Doctoral Degrees (Surgery)

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    Aspects on advanced procedures during endoscopic retrograde cholangiopancreatography (ERCP) for complex hepatobiliary disorders
    (Stellenbosch : Stellenbosch University, 2021-03) Lubbe, Jeanne Adele; Moore, Samuel; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Surgical Sciences.
    Background: The rapid development in endoscopic technology and associated skills has led to an increase in more advanced procedures being performed during endoscopic retrograde cholangiopancreatography (ERCP). Knowledge is limited regarding clinical value, integration, and outcomes for single operator cholangiopancreatoscopy (SOCP) and endoscopic intervention in the different Bismuth-Corlette (B-C) locations in the hepatic hilum. Objectives: To determine the clinical value of SOCP in the diagnosis and treatment of complex hepatobiliary and pancreatic disease. To describe the nationwide integration of SOCP and the extent to which adverse events are influenced when SOCP is added to ERCP. To compare adverse events and reintervention rates after endoscopic stenting for malignant obstruction in the distal and hilar locations of the biliary tree. To compare outcomes after endoscopic transpapillary (ETP) and percutaneous transhepatic (PTH) stenting in the palliation of malignant hilar obstruction (MHO). Methods: In study I all SOCP procedures performed between March 2007-December 2014 at a tertiary highvolume endoscopy unit were separately graded according to a predefined 4-graded scale estimating therapeutic value and diagnostic yield. Study II was a nationwide case-control study nested within the cohort of ERCP procedures, with- or without SOCP, and registered in the Swedish Registry for Gallstone Surgery and ERCP (GallRiks) between 2007-2012. To assess risk factors for adverse events, multivariate logistic regression was performed, and odds ratios (OR) calculated. The GallRiks registry was also utilised in study III where all patients undergoing endoscopic stenting for malignant biliary obstruction between 2010-2017 (based on International Classification of Diseases (ICD) coding), were included. Kaplan-Meier analysis was employed to calculate stent patency and Cox proportional hazard models to calculate the risk for recurrent biliary obstruction after single metal stent placement. To compare ETP and PTH drainage approaches, a retrospective deconstructed analysis of palliative stenting procedures for MHO at two specialised referral centres over a 5-year period was performed. Within-group analyses were performed to explore outcomes for different B-C types and Kaplan-Meier and restricted mean survival time analyses were performed to calculate and compare duration of therapeutic success. Results: In 365 SOCP procedures, SOCP was found be of pivotal importance in 19% of patients, of great clinical significance in 44%, and did not affect clinical decision-making or alter clinical course in 37% of patients. In study II a learning curve was observed after first introduction of 408 SOCP procedures, and postprocedural adverse events (19.1% vs. 14.0%), pancreatitis (7.4% vs. 3.9%) and cholangitis (4.4% vs. 2.7%) were more prevalent when SOCP was added to ERCP. After multivariate analysis, the risk for postprocedural adverse events remained (OR 1.35, 95% CI [1.04 - 1.74]). In 4623 ERCP procedures performed for stenting of malignant strictures (1364 hilar), adverse events and 6-month reintervention rates were increased after hilar stenting compared to distal stenting (17.2% vs. 12.0%, 73.4% vs. 55.9%). On multivariate analysis the risk for reintervention was three times higher after single metal stent placement in the hilum compared to the distal biliary tree (HR 3.47, 95% CI [2.01-6.00], p<0.001). In 293 patients undergoing palliative stenting for MHO (52.2% ETP, 47.8% PTH), access and bridging success in the ETP and PTH groups were 83.5% vs. 97.2% and 90.2% vs. 84.5%, respectively. Technical and therapeutic success were equivalent between the two groups, but duration of therapeutic success was longer after ETP drainage, with a 3-month gain in duration of therapeutic success after adjustment for B-C type (95% CI [26-160], p=0.006). Cholangitis rates were equivalent (21.4% vs. 24.7%), while pancreatitis was more common in the ETP group and deaths more common in the PTH group. Conclusions: When added to ERCP, SOCP contributes significant clinical value in 64% of cases. However, there is an increased risk of intra- and postprocedural adverse events which, together with a learning curve, suggests that it should likely be performed in specialised high-volume centres. Regarding endoscopic intervention for MHO, stenting in the hepatic hilum compared to the distal biliary tree is associated with more adverse events and decreased stent patency. When comparing palliative ETP with PTH stenting for MHO, both approaches have similar technical and therapeutic success, with ETP drainage being more durable. Future studies should explore the complimentary role of both approaches in specific B-C types.
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    An investigation into the causes of intraocular inflammation in HIV-positive and HIV-negative patients in the Western Cape Province, South Africa
    (Stellenbosch: Stellenbosch University, 2018-03) Smit, Derrick Peter; Meyer, David; Stellenbosch University. Faculty of Health Sciences. Dept. of Surgical Sciences. Ophthalmology.
    ENGLISH SUMMARY: The causes of intraocular inflammation are divided into 3 large groups namely infectious, non-infectious and idiopathic. This research project set out to establish the prevalence of these 3 large groups and their different subgroups in an effort to determine whether HIV infection plays an important role in how frequently they occur in the Western Cape Province. Out of a total of 106 participants with uveitis enrolled in this study, 66 cases (62.3%) were HIV- and 40 (37.7%) HIV+ with a median CD4+ cell count of 242 x 106/l. The majority of participants were black (n=52; 49.1%) or of mixed ethnicity (n=49; 46.2%) and 59.6% of blacks were HIV+ versus 16.3% of mixed ethnicity participants. Anatomically, most cases were either anterior uveitis (58.5%) or panuveitis (32.1%) while infectious uveitis (n=70; 66.0%) was more common than non-infectious (n=18; 17.0%) or idiopathic (n=18; 17.0%) uveitis. An infectious cause was found in 80.0% of HIV+ cases versus 57.6% in HIV- cases. Intraocular tuberculosis (IOTB) was the most common cause of infectious uveitis in this study (n=35; 33.0%) where possible IOTB (n=23; 21.7%) was more common than probable IOTB (n=12; 11.3%). Tuberculin skin testing alone was more sensitive (90.3% vs 85.7%) and had a higher negative predictive value (92.1% vs 81.5%) than QuantiFERON alone and the latter therefore does not warrant the extra expense in our highly endemic setting. Herpetic uveitis formed the second largest group (n=13; 12.2%) with VZV (53.8%) responsible for more cases than CMV (38.5%) and HSV (7.7%). Syphilis was the third most common cause of infectious uveitis (n=11; 10.4%). Using a novel immunoblot approach the study investigated the relationship between ocular and neurosyphilis and demonstrated that these 2 conditions do not always co-exist. HIV infection was present in 31.4% of IOTB cases, 61.5% of herpetic cases and 81.8% of syphilitic cases. Toxoplasma (n=4; 3.8%), Rubella virus and poststreptococcal uveitis (n=3; 2.8% each) as well as HIV-induced uveitis (n=1; 0.9%) were responsible for the remainder of the infectious uveitis cases. EBV was often identified on multiplex PCR (n=11; 10.4%) but no evidence of active intraocular replication or antibody production was found to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified (n=9; 81.8%). Sarcoidosis and HLA-B27 associated anterior uveitis (n=8; 7.5% each) were the most common causes of non-infectious uveitis. All patients with ocular sarcoid and 75% of patients with HLA-B27 uveitis were HIV-. The percentage of idiopathic cases in this study was lower than in many similar studies (n=18; 17.0%). This is likely due to the high percentage of cases of possible IOTB diagnosed using a recently proposed classification as many of those cases would have been labelled as idiopathic in other studies. The majority of idiopathic uveitis cases were HIV- (n=12; 66.7%). This study revealed that infectious uveitis is the commonest form of uveitis in both HIV+ and HIV- patients but that the specific pathogens differ between patients with and without HIV infection.