C.P. Neal

Cystic Lesions of the Pancreas

Background/Aims: Due to enhanced imaging modalities, pancreatic cysts are being increasingly detected, often as an incidental finding. They comprise a wide range of differing underlying pathologies from completely benign through premalignant to frankly malignant. The exact diagnostic and management pathway of these cysts remains problematic and this review attempts to provide an overview of the pathology underlying pancreatic cystic lesions and suggests appropriate methods of management. Methods: A search was undertaken with a Pubmed database to identify all English articles using the keywords ‘pancreatic cysts’, ‘serous cystadenoma’, ‘intraductal papillary mucinous tumour’, ‘pseudocysts’, ‘mucinous cystic neoplasm’ and ‘solid pseudopapillary tumour’. Results: The mainstay of assessment of pancreatic cysts is cross-sectional imaging incorporating CT and MRI. Fine-needle aspiration (FNA) (often with endoscopic ultrasound) may provide valuable additional information but can lack sensitivity. Symptomatic cysts, increasing age and multilocular cysts (with a solid component and thick walls) are predictors of malignancy. A raised cyst aspirate CEA, CA 19-9 and mucin content (including abnormal cytology), if present, can accurately distinguish premalignant and malignant cysts from benign ones. Conclusion: In summary, all patients with pancreatic cystic lesions, whether asymptomatic or symptomatic, must be thoroughly investigated to ascertain the underlying nature of the cyst. Small asymptomatic cysts (<3 cm) with no suspicious features on imaging or FNA may be safely followed up. Follow-up should continue for at least 4 years, with a repeat FNA if needed. An algorithm for the management of pancreatic cystic tumours is also suggested.

Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma

BackgroundSerological proinflammatory markers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been associated with reduced survival for many different types of cancer. This study determined the prognostic value of the preoperative value of these markers in patients with resectable pancreatic adenocarcinoma.MethodsConsecutive patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were entered into our database from 2001 to the present day. CRP, NLR, and PLR at the time of presentation were recorded as well as overall and disease-free survival.ResultsSeventy-four patients were identified. Overall median survival was 35.0 months and median disease-free survival was 27.0 months. Follow-up ranged from 1 to 125.8 months. Preoperative NLR was significantly greater in those patients who developed recurrence in the follow-up period (4.5 vs. 3.1). CRP and PLR were not found to differ significantly between the two groups. Kaplan-Meier survival analysis of patients with NLR > 5 demonstrated a disease-free survival of 12 months compared with 52 months for those patients with NLR < 5 (pxa0<xa00.001).ConclusionPreoperative NLR offers important prognostic information regarding disease-free survival following curative resection of pancreatic ductal adenocarcinoma.

Prognostic performance of inflammation-based prognostic indices in patients with resectable colorectal liver metastases

AbstractnA range of prognostic cellular indices of the systemic inflammatory response, namely the neutrophil–lymphocyte ratio (NLR), derived NLR (dNLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), combination of platelet count and neutrophil–lymphocyte ratio (COP–NLR) and prognostic nutritional index (PNI), have been developed and found to have prognostic utility across varied malignancies. The current study is the first to examine the prognostic value of these six inflammatory scores in patients with resectable colorectal liver metastases (CRLM). Data from 302 consecutive patients undergoing surgery for resectable CRLM were evaluated. The prognostic influence of clinicopathological variables and the inflammatory scores NLR, dNLR, PLR, LMR, COP–NLR and PNI upon overall survival (OS) and cancer-specific survival (CSS) were determined by log-rank analysis and univariate and multivariate Cox regression analyses. High preoperative NLR was the only inflammatory variable independently associated with shortened OS (HR 1.769, 95xa0% CI 1.302–2.403, Pxa0<xa00.001) or CSS (HR 1.927, 95xa0% CI 1.398–2.655, Pxa0<xa00.001) following metastasectomy. When NLR was replaced by dNLR in analyses, high dNLR was independently associated with shortened OS (HR 1.932, 95xa0% CI 1.356–2.754, Pxa0<xa00.001) and CSS (HR 1.807, 95xa0% CI 1.209–2.702, Pxa0=xa00.004). The inflammatory scores PLR, LMR, COP–NLR and PNI demonstrated no independent association with either overall or cancer-specific survival in the study population. Our findings support high preoperative NLR and dNLR as independent prognostic factors for poor outcome in patients undergoing CRLM resection, with prognostic value superior to other cellular-based systemic inflammatory scores.

Clinical Risk Score predicts yield of staging laparoscopy in patients with colorectal liver metastases

Resection offers the only realistic chance of cure for hepatic colorectal metastases. The aim of this study was to examine the potential of laparoscopy and laparoscopic intraoperative ultrasonography (IOUS) for detecting incurable disease, and to determine whether the Clinical Risk Score (CRS) is useful in selecting patients for laparoscopy before hepatic resection.

Preoperative Early Warning Scores Can Predict In-Hospital Mortality and Critical Care Admission Following Emergency Surgery

BACKGROUNDnEWS is frequently used to monitor acute admissions requiring emergency surgery. This study examined preoperative early warning scoring (EWS) and its ability to predict mortality and critical care admission. Postoperative EWS was also evaluated as a predictor of mortality.nnnMETHODSnPreoperative EWS, age, physiologic and operative severity (POSSUM) scores, ASA grade, and serology were compared in 280 patients undergoing emergency surgery.nnnRESULTSnTwo hundred eighty patients were identified with a mortality of 15%. Among the physiological scoring systems, ASA grade and POSSUM scores were the best predictors of mortality (AUC values of 0.81). EWS, APACHE II, and age were the next best predictors (AUC values of 0.70). Postoperative APACHE II and EWS both predicted mortality. EWS on day 2 postoperatively was the best overall predictor of mortality of all the variables studied (AUC value of 0.83). Survival between patients with improving or stable EWS and those with deteriorating or failing to improve EWS was also found to be significantly different (P < 0.001). In addition, both EWS on admission and EWS 1 h preoperatively were found to predict critical care requirement postoperatively (AUC value of 0.78).nnnCONCLUSIONSnEWS can predict the need for critical care admission and mortality following emergency surgery. In particular, the progression of EWS preoperatively, that is, whether scores improve or deteriorate, is a highly significant factor in predicting survival following emergency surgery. These findings support the use of EWS in monitoring the acute surgical patient.

Surrogate Markers of Resectability in Patients Undergoing Exploration of Potentially Resectable Pancreatic Adenocarcinoma

Despite extensive preoperative staging, a significant number of pancreatic cancers are unresectable at surgical exploration. Patients undergoing pancreatic exploration with a view to resection were studied and comparisons are then made between those undergoing resection and a bypass procedure to identify surrogate markers of unresectability. One hundred thirteen consecutive patients underwent pancreatic exploration for head-of-pancreas (HOP) adenocarcinoma with curative intent. Fifty-five underwent pancreaticoduodenectomy and 58 underwent a bypass procedure. Student’s t test, receiver operator characteristics (ROC) and logistic regression were used to compare the predictive value of preoperative patient variables collected retrospectively. The bypass group had a significantly higher median CA19.9 than the resection group (Pu2009=u20090.003). Platelet count and neutrophil–lymphocyte ratio (NLR) were also significantly different (Pu2009=u20090.013 and Pu2009=u20090.026, respectively). ROC analysis indicated that age ≤65, platelet count >297u2009×u2009109/l, CA19.9 ≤473xa0Ku/l, and CA19.9–bilirubin ratio were predictive variables for resectable disease. NLR and CA19.9–bilirubin ratio had specificity values of 92.9 and 97.0%, respectively. From logistic regression, a raised CA19.9 was found to be an independent risk factor for unresectable disease (Pu2009=u20090.031). A significant proportion of patients with HOP adenocarcinoma are understaged preoperatively. Preoperative serology including platelet count, NLR, CA19.9, and CA19.9–bilirubin ratio may be used as additional discriminators of resectability particularly for high-risk patients.

Early Warning Scores Predict Outcome in Acute Pancreatitis

The Early Warning Score (EWS) is a widely used general scoring system to monitor patient progress with a varying score of 0-20 in critically unwell patients. This study evaluated the EWS system compared with other established scoring systems in patients with acute pancreatitis. EWS scores were compared with APACHE scores, Imrie scores, computed tomography grading scores, and Ranson criteria for 110 admissions with acute pancreatitis. A favorable outcome was considered to be survival without intensive therapy unit admission or surgery. Nonsurvivors, necrosectomy, and critical care admission were considered adverse outcomes. EWS was the best predictor of adverse outcome in the first 24 hours of admission (receiver operating curve, 0.768). The most accurate predictor of mortality overall was EWS on day 3 of admission (receiver operating curve, 0.920). EWS correlated with duration of intensive therapy unit stay and number of ventilated days (P<0.05) and selected those who went on to develop pancreas-specific complications such as pseudocyst or ascites. EWS of 3 or above is an indicator of adverse outcome in patients with acute pancreatitis. EWS can accurately and reliably select both patients with severe acute pancreatitis and those at risk of local complications.

Chemoprevention of Pancreatic Cancer: A Review of the Molecular Pathways Involved, and Evidence for the Potential for Chemoprevention

Background: Pancreatic cancer has a poor prognosis. The use of drugs or natural agents which inhibit or slow down tumour growth therefore has important potential in the development of future therapies. Methods: A literature search of the PubMed and ISI Web of Science databases was undertaken to review the current data available on the alterations in signalling pathways found in pancreatic carcinogenesis, in order to identify sites that could be targeted by chemopreventive agents. Several agents of particular relevance to pancreatic cancer were identified, and their possible mechanisms of action reviewed. Results: Chemopreventive agents such as non-steroidal anti-inflammatory drugs, green tea constituents, and antioxidants have been shown to target various steps in intracellular signalling pathways, particularly those controlling cell proliferation and survival. Work on cell lines and animal models has shown that some of these agents may be able to modulate the growth of pancreatic tumours. Initial clinical trials of some chemopreventives in pancreatic cancer have been undertaken, and have yielded mixed results, prompting the need for further studies. Conclusion: As the molecular pathology of pancreatic cancer becomes better understood, sites of action of chemopreventive substances have been uncovered. Several agents have shown promising results by their ability to inhibit pancreatic carcinogenesis in laboratory studies. If these effects can be successfully translated into human studies then these agents may prove to be valuable adjuvant therapies in the future.

Combined percutaneous–endoscopic stenting of malignant biliary obstruction: results from 106 consecutive procedures and identification of factors associated with adverse outcome

BackgroundIn patients in whom attempted endoscopic stenting of malignant biliary obstruction fails, combined percutaneous–endoscopic stenting and percutaneous stenting using expandable metallic endoprostheses offer alternative approaches to biliary drainage. Despite the popularity of the percutaneous route, there is no available evidence to support its superiority over combined stenting in this patient group. The objective of this study was to present the short- and long-term results of a large series of combined percutaneous–endoscopic stenting procedures and identify factors associated with adverse outcome. MethodsData were retrospectively collected on patients undergoing combined percutaneous–endoscopic biliary stenting for malignant biliary obstruction between January 2002 and December 2006. Short- and long-term outcomes were recorded, and pre-procedure variables correlated with adverse outcome. ResultsCombined biliary stenting was technically successful in 102 (96.2%) of 106 patients. Procedure-associated mortality rate was 0%. In-hospital morbidity and mortality rates were 24.5% and 16.7%, respectively, with the majority of deaths resulting from biliary sepsis. Median survival was 100xa0days, with a 13.7% stent occlusion rate. On multivariable analysis, baseline American Society of Anaesthesiologists (ASA) grade, decreasing serum albumin and increasing leucocyte count were independently associated with in-hospital mortality following combined stenting. ConclusionCombined biliary stenting is associated with short- and long-term outcomes equal to those reported in recent series of percutaneous transhepatic stenting. Randomised control trials, including cost-effectiveness analyses, are required to further compare these techniques. Outcomes following combined stenting may be further improved by early recognition and treatment of sepsis and scrupulous management of co-morbid disease.

Combined biliary and gastric bypass procedures as effective palliation for unresectable malignant disease

Background:u2002 Although endoscopic treatment of jaundice is increasingly used in the palliation of unresectable malignant disease, surgical bypass still has a role to play in this setting. This study aimed to reappraise the short‐term and long‐term results of combined biliary/gastric bypass (hepaticojejunostomy and gastrojejunostomy) as palliation for unresectable malignant disease.