- Surgery (Austin & Northern Health) - Theses
Surgery (Austin & Northern Health) - Theses
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ItemConsiderations for surgical intervention in metastatic cancer to the spine: evaluation of risk factors for pathologic fracture and spinal cord compression, and analysis of pre-operative scoring systems for the prognostication and treatment of patients with spinal metastasesHibberd, Catherine ( 2014)The spine has structural load bearing and neural-protective functions, and tumour growth and bony destruction caused by spinal metastases results in pathologic fracture and cord compression, causing pain, neurological deficit, impaired function and quality of life. Surgery is the only method to immediately stabilise the spine and decompress the spinal cord. Survival prognosis is one of the key factors in selecting patients for surgery, and there are a number of scoring systems aimed at prognostication and treatment decision making for patients with spinal metastases, however these differ in the parameters assessed and prognostic value. The ability to predict those patients with spinal metastases most likely to progress to pathological fracture or develop spinal cord compression may simplify the surgical decision-making process and enable earlier surgical intervention, with the potential to prevent permanent neurological deficit and disability and maintain function and quality of life for the remainder of the patient's life. This thesis considers the complexities of treatment decision making for patients with spinal metastases, with two major aims: 1) An evaluation of patient risk factors and radiological parameters associated with pathological fracture and metastatic epidural spinal cord compression, and 2) Validation of survival prognostication of current pre-operative prognostic scoring systems, in order to optimise the treatment decision-making process. The methodology involved retrospective assessment of clinical and radiological parameters of 72 patients with spinal metastases who had undergone decompressive and/or stabilisation surgery for pathological fracture and/or metastatic epidural spinal cord compression or nerve root compression. The items assessed for association with pathological fracture or metastatic epidural spinal cord compression were: tumour size, location, type and lesion morphology, disease burden, pain and function. Pre-operative scores were calculated for each patient, and the prognostic value of each scoring system evaluated by comparison of predicted and actual survival. The results showed that tumour size within the vertebral body, vertebral endplate and three-column involvement, tumour growth rate, multiple vertebral metastases, and pain were associated with increased risk for pathological fracture. Vertebral posterior element and costovertebral joint involvement by tumour, primary tumour growth rate and presence of visceral metastases were associated with metastatic epidural spinal cord or nerve root compression. All patients with pathological fracture had at least one of three risk factors – pain; >25% tumour occupancy of vertebral body; and endplate or 3-column involvement – and incidence of pathological fracture increased with higher number of risk factors. The Revised Tokuhashi, Bauer, Modified Bauer, and Tomita scoring systems were the most reliable for survival prediction. It is concluded that these risk factors should be considered in the decision-making process for surgery for spinal metastases. Patients with spinal metastases causing pain, greater than 25% occupancy of the vertebral body and involving the vertebral endplate or all three columns should be considered for prophylactic or therapeutic decompressive and stabilization surgery. As a component of comprehensive treatment planning, we recommend the use of Revised Tokuhashi, Modified Bauer, and Tomita scoring systems due to their favourable survival prognostic accuracy and clearly outline of treatment strategy according to prognostic group.
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ItemThe Effect of Co-stimulation Blockade on Survival of Xenogeneic Pancreatic Beta-cellsYap, Zeng Zeng ( 2014)Diabetes mellitus is a chronic disease affecting millions of people worldwide. Currently, the only potential cure is through pancreatic transplantation, either as whole organ or with pancreatic islet cells. However, the morbidity associated with immunosuppression and the scarcity of donor organs do not support the common practice of pancreatic transplantation. Both these factors can potentially be addressed by xenotransplantation of genetically modified cells that are capable of attenuating the immune system. The costimulation pathway of the immune system was the focus of this project, in particular blockade of the ICOS (inducible costimulation molecule) and CTLA-4 (cytotoxic T lymphocyte associated antigen 4) pathways to prolong xenograft survival. To address the problem of diabetes as well as investigate the efficacy of costimulation blockade on xenograft survival, rat insulinoma (beta) cell lines (INS-1E) stably expressing either ICOS-Ig or CTLA4-Ig were generated. The secreted proteins were demonstrated to be biologically active in xenogeneic mixed lymphocyte reactions by their ability to inhibit lymphocyte proliferation. Unfortunately, the in vivo effect of these transgenic INS-1E cells on xenograft survival was unable to be determined because of their failure to establish as tumours due to the slow growth rate of these cells following subcutaneous injection into BALB/c mice. The aim of the second part of this project was to assess the effect of rationally mutated ICOS-Ig on xenograft survival. PIEC (pig iliac endothelial cells) stably expressing ICOS-Ig with single (K52/S and S76/E) and combined (K52/S + S76/E) amino acid mutations were generated. In vitro, compared to wild type ICOS-Ig, the mutants with single amino acid substitutions showed stronger binding avidity to ICOS ligand. This increase in binding avidity however did not translate into superior inhibition of lymphocyte proliferation compared to wild type ICOS-Ig in xenogeneic mixed lymphocyte reactions. Similarly in vivo, the PIECs secreting mutated forms of ICOS-Ig did not prolong xenograft survival after subcutaneous injection of these cells into BALB/c mice. These data suggest that despite their higher avidity, the ICOS-Ig mutants are not biologically more superior than wild type ICOS-Ig both in vitro and in vivo.
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ItemGastrin-mediated adaptive responses to hypoxia in colorectal cancerWestwood, David Alexander ( 2014)Over the past two decades the potential biological activities exerted by gastrin precursors on colorectal tumourigenesis have gradually widened to include mitogenesis, apoptosis resistance, stimulation of angiogenesis and promotion of cell migration and invasion. However, the molecular mechanisms underlying this plethora of biological effects are unclear. Furthermore, the interplay between gastrin precursors and the colorectal tumour microenvironment has been a relatively neglected area of gastrin research. This thesis investigates these two important areas of gastrin biology and is the first study to report that hypoxia-inducible gastrin gene expression in colorectal cancer cells mediates resistance against hypoxia-inducible cell death in vitro and in vivo and may contribute to the development of distant metastatic disease.
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ItemIntravenous lignocaine followed by a 24-hour postoperative subcutaneous infusion shortens length of hospital stay after open radical retropubic prostatectomy: a blinded, randomised, placebo-controlled multicentre trialWEINBERG, LAURENCE ( 2014)Introduction: An alternative method of administering lignocaine for its beneficial anti-inflammatory and analgesic effects to improve and accelerate postoperative recovery is to administer the local anaesthetic solution by a continuous intravenous infusion. However, in patients undergoing major abdominal surgery, intravenous lignocaine combined with a 24-hour continuous subcutaneous infusion has not been systematically examined for efficacy and safety. A subcutaneous infusion of lignocaine may be an effective strategy to continue systemic lignocaine into the early postoperative period. Subcutaneous delivery may be more advantageous than an intravenous infusion, being technically easier to deliver, safer and cost-effective. Drug tolerance may also be less likely to develop. A significant advantage of subcutaneous infusions over intravenous drug delivery methods is that plasma levels are more stable, and symptom control may be achieved without the toxic effects of peaks and troughs resulting from episodic drug administration or a prolonged continuous intravenous infusion. However, it is unknown whether this intervention will impact clinically on important postoperative outcomes, such as length of hospital stay and accelerated postoperative rehabilitation. Before a combination of intravenous lignocaine and subcutaneous lignocaine is adopted as a feasible and efficacious technique for patients undergoing major abdominal surgery, it needs to be investigated in a randomised controlled clinical trial to measure its benefits and harm, and to better define its role in therapy. Study aims: The aims of this study are to evaluate whether a combination of intravenous lignocaine followed by a postoperative 24-hour subcutaneous infusion is beneficial in decreasing length of hospital stays, improving analgesia, and reducing opioid consumption compared to placebo. This study will also quantify the safety of this technique in a perioperative setting. The study was designed to test the hypothesis that perioperative systemic lignocaine infusion in this combination enhances recovery and shortens length of hospital stay after an open radical retropubic prostatectomy. Methods: The Austin and Box Hill Human Research Ethics Committees approved this study. This was a blinded, randomised, placebo-controlled, multicentre trial at two university teaching hospitals. Patients undergoing open radical retropubic prostatectomy were randomised to receive intravenous lignocaine (bolus injection 1.5 mg/kg), then an intravenous infusion (1.5 mg/kg/hr) during surgery, followed by iv subcutaneous infusion for 24 hours (1.5 mg/kg/hr) (Lignocaine group), or a Placebo group who received an equal volume of normal saline delivered at the same infusion rates and over the same time period. General anaesthesia, including the use intraoperative opioids, was standardized, and no patient received regional analgesia or anaesthesia, surgical wound catheters, or infiltration of the surgical wound with local anaesthetic solutions. All patients received morphine patient-controlled analgesia postoperatively in a standardized dosing regime. The primary aim of this study is to evaluate whether a combination of intravenous lignocaine followed by a postoperative 24-hour subcutaneous infusion is beneficial in decreasing the length of hospital stay compared to placebo. Important secondary outcomes included comparing intraoperative haemodynamics (heart rate, blood pressure), Bispectral index (BIS), and end-tidal sevoflurane concentrations required to maintain 1 MAC of anaesthesia. In addition, postoperative pain using a Visual Analogue Scale at the incision site measured at rest and with coughing, morphine and rescue analgesia consumption, need for rescue anti-emetic therapy, and patient satisfaction were also evaluated. Opioid-related and lignocaine-related side effects were critically examined including the measurement of plasma lignocaine levels performed in the immediate postoperative period and at 24 hours prior to the discontinuation of the lignocaine subcutaneous infusion. Results: The Lignocaine group had 37 patients and the control group had 38 patients. Patient demographics were similar between groups. The mean duration for surgery was 155.7 minutes (SD: 34.2) for the Lignocaine group and 141.6 minutes (SD: 44.6) for the Placebo group (estimated difference: 14.1 minutes, 95% CI: -4.27 to 32.47, p = 0.13). In the Lignocaine group, the mean highest heart rate recorded was 97.5 beats/minute vs. 103.8 beats/minute in the Placebo group (estimated difference: 6.3 beats/minute; 95% CI: 2.4 to 10.3 beats/minute, p = 0.001). Intraoperatively, the Lignocaine group had lower heart rates [52.1 beats/minute vs. 59.0 beats/minute; estimated difference: 6.8 beats/minute; 95% CI: 3.3 to 10.3 beats/minute, p = 0.001]. The mean BIS is the Lignocaine group was lower than that in the Placebo group (43.4% vs. 49.8%; estimated difference 6.3%, 95% CI: 3.0% to 9.7%, p = 0.001). Despite the BIS being lower in the Lignocaine group, the average concentration of sevoflurane required to maintain 1 MAC of anaesthesia was lower in the Lignocaine group [1.49% vs. 1.89%; estimated difference 0.39%, 95% CI: 0.26% to 0.5%, p = 0.001]. The Lignocaine group had a shorter length of hospital stay [3.3 days (SD: 0.8) vs. 4.7 days (SD: 3.2), estimated difference 1.3 days; 95% CI: 0.2 to 2.4, p = 0.02]. The Lignocaine group required less morphine during the first 24 hours [mean 38 mg (SD: 24) vs. 52 mg (SD: 27); estimated difference 14 mg; 95% CI 2 to 26 mg, p = 0.02]. The mean Visual Analogue Scores for pain at rest one hour postoperatively were 3.73 units for the Placebo group and 1.93 units for the Lignocaine group. On average, the Placebo group scored 1.80 units higher than the Lignocaine group at this time point (95% CI: 0.73 to 2.88, p = 0.001). There was no difference in rest pain at 24 hours. There were also no significant differences in pain on movement over the 24-hour period. Among secondary endpoints, the time taken to tolerate free fluids and a light ward diet were shorter in the Lignocaine group. Time to mobilize was also shorter in the Lignocaine group. Other secondary endpoints were similar. In the Lignocaine group, the mean plasma lignocaine level after surgery was 1.36 mcg/mL (SD: 0.48), range 0.5 mcg/mL to 2.19 mcg/mL; and at 24 hours postoperatively was 3.1 mcg/mL (SD: 0.95); range 1.1 mcg/mL to 4.96 mcg/mL. Lignocaine levels in the Placebo group were always less than 0.5 mcg/mL. No patient experienced complications associated with lignocaine infusion. Conclusions: Intravenous lignocaine followed by a 24-hour subcutaneous infusion resulted in a shorter length of hospital stay and accelerated acute rehabilitation after open radical retropubic prostatectomy. Furthermore, subcutaneous infusion of lignocaine was an effective strategy to continue systemic lignocaine into the early postoperative period. To date, this is the first randomised clinical trial evaluating the use of subcutaneous lignocaine in this setting, and therefore adds to the growing body of literature supporting the use of lignocaine via this route for open abdominal surgery.
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ItemPrognostic factors in urological malignanciesSENGUPTA, SHOMIK ( 2014)BACKGROUND: The management of urologic cancers relies heavily on the implicit or explicit application of prognostic models. This may range from the appropriate selection of diagnostic tests based upon the pre-test probability of a positive finding, to an informed decision on choice of treatment modality or enrolment in suitable clinical trials. While some prognostic factors such as stage and grade are time-tested, others such as molecular and immunohistochemical markers or surgical approach are new and evolving. Furthermore, the literature abounds with nomograms, models, risk tables or groups which utilize varying combinations of predictor variables to prognosticate on myriad outcomes of interest. The aim of this body of work was to enhance our understanding of prognostication in urologic malignancies, particularly prostate cancer, renal cancer and urothelial cancer of the bladder, in various clinical settings. METHODS: Details of methodology vary – specifics are outlined in the relevant chapters. In general terms, an appropriate study population was defined based upon the hypothesis. Variables of interest were extracted from suitable database and / or clinical records, or assessed in the laboratory. Associations between predictors and outcomes were analysed using univariate and (where suitable) multivariate regression techniques. PRINCIPAL RESULTS: • PSA kinetics provide important prognostic information in various clinical settings, including prior to surgical treatment and after hormonal therapy • A persistently detectable PSA following radical prostatectomy is associated with a greater risk of progression and death, but with a long natural history • Younger patients with prostate cancer have less aggressive features, but a proportionately greater risk of progression and death despite curative surgical treatment • Obese patients with prostate cancer have more adverse pathologic features, but similar oncological outcomes compared to those of normal weight • A positive family history is associated with an increased risk of developing prostate cancer, but similar oncologic outcomes following surgical treatment • Gleason scoring has evolved over time, with consequent changes in the prognostic implications thereof • So-called “insignificant” prostate cancer has similar oncological outcomes to low-risk cancers overall, following surgical treatment • Patient suitability for brachytherapy as a single modality can be judged based on the clinically assessed risk of lymph node or seminal vesicle involvement • Clinical factors can predict the risk of nodal metastasis, thus allowing the rational selection of patients for pelvic lymphadenectomy at the time of radical prostatectomy • RALRP is associated with a lower rate of +SM compared to ORP, even after adjusting for known clinical and pathological risk factors • Renal cancers in solitary kidneys associated with vena caval extension may be treated by nephron-sparing surgery where technically suitable, although a high risk of disease progression and death remains • The pre-operative erythrocyte sedimentation rate provides independent prognostic information in patients with renal cancer • Renal lesions with low nephrometry score as measured using the R.E.N.A.L. have a greater likelihood of having benign or indolent histology • Histologic coagulative tumour necrosis within renal cancers is associated with poorer oncological outcomes after surgical treatment • Expression of the oncogene c-kit is rare within high-grade or sarcomatoid renal cancers • Muscle invasive urothelial cancers of the bladder are often infiltrated by profuse numbers of lymphocytes with a variety of phenotypes, although they appear not to impact on the risk of progression or death after surgical treatment • Peri-operative chemotherapy has been increasing in its use over recent years, and appears to reduce the risk of recurrence after surgical treatment of urothelial cancer of the bladder CONCLUSIONS: Many of the findings summarized above have had important implications for practice. For instance: • PSA kinetics are now in widespread use at various stages of prostate cancer management • Gleason scores from patients treated some time ago are often re-interpreted according to revised criteria
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ItemIdentification of genetic changes in prostate tissue of men with prostate cancer from multiple breast cancer familiesKavanagh, Liam ( 2013)Introduction: Male BRCA2 mutation carriers are at higher risk of developing aggressive prostate cancer. My research looks at DNA changes in prostate cancer specimens from men positive for a BRCA2 mutation. The first project involves DNA analysis of HG PIN tissue to look for loss of heterozygosity (LOH) in those carriers of a BRCA2 mutation. The purpose of looking for LOH in HG PIN of BRCA2 positive carriers is to ascertain if this tissue is a genomic predictor for tumorigenesis in this population. We also considered that whole exome copy-number analysis (CNA) of prostate cancer tissue, as well as HG PIN and normal prostate tissue from these BRCA2 men, may provide additional insight. Another inheritable mutation associated with prostate cancer is the HOXB13 mutation. We explored our cohort of prostate cancer men from breast cancer-rich families for the incidence of this mutation and impact on survival. We also investigated the incidence of the HOXB13 mutation in breast cancer women from breast cancer-rich families. Patients and Methods: Ten BRCA2 positive participants, from the kConFab cohort of high-risk breast cancer families, were identified , with access to archival prostate tissue specimens. Loss of heterozygosity (LOH) at the BRCA2 gene was examined using mutation specific PCR and sequencing of DNA from laser microdissected HG PIN. We also dispatched 15 DNA samples to Affymetrix for CNA: 9 prostate adenocarcinoma tissue DNA samples with 4 matched normal prostate tissue samples and 2 matched HG PIN samples. This data was analysed using specific software for microarray genetic analysis. For the HOXB13 study, the G84E variant was screened for using high resolution melting analysis in germ-line DNA in the index case or youngest affected member of 898 high-risk breast cancer families and in 1097 population controls. Results: Within this cohort of 10 pathogenic BRCA2 carriers, no patient displayed LOH at the mutation locus within HG PIN, irrespective of whether or not corresponding adenocarcinoma DNA displayed LOH. For the CNA project, our samples showed common sites of amplification at 8q, as well as deletions at 10q and 13q. Six out of 898 multi-case breast cancer families had carriers of the HOXB13 G84E variant: three families had either a single or multi-case family history of prostate cancer (3/99) and three had a personal and family history of breast cancer (3/799). Conclusion: Although HGPIN is considered a precursor to cancer, as no LOH was observed, this assay does not provide a genetic marker that may be considered a positive predictor of tumorigenesis in BRCA2 carriers. Regarding the CNA study, this is the first genomic analysis of this specific patient group, with our results have validated previous results of CNA in prostate cancer, as well as demonstrating the highly heterogenous nature of copy-number changes in this subset of patients. We confirm an association of the HOXB13 G84E variant with good prognosis prostate cancer in non BRCA1 or BRCA2 breast cancer families but we found no evidence for an increased risk of familial breast cancer.
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ItemProfiling tumour infiltrating lymphocytes in prostate cancerRajarubendra, Nieroshan ( 2013)The purpose of this study was to understand the T cell processes that take place in prostate pathology. The subset of T cells and their functional and activational status was determined using flow cytometry and immunohistochemistry. Furthermore the use of androgen deprivation therapy (ADT) on the impact on T cells was also determined. The three main conditions of prostate pathology investigated were benign prostatic hyperplasia (BPH), chronic abacterial prostatitis (CAP) and prostate cancer (PCa). Patients with BPH were used as the control group. The results in CAP showed a trend of an active immune process, where there was an influx of CD4+ T lymphocytes cells (9.45%, p 0.1407) in prostate tissue and a reduction in T regulatory (Treg) cells (2.32%, p 0.0675) in the tissue and the blood (3.13%, p 0.0042). In PCa tissue there was an influx of both CD4+ T lymphocytes (9.63%, p 0.0296) and CD8+ lymphocytes (12.81%, p 0.0063). Correspondingly a trend was seen with an increase in Treg cells in prostate tissue (2.12%, p 0.2480). This resulted in the ratios between CD4:CD8, CD4:Treg and CD8:Treg in PCa to be similar to BPH indicating a net homeostasis in immune action. The use of Treg cells as a prognostic indicator was compared to current pathological markers, where a higher number of Treg cells was seen in patients with extraprostatic spread (3.52%, p 0.0371), seminal vesicle extension (10.74%, p 0.0249), PSA relapse (4.39%, p 0.0162) and higher Gleason score (3.89%, p 0.0376). Despite showing a homeostatic picture in PCa, the functional status of CD8+ T lymphocytes was assessed. There were lower proportions of naïve T cells (9.86%, p 0.0068) and central memory T cells (8.60%, p 0.0258) in PCa tissue. While there was an increase in terminal effector T cells (12.06%, p 0.0019) and effector memory T cells (8.63%, p 0.0253). This implied that the tumour cells had been recognized and a shift in the dynamics towards a local cytotoxic environment. These cytotoxic T lymphocytes were activated as demonstrated by increased expression of CD69 (13.35%, p 0.0083). Despite showing activation, the effectiveness of these cells in the implementation of an anti-tumour response was assessed by evaluating the distribution of cytokines IFNγ, TGFβ and IL-10. However no clear pattern was seen, but it will require further investigation with a larger sample population. The use of ADT has been shown to reverse thymic involution and restore peripheral T cell population. However from this study there was no difference seen in the subset numbers, functional and activational status of T lymphocytes. From this study, the profile of prostatic pathology is better understood. The T cell profile especially in the in the local tumour environment of PCa shows a dynamic process between cytotoxic and immunosuppressive cells. This will allow for the development of further studies to understand the immune interaction with PCa.
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ItemSafety and efficacy of radial artery conduits for coronary artery bypass surgeryRuengsakulrach, Permyos ( 2001-06)Coronary artery bypass grafting (CABG) is the most common cardiac surgical operation performed in western countries, and is also increasingly being performed in developing countries. However the long-term results of CABG using the saphenous vein graft have not been satisfactory. Surgeons have therefore been seeking a better conduit. The radial artery (RA) is a potentially suitable alternative conduit and has to date provided good early results. This thesis investigates the utility of the RA as a coronary artery bypass graft from a number of perspectives. It demonstrates the safety of RA harvesting by examining hand collateral circulation using anatomical dissection, physical examination using the modified Allen test, measuring digital blood pressure, and examining the flow velocity in the digital artery using Doppler ultrasound. Anatomical examinations revealed consistent continuity between the RA and ulnar artery in the hand through either superficial or deep palmar arches. The modified Allen test was found to be useful as a screening test compared with the Doppler dynamic test and digital blood pressure index. A histological comparison was made between pre-existing intimal disease in the RA compared with that in the standard conduit the internal thoracic artery (ITA). The RA showed a higher prevalence and degree of intimal disease than ITA. Risk factors for intimal hyperplasia in the RA were age, diabetes, smoking and peripheral vascular disease. The only predictor for medial calcification was age. (For complete abstract open document)
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ItemThe effect of laser induced thermal ablation on liver tumoursNIKFARJAM, MEHRDAD ( 2005-11)Laser thermal ablation (LTA) is an in situ ablative technique that induces heat destruction of liver tumours. Despite increasing clinical use of LTA, reports of long-term outcomes and limitation of treatment in specific cohorts of patients with liver tumours are lacking. In addition, the mechanisms of action of therapy have not been fully elucidated. This study highlights the long-term clinical results and limitations of LTA in the treatment of a cohort of patients with unresectable colorectal liver metastases and examines the mechanisms of action of thermal ablative injury in a murine model.
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ItemManagement of young patients with colorectal cancerWarrier, Satish Kumar ( 2013)Introduction: Young Patients with Colorectal Cancer (CRC) pose diagnostic and management challenges. A young age denotes an increased risk of a familial syndrome. The thesis aim was to identify how colorectal surgeons manage young colorectal cancer based on the likelihood of hereditary colorectal cancer. We sought to investigate the reliability of endoscopic biopsies, how compliance with post- operative surveillance guidelines influenced the metachronous colorectal cancer rate, and how quality of life was altered by the extent of colectomy. Young CRC patients’ views to varying aspects of colorectal surgery were also tested. Methods: Scenario based electronic surveys were sent to members of the Colorectal surgical society of Australia and New Zealand (CSSANZ), American Society of Colorectal Surgeons (ASCRS) and Association of Coloproctology of Great Britain and Ireland (ACPGBI). DNA mismatch repair protein immunohistochemical testing was compared between matched pairs of preoperative and postoperative samples in patients with known Lynch syndrome. Subsequently, the effect of radiation on the reliability of this technique was tested in a cohort age less than 50. The influence of compliance with post surgical surveillance intervals on metachronous colon cancers was studied in patients with known Lynch syndrome. The influence of an extended colectomy on QOL and bowel function was tested using the Short form- 36 (SF 36) form. Patients’ perspectives and priorities to various aspects of their care including extent of colectomy were tested. Results: A wide spectrum of practices were identified between countries, although the majority would offer an extended colectomy in the presence of known Lynch syndrome, not all would test for this prior to index colectomy. Lynch syndrome could be reliability tested using endoscopic biopsies, and post radiation samples were reliable providing viable tumor was left. Compliance with postoperative surveillance guidelines did not obviate the risk of second primary colorectal cancer, although the stage of disease was less. Short term and medium term quality of life and bowel function were similar between total colectomy and segmental colectomy groups. Young patients would prefer an extended colectomy to reduce the risk of future CRC despite the risk of worsening bowel function. Conclusion: Lynch syndrome can be identified from endoscopic biopsies using DNA MMR immunohistochemical testing and an extended colectomy should be strongly considered in such patients when diagnosed at a young age. Bowel function and quality of life are not dramatically affected by this approach, and young patients are willing to adopt this approach even with the prospect of worse bowel function. Further education among colorectal surgeon society members is required.
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