Calvin S.H. Ng

Prevalence of survivor bias in observational studies on fresh frozen plasma: erythrocyte ratios in trauma requiring massive transfusion

Observational studies on transfusion in trauma comparing high versus low plasma:erythrocyte ratio were prone to survivor bias because plasma administration typically started later than erythrocytes. Therefore, early deaths were categorized in the low plasma:erythrocyte group, whereas early survivors had a higher chance of receiving a higher ratio. When early deaths were excluded, however, a bias against higher ratio can be created. Survivor bias could be reduced by performing before-and-after studies or treating the plasma:erythrocyte ratio as a time-dependent covariate. We reviewed 26 studies on blood ratios in trauma. Fifteen of the studies were survivor bias-unlikely or biased against higher ratio; among them, 10 showed an association between higher ratio and improved survival, and five did not. Eleven studies that were judged survivor bias-prone favoring higher ratio suggested that a higher ratio was superior. Without randomized controlled trials controlling for survivor bias, the current available evidence supporting higher plasma:erythrocyte resuscitation is inconclusive.

Prophylactic ilioinguinal neurectomy in open inguinal hernia repair: a double-blind randomized controlled trial.

Objective:We conducted a double-blinded randomized controlled trial to investigate the short- to mid-term neurosensory effect of prophylactic ilioinguinal neurectomy during Lichtenstein repair of inguinal hernia. Method:One hundred male patients between the age of 18 and 80 years with unilateral inguinal hernia undergoing Lichtenstein hernia repair were randomized to receive either prophylactic ilioinguinal neurectomy (group A) or ilioinguinal nerve preservation (group B) during operation. All operations were performed by surgeons specialized in hernia repair under local anesthesia or general anesthesia. The primary outcome was the incidence of chronic groin pain at 6 months. Secondary outcomes included incidence of groin numbness, postoperative sensory loss or change at the groin region, and quality of life measurement assessed by SF-36 questionnaire at 6 months. All follow-up and outcome measures were carried out by a designated occupational therapist at 1 and 6 months following surgery in a double-blinded manner. Results:The incidence of chronic groin pain at 6 months was significantly lower in group A than group B (8% vs. 28.6%; P = 0.008). No significant intergroup differences were found regarding the incidence of groin numbness, postoperative sensory loss or changes at the groin region, and quality of life measurement at 6 months after the operation. Conclusions:Prophylactic ilioinguinal neurectomy significantly decreases the incidence of chronic groin pain after Lichtenstein hernia repair without added morbidities. It should be considered as a routine surgical step during the operation.

Inflammatory Response to Pulmonary Ischemia–Reperfusion Injury

Lung ischemia–reperfusion (IR) injury is one of the most important complications following lung transplant and cardiopulmonary bypass. The pulmonary dysfunction following lung IR has been well documented. Recent studies have shown that ischemia and reperfusion of the lung may each play significant yet differing roles in inducing lung injury. The mechanisms of injury involving neutrophil activation, and the release of numerous inflammatory mediators and oxygen radicals also contributes to lung cellular injury, pneumocyte necrosis, and apoptosis. We herein review the current understanding of the underlying mechanism involved in lung IR injury. The biomolecular mechanisms and interactions which lead to the inflammatory response, pneumocyte necrosis, and apoptosis following lung IR therefore warrant further investigation.

Pulmonary ischaemia-reperfusion injury: role of apoptosis

The central role of lung ischaemia–reperfusion injury in pulmonary dysfunction after cardiac surgery, particularly thoracic organ transplantation, has been well recognised. Lung tissue necrosis after prolonged ischaemia is known to worsen lung function, which was believed to be due largely to adjacent tissue inflammation. Recent studies suggest that lung apoptosis following ischaemia–reperfusion could be equally important in the development of post-operative lung dysfunction. The current literature on the mechanism and pathways involved in pulmonary dysfunction and, in particular, its relationship with apoptosis after lung ischaemia–reperfusion is briefly reviewed here. A better understanding of lung apoptosis, as well as the upstream pathways, may help in the development of therapeutic strategies that could benefit patients undergoing cardiac and lung transplantation.

Thoracotomy Is Associated With Significantly More Profound Suppression in Lymphocytes and Natural Killer Cells Than Video-Assisted Thoracic Surgery Following Major Lung Resections for Cancer

Major surgery is immunosuppressive, and this could have an impact on postoperative tumor immunosurveillance and, therefore, long-term survival in cancer patients. Video-assisted thoracic surgery (VATS) lung resection is a new alternative surgical approach to thoracotomy for patients with early lung cancer. This is a pilot study to examine the postoperative changes in leukocytes, lymphocyte subsets, B cells, T cells, and natural killer (NK) cells in non-small-cell lung cancer (NSCLC) patients undergoing lung resection with VATS versus thoracotomy approaches. Twenty-one consecutive patients with resectable primary NSCLC were assigned to VATS or thoracotomy approach over a 3-month period. Blood samples were collected preoperatively and at postoperative days (POD) 1, 3, and 7 for flow cytometry determination of total leucocytes, B cells, NK cells, lymphocytes, total T cells, and T4 and T8 cell numbers. There were no demographic differences between the two groups. Compared with the preoperative values, significantly increased total white cell numbers were detected at POD 1, 3, and 7 in all patients. At POD 1, although T8 cells and NK cells were reduced in both groups, total T cell, T4 cell, and lymphocyte numbers were significantly reduced only in the thoracotomy group. At POD 7, NK cell numbers were significantly lower in the thoracotomy group than that in the VATS group. No significant intra- or intergroup differences were seen with B cells. No significant differences in survival or disease-free survival were found between the two groups. Thus, VATS major lung resection for NSCLC is associated with less, as well as quicker recovery from, postoperative immunosuppression compared with the thoracotomy approach. The clinical relevance of better preserved cellular immunity in the early postoperative period warrants confirmation from large randomized trials.

Is Minimal Access Surgery for Cancer Associated with Immunologic Benefits

Minimal-access surgical techniques have been shown to be beneficial to patients in terms of shorter convalescence, reduced pain, and improved cosmesis. Although systemic immune function is better preserved following laparoscopic procedures when compared with their respective open approaches, CO2 pneumoperitoneum may significantly affect local (i.e., infra-abdominal) cellular immunity by reducing regional macrophage function. Results to date are conflicting with regard to the impact of closed and open methods on intraabdominal immunity. Impaired cellular immunity after CO2 pneumoperitoneum may have significant undesirable intra-abdominal effects on tumor surveillance after oncological surgery; however, at present, there is no clinical evidence to support this position. The VATS techniques avoid the use of CO2 insufflation, which may offer some advantages from the immune function perspective over laparoscopic procedures accomplished with CO2 pneumoperitoneum. Better preservation of early postoperative cellular immune function and attenuated disturbance in the inflammatory mediators are likely contributing factors to the clinical benefits that follow laparoscopic surgery and VATS. Larger multi-center randomized trials are needed to confirm the potential benefits of minimal-access surgery on patient survival after cancer surgery. Future research should focus on the effects of minimal-access surgery on other mediators (such as MMP-9, IGFBP-3, IL-12, IL-17, and IL-23) that may be important in tumor cell dissemination, deposition, and propagation in the early postoperative period. Furthermore, additional searches for other factors or mediators, heretofore unrecognized, should be carried out. Such studies will, we hope, increase our knowledge and understanding of the impact of surgery on immune and other physiologic functions.

Randomized, double-blinded, placebo-controlled trial of intravenously administered hyoscine N-butyl bromide in patients undergoing colonoscopy with patient-controlled sedation.

BACKGROUND A prospective, double-blinded, placebo-controlled randomized trial was conducted to investigate the effect of the antispasmodic hyoscine N-butyl bromide (Buscopan) during colonoscopy. METHODS A total of 120 patients undergoing colonoscopy were randomized to receive either 40 mg of hyoscine N-butyl bromide (n=60) or normal saline solution (n=60) intravenously as premedication. Colonoscopy was performed under patient-controlled sedation. Outcome measures included cecal intubation and total procedure time, demanded and administered doses of patient-controlled sedation, spasm score, pain score, endoscopist satisfaction score, patient willingness to repeat colonoscopy, and vital signs (blood pressure, pulse rate) during colonoscopy. RESULTS Mean cecal intubation time in the hyoscine N-butyl bromide group was significantly longer than the control group (12.20 vs. 9.74 minutes; p=0.04; but correction for multiple testing of data removed this significance). The use of hyoscine N-butyl bromide was associated with a significantly lower endoscopist mean satisfaction score (6.47 vs. 7.30; p=0.04; but correction for multiple testing of data removed this significance), higher demanded and administered mean doses of patient-controlled sedation (respectively, 34.80 and 7.25 vs. 24.20 and 5.87; p=0.045; p=0.04, respectively; but correction for multiple testing of data removed these findings of significance), fewer patients willing to repeat colonoscopy (60% vs. 83.9%; p=0.005), and more hemodynamic instability (p<0.001) when compared with the control group. No significant difference was found in the total procedure time, spasm score, or pain score. CONCLUSIONS Premedication with intravenously administered hyoscine N-butyl bromide impedes colonoscope insertion and causes greater patient discomfort, as well as hemodynamic instability.

MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non–Small Cell Lung Carcinoma with Poor Prognosis

Purpose: Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naïve non–small cell lung carcinoma (NSCLC). Experimental Design: Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METΔ14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively. Results: METΔ14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METΔ14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METΔ14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio ≥5) was mutually exclusive to the major driver genes except METΔ14. Oncogenic METΔ14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METΔ14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METΔ14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis. Conclusions: The high incidence of METΔ14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients. Clin Cancer Res; 22(12); 3048–56. ©2016 AACR. See related commentary by Drilon, p. 2832

OPTIMUM DURATION OF PROPHYLACTIC ANTIBIOTICS IN ACUTE NON‐PERFORATED APPENDICITIS

Background:  The effect of extended prophylactic antibiotic therapy on postoperative infective complications such as wound infection and intra‐abdominal abscess for non‐perforated appendicitis is poorly defined.

Video-assisted thoracic surgery lobectomy for pulmonary sequestration

Pulmonary sequestration is a rare developmental abnormality, and the patients usually present with recurrent pneumonia. We report a case of video-assisted thoracic surgery lobectomy in a 32-year-old woman with an intrapulmonary sequestration in the left lower lobe.