Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom.

PURPOSE: There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS: Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)-LNRS 1, complete response; 2, <10% residual tumor; 3, 10%-50% residual tumor; 4, >50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS: In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION: Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.

The Role of Circulating Protein and Metabolite Biomarkers in the Development of Pancreatic Ductal Adenocarcinoma (PDAC): A Systematic Review and Meta-analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and this is attributed to it being diagnosed at an advanced stage. Understanding the pathways involved in initial development may improve early detection strategies. This systematic review assessed the association between circulating protein and metabolite biomarkers and PDAC development. METHODS: A literature search until August 2020 in MEDLINE, EMBASE, and Web of Science was performed. Studies were included if they assessed circulating blood, urine, or salivary biomarkers and their association with PDAC risk. Quality was assessed using the Newcastle-Ottawa scale for cohort studies. Random-effects meta-analyses were used to calculate pooled relative risk. RESULTS: A total of 65 studies were included. Higher levels of glucose were found to be positively associated with risk of developing PDAC [n = 4 studies; pooled relative risk (RR): 1.61; 95% CI: 1.16-2.22]. Additionally, an inverse association was seen with pyridoxal 5'-phosphate (PLP) levels (n = 4 studies; RR: 0.62; 95% CI: 0.44-0.87). Meta-analyses showed no association between levels of C-peptide, members of the insulin growth factor signaling pathway, C-reactive protein, adiponectin, 25-hydroxyvitamin D, and folate/homocysteine and PDAC risk. Four individual studies also reported a suggestive positive association of branched-chain amino acids with PDAC risk, but due to differences in measures reported, a meta-analysis could not be performed. CONCLUSIONS: Our pooled analysis demonstrates that higher serum glucose levels and lower levels of PLP are associated with risk of PDAC. IMPACT: Glucose and PLP levels are associated with PDAC risk. More prospective studies are required to identify biomarkers for early detection.

Immune cell infiltrates as prognostic biomarkers in pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

Immune cell infiltration has been identified as a prognostic biomarker in several cancers. However, no immune based biomarker has yet been validated for use in pancreatic ductal adenocarcinoma (PDAC). We undertook a systematic review and meta-analysis of immune cell infiltration, measured by immunohistochemistry (IHC), as a prognostic biomarker in PDAC. All other IHC prognostic biomarkers in PDAC were also summarised. MEDLINE, EMBASE and Web of Science were searched between 1998 and 2018. Studies investigating IHC biomarkers and prognosis in PDAC were included. REMARK score and Newcastle-Ottawa scale were used for qualitative analysis. Random-effects meta-analyses were used to pool results, where possible. Twenty-six articles studied immune cell infiltration IHC biomarkers and PDAC prognosis. Meta-analysis found high infiltration with CD4 (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.51-0.83.) and CD8 (HR = 0.68, 95% CI = 0.55-0.84.) T-lymphocytes associated with better disease-free survival. Reduced overall survival was associated with high CD163 (HR = 1.62, 95% CI = 1.03-2.56). Infiltration of CD3, CD20, FoxP3 and CD68 cells, and PD-L1 expression was not prognostic. In total, 708 prognostic biomarkers were identified in 1101 studies. In summary, high CD4 and CD8 infiltration are associated with better disease-free survival in PDAC. Increased CD163 is adversely prognostic. Despite the publication of 708 IHC prognostic biomarkers in PDAC, none has been validated for clinical use. Further research should focus on reproducibility of prognostic biomarkers in PDAC in order to achieve this.

Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes.

This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.

Early and delayed presentation of traumatic small bowel injury.

Traumatic small bowel injury (TSBI) is rare and presents in only 1% of patients following blunt trauma. Delay in diagnosis can result in significant morbidity so a high index of suspicion is required in patients with abdominal injuries and a significant mechanism of injury. We discuss three cases of TSBI with varying presentations, and discuss their investigation and treatment.