Indeterminate Pulmonary Nodules in Resected Liver Metastases from Colorectal Cancer: A Comparison of Patient Outcomes.

AIMS: Hepatic metastasectomy remains the only potentially curative treatment for colorectal liver metastases (CRLM). Some of these patients develop indeterminate pulmonary nodules (IPNs). This study aimed to compare outcomes of patients with and without IPN undergoing resection of CRLM to ascertain whether their presence is clinically significant. METHODS: Cases and controls were identified from a prospectively maintained database of CRLM resections. Patients with staging radiology demonstrating IPNs were included as cases. Controls were matched to the cases by four primary factors: age, type of resection (primary or redo), clinical risk score (CRS) and chemotherapy. RESULTS: The median disease-free survival (DFS) and overall survival (OS) for the cases were 7.0 months (95% CI 4.8-9.2) and 28.6 months (95% CI 21.2-36.0), respectively, and 12.0 months (95% CI 10.7-13.2) and 30.5 months (95% CI 19.4-41.6) for the controls. The 1-, 3- and 5-year survival rates were 92.7, 39.7 and 0.0% for the IPN group, and 92.4, 32.9 and 21.9% for those without. In total, 60.7% of IPN patients progressed to lung metastases, of which 39.3% underwent pulmonary resections. DFS was significantly shorter in the IPN group (p = 0.022), but OS was not significantly different (p = 0.421). The presence of IPN was independently associated with a shortened DFS (p = 0.027), as was a CRS of 3 or greater (p = 0.007). CONCLUSION: This study suggests that IPN does not significantly affect OS, but may predict earlier disease recurrence. IPN presence alone should not preclude radical resection but could be used to prompt more careful post-operative surveillance to detect lung metastases at a potentially operable stage.

Imaging of indeterminate pancreatic cystic lesions: a systematic review.

BACKGROUND: Pancreatic cystic lesions are an increasing problem and investigation of these cysts can be fraught with difficulty. There is currently no gold standard for diagnosis or surveillance. This review was undertaken to determine the present reliability of the characterisation, assessment of malignant potential and diagnosis of pancreatic cystic lesions using available imaging modalities. METHODS: A Medline search using the terms 'pancreatic', 'pancreas', 'cyst', 'cystic', 'lesions', 'imaging', 'PET'. 'CT', 'MRI' and 'EUS' was performed. Publications were screened to include studies examining the performance of CT, MRI, MRCP, EUS and 18-FDG PET in the determination of benign or malignant cysts, cyst morphology and specific diagnoses. RESULTS: Nineteen studies were identified that met the inclusion criteria. 18-FDG PET had a sensitivity and specificity of 57.0-94.0% and 65.0-97.0% and an accuracy of 94% in determining benign versus malignant cysts. CT had a sensitivity and specificity of 36.3-71.4% and 63.9-100% in determining benign disease but had an accuracy of making a specific diagnosis of 39.0-44.7%. MRI had a sensitivity and specificity of 91.4-100.0% and 89.7% in assessing main pancreatic duct communication. CONCLUSION: CT is a good quality initial investigation to be used in conjunction with clinical data. MRCP can add useful information regarding MPD communication but should be used judiciously. PET may have a role in equivocal cases to determine malignancy. Further examination of CT-PET in this patient group is warranted.

Surgical therapy in chronic pancreatitis.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas which causes chronic pain, as well as exocrine and endocrine failure in the majority of patients, together producing social and domestic upheaval and a very poor quality of life. At least half of patients will require surgical intervention at some stage in their disease, primarily for the treatment of persistent pain. Available data have now confirmed that surgical intervention may produce superior results to conservative and endoscopic treatment. Comprehensive individual patient assessment is crucial to optimal surgical management, however, in order to determine which morphological disease variant (large duct disease, distal stricture with focal disease, expanded head or small duct/minimal change disease) is present in the individual patient, as a wide and differing range of surgical approaches are possible depending upon the specific abnormality within the gland. This review comprehensively assesses the evidence for these differing approaches to surgical intervention in chronic pancreatitis. Surgical drainage procedures should be limited to a small number of patients with a dilated duct and no pancreatic head mass. Similarly, a small population presenting with a focal stricture and tail only disease may be successfully treated by distal pancreatectomy. Long-term results of both of these procedure types are poor, however. More impressive results have been yielded for the surgical treatment of the expanded head, for which a range of surgical options now exist. Evidence from level I studies and a recent meta-analysis suggests that duodenum-preserving resections offer benefits compared to pancreaticoduodenectomy, though the results of the ongoing, multicentre ChroPac trial are awaited to confirm this. Further data are also needed to determine which of the duodenum-preserving procedures provides optimal results. In relation to small duct/minimal change disease total pancreatectomy represents the only valid surgical option for the treatment of pain. Though previously dismissed as a valid treatment due to the resultant brittle diabetes, the advent of islet cell autotransplantation has enabled this procedure to produce excellent long-term results in relation to pain, endocrine status and quality of life. Given these excellent short- and long-term results of surgical therapy for chronic pancreatitis, and the poor symptom control provided by conservative and endoscopic treatment (coupled to near inevitable progression to exocrine and endocrine failure), it is likely that future years will see a further shift towards the earlier and more frequent surgical treatment of chronic pancreatitis. Furthermore, the expansion of islet cell autotransplantation to a wider range of pancreatic resections has the potential to even further improve the outcomes of surgical treatment for this problematic yet increasingly common disease.

The prognostic value of circulating big endothelin-1 in patients undergoing potentially curative resection for colorectal cancer.

AIM: Elevated circulating endothelin-1 (ET-1) has been demonstrated in patients with colorectal cancer (CRC). The aim of this study was to examine the prognostic value of plasma big ET-1, the stable precursor of ET-1, in cancer-specific survival in patients having curative surgery for CRC. METHOD: Seventy-seven patients undergoing potentially curative surgery for CRC between January 2000 and January 2001 were studied. Clinicopathological data were obtained from a prospectively maintained database including long-term follow-up information (median follow up 84 months). The influence of plasma big ET-1 and clinicopathological variables upon over cancer-specific survival was determined by univariate and multivariable analysis. RESULTS: On univariate analysis, advanced Dukes' stage, tumour size and patient age were associated with shortened overall survival. Advanced Dukes' stage was the only factor associated with shortened survival on multivariable analysis. Plasma big ET-1 showed no association with either overall or cancer-specific survival following CRC resection. CONCLUSION: Plasma big ET-1 appears to have no prognostic value in primary CRC.

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

BACKGROUND: Serological 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. METHODS: Consecutive 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. RESULTS: Seventy-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 (p < 0.001). CONCLUSION: Preoperative NLR offers important prognostic information regarding disease-free survival following curative resection of pancreatic ductal adenocarcinoma.

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

BACKGROUND: In 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. METHODS: Data 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. RESULTS: Combined 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 100 days, 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. CONCLUSION: Combined 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.

Justifying the expense of the cancer Clinical Nurse Specialist.

In order to maximise patient care, assessment of the adequacy of the service provision by the Clinical Nurse Specialist (CNS) must be regularly undertaken. This study attempted to determine whether CNSs were providing an adequate service via retrospective and prospective audit. The results of a comprehensive audit of the work of the CNS within a tertiary referral Hepatobiliary Unit are presented. The audit involved postal and telephone questionnaires as well as prospective collection of data. The majority of responses from patients were positive, with many finding the CNS a useful and well-utilised contact. Overall, the CNSs performed well in each of their designated tasks; however, areas were still identified which could be further improved. Audit is essential in providing feedback to the CNS and to identify areas which require improvement. The CNS has evolved to meet a clinical gap in patient care, and as a result, the role of a CNS is frequently nebulous or poorly defined. This renders evaluation of the CNS problematic and fraught with difficulties. However, a thorough assessment can still be made using carefully constructed audit looking at each task of the CNS.

Cystic lesions of the pancreas. A diagnostic and management dilemma.

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. and IAP.

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 (P = 0.003). Platelet count and neutrophil-lymphocyte ratio (NLR) were also significantly different (P = 0.013 and P = 0.026, respectively). ROC analysis indicated that age < or =65, platelet count >297 x 10(9)/l, CA19.9 < or =473 Ku/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 (P = 0.031). 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.

Progression of early warning scores (EWS) in patients with acute pancreatitis: a re-evaluation of a retrospective cohort of patients.

INTRODUCTION: Early warning scores (EWS) is a physiological scoring system measured hourly. This study determined how progression of EWS affected outcome in acute pancreatitis. METHODS: The single worst EWS score for each 24 h period following admission was recorded for 110 patients with acute pancreatitis. Scores falling below 3 were defined as improving; scores which remained at 3 or rising were considered deteriorating. RESULTS: Deteriorating EWS values were associated with a greatly increased risk of mortality (p<0.001). All patients within the groups, who died, had an adverse outcome or had severe pancreatitis, demonstrated a failure to improve on a median admission EWS of >or=3 or a deterioration of their median EWS to above this. This progression occurred within 48 h of admission. Evaluating the progression of EWS (that is, improving or deteriorating scores) resulted in an improvement in the sensitivity and specificity in predicting adverse outcome, mortality or severe pancreatitis when compared to previously published data on EWS scores alone, on days 1 to 3 following admission. CONCLUSION: Deteriorating EWS values within the 48 h from admission are associated with adverse outcome or death in acute pancreatitis. Measuring progression of EWS over 72 h from admission can further improve accuracy of this monitoring system for acute pancreatitis.

Role of ultrasonography in the detection of resectable recurrence after hepatectomy for colorectal liver metastases.

BACKGROUND: Recurrence develops in most patients after hepatectomy for colorectal liver metastases. Repeat resection is feasible in some of these patients. The aim of this study was to evaluate an ultrasound-based follow-up protocol in the detection of resectable recurrent disease. METHODS: All patients undergoing hepatectomy for colorectal liver metastases at a single hepatobiliary referral centre in the UK from January 1999 to December 2004 were identified. Variables reviewed included rates of recurrence, mode and timing of detection, rates of repeat hepatectomy and survival. RESULTS: During the study period 191 patients underwent initial resection of colorectal liver metastases, of whom 109 developed recurrent disease. In total, 21 patients underwent potentially curative intervention, including 16 hepatic resections, four pulmonary resections and one staged pulmonary/hepatic resection. Ten of 72 patients who presented with recurrent disease within 12 months after initial resection were amenable to curative resection, compared with 11 of 37 patients presenting after 12 months. Sonographic surveillance identified all of the potentially resectable recurrent hepatic disease in the series. CONCLUSION: Ultrasonography is effective in the detection of potentially resectable hepatic recurrence after hepatectomy for colorectal liver metastases; however, routine chest imaging is needed.

Tumour characteristics predictive of survival following resection for ductal adenocarcinoma of the head of pancreas.

AIMS: We have maintained a highly conservative policy in selecting patients with carcinoma of the head of pancreas for resection. This has been based on tumour size, evidence of lymph node involvement or local invasion outside of the gland at laparotomy, laparoscopy or CT imaging. This study investigated our survival rates following pancreatic resection and examined clinicopathological predictors of survival. METHODS: Sixty-two consecutive patients undergoing pancreatic resections for malignancy were identified from 1999 onwards. Thirty-three underwent resection for pancreatic ductal adenocarcinoma and were included in our analysis, the remainder included resections for ampullary adenocarcinoma (n=20) or other malignancies (n=9). Patient, tumour and operative characteristics were analysed to assess predictors of survival following resection (Kaplan-Meier survival curves). RESULTS: Median survival following resection for ductal pancreatic adenocarcinoma was 54 months (ampullary adenocarcinomas achieved a median survival of 62 months) and thirty-day mortality was 2.7% (n=1). Survival was not associated with any demographic or intraoperative factors, such as blood loss, operative duration or anaesthetic technique. Survival curves were significantly worse when perineural or vascular invasion was evident histologically (p=0.023 and 0.0023 respectively). Patients with positive lymph nodes had a significantly shorter survival (p=0.0030) especially when lymph node status was expressed as a percentage of total lymph node yield. If more than 20% of retrieved lymph nodes were positive for tumour, this was a clear predictor of survival (p<0.0001). A positive resection margin was also associated with shortened survival (p=0.0291). CONCLUSION: Despite the advances made in the management of pancreatic cancer, tumour biology still dictates long-term survival. A highly selective surgical approach to the management of these patients results in good long-term survival.

Molecular prognostic markers in resectable colorectal liver metastases: a systematic review.

BACKGROUND: Determination of prognosis in patients with resectable colorectal liver metastases (CLM) is desirable in order to improve case selection for surgery and tailor adjuvant treatment according to individual recurrence risk. Conventional clinicopathological factors lack the sensitivity to accurately achieve this goal. Consideration of tumour biology and the identification of molecular prognostic markers may allow more accurate risk stratification. METHOD: This systematic review examines evidence from published manuscripts looking at molecular markers in resectable colorectal liver metastases and their correlation with disease recurrence and survival following hepatectomy. RESULTS: Studies have yielded promising results in the search for prognostic molecular markers of CLM. Molecular biomarkers from varied aspects of tumour biology have been examined and a number of these, including proliferation indices, telomerase, thymidylate synthase, microvessel density and thrombospondin-1 appear to have prognostic utility in this context. Validation of other markers, notably p53, has been limited by a failure of methodologies to account for their biological complexity. CONCLUSIONS: A biomarker-based approach may yield significant benefits through informed treatment of resectable metastatic colorectal malignancy. Standardised retrospective analyses are necessary to confirm preliminary findings and identify existing and novel markers for inclusion into prospective studies. Assessment and verification of multiple molecular markers in this manner may allow molecular profiling of metastases and tailoring of therapy according to the biological aggressiveness of individual tumours. The advent of genomic- and proteomic-based technologies will allow the simultaneous analysis of multiple molecular markers and the derivation of disease profiles associated with disease recurrence and poor survival.

Clinical aspects of natural anti-angiogenic drugs.

Natural products represent a rich resource for drug delivery and are currently being exploited to target tumour angiogenesis. A vast array of products of natural origin have been shown to have anti-angiogenic potential in preclinical models, including purified endogenous inhibitors, and exogenous compounds derived from varied species of plant, animal and micro-organism. Over a dozen of these agents have now entered clinical trial. This review discusses evidence for the efficacy of this drug class and key issues in the translation of pre-clinical results into the development of efficacious drugs for clinical use.

Changes in the Wnt signalling pathway in gastrointestinal cancers and their prognostic significance.

Many steps in the Wnt signalling pathway may be altered during the process of carcinogenesis. This Review focuses on the changes observed in gastrointestinal cancers. A literature search was undertaken and the currently available data summarised. Understanding the alterations to this signalling pathway may help to reveal future targets for therapeutic agents. In addition, since in some tumours, levels of components of the Wnt pathway have been found to correlate with clinical stage, their potential use as prognostic indicators is highlighted.

Molecular prognostic markers in pancreatic cancer: a systematic review.

Pancreatic cancer is one of the most lethal tumours of the gastrointestinal tract. The ability to predict which patients would benefit most from surgical intervention and/or chemotherapy would be a great clinical asset. Considerable research has focused on identifying molecular events in pancreatic carcinogenesis, and their correlation with clinicopathological variables of pancreatic tumours and survival. This systematic review examined evidence from published manuscripts looking at molecular markers in pancreatic cancer and their correlation with tumour stage and grade, response to chemotherapy and long-term survival. A literature search was undertaken using PubMed and MEDLINE search engines, using the keywords p53, p21, p16, p27, SMAD4, K-ras, cyclin D1, Bax, Bcl-2, EGFR, EGF, c-erbB2, HB-EGF, TGFbeta, FGF, MMP, uPA, cathepsin, heparanase, E-cadherin, laminins, integrins, TMSF, CD44, cytokines, angiogenesis, VEGF, IL-8, beta-catenin, DNA microarray, and gene profiling. A bewildering number of biomarkers are currently under evaluation. For the most part, the evidence regarding their application as prognostic indicators is conflicting. The advent of gene microarray and mass spectrometric protein profiling offers the potential to examine many different biomarkers simultaneously. This 'protein/gene signature' could revolutionise work in this field and allow researchers to develop accurate and reproducible predictions of survival based on protein or gene profiles.

Catecholamine inotropes as growth factors for Staphylococcus epidermidis and other coagulase-negative staphylococci.

Drugs commonly used in intensive care settings were assayed for their ability to affect the growth of Staphylococcus epidermidis in a minimal salts medium containing 30% serum. Of 28 compounds tested, the inotropic catecholamines adrenaline, dobutamine, dopamine, isoprenaline and noradrenaline significantly stimulated bacterial growth. These drugs, but not structurally similar compounds lacking a dihydroxybenzoyl moiety (such as tyramine, phenylephrine and salbutamol), were able to remove iron from iron-saturated transferrin and to supply transferrin-bound 55Fe to S. epidermidis cells. Similar results were observed with a range of coagulase-negative staphylococci associated with line infections, but not with Staphylococcus aureus (including MRSA).

Indications and outcomes for 100 patients managed with a pectoralis major flap within a UK maxillofacial unit.

There are few studies reporting the role of the pedicled pectoralis major (PPM) flap in modern maxillofacial practice. The outcomes of 100 patients (102 flaps) managed between 1996 and 2012 in a UK maxillofacial unit that preferentially practices free tissue reconstruction are reported. The majority (88.2%) of PPM flaps were for oral squamous cell carcinoma (SCC), stage IV (75.6%) disease, and there was substantial co-morbidity (47.0% American Society of Anesthesiologists 3 or 4). The PPM flap was the preferred reconstruction on 80.4% of occasions; 19.6% followed free flap failure. Over half of the patients (57%) had previously undergone major surgery and/or chemoradiotherapy. Ischaemic heart disease (P=0.028), diabetes mellitus (P=0.040), and methicillin-resistant Staphylococcus aureus (MRSA) infection (P=0.013) were independently associated with flap loss (any degree). Free flap failure was independently associated with total (2.0%) and major (6.9%) partial flap loss (P=0.044). Cancer-specific 5-year survival for stage IV primary SCC and salvage surgery improved in the second half (2005-2012) of the study period (22.2% vs. 79.8%, P=0.002, and 0% vs. 55.7%, P=0.064, respectively). There were also declines in recurrent disease (P=0.008), MRSA (P<0.001), and duration of admission (P=0.014). The PPM flap retains a valuable role in the management of advanced disease combined with substantial co-morbidity, and following free flap failure.

Oral and maxillofacial surgery "presentation hot spots" in the United Kingdom over the last decade from the BAOMS annual meetings.

The annual scientific meeting of the British Association of Oral and Maxillofacial Surgeons (BAOMS) is primarily a national meeting with a minor international contribution (3%). In the 10 years between 2002 and 2011 there were 1639 oral and poster presentations, and there was a significant increase in the total number of presentations (93-313, p<0.001). There have also been substantial increases in the proportion of poster (36-80%, p=0.005) and clinical presentations (88-94%, p=0.02). The 10 most productive units contributed roughly half of all UK presentations, whilst the top 5 deaneries contributed 61%. The trends in output by the most productive units are noted and the total output of units and deaneries within the United Kingdom (UK) is shown on a colour map. The information will be of value to trainees when considering the merits of a training unit and region.