Joe Buttler

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Discussion About Precision Oncology In Vascular Surgery

Although molecular markers are being used more frequently to select patients for systemic targeted agents, only imaging modalities are used to stage patients and assess suitability for operative resection. Decisions on primary surgery or a neoadjuvant approach are made without biological measures of tumor aggressiveness, or the risk of occult metastatic disease. This is exemplified in pancreatic ductal adenocarcinoma (PDAC), which has overtaken breast cancer to become the third most common cause of cancer death in the USA. An online paper writing service offers an original surgical papers crafted by our professional essay writers.

 Surgical resection offers the only chance of cure, with chemotherapy adding modest benefit, but surgery can be associated with significant morbidity and mortality risk. Even with complete resection and adjuvant chemotherapy, the 5-year survival rate is only approximately 20% with approximately 30% succumbing within the first year (mostly due to distant metastatic disease). This high metastatic recurrence rate indicates current staging modalities for PDAC cannot identify patients with occult metastases and aggressive biology. For these patients, surgical resection brings uncertain benefit.

Whipple pancreaticoduodenectomy can be associated with significant mortality risk and morbidity that leads to long postoperative recovery periods of 3 to 6 months, which presents significant implications on patients’ quality of life.9 Hence, better selection methods are urgently needed.

Prognosis prediction tools such as nomograms have been developed for many cancer types to better inform treatment decisions. The most widely used tool in resectable PDAC is the prognostic nomogram developed at the Memorial Sloan-Kettering Cancer Center (MSKCC). These, however, can only be applied after resection as they include clinicopathological variables only available following assessment of the resected specimen.

Numerous molecular biomarkers with potential clinical utility have been studied in PDAC, but few have been independently validated. Our group and others have demonstrated that aberrant expression of S100A2 and S100A4 calcium-binding proteins, both of which function to accentuate tumor aggressiveness and metastasis, are associated with poor survival in PDAC. Using RNA sequencing and methylation arrays, we recently reported hypomethylation of S100A2 is associated with the prognostic “Squamous” subtype of PDAC. This poor prognostic subtype is consistently defined in molecular classifications of PDAC and S100A2 remains a highly significant gene in each classifier.

Here, we assess and validate the prognostic value of these 2 molecules in 1184 patients. Aberrant expression of these biomarkers stratify patients with resectable pancreatic cancer into 3 distinct prognostic groups in a training set (n = 518) and form the basis of a biomarker-based preoperative nomogram aimed at identifying those at high risk of early recurrence. This nomogram was validated in 2 further cohorts (n = 198 and 468), and the proof-of-concept feasibility of its preoperative use was assessed using preoperative endoscopic ultrasound fine-needle aspiration (EUS-FNA) biopsies. Always choose the best write my paper service that guarantees timely delivery.


Patients and Tissue Specimens

Detailed clinicopathological and outcome data were obtained for 3 cohorts of consecutive unselected patients, totaling 1184, with primarily resected PDA. None of the patients received neoadjuvant chemo- or radiotherapy. All cohorts displayed clinical and pathological features consistent with the behavior of PDAC and are similar to published PDAC cohorts worldwide. 

The diagnosis and all pathological features were reviewed centrally by at least 1 specialist pancreatic histopathologist, and the date and cause of death were obtained from Central Cancer Registries or treating clinicians. RNA sequencing data were generated as part of the APGI's contribution to the ICGC, and sample processing and data analysis was performed as previously described.