Peter Metrakos

Portal vein embolization stimulates tumour growth in patients with colorectal cancer liver metastases

OBJECTIVES Portal vein embolization (PVE) can facilitate the resection of previously unresectable colorectal cancer (CRC) liver metastases. Bevacizumab is being used increasingly in the treatment of metastatic CRC, although data regarding its effect on post-embolization liver regeneration and tumour growth are conflicting. The objective of this observational study was to assess the impact of pre-embolization bevacizumab on liver hypertrophy and tumour growth. METHODS Computed tomography scans before and 4 weeks after PVE were evaluated in patients who received perioperative chemotherapy with or without bevacizumab. Scans were compared with scans obtained in a control group in which no PVE was administered. Future liver remnant (FLR), total liver volume (TLV) and total tumour volume (TTV) were measured. Bevacizumab was discontinued ≥ 4 weeks before PVE. RESULTS A total of 109 patients and 11 control patients were included. Portal vein embolization induced a significant increase in TTV: the right lobe increased by 33.4% in PVE subjects but decreased by 34.8% in control subjects (P < 0.001), and the left lobe increased by 49.9% in PVE subjects and decreased by 33.2% in controls (P= 0.022). A total of 52.8% of the study group received bevacizumab and 47.2% did not. There was no statistical difference between the two chemotherapy groups in terms of tumour growth. Median FLR after PVE was similar in both groups (28.8% vs. 28.7%; P= 0.825). CONCLUSIONS Adequate liver regeneration was achieved in patients who underwent PVE. However, significant tumour progression was also observed post-embolization.

Predictors of response to radio‐embolization (TheraSphere®) treatment of neuroendocrine liver metastasis

BACKGROUND Neuroendocrine tumours (NET) frequently metastasize to the liver. NET liver metastasis has been shown to respond to Yttrium-90 microspheres therapy. The aims of the present study were to define factors that predict the response to radio-embolization in patients with NET liver metastases. METHODS From January 2006 until March 2009, all patients with NET liver metastasis that received radio-embolization using TheraSphere® (glass microspheres) were reviewed. The response was determined by a change in the percentage of necrosis (ΔN%) after the first radio-embolization based on the modified RECIST criteria (mRECIST) criteria. The following confounding variables were measured: age, gender, size of the lesions, liver involvement, World Health Organization (WHO) classification, the presence of extra-hepatic metastasis, octereotide treatment and previous operative [surgery and (RFA)] and non-operative treatments (chemo-embolization and bland-embolization). RESULTS In all, 25 patients were identified, with a median follow-up of 21.7 months. The median age was 64.6 years, 28% had extra-hepatic metastasis and 56% were WHO stage 2. Post-treatment, the mean ΔN% was 48.4%. Previous surgical therapy was a significant predictor of the response with a response rate of 66.7 ΔN% vs. 31.5 ΔN% (P= 0.02). Bilateral liver disease, a high percentage of liver involvement and large metastatic lesions were inversely related to the degree of tumour response although did not reach statistical significance. CONCLUSION Radio-embolization increased the necrosis of NET liver metastasis mainly in patients with less bulky disease. This may imply that surgical therapy before radio-embolization would increase the response rates.

Successful salvage of kidney allografts threatened by ureteral stricture using pyelovesical bypass.

Ureteral stricture is the most common urologic complication after renal transplantation. When endourologic management fails, open ureteral reconstruction remains the standard treatment. The complexity of some of these procedures makes it necessary to explore other means of repair. This study evaluated the intermediate‐term outcome of subcutaneous pyelovesical bypass graft (SPBG) on renal transplant recipients. We reviewed 8 patients (6 male and 2 female; mean age 52 years) with refractory ureteral strictures postrenal transplantation, who received SPBG as salvage therapy. All patients failed endourologic management and half failed open management of their strictures. After a mean follow‐up of 19.4 months, 7 out of 8 renal grafts have good function with mean GFR of 58.5 mL/min/1.73 m2, without evidence of obstruction or infection. One patient lost his graft due to persistent infection of the SPBG and one patient developed a recurrent urinary tract infection managed with long‐term antibiotics. SPBG offers a last resort in the treatment of ureteral stricture after renal transplantation refractory to conventional therapy.

Randomized clinical trial of the impact of insulin therapy on liver function in patients undergoing major liver resection

Postoperative liver dysfunction is the major source of morbidity and mortality in patients undergoing partial hepatectomy. This study tested the benefits of a metabolic support protocol based on insulin infusion, for reducing liver dysfunction following hepatic resection.

Staged hepatectomy for bilobar colorectal hepatic metastases

OBJECTIVES This study describes the management of patients with bilobar colorectal liver metastases (CRLM). METHODS A retrospective collection of data on all patients with CRLM who were considered for staged resection (n= 85) from January 2003 to January 2011 was performed. Patients who underwent one hepatic resection were considered to have had a failed staged resection (FSR), whereas those who underwent a second or third hepatic resection to produce a cure were considered to have had a successful staged resection (SSR). Survival was calculated from the date of diagnosis of liver metastases. Complete follow-up and dates of death were obtained from the Government of Quebec population database. RESULTS Median survival was 46 months (range: 30-62 months) in the SSR group and 22 months (range: 19-29 months) in the FSR group. Rates of 5-year survival were 42% and 4% in the SSR and FSR groups, respectively. Fifteen of the 19 patients who remained alive at the last follow-up date belonged to the SSR group. CONCLUSIONS In patients in whom staged resection for bilobar CRLM is feasible, surgery would appear to offer benefit.

Post-transplant venous thromboembolic events and their effect on graft survival.

Venous thromboembolic events (VTEs) are a major cause of post-operative morbidity and mortality. Our objective is to establish the prevalence of VTEs in kidney transplant recipients and assess its impact on graft survival. Data regarding renal transplant patients with VTEs from 1985 to 2010 were identified and analyzed. After excluding recipients of combined grafts and late VTE development, 1596 recipients were included in this analysis. The prevalence of post-operative VTEs and graft survival were determined. Cox regression was used to analyze the survival data and data on prognostic (confounding) variables. The observed prevalence of VTEs in kidney transplant recipients was 1.6%. Of the 1596 kidney recipients, 25 recipients who developed VTEs had a mean graft survival of 12.3 years (compared with 20.5 years in patients without). The hazard ratio was 1.1 (95% confidence interval: 0.4-3.0, P = 0.447). The prevalence of VTEs post kidney transplantation is small. Although it did not reach statistical significance, it increased the risk of graft failure by 30%.

Reflex Testing for Germline BRCA1, BRCA2, PALB2, and ATM Mutations in Pancreatic Cancer: Mutation Prevalence and Clinical Outcomes From Two Canadian Research Registries

PurposeWe investigated the translational value of reflex testing for germline mutations in four homology-directed DNA repair predisposition genes (BRCA1, BRCA2, PALB2, and ATM) in consecutive patients with pancreatic adenocarcinoma.MethodsOne hundred fifty patients with French-Canadian (FC) ancestry were evaluated for founder mutations, and 114 patients were subsequently assessed by full gene sequencing and multiplex ligation-dependent probe amplification for nonfounder mutations. Two hundred thirty-six patients unselected for ancestry were also assessed for mutations by full gene sequencing.ResultsThe FC founder mutation prevalence among the 150 patients was 5.3% (95% CI, 2.6% to 10.3%), and the nonfounder mutation prevalence across the four genes among the 114 patients tested was 2.6% (95% CI, 0.6% to 7.8%). In the case series unselected for ancestry, 10.0% (95% CI, 2.7% to 26.4%) of patients reporting Ashkenazi Jewish (AJ) ancestry carried an AJ founder mutation, with no nonfounder mutations identified...

The deteriorating quality of organ donors

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Developing a prognostic score for early prediction of graft and patient survival after orthotopic liver transplantation

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