Proteomic analysis identifies dysregulated proteins and associated molecular pathways in a cohort of gallbladder cancer patients of African ancestry.

BACKGROUND: Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry. This study aimed to determine dysregulated proteins in South African GBC patients to identify potential mechanisms of the disease progression and plausible biomarkers. METHODS: Tissues (27 GBC, 13 Gallstone disease, and 5 normal tissues) and blood plasma (54 GBC and 73 Benign biliary pathology) were obtained from consenting patients. Protein extraction was performed on all tissues and liquid chromatography-mass spectrometry was used for proteomic profiling. A project-specific spectral library was built using the Pulsar search algorithm. Principal component and Spearman's rank correlation analyses were performed using PAST (V4.07b). Pathway and Network analyses were conducted using REACTOME (v3.7) and stringAPP (v1.7.0), respectively. RESULTS: In the tissue sample group, there were 62 and 194 dysregulated proteins in GBC compared to normal and gallstone groups, respectively. In the plasma group, there were 33 altered proteins in GBC compared to the benign biliary pathology group. We found 9 proteins (APOA1, APOA2, RET4, TTR, HEMO, HBB, HBA, PIGR, and APOE) to be commonly dysregulated in both tissue and plasma. Furthermore, a subset analysis demonstrated that 2 proteins, S100A8 and S100A9, were downregulated in GBC patients with GD history compared to those without. Pathway analysis showed that the dysregulated proteins in GBC patients were enriched in pathways involved in smooth muscle contraction, metabolism, ECM organization, and integrin cell surface interactions. CONCLUSION: The identified dysregulated proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and plasma samples suggests their potential utility as biomarkers of GBC in this sample cohort.

Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman's correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance.

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

Role of different immune cells and metabolic pathways in modulating the immune response in pancreatic cancer (Review).

Pancreatic cancer is an aggressive cancer, making it a leading cause of cancer­related deaths. It is characteristically resistant to treatment, which results in low survival rates. In pancreatic cancer, immune cells undergo transitions that can inhibit or promote their functions, enabling treatment resistance and tumor progression. These transitions can be fostered by metabolic pathways that are dysregulated during tumorigenesis. The present review aimed to summarize the different immune cells and their roles in pancreatic cancer. The review also highlighted the individual metabolic pathways in pancreatic cancer and how they enable transitions in immune cells. Finally, the potential of targeting metabolic pathways for effective therapeutic strategies was considered.

Breast Cancer Cells Induce a Pro-inflammatory Response to Mitigate Immune Mediation in a 3D Culture Model.

BACKGROUND: Growth factors and cytokines mediate complex interactions between cells within the breast tumour microenvironment. In advanced cancer, an excess of regulatory T (TREG) lymphocytes and lack of natural killer (NK) cells in tumour-infiltrating lymphocyte populations may reflect a shift to pro-tumorigenic adaptive immune mechanisms. To facilitate targeted assessment of the interactions between tumour and immune cells ex vivo, three-dimensional (3D) culture systems are able to better recapitulate the in vivo microenvironment, recreating the anatomy of tumours. MATERIALS AND METHODS: We used 3D breast tumour models to determine morphological alterations, and the levels of secreted transforming growth factor-ß (TGFß) and induced cytokines. 3D luminal phenotype models and basal phenotype models were generated by culturing NK cells and CD4+CD25+ TREG cells with MCF-7 cells and MDA-MB-231 cells respectively, in growth factor-reduced Matrigel. TGFß was qualitatively assessed by immunolocalisation and cytokine data from culture supernatant was acquired with a multiplex cytokine assay. Traditional statistical analysis and principal component analysis were employed to unravel the cytokine response. RESULTS AND CONCLUSION: We identified that an interleukin-6 (IL6)-chemokine axis associated with TGFß is primarily responsible for differences detected between breast cancer models, with luminal and basal phenotype tumours responding differentially to immune mediation. Identified cytokines are implicated in facilitating tumour cell subversion of immune cell function to promote an invasive phenotype. Moreover, the disruption of the extracellular matrix and failure to form well-differentiated tumour masses/networks is indicative of enhanced malignancy. Tumour cells are implicated in promoting a pro-inflammatory microenvironment to attenuate NK cell function and in inducing a pro-tumorigenic profile that is facilitated by TREG lymphocytes.

SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways.

Pancreatic cancer accounts for 2.8% of new cancer cases worldwide and is projected to become the second leading cause of cancer-related deaths by 2030. Patients of African ancestry appear to be at an increased risk for pancreatic ductal adenocarcinoma (PDAC), with more severe disease and outcomes. The purpose of this study was to map the proteomic and genomic landscape of a cohort of PDAC patients of African ancestry. Thirty tissues (15 tumours and 15 normal adjacent tissues) were obtained from consenting South African PDAC patients. Optimisation of the sample preparation method allowed for the simultaneous extraction of high-purity protein and DNA for SWATH-MS and OncoArray SNV analyses. We quantified 3402 proteins with 49 upregulated and 35 downregulated proteins at a minimum 2.1 fold change and FDR adjusted p-value (q-value) ≤ 0.01 when comparing tumour to normal adjacent tissue. Many of the upregulated proteins in the tumour samples are involved in extracellular matrix formation (ECM) and related intracellular pathways. In addition, proteins such as EMIL1, KBTB2, and ZCCHV involved in the regulation of ECM proteins were observed to be dysregulated in pancreatic tumours. Downregulation of pathways involved in oxygen and carbon dioxide transport were observed. Genotype data showed missense mutations in some upregulated proteins, such as MYPN, ESTY2 and SERPINB8. Approximately 11% of the dysregulated proteins, including ISLR, BP1, PTK7 and OLFL3, were predicted to be secretory proteins. These findings help in further elucidating the biology of PDAC and may aid in identifying future plausible markers for the disease.

Immunotherapeutic strategies in pancreatic ductal adenocarcinoma (PDAC): current perspectives and future prospects.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest human malignancies with a dismal prognosis. During PDAC progression, the immune response is affected as cancer cells evade detection and elimination. Recently, there have been advances in the treatment of PDAC using immunotherapy, although a lot more work is yet to be done. In this review, we discuss these advances, challenges and potentials. We focus on existing and potential immune targets for PDAC, drugs used to target them, and some clinical trials conducted so far with them. Finally, novel targets in the tumour microenvironment such as stromal cells and other potential future areas to explore including bacterial therapy and the use of neoantigens in immunotherapy are highlighted.

Increased expression of plakoglobin is associated with upregulated MAPK and PI3K/AKT signalling pathways in early resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, and it is associated with a 5-year survival rate of <10% due to limited early detection methods and ineffective therapeutic options. Thus, an improved understanding of the mechanisms involved in the early stages of PDAC tumorigenesis is crucial in order to identify potential novel diagnostic and therapeutic targets. The most common signalling aberrations in PDAC occur in the Wnt/Notch signalling pathway, as well as within the epidermal growth factor receptor (EGFR) pathway and its associated ligands, EGF and transforming growth factor-ß. In addition, the RAS family of oncogenes, which act downstream of EGFR, are found mutated in most pancreatic cancer samples. Plakoglobin, a component of the EGFR signalling pathway, serves an important role in normal cell adhesion; however, its role in PDAC is largely unknown. The present study used transcriptome sequencing and focussed proteome microarrays to identify dysregulated genes and proteins in PDAC. The presence of upregulated plakoglobin expression levels was identified as a distinguishing feature between the PDAC microenvironment and normal pancreatic tissue. Furthermore, plakoglobin was demonstrated to be associated with the differential upregulation of the PI3K/AKT and MAPK signalling pathways in the tumour microenvironment, which suggested that it may serve an important role in PDAC tumourigenesis.

Transient Expression of Interleukin-21 in the Second Hit of Acute Pancreatitis May Potentiate Immune Paresis in Severe Acute Pancreatitis.

OBJECTIVES: Interleukin-21 (IL-21) is a cytokine associated with tissue inflammation, autoimmune and infectious diseases. Organ dysfunction and death can occur in patients with acute pancreatitis (AP) in two distinct clinical phases. Initially, a systemic inflammatory response syndrome may be followed by systemic sepsis from infected pancreatic necrosis, known as the "second hit." The expression and possible role of IL-21 in AP has not been established. METHODS: Thirty-six patients with mild, moderate, and severe AP (SAP) were enrolled. Peripheral blood samples of patients were drawn on days 7, 9, 11, and 13. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine the expression and concentration of IL-21. RESULTS: Interleukin-21 mRNA levels increased significantly at day 9 in severe (P = 0.002) pancreatitis compared with both the mild and control patient groups. At the protein level, IL-21 was elevated in SAP patients compared with those with mild pancreatitis, although this was not significant. Furthermore, day 9 IL-21 was elevated in septic SAP patients and patients with pancreatic necrosis. CONCLUSIONS: Interleukin-21 is transiently elevated in SAP compared with the mild/moderate group, and hence IL-21 may contribute to the immune imbalance that occurs in AP.

The thick left ventricular wall of the giraffe heart normalises wall tension, but limits stroke volume and cardiac output.

Giraffes--the tallest extant animals on Earth--are renowned for their high central arterial blood pressure, which is necessary to secure brain perfusion. Arterial pressure may exceed 300 mmHg and has historically been attributed to an exceptionally large heart. Recently, this has been refuted by several studies demonstrating that the mass of giraffe heart is similar to that of other mammals when expressed relative to body mass. It thus remains unexplained how the normal-sized giraffe heart generates such massive arterial pressures. We hypothesized that giraffe hearts have a small intraventricular cavity and a relatively thick ventricular wall, allowing for generation of high arterial pressures at normal left ventricular wall tension. In nine anaesthetized giraffes (495±38 kg), we determined in vivo ventricular dimensions using echocardiography along with intraventricular and aortic pressures to calculate left ventricular wall stress. Cardiac output was also determined by inert gas rebreathing to provide an additional and independent estimate of stroke volume. Echocardiography and inert gas-rebreathing yielded similar cardiac outputs of 16.1±2.5 and 16.4±1.4 l min(-1), respectively. End-diastolic and end-systolic volumes were 521±61 ml and 228±42 ml, respectively, yielding an ejection fraction of 56±4% and a stroke volume of 0.59 ml kg(-1). Left ventricular circumferential wall stress was 7.83±1.76 kPa. We conclude that, relative to body mass, a small left ventricular cavity and a low stroke volume characterizes the giraffe heart. The adaptations result in typical mammalian left ventricular wall tensions, but produce a lowered cardiac output.

Cystatin C- and creatinine-based equations in the assessment of renal function in HIV-positive patients prior to commencing Highly Active Antiretroviral Therapy.

BACKGROUND: We evaluated the accuracy and precision of creatinine- and cystatin C-based prediction equations for estimating glomerular filtration rate compared to measured glomerular filtration rate in an antiretroviral-naive human immunodeficiency virus population. METHODS: The study population consisted of 100 treatment-naive HIV patients. Glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, as well as cystatin C-based equations (CKD-EPIcystatin C, cystatin Cvan Deventer and CKD-EPIcombined)) compared to (51)Cr-EDTA plasma clearance-measured glomerular filtration rate. We calculated percentage bias, standard deviation of the differences, accuracy within 15 and 30% of measured glomerular filtration rate and sensitivity and specificity for predicting measured glomerular filtration rate <60 mL/min/1.73 m(2). RESULTS: Bias for all estimating glomerular filtration rate equations ranged from -9.4% to 38.4%. The CKD-EPIcombined without ethnicity correction factor equation had the least bias, 2.9% (-2.9 to 8.8). Bias was higher for the Modification of Diet in Renal Disease and CKD-EPI equation with the African-American ethnicity factor (38.4 and 33.7%) than without (14.2 and 15.3%). Standard deviation of the differences ranged from 29.2% (CKD-EPIcombined without ethnicity factor) to 54.0% (Modification of Diet in Renal Disease with ethnicity factor). Accuracy within 30% of measured glomerular filtration rate ranged from 78% for CKD-EPIcombined without ethnicity factor to 56.7% for the Cockcroft-Gault equation. Sensitivity for creatinine-based equations was less than 50% and for the CKD-EPIcystatin C equation was 75%. CONCLUSION: Sensitivity of creatinine-based equations for predicting glomerular filtration rate was poor in this group of patients. The CKD-EPIcombined equation performed better than creatinine-based equations.

Establishment of a heterotypic 3D culture system to evaluate the interaction of TREG lymphocytes and NK cells with breast cancer.

Three-dimensional (3D) culture approaches to investigate breast tumour progression are yielding information more reminiscent of the in vivo microenvironment. We have established a 3D Matrigel system to determine the interactions of luminal phenotype MCF-7 cells and basal phenotype MDA-MB-231 cells with regulatory T lymphocytes and Natural Killer cells. Immune cells were isolated from peripheral blood using magnetic cell sorting and their phenotype validated using flow cytometry both before and after activation with IL-2 and phytohaemagglutinin. Following the establishment of the heterotypic culture system, tumour cells displayed morphologies and cell-cell associations distinct to that observed in 2D monolayer cultures, and associated with tissue remodelling and invasion processes. We found that the level of CCL4 secretion was influenced by breast cancer phenotype and immune stimulation. We further established that for RNA extraction, the use of proteinase K in conjunction with the Qiagen RNeasy Mini Kit and only off-column DNA digestion gave the best RNA yield, purity and integrity. We also investigated the efficacy of the culture system for immunolocalisation of the biomarkers oestrogen receptor-α and the glycoprotein mucin 1 in luminal phenotype breast cancer cells; and epidermal growth factor receptor in basal phenotype breast cancer cells, in formalin-fixed, paraffin-wax embedded cultures. The expression of these markers was shown to vary under immune mediation. We thus demonstrate the feasibility of using this co-culture system for downstream applications including cytokine analysis, immunolocalisation of tumour biomarkers on serial sections and RNA extraction in accordance with MIQE guidelines.

Enuresis in South African children: prevalence, associated factors and parental perception of treatment.

UNLABELLED: Study Type--Symptom Prevalence (prospective cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Nocturnal enuresis is a common childhood problem. Although its prevalence is known in many countries, no data are available from South Africa and it is difficult to extrapolate data from developed countries to a population with such diverse conditions and resource-poor settings. This study is the first to report on the 16% prevalence rate and the low level of parental knowledge of enuresis in South African children aged between 5 and 10 years. OBJECTIVES: • To establish the prevalence of NE in 5-10 year old South African children in a cross-sectional study using a parent-completed questionnaire. • To establish the parental perception and associated factors of mono-symptomatic nocturnal enuresis (MNE) treatment and treatment success rates in 5-10 year old children from South Africa. PATIENTS AND METHODS: • A total of 4700 questionnaires were distributed to children at 37 selected schools willing to participate from South Africa. Parents anonymously filled out the questionnaire. • Data were reported as frequencies and percentages of NE in tables according to different gender and age groups. • The Chi-square test compared proportions between groups and Fisher's Exact test corrected for small numbers of observations (n ≤ 5). Age differences were determined using Student's t-test. A P-value ≤ 0.5 was considered to be statistically significant. RESULTS: • The questionnaire's response rate was 72.1%, with 3389 children included in the study. • The overall prevalence of NE was 16.0%-14.4% of children suffered from mono-symptomatic NE (MNE). The prevalence of NE in boys was double that in that in girls. • Only 28.3% had received some form of treatment, whereas 13.5% had been medically treated by a doctor. Parents' awareness of treatment modalities available is outdated and most of the management of MNE was done by parents themselves, albeit with low success rates. • A positive family history was found in 50.5% of children suffering from MNE. • Constipation was a problem in 15.8% of children with enuresis. CONCLUSIONS: • This is the first study to estimate the prevalence of NE and report on the parental perception and possible associated factors of enuresis in children from South Africa. The study showed that South African children have a similar prevalence rate of NE (16%) when compared with other countries. • The possible associated factors with MNE in South Africa include constipation and a family history of enuresis. • Finally, there are low levels of parental knowledge of treatment modalities of MNE, leaving many children untreated.

Prevalence of residual left ventricular structural changes after one year of antihypertensive treatment in patients of African descent: role of 24-hour pulse pressure.

OBJECTIVES: One year of antihypertensive therapy may normalise left ventricular (LV) structure in 51% of hypertensive patients of European descent. Whether similar effects can be achieved in patients of African descent, who have a high prevalence of concentric LV hypertrophy (LVH) and remodelling, is unknown. METHODS: In 103 hypertensive patients in the Baragwanath Hypertension study we evaluated the prevalence of residual LV structural changes (echocardiography) after four and 13 months of stepwise antihypertensive therapy. RESULTS: After 13 months of therapy, 24-hour blood pressure control was achieved in 47% of patients. At baseline, 51.5% of patients had concentric LVH, 19% eccentric LVH and 12% concentric LV remodelling. Despite changes in LV mass index (p < 0.01) and relative wall thickness (p < 0.05) with treatment, the proportion of patients with a normal LV mass or geometry increased only from 17.5 to 25% (p > 0.05), while 26% remained with concentric LVH (p < 0.001 compared to baseline), 25% with eccentric LVH and 23% with concentric LV remodelling (p < 0.05 compared to baseline). Residual structural changes were associated with 24-hour pulse pressure (p = 0.02), but not with 24-hour systolic or diastolic blood pressure or clinic blood pressure. CONCLUSIONS: Even after a year of antihypertensive therapy, a high proportion (74%) of hypertensives of African ancestry retained residual LV structural changes, an effect that was associated with 24-hour pulse pressure but not systolic or diastolic blood pressures or clinic blood pressure in this ethnic group.

Modeling of cellular arginine uptake by more than one transporter.

Determining the kinetic constants of arginine uptake by endothelial cells mediated by more than one transporter from linearization of data as Eadie-Hofstee plots or modeling which does not include the concentration of trace radiolabeled amino acid used to measure uptake may not be correct. The initial rate of uptake of trace [³H]L-arginine by HUVECs and ECV304 cells in the presence of a range of unlabeled arginine and modifiers was used in nonlinear models to calculate the constants of arginine uptake using GraphPad Prism. Theoretical plots of uptake derived from constants determined from Eadie-Hofstee graphs overestimated uptake, whereas those from the nonlinear modeling approach agreed with experimental data. The contribution of uptake by individual transporters could be modeled and showed that leucine inhibited the individual transporters differently and not necessarily competitively. N-Ethylmaleimide inhibited only y⁺ transport, and BCH may be a selective inhibitor of y⁺L transport. The absence of sodium reduced arginine uptake by y⁺L transport and reduced the K(m)', whereas reducing sodium decreased arginine uptake by y⁺ transport without affecting the K (m)'. The nonlinear modeling approach using raw data avoided the errors inherent in methods deriving constants from the linearization of the uptake processes following Michaelian kinetics. This study provides explanations for discrepancies in the literature and suggests that a nonlinear modeling approach better characterizes the kinetics of amino acid uptake into cells by more than one transporter.

Multimodality scar management program.

BACKGROUND: This trial was undertaken to assess the efficacy of a multimodality management regime used for the prevention of hypertrophic scars. It follows previous research and experience (A.D. Widgerow et al, Aesthetic Plast Surg, 24(3):227-234, 2000) with a similar program but with the addition of active agents with specific effects against prolonged inflammation and enhanced hydrative capacity. The modalities specifically targeted are tension on the scar, hydration of the scar, collagen maturation, and controlled inflammation. METHODS: Tape was impregnated with a combination of agents providing an occlusive dressing aimed at combatting exaggerated scarring. Patients who had undergone surgery were stratified into four groups: Group 1, 60 patients/60 scars following simple skin excisions, 30 treated scars, 30 untreated scars; Group 2, 20 patients/40 scars, each patient with two excisions, one treated, one untreated; Group 3, 10 patients/20 scars following bilateral breast surgery, one side treated with tape alone, one side treated with tape and gel; Group 4, 30 patients with varying cosmetic procedures/50 scars, all treated and compared with historical outcomes for hypertrophic scarring. Thus, 170 scars were assessed in 120 patients. RESULTS: Results were assessed at 1, 2, and 6 months using a combination of accepted scar assessment techniques. By amalgamating the Vancouver, Manchester, and morphologic table systems together with Patient and Observer Scar Assessment analyses, a comprehensive assessment of scar outcomes was undertaken and comparisons were made with control groups. CONCLUSION: Treated groups showed improvement outcomes in all variations of assessment. Patient and observer assessments correlated well, and morphologic appearances of the scars following the final assessment at 6 months showed statistically significant positive scar outcomes in the treatment groups. The multimodality approach to scar control showed significant benefits in the patient groups tested in this series.

Assessment of the medial head of the gastrocnemius muscle in functional compression of the popliteal artery.

OBJECTIVE: Nonfunctional popliteal entrapment is due to embryologic maldevelopment within the popliteal fossa. Functional entrapment occurs in the apparent absence of an anatomic abnormality. Gastrocnemius hypertrophy has been associated with the latter. Both forms of entrapment may cause arterial injury and lower limb ischemia. This study assessed the attachment of the medial head of the gastrocnemius muscle in healthy occluders and healthy nonoccluders. METHODS: Provocative tests were used to identify 58 nonoccluders and 16 occluders. Ten subjects from each group underwent magnetic resonance imaging evaluation of the popliteal fossa. The medial head of the gastrocnemius muscle attachment was assessed in the supracondylar, pericondylar, and intercondylar areas. RESULTS: In the occluder group, significantly more muscle was attached towards the femoral midline (supracondylar), around the lateral border of the medial condyle (pericondylar), and within the intercondylar fossa. CONCLUSION: The more extensive midline position of the medial head of the gastrocnemius in occluders is likely to be a normal embryological variation. Forceful contraction results in compression and occlusion of the adjacent popliteal artery. The clinical significance of these anatomic variations remains unclear. However, these new observations may provide insight for future analysis of the causes and natural history of functional compression and the potential progression to clinical entrapment.

Lavage drain extension for local anaesthetic instillation into abdominal wounds.

BACKGROUND: A new device made by ThebeMedicare allows efficient local anaesthetic washout of wound areas, by utilising an attachment to an existing drain. The aim of this trial was to explore 'proof of concept' in patients undergoing abdominoplasty procedures. PATIENTS AND METHODS: Thirty-one patients who had undergone abdominoplasty procedures were selected for instillation of a local anaesthetic preparation, ropivacaine (Naropin, AstraZeneca) into the wound site on day 1 and 2 after surgery, followed by early mobilisation. Efficacy of the system, patient comfort and mobilisation were documented. RESULTS: The abdominoplasty patients experienced no discomfort from the procedure and claimed effective relief of pain for an average of 12 hours following instillation of local anaesthetic. All mobilised effectively. The device worked well, with no technical problems. CONCLUSION: The lavage drain extension has proved to be a cost-effective and efficient way of providing postoperative pain control and promoting early mobilisation in this patient group.

Is Degenerative Spondylolisthesis a Contraindication for Total Disc Replacement? Kineflex Lumbar Disc Replacement in 7 Patients With 24-Month Follow-up.

BACKGROUND: Degenerative spondylolisthesis is associated with a significant segmental kyphosis at the level of the listhesis. We treated 7 disc spaces with Grade 2 listhesis and/or kyphosis of the slipped disc level with Kineflex disc replacement. METHODS: Out of a single-center prospective registry, involving 310 lumbar disc replacement patients, 7 patients underwent a single-level Kineflex disc replacement at the level of a degenerative spondylolisthesis with either segmental kyphosis or a Grade 2 slip. Preoperative and follow-up radiological parameters studied were: pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis L1-S1, degree of segmental listhesis, segmental lordosis, and range of motion (ROM). Clinical outcome measures were Visual Analog Scale pain score (VAS), Oswestry Disability Index (ODI), and patient satisfaction. RESULTS: Five replacements were performed at the L4-L5 level, and 2 were performed at a L3-4 level, above a pre-existing L4-S1 posterolateral fusion. Mean age was 50 (32-62) years. Average follow-up was 23.8 ± 13.1 months. Six of 7 patients considered their outcome as good or excellent. The mean VAS score decreased from 8.4 ± 1.9 to 2.7 ± 2.2 (P < .01). The ODI decreased from 45.2 ± 9.9 preoperatively to 19.7 ± 12.8 (P < .01). There were increases in lumbar lordosis (from 47.4o ± 10.6 to 61.3o ± 8.0 (P < .03)), in segmental lordosis (from 0.17° ± 7.0° to 16.4° ± 2.0° (P < .03)), and in sacral slope (from 34.5° ± 4.8° to 40.7° ± 4.5° (P < .03)). There were decreases in pelvic tilt (from 22.6° ± 6.3° to 15.5° ± 5.9° (P < .05)), and degree of segmental listhesis (from 24.4% ± 7.7 to 3.7% ± 3.4 (P < .03)). Pelvic incidence and ROM did not change. CONCLUSIONS: Disc replacement resulted in significant improvement in clinical outcome and excellent sagittal balance and slip correction. However, the influence of improved sagittal spinal alignment on clinical outcomes needs to be investigated in larger studies including a control group. CLINICAL RELEVANCE: This study is the first focused on disc replacement in degenerative spondylolisthesis.

Lumbar disc replacement for junctional decompensation after fusion surgery: clinical and radiological outcome at an average follow-up of 33 months.

BACKGROUND: Failed fusion surgery remains difficult to treat. Few published data on disc replacement surgery after failed fusion procedures exist. Our objective was to evaluate outcomes of junctional lumbar disc replacement after previous fusion surgery and to correlate outcome with radiological changes to parameters of sagittal balance. METHODS: Out of a single-center prospective registry of 290 patients with 404 lumbar disc replacements, 27 patients had had a previous lumbar fusion operation on 1 to 4 lumbar segments and had completed a mean follow- up of 33 months (range: 18-56). We correlated the clinical outcome measures (patient satisfaction, 10-point pain score, and Oswestry Disability Index [ODI] score) to parameters of spinal sagittal alignment (sacral tilt, pelvic tilt, pelvic incidence, and lumbar lordosis). RESULTS: Postoperative hospital stay averaged 3.3 days (range: 2-8). Previously-employed patients went back to their jobs with a mean of 32 days (range: 21-42) after the procedure. At the latest follow-up, 1 of the patients considered the outcome to be poor, 3 fair, 8 good, and 15 excellent. Twenty-four patients "would undergo the operation again." Average pain score decreased from 9.1 ± 1.0 (SD) to 3.2 ± 2.1 (P < .01). Average ODI decreased from 50.2 ± 9.9 preoperatively to 21.7 ± 14.2 (P ≤ .01). We found the change in pelvic tilt to be an independent predictor of better clinical outcome by multivariate analysis (P < .05). CONCLUSIONS: In patients with junctional failure adjacent to a previous posterolateral fusion, disc replacement at the junctional level(s), compared with osteotomy and fusion surgery, offers the advantage of maintaining segmental mobility and correcting the flat-back deformity through a single approach with less operative time and blood loss. Early- to intermediate-term results are promising. The influence of changes in spinal sagittal alignment on clinical outcome needs to be addressed in future research. CLINICAL RELEVANCE: This is the first study on "junctional disc replacement patients" correlating clinical outcome to changes in spinal/pelvic alignment.