FGL1 in plasma extracellular vesicles is correlated with clinical stage of lung adenocarcinoma and anti-PD-L1 response.

Fibrinogen-like protein-1 (FGL1) is confirmed a major ligand of lymphocyte activation gene-3 which could inhibit antigen-mediated T-cell response and evade immune supervision. Although hepatocytes secrete large amounts of FGL1, its high expression also be detected in solid tumors such as lung cancer, leading to a poor efficacy of immune checkpoint inhibitors therapy. Here we reported that FGL1 was overexpressed in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma. However, FGL1 in tissue and plasma can only distinguish LUAD patients from healthy donors and cannot correlate with clinical Tumor Node Metastasis (TNM) stage. Using lung cancer cell lines, we confirmed that FGL1 can be detected on extracellular vesicles (EVs) and we established a method using flow cytometry to detect FGL1 on the surface of EVs, which revealed that FGL1 could be secreted via EVs. Both animal model and clinical samples proved that plasma FGL1 in EVs would increase when the tumor was loaded. The level of FGL1 in plasma EVs was correlated with clinical TNM stage and tumor size, and a higher level indicated non-responsiveness to anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy. Its effect on tumor progression and immune evasion may be achieved by impairing the killing and proliferating capacities of CD8+ T cells. Our result demonstrates that FGL1 levels in plasma EVs, but not total plasma FGL1, could be a promising biomarker that plays an important role in predicting anti-PD-L1 immune therapy in LUAD and suggests a new strategy in LUAD immunotherapy.

A head-to-head comparison of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in patients with nasopharyngeal carcinoma: a single-center, prospective study.

PURPOSE: We aimed to compare the staging efficiency of [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT in nasopharyngeal carcinoma (NPC) patients. METHODS: Thirty-nine patients with pathologically confirmed NPC were enrolled in this prospective study. Each patient underwent paired [68Ga]Ga-DOTATATE and [68Ga]Ga-FAPI PET/CT on 2 successive days. The accuracy of two PET/CT for assessing T, N, and M stages was compared by using head-and-neck MRI, histopathologic diagnosis and follow-up results as reference standards. The radiotracer uptake derived from two PETs was also compared. RESULTS: For treatment-naïve patients, [68Ga]Ga-DOTATATE PET/CT showed identical sensitivity for the primary tumours but clearer tumor delineation induced by higher tumour-to-background (TBR) ratio (19.1 ± 8.7 vs. 12.4 ± 7.7, P = 0.003), compared with [68Ga]Ga-FAPI PET/CT. Regarding cervical lymph node (CLN) metastases, [68Ga]Ga-DOTATATE PET had significantly better sensitivity and accuracy based on neck sides (98% vs. 82%, P < 0.001; 99% vs. 88% P = 0.008), neck levels (98% vs. 78%, 99% vs. 97%; both P < 0.001) and individual nodes (89% vs. 56%, 91% vs. 76%; both P < 0.001), and higher TBR (8.1 ± 4.1 vs. 6.3 ± 3.7, P < 0.001). Additionally, [68Ga]Ga-DOTATATE PET/CT revealed higher sensitivity and accuracy for distant metastases (96% vs. 53%, 95% vs. 52%; both P < 0.001), particularly in bone metastases (99% vs. 49%, 97% vs. 49%; both P < 0.001). For post-treatment patients, [68Ga]Ga-DOTATATE PET/CT identified one more true-negative case than [68Ga]Ga-FAPI PET/CT. CONCLUSION: [68Ga]Ga-DOTATATE PET/CT performed better than [68Ga]Ga-FAPI PET/CT in visualizing the primary tumours, detecting the metastatic lesions and identifying the local recurrence, suggesting [68Ga]Ga-DOTATATE PET/CT may be superior to [68Ga]Ga-FAPI PET/CT for NPC staging.

Biomarkers of lipid metabolism in gastric cancer: a case control study.

BACKGROUND: The aim of this study was to explore the correlation between biomarkers of lipid metabolism and gastric cancer. METHODS: 1120 gastric cancer patients and 1134 health examiners enrolled in this study. The clinic data and serum lipid level, including Total cholesterol (TC), Triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C) and High-density lipoprotein cholesterol (HDL-C), were collected. RESULTS: Serum TG and LDL-C levels in patients with gastric cancer were higher than those in the control group. HDL-C levels were lower than the control group (P < 0.05). HDL-C and LDL-C were significantly correlated with the risk of gastric cancer. Concentrating on clinicopathological features, increased TG was more frequently in male patients with distal gastric cancer, N0 stage and early TNM stage. Increased TC was more frequently in early T, N and TNM stage. Decreased HDL-C was more common in distal location and low-undifferentiated gastric cancer. LDL-C elevation was more common in distal gastric cancer and early T stage. CONCLUSIONS: The serum lipid level of gastric cancer patients was higher than healthy controls. HDL-C and LDL-C abnormal correlated with gastric cancer risk. However, as the progresses of gastric cancer, poor patient intake, increased tumor consumption, and continuous declining in nutritional status, the levels of TC and TG gradually decreased in advanced gastric cancer.

A dataset resource for clinically associated phosphosites in hepatocellular carcinoma.

Phosphorylation is one of the most common post-translational modifications (PTMs) and is closely related to protein activity and function, playing a critical role during cancer development. Quantitative phosphoproteomic strategies have been widely used to study the underlying mechanisms of cancer progression or drug resistance. In this report, we analyzed the association of phosphosite levels originated from our previously reported proteogenomic study in hepatocellular carcinoma (HCC) with clinical parameters, including prognosis, recurrence, and Tumor-Node-Metastasis (TNM) stages. By using both the log-rank test and univariate Cox proportional hazards regression analysis, we found that the abundance levels of 1712 phosphosites were associated with prognosis and those of 393 phosphosites associated with recurrence. Besides, 692 phosphosites had different abundance levels among TNM stages (I, II, III+IV) by Analysis of Variance (ANOVA) test. Gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using proteins with these statistically significant phosphosites. In conclusion, we provided a dataset resource for clinically associated phosphosites in HCC, which may be beneficial to liver cancer related basic research.

Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

A novel analytical approach for outcome prediction in newly diagnosed NSCLC based on [18F]FDG PET/CT metabolic parameters, inflammatory markers, and clinical variables.

OBJECTIVES: To develop a novel analytical approach based on 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) metabolic parameters, serum inflammatory markers, and clinical variables to improve the outcome prediction in NSCLC. METHODS: A total of 190 newly diagnosed NSCLC patients who underwent pretreatment [18F]FDG PET/CT were retrospectively enrolled and divided into a training cohort (n = 127) and a test cohort (n = 63). Cox regression analysis was used to investigate the predictive values of PET metabolic parameters, inflammation markers, and clinical variables for progression-free survival (PFS) and overall survival (OS). Based on the results of multivariate analysis, PET-based, clinical, and combined models were constructed. The predictive performance of different models was evaluated using time-dependent ROC curve analysis, Harrell concordance index (C-index), calibration curve, and decision curve analysis. RESULTS: The combined models incorporating SULmax, MTV, NLR, and ECOG PS demonstrated significant prognostic superiority over PET-based models, clinical models, and TNM stage in terms of both PFS (C-index: 0.813 vs. 0.786 vs. 0.776 vs. 0.678, respectively) and OS (C-index: 0.856 vs. 0.792 vs. 0.781 vs. 0.674, respectively) in the training cohort. Similar results were observed in the test cohort for PFS (C-index: 0.808 vs. 0.764 vs. 0.748 vs. 0.679, respectively) and OS (C-index: 0.836 vs. 0.785 vs. 0.726 vs. 0.660, respectively) prediction. The combined model calibrated well in two cohorts. Decision curve analysis supported the clinical utility of the combined model. CONCLUSIONS: We reported a novel analytical approach combining PET metabolic information with inflammatory biomarker and clinical characteristics, which could significantly improve outcome prediction in newly diagnosed NSCLC. KEY POINTS: • The nomogram incorporating SULmax, MTV, NLR, and ECOG PS outperformed the TNM stage for outcome prediction in patients with newly diagnosed NSCLC. • The established nomogram could provide refined prognostic stratification.

The combination of preoperative fibrinogen-to-albumin ratio and postoperative TNM stage (FAR-TNM) predicts the survival in gastric cancer patients after gastrectomy.

OBJECTIVE: There are many factors that affect the survival of patients with gastric cancer, such as TNM stage, the patient's nutritional status, inflammation, and so on. In this study, the prognostic significance of preoperative fibrinogen-to-albumin ratio (FAR) and postoperative TNM staging in patients with gastric cancer was retrospectively studied. METHODS: A total of 265 patients (surgery dates from January 2007 to December 2013) were included in this retrospective study. All the patients were confirmed by pathology after operation. Categorical variables were compared using the χ2 test. Kaplan-Meier and log-rank tests were used for survival analysis. Cox proportional hazard models were used to assess prognostic factors. Nomogram was applied to predict the prognosis of overall survival (OS). RESULTS: The higher the FAR value, the more lymph node metastasis, the later the TNM stage, and the shorter the survival time. We established a new scoring system, the FAR-TNM score, which combined FAR and TNM stage. The FAR-TNM score was significantly related to tumor location, tumor size, Bormann types, differentiation, operative type, vascular invasion, nerve invasion, depth of invasion, lymphatic metastasis, and advanced TNM stage. Multivariate Cox regression analysis demonstrated that tumor location, TNM stage, adjuvant chemotherapy, and FAR-TNM score were independent prognostic elements for OS in patients with GC. CONCLUSIONS: The FAR-TNM score was a valuable independent prognostic indicator for GC patients after surgery, which can help clinicians to assist the treatment and long-term management of patients with gastric cancer.

Significance of ypTNM stage in determining the prognosis and therapy after surgery for locally advanced rectal cancer.

BACKGROUND: In the current NCCN guidelines, the prognosis and adjuvant chemotherapy of patients who underwent neoadjuvant chemoradiotherapy (nCRT) are based on pre-radiotherapy clinical TNM (cTNM) stage. However, the value of neoadjuvant pathologic TNM (ypTNM) stage is not clearly described. METHODS: This retrospective study investigated the prognosis and adjuvant chemotherapy which based on ypTNM stage compared to cTNM stage. Between 2010 and 2015, a total of 316 rectal cancer patients who underwent nCRT, followed by total mesorectal excision (TME), were included for analysis. RESULTS: Our findings revealed that cTNM stage was the only significant independent factor in the pCR group (HR = 6.917, 95% CI: 1.133-42.216, P = 0.038). In the non-pCR group, ypTNM stage was more important than cTNM stage in prognosis (HR = 2.704, 95% CI: 1.811-4.038, P < 0.001). In ypTNM III stage group, there was a statistically significant difference in prognosis between the patients with and without adjuvant chemotherapy (HR = 1.943, 95% CI: 1.015-3.722, P = 0.040), but there was no significant difference in cTNM III stage group (HR = 1.430, 95% CI: 0.728-2.806, P = 0.294). CONCLUSIONS: We concluded that ypTNM stage, rather than cTNM stage, might be a more important factor in the prognosis and adjuvant chemotherapy of patients with rectal cancer who underwent nCRT.

Clinical significance of tumor deposits in gastric cancer after radical gastrectomy: a propensity score matching study.

OBJECTIVE: The value of tumor deposits (TDs) in the prognosis and staging of gastric cancer (GC) is still under debate. This study aims to evaluate the prognostic value of TDs and the best ways to incorporate TDs in the TNM classification of GC. METHODS: Patients (n = 3460) undergoing curative gastrectomy for GC in the West China Hospital from 2005 to 2017 were retrospectively reviewed and divided into two groups according to the TD status (positive vs. negative). Later, clinicopathological features and overall survival (OS) between the two groups were compared. Thereafter, the associations between the presence of TD and other clinicopathological factors were evaluated through logistic regression. In addition, univariate and multivariate Cox regression were conducted for determining prognostic factors. The possibility of selection bias was reduced through conducting the 1:1 propensity score matching (PSM) analysis. The modified classification systems proposed previously that incorporated TDs into the TNM staging system were assessed. RESULTS: There were 10.5% of patients (362/3460) diagnosed with TDs. TDs were significantly related to unfavorable factors such as advanced T stage and N stage and independently associated with poor prognosis. The 5-year OS of patients with TDs was significantly lower than that of patients without TDs (31.0% vs. 60.9%, P < 0.001), whereas higher than that of patients with peritoneal metastasis (31.0% vs. 5.0%, P < 0.001). In patients receiving chemotherapy, the 5-year OS of patients with TDs was also significantly lower than that of patients without TDs (42.0% vs. 50.9%, P = 0.026). Moreover, the system incorporating TDs in the TNM classification as metastatic lymph nodes outperformed others. CONCLUSIONS: TDs are related to the aggressive characteristics and are an independent prognostic factor for GC. Incorporating TDs in the TNM classification as the metastatic lymph nodes increases the accuracy in predicting prognosis.

Stratifying non-small cell lung cancer patients using an inverse of the treatment decision rules: validation using electronic health records with application to an administrative database.

BACKGROUND: To validate a stratification method using an inverse of treatment decision rules that can classify non-small cell lung cancer (NSCLC) patients in real-world treatment records. METHODS: (1) To validate the index classifier against the TNM 7th edition, we analyzed electronic health records of NSCLC patients diagnosed from 2011 to 2015 in a tertiary referral hospital in Seoul, Korea. Predictive accuracy, stage-specific sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and c-statistic were measured. (2) To apply the index classifier in an administrative database, we analyzed NSCLC patients in Korean National Health Insurance Database, 2002-2013. Differential survival rates among the classes were examined with the log-rank test, and class-specific survival rates were compared with the reference survival rates. RESULTS: (1) In the validation study (N = 1375), the overall accuracy was 93.8% (95% CI: 92.5-95.0%). Stage-specific c-statistic was the highest for stage I (0.97, 95% CI: 0.96-0.98) and the lowest for stage III (0.82, 95% CI: 0.77-0.87). (2) In the application study (N = 71,593), the index classifier showed a tendency for differentiating survival probabilities among classes. Compared to the reference TNM survival rates, the index classification under-estimated the survival probability for stages IA, IIIB, and IV, and over-estimated it for stages IIA and IIB. CONCLUSION: The inverse of the treatment decision rules has a potential to supplement a routinely collected database with information encoded in the treatment decision rules to classify NSCLC patients. It requires further validation and replication in multiple clinical settings.

Patterns and prognostic predictive value of perineural invasion in esophageal squamous cell carcinoma.

BACKGROUND: The pathological phenotype of perineural invasion (PNI) in squamous cell carcinoma (ESCC) is prevalent but highly heterogeneous. METHODS: Postoperative specimens from all patients with ESCC at Shaanxi Provincial People's Hospital were evaluated for PNI using haematoxylin and eosin (H&E) staining and S100 immunohistochemistry (IHC). We determined the correlation between PNI status and clinical outcomes. RESULTS: Among 349 ESCC cases, PNI was identified in 127 patients (36.3%), and four subtypes of PNI were identified in our study. Correlation analysis confirmed that PNI was related to tumour invasion depth (pT stage) and lymph node status (pN stage) (P < 0.05). Multivariate analysis showed that PNI (P = 0.001) was an independent factor affecting disease-free survival (DFS) in ESCC, and a similar result was found for overall survival (OS) (P = 0.017). Further analysis revealed that PNI status was a prognostic factor of DFS (P < 0.001) and OS (P = 0.003) exclusively in pN-negative patients. We also found that patients with the PNI-a subtype had better DFS (P = 0.002) and OS (P = 0.002) than patients with the other three subtypes (PNI-b, c, d). CONCLUSION: The pathological phenotypes of PNI are diverse, and the identification of PNI subtypes has important clinical guiding value.

Circular RNA mitochondrial translation optimization 1 correlates with less lymph node metastasis, longer disease-free survival, and higher chemotherapy sensitivity in gastric cancer.

OBJECTIVE: Circular-mitochondrial translation optimization 1 (circ-MTO1) inhibits the progression of gastric cancer by regulating the growth, apoptosis, and invasion of tumor cells. However, its clinical potential as a biomarker for gastric cancer remains to be further evaluated. This study aimed to assess circ-MTO1 expression and its correlation with clinical features and prognosis in gastric cancer patients, as well as the effect of circ-MTO1 on the sensitivity to chemotherapy in gastric cancer cells. METHODS: Circ-MTO1 in tumor and adjacent tissues of 97 gastric cancer patients undergoing resection was examined by reverse transcription-quantitative polymerase chain reaction. HGC-27 and NCI-N87 cells transfected by circ-MOT1 overexpression plasmid (OE-circ-MOT1) and negative control (OE-NC) were treated with 0-6.4 µM oxaliplatin. Relative cell viability was detected using Cell Counting Kit-8. RESULTS: Circ-MTO1 was insufficiently expressed in gastric tumor tissue (median (interquartile range): 0.403 (0.288-0.518)) compared with adjacent tissue (median (interquartile range): 1.000 (0.715-1.524)) (p < 0.001). Besides, tumor circ-MTO1 was correlated with less lymph node metastasis (p = 0.014) and low TNM stage (p = 0.039), while was not correlated with demographic features or other clinical characteristics (all p > 0.05). Furthermore, tumor circ-MTO1 high expression was independently correlated with prolonged disease-free survival (DFS) (p = 0.013, adjusted hazard ratio (95% confidential interval): 0.314 (0.126-0.782)), but was not correlated with overall survival (p > 0.05). Lastly, in gastric cancer cells, OE-circ-MTO1 apparently decreased relative cell viabilities at oxaliplatin concentrations of 0.4, 0.8, 1.6, and 3.2 µM (all p < 0.05). CONCLUSION: Circ-MTO1 correlates with less lymph node metastasis, prolonged DFS, and improved chemotherapy sensitivity in gastric cancer.

Clinical, Pathological, and Prognostic Analysis of Urachal Carcinoma.

OBJECTIVE: The aim of this study was to improve understanding the clinical, pathologic, and prognostic features of urachal carcinoma (UrC), a retrospectively descriptive study was done in 2 clinical centers. METHODS: After excluding the 2 missed patients, the clinical and pathological data of 59 patients with UrC, who were diagnosed or treated at 2 clinical centers between 1986 and 2019, was retrospectively analyzed. SPSS 22.0 (IBM) and GraphPad Prism 8.0.1 were used for statistics and data visualization. Survival data were analyzed by the Kaplan-Meier method and Log-rank tests. Cox proportional hazards regression were performed for find risk factors on predicting the prognosis. RESULTS: Of all 59 patients, 47 were male and 12 were female. The median age at diagnosis was 51.6 years (range: 22-84 years). Gross hematuria was the most common symptom (79.66%). The majority of urachal neoplasms were adenocarcinomas (94.92%). Forty-two patients (72.41%) underwent extended partial cystectomy with en bloc resection of the entire urachus. The mean follow-up was 52 months (3-277 months). Median overall survival was 52.8 months (4-93 months). The 3-year cancer-specific survival (CSS) rate and 5-year CSS rate were 69.1% and 61.2%. There was no significant difference among localized T stage, tumor histologic grade and surgical procedures in determining prognosis by survival analyze. While patients with high-risk TNM stage (local abdominal metastasis, lymph node metastasis, or distant metastasis) (p = 0.003) and positive surgical margin (p < 0.001) had significantly worse prognosis. CONCLUSIONS: The results indicate that high-risk TNM stage and positive surgical margin are risk predictors of prognosis. Localized T stage, histologic grade, and surgical procedure cause no significant effect on patient prognosis. The extended partial cystectomy is the recommended surgical approach for patients with UrC. Active multimodal treatments may improve the survival of patients with recurrent and metastatic disease.

RECK Variants are Associated with Clinicopathological Features and Decreased Susceptibility in Mexican Patients with Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death worldwide. Down-regulation of the cysteine-rich reversion-inducing protein with Kazal motifs (RECK) has been confirmed in numerous human cancers and is clinically associated with metastasis. This study aims to explore, for the first time, the possible association of the RECK variants rs11788747 and rs10972727 with CRC susceptibility and clinicopathological features. DNA from 130 CRC patients and 130 healthy blood donors was analyzed. Identification of genetic variants was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Association was calculated using the odds ratio (OR) test and P values were adjusted using the Bonferroni test. Individuals carrying the G/G genotype for the rs11788747 variant showed a lower risk of colorectal cancer (OR 0.33; 95% CI 0.16-0.70; P = 0.006). Patients older than 50 years who carry the G/G genotype have a lower risk of CRC (OR 0.26; 95% CI 0.09-0.73; P = 0.019) and of developing advanced tumor-nodule-metastasis (TNM) stages (OR 0.23; 95% CI 0.09-0.54; P = 0.001). Individuals carrying the A/A genotype of the rs10972727 variant also showed decreased risk of CRC (OR 0.38; 95% CI 0.19-0.77; P = 0.011), and were associated with age (over 50 years), sex, advanced TNM stages, and tumor location in the colon. Our results suggest that the RECK variants studied here (rs11788747 and rs10972727) are associated with decreased CRC risk, TNM stages and tumor location.

Upregulation of miR-886 indicates poor prognosis and promotes tumour progression of prostate cancer.

Prostate cancer is a heterogeneous disease with high incidence and mortality. The functional role of miR-886 has been reported in various cancers and its dysregulation in prostate cancer was also found. Whether miR-886 was involved in the development of prostate cancer remains unclear, which was explored. miR-886 was evaluated in prostate cancer by RT-qPCR, and its clinical value was also assessed. Additionally, the role of miR-886 in prostate cancer cells was assessed by MTT and transwell assay. miR-886 was upregulated and was associated with the Gleason score and TNM stage of prostate cancer patients. miR-886 could predict the poor survival of patients. Moreover, miR-886 was a tumour promoter, of which the upregulation significantly promoted major cellular processes of prostate cancer. miR-886 mediated the disease development and predicted the clinical outcomes of patients. The knockdown of miR-886 inhibits cellular processes of prostate cancer, which provides a novel therapeutic target.

In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study.

BACKGROUND: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death. METHODS: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up. RESULTS: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes. CONCLUSIONS: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.

The prognostic value of tumor deposits and the impact on the TNM classification system in esophageal cancer patients.

OBJECTIVE: To explore the prognostic significance of tumor deposits (TDs), isolated tumor foci lacking residual lymph nodes, in esophageal cancer (EC). METHODS: A retrospective review of patients with EC undergoing esophagectomy between 2005 and 2017 was conducted. The prognostic value of TD was evaluated using a Cox regression model. Patients from different sources and periods were split into discovery and validation sets. A propensity score matching model was used in the validation set to reduce the confounding bias. The impact of TD on the TNM classification system was evaluated. RESULTS: The discovery and validation sets included 179 and 2875 patients, respectively. Propensity-matched patients with and without TDs were constructed in the validation set with 132 patients in each group. Overall survival (p < .001 and p = .004, respectively) and disease-free survival (p < .001 and p = .019, respectively) were both decreased in TD positive patients in the discovery set and propensity-matched groups of validation set. Classifying patients with TDs into pN3 stage improved the discriminative power of the current TNM staging system. CONCLUSIONS: TD is an independent prognostic factor for EC. The inclusion of TD in the TNM staging system may upstage appropriate patients to help guide therapy, and future studies are warranted.

The clinical significance of preoperative serum fibrinogen levels and platelet counts in patients with gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which might potentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients. METHODS: The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan-Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery. RESULTS: The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p < 0.001 and p < 0.001, respectively). In GBC, fibrinogen levels were associated with tumor depth (p = 0.001), lymph node metastasis (p = 0.002), distant metastasis (p < 0.001) and Tumor Node Metastasis (TNM) stage (p < 0.001). The levels in TNM stage IV disease were significantly higher than stage III or stage I + II disease (p = 0.048 and p < 0.001, respectively), and in TNM stage III disease were significantly higher than stage I + II disease (p = 0.002). Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p < 0.001). However, thrombocytosis was not significantly associated with overall survivals (p > 0.05) in multivariate analysis. CONCLUSIONS: The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.

Role of "Stiff Rim" sign obtained by shear wave elastography in diagnosis and guiding therapy of breast cancer.

Background: Because the halo around the tumor in shear wave elastography (SWE) is defined as the "stiff rim" sign, the diagnosis of breast lesions with the stiff rim sign is popular. However, only a few studies have described the stiff rim sign quantitatively. Objective: This study aimed to investigate the usefulness of the stiff rim sign in the diagnosis and tumor, node, metastasis stage of breast cancer. Methods: Two hundred and ten breast lesions were analyzed retrospectively. The maximum, mean, minimum Young's modulus (YM), and the YM standard deviation in the lesion, the peritumoral stiffness (shell), and the region containing lesion and shell were obtained. The suspicious SWE feature with the best diagnostic performance was chosen to downgrade or upgrade the Breast Imaging Reporting and Data System (BI-RADS) classification. The coincidence rates of SWE and B-mode ultrasound in T staging and their positive predictive value (PPV) for T staging were compared. Results: The presence of "stiff rim" sign was selected to upgrade or downgrade the BI-RADS classification because of its best performance. In pathological benign lesions, 18.9% (25 of 132) of lesions should undergo biopsy if BI-RADS combined with the stiff rim sign were referred while it was 57.6% (76 of 132) if BI-RADS alone was referred. The coincidence rate of T2 staging evaluated by SWE was significantly higher than B-mode ultrasound (about 30% increase, P < 0.001). The PPVs of SWE for T1 and T2 staging were higher than B-mode ultrasound (P < 0.05). Conclusions: BI-RADS combined with "stiff rim" sign is expected to improve the diagnostic performance of breast lesions to avoid unnecessary biopsy. The maximum diameter of the lesion measured in SWE is more accurate than B-mode ultrasound in the estimation of T staging, which is beneficial to the treatment and prognosis of breast cancer.

Outcome of radical surgery for gallbladder carcinoma according to TNM stage: implications for adjuvant therapeutic strategies.

PURPOSE: Outcomes following surgery for advanced gallbladder carcinoma remain unsatisfactory. This study aimed to determine the surgical outcome and effectiveness of adjuvant chemotherapy according to TNM stage in patients with gallbladder carcinoma. METHODS: A total of 200 patients undergoing surgery for gallbladder carcinoma were enrolled. Clinicopathological data were evaluated and surgical outcomes were compared between patients with and without adjuvant chemotherapy according to TNM stage. RESULTS: The 5-year overall survival (OS) after resection for patients with stage I (n = 27), IIA (n = 18), IIB (n = 28), IIIA (n = 25), IIIB (n = 43), IVA (n = 7), and IVB (n = 52) disease was 90.8%, 94.4%, 73.6%, 33.7%, 57.7%, 14.3%, and 11.8%, respectively (p < 0.001). R0 resection was performed in all patients with stage I or II disease, in 89.7% of those with stage III disease, and 69.5% of those with stage IV disease. For patients with stage III disease, adjuvant chemotherapy was associated with improved OS (5-year OS, 60.9% vs. 41.1%; p = 0.028) and was an independent prognostic factor (hazard ratio, 2.045; p = 0.039). For patients with stage IV disease, adjuvant chemotherapy appeared to affect OS (5-year OS, 25.1% vs. 5.3%; p = 0.041); R0 resection (hazard ratio, 1.882; p = 0.040) was the only independent prognostic factor. CONCLUSION: TNM stage clearly predicts survival after resection of gallbladder carcinoma. R0 resection with adjuvant chemotherapy is recommended for long-term survival in the multimodal management of patients with stage III or IV gallbladder carcinoma.