Node Ratio Research Articles

Hashimoto's thyroiditis is negatively associated with lymph node metastasis in PTMC.

The association between Hashimoto's thyroiditis (HT) and lymph node metastasis (LNM) of papillary thyroid microcarcinoma (PTMC) remains poorly understood. We aimed to elucidate the impact of HT on PTMC and its association with LNM. A retrospective cohort study was conducted at a single cancer referral center. Patients diagnosed with PTMC and complete clinicopathological results between January 2013 and June 2018 were included. Propensity score matching (PSM) and logistic regression analysis were performed to evaluate the difference in LNM characteristics between patients with and without HT. Among the 9929 PTMC patients, 2389 (24.1%) were pathologically diagnosed with HT. After PSM using variables including age, sex, primary tumor size, central neck dissection, extrathyroidal extension (ETE), gross ETE, multifocality and bilaterality, we identified 2324 pairs of patients for analysis. Patients with HT had a significantly lower incidence of LNM in the central neck (40.9% vs 56.2%, P < 0.001) and lateral neck (11.6% vs 14.2%, P = 0.016), a lower incidence of extranodal extension (ENE) (10.1% vs 17.0%, P < 0.001), fewer positive lymph nodes (median [IQR], 0 [0 to 2] vs 1 [0 to 3], P < 0.001), and a lower lymph node ratio (median [IQR], 0.00 [0.00 to 0.15] vs 0.12 [0.00 to 0.33], P < 0.001) than those without HT. Logistic regression analysis indicated that patients with HT had a significantly reduced risk of CLNM and LLNM compared to those without HT. Our study indicated a negative association between HT and LNM in PTMC.

479. TRANSTHORACIC VERSUS TRANSABDOMINAL SURGICAL APPROACH FOR SIEWERT TYPE II ESOPHAGOGASTRIC JUNCTIONAL ADENOCARCINOMAS—A PROPENSITY SCORE-MATCHED ANALYSIS

Abstract Background Esophagogastric junctional(EGJ) adenocarcinoma is a complex type of cancer that varies in etiology and disease pattern depending on the tumor level. There is increasing evidence on the need for different surgical approaches for different Siewert types. The optimal surgical approach for Siewert type II cancer remains controversial. This study aims to compare the oncological and surgical safety of transthoracic and transabdominal approaches for type II cancers. Methods The study included patients who underwent resection for Siewert type II adenocarcinomas from 2003–2020 in a single tertiary center using transthoracic (TT) and transabdominal (TA) approaches with macroscopic tumor clearance. The TT approach referred to Lewis-Tanner esophagogastrectomy, while the TA approach included total gastrectomy and proximal gastrectomy. Data from a prospectively-managed database were analyzed to compare postoperative morbidity and mortality rates, lymph node harvest, completeness of resection and overall survival between the two groups. Propensity score matching (PSM) was used in further analyses. Results Excluding R2 resections, there were 54 patients in the TT and 45 (proximal gastrectomy:23) in the TA groups. cT stages were comparable. In TT group, median tumor length was 6 cm (vs. 3 cm,p = 0.000), 18.5% with esophageal extension of &amp;gt;4 cm above EGJ;75.9% had nodal metastases (vs. 47.7%, p = 0.004);20.4% underwent neoadjuvant therapy (vs. 6.8%, p = 0.057). Anastomotic leak and cardiopulmonary complication rates, R0 resection rates, nodal yield and positive lymph node ratios were comparable. Proximal margin was involved in 15.9% for TA (vs. 5.6%, p = 0.092). Overall median survival times were similar (TT vs. TA: 42vs.65 months, p = 0.557). PSM yielded 33 patients per group. Only one in TT group had &amp;gt;4 cm esophageal involvement. Cardiac complication rate in TT group was 23.6%(vs. 3.5%, p = 0.024). Conclusion After correcting for selection bias, positive lymph node ratio, resection margin and overall survival did not differ for the TT and TA approaches. Resection by the TT approach is associated with more cardiac complications. For Siewert type II tumors with limited thoracic esophageal extension, the TA approach is safe and should be sufficient.

Development and external validation of a nomogram predicting overall survival for Gastric adenocarcinoma patients with radical gastrectomy

Purpose The aim of this study was to develop and externally validate a nomogram to accurately predict the overall survival (OS) of patients with gastric adenocarcinoma who underwent radical gastrectomy. Materials and Methods A total of 3492 patients with gastric adenocarcinoma who underwent radical gastrectomy from 2012 to 2017 were included as the training cohort. Survival analysis was performed via Kaplan Meier method and log-rank test. Independent postoperative prognostic factors in patients with gastric adenocarcinoma were analyzed using univariate and multifactorial COX analysis methods. The prognosis nomogram was established in the training cohort and verified externally in the Surveillance, Epidemiology and End Results (SEER) database. Results According to the univariate and multifactorial COX analyses, metastatic lymph node ratio (MLNR) and five other independent prognostic factors (age at surgery, type of gastrectomy, tumor size, T stage, and pathological grade) were included in the prognostic nomogram. The nomogram had better prognostic predictive ability than the American Joint Committee on Cancer (AJCC) TNM staging in both the training (C-index: 0.736 VS. 0.668) and external validation cohort (C-index: 0.712 VS. 0.627). The calibration plots showed that the predicted survival rate was in good agreement with the actual survival rate. And the decision curve analysis (DCA) curves revealed that nomogram showed stronger ability in predicting 1-year, 3-year, and 5-year OS. Conclusion This study estimated the excellent prognostic predictive power and clinical application potential of the MLNR-based nomogram, which may be used to facilitate postoperative clinical treatment decisions and potentially improve patient survival outcomes.

Lymph Node Ratio as a Prognostic Factor for Oral Tongue Squamous Cell Carcinoma: A Retrospective Study.

Background Oral squamous cell carcinoma (OSCC) incidence and its mortality have increased recently. The oral part of the tongue is one of the commonest sites for OSCC. Apart from Tumour-Node-Metastasis (TNM) staging, lymph node ratio (LNR) has been implicated as one of the useful predictors for the better clinical outcome of the disease. The aim of the present study was to assess the LNR as a prognostic factor for patients having oral tongue squamous cell carcinoma (OTSCC). Materials and methods It is a retrospective study of 122 patients with OTSCC who were managed primarily by surgery with curative intent from January 2014 to December 2016. The mean lymph node ratio was measured and compared with various parameters of clinical outcome such as five-year overall survival (OS), five-year disease-free survival (DFS), locoregional failure (LRF) within three years, and distant metastasis (DM) within five years using Kruskal-Wallis Test followed by Mann-Whitney Post Hoc Test. The association of LNR with other tumor characteristic features like perineural invasion, extra-nodal extension (ENE), and histopathological grading was also elicited. Results The study population's mean age was 50.5 ± 11.77 years. Among them, 85 were males and 37 were females.On comparingthe mean LNR value with patient status after primary treatment, the patients with minimal LNR value had statistically significant five-year OS and five-year DFS (p< 0.001). High mean LNR values were associated with other adverse features like perineural invasion and ENE, which were statistically significant (p<0.001). Receiver operator characteristics (ROC) curve analysis for the LNR parameter for determining the cut-off (0.02) between OS and DFS had 86% sensitivity and 40% specificity. Conclusion The LNR could be an important prognosis factor for OTSCC that helps in determining better clinical outcomes.

A Novel Injection Protocol Using Voluven®-Assisted Indocyanine Green with Improved Near-Infrared Fluorescence Guidance in Breast Cancer Sentinel Lymph Node Mapping—A Translational Study

BackgroundNear-infrared (NIR) fluorescence-guided surgery with indocyanine green (ICG) has been demonstrated to provide high sensitivity in sentinel lymph node biopsy (SLNB) for breast cancer but has several limitations, such as unstable pharmacokinetics, limited fluorescence brightness, and undesired diffusion to neighboring tissues. This paper investigates the use of Voluven® as the solvent for ICG fluorescence-guided SLNB (ICG-SLNB).MethodsThe photophysical properties of ICG in water and Voluven® were evaluated in laboratory experiments and in a mouse model. Nine patients with early breast cancer underwent subareolar injection of diluted ICG (0.25 mg/ml) for ICG-SLNB. Six of the nine patients received ICG dissolved in Voluven® (ICG:Voluven®), while three were administered ICG dissolved in water (ICG:water); a repetitive injection-observation protocol was followed for all patients. The mapping image quality was evaluated.ResultsLaboratory experiments and in vivo mouse study showed improved fluorescence and better targeting using Voluven® as the solvent. ICG-SLNB with a repetitive injection-observation protocol was successfully performed in all nine patients. ICG:Voluven® administration had an overall better signal-to-background ratio (SBR) in sequential sentinel lymph nodes. The rates of transportation within the lymphatics were also improved using ICG:Voluven® compared with ICG:water.ConclusionsFrom basic research to animal models to in-human trial, our study proposes a repetitive injection-observation technique with ICG:Voluven®, which is characterized by better transportation and more stable mapping quality for ICG-SLNB in breast cancer patients.

Lymph node ratio as a tool to stratify patients with N1b papillary thyroid cancer.

The prognostic significance of lymph node ratio (LNR) in N1b papillary thyroid cancer is unclear. Therefore, the impact of LNR on disease-specific mortality (DSM) and overall survival (OS) in patients with N1b papillary thyroid cancer (PTC) needs to be defined. We used the Surveillance, Epidemiology, and End Results (SEER) database of patients who had undergone thyroidectomy and lymph node dissection. Factors associated with DSM and OS were analyzed and identified using univariate and multivariate Cox proportional risk models. X-tile software was used to find the best cutoff value of LNR. Kaplan-Meier estimates for DSM were plotted for LNR and were compared with the log-rank test. The ROC curve evaluated the validity of the model. A total of 3223 patients with N1b PTC were identified in the SEER database between 1975 and 2019. The best cutoff value for LNR was 0.6. The multivariate Cox proportional risk model showed that age, race, T3/T4 classification, distant metastasis, extent of surgery, number of metastatic lymph nodes, and LNR > 0.6 were independent risk factors for DSM (all p < 0.05). Age, sex, T4 classification, distant metastasis, extent of surgery, and LNR > 0.6 were independent risk factors for OS (all p < 0.05). The Kaplan-Meier method plotted a cumulative risk curve and showed that patients with LNR > 0.6 had a significantly higher risk of DSM than patients with LNR ≤ 0.6 (p = 0.002). LNR was a powerful predictor of DSM and OS in N1b PTC patients. LNR could be a useful tool for the stratification of PTC patients with lateral neck metastases.

Lymph node ratio is a prognostic indicator for locally advanced esophageal squamous cell carcinoma after neoadjuvant immunochemotherapy.

The lymph node ratio (LNR) is regarded as a prognostic indicator in esophageal cancer (EC), but its applicability to neoadjuvant immunochemotherapy (NICT) in esophageal squamous cell carcinoma (ESCC) remains unexplored. This retrospective study, conducted between 2019 and 2021, analyzed ESCC patients who underwent radical esophagectomy following NICT. Patients were divided into two groups based on their LNR values according to the X-tile software: Low-LNR group (LNR 0-10%) and High-LNR group (LNR 10-100%). The association between LNR and clinical outcomes in ESCC after NICT were analyzed. A total of 212 ESCC patients who underwent surgery after NICT were included in this study, among which, 169 (79.7%) and 43 (20.3%) cases were allocated to the Low- and High-LNR groups, respectively. Pathologic complete response (PCR) was observed in 28.3% (60/212) of the overall cohort. Patients in the Low-LNR group demonstrated a significantly improved 3-year overall survival (OS) (81.7% vs 55.3%; P < 0.001) and disease-free survival (DFS) (79.9% vs 37.4%; P < 0.001). These findings were consistent among those with non-PCR (3-year DFS was 73.7% vs 37.4%; P < 0.001, and the 3-year OS was 78.9% vs 55.3%; P < 0.001, respectively). High LNR was associated with a 4.013-fold increased risk of relapse and a 7.026-fold elevated risk of death. Compared to the post-neoadjuvant therapy pathologic lymph nodes staging (ypN), LNR exhibited similar prognostic capabilities for DFS and OS. To the best of our knowledge, this study is the first to investigate the prognostic value of LNR in ESCC after NICT, suggesting that LNR may serve as a viable alternative to the ypN stage for prognostication in ESCC patients treated with NICT.

Exploring the most appropriate lymph node staging system for node-positive breast cancer patients and constructing corresponding survival nomograms.

The lymph node (LN) status is a crucial prognostic factor for breast cancer (BC) patients. Our study aimed to compare the predictive capabilities of three different LN staging systems in node-positive BC patients and develop nomograms to predict overall survival (OS). We enrolled 71,213 eligible patients from the SEER database, and 667 cases from our hospital were used for external validation. All patients were divided into two groups based on the number of removed lymph nodes (RLNs). The prognostic abilities of pN stage, positive LN ratio (LNR), and log odds of positive LN (LODDS) were compared using the C-indexes and AUC values. LASSO regression was performed to identify significant factors associated with prognosis and develop corresponding nomogram models. Our study found that LNR had superior predictive performance compared to pN and LODDS among patients with RLNs < 10, while pN performed better in patients with RLNs ≥ 10. In the training set, the nomogram models exhibited excellent clinical applicability, as evidenced by the C-indexes, ROC curves, calibration plots, and decision curve analysis curves. Moreover, the nomogram classification accurately differentiated risk subgroups and improved discrimination. These results were externally validated in the validation cohort. Physicians should select different LN staging systems based on the number of RLNs. Our novel nomograms demonstrated excellent performance in both internal and external validations, which may assist in patient counseling and guide treatment decision-making.

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

The Prognostic Significance of Lymph Node Ratio for Esophageal Cancer: A Meta-Analysis

IntroductionThis meta-analysis aimed to investigate the prognostic significance of positive lymph node ratio (LNR) in patients with esophageal cancer. Materials and methodsThe meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We conducted a systematic search of relevant literature published until April 2022 in PubMed, EMBASE, and the Cochrane Library. The primary and secondary outcomes were overall survival (OS) and disease-free survival (DFS), with corresponding hazard ratios (HR) and 95% confidence intervals (CI). The included studies were subgrouped based on age, study area, adjuvant therapy, sensitivity analysis, and assessment of publication bias. We analyzed and discussed the results. ResultsWe included 21 studies with 29 cohorts and 11,849 patients. The Newcastle-Ottawa Scale scores of the included studies were no less than six, indicating high research quality. The combined results of HR and 95% CI showed that patients with esophageal cancer with a lower LNR had better OS (HR, 2.58; 95% CI, 2.15-3.11; P < 0.001) and DFS (HR, 3.07; 95% CI, 1.85-5.10; P < 0.001). The subgroup analysis suggested that geographic region, age, and adjuvant therapy affected OS. When any cohort was excluded, no significant changes were observed in the pooled HR of the OS group, indicating reliable and robust results. Egger's and Begg's tests showed no potential publication bias in the studies that used OS as an outcome measurement index, indicating reliable results. Sensitivity analyses and assessments of publication bias (<10) were not performed because of an insufficient number of DFS studies. ConclusionPatients with a lower positive LNR had a higher survival rate, suggesting that positive LNR may be a promising predictor of EC prognosis in esophageal cancer. After radical resection of esophageal cancer, the ratio of the number of dissected lymph nodes to the number of positive lymph nodes in patients with esophageal cancer should be considered to accurately evaluate the prognosis.

The value of lymph nodes ratios in the prognosis of resectable remnant gastric cancer through the retrospective propensity score matching analysis

PurposeCurrently, the characteristics and prognosis of remnant gastric cancer (RGC) are not fully understood yet. The present study aimed to describe the details of clinicopathological features of resectable RGC and investigated the factors affecting survival after the curative operation.MethodsFrom Jan. 2006 to Dec. 2015, a total of 118 resectable RGC patients (the RGC group) and 236 age-, sex- and TNM stages-matched resectable gastric cancer (GC) patients (the control group) were recruited retrospectively. Clinicopathological characteristics and overall survival were compared between the two groups.ResultsThe overall survival rate was 46.61% for RGC patients compared to 55.08% for control groups (P < 0.01), and the mean overall survival time of RGC patients was 40.23 ± 32.27 months, compared to 55.06 ± 34.29 months in the control group (P = 0.023 after matching). The overall survival (OS) of RGC patients with stage IIb was much worse than IIa (P < 0.001) and similar to IIIa (P = 0.463) and IIIb (P = 0.014). Multivariate Cox proportional hazards model analysis revealed that TNM stage (HR: 3.899, P < 0.001) and lymph nodes ratio (LNR) (HR: 2.405, P = 0.028) were independent prognostic significance to OS.ConclusionsThe OS of RGC was much worse than GC with similar TNM stages, and LNR might consider a highly reliable indicator to evaluate the prognostic in RGC.

Comparison of alternative N-staging models in patients with oral cancer. Is nodal yield or burden the most critical parameter?

BackgroundThere is increasing evidence in the literature that alternative N-classification systems offer a simpler and more precise risk stratification than the current N- classification in patients with oral squamous cell carcinoma. The purpose of this study is to compare three broadly proposed models incorporating lymph node ratio, log odds of positive lymph nodes and number of positive lymph nodes regarding disease-free and overall survival. MethodsThis is a retrospective study of patients treated in a single center between 2013 and 2019. Cox proportional hazard models, Kaplan Meier curves, the long rank test and the area under the curve were implemented to compare the risk-stratification ability of the three models. Moreover, a hazard ratio plot was calculated to investigate the association between nodal yield and disease-free survival. Results231 patients were included. All three proposed N-models were significantly correlated to the patient's prognosis in the multivariate analysis. Pairwise comparisons between the groups showed that the current pN classification offers the worst stratification and that the model incorporating the number of positive lymph nodes had a better performance for predicting both endpoints. Finally, a decrease in hazard ratio was observed with each additional lymph node removed up to the number of 39 lymph nodes. ConclusionsThe model incorporating the nodal burden offered a better predictive ability. The current N-classification cannot adequately identify patients with different prognosis. A non-linear relationship was found between nodal yield and survival, which could be the disadvantage of the lymph node ratio and log odds models.

Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.

Prognostic significance of metastatic lymph node ratio in gastric cancer: a Western-center analysis

BackgroundTumor-node-metastasis (TNM) staging is the central gastric cancer (GC) staging system, but it has some disadvantages. However, the lymph node ratio (LNR) can be used regardless of the type of lymphadenectomy and is considered an important prognostic factor. This study aimed to evaluate the relationship between LNR and survival in patients who underwent curative GC surgery.MethodsAll patients who underwent radical gastric surgery between January 2014 and June 2022 were retrospectively evaluated. Clinicopathological features of tumors, TNM stage, and survival rates were analyzed. LNR was defined as the ratio between metastatic lymph nodes and total lymph nodes removed. The LNR groups were classified as follows: LNR0 = 0, 0.01 < LNR1 ≤ 0.1, 0.1 < LNR2 ≤ 0.25 and LNR3 > 0.25. Tumor characteristics and overall survival (OS) of the patients were compared between LNR groups.ResultsAfter exclusion, 333 patients were analyzed. The mean age was 62 ± 14 years. According to the LNR classification, no difference was found between groups regarding age and sex. However, TNM stage III disease was significantly more common in LNR3 patients. Most patients (43.2%, n = 144) were in the LNR3 group. In terms of tumor characteristics (lymphatic, vascular, and perineural invasion), the LNR3 group had significantly poorer prognostic factors. The Cox regression model defined LNR3, TNM stage II—III disease, and advanced age as independent risk factors for survival. Patients with LNR3 demonstrated the lowest 5-year OS rate (35.7%) (estimated mean survival was 30 ± 1.9 months) compared to LNR 0–1–2.ConclusionOur study showed that a high LNR was significantly associated with poor OS in patients who underwent curative gastrectomy. LNR can be used as an independent prognostic predictor in GC patients.

A novel trivalent non-Fc anti-CD3 Collabody preferentially induces Th1 cell apoptosis in vitro and long-lasting remission in recent-onset diabetic NOD mice.

Specific anti-CD3 treatment is deemed to be a promising therapy for allograft rejection and type 1 diabetes (T1D). Fc receptor (FcR) reduced-binding antibodies, by avoiding adverse effects of Fc and FcR interaction, have good therapeutic potential. We generated a trivalent anti-mouse-CD3 Collabody, h145CSA, by using a triplex-forming collagen-like peptide (Gly-Pro-Pro)10 to drive the trimerization of the Fab fragments. Exposure to h145CSA, but not its bivalent counterparts 145-2C11 and h145chIgGAA (FcR reduced-binding format), upregulates FasL expression on Th1 cells and causes Th1 cell apoptosis. Administration of h145CSA invokes minimal mitogenic effects in mice. The ability of multiple dosing of h145CSA to induce splenic CD4+ T-cell depletion is comparable to bivalent antibodies but is characterized by more rapid CD4+ T-cell recovery kinetics. h145CSA is more potent than h145chIgGAA in inducing long-lasting remission in recent-onset diabetic NOD mice. Its therapeutic effect is accompanied by a significantly lower percentage of CD4+IFNγ+ T cells and a higher Treg/Th1 ratio in pancreatic and mesenteric lymph nodes. The results of our study demonstrate that trivalent non-Fc anti-CD3 Collabody has the potential to be used in the treatment of T1D.

Ca 125 is an independent prognostic marker in resected pancreatic cancer of the head of the pancreas.

The prognostic value of carbohydrate antigen 125 (Ca 125) is emerging also in pancreatic cancer (PDAC). In this study, we aim to define the prognostic value of Ca 125 in resected PDAC of the head of the pancreas. This is a single-center, retrospective study. Data from patients with a pre-operative assay of Ca 125 who underwent a pancreatic resection for PDAC between 2010 and 2018 were analyzed. As per National Comprehensive Cancer Guidelines, tumors were classified in resectable (R-PDAC), borderline resectable (BR-PDAC), and locally advanced (LA-PDAC). The Kaplan-Meier method was used to evaluate the overall survival. Cox proportional hazard regression was used to evaluate the role of pre-operative Ca 125 in predicting survival (while adjusting for confounders). The maximally selected log-rank statistic was used to identify a Ca 125 cut-off defining two groups with different survival probability. Inclusion criteria were met by 207 patients (R-PDAC: 80, BR-PDAC: 91, and LA-PDAC: 36). Ca 125 predicted overall survival before and after adjusting for confounding factors in all categories of anatomic resectability (R-PDAC: HR = 4.3; p = 0.0249) (BR-PDAC: HR = 7.82; p = 0.0024) (LA-PDAC: HR = 11.4; p = 0.0043). In BR-PDAC and LA-PDAC (n = 127), the division in two groups (high vs. low Ca 125) correlated with T stage (p = 0.0317), N stage (p = 0.0083), mean LN ratio (p = 0.0292), and tumor grading (p = 0.0143). This study confirmed the prognostic value of Ca125 in resected pancreatic cancer and, therefore, the importance of biologic over anatomic resectability. Ca 125 should be routinely assayed in surgical candidates with PDAC.

Clinicopathological characteristics of HER2-low breast cancer: a retrospective study

Human Epidermal Growth Factor Receptor-2 (HER2)-negative breast cancers (BCs) contain HER2-low and HER2-zero ones. HER2-low breast cancer has been receiving wide-spread concerns as the marvelous effect of novel anti-HER2 antibody-drug conjugates, however, the characteristic remains unknown. Our aim was to explore the differences of clinicopathological indicators and survival outcomes between HER2-low and HER2-0 breast cancers. We retrospectively analyzed 501 invasive breast cancer patients with complete data on HER2 status from 2017 to 2021 in our single center, of whom 415 HER2 negative patients were included for subsequent analysis. Each cohort was further divided into hormone receptor (HR) positive and HR negative subgroup. Clinicopathological factors and survival outcomes were collected and compared between HER2-low BCs and HER2-0 BCs. HER2-low BCs was obviously higher in HR positive BCs, with 277 (90.5%) HER2-low HR positive patients, 29 (9.5%) HER2-low HR negative patients, 68 (62.4%) HER2-0 HR positive patients and 41 (37.6%) HER2-0 HR negative patients (P < 0.001). Significant differences between HER2-low BCs and Her2-0 BCs were observed in lymph node ratio (LNR) (mean rank, 215 vs. 188 P = 0.014), estrogen receptor (ER)expression (90.5% vs. 62.4% P < 0.001), progesterone receptor (PR) expression (84.3% vs. 56.9% P < 0.001), Ki-67 expression (46.4% vs. 61.5% P < 0.001), androgen receptor (AR) expression (68% vs. 50.5% P < 0.001), adjuvant chemotherapy (69% vs. 79.8% P = 0.03). HER2-low BCs had lower histological grade than HER2-0 BCs, with grade I–II (68.7% vs. 43.1%) and grade III (22.2% vs. 43.1%) P < 0.01. No statistical differences were detected between the two groups for DFS and DDFS. Our results demonstrated that HR and AR status was closely related to HER2-low breast cancers. Further exploration about survival prognosis of HER2-low breast cancer is badly needed.

HPV disrupt the cytoskeleton in oral squamous cell carcinomas from non-oropharyngeal sites via the E-cadherin/Mena/SMA pathway

In this paper, we aimed to evaluate the mechanism of actin cytoskeleton disruption, in oral squamous cell carcinoma (OSCC). A total of 43 patients with surgically resected OSCCs located in non-oropharyngeal regions were randomly selected. The expression of E-cadherin, β-catenin, smooth muscle actin (SMA), Mena, maspin, V-set and immunoglobulin domain containing 1 (VSIG1), β human chorionic gonadotropin (βhCG), and angiotensin-converting enzyme (ACE) was assessed via immunohistochemistry (IHC) and evaluated in association with the prevalence of high-risk human papillomavirus (HPV). Mena positivity (n = 30; 69.77%) was more frequent in poorly differentiated OSCC of the tongue and lips with high-risk HPV viral DNA and a lymph node ratio (LNR) ≤ 2.5. Loss of E-cadherin was more prevalent among poorly differentiated stage pT4N1 tumors with an LNR ≤ 2.5 and perineural invasion. These cases were classified as SMA-high tumors. Independent negative prognostic factors included high Mena expression, loss of E-cadherin, high SMA expression, and the presence of high-risk HPV. No VSIG1 positivity was observed. In conclusion, in non-oropharyngeal OSCC, cytoskeleton activity might be driven by the Mena/E-cadherin/SMA axis, reflecting active epithelial-mesenchymal interaction. High Mena intensity is an indicator of poorly differentiated carcinomas with high-risk HPV and unfavorable prognosis.

Combination of the Ratio Between Negative and Harvested Lymph Nodes and Metastatic Lymph Node Count as a Prognostic Indicator in Stage III Colon Cancer: A Retrospective Cohort Study.

This study aimed to investigate the relationship between the ratio of negative lymph nodes (NLN) number to the number of metastatic lymph nodes (MLN) and the harvested lymph nodes (HLN) number ratio survival rate and compare its prognostic value. This retrospective cohort study included 207 stage III colon cancer patients between 2010 and 2018 at a single center. NLN/MLN and NLN/HLN cut-off values were determined with the receiver operating characteristic (ROC) curve according to 5-year survival. The patients were divided into high-risk and low-risk groups according to the cut-off value. These 2 groups were evaluated according to the clinicopathological data of the patients. The time-dependent ROC curve showed the optimal cut-off values of NLN as 3.86 and .79, respectively. These values show 83 patients in the high-risk group and 124 in the low-risk group. There was no difference between the groups in tumor localization and T stage. According to Kaplan-Meier survival analysis, mean survival was 35.88 months in the high-risk group and 50.18 months in the low-risk group. The risk of death in the high-risk group was 305% compared to the low-risk group (Hazard Ratio: 3.05, 95% 1.91 - 4.88) (P < .001). NLNs are among the critical prognostic factors in colon cancer. Although NLNs have a positive correlation with the survival rate of the patients, there is no statistical difference in tumor T stage and localization.

Comparation between novel online models and the AJCC 8th TNM staging system in predicting cancer-specific and overall survival of small cell lung cancer.

Most of previous studies on predictive models for patients with small cell lung cancer (SCLC) were single institutional studies or showed relatively low Harrell concordance index (C-index) values. To build an optimal nomogram, we collected clinicopathological characteristics of SCLC patients from Surveillance, Epidemiology, and End Results (SEER) database. 24,055 samples with SCLC from 2010 to 2016 in the SEER database were analyzed. The samples were grouped into derivation cohort (n=20,075) and external validation cohort (n=3,980) based on America's different geographic regions. Cox regression analyses were used to construct nomograms predicting cancer-specific survival (CSS) and overall survival (OS) using derivation cohort. The nomograms were internally validated by bootstrapping technique and externally validated by calibration plots. C-index was computed to compare the accuracy and discrimination power of our nomograms with the 8th of version AJCC TNM staging system and nomograms built in previous studies. Decision curve analysis (DCA) was applied to explore whether the nomograms had better clinical efficiency than the 8th version of AJCC TNM staging system. Age, sex, race, marital status, primary site, differentiation, T classification, N classification, M classification, surgical type, lymph node ratio, radiotherapy, and chemotherapy were chosen as predictors of CSS and OS for SCLC by stepwise multivariable regression and were put into the nomograms. Internal and external validations confirmed the nomograms were accurate in prediction. C-indexes of the nomograms were relatively satisfactory in derivation cohort (CSS: 0.761, OS: 0.761) and external validation cohort (CSS: 0.764, OS: 0.764). The accuracy of the nomograms was superior to that of nomograms built in previous studies. DCA showed the nomograms conferred better clinical efficiency than 8th version of TNM staging system. We developed practical nomograms for CSS (https://guowei2020.shinyapps.io/DynNom-CSS-SCLC/) and OS (https://drboidedwater.shinyapps.io/DynNom-OS-SCLC/) prediction of SCLC patients which may facilitate clinicians in individualized therapeutics.