Technical and analytical approach to biventricular pressure-volume loops in swine including a completely endovascular, percutaneous closed-chest large animal model.

Pressure-volume (PV) loop analysis is a sophisticated invasive approach to quantifying load-dependent and independent measures of cardiac function. Biventricular (BV) PV loops allow left and right ventricular function to be quantified simultaneously and independently, which is important for conditions and certain physiologic states, such as ventricular decoupling or acute physiologic changes. BV PV loops can be performed in an entirely endovascular, percutaneous, and closed-chest setting. This technique is helpful in a survival animal model, as a percutaneous monitoring system during endovascular device experiments, or in cases where chest wall compliance is being tested or may be a confounder. In this article, we describe the end-to-end implementation of a completely endovascular, totally percutaneous, and closed-chest large animal model to obtain contemporaneous BV PV loops in 40 to 70 kg swine. We describe the associated surgical and technical challenges and our solutions to obtaining endovascular BV PV loops, closed-chest cardiac output, and stroke volume (including validation of the correction factor necessary for thermodilution), as well as how to perform endovascular inferior vena cava occlusion in this swine model. We also include techniques for data acquisition and analysis that are required for this method.

Trauma care and referral patterns in Rwanda: implications for trauma system development.

BACKGROUND: Trauma remains a leading cause of death worldwide. The development of trauma systems in low-resource settings may be of benefit. The objective of this study was to describe operative procedures performed for trauma at a tertiary care facility in Kigali, Rwanda, and to evaluate geographical variations and referral patterns of trauma care. METHODS: We retrospectively reviewed all prospectively collected operative cases performed at the largest referral hospital in Rwanda, the Centre Hospitalier Universitaire de Kigali (CHUK), between June 1 and Dec. 1, 2011, for injury-related diagnoses. We used the Pearson χ² and Fisher exact tests to compare cases arising from within Kigali to those transferred from other provinces. Geospatial analyses were also performed to further elucidate transfer patterns. RESULTS: Over the 6-month study period, 2758 surgical interventions were performed at the CHUK. Of these, 653 (23.7%) were for trauma. Most patients resided outside of Kigali city, with 337 (58.0%) patients transferred from other provinces and 244 (42.0%) from within Kigali. Most trauma procedures were orthopedic (489 [84.2%]), although general surgery procedures represented a higher proportion of trauma surgeries in patients from other provinces than in patients from within Kigali (28 of 337 [8.3%] v. 10 of 244 [4.1%]). CONCLUSION: To our knowledge, this is the first study to highlight geographical variations in access to trauma care in a low-income country and the first description of trauma procedures at a referral centre in Rwanda. Future efforts should focus on maturing prehospital and interfacility transport systems, strengthening district hospitals and further supporting referral institutions.

CONTEXTE: Les traumatismes demeurent l'une des principales causes de décès dans le monde. La mise au point de systèmes de traumatologie dans des milieux défavorisés pourrait toutefois contribuer à améliorer la situation. Notre étude avait pour objectif de décrire les interventions chirurgicales pratiquées sur les victimes de traumatismes dans un établissement de soins tertiaires de Kigali, au Rwanda, et d'évaluer les variations géographiques et les habitudes d'orientation des patients dans le domaine de la traumatologie. MÉTHODES: Nous avons évalué rétroactivement les données recueillies de façon prospective sur l'ensemble des interventions réalisées au plus grand centre hospitalier régional du Rwanda, le Centre hospitalier universitaire de Kigali (CHUK), du 1er juin au 1er décembre 2011 pour les diagnostics liés à des blessures. Nous avons eu recours au test χ² de Pearson et au test exact de Fisher pour comparer les cas issus de la province de Kigali à ceux provenant d'autres provinces. Nous avons en outre effectué des analyses géospatiales afin de mieux comprendre les habitudes d'orientation des patients. RÉSULTATS: Au cours des 6 mois de l'étude, 2758 interventions chirurgicales ont été pratiquées au CHUK, dont 653 (23,7 %) pour des traumatismes. La majorité des patients résidaient à l'extérieur de la capitale : 337 (58,0 %) d'entre eux avaient été transférés d'autres provinces, et 244 (42,0 %), d'ailleurs dans la province. Si la plupart des interventions chirurgicales étaient orthopédiques (489, soit 84,2 %), les patients d'autres provinces ont plus souvent subi des interventions générales que leurs compatriotes de la province de Kigali (28 sur 337, soit 8,3 %, par rapport à 10 sur 244, soit 4,1 %). CONCLUSION: À notre connaissance, il s'agit de la première étude mettant en lumière les variations géographiques de l'accès aux soins en traumatologie dans un pays à faible revenu et de la première description des interventions chirurgicales pratiquées sur des victimes de traumatismes dans un centre régional du Rwanda. Les travaux à venir devraient être axés sur le développement des systèmes de transport avant l'hospitalisation et entre les établissements, le renforcement des hôpitaux de district et l'augmentation du soutien aux centres régionaux.

Acute care surgery in Rwanda: Operative epidemiology and geographic variations in access to care.

BACKGROUND: Surgical management of emergent, life-threatening diseases is an important public health priority. The objectives of this study were to (1) describe acute care general surgery procedures performed at the largest referral hospital in Rwanda and (2) understand the geographic distribution of disease presentations and referral patterns. METHODS: We performed a retrospective review of prospectively collected acute care surgery cases performed at the Centre Hospitalier Universitaire de Kigali (CHUK) in Rwanda between June 1 and December 1, 2011. Using Pearson's χ(2) test and the Fisher exact test, we compared cases originating from within Kigali and transfers from other provinces. Geospatial analyses also were used to further describe transfer patterns. RESULTS: During the study period, 2,758 surgical interventions were performed, of which 25.6% (707/2,758) were general surgery operations. Of these, 45.4% (321/707) met the definition of acute care surgery. Only about one-third-32.3% (92/285)-of patients resided within Kigali, whereas about two-thirds-67.7% (193/285)-were transferred from other provinces. Most patients transferred from other provinces were younger than 18 years of age (40.4%; 78/193), and 83.0% (39/47) of patients older than 50 years of age originated from outside of Kigali. Specific operative indications and surgical procedures varied substantially between patients from Kigali and patients transferred from other provinces. CONCLUSION: Emergency surgical conditions remain important contributors to the global burden of disease, particularly in low- and middle-income countries. Geographic variations exist in terms of operative diagnoses and procedures, which implies a need for improved access to surgical care at the district level with defined transfer mechanisms to greater-level care facilities when needed.

Gram negative bacteria increase non-small cell lung cancer metastasis via Toll-like receptor 4 activation and mitogen-activated protein kinase phosphorylation.

Surgery is required for the curative treatment of lung cancer but is associated with high rates of postoperative pneumonias predominantly caused by gram negative bacteria. Recent evidence suggests that these severe infectious complications may decrease long term survival after hospital discharge via cancer recurrence, but the mechanism is unclear. Lung cancer cells have recently been demonstrated to express Toll-like receptors (TLR) that mediate pathogen recognition. We hypothesized that incubation of non-small cell lung cancer (NSCLC) cells with heat-inactivated Escherichia coli can augment cancer cell adhesion, migration and metastasis via TLR4 signaling. Incubation of murine and human NSCLC cells with E. coli increased in vitro cell adhesion to collagen I, collagen IV and fibronectin, and enhanced in vitro migration. Using hepatic intravital microscopy, we demonstrated that NSCLC cells have increased in vivo adhesion to hepatic sinusoids after coincubation with gram negative bacteria. These enhanced cell adhesion and migration phenotypes following incubation with E. coli were attenuated at three levels: inhibition of TLR4 (Eritoran), p38 MAPK (BIRB0796) and ERK1/2 phosphorylation (PD184352). Incubation of murine NSCLC cells in vitro with E. coli prior to intrasplenic injection significantly augmented formation of in vivo hepatic metastases 2 weeks later. This increase was abrogated by NSCLC TLR4 blockade using Eritoran. TLR4 represents a potential therapeutic target to help prevent severe postoperative infection driven cancer metastasis.

Functional outcomes and quality of life after proximal gastrectomy with esophagogastrostomy using a narrow gastric conduit.

BACKGROUND: The best surgical approach for tumors of the proximal stomach remains controversial. For proximal gastrectomy (PG), the evidence regarding quality of life (QoL) and functional outcomes is controversial. Moreover, there are limited data from non-Asian settings. METHODS: All patients who underwent PG from September 2005 to July 2013 were identified from an institutional database. Demographic, perioperative and pathologic characteristics were retrieved. Symptom scores (0 = best/4 = worst) for reflux symptoms, dysphagia and validated QoL metrics (FACT scale, where a higher score is better) were assessed during early and late follow-up. Eligible patients for analysis were those with no evidence of recurrence. RESULTS: Of 465 upper gastrointestinal cancer resections, 50 were PG for adenocarcinoma (42; 84%), neuroendocrine carcinoma (5; 10%) or other pathologies (3; 6%). R0 resection was achieved in 44 (89.8%) of 49 patients with malignant tumors. Median lymph node collection was 32 (range 7-57). QoL scores did not differ from preoperative to early follow-up but increased compared to both at late follow-up [preoperative, 125 (interquartile range 105-140); early follow-up, 122.5 (97-142); late follow-up, 147 (132-159); p < 0.05]. At early and late follow-up, 9 (21.4%) of 42 and 10 (33.3%) of 30 patients reported reflux symptoms, but most were mild. Endoscopic signs of esophagitis were found in 7 (29%) of 24 patients, but only two of these reported reflux symptoms. Conversely only three of eight patients with reflux symptoms had esophagitis on endoscopy. CONCLUSIONS: Global QoL is not reduced early after PG, and increases compared to baseline at late follow-up. Although reflux symptoms are reported by a quarter of patients, most are mild, and there is little correlation with esophagitis. PG should remain a viable option in the management of proximal gastric tumors.

Lipopolysaccharide-induced toll-like receptor 4 signaling enhances the migratory ability of human esophageal cancer cells in a selectin-dependent manner.

BACKGROUND: Esophageal cancer is an aggressive malignancy, and emerging data suggest that postoperative infections may promote cancer progression. Systemic exposure to lipopolysaccharide (LPS), a Gram-negative bacterial antigen involved in such infections, has been shown to increase cancer cell adhesion to the hepatic sinusoids in vivo. We investigated the direct impact of LPS on the migratory ability of esophageal cancer cells via the LPS receptor toll-like receptor 4 (TLR4). METHODS: Human esophageal squamous carcinoma cell lines and immortalized normal esophageal mucosa cells were tested for TLR4 surface expression by reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. TLR4 signaling in response to LPS stimulation was tested in these cells by measuring p38 MAP kinase phosphorylation on Western blot. The impact of TLR4 signaling was measured by static adhesion assays in vitro and on early in vivo migration by intravital microscopy of the liver. RESULTS: Upon LPS stimulation, phosphorylation of p38 was detected in the human esophageal cancer cells HKESC-2. Also, LPS-stimulated HKESC-2 cells showed a twofold increased adhesion to fibronectin and to hepatic sinusoidal endothelium. These effects were abolished by TLR4 inhibition using the small-molecule inhibitor eritoran. Adhesion to fibronectin and hepatic sinusoidal endothelium was also diminished by blockade of p38 phosphorylation and inhibitors of selectin-selectin ligand binding. CONCLUSION: LPS can increase the migratory ability of human esophageal cancer cells by increasing their adhesive properties through TLR4 signaling and selectin ligands. TLR4, p38, and selectin blockade may therefore prove to be a new therapeutic strategy for this aggressive malignancy.

LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis.

Infectious complications resulting from resection of colorectal cancer (CRC) elevates the risk of cancer recurrence and metastasis, but the reason for this risk relationship is unknown. Defining the mechanisms responsible may offer opportunities to improve outcomes in a majority of patients whose tumors are resected as part of their therapy. The complex formed between Toll receptor TLR4 and myeloid differentiation factor MD2 defines a major cell surface receptor for lipopolysaccharide (LPS), a gram-negative bacterial antigen that has been implicated in infectious complications after CRC resection. As the TLR4/MD2 complex is expressed on CRC cells, we hypothesized that LPS may promote liver metastasis in CRC by stimulating TLR4 signaling. In support of this hypothesis, we report here that LPS enhances liver metastasis of human CRC cells that express TLR4/MD2 after intrasplenic graft of immunocompromised nude mice. Compared with TLR4 nonexpressing, nonmetastatic CRC cells, we observed increased in vitro adherence to different extracellular matrices and human umbilical vein endothelial cells (HUVEC). Furthermore, we observed an increased likelihood of in vivo capture within hepatic sinusoids after LPS treatment. No differences were apparent in phosphorylation of p38 and MAPK isoforms, but in metastatic CRC cells expressing surface TLR4 treatment with LPS increased Ser473 phosphorylation of AKT kinase. We showed that enhanced adherence elicited by LPS in these cells could be blocked at three different levels, using Eritoran (TLR4 small molecule antagonist), PI-103 (PI3K inhibitor), or anti-ß1 integrin blocking antibodies. Taken together, the results indicate that stimulation of the TLR4/MD2 complex by LPS activates PI3K/AKT signaling and promotes downstream ß1 integrin function, thereby increasing the adhesiveness and metastatic capacity of CRC cells. Our findings suggest that inhibiting LPS-induced TLR4 signaling could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of CRC resection.

Effect of the ACGME duty hours restrictions on surgical residents and faculty: a systematic review.

PURPOSE: Educators in surgical training programs are concerned that the Accreditation Council for Graduate Medical Education (ACGME) duty hours limitations may adversely affect surgical residents' education, especially their operative experience, so the authors aimed to evaluate the impact of duty hours reductions on surgical residency. METHOD: The authors searched English- and French-language literature (2000-2008) for articles about the impact of duty hours restrictions on surgical residents' education and well-being and on faculty educators. They used the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ERIC. The authors included every report that examined the effects of duty hours limits on surgical training, excluding opinion papers and editorials. Two reviewers independently performed data extraction and quality assessment for all reports and resolved disagreements by consensus. RESULTS: The authors retrieved 1,146 reports and included 56 in the study. They compiled positive and negative outcomes on (1) residents' education, (2) resident lifestyle, and (3) surgical faculty. Overall, the effects of duty hours reductions on residents' education and lifestyle were positive or neutral, but the effects on surgical faculty were negative. The 16 articles with the highest-quality scores had 27 positive themes and 11 negative themes. CONCLUSIONS: This is the largest and most current review of the literature addressing the effect of the ACGME duty hours limitations on surgical training. Limitations had a positive effect on residents but a negative effect on surgical faculty. Importantly, duty hours limitations did not adversely affect surgical residents' operating-room experience.