Low-pressure laparoscopy may ameliorate intracranial hypertension and renal hypoperfusion

BACKGROUND: Increased abdominal pressure is associated with elevations in the intracranial pressure (ICP) and impaired renal function. These adverse effects are potentially important in clinical situations such as severe abdominal trauma and laparoscopic donor nephrectomy. It was hypothesized that the secondary elevation of ICP leads to release of vasoconstrictors, which may affect renal function by decreasing the renal blood flow (RBF). We investigated the effect of laparoscopy on ICP and renal blood flow in a porcine model. MATERIALS AND METHODS: The abdominal pressure of swine (N = 5; 20-25 kg) was gradually increased from baseline to 5, 15, and 25 mm Hg by insufflation of nitrogen into the abdominal cavity. The ICP was measured using a Camino monitor, and RBF was simultaneously measured using a Transonic Doppler probe placed on the renal artery. Results were analyzed using repeated measures ANOVA and the paired t-test. RESULTS: No significant change from baseline was observed in ICP and RBF when the abdominal pressure was 5 mm Hg. However, both ICP and RBF were affected by increasing the abdominal pressure to 15 and 25 mm Hg (P = 0.035 and 0.04 for ICP and P = 0.074 and 0.034 for RBF, respectively). CONCLUSIONS: Low-pressure laparoscopy may reduce the adverse effects of pneumoperitoneum on ICP and RBF. It may be advisable to use low pressures in laparoscopic surgery, especially when changes in ICP or renal perfusion may have significant clinical implications.     

Outcomes of Pheochromocytoma Management in the Laparoscopic Era

Background Laparoscopic adrenalectomy (LA) is the preferred surgical approach for pheochromocytomas. We have investigated the changes in diagnosis, management and outcome of pheochromocytomas treated since the widespread advent of LA. Methods Data were collected retrospectively from 96 patients with pheochromocytomas that had been surgically treated at three tertiary referral centers. Results There were 53 females. Mean age was 47 years (10–81). Tumors were found incidentally in 40% of patients. Of the 96 patients, 12 (13%) had familial syndromes. CT or MRI localized the adrenal lesion in all patients. MIBG scans obtained from 32 patients were concordant with the CT/MRI in 19, were false negative in 9 and misleading in 1, and altered management in only 3 patients. Mean tumor size was 5.6 cm (1.8–17). There were 92 adrenal pheochromocytomas and 9 paragangliomas. Laparoscopy was successful in 67 of 74 (91%) patients, with 20 of 67 (30%) having tumors of 6 cm or greater in size. Conversions to open procedures were performed in patients with 4 left, 2 right pheochromocytomas and 1 paraganglioma. Of the patients, 22 had an open procedure due to suspicion of malignancy or large tumors. Malignancy was observed in 4 of 92 (4.3%) pheochromocytomas and 4 of 9 (44%) paragangliomas. Average follow-up was 22 months (1–122). There were seven recurrences. Postoperative biochemical tests available in 64 patients were normal in 90%. Conclusions The diagnosis of pheochromocytoma was made incidentally in 40% of patients. MIBG is not necessary for unilateral non-hereditary pheochromocytomas localized by CT/MRI. LA is possible with excellent results in most patients, including for treatment of lesions 6 cm or greater in size with no signs of invasion. Laparoscopy should be used cautiously for paragangliomas because of a high rate of malignancy.     

Metastasis Suppressors and Their Roles in Breast Carcinoma

Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus distinct from tumor suppressors. As the biology underlying functional mechanisms of metastasis suppressors becomes clearer, it is evident that metastasis suppressors could be harnessed as direct drug targets, prognostic markers, and to understand the fundamental biology of the metastatic process. Metastasis suppressors vary widely in their cellular localization: they are found in every cellular compartment and some are secreted. In general, metastasis suppressors appear to regulate selectively how cells respond to exogenous signals, by affecting signaling cascades which regulate downstream gene expression. This review briefly summarizes current functional and biochemical data on metastasis suppressors implicated in breast cancer. We also present a schematic integrating known mechanisms for these metastasis suppressors highlighting potential targets for therapeutic intervention.     

Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with Alemtuzumab

Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow and T Cell Memory, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4-5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R-) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R- patients predepletion may require a prolonged period of prophylaxis.     

Endoscopically stapled diverticulostomy for Zenker’s diverticulum: results of a multidisciplinary team approach

Background  

A variety of open and endoscopic surgical approaches for the treatment of Zenker’s diverticulum have been described. In recent years, growing evidence has shown that the endoscopic techniques are superior to the open approaches in many aspects. Among the endoscopic techniques, endoscopically stapled diverticulostomy (ESD) appears to have better efficacy and safety than the other endoscopic techniques.     

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell–promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.     

Nanostructure of collagen fibrils in human nucleus pulposus and its correlation with macroscale tissue mechanics

Collagen fibrils are the main structural components of the nucleus pulposus tissue in the intervertebral discs. The structure–property relationship of the nucleus pulposus (NP) tissues is still unclear. We investigated the structure of individual collagen fibrils of the NP and evaluated its correlation with the bulk mechanical properties of the tissue. Collagen fibrils were extracted from the NP of discs retrieved from adolescents during scoliosis correction surgery, and the extracts were confirmed by SDS‐PAGE. The diameters of the individual collagen fibrils were measured through atomic force microscopy, and the compressive mechanical properties of the tissues were evaluated by confined compression. The correlations between the nanoscale morphology of the collagen fibrils and the macroscale mechanical properties of the tissues were evaluated by linear regression. The SDS‐PAGE results showed that the fibril extracts were largely composed of type II collagen. The mean diameter of the collagen fibrils was 92.1 ± 26.54 nm; the mean swelling pressure and compressive modulus of the tissues were 6.15 ± 4.3 kPa and 1.23 ± 0.7 MPa, respectively. The mean fibril diameter had no linear correlation (R² = 0.30) with the swelling pressure of the tissues. However, it had a mild linear correlation with the compressive modulus (p = 0.023, R² = 0.68). This is the first study, to our knowledge, to evaluate the nanostructure of the individual collagen fibrils of the nucleus pulposus and its relationship with macroscale mechanical properties of the NP tissues. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:497–502, 2010     

The Preventable Productivity Burden of Kidney Disease in Australia

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