Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

Use of chemotherapy and radiofrequency ablation to treat colorectal cancer metastases: a retrospective review of The Ottawa Hospital Cancer Centre over 7 years.

BACKGROUND: Almost 40% of people diagnosed with colorectal cancer will die from their disease, most with metastatic spread. When feasible, hepatic resection offers the greatest probability of cure for isolated liver metastases, but there are barriers to curative resection. Those barriers include the extent and distribution of lesions within the liver, extrahepatic disease, comorbidities, and age. Chemotherapy is often administered before or after resection with the intention of improving disease-free and overall survival. The timing of chemotherapy (adjuvant vs. neoadjuvant vs. perioperative) for patients undergoing potentially curative hepatic resection of metastasis of colorectal cancer origin is controversial. METHODS: Colorectal cancer patients with liver metastases resected at The Ottawa Hospital between January 1, 2003, and December 31, 2009, were identified, and their clinical records were retrospectively reviewed. Patients receiving intraoperative radiofrequency ablation (rfa) as part of their management were included. Factors associated with overall and disease-free survival were evaluated. RESULTS: The 168 identified patients (57% men, 43% women) had a median age of 63 years (range: 31-84 years). After hepatectomy, 10% had positive resection margins. Intraoperative rfa was used in 25 patients (15%). Chemotherapy was administered in the neoadjuvant (19%), adjuvant (31%), or "perioperative" (both neoadjuvant and adjuvant, 50%) setting. Use or omission of intraoperative rfa was not associated with a difference in overall survival (hazard ratio: 0.99; 95% confidence interval: 0.53 to 1.84; p = 0.97). CONCLUSIONS: Compared with patients who did not receive chemotherapy, those who received chemotherapy, regardless of timing, experienced improved overall survival and disease-free survival. Use of rfa where required as an adjunct to hepatic resection appears to be effective and is not associated with worse overall survival.

Systematic review and meta-analysis of liver resection for metastatic melanoma.

BACKGROUND: The multidisciplinary management of metastatic melanoma now occasionally includes major hepatic resection. The objective of this work was to conduct a systematic review of the literature on liver resection for metastatic melanoma. METHODS: MEDLINE, Embase, the Cochrane Library and Scopus were searched (1990 to December 2012). Studies with at least ten patients undergoing liver resection for metastatic melanoma were included. Data on the outcomes of overall survival (OS) and/or disease-free survival (DFS) were abstracted and synthesized. Hazard ratios (HRs) were derived from survival curves and subjected to meta-analysis using random-effects models. RESULTS: Twenty-two studies involving 579 patients (13 per cent weighted resection rate) who underwent liver resection were included. Study quality was poor to moderate. Median follow-up ranged from 9 to 59 months. Median DFS ranged from 8 to 23 months, and median OS ranged from 14 to 41 months (R0, 22-66 months, R2, 10-16 months; R0 versus R1/R2: HR 0.52, 95 per cent confidence interval (c.i.) 0.37 to 0.73). The OS rate was 56-100 per cent at 1 year, 34-53 per cent at 3 years and 11-36 per cent at 5 years. Median OS with non-operative management ranged from 4 to 12 months. Comparison of OS with resection and non-operative management favoured resection (HR 0.32, 95 per cent c.i. 0.22 to 0.46). CONCLUSION: Radical resection of liver metastases from melanoma appears to improve overall survival compared with non-operative management or incomplete resection, but this observation requires future confirmation as selection bias may have confounded the results.

Diagnosis and management of hepatocellular carcinoma: results of a consensus meeting of The Ottawa Hospital Cancer Centre.

Hepatocellular carcinoma (HCC) is an uncommon tumour, but its incidence is increasing in Canada and elsewhere. Currently, there are no Canadian recommendations for diagnosis and treatment of hcc, and possible options may have regional limitations. A consensus symposium was held in the Ottawa region to consider current diagnostic and management options for hcc. These recommendations were developed: Diagnosis-with adequate imaging, a biopsy is not required pre-surgery, but is required before the start of systemic therapy; lesions smaller than 1 cm should be followed and not biopsied; repeat biopsies should be core tissue biopsies; magnetic resonance imaging is preferred, but triphasic computed tomography imaging can be useful. Resection-recommended for localized HCC. Radiofrequency ablation-recommended for unresectable or non-transplantable HCC; should not be performed in the presence of ascites. Trans-arterial chemoembolization (TACE)-doxorubicin with lipiodol is the agent of choice; trans-catheter embolization is an alternative for patients if TACE is not tolerated or is contraindicated. Medical management-first-line sorafenib should be considered the standard of care. Transplantation-suitable patients meeting Milan criteria should be assessed for a graft regardless of other treatments offered. The authors feel that the recommendations from this consensus symposium may be of interest to other regions in Canada.

Broad-based fellowships: a cornerstone of minimally invasive surgery education and dissemination.

Aware of the trends in surgery and of public demand, many residents completing a 5-year training program seek fellowships in minimally invasive surgery (MIS) because of inadequate exposure to advanced MIS during their residency. A survey was designed to evaluate the effectiveness of a broad-based fellowship in advanced laparoscopic surgery offered in an academic health science center. The questionnaire was mailed to all graduates. Data on demographics, comfort level with specific laparoscopic procedures, and opinions regarding the best methods of acquiring these skills were collected. Most of the surgeons entered the fellowship directly after residency. The majority of these surgeons are academic surgeons. Fellows performed a median of 187 cases by the end of their training and felt comfortable operating on foregut, hindgut, and end organ. A full year of training was found to be the best format for appropriate skill transfer. A broad-based MIS fellowship meets the needs of both academic and community surgeons desiring to perform advanced laparoscopic procedures.

The management of temperature during cardiopulmonary bypass: effect on neuropsychological outcome.

Laboratory studies demonstrate that mild degrees of brain cooling (2 degrees C to 5 degrees C) confer substantial protection from ischemic brain injury, and that mild elevation of brain temperature can be markedly deleterious. During hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic and then rewarmed at a time when they are exposed to neurological insults. Our studies show that during rewarming, peak brain temperatures near 39 degrees C often are achieved inadvertently. We hypothesize that maintaining brain temperature < or = 34 degrees C during and after CPB will reduce the incidence of postoperative neuropsychological deficits. We present safety data from a study of 30 patients assigned either to conventional hypothermic CPB with rewarming or a protocol where brain temperature is raised only to 34 degrees C at the time of separation from CPB. There was no difference in bleeding, cardiac morbidity, or time to extubation between groups. We designed a neuropsychological test battery to detect postoperative neuropsychological deficits and tested its usefulness in a preliminary sample of 15 patients undergoing hypothermic CPB. We found patient acceptability and compliance were good. Sensitivity also seemed adequate in that 30% of patients were identified as having deteriorated at 1 week postoperatively compared to preoperatively, a result similar to that reported by others. Clinical trials of the efficacy of mild hypothermia in modulating brain injury in humans are needed before techniques of CPB can be designed to optimize neuroprotection.