of PFS. [ABSTRACT FROM AUTHOR]

Background: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection. Methods: We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration. Results: The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen. Conclusions: Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the second most common malignancy in Europe and a leading cause of cancer-related death. Almost 50% of patients with CRC develop liver metastases, which heralds a poor prognosis unless metastases can be downsized to surgical resection or ablation. The FOXFIRE trial examines the hypothesis that combining radiosensitising chemotherapy (OxMdG: oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radioembolisation) using yttrium-90 resin microspheres (SIR-Spheres®; Sirtex Medical Limited, North Sydney, Australia) as a first-line treatment for liver-dominant metastatic CRC will improve clinical outcomes when compared to OxMdG chemotherapy alone. Methods/Design: FOXFIRE is an open-label, multicentre, randomised controlled trial of OxMdG with or without the addition of SIRT (1:1 randomisation). Eligible adult patients have histologically confirmed colorectal adenocarcinoma, liver metastases measurable on computed tomography scan and untreatable by either surgical resection or local ablation, and they may have limited extra-hepatic disease, defined as =5 nodules in the lung and/or one other metastatic site which is amenable to future definitive treatment. Eligible patients may have received adjuvant chemotherapy following resection of the primary tumour, but are not permitted to have previously received chemotherapy for metastatic disease, and must have a life expectancy of =3 months and a WHO performance status of 0-1. The primary outcome is overall survival. Secondary outcomes include progression free survival (PFS), liver-specific PFS, patient-reported outcomes, safety, response rate, resection rate and cost-effectiveness. FOXFIRE shares a combined statistical analysis plan with an international sister trial called SIRFLOX. Discussion: This trial is establishing a network of SIRT centres and 'feeder' chemotherapy-only centres to standardise the delivery of SIRT across the whole of the UK and to provide greater equity of access to this highly specialised liver-directed therapy. The FOXFIRE trial will establish the potential role of adding SIRT to first-line chemotherapy for unresectable liver metastatic colorectal cancer, and the impact on current treatment paradigms for metastatic CRC. [ABSTRACT FROM AUTHOR]

Background: Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC). Methods: YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence. Results: YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001). Conclusions: ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC. [ABSTRACT FROM AUTHOR]

Background: Distant metastases stemming from a papillary thyroid carcinoma (PTC) are quite rare. Here we report an exceptional case of PTC presenting with cervical lymphatic and uterine metastases. This is the first case report of a PTC with uterine involvement.Case Presentation: A 60-year-old Chinese woman came to our hospital complaining of discomfort in the throat that she had been experiencing for about half a month. PTC and cervical lymphatic metastasis were diagnosed after ultrasound examinations. A massive heterogeneous mass was found beside the uterus during the pre-operative checkup and a diagnosis of ovarian carcinoma was suspected after a thorough case discussion. However, it proved to be a metastasis from the PTC as determined by pathological and immunohistochemical examinations after the operation. The patient declined further treatments. She was followed for 22 months with no sign of recurrence detected.Conclusions: In this report, an unusual case of PTC was presented. The patient had not only regional lymphatic metastasis, but also had a massive metastasis in the uterine corpus, which was initially misdiagnosed as ovarian carcinoma. This case is of interest because of its rarity and exceptionally good prognosis. The reason for the misdiagnosis was attributed to overlooking the possibility of a distant metastasis coming from a PTC. This case raises the issue that completing an iodine-131 scan before operating on patients with PTC may be warranted. [ABSTRACT FROM AUTHOR]

Background: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. Methods: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Results: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. Conclusion: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process. [ABSTRACT FROM AUTHOR]