Renal Protection Against Ischemia Reperfusion Injury: Hemoglobin-based Oxygen Carrier-201 Versus Blood as an Oxygen Carrier in Ex Vivo Subnormothermic Machine Perfusion.

BACKGROUND: The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine donation after circulatory death kidneys. Since using blood as a clinical perfusate has limitations, including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier (HBOC-201) in oxygen delivery to the kidney for renal protection. METHODS: Pig kidneys (n = 5) were procured after 30 minutes of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with histidine tryptophan ketoglutarate solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4 hours with HBOC-201 and blood. Thereafter, kidneys were reperfused with normothermic (37°C) oxygenated blood for 4 hours. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers, neutrophil gelatinase-associated lipocalin 1, and interleukin 6 were also assessed. RESULTS: HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood-perfused kidneys had vastly reduced acute tubular necrosis scores and degrees of terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining versus kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. CONCLUSIONS: HBOC-201 is an excellent alternative to blood as an oxygen-carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys.

Machine preservation of donor kidneys in transplantation.

With increasing demands for 'less than ideal' kidneys for transplantation, machine perfusion of kidneys has been utilized to improve the preservation of kidneys during storage. Hypothermic machine perfusion (HMP) of renal allografts has been shown to reduce delayed graft function rates in both expanded criteria and donation after cardiac death renal allografts. However, the beneficial impact upon long-term graft function is unclear. There has been emerging evidence that both subnormothermic (room temperature) and normothermic machine perfusion (NMP) of allografts have beneficial effects with regards to early graft function, survival and injury in pre-clinical and early clinical studies. Additionally, machine perfusion allows functional assessment of the organ prior to transplantation. Ultimately, the greatest benefit of machine perfusion may be the ability to treat the organ with agents to protect the graft against ischemia reperfusion injury, while awaiting transplantation.

Do Moderate Surgical Treatment Delays Influence Survival in Colon Cancer?

BACKGROUND: Studies examining treatment delay and survival after surgical treatment of colon cancer have varied in quality and outcome, with little evidence available regarding the safety of longer surgical treatment wait times. OBJECTIVE: Our study examined the effect of surgical treatment wait times on survival for patients with stage I to III colon cancer. DESIGN: A subset cohort analysis was performed using data from a prospectively maintained database. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Data on all of the patients undergoing elective surgery for stage I to III colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database. MAIN OUTCOME MEASURES: We examined the impact of prolonged wait time to surgery on disease-free and overall survival. Patients were divided into 2 groups based on a treatment wait time of ≤30 or >30 days and were compared using a Cox proportional hazards model. A subgroup analysis was performed using alternative treatment delay cutoffs of 60 and 90 days. RESULTS: There were 908 patients with stage I to III colon cancer treated over the study period, with a median treatment wait time of 38 days (interquartile range, 21-61 days); 368 patients were treated within 30 days, and 540 were treated beyond 30 days from diagnosis. In adjusted multivariate analysis, a treatment delay of >30 days was not associated with decreased disease-free survival (HR = 0.89 (95% CI, 0.61-1.3); p = 0.52) or overall survival (HR = 0.82 (95% CI, 0.63-1.1); p = 0.16). Likewise, subgroup analysis using alternative treatment delay cutoffs of 60 and 90 days did not demonstrate an adverse effect on survival. LIMITATIONS: This study was limited by retrospective analysis. CONCLUSIONS: Despite longer median treatment wait times from diagnosis to surgery, with the majority of patients exceeding 30 days and many experiencing delays of 2 to 3 months, no adverse impact on survival was observed. Patients who require additional consultations or investigations preoperatively may safely have their surgery moderately delayed to minimize their perioperative risk without any evidence that this will compromise treatment outcomes. See Video Abstract at http://links.lww.com/DCR/A397.

Emergency surgery for colorectal cancer does not result in nodal understaging compared with elective surgery.

BACKGROUND: It has been suggested that inadequate lymph node harvest may result in pathologically understaged or indeterminate staging of patients with colorectal cancer (CRC). We compared the adequacy of nodal staging in patients undergoing emergency surgery compared with elective surgery for CRC. METHODS: Using a prospectively collected CRC surgery database at a tertiary care centre, we performed a cohort study. The mean number of lymph nodes harvested and the proportion of patients who had inadequate staging (< 12 nodes harvested) were compared between emergency and elective surgery cohorts. Our analysis was adjusted for tumour site, type of resection, surgical training and pathologic stage. RESULTS: A total of 1279 of 1356 (94%) enrolled patients had nodal data available for analysis; 161 (13%) patients had emergency surgery and 1118 (87%) had elective surgery. The mean number of nodes removed was higher in the emergency surgery group (mean difference +2.8, 95% confidence interval [CI] 0.6-5.1, p = 0.012). The proportion of patients with inadequate nodal staging did not differ between groups (emergent 16%, elective 17%, p = 0.79). The odds of adequate nodal staging, adjusting for site, type of resection, training and stage was no different between groups (OR 0.80, 95% CI 0.47-1.35, p = 0.41). CONCLUSION: The evidence does not support the common belief that emergency surgery is more commonly understaged in CRC. Our data suggest emergency surgery resulted in a significant increase in the average number of nodes harvested, with no difference in inadequate nodal staging.

CONTEXTE: Il semble qu'une méthode erronée de prélèvement de lymphonoeuds pourrait expliquer pourquoi le stade d'évolution du cancer colorectal (CCR) est sous-évalué ou qu'il est impossible de le déterminer chez certains patients. On a comparé la méthode de détermination de l'atteinte des lymphonoeuds chez des patients atteints d'un CCR devant subir une chirurgie d'urgence à celle utilisée chez des patients devant subir une chirurgie non urgente. MÉTHODES: En utilisant une base de données prospectives sur des chirurgies du côlon pratiquées dans un établissement de soins tertiaires, on a comparé le nombre moyen de prélèvements de lymphonoeuds et la proportion de patients pour lesquels le stade d'évolution était erroné (prélèvement de < 12 lymphonoeuds) entre la cohorte de patients ayant subi une chirurgie d'urgence et celle ayant subi une chirurgie non urgente. Les résultats de notre analyse ont été ajustés en fonction du siège des tumeurs, du type de résection, de la formation chirurgicale et du stade pathologique. RÉSULTATS: Pour 1279 (94 %) des 1356 patients recrutés, on disposait des données sur les lymphonoeuds; 161 patients (13 %) avaient subi une chirurgie d'urgence et 1118 (87 %), une chirurgie non urgente. Le nombre moyen de lymphonoeuds prélevés était plus élevé pour le groupe de patients ayant subi une chirurgie d'urgence (écart moyen +2,8, intervalle de confiance [IC] à 95 % 0,6­5,1, p = 0,012). Mais la proportion de patients pour lesquels le stade d'évolution de la maladie était erroné ne différait pas entre les groupes (intervention d'urgence 16 %, intervention non urgente 17 %, p = 0,79). La probabilité que le stade d'évolution soit exact, l'ajustement en fonction du siège des tumeurs, du type de résection, de la formation chirurgicale et du stade d'évolution ne différaient pas entre les groupes (RR 0,80, IC à 95 % 0,47­1,35, p = 0,41). CONCLUSION: Les résultats de notre étude ne confirment pas la croyance répandue selon laquelle le stade d'évolution du CCR est plus souvent sous-évalué chez les patients ayant subi une chirurgie d'urgence. En effet, nos données semblent indiquer que les chirurgies d'urgence étaient associées à un nombre plus élevé de lymphonoeuds prélevés, mais qu'il n'y avait aucune différence pour ce qui est des erreurs de détermination du degré d'atteinte des lymphonoeuds.

Laparoscopic surgery for Crohn's disease: a meta-analysis of perioperative complications and long term outcomes compared with open surgery.

BACKGROUND: Previous meta-analyses have had conflicting conclusions regarding the differences between laparoscopic and open techniques in patients with Crohn's Disease. The objective of this meta-analysis was to compare outcomes in patients with Crohn's disease undergoing laparoscopic or open surgical resection. METHODS: A literature search of EMBASE, MEDLINE, The Cochrane Central Register of Controlled Trials and the US National Institute of Health's Clinical Trials Registry was completed. Randomized clinical trials and non-randomized comparative studies were included if laparoscopic and open surgical resections were compared. Primary outcomes assessed included perioperative complications, recurrence requiring surgery, small bowel obstruction and incisional hernia. RESULTS: 34 studies were included in the analysis, and represented 2,519 patients. Pooled analysis showed reduced perioperative complications in patients undergoing laparoscopic resection vs. open resection (Risk Ratio 0.71, 95% CI 0.58 - 0.86, P = 0.001). There was no evidence of a difference in the rate of surgical recurrence (Rate Ratio 0.78, 95% CI 0.54 - 1.11, P = 0.17) or small bowel obstruction (Rate Ratio 0.63, 95% CI 0.28 - 1.45, P = 0.28) between techniques. There was evidence of a decrease in incisional hernia following laparoscopic surgery (Rate Ratio 0.24, 95% CI 0.07 - 0.82, P = 0.02). CONCLUSIONS: This is the largest review in this topic. The results of this analysis are based primarily on non-randomized studies and thus have significant limitations in regards to selection bias, confounding, lack of blinding and potential publication bias. Although we found evidence of decreased perioperative complications and incisional hernia in the laparoscopic group, further randomized controlled trials, with adequate follow up, are needed before strong recommendations can be made.