Recent Advances in Pancreatic Neoplasms

Pancreatic neoplasms include different pathological entities with variable biological behavior and different treatment modalities. Surgery and adjuvant therapy are the cornerstones of the therapeutic approach; however, even after radical resection, the majority of patients experience disease recurrence and the prognosis of pancreatic cancer remains dismal. A multimodal therapeutic approach, based on a combination of neoadjuvant therapy, chemotherapy, radiotherapy, immunotherapy and surgery, appears fundamental to improving the outcomes. This Special Issue of the Journal of Clinical Medicine, entitled “Recent Advances in Pancreatic Neoplasms”, focuses on possible new strategies to treat pancreatic neoplasms

Sarcopenia in Children With End-Stage Liver Disease on the Transplant Waiting List

Sarcopenia predicts morbidity and mortality in adults with end-stage liver disease (ESLD) and is determined by total psoas muscle area (tPMA) measurement from computed tomography (CT) imaging. Recently developed pediatric age- and sex-specific tPMA growth curves provide the opportunity to ascertain prevalence and impact of sarcopenia in children awaiting liver transplantation (LT). This retrospective single-center study evaluated sarcopenia in children between 1 and 16 years with ESLD and a clinically indicated abdominal CT less than 3 months before first isolated LT. Sarcopenia was defined as tPMA z score less than −2 measured at the intervertebral L4-5 level. Patient demographic, biochemical, and outcome data were recorded. tPMA was compared with other measures of nutritional status using univariate and multivariate logistic analyses. Outcome measures included 1-year morbidity events and mortality after LT. CT images from 25 (64% female) children with median age of 5.50 (interquartile range [IQR], 3.75-11.33) years were reviewed. Ten children (40%) had a tPMA z score less than −2. Sarcopenia was associated with lower z scores for weight (odds ratio [OR], 0.38; P = 0.02), height (OR, 0.32; P = 0.03), and nutritional support before LT (OR, 12.93; P = 0.01). Sarcopenic children had a longer duration of pediatric intensive care unit (PICU) stay (3.50 [IQR, 3.00-6.00] versus 2.00 [IQR, 2.00-3.50] days; P = 0.03). Sarcopenia was prevalent in 40% of children with ESLD awaiting LT, and lower tPMA z score was associated with deficient anthropometrics and need for nutritional support before LT. Post-LT PICU duration was increased in children with sarcopenia, reflecting adverse outcomes associated with muscle loss. Further studies are needed to elucidate the underlying mechanisms of sarcopenia in children with ESLD

PANCREATODUODENECTOMY FOR MALIGNANCY: FACTORS INFLUENCING SURGICAL AND ONCOLOGICAL OUTCOMES

Introduction: Fit patients with a resectable pancreatic head adenocarcinoma (PDAC), ampullary adenocarcinoma (AA) or distal cholangiocarcinoma (CC) may be offered pancreatoduodenectomy (PD) with curative-intent. However, perioperative morbidity and cancer recurrence rates are high. This thesis aimed to explore the factors influencing PD outcomes. A focus was placed on nutrition, postoperative complications, and recurrence in AA patients. It is hoped the findings will guide patient selection/consenting and have implications for patient management. Methods: A retrospective cohort study of patients who underwent PD for histologically-confirmed malignancy was carried out (2012-2015). Twenty-nine centres from eight countries were involved. Data on the following were collected: preoperative comorbidities and investigations, neoadjuvant treatment, operative details, postoperative complications, histology, adjuvant treatment, cancer recurrence, palliative treatment, and overall survival (OS). Results: In total, 1484 patients were included; 885 (59.6%), 394 (26.5%) and 205 (13.8%) had PDAC, AA and CC, respectively. Overall morbidity, major morbidity (Clavien-Dindo grade 11 ≥III) and 90-day mortality rates were 53.4%, 16.9% and 3.8%, respectively. A high body mass index (BMI), an American Society of Anesthesiologists (ASA) grade >II and a classic Whipple approach all correlated with morbidity. Additionally, ASA grade >II patients were at increased risk of major morbidity and a raised BMI correlated with a greater risk of pancreatic leak. Almost half of the cohort received nutritional support (NS). Of these, 55.6% received parenteral nutrition (PN). In total, 19.6% of the patients who had an uneventful postoperative recovery received PN. Among the PDAC cohort, commencing adjuvant chemotherapy (AC) correlated with improved OS, and those who experienced major morbidity commenced AC less frequently. Among the AA cohort, 176 patients (44.7%) developed recurrence and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). A higher number of resected nodes, histological T stage >II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin all correlated with AA recurrence. Further, ≥1 positive margin, PPFI and PNI were associated with reduced time-to-recurrence. Conclusions: A considerable number of the patients that had an uneventful recovery received PN. Patients with a high BMI or ASA grade had worse perioperative outcomes. Those who experienced major morbidity commenced AC less frequently. Numerous histopathological predictors of AA recurrence and reduced time-to-recurrence were identified

Improving Outcome in Gastrointestinal and Hepatopancreaticobiliary Surgical Oncology by Preoperative Risk Assessment and Optimization of Perioperative Care

This chapter discusses the most important challenges in the perioperative phase of the oncology patient undergoing surgery of the gastrointestinal tract. Because of the aging population, the surgeon is ever more confronted with frail patients at risk for an adverse surgical outcome. The chapter therefore reviews factors contributing to an impaired postoperative outcome such as sarcopenia, frailty, cachexia, and malnutrition and gives an insight into their pathophysiology. Next, it provides an overview of validated preoperative classification systems to identify the patients at risk for surgical complications. Furthermore, it discusses the most essential recommendations of standardized care for patients undergoing hepatopancreaticobiliary, gastric, and colorectal surgery. Special attention is paid to the use of clinical pathways in the perioperative phase that are aimed at a multimodal approach of reducing surgical morbidity by lowering the perioperative physiological and psychological stress. Recent literature is discussed regarding care in the intensive care unit, and the final paragraph focuses on improving postoperative outcome by means of prehabilitation or exercise as well as dietary interventions and optimized nutrition

The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature

Background There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes. Methods A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data. Results 201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation. Conclusion There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined

Fit for surgery? The impact of muscular and cardiopulmonary function on surgical outcomes after major abdominal surgery

Background: Poor physical function predicts outcomes after major abdominal surgery. The aim of this thesis is to assess the ability of perioperative patients’ function to prognose adverse surgical outcome and the efficacy of supervised pre-operative exercise programs to reduce adverse surgical outcomes. Methods: Reliability of ultrasound to measure Vastus Lateralis (VL) size, architecture and quality was assessed. Differences in VL size and quality between hepatobiliary surgery patients, old healthy adults and master athletes (MAs) were assessed. Ability of preoperative cardiopulmonary exercise testing, VL size, architecture and quality assessment, body composition using abdominal computed tomography scans, maximum isometric knee extension, rate of force development during maximum voluntary contraction (MVC) and changes in VL size and architecture during in-hospital recovery to prognose surgical outcome were assessed. Effectiveness of supervised pre-operative exercise programs to improve patient fitness and surgical outcome was assessed with a systematic review and meta-analysis. Results: Ultrasound images showed varying degrees of intra-rater (Intraclass correlation coefficient [ICC]≥0.824), inter-rater (ICC≥0.520) and inter machine (against magnetic resonance imaging) (ICC≥0.892) reliability. Pre-operative VL quality was lower in hepatobiliary surgery patients compared to healthy older adults and MAs (18.9±6.0, 26.7±4.9 and 28.3±7.0, respectively, p<0.001). Pre-operative low Psoas muscle index and high equivalents of carbon dioxide increased the risk of 3-years mortality (Hazard ratio [95% confidence interval]: 2.372 [1.246-4.515], p=0.009). Patients who performed two supervised exercise sessions per week before surgery showed higher six-minute walk distance (mean difference between groups [95%CI]: +47 [20-75] m., p<0.001) and lower relative risk (RR) of post-operative complications (RR [95%CI]: 0.59 [0.46-0.75], p<0.001) compared to patients following usual care (UC). Patients undergoing abdominal aortic aneurysms repair that performed a prehabilitation program showed similar peak oxygen uptake compared to UC group (mean difference between groups [95%CI]: 1.42 [0.51-2.34] ml·kg-1·min-1, p<0.001). Conclusion: Cardiopulmonary fitness and psoas muscle mass can predict long-term mortality. Two or more weekly supervised sessions are needed to improve fitness and surgical outcome

Predicting the severity of postoperative pancreatitis and postoperative pancreatic fistulae following major pancreatic resection

Postoperative pancreatic fistula (POPF) represents the leading cause of morbidity and mortality following partial pancreatectomy. Emerging evidence has challenged the traditional understanding of POPF and redefined its relationship to postoperative pancreatitis. The aim of this thesis was to synthesize the recent evidence, characterise the risk factors for postoperative pancreatitis and POPF, and to identify a prognostic indicator to facilitate the risk stratification of patients undergoing major pancreatic resection. Firstly, we evaluate established risk factors, including parameters that comprise the Fistula Risk Score. We then evaluate the utility of pancreatic enzyme concentrations in postoperative drain fluid to predict for clinically relevant fistulae. From these results, we propose lipase-to-amylase ratio as a novel predictor for clinically relevant POPF and demonstrate its correlation with acinar cell density at the pancreatic resection margin. Post-pancreatectomy acute pancreatitis (PPAP) has recently been recognized as a distinct postoperative complication. The second part of this thesis presents a validation study for the 2021 International Study Group on Pancreatic Surgery (ISGPS) consensus criteria for diagnosis and grading of PPAP. Our results support the utility of a universally accepted definition and the need for future studies to better characterise PPAP as a clinical entity. This work highlights key areas warranting further research and provides important insights into PPAP and POPF pathophysiology that should interest future investigators. Our findings lend further evidence to the importance of acinar cell density as an intrinsic risk factor, the role of PPAP in driving POPF pathogenesis, and the mechanisms of iatrogenic acinar cell injury that represent new targets for risk mitigation strategies