Early results of the extracardiac conduit Fontan operation

BACKGROUND: Among the modifications of the Fontan operation, the extracardiac approach may offer the greatest potential for optimizing early postoperative ventricular and pulmonary vascular function, insofar as it can be performed with short periods of normothermic partial cardiopulmonary bypass and without cardioplegic arrest in most cases. In this study, we reviewed our experience with the extracardiac conduit Fontan operation, with a focus on early postoperative outcomes. METHODS AND RESULTS: Between July 1992 and April 1997, 51 patients (median age 4.9 years) underwent an extracardiac conduit Fontan operation. Median cardiopulmonary bypass time was 92 minutes and has decreased significantly over the course of our experience. Intracardiac procedures were performed in only 5 patients (10%), and the aorta was crossclamped in only 11 (22%). Intraoperative fenestration was performed in 24 patients (47%). There were no early deaths. Fontan failure occurred in 1 patient who was a poor candidate for the Fontan procedure. Transient supraventricular tachyarrhythmias occurred in 5 patients (10%). Median duration of chest tube drainage was 8 days. Factors significantly associated with prolonged resource use (mechanical ventilation, inotropic support, intensive care unit stay, and hospital stay) included longer bypass time and higher Fontan pressure. At a median follow-up of 1.9 years, there was 1 death from bleeding at reoperation. CONCLUSIONS: The extracardiac conduit Fontan procedure can be performed with minimal mortality and morbidity. Improved results may be related to advantages of the extracardiac approach and improved preservation of ventricular and pulmonary vascular function.     

A total ban on alcohol advertising: presenting the public health case

Evidence from burden of disease and economic costing studies amply indicate that the public health burden from hazardous and harmful use of alcohol in South Africa warrants drastic action. Evidence that banning alcohol advertising is likely to be an effective intervention is reflected in WHO strategy documents on non-communicable diseases and harmful use of alcohol. Studies on young people furthermore support arguments refuting the claim that advertising only influences brand choice. Given the weakness of relying on industry self-regulation, the government is considering legislation to ban alcohol advertising, resulting in heated debate. Tobacco control and studies investigating the effect of alcohol advertising bans on consumption and alcohol-related deaths point to the effectiveness of such action - ideally supplemented by other policy interventions. Arguments against an advertising ban include possible communication sector job losses, but these are likely to have been exaggerated. Banning alcohol advertising will necessitate greater scrutiny of digital media, satellite television and merchandising to reduce the likelihood of subverting the ban.     

Insulinlike growth factor-I-mediated migration and invasion of human colon carcinoma cells requires activation of c-Met and urokinase plasminogen activator receptor

OBJECTIVE: To determine whether insulinlike growth factor-I (IGF-I) and hepatocyte growth factor (HGF) cooperate to induce migration and invasion of human colorectal carcinoma (CRC) cells and whether the effects of IGF-I and/or HGF are mediated through activation of the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system, a central mediator of tumor-cell migration and invasion. SUMMARY BACKGROUND DATA: CRC cells must invade through the basement membrane of the colon and migrate to form metastases. CRC cells are known to overexpress IGF-I receptor (IGF-IR), c-Met, and uPAR, 3 cell-surface receptors known to mediate cell migration and invasion. We hypothesized that IGF-IR and c-Met cooperate to induce migration and invasion in CRC cells and that this signaling is dependent on uPAR. METHODS: KM12L4 human CRC cells were treated with IGF-I, HGF, or IGF-I + HGF in transwell migration and invasion chambers; cells that had migrated or invaded were counted. To determine the role of c-Met in IGF-I-induced migration and invasion, c-Met was inhibited by infection of cells with an adenovirus containing a c-Met ribozyme; transwell assays were then repeated. To determine the role of the uPA/uPAR system in IGF-I-induced CRC cell migration and invasion, transwell assays were repeated after pretreating cells with the uPA inhibitor amiloride or with neutralizing antibodies to uPA and uPAR. RESULTS: IGF-I and HGF, alone or in combination, increased cell migration and invasion. The c-Met ribozyme inhibited IGF-I- and HGF-mediated migration and invasion, indicating that c-Met is essential for these processes. uPA and uPAR inhibition blocked IGF-I- and HGF-mediated migration and invasion, suggesting that uPAR is downstream of IGF/IGF-IR and HGF/c-Met in the signaling pathways that mediate cell migration and invasion. CONCLUSIONS: IGF-I and HGF cooperate to induce migration and invasion of CRC cells, and c-Met and uPA/uPAR are required for IGF-I-mediated migration and invasion. In our in vitro model of CRC migration and invasion, uPA and uPAR appear to be downstream of IGF-IR and c-Met and are required for migration and invasion. Elucidation of the pathways that contribute to tumor progression and metastasis should provide a foundation for the rational development and use of targeted therapies for CRC.     

Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes

Background

Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay.

Methods

Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay.

Results

Fifty patients were analyzed—25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality.

Conclusions

Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes.

     

Fibrillin microfibrils are reduced in skin exhibiting striae distensae

Striae distensae (striae: stretch marks) are a common disfiguring condition associated with continuous and progressive stretching of the skin—as occurs during pregnancy. The pathogenesis of striae is unknown but probably relates to changes in those structures that provide skin with its tensile strength and elasticity. Such structures are components of the extracellular matrix, including fibrillin, elastin and collagens. Using a variety of histological techniques, we assessed the distribution of these extracellular matrix components in skin affected by striae. Pregnant women were assessed for the presence of striae, and punch biopsies were obtained from lesional striae and adjacent normal skin. Biopsies were processed for electron microscopy, light microscopy and immunohistochemistry. For histological examination, 7 μm frozen sections were stained so as to identify the elastic fibre network and glycosaminoglycans. Biopsies were also examined with a panel of polyclonal antibodies against collagens I and III, and fibrillin and elastin. Ultrastructural analysis revealed alterations in the appearance of skin affected by striae compared with that of normal skin in that the dermal matrix of striae was looser and more floccular. Light microscopy revealed an increase in glycosaminoglycan content in striae. Furthermore, the number of vertical fibrillin fibres subjacent to the dermal–epidermal junction (DEJ) and elastin fibres in the papillary dermis was significantly reduced in striae compared with normal skin. The orientation of elastin and fibrillin fibres in the deep dermis showed realignment in that the fibres ran parallel to the DEJ. However, no significant alterations were observed in any other extracellular matrix components. This study identifies a reorganization and diminution of the elastic fibre network of skin affected by striae. Continuous strain on the dermal extracellular matrix, as occurs during pregnancy, may remodel the elastic fibre network in susceptible individuals and manifest clinically as striae distensae.