The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Development of a T Cell Receptor Targeting an HLA-A*0201 Restricted Epitope from the Cancer-Testis Antigen SSX2 for Adoptive Immunotherapy of Cancer.

The clinical success of adoptive immunotherapy of cancer relies on the selection of target antigens that are highly expressed in tumor cells but absent in essential normal tissues. A group of genes that encode the cancer/testis or cancer germline antigens have been proposed as ideal targets for immunotherapy due to their high expression in multiple cancer types and their restricted expression in immunoprivileged normal tissues. In the present work we report the isolation and characterization of human T cell receptors (TCRs) with specificity for synovial sarcoma X breakpoint 2 (SSX2), a cancer/testis antigen expressed in melanoma, prostate cancer, lymphoma, multiple myeloma and pancreatic cancer, among other tumors. We isolated seven HLA-A2 restricted T cell receptors from natural T cell clones derived from tumor-infiltrated lymph nodes of two SSX2-seropositive melanoma patients, and selected four TCRs for cloning into retroviral vectors. Peripheral blood lymphocytes (PBL) transduced with three of four SSX2 TCRs showed SSX241-49 (KASEKIFYV) peptide specific reactivity, tumor cell recognition and tetramer binding. One of these, TCR-5, exhibited tetramer binding in both CD4 and CD8 cells and was selected for further studies. Antigen-specific and HLA-A*0201-restricted interferon-γ release, cell lysis and lymphocyte proliferation was observed following culture of TCR engineered human PBL with relevant tumor cell lines. Codon optimization was found to increase TCR-5 expression in transduced T cells, and this construct has been selected for development of clinical grade viral vector producing cells. The tumor-specific pattern of expression of SSX2, along with the potent and selective activity of TCR-5, makes this TCR an attractive candidate for potential TCR gene therapy to treat multiple cancer histologies

Longevity of a resin-modified glass ionomer cement and a polyacid-modified resin composite restoring non-carious cervical lesions in a general dental practice

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Long-term prospective survival studies of resin-modified glass ionomer cements (RMGICs) and polyacid-modified resin composites (compomers) placed in non-carious cervical lesions (NCCLs) are lacking from general dental practice. Short-term studies have shown an unsatisfactory clinical performance for several materials. Methods: One practitioner placed 87 compomer (Compoglass, Vivadent-Ivoclar) and 73 encapsulated RMGIC (Fuji II LC, GC Int.) restorations in NCCLs for 61 adults. Compoglass was placed using SCA primer and Fuji II LC using GC Dentin Conditioner. No cavity preparation was undertaken. The Kaplan-Meier method was used for estimating the cumulative survivals for those restorations that were replaced, with the probability level set at a=0.05 for statistical significance. Results: Restorations were judged unsatisfactory (by the practitioner and the subjects) because of surface and marginal loss of material (68.8 per cent), dislodgement (18.8 per cent) and discoloration (12.4 per cent), these modes being similar for both materials (P=0.35). Unsatisfactory restorations were replaced in 121 (75.6 per cent) instances. After periods of up to five years, cumulative survival estimates were 14.9 (5.8 Standard Error) per cent for Compoglass and zero per cent for Fuji II LC (P=0.74). Median survivals were 30 months for Compoglass and 42 months for Fuji II LC. Conclusion: Both materials had high long-term unsatisfactory performances when placed in non-prepared NCCLs in a general dental practice.RJ Smales and KKW N