Hepatic Resection Following Selective Internal Radiation Therapy for Colorectal Cancer Metastases in the FOXFIRE Clinical Trial: Clinical Outcomes and Distribution of Microspheres.

The FOXFIRE (5-Fluorouracil, OXaliplatin and Folinic acid ± Interventional Radio-Embolisation) clinical trial combined systemic chemotherapy (OxMdG: Oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radio-embolisation) using yttrium-90 resin microspheres in the first-line management for liver-dominant metastatic colorectal cancer (CRC). We report clinical outcomes for patients having hepatic resection after this novel combination therapy and an exploratory analysis of histopathology. Multi-Disciplinary Teams deemed all patients inoperable before trial registration and reassessed them during protocol therapy.

Curcumin inhibits cancer stem cell phenotypes in ex vivo models of colorectal liver metastases, and is clinically safe and tolerable in combination with FOLFOX chemotherapy.

In vitro and pre-clinical studies have suggested that addition of the diet-derived agent curcumin may provide a suitable adjunct to enhance efficacy of chemotherapy in models of colorectal cancer. However, the majority of evidence for this currently derives from established cell lines. Here, we utilised patient-derived colorectal liver metastases (CRLM) to assess whether curcumin may provide added benefit over 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) in cancer stem cell (CSC) models.

Combining curcumin (C3-complex, Sabinsa) with standard care FOLFOX chemotherapy in patients with inoperable colorectal cancer (CUFOX): study protocol for a randomised control trial.

Background: The need for low toxicity adjuncts to standard care chemotherapy in inoperable colorectal cancer, with potential to improve outcomes and decrease the side-effect burden, is well recognised. Addition of the low toxicity diet-derived agent, curcumin (the active ingredient of turmeric), to standard oxaliplatin-based therapy has shown promise in numerous pre-clinical studies.

Methods/design: This study is the first to combine daily oral curcumin with standard care FOLFOX-based (5-fluorouracil, folinic acid and oxaliplatin) chemotherapy in colorectal cancer patients with inoperable liver metastases: the CUFOX trial.

Characterization and propagation of tumor initiating cells derived from colorectal liver metastases: trials, tribulations and a cautionary note.

Tumor initiating cells (TIC) are increasingly being put forward as a potential target for intervention within colorectal cancer. Whilst characterisation and outgrowth of these cells has been extensively undertaken in primary colorectal cancers, few data are available describing characteristics within the metastatic setting. Tissue was obtained from patients undergoing surgical resection for colorectal liver metastases, and processed into single cell suspension for assessment.

Overexpression of the Nek2 kinase in colorectal cancer correlates with beta-catenin relocalization and shortened cancer-specific survival.

The serine/threonine kinase Nek2 (NIMA-related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing induction of aneuploidy in vitro. Overexpression may also enable tumour progression through effects upon Akt signalling, cell adhesion markers and the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC).

Staging laparoscopy for hilar cholangiocarcinoma in 100 patients.

Purpose: Accurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease.

Prolonged biologically active colonic tissue levels of curcumin achieved after oral administration--a clinical pilot study including assessment of patient acceptability.

Curcumin, the main constituent of turmeric, is suspected to possess cancer chemopreventive properties. Pharmacokinetic and pharmacodynamic parameters have been reported, but few data exist describing whether methodologies are suitably robust for curcuminoid detection in colonic biopsy specimens. Information on the acceptability of prolonged administration of daily curcumin is not available.

Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma.

In order to achieve a better outcome for pancreatic cancer patients, reliable biomarkers are required which allow for improved diagnosis. These may emanate from a more detailed molecular understanding of the aggressive nature of this disease. Having previously reported that Notch3 activation appeared to be associated with more aggressive disease, we have now examined components of this pathway (Notch1, Notch3, Notch4, HES-1, HEY-1) in more detail in resectable (n = 42) and non-resectable (n = 50) tumours compared to uninvolved pancreas.

Primary liver cancer incidence and survival in ethnic groups in England, 2001-2007.

Background: The patterns of primary liver cancer incidence and survival are not known for detailed ethnic groups within the UK.

Methods: Data on patients resident in England diagnosed with primary liver cancer (ICD-10 C22) between 2001 and 2007 were extracted from the National Cancer Data Repository. Age-standardised incidence rate ratios (IRRs) were calculated for different ethnic groups separately for males and females, using the White ethnic groups as baselines.

Influence of hepatic parenchymal histology on outcome following right hepatic trisectionectomy.

Background: Histological abnormalities in the non-tumour-bearing liver (NTBL) may influence outcome following hepatectomy. Effects will be most pertinent following right trisectionectomy but have yet to be specifically examined in this context. This study aimed to investigate the influence of perioperative factors, including NTBL histology, on outcome following right trisectionectomy.

Incidence and survival for hepatic, pancreatic and biliary cancers in England between 1998 and 2007.

Introduction: Hepatic, pancreatic and biliary (HPB) cancers are a group of diverse malignancies managed ideally in specialist centres. This study describes recent patterns in the incidence and survival of HPB cancers in England over a ten year period (1998-2007).

Methods: Data on 99,379 English patients (50,656 males; 48,723 females) diagnosed with HPB cancers between 1998 and 2007 were extracted from the National Cancer Data Repository.

Curcumin: the potential for efficacy in gastrointestinal diseases.

Curcumin is a naturally occurring phytochemical and an extract of turmeric. Extensive in vitro and in vivo data have paved the way for curcumin to become the subject of clinical trials. Curcumin modulates key signalling pathways important in cellular processes.

Is intraoperative confirmation of malignancy during pancreaticoduodenectomy mandatory?

Introduction: Differentiating between chronic pancreatitis and pancreatic adenocarcinoma can be difficult due to considerable overlap in disease presentation and radiological signs and the frequent co-existence of the two conditions. In this situation, surgeons may have to proceed to "blind" pancreaticoduodenectomy or attempt to confirm malignancy intraoperatively with frozen section (FS) histology.

Methods: This study attempted to ascertain the false-negative and false-positive rates of undertaking pancreaticoduodenectomies (PD) based on clinical suspicion (CS) or after intraoperative confirmation of malignancy using FS histology.

Improving the diagnostic yield from staging laparoscopy for periampullary malignancies: the value of preoperative inflammatory markers and radiological tumor size.

Objectives: The role of laparoscopy in staging periampullary malignancies is to detect small-volume metastatic disease not visible on preoperative imaging. Owing to improvements in preoperative imaging, some centers no longer undertake routine laparoscopic staging, whereas others still find it a useful pre-exploration tool.

Methods: This study investigated the diagnostic yield of staging laparoscopies in 137 consecutive potentially resectable patients with periampullary malignancies.

Bilirubin levels predict malignancy in patients with obstructive jaundice.

Background: Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease.

Methods: A total of 1,026 patients with obstructive jaundice were identified.

Preoperative systemic inflammation and infectious complications after resection of colorectal liver metastases.

Background: Postoperative complications are associated with a poor long-term prognosis after resection of colorectal liver metastases via an undetermined mechanism. The preoperative systemic inflammatory response, itself a predictor of poor survival, was recently shown to independently predict postoperative infectious complications after primary colorectal cancer resection.

Objective: To examine the association of postoperative infectious complications with preoperative systemic inflammation and survival in patients undergoing resection of colorectal liver metastases.

A simple, safe technique for the drainage of pancreatic pseudocysts.

Background: A number of methods are available for the drainage of pancreatic pseudocysts, including percutaneous, endoscopic and open approaches. In Leicester, we developed a combined radiological and endoscopic technique (predating the use of endoscopic/ultrasound) to allow drainage of pancreatic pseudocysts into the stomach. The aim of the study was to evaluate the long-term results of this approach.

Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo.

The aims of this study were to determine potency of oxaliplatin in combination with curcumin in oxaliplatin-resistant cell lines in vitro and to evaluate the efficacy of a novel curcumin formulation (Meriva®) alone and in combination with oxaliplatin in colorectal tumor-bearing mice, exploring relevant pharmacodynamic markers in vivo. Oxaliplatin-resistant HCT116 p53wt and p53(-/-) cell lines were generated, and the effects of oxaliplatin in combination with curcumin on resistance- and proliferation-associated proteins investigated. Eighty nude mice were implanted with HCT116 p53wt colorectal cancer cells before randomization into the following treatment groups: control; Meriva only; oxaliplatin only; Meriva + oxaliplatin.

Determination of anthocyanins in the urine of patients with colorectal liver metastases after administration of bilberry extract.

Anthocyanins possess cancer chemopreventive properties in preclinical models. Their clinical pharmacology is only poorly understood. In this pilot study, anthocyanins and their metabolites were analysed in the urine of two patients with colorectal liver metastases.

A review of factors predicting perioperative death and early outcome in hepatopancreaticobiliary cancer surgery.

Objectives: In the context of comparisons of surgical outcomes, risk adjustment is the retrospective adjustment of a provider's or a surgeon's results for case mix and/or hospital volume. It allows accurate, meaningful inter-provider comparison. It is therefore an essential component of any audit and quality improvement process.

Caveat reporting in ultrasound interpretation of surgical pathology: a comparison of sonographer versus radiologist.

Background: Radiology reports provide specialist interpretation of images and relate these findings to the patient's symptoms and signs. This study compared ultrasound (USS) reports generated by radiologists and sonographers to determine if any significant or clinically relevant differences existed.

Methods: A retrospective analysis of 624 consecutive USS reports was carried out.

Liver metastases from colorectal cancer: radioembolization with systemic therapy.

The majority of patients with advanced colorectal cancer die from hepatic metastases caused by disease progression; therefore, several novel technologies are in clinical development to potentially improve local control of liver disease. Radioembolization is a technique for administering radiotherapy internally to unresectable primary or secondary hepatic malignancies in a single procedure. This technique involves the injection of resin or glass microspheres that contain (90)Y into the arterial supply of the liver.

Surgical bypass vs. endoscopic stenting for pancreatic ductal adenocarcinoma.

Background: The majority of patients with pancreatic cancer are non-resectable and jaundiced at presentation. Methods of palliation in such patients with locally advanced disease comprise endoscopic placement of a biliary endoprosthesis or surgical bypass.

Methods: This retrospective study compared morbidity, mortality, hospital stay, readmission rate and survival in consecutive patients with incurable locally advanced pancreatic ductal adenocarcinoma.

Pilot study of oral anthocyanins for colorectal cancer chemoprevention.

Naturally occurring anthocyanins possess colorectal cancer chemopreventive properties in rodent models. We investigated whether mirtocyan, an anthocyanin-rich standardized bilberry extract, causes pharmacodynamic changes consistent with chemopreventive efficacy and generates measurable levels of anthocyanins in blood, urine, and target tissue. Twenty-five colorectal cancer patients scheduled to undergo resection of primary tumor or liver metastases received mirtocyan 1.

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

Background: 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.

Methods: All patients undergoing simultaneous biliary and gastric bypass procedures for unresectable malignant disease between August 2000 and January 2006 were identified and outcomes reviewed.