Adverse impact of tumor deposits in lymph node negative rectal cancer - a national cohort study.

PURPOSE: This study aimed to investigate the prognostic effect of tumor deposits (TDs) in lymph node negative rectal cancer. METHODS: Patients who had undergone surgery for rectal cancer with curative intention between 2011 and 2014 were extracted from the Swedish Colorectal Cancer Registry. Patients with positive lymph nodes, undisclosed TD status, stage IV disease, non-radical resections, or any outcome (local recurrence (LR), distant metastasis (DM) or mortality) within 90 days after surgery were excluded. TDs status was based on histopathological reports. Cox-regression analyses were used to examine the prognostic impact of TDs on LR, DM, and overall survival (OS) in lymph node-negative rectal cancer. RESULTS: A total of 5455 patients were assessed for inclusion of which 2667 patients were analyzed, with TDs present in 158 patients. TD-positive patients had a lower 5-year DM-free survival (72.8%, p < 0.0001) and 5-year overall survival (75.9%, p = 0.016), but not 5-year LR-free survival (97.6%) compared to TD-negative patients (90.2%, 83.1% and 95.6%, respectively). In multivariable regression analysis, TDs increased the risk of DM [HR 4.06, 95% CI 2.72-6.06, p < 0.001] and reduced the OS [HR 1.83, 95% CI 1.35-2.48, p < 0.001]. For LR, only univariable regression analysis was performed which showed no increased risk of LR [HR 1.88, 95% CI 0.86-4.11, p = 0.11]. CONCLUSION: TDs are a negative predictor of DM and OS in lymph node-negative rectal cancer and could be taken into consideration when planning adjuvant treatment.

N1c colon cancer and the use of adjuvant chemotherapy: a current audit of the National Cancer Database.

AIM: Colorectal cancer staging has evolved to define N1c as the presence of tumour deposits without concurrent positive lymph nodes. Work to date reports poor prognosis in N1c colon cancer, with Stage III categorization and adjuvant chemotherapy (AC) recommended. No study has yet evaluated the prevalence, treatment compliance or treatment-related outcomes on a national scale. We aimed to evaluate the prevalence of N1c colon cancer, use, outcomes and factors associated with AC in the USA. METHOD: The National Cancer Database was reviewed for N1cM0 colon adenocarcinomas that underwent resection from 2010 to 2016. Cases were stratified into 'AC' or 'no AC' cohorts. The Kaplan-Meier method was used to estimate overall survival (OS) and compare the AC and no AC cohorts using the log-rank test. Multivariable logistic regression identified factors associated with AC. The main outcome measures were the prevalence and factors associated with AC use and its impact in N1c disease. RESULTS: Of the 5684 (1.59% of 357 752) colon adenocarcinomas that were N1c, 55% (n = 3071) received AC. AC significantly improved 1-, 3- and 5-year OS compared with no AC (96.2%, 80%, 67.4% and 72.9%, 48.5%, 33.8%, respectively; P < 0.001). Compared with the no AC group, AC patients were younger, had less comorbidity, were of the male gender and received minimally invasive surgery at an academic treatment centre (all P < 0.05). Socioeconomic and procedural factors significantly impacted the use of AC. CONCLUSION: In the USA, AC is underutilized in N1c colon cancer despite significantly improved OS. Socioeconomic and procedural factors associated with AC were identified, highlighting disparities in AC use and opportunities to improve oncological outcomes and survival.

Prognostic value of tumor deposits in rectal cancer: A monocentric series of 505 patients.

BACKGROUND AND OBJECTIVES: It has been suggested that tumor deposits (TDs) may have a worse prognosis in rectal cancer compared with colonic cancer. The aim of this study was to assess TDs prognosis in rectal cancer. METHODS: Patients who underwent total mesorectum excision for rectal adenocarcinoma (2011-2016) were included. A case-matched analysis was performed to assess the accurate impact of TDs for each pN category after exclusion of synchronous metastasis. RESULTS: A total of 505 patients were included. TDs were observed in 99 (19.6%) patients, (pN1c = 37 [7.3%]). TDs were associated with pT3-T4 stage (P = .037), synchronous metastasis (P = .003), lymph node (LN) invasion (P = .041), vascular invasion (P = .001), and perineural invasion (P < .001). TD was associated with a worse 3-year disease-free survival (DFS) among pN0 (51.2% vs 79.8%; P < .001); pN1 patients (35.2% vs 70.1%; P = .004) but not among pN2 patients (37.5% vs 44.7%; P = .499). After matching, pN1c patients had a worse 3-year DFS compared with pN0 patients (58.6% vs 82.4%; P = .035) and a tendency toward a worse DFS among N1 patients (40.1% vs 64.2%; P = .153). DFS was worse when one TD was compared with one invaded LN (40.8% vs 81.3%; P < .001). CONCLUSION: In rectal cancer, TDs have a metastatic risk comparable to a pN2 stage which may lead to changes in adjuvant treatment.

Prognostic value of N1c in colorectal cancer: a large population-based study using propensity score matching.

PURPOSE: We conducted this large population-based study to investigate the prognostic significance of N1c. METHODS: Patients diagnosed with colorectal cancer from the surveillance, epidemiology, and end results (SEER) database between January 1, 2010, and December 31, 2010, were included in the sample. The primary outcome of interest used in our study was cause-specific survival (CSS). Cox proportional hazards models and Kaplan-Meier methods were used to evaluate the prognostic value of N1c. Propensity score matching (PSM) was implemented to reduce the possibility of selection bias using a logistic regression model. RESULTS: A total of 19,991 patients diagnosed with colorectal cancer were identified from the SEER database. The median follow-up time of the whole cohort was 60 months (0-71 months). Multivariate Cox analysis showed that N1c was associated with significantly higher risk of colorectal cancer-specific mortality compared with N0 (HR = 1.962, 95%CI = 1.642 to 2.343, P < 0.001) and N1a (HR = 0.818, 95%CI = 0.678 to 0.987, P = 0.036); N1c was associated with significantly lower risk of colorectal cancer-specific mortality compared with N2a (HR = 1.296, 95%CI = 1.081 to 1.554, P = 0.005) and N2b (HR = 1.663, 95%CI = 1.391 to 1.989, P < 0.001). Yet the CSS difference between N1b and N1c did not achieve statistical difference (HR = 1.089, 95%CI = 0.909 to 1.304, P = 0.354). CONCLUSIONS: The large population-based and propensity score-matched study with long follow-up time provides the first evidence that CSS difference between N1b and N1c does not achieve a statistical difference.

Prognostic value and characteristics of N1c colorectal cancer.

AIM: The presence of tumour deposits (TDs) in colorectal cancer (CRC) is associated with poor prognosis. The seventh edition of TNM subclassified a new nodal stage, N1c, characterized by the presence of TDs without any concurrent positive lymph node (LN). It is not clear if the N1c category is or is not equal to LN metastasis. We aimed to examine the prevalence, characteristics and prognostic significance of this new subcategory. METHOD: Consecutive patients who underwent surgery for CRC in two centres (2011-2014) were analysed. N1 cM0 patients were matched against non-N1 cM0 (N0, N1a and N1b) patients for 3-year overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 1122 patients with 648 (57.8%) colonic cancers. In 57 patients (5.1%), N1c status was associated with rectal cancers [rectum = 33/57 (57.9%) vs colon = 24/57 (42.1%); P = 0.029], a higher pathological tumour stage [pT3-T4 N1c = 55/843 (6.5% vspT3-T4 non-N1c = 2/279 (0.7%); P < 0.0001] and vascular emboli [n = 35 (61.4%) vs n = 552 (51.8%); P = 0.0305]. Synchronous metastasis was observed in 23 cases (40%). After a mean follow-up of 31 months, 3-year OS for M0 patients, was 89.4%, 89.1%, 86.6% and 81.8% for N0, N1a, N1b and N1c tumours, respectively. DFS was significantly worse for N1c than for N0 (P = 0.0169), with N1c status having a significant effect on DFS in colonic cancers (P = 0.014). The presence of more than one TD was associated with a significantly worse DFS (P = 0.021). CONCLUSION: Our results indicate that N1c CRC patients should be included among high-risk patients for whom it is widely accepted that adjuvant chemotherapy should be considered.

Atomically Dispersed Pd-N1C3 Sites on a Nitrogen-Doped Carbon Nanosphere for Semi-hydrogenation of Acetylene.

Rationally designing efficient catalysts for semi-hydrogenation of acetylene is significant but challenging. Herein, Pd isolated single-atom sites (ISAS) on a covalent-organic-framework (COF)-derived nanosphere (Pd-ISAS/CN) are synthesized by a COF-absorption-pyrolysis strategy. This synthetic strategy is also applicable for Pt and Ru ISAS catalysts, demonstrating that it is a general method to synthesize noble-metal ISAS on COF-derived carbon materials. Pd-ISAS/CN exhibits outstanding reactivity and high selectivity for semi-hydrogenation of acetylene, with 92% conversion of acetylene, 80% selectivity toward ethylene at 100 °C, and corresponding activity is as high as 712 molacetylene molmetal-1 h-1. Extended X-ray absorption fine structure (EXAFS) measurement and density functional theory (DFT) calculation reveal the Pd-N1C3 sites from Pd-ISAS/CN efficiently boost the reactivity for semi-hydrogenation of acetylene. This work will bring inspiration to rationally design noble-metal-based ISAS catalysts derived from COF materials and boost catalytic performance by optimizing the coordination environment of catalytic sites.

Symmetry-Breaking p-Block Antimony Single Atoms Trigger N-Bridged Titanium Sites for Electrocatalytic Nitrogen Reduction with High Efficiency.

The electrochemical nitrogen reduction reaction (eNRR) under mild conditions emerges as a promising approach to produce ammonia (NH3) compared to the typical Haber-Bosch process. Herein, we design an asymmetrically coordinated p-block antimony single-atom catalyst immobilized on nitrogen-doped Ti3C2Tx (Sb SA/N-Ti3C2Tx) for eNRR, which exhibits ultrahigh NH3 yield (108.3 µg h-1 mgcat-1) and excellent Faradaic efficiency (41.2%) at -0.3 V vs RHE. Complementary in situ spectroscopies with theoretical calculations reveal that the nitrogen-bridged two titanium atoms triggered by an adjacent asymmetrical Sb-N1C2 moiety act as the active sites for facilitating the protonation of the rate-determining step from *N2 to *N2H and the kinetic conversion of key intermediates during eNRR. Moreover, the introduction of Sb-N1C2 promotes the formation of oxygen vacancies to expose more titanium sites. This work presents a strategy for single-atom-decorated ultrathin two-dimensional materials with the aim of simultaneously enhancing NH3 yield and Faradaic efficiency for electrocatalytic nitrogen reduction.