July-August 2017

Synopsis: Incisional hernia remains a frequent complication of abdominal surgery with significant morbidity to patients and costs to society. High-risk patient groups have an incidence of incisional hernia up to 30%. This study sought to explore the effect of prophylactic mesh reinforcement among two high-risk groups of patients, those with abdominal aortic aneurysm and those with BMI above 27kg/m2. The study enrolled 498 patients in 11 hospitals in Austria, Germany, and the Netherlands from 2009 to 2012. In addition to falling into the previously detailed high-risk groups, patients had to be over 18 years and undergoing elective midline laparotomy. Exclusion criteria included emergency surgery, prior incisional hernia, participation in other trials, life expectancy less than 24 months (the follow-up period of the study), pregnancy, immune suppression within 2 weeks before surgery, and bovine allergy. Patients were allocated to treatment group after completion of the abdominal portion of the operation and before closure. The closure was performed by the operating surgeon, which included general surgeons, vascular surgeons, urologists, and gynecologists. The primary sutured closure was performed with #1 MonoPlus (polydioxanone, same material as PDS) with a recommended 4:1 suture length:wound length ratio. Mesh reinforcement was performed with a lightweight polypropylene mesh with a recommended 3 cm overlap, secured with Tisseel fibrin glue after creating either flaps above the anterior rectus fascia (onlay) or between the posterior rectus fascia/peritoneum and rectus muscle (sublay). Patients were followed for up to 2 years with clinical exams and, in most cases, radiologic examination (70% of the 376 patients who completed follow-up) to detect incisional hernia. 92 (19%) of 480 patients developed incisional hernia during the 2 years of follow-up, including 31% of the primary suture group, 13% of the onlay group, and 18% of the sublay group. The difference in hernia incidence was significantly different only between primary suture and onlay mesh (OR 0.37, 95% CI 0.2-0.69). For primary suture versus sublay mesh, the threshold for statistical significance was close, but not met (OR 0.55, 95% CI 0.3-1.0). The authors noted that “non-equivalence of the experimental treatments cannot be ruled out” regarding onlay versus sublay (OR 1.39, 0.73-2.65). The only increased complication related to onlay position was increased early seroma rate, which was reportedly of no clinical consequence. Notably, in the subgroup analysis, only the comparisons between mesh reinforcement (both onlay and sublay) and primary suture in the AAA patients were statistically significant, while all comparisons in the BMI>27 subgroup fell short of a p value below 0.05. Care should be taken to apply these results only to the specific patients and clinical situations included in the study, with some skepticism in the applicability of this technique to obese patients. Further, it is important to recognize key technical factors from the study, including the lack of use of the small-bites technique described in the STITCH trial (2015, published well-after the enrollment period of this trial) and the use of fibrin glue for mesh fixation.

Synopsis: The desire to avoid the negative effects of the systemic inflammatory response (SIRS) and other complications associated with cardiopulmonary bypass led to a resurgence in the practice of off-pump coronary artery bypass grafting (OPCABG) in the 1990's. Several large, randomized trials have called into question the theorized benefits of OPCABG compared to the traditional on-pump approach. This study by Shroyer et al is a five-year follow up to the original Randomized On/Off Bypass (ROOBY) trial performed across 18 centers within the Department of Veterans Affairs (VA) Cooperative Studies Program. The original trial demonstrated no differences in short term outcomes (30 day or in hospital mortality or morbidity) between the off-pump and on-pump group, but did show a higher rate of the 1 year composite endpoint of all cause mortality, nonfatal MI, or repeat revascularization in the off-pump group (9.9% vs. 7.4%, p=0.04). Furthermore, OPCABG was associated with higher rates of incomplete revascularization as compared to on-pump, as defined by completion of the number of planned grafts (17.8% vs. 11.1%, p<0.001), and lower patency rates at one year angiography (82.6 vs. 87.8%, p<0.001). This five year follow up study was a retrospective review of the original cohort of randomized patients and baseline characteristics were not significantly different between groups. The primary endpoint of 5 year all cause mortality was higher in the off pump group than in the on-pump group (15.2% vs. 11.9, p=0.02). The OPCABG group also had a higher rate of the primary composite endpoint of major adverse cardiovascular events (MACE) - 31.0% - as compared to the on pump group - 27.1% (p=0.046). There were no statistically significant differences between groups in secondary outcomes of 5 year death rate from cardiac causes, rate of nonfatal MI, or rate of repeat revascularization, at the pre-specified threshold of p=0.01. Overall this study confirmed the findings of the international CABG Off or On Pump Revascularization Study (CORONARY) and demonstrated that off pump CABG was associated with higher five year mortality and MACE and did not confer any advantage in selected long term clinical outcomes. Though OPCABG may be a suitable approach for selected populations, these data argue against the adoption of OPCABG as a default revascularization strategy. 

Synopsis: Dabigatran (Pradaxa) is a direct thrombin inhibitor used as an oral anticoagulant for non-valvular atrial fibrillation, DVT, and PE. The RE-VERSE AD trial is a pragmatic-designed multicenter prospective single-cohort study assessing the use of idarucizumab, an IV infusion of a humanized monoclonal antibody fragment that binds dabigatran, to reverse the anticoagulation effects in the setting of life-threatening bleeding (intracranial hemorrhage, GI bleed, etc) or for urgent surgery (must be in OR within 8 hours). Results demonstrated 100% reversal of dabigatran effects on coagulation studies within 4 hours of infusion; 1.8% required a second infusion for recurrent bleeding; 4.8% had thrombotic events at 30d and 6.8% had thrombotic events at 90d; 98.6% of interventionalists subjectively assessed bleeding as normal to mildly abnormal; and 30d mortality was ~13% and 90d mortality was ~19%. The major limitations of the study are 1) the study is industry sponsored by the company that creates dabigatran and idarucizumab with potential conflicts of interest, and 2) there was no control group for comparative analysis.

Synopsis: The observation that lymph node metastasis often precedes systemic disease suggests a sequential progression, in which the primary tumor seeds lymph node metastases that – in turn – seed distant metastases. However, it is unknown whether a single metastatic subclone evolves in the primary tumor, subsequently spreading to lymph nodes and distant sites, or whether multiple subclones in the primary tumor independently seed lymphatic and distant metastases. To study the evolutionary relationship between lymphatic and distant metastases, archival biopsy samples (primary tumor, lymph nodes and metastasis) from 17 patients with colon cancer were analyzed to construct phylogenetic trees, by quantifying somatic variants in hypermutable polyguanine repeats. In 6 out of 17 tumors (35%), there was a common subclone origin of lymphatic and distant metastases. Moreover, for 33 of 45 (73%) lymph node metastases, the distance to the primary tumor on the phylogenetic tree was shorter than the distance to distant metastases; and 31 of 45 (69%) distant metastases had a shorter genetic distance to the primary tumor than to any lymph node metastasis. The authors suggest these data provide strong evidence of independent origins of lymph node and distant lesions. It remains to be determined whether similar phylogenetic relationships exist for other tumors (e.g., non-GI malignancies, where the distribution of metastases is not segregated between the (1) portal circulation and (2) lymphatic>thoracic duct>systemic circulation). Additionally, if independent seeding is the dominant pathway for lymphatic and distant metastasis, the clinical association between lymphatic involvement and distant metastasis needs further exploration. 

Synopsis:More childhood deaths are due to trauma than all other causes of pediatric mortality combined. This retrospective, population-based cohort study utilized the Kids Inpatient Database (KID) as a representative sample (at the time, KID provided incident-level data from an 80% weighted sample of pediatric discharges from almost 4,000 hospitals in 38 states). In total, the study included 153,380 injured children treated at pediatric trauma centers (22.3%), general trauma centers (45.2%), and non trauma centers (32.6%). Mortality at these trauma centers (TCs) were 1.0% at pediatric TCs, 1.4% and dual-verified TCs (hospitals that treat pediatric and adult trauma), and 2.1% at general TCs. Admission to level 1 pediatric TCs was associated with a significant mortality benefit (OR 0.6 [0.4-0.9]) vs. general TCs, suggesting a survival benefit for injured children. No difference was found between mortality of general TCs and dual-certified TCs, and interestingly, no statistically significant difference was found between pediatric TCs and the dual-certified TCs. Pediatric trauma mortality is rare, and additional study power may have teased out this difference. Still, as 17 million children do not have timely access to pediatric TCs, this remains a serious issue for the healthy and safety of our pediatric population.