Neoadjuvant therapy for pancreatic cancer changes the composition of the pancreatic parenchyma.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a prominent complication following pancreatic cancer resections. The primary aim of this study was to evaluate the histological changes that occur in the pancreas due to neoadjuvant therapy (NAT) by comparing the acinar, collagen and fat scores in resected PDAC specimens of patients who did and did not receive NAT. Secondary aims included (1) the difference in rates of POPF in PDAC patients who received NAT versus upfront resection; and (2) the association between acinar/collagen/fat scores and the development of POPF. METHODS: Consecutive patients who underwent pancreaticoduodenectomy for PDAC, with and without NAT were included for analysis. Acinar, collagen and fat scores were determined from histology slides of the pancreatic resection margin. RESULTS: One hundred and thirty-four patients were included. There was a significant decrease in the median acinar score (48 vs 23, p = 0.003) and increase in the collagen score (28 vs 50, p = 0.011) for patients who received NAT and a significant correlation with the number of cycles of NAT. This study found no statistical difference between NAT and the development of POPF. CONCLUSION: The use of NAT in the treatment of PDAC changes the composition of the pancreas.

Non-Surgical Interventions for the Prevention of Clinically Relevant Postoperative Pancreatic Fistula-A Narrative Review.

Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor.

Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula: a diagnostic accuracy systematic review and meta-analysis.

BACKGROUND: Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis. METHODS: Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies. RESULTS: Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1. CONCLUSIONS: The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes.

Drain fluid biomarkers for prediction and diagnosis of clinically relevant postoperative pancreatic fistula: A narrative review.

Clinically relevant postoperative pancreatic fistula (CR-POPF) has continued to compromise patient recovery post-pancreatectomy despite decades of research seeking to improve risk prediction and diagnosis. The current diagnostic criteria for CR-POPF requires elevated drain fluid amylase to present alongside POPF-related complications including infection, haemorrhage and organ failure. These worrying sequelae necessitate earlier and easily obtainable biomarkers capable of reflecting evolving CR-POPF. Drain fluid has recently emerged as a promising source of biomarkers as it is derived from the pancreas and hence, capable of reflecting its postoperative condition. The present review aims to summarise the current knowledge of CR-POPF drain fluid biomarkers and identify gaps in the field to invigorate future research in this critical area of clinical need. These findings may provide robust diagnostic alternatives for CR-POPF and hence, to clarify their clinical utility require further reports detailing their diagnostic and/or predictive accuracy.