Preoperative assessment and optimisation for pelvic exenteration in locally advanced and recurrent rectal cancer: A review.

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints.

Investigation of thermally induced damage to surrounding nerve tissue when using curettage and cementation of long bone tumours, modelled in cadaveric porcine femurs.

INTRODUCTION: Curettage with cement augmentation is a technique used in the treatment of bone tumours. Thermal energy released during the cement polymerisation process can damage surrounding tissues. This study aims to record temperature changes at various sites on and around bone during the cementing process. We hypothesised that adjacent structures, such as the radial nerve, may be threatened by this process in the clinical setting. MATERIALS AND METHODS: Using 18 porcine femurs as a model of the human humerus, we used thermocouples and a thermal imaging camera to measure changes in temperature during the cementing process. Fractures were created in nine samples to establish whether a discontinuity of the cortex had an effect on thermal conduction. RESULTS: Significantly higher temperatures were recorded in samples with a fracture compared to those without a fracture. The site overlying the centre of the cement bolus (hypothetical site of the radial nerve) demonstrated higher temperatures than all other sites on the same cortex. When considering the radial nerve site, over half the samples demonstrated temperatures exceeding 47 °C for over a minute. When a threshold of 50 °C for more than 30 s was considered, three samples without a fracture exceeded this value compared to two with a fracture. CONCLUSION: The temperatures recorded were sufficient to cause damage to neural tissue. Limiting thermal exposure to soft tissues is recommended. Increased attention is required when using larger cement boluses, or where bone quality is poor or a fracture, iatrogenic or preexisting, is present.

Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility.

BACKGROUND: Normal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Previous image analysis approaches have successfully extracted properties related to the temporal frequency of motility modes, but robust measures of contraction magnitude, especially from in vivo image data, remain challenging to obtain. METHODS: We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motion. KEY RESULTS: We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild types. CONCLUSIONS & INFERENCES: Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.

An Inducible Reconstitution System for the Real-Time Kinetic Analysis of Protease Activity and Inhibition Inside the Membrane.

Intramembrane proteases are an ancient and diverse group of multispanning membrane proteins that cleave transmembrane substrates inside the membrane to effect a wide range of biological processes. As proteases, a clear understanding of their function requires kinetic dissection of their catalytic mechanism, but this is difficult to achieve for membrane proteins. Kinetic measurements in detergent systems are complicated by micelle fusion/exchange, which introduces an additional kinetic step and imposes system-specific behaviors (e.g., cooperativity). Conversely, kinetic analysis in proteoliposomes is hindered by premature substrate cleavage during coreconstitution, and lack of methods to quantify proteolysis in membranes in real time. In this chapter, we describe a method for the real-time kinetic analysis of intramembrane proteolysis in model liposomes. Our assay is inducible, because the enzyme is held inactive by low pH during reconstitution, and fluorogenic, since fluorescence emission from the substrate is quenched near lipids but restored upon proteolytic release from the membrane. The precise measurement of initial reaction velocities continuously in real time facilitates accurate steady-state kinetic analysis of intramembrane proteolysis and its inhibition inside the membrane environment. Using real data we describe a step-by-step strategy to implement this assay for essentially any intramembrane protease.

A combined light sheet fluorescence and differential interference contrast microscope for live imaging of multicellular specimens.

We describe a microscope capable of both light sheet fluorescence microscopy and differential interference contrast microscopy (DICM). The two imaging modes, which to the best of our knowledge have not previously been combined, are complementary: light sheet fluorescence microscopy provides three-dimensional imaging of fluorescently labelled components of multicellular systems with high speed, large fields of view, and low phototoxicity, whereas differential interference contrast microscopy reveals the unlabelled neighbourhood of tissues, organs, and other structures with high contrast and inherent optical sectioning. Use of a single Nomarski prism for differential interference contrast microscopy and a shared detection path for both imaging modes enables simple integration of the two techniques in one custom microscope. We provide several examples of the utility of the resulting instrument, focusing especially on the digestive tract of the larval zebrafish, revealing in this complex and heterogeneous environment anatomical features, the behaviour of commensal microbes, immune cell motions, and more.

Total hip replacement and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck: a seven- to ten-year follow-up report of a prospective randomised controlled trial.

We reviewed the seven- to ten-year results of our previously reported prospective randomised controlled trial comparing total hip replacement and hemiarthroplasty for the treatment of displaced intracapsular fracture of the femoral neck. Of our original study group of 81 patients, 47 were still alive. After a mean follow up of nine years (7 to 10) overall mortality was 32.5% and 51.2% after total hip replacement and hemiarthroplasty, respectively (p = 0.09). At 100 months postoperatively a significantly greater proportion of hemiarthroplasty patients had died (p = 0.026). Three hips dislocated following total hip replacement and none after hemiarthroplasty. In both the total hip replacement and hemiarthroplasty groups a deterioration had occurred in walking distance (p = 0.02 and p < 0.001, respectively). One total hip replacement required revision compared with four hemiarthroplasties which were revised to total hip replacements. All surviving patients with a total hip replacement demonstrated wear of the cemented polyethylene component and all hemiarthroplasties had produced acetabular erosion. There was lower mortality (p = 0.013) and a trend towards superior function in patients with a total hip replacement in the medium term.

A medium-term comparison of hybrid hip replacement and Birmingham hip resurfacing in active young patients.

We compared the medium-term clinical and radiological results of hybrid total hip replacement (THR) with metal-on-metal Birmingham hip resurfacing (BHR) in two groups of 54 young patients matched for age, gender, body mass index and pre-operative levels of activity. The clinical outcome was assessed by the University of California, Los Angeles (UCLA) activity score, the Oxford Hip Score (OHS) and the EuroQol scores. Radiologically, all hips were assessed for migration and osteolysis, the hybrid THRs for polyethylene wear and the BHRs for a pedestal sign. The mean follow-up of the patients with a hybrid THR was ten years and for those with a BHR, nine years. Four patients with a hybrid THR and one with a BHR had died. In each group five were lost to follow-up. The revision rate of the hybrid THRs was 16.7% (9 of 54) and of the BHRs 9.3% (5 of 54) (p = 0.195). Radiographs of a further eight hybrid THRs demonstrated wear and osteolysis, and they await revision (p = 0.008). Of the unrevised BHRs 90% had radiological changes, of which approximately 50% had progressed over the previous four years. All hybrid THRs demonstrated linear polyethylene wear with a mean of 1.24 mm (0.06 to 3.03). The BHRs recorded superior OHS (p = 0.013), UCLA (p = 0.008), and EuroQol visual analogue scores (p = 0.009). After nine years, patients with BHRs remained more active and had a lower rate of revision than those with hybrid THRs. Both groups demonstrated progressive radiological changes at medium-term follow-up.

Does postoperative hand elevation reduce swelling? A randomized study.

The purpose of this study was to assess the effect of limb elevation on hand swelling after surgery. We prospectively randomized 113 patients undergoing fasciectomy or a trapeziectomy into one of two groups. The first group had the hand elevated postoperatively and the hands of the second group were not elevated. Hand swelling was assessed using a volumetric method. Although the swelling was less in the elevated group this did not reach statistical significance. Subgroup analysis revealed no further significant differences. There were no complications in patients who did not have limb elevation. This study does not support the routine use of elevation for 24 hours after fasciectomy for Dupuytren's disease and trapeziectomy to reduce hand swelling.

Morbidity and mortality after closure of loop ileostomy.

BACKGROUND: A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD: A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS: Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS: Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.

Nicorandil-induced severe perianal ulceration.

BACKGROUND: Nicorandil is a potassium channel activator used in the prevention and long-term treatment of angina pectoris. It is widely prescribed and its use is supported by data from powerful randomised controlled trials. The colorectal community is becoming increasingly aware of a subgroup of patients with anal ulceration and other gastrointestinal manifestations of nicorandil use. METHODS: This study is a retrospective review of patients identified as having nicorandil-induced perianal ulceration. We report our experience of 11 patients. RESULTS: All eleven patients experienced severe debilitating ulceration of the perianal area and perineum. Multiple therapies were tried unsuccessfully before the association with nicorandil was recognised. Upon recognition of the association of nicorandil with these ulcers, the therapy was stopped resulting in resolution of the perianal symptoms. CONCLUSIONS: Nicorandil is a rare cause of severe perianal ulceration. This association should be recognised as these ulcers are resistant to other forms of treatment but heal well on ceasing nicorandil use.

Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.

BACKGROUND: Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial. METHODS: In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed. RESULTS: After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component. CONCLUSIONS: Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.

Treatment of the young active patient with osteoarthritis of the hip. A five- to seven-year comparison of hybrid total hip arthroplasty and metal-on-metal resurfacing.

We compared the five- to seven-year clinical and radiological results of the metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in two groups of 54 hips, matched for gender, age, body mass index and activity level. Function was excellent in both groups, as measured by the Oxford hip score, but the Birmingham hip resurfacings had higher University of California at Los Angeles activity scores and better EuroQol quality of life scores. The total hip arthroplasties had a revision or intention-to-revise rate of 8%, and the Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear and osteolysis under observation, and 8% of Birmingham hip resurfacings showed migration of the femoral component. Polyethylene wear was present in 48% of the hybrid hips without osteolysis. Of the femoral components in the Birmingham hip resurfacing group which had not migrated, 66% had radiological changes of unknown significance.

The use of the long gamma nail in proximal femoral fractures.

The results of 100 'Long Gamma Nails' (LGN) inserted in 97 patients, for the treatment of complex proximal femoral fractures and pathological lesions, are reported. The mean patient age was 74 (16-98). Seven significant complications occurred; four lag screws cut out, one broken nail, one infected non-union and one peri-prosthetic fracture. Five patients underwent revision either to total hip arthroplasty or exchange nailing. Seventy patients had follow-up of greater than 2 months (mean 10.8 months). Success was defined as stability of the fracture until union or death; this was achieved in 85% of cases. The mortality was 10% at 30 days and 25% at 1 year. The complication rate fell with increasing experience. Complex proximal femoral fractures are difficult to treat with all implants demonstrating high complication rates. The long gamma nail allowed early weight bearing and was effective in 85% of cases. Malpositioning of the implant should be avoided, as this was the leading cause of failure. Surgeon experience is an important factor but training of surgeons does not adversely affect outcome.

Gluteal fascial transposition for trochanteric bursitis.

We report a new surgical technique for refractory trochanteric bursitis, performed in 43 patients between May 1988 and December 2003. Fourteen patients had developed trochanteric bursitis after primary total hip arthroplasty (THA), six after revision THA, 17 for no definable reason (idiopathic) and seven after trauma. Follow-up ranged from six months to 15 years (mean five years). Outcome was measured by the patients symptoms at interview and whether the patient would have had the procedure again. Outcome depended on aetiology: 100% of traumatic, 88% of idiopathic and 64% after primary THA were successful. All operations after revision THA were unsuccessful. Transposition of the gluteal fascia is indicated in patients with idiopathic, traumatic and post primary THA trochanteric bursitis, but not after revision THA. (Hip International 2005; 15: 212-7).

Improvement in cognitive function after right temporal arteriovenous malformation excision.

A patient is presented in whom right temporal AVM excision led to improved cognitive function. Neuropsychological assessment showed a significant postoperative improvement in Performance IQ (p = < 0.05), Full Scale IQ (p = < 0.05), and clinically in visual memory (p = < 0.10). Reversal of vascular steal may lead to increases in cognitive function. We recommend that patients undergoing AVM excision have a complete neuropsychological evaluation.

Interaction between Ran and Mog1 is required for efficient nuclear protein import.

Mog1 is a nuclear protein that interacts with Ran, the Ras family GTPase that confers directionality to nuclear import and export pathways. Deletion of MOG1 in Saccharomyces cerevisiae (Deltamog1) causes temperature-sensitive growth and defects in nuclear protein import. Mog1 has previously been shown to stimulate GTP release from Ran and we demonstrate here that addition of Mog1 to either Ran-GTP or Ran-GDP results in nucleotide release and formation of a stable complex between Mog1 and nucleotide-free Ran. Moreover, MOG1 shows synthetic lethality with PRP20, the Ran guanine nucleotide exchange factor (RanGEF) that also binds nucleotide-free Ran. To probe the functional role of the Mog1-Ran interaction, we engineered mutants of yeast Mog1 and Ran that specifically disrupt their interaction both in vitro and in vivo. These mutants indicate that the interaction interface involves conserved Mog1p residues Asp(62) and Glu(65), and residue Lys(136) in yeast Ran. Mutations at these residues decrease the ability of Mog1 to bind and release nucleotide from Ran. Furthermore, the E65K-Mog1 and K136E-Ran mutations in yeast cause temperature sensitivity and mislocalization of a nuclear import reporter protein, similar to the phenotype observed for the Deltamog1 strain. Our results indicate that a primary function of Mog1 requires binding to Ran and that the Mog1-Ran interaction is necessary for efficient nuclear protein import in vivo.

Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.

The trafficking of macromolecules between cytoplasm and nucleus through nuclear pore complexes is mediated by specific carrier molecules such as members of the importin-beta family. Nuclear pore proteins (nucleoporins) frequently contain sequence repeats based on FG cores and carriers appear to move their cargo through the pores by hopping between successive FG cores. A major question is why some macromolecules are transported while others are not. This selectivity may be generated by the ability to bind FG repeats, a local concentration of carrier-cargo complexes near the entrance to the pore channel, and steric hindrance produced by high concentrations of nucleoporins in the channel.