Rectal cancer: prognostic indicators of long-term outcome in patients considered for surgery.

PURPOSE: Patients and clinicians seek an accurate prognosis after resectional surgery for rectal cancer. The aim of this study was to determine long-term outcomes after potentially curative surgery for rectal cancer with particular focus on factors associated with longer-term survival that are available to surgeons in the early post-operative setting. METHODS: We conducted a retrospective review of a prospectively gathered database of all primary rectal adenocarcinomas considered for surgery in the University Hospitals of Leicester National Health Service (NHS) Trust between 1998 and 2007. Survival was calculated using a Kaplan-Meier method. Factors thought to be associated with survival were subjected to univariate analysis followed by Cox proportion regression. RESULTS: One thousand and twelve patients with primary rectal adenocarcinoma diagnosed between 1998 and 2007 were identified. Eight hundred and fifty three patients did not have metastases at the time of presentation and 726 patients underwent major resectional surgery. Five-year survival was 66 %. Patients' age, Dukes' stage, UICC stage, nodal involvement and circumferential resection margin status were independently associated with long-term survival on multivariate analysis. CONCLUSION: This is one of the largest series of rectal cancers from a single NHS trust. We have demonstrated that age, Dukes' stage and CRM status are associated with long-term survival. These clinical factors are readily available to the surgeon at the time of first post-operative review and can provide a good clinical guide to prognosis.

Complement C1q-dependent engulfment of alpha-synuclein induces ENS-resident macrophage exhaustion and accelerates Parkinson's-like gut pathology.

Deposition of misfolded α-synuclein (αsyn) in the enteric nervous system (ENS) is found in multiple neurodegenerative diseases. It is hypothesized that ENS synucleinopathy contributes to both the pathogenesis and non-motor morbidity in Parkinson's Disease (PD), but the cellular and molecular mechanisms that shape enteric histopathology and dysfunction are poorly understood. Here, we demonstrate that ENS-resident macrophages, which play a critical role in maintaining ENS homeostasis, initially respond to enteric neuronal αsyn pathology by upregulating machinery for complement-mediated engulfment. Pharmacologic depletion of ENS-macrophages or genetic deletion of C1q enhanced enteric neuropathology. Conversely, C1q deletion ameliorated gut dysfunction, indicating that complement partially mediates αsyn-induced gut dysfunction. Internalization of αsyn led to increased endo-lysosomal stress that resulted in macrophage exhaustion and temporally correlated with the progression of ENS pathology. These novel findings highlight the importance of enteric neuron-macrophage interactions in removing toxic protein aggregates that putatively shape the earliest stages of PD in the periphery.

Fresh frozen cadavers: an under-utilized resource in laparoscopic colorectal training in the United Kingdom.

AIM: To describe the use of fresh frozen cadavers in laparoscopic colorectal training. METHOD: The cadavers are washed and frozen to -20°C within a week of procurement before being thawed at room temperature prior to use. RESULTS: Fresh frozen cadavers provide perfect anatomy, normal tissue consistency and a realistic operative training experience. CONCLUSION: Fresh frozen cadavers have a number of clear advantages over other training models in laparoscopic colorectal surgery but are currently not widely used.

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.

The RAPID protocol enhances patient recovery after both laparoscopic and open colorectal resections.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs can accelerate recovery and shorten the hospital stay after colorectal resections. The RAPID (remove, ambulate, postoperative analgesia, introduce diet) protocol is a simplified ERAS program that consists of a simplified, user-friendly single-page pro forma schedule. This study aimed to evaluate the impact of the RAPID protocol on patients undergoing both laparoscopic and open colorectal resections in two specialized colorectal units. METHODS: A prospective, two-center study assessed 117 age-matched patients undergoing open or laparoscopic colorectal resection to compare the postoperative course for patients using the RAPID protocol with those treated in a traditional manner. RESULTS: Of the 117 patients studied, 70 underwent laparoscopic resection (55 with the RAPID protocol) and 47 underwent open resection (25 with the RAPID protocol). Patients undergoing laparoscopic resections with the RAPID protocol had a significantly shorter hospital stay (p = 0.01) and tolerance of a full diet (p = 0.002). Similarly, patients undergoing open resections with the RAPID protocol also have a significantly shorter hospital stay (p = 0.04). CONCLUSION: The RAPID protocol is a user-friendly, easy, and effective tool that facilitates earlier tolerance of diet and discharge from the hospital for patients undergoing laparoscopic or open colorectal resections.

Characterisation of Interleukin-8 and monocyte chemoattractant protein-1 expression within the abdominal aortic aneurysm and their association with mural inflammation.

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are characterised by chronic transmural inflammation. This study investigated the expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) within the AAA, and their relationship with mural inflammation. METHODS: Biopsies were obtained from 25 AAAs, 15 abdominal aortas, and 10 atherosclerotic thoracic aortas. IL-8 and MCP-1 expression was measured in homogenised specimens by ELISA. Infiltrate composition and localised expression of IL-8 and MCP-1 were determined through immunohistochemistry. RESULTS: ELISA analysis demonstrated that IL-8 and MCP-1 were raised in the AAA compared to the controls [(IL-8, AAA vs. abdominal aorta: >28-fold, P<.001; AAA vs. thoracic aorta: >28-fold, P<.001) (MCP-1, AAA vs. abdominal aorta: 9-fold, P<.001; AAA vs. thoracic aorta: 19-fold, P<.001)]. Immunohistochemistry revealed that IL-8 was localised to the inflammatory infiltrate, which consisted predominantly of CD3(+) T- and CD20(+) B-lymphocytes. MCP-1 was predominantly expressed by CD68(+) macrophages. Increasing IL-8 expression was associated with an increase in mural inflammation, and an increase in CD3(+) T-lymphocytes of CD4(+) phenotype within the infiltrate population. CONCLUSION: Pathways involving IL-8 and MCP-1 may be involved in AAA pathogenesis. IL-8 may be directly involved in the chemotaxis of T(H)-lymphocytes into the AAA wall.

A case of toxic megacolon in a patient with collagenous colitis.

Collagenous colitis is an uncommon inflammatory bowel disease, the aetiology of which is unknown. We report a case of toxic megacolon in a patient with collagenous colitis, a previously unreported complication.

Endovascular abdominal aortic aneurysm repair.

The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique.

A fructose bisphosphate activated lactate dehydrogenase in the liver fluke Fasciola hepatica.

Lactate dehydrogenase of Fasciola hepatica showed typical Michaelis-Menten kinetics at pH 7.2, with respect to pyruvate. Addition of physiological levels of fructose bisphosphate activated the enzyme at all substrate concentrations tested; the response to this effector being hyperbolic in nature. As well as depending upon the fructose bisphosphate concentration, the Vmax and Km are modified by different buffers. The degree of activation is much greater using Tris-HCl than phosphate buffer. The pH optimum occurs at pH 6.5 whether using physiological levels of substrate in the presence or absence of fructose bisphosphate, or high levels of substrate. Of the potential effectors tested, significant inhibition was shown by the nucleoside triphosphates, especially ATP. The importance of this inhibition, coupled with the activation by fructose bisphosphate is discussed. Fasciola hepatica lactate dehydrogenase is unusual in that it does not catalyse the reverse reaction to any measurable extent. That is, lactate oxidation is negligible unless the effector fructose bisphosphate is present. Use was made of this fact to visualise the isoenzymes of lactate dehydrogenase separated by polyacrylamide disc gel electrophoresis. Five isoenzyme bands became apparent when stained in this manner.

Severe disease in adult dairy cattle in three UK dairy herds associated with BVD virus infection.

During 1993 outbreaks of diarrhoea in adult dairy cows in three geographically unrelated herds were found to be caused by bovine viral diarrhoea virus (BVDV). The affected animals showed signs of acute watery diarrhoea, agalactia and pyrexia (39.4 to 42 degrees C). Ulceration of the buccal mucosa, a mucoid nasal discharge and stiffness were inconsistent signs. The disease spread rapidly in each case. The diagnosis was confirmed by the isolation of non-cytopathic BVDV from blood and tissues and by the demonstration of significantly rising titres to BVDV by an ELISA. The highest morbidity recorded was 40 per cent with one herd experiencing a 10 per cent mortality. There was no increased incidence of abortion in any of the herds, either at the time of or subsequent to the outbreaks of diarrhoea. In one herd the purchase of a persistently viraemic heifer 14 days before the outbreak was thought to be the source of infection, but in the other two herds the source was not established.

Predisposition to repeat breeding in UK cattle and success of artificial insemination alone or in combination with embryo transfer.

To investigate whether there was a subpopulation of repeat breeders (cows or heifers that returned to oestrus after three inseminations) that were less fertile after a fourth artificial insemination (AI) with or without additional embryo transfer, and to estimate the efficacy of AI plus embryo transfer to overcome repeat breeding problems, a two-part investigation was carried out. Part 1 involved 85 repeat breeders and 85 controls subjected to AI alone. In part 2, 128 repeat breeders received AI on day 0 plus an embryo transfer seven days later, while controls received embryo transfer alone on day 7. In repeat breeders, the interval between calving and pregnancy was 80 days longer than in the controls (P=0.01), irrespective of previous fertility treatment which had mainly focused on the ovaries. The incidence of dystocia was similar in repeat breeders and in controls, but repeat breeders had a higher previous incidence of moderate uterine infection compared with controls (P=0.04). In repeat breeder cows, pregnancy rates for AI alone were 30 per cent after the fourth AI (controls: 45 to 64 per cent after one to three inseminations) compared with 52.6 per cent after a fourth AI with embryo transfer (controls with embryo transfer alone: 49 per cent). Successful pregnancies after a fourth AI plus embryo transfer produced a 6.25 per cent incidence of twins.

An algorithm for the management of bile leak following laparoscopic cholecystectomy.

INTRODUCTION: The management of bile leaks following laparoscopic cholecystectomy has evolved with increased experience of ERCP and laparoscopy. The purpose of this study was to determine the impact of a minimally invasive management protocol. PATIENTS AND METHODS: Twenty-four patients with a bile leak following laparoscopic cholecystectomy were recorded consecutively between 1993 and 2003. Between 1993-1998, 10 patients were managed on a case-by-case basis. Between 1998-2003, 14 patients were managed according to a minimally invasive protocol utilising ERC/biliary stenting and re-laparoscopy if indicated. RESULTS: Bile leaks presented as bile in a drain left in situ post laparoscopic cholecystectomy (8/10 versus 10/14) or biliary peritonitis (2/10 versus 4/14). Prior to 1998, neither ERC nor laparoscopy were utilised routinely. During this period, 4/10 patients recovered with conservative management and 6/10 (60%) underwent laparotomy. There was one postoperative death and median hospital stay post laparoscopic cholecystectomy was 10 days (range, 5-30 days). In the protocol era, ERC +/- stenting was performed in 11/14 (P = 0.01 versus pre-protocol) with the main indication being a persistent bile leak. Re-laparoscopy was necessary in 5/14 (P = 0.05 versus preprotocol). No laparotomies were performed (P < 0.01 versus pre-protocol) and there were no postoperative deaths. Median hospital stay was 11 days (range, 5-55 days). CONCLUSIONS: The introduction of a minimally invasive protocol utilising ERC and re-laparoscopy offers an effective modern algorithm for the management of bile leaks after laparoscopic cholecystectomy.

A novel phosphagen phosphotransferase in the plerocercoids of Schistocephalus solidus (Cestoda: Pseudophyllidea).

Neither phosphagens nor phosphagen phosphotransferase activity could be detected in Fasciola hepatica, Hymenolepis diminuta, Moniezia expansa or in the plerocercoids of Ligula intestinalis. The plerocercoids of Schistocephalus solidus, however, possess an active taurocyamine phosphotransferase, although it too contains no detectable phosphagens. The taurocyamine phosphotransferase of S. solidus has an absolute requirement for a divalent metal ion and ATP could not be replaced by ITP, GTP, CTP or UTP as the phosphate donor. The role of phosphagens in helminths is discussed.

Separation of Mycobacterium leprae from contamination with armadillo-liver-derived "pigment" particles.

Mycobacterium leprae isolated from armadillo liver by the widely used IMMLEP protocol is sometimes contaminated with a particulate "pigment." This paper describes a simple, efficient, and rapid method for purifying large quantities of contaminated bacteria, which may readily be used as an additional step added at the end of the protocol when necessary. The process involves a discontinuous Percoll gradient and generates an essentially pure fraction containing greater than 90% of the original bacteria, and a fraction of "pigment" slightly contaminated with bacteria. Use of the system should release large additional numbers of pure M. leprae suitable for use in human vaccine trials.

Fasciola hepatica: carbohydrate metabolism of the adult.

Glycogen (or exogenous glucose) was the only energy source utilized by adult Fasciola hepatica under a number of different incubation conditions. When exogenous glucose was present in the incubation medium, significant amounts of lactate were excreted. Anaerobically, in the presence of glucose, lactate accounted for 20% of the total end products measured. In the absence of glucose, organic acid production accounted for approximately 60% of glycogen carbon utilized; this value was reduced to 40% in the presence of exogenous glucose. There was no appreciable Pasteur effect.