Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/− axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients

Multilayered Porous Titanium-Based 3rd Generation Biomaterial Designed for Endosseous Implants

This work proposes a novel complex multi-layered material consisting of porous titanium as a substrate and a complex coating consisting of a chitosan film engulfing microsphere loaded with growth factors such as BMP2 (bone morphogenic protein 2) and IGF1 (insulin-like growth factor-1). The microspheres were obtained through deposition of dual layers of calcium cross linked pectin–chitosan/pectin polyelectrolyte onto a BSA (bovine serum albumin) gel core. The multilayer was conceived to behave like a 3rd generation biomaterial, by slow delivery of viable growth factors around implants, and to assist the healing of implantation wound and the development of new vital bone. The biologic effect of the delivery of growth factors was studied in vitro, on MSC-CD1 mesenchymal stem cells, and in vivo, on CD1 mice. Proliferation and differentiation of cells were accelerated by growth factors, especially IGF1 for proliferation and BMP2 for differentiation. In vivo tests analyzed histologically and by MicroCT show a more structured tissue around BMP2 samples. The present concept will give the best clinical results if both growth factors are delivered together by a coating film that contains a double population of microcarriers

Preventing Breast Cancer-Related Lymphedema: Feasibility of Axillary Reverse Mapping Technique

Introduction. Our study aimed to determine the feasibility of axillary reverse mapping (ARM) technique, the identification rate of ARM nodes and their metastatic involvement, as well as to identify the factors that influence the identification and metastatic involvement. Material and methods. In total, 30 breast cancer patients scheduled for axillary lymph node dissection were enrolled in our study. The lymphatic nodes that drain the arm were identified by injecting 1 mL of blue dye in the ipsilateral upper arm; then, the ARM nodes were resected along with the other lymph nodes and sent for histological evaluation. Results. Identification of ARM node was successful in 18 patients (60%) and 22.22% of the identified ARM lymph nodes had metastatic involvement. Patients with identified ARM nodes had a significant lower BMI and a statistically significant relationship between axillary lymph node status and ARM node metastases was proven. Most of ARM lymph nodes (96.3%) were found above the intercostobrachial nerve, under the axillary vein and lateral to the thoracodorsal bundle. Conclusions. The ARM procedure is easy to reproduce but might not be appropriate for patients with a high BMI. The rate of metastatic involvement of ARM nodes is significant and no factor can predict it, showing that the preservation of these nodes cannot be considered

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)