Retroperitoneoscopic adrenalectomy - introducing a new surgical technique in South Africa.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) is purported to be superior to the laparoscopic transperitoneal approach (LA) in patients with a select spectrum of benign adrenal pathologies. Advantages attributed to the technique include minimal blood loss, shortened operative times, and decreased postoperative pain, explained anatomically by the direct access to the adrenal gland. Reduced workspace is a limitation. METHODS: A retrospective review of 22 consecutive PRAs performed in a single centre between 1 September 2016 and 30 October 2020 is presented. Two experienced laparoscopic surgeons operated on all patients after acquiring the technique at international centres. Suitable candidates were carefully pre-selected. Non-benign pathology, high vascularity, body mass index (BMI) ≥ 45 kg/m2 and anatomical concerns on prior computed tomography (CT) imaging were exclusion criteria. RESULTS: Twenty-two PRAs were performed for a spectrum of benign adrenal pathologies. Twenty-one surgeries (95%) were completed. A single case of pheochromocytoma required conversion. The procedure was safe, a minor postoperative complication (pneumaturia) occurred in one case, and the mortality rate was 0%. Median operative time (80 minutes) is comparable to other reported series in the literature, with a modest linear descending tendency noted over the study period. Underlying pathology influenced operative times. Pheochromocytomas proved to be most challenging and required careful preoperative evaluation. CONCLUSION: The PRA procedures performed at Tygerberg Academic Hospital were safe and reproducible in a select group of cases with benign adrenal pathology. Endocrine surgeons proficient with laparoscopic techniques should be encouraged to use the PRA approach when encountering adrenal neoplasms that fit the criteria.

Duodenojejunal intussusception due to an inflammatory fibroid polyp: a mimic of acute pancreatitis.

SUMMARY: This report describes an extremely unusual cause of acute pancreatitis. It highlights the value of cross-sectional imaging, in the absence of alcohol and gallstone aetiology, to establish a diagnosis and direct management. Computed tomography (CT) revealed a duodenal jejunal intussusception. A benign inflammatory fibroid tumour, acting as a lead point, was surgically resected and the patient made an unremarkable recovery without further episodes of acute pancreatitis.

Abdominoperineal resection in the prone position: early outcomes at a tertiary institution in the Western Cape, South Africa.

BACKGROUND: Extra-levator abdominoperineal resection (ELAPE) performed in the prone jack-knife position is a new technique in the developing world. Literature on the outcomes of ELAPE in a developing country context is scarce. The objective was to assess early outcomes after ELAPE in the prone jack-knife position, and to compare outcomes of patients who underwent the abdominal part of the procedure performed laparoscopically with an open group, at a tertiary institution in Cape Town. METHODS: Records of patients who underwent ELAPE for rectal adenocarcinoma from February 2011 to February 2017 at Tygerberg Hospital were retrospectively reviewed. Variables of interest included staging, rate of circumferential resection margin involvement (CRMI), intraoperative tumour perforation (IOP), perineal wound complications, early postoperative morbidity, length of intensive care unit (ICU) stay, duration of postoperative hospital stay and 30-day mortality rate. RESULTS: 52 patients (median age: 59 years) were included in the analysis. CRMI was evident in 16% (8/49) of patients and IOP in 6% (3/52). Perineal wound complications occurred in 32% (16/50) of patients. Median length of ICU and postoperative hospital stay was 3 days and 7 days, respectively. Overall morbidity was 47% (24/51) and the 30-day mortality rate was 3% (2/52). A significant difference in length of hospital stay was evident between the open and laparoscopic groups (11.5 days vs 6 days). CONCLUSION: Prone abdominoperineal resection (APR), ELAPE, and laparoscopic ELAPE are acceptable and feasible procedures for patients with rectal cancer in the developing world, with outcomes being comparable to those determined in the developed world.

The endovascular management of penetrating carotid artery injuries: long-term follow-up.

OBJECTIVES: To review a single-centre experience with stent-graft treatment of penetrating carotid artery injuries and long-term follow-up. METHODS: All stable patients with carotid artery injuries presenting between August 1998 and February 2009 were considered for endovascular treatment. Patients were selected based on clinical and radiological criteria and data were prospectively collected. Follow-up was conducted clinically, angiographically and by telephonic contact. Endpoints were stroke, death and any other stent-graft-related complications. RESULTS: A total of 128 patients were treated, of whom only 19 were selected for endovascular management. The recorded technical success rate was 100%, with one early stroke and one non-stent-graft-related procedural death. A further four patients were lost to follow-up. The remaining 14 patients had a mean follow-up of nearly 4 years. No stent-graft-related late deaths, strokes or other complications were reported, although one instance of late stent-graft occlusion was documented. CONCLUSION: Endovascular management of penetrating carotid artery injuries is safe and the long-term outcomes justify a more liberal application of this technique in selected patients.

Metabolic surgery in South Africa: an initial academic hospital experience.

BACKGROUND: In South Africa, 42.0% of adult females and 13.5% of adult males are classified as obese, the highest recorded numbers in Sub-Saharan Africa. Metabolic surgery has been proven to be a safe and effective treatment, yet due to demand on government resources has only been performed to a limited extent in public hospitals. The aim of this study was to describe the safety and efficacy of performing metabolic surgery at a single academic hospital in South Africa. METHOD: This was a single centre retrospective review of 57 metabolic surgery procedures performed from October 2011 to September 2017 at Tygerberg Hospital, Cape Town, South Africa. The primary outcome was safety including mortality and adverse events. Secondary outcomes included effect of surgery on weight and diabetes resolution. RESULTS: A total of 57 patients underwent laparoscopic metabolic surgery, of which 44 (83.0%) were female with a mean age (standard deviation) of 42.8 (8.0) years. Fifty-six patients (98%) underwent Roux-and-Y gastric bypass and one (2%) had a sleeve gastrectomy performed. There were no mortalities and overall morbidity was 14.0%, with 3 (5.3%) classified as major and 5 (8.8%) as minor. The follow-up rate at 1 year was 100%. Mean preoperative body mass index (BMI) was 58.8 kg/m2, and comorbidities included hypertension (59.6%), Type 2 Diabetes (42.1%), and dyslipidaemia (36.8%). There were no conversions to open surgery and at one year the mean (95% confidence interval) percentage excess body mass index loss was 50.4% (44.0-56.8%). CONCLUSION: Metabolic surgery can be performed safely in the public sector in South Africa, with short-term safety and efficacy outcomes comparable to international reports. Larger scale studies are needed to determine long-term outcomes and cost-effectiveness.

Surgical and endovascular management of penetrating innominate artery injuries.

OBJECTIVE: To review our management of penetrating innominate artery injuries by open and endovascular techniques. METHODS: Data regarding patient demography, clinical presentation, investigations, associated injuries, pathology, management, complications and mortality, were collected on patients treated at a single centre over 18 years. RESULTS: 39 innominate artery injuries were treated. There were 36 men and three women, with a mean age of 27 years (range 18-49). Thirty-eight injuries were due to stabwounds and one was the result of a gunshot wound. The most common clinical presentations were shock (47%) and haematoma(42%). Twenty-three patients had associated injuries. The most common pathology was false aneurysm in 21 patients followed by 13 actively bleeding injuries, 4 arteriovenous fistulas and 1 arterial occlusion. Thirty-four patients underwent surgical and five endovascular repair. Overall survival was 79%. The stroke rate for surviving patients was 6%. Patients treated with endovascular stenting had shorter hospital and intensive care unit stays than those treated with surgery. CONCLUSIONS: Innominate artery injuries have high rates of morbidity and mortality. A vascular surgical approach with pre-operative angiography, when possible and careful surgical planning by a dedicated team promotes better surgical results. Endovascular and hybrid procedures can become the method of choice when treating stable patients.

Profilin II is alternatively spliced, resulting in profilin isoforms that are differentially expressed and have distinct biochemical properties.

We deduced the structure of the mouse profilin II gene. It contains five exons that can generate four different transcripts by alternative splicing. Two transcripts encode different profilin II isoforms (designated IIa and IIb) that have similar affinities for actin but different affinities for polyphosphoinositides and proline-rich sequences. Profilins IIa and IIb are also present in humans, suggesting that all mammals have three profilin isoforms. Profilin I is the major form in all tissues, except in the brain, where profilin IIa is most abundant. Profilin IIb appears to be a minor form, and its expression is restricted to a limited number of tissues, indicating that the alternative splicing is tightly regulated. Western blotting and whole-mount in situ hybridization show that, in contrast to the expression of profilin I, the expression level of profilin IIa is developmentally regulated. In situ hybridization of adult brain sections reveals overlapping expression patterns of profilins I and IIa.

Clinical significance of t(14; 18)-positive cells in the circulation of patients with stage III or IV follicular non-Hodgkin's lymphoma during first remission.

PURPOSE: To evaluate polymerase chain reaction (PCR) analysis as a method for the detection of circulating lymphoma cells in patients with stage III and IV t(14; 18)-positive follicular Non-Hodgkin's lymphoma (NHL) in first remission in a longitudinal prospective study. PATIENTS AND METHODS: Peripheral blood or bone marrow from eight patients with stage III and IV t(14; 18)-positive NHL was studied using PCR to detect the presence of t(14; 18)-positive cells in the circulation at different times during first remission. RESULTS: In four of six patients with no clinical evidence of disease (NCED), t(14; 18)-positive cells were detectable in the circulation. In one of two patients with clinical evidence of disease (CED), no t(14; 18)-positive cells were found at the four different occasions tested during first remission. First-remission duration ranged from 17 to 81+ months. The duration from the first PCR determination in remission until first relapse or the end of the observation period ranged from 10 to 37+ months. CONCLUSION: In patients with t(14; 18)-positive follicular NHL stage III and IV, treated with conventional remission induction therapy, the presence or absence of t(14; 18)-positive cells in the circulation shows no obvious correlation with the clinical remission status and the remission duration.

Detection of residual disease in translocation (14;18) positive non-Hodgkin's lymphoma, using the polymerase chain reaction: a comparison with conventional staging methods.

This paper reports the detection of residual lymphoma cells in blood and bone marrow samples from patients with translocation (t) (14;18) positive non-Hodgkin's lymphoma by the polymerase chain reaction (PCR) compared with conventional staging techniques. In 15 of 22 samples, in which no lymphoma cells could be detected by morphological examination, t(14;18) positive cells were detected by PCR. In 13 of 21 samples, in which a monoclonal B-cell population was not detectable by immunological marker analysis, PCR was positive. The clinical status (physical examination, imaging techniques, leucocyte count, and occasionally morphology and immunological marker analysis) was documented in 30 patients at the time of PCR analysis. In three of 19 patients with clinical evidence of disease, circulating t(14;18) positive cells were not detectable by PCR. Five of 11 patients in clinical remission from 7 to 47 months, showed t(14;18) positive cells in the blood. Our data show that PCR analysis in t(14;18) positive non-Hodgkin's lymphoma offers a powerful tool in the study of residual disease.

Genomic organization of the translocations (8;14) and (14;18) in a new lymphoma cell line.

We generated a new lymphoma cell line carrying the translocations (8;14) and (14;18) and studied the genomic organization and expression of the BCL-2 and MYC genes. Polymerase chain reaction (PCR) and Southern analysis showed that the breakpoints of t(14;18) were located in the major breakpoint region (mbr) of the BCL-2 gene and just 5' of JH6 in the IgH locus. The breakpoints of the t(8;14) were located upstream of exon 2 in the non-coding region of the MYC gene and near the switch region of the IgH locus. Both IgH loci were involved in chromosomal translocations resulting in the absence of a functional B-cell receptor. Normal BCL-2 and truncated MYC transcripts were detected in these cells. The BCL-2 protein was expressed.

Detection of circulating breast tumor cells by differential expression of marker genes.

PURPOSE: We undertook a systematic approach to identify breast cancer (BC) marker genes with molecular assays and evaluated these marker genes for the detection of minimal residual disease in peripheral blood mononuclear cells (PBMCs). EXPERIMENTAL DESIGN: We used serial analysis of gene expression to identify a range of genes that were expressed in BC but absent in the expression profiles of blood and bone marrow cells. Next, we evaluated a panel of four marker genes (p1B, PS2, CK19, and EGP2) by real-time quantitative PCR in 103 PBMC samples from patients with metastatic BC (stage III/IV) and in 96 PBMC samples from healthy females. RESULTS: Increased marker gene expression of at least one marker was seen in 33 of 103 patients. Using quadratic discriminant analysis including all four marker genes, we determined a discriminant value with 29% positivity in the BC patient group that did not yield false positive results among the healthy females. CONCLUSIONS: Real-time PCR for the simultaneous expression of multiple cancer-specific genes may ensure the specificity required for the clinical application of mRNA expression-based assays for occult tumor cells.

Persistent T cell and B cell activities in the duodenal mucosa of AIDS patients.

OBJECTIVE: As HIV infection most commonly occurs via a mucosal surface, and as gastrointestinal symptoms are very frequent among HIV-infected patients, we investigated the functional properties of residual lymphocytes in the duodenal mucosa from HIV-infected individuals. DESIGN: Duodenal biopsies and blood samples were obtained from 19 HIV-infected patients [Centers for Disease Control and Prevention (CDC) stage III] and from 19 controls. METHODS: Phenotypic analysis of lymphocytes was performed by flow cytometry and/or immunocytochemistry. Interferon gamma (IFN-gamma), interleukin (IL) 4 and immunoglobulin secretions were analysed by enzyme-linked immunospot techniques. The phenotype of cytokine-producing cells was analysed by flow cytometry. RESULTS: The proportions of duodenal T lymphocytes from HIV-infected patients spontaneously secreting IFN-gamma or IL-4 were not lower than those from healthy controls. In patients with a high intestinal mucosal viral load, they were higher than in controls (P < 0.05). The proportions of immunoglobulin-secreting cells were significantly raised in HIV-infected patients for the three main isotypes. CONCLUSIONS: T- and B-cell populations of the intestinal mucosa remain functional or are even activated in patients with AIDS, even when the numbers of both mucosal and circulating CD4+ lymphocytes are strongly decreased.

Dimerization of profilin II upon binding the (GP5)3 peptide from VASP overcomes the inhibition of actin nucleation by profilin II and thymosin beta4.

Profilin II dimers bind the (GP5)3 peptide derived from VASP with an affinity of approximately 0.5 microM. The resulting profilin II-peptide complex overcomes the combined capacity of thymosin beta4 and profilin II to inhibit actin nucleation and restores the extent of filament formation. We do not observe such an effect when barbed filament ends are capped. Neither can profilin I, in the presence of the peptide, promote actin polymerization during its early phase consistent with a lower affinity. Since a Pro17 peptide-profilin II complex only partially restores actin polymerization, the glycine residues in the VASP peptide appear important.

Regulation of phosphoinositide hydrolysis induced by histamine and guanine nucleotides in human HeLa carcinoma cells. Calcium and pH dependence and inhibitory role of protein kinase C.

The regulation of phospholipase C has been investigated in both intact and streptolysin-O permeabilized human HeLa carcinoma cells. Stimulation of phospholipase C by histamine and guanosine-5'-O-thiotriphosphate (GTP[S]) requires the presence of at least 10 nM free Ca2+, but is not significantly further increased by raising [Ca2+]i to greater than 10(-6) M. The pH optimum of the inositol phosphate response is at pH 6.8, while small changes in intracellular pH, as occur during hormonal stimulation (0.2-0.4 unit) attenuate the histamine/GTP[S]-induced stimulation of phospholipase C. Increasing cellular cAMP levels, either through addition of cell permeable cAMP analogues to intact cells or by stimulation with isoproterenol, does not affect histamine responsiveness, arguing against cross-talk between both signalling pathways. In contrast, we found that the response to histamine and/or GTP[S] is largely inhibited after brief pretreatment of the cells with phorbol esters or synthetic diacylglycerol prior to permeabilization, suggesting that protein kinase C exerts feedback inhibition at the level of, or downstream from, the putative GTP-binding protein.

A new B-cell line showing a complex translocation (8;14;18) and BCL2 rearrangement.

A cell line named ROS-50 (Rotterdam suspension cell line no. 50) has been established from peripheral blood of a 69-year-old male with acute lymphoblastic leukemia (FAB type L3). Among the aberrations, cytogenetic analysis showed the presence of 14q+, 18q-, and two 8q- marker chromosomes. With fluorescence in situ hybridization (FISH) we characterized the chromosomal translocations, t(8;14) and t(14;18), in which the same chromosome 14 is involved. PCR analysis demonstrated the presence of on IGH-BCL2 rearrangement with a breakpoint in the minor cluster region (mcr) confirming the t(14;18) characteristic for follicular lymphoma. Additional studies showed high expression of BCL2 protein, an early B-cell immunophenotype, and an unusual pattern of IGH gene rearrangement.

Human oesophagus: a convenient antigenic substrate for the determination of anti-endomysium antibodies in the serological diagnosis of coeliac disease.

OBJECTIVE: Immunoglobulin (Ig) A-class anti-endomysium antibodies are superior to other current antibody tests for detecting coeliac disease. We aimed to evaluate the suitability of human oesophagus for the determination of anti-endomysium antibodies. DESIGN: The specificity of monkey and human oesophageal tissue as antigenic substrate were compared using indirect immunofluorescence analysis. PATIENTS AND METHODS: Overall, 159 individuals were studied: 56 patients with biopsy-proven coeliac disease (39 with active disease) and 103 controls. The patients' IgA-class anti-endomysium antibodies were compared using unfixed cryostat sections of human and monkey oesophagus. Indirect immunofluorescence analysis was performed with an initial serum sample dilution of 1:5, and if positive, the highest dilution yielding a positive reaction was reported. RESULTS: The anti-endomysium antibody test was positive in 38 out of 39 patients with active coeliac disease using monkey oesophagus (sensitivity 97%) and in all 39 patients with active coeliac disease using human oesophagus (sensitivity 100%). Ten out of 17 coeliac patients on a gluten-free diet had positive anti-endomysium antibodies using monkey oesophagus and 12 using human oesophagus as the antigenic substrate. This test was negative in all 103 controls using both substrates. CONCLUSIONS: Our study shows that human oesophageal tissue can be used instead of monkey tissue for determining anti-endomysium antibodies. Human tissue is a more sensitive antigenic substrate than monkey oesophagus and can be used to determine low titres of antibodies. Improving the diagnostic sensitivity of the anti-endomysium antibody test would make an important contribution to screening for coeliac disease.

Adhesion molecules and leukocyte common antigen on monocytes and granulocytes during hemodialysis.

As contact of blood with artificial membranes may activate cell adhesiveness, we investigated in 5 patients the expression of several adhesion-promoting molecules on monocytes and granulocytes during hemodialysis on cuprophane (CU), cellulose acetate (CA), and polyacrylonitrile (PAN) membranes. After staining with specific fluorescent monoclonal antibodies, flow cytometric analysis was performed to evaluate the expression of CD11b (= Mac 1, CR3, or C3bi receptor), CD11a (= leukocyte function antigen 1 or LFA-1, or gp 180/95), CD54 (= intercellular adhesion molecule 1 or ICAM 1), and CD45 (= leukocyte common antigen) on circulating leukocytes. Granulocytopenia occurred at 15 minutes with CU and CA but not with PAN; significant monocytopenia occurred on the contrary with all 3 membranes. The drop in monocyte counts was maximal at 15 minutes on CU and CA, and at 180 minutes on PAN; it was also more important with CU (88 +/- 2.6%, alpha = 0.005) and CA (66.4 +/- 4.1%, alpha = 0.01) than with PAN (36.2 +/- 6.2%). Hemodialysis on CU, CA, and PAN was associated with a 2- to 3-fold CD11b and CD45 overexpression on peripheral monocytes; these molecules also increased on circulating granulocytes but to a lesser extent on PAN than on CU and CA (alpha < 0.05). There were no hemodialysis-induced changes in CD11a and CD54 expression on circulating monocytes or granulocytes. The upregulation of CD11b may provide a molecular mechanism for the sequestration of monocytes and granulocytes in the circulation during hemodialysis, while upregulation of CD45 might reflect mechanisms regulating the leukocyte activation state.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromocriptine-induced decrease in blood pressure in conscious spontaneously hypertensive rats: evidence for a peripheral site of action.

The aim of the study was to discover whether the dopamine agonist bromocriptine has a central or peripheral site of action on blood pressure. An intraperitoneal injection of bromocriptine (0.5 mg kg-1) induced a long-lasting decrease in blood pressure in conscious spontaneously hypertensive rats (SHR). This effect was blocked by peripheral pretreatment with haloperidol or domperidone, but not by central treatment with haloperidol. A central injection of bromocriptine had only minor effects on blood pressure. These results suggest that primarily peripheral, rather than central, mechanisms are involved in the hypotensive effects of bromocriptine.

Financial time series prediction using least squares support vector machines within the evidence framework.

The Bayesian evidence framework is applied in this paper to least squares support vector machine (LS-SVM) regression in order to infer nonlinear models for predicting a financial time series and the related volatility. On the first level of inference, a statistical framework is related to the LS-SVM formulation which allows one to include the time-varying volatility of the market by an appropriate choice of several hyper-parameters. The hyper-parameters of the model are inferred on the second level of inference. The inferred hyper-parameters, related to the volatility, are used to construct a volatility model within the evidence framework. Model comparison is performed on the third level of inference in order to automatically tune the parameters of the kernel function and to select the relevant inputs. The LS-SVM formulation allows one to derive analytic expressions in the feature space and practical expressions are obtained in the dual space replacing the inner product by the related kernel function using Mercer's theorem. The one step ahead prediction performances obtained on the prediction of the weekly 90-day T-bill rate and the daily DAX30 closing prices show that significant out of sample sign predictions can be made with respect to the Pesaran-Timmerman test statistic.

Dimensional differences in the craniofacial morphologies of groups with deep and shallow mandibular antegonial notching.

Certain craniofacial characteristics were identified on the lateral cephalograms of 40 untreated subjects with shallow mandibular antegonial notches and 40 subjects with deep notches. Subjects with shallow notches demonstrated more on the morphological characteristics usually associated with horizontal mandibular growth patterns than did subjects with deep notches, and their mandibles were positioned more protrusively. In general, the mandibles of the shallow notch subjects proved to be longer than mandibles of the deep notch subjects. On average, mandibles with deep notches showed greater gonial angles, deeper posterior ramus notch depths, and larger occlusal plane inclinations. The total anterior facial height of shallow notch subjects was much smaller than that of the deep notch subjects. The maxillae in deep notch subjects were more retrusive in relation to the cranial base when compared with the shallow notch subjects. A discriminant analysis was used to determine which combinations of variables were most consistently related to either deep or shallow mandibular antegonial notches. Eighty percent (80%) of the cases were classified correctly as deep or shallow notch cases by means of this discriminant function.