Linda J. Veit

VATS Lobectomy Has Better Perioperative Outcomes Than Open Lobectomy: CALGB 31001, an Ancillary Analysis of CALGB 140202 (Alliance)

BACKGROUND The short-term superiority of video-assisted thoracoscopic surgery lobectomy compared with open lobectomy for early-stage lung cancer has been suggested by single-institution studies. Lack of equipoise limits the feasibility of a randomized study to confirm this. The hypothesis of this study (CALGB 31001) was that VATS lobectomy results in shorter length of hospital stay and fewer complications compared with open lobectomy in stages I and II non-small cell lung cancer in a multi-institutional setting. METHODS Five hundred nineteen patients whose tumors had been collected as part of CALGB 140202 (lung cancer tissue bank) were eligible. Propensity-scoring using age, race, sex, performance status, comorbidities, histology, tumor stage, and size as independent variables was used to create a 1:1 matched group of 175 pairs of patients. McNemars test for binary variables and Wilcoxon signed-rank test for continuous variables were used to assess differences in length of hospital stay, complications, and discharge dispositions between the groups. Comparison of disease-free and overall survival between the two approaches was done using the log-rank test. Probability values of less than 0.05 were considered significant. RESULTS The matched data on length of hospital stay, complications, and discharge dispositions significantly favored the video-assisted thoracoscopic surgery group. There was no statistically significant difference in survival between the two approaches. CONCLUSIONS This multi-institutional study supports the assertion that thoracoscopic lobectomy results in shorter hospital length of stay, fewer perioperative complications, and greater likelihood of independent home discharge compared with open lobectomy for early-stage lung cancer. Survival was comparable between the two groups.

Preoperative evaluation of stage I and stage II non-small cell lung cancer

The appropriate preoperative evaluation for occult metastasis in patients with potentially resectable lung cancer remains controversial. The records of 265 patients with stage I and II non-small cell lung cancers who underwent resection with curative intent were reviewed to determine if there was a survival benefit of negative preoperative scanning to detect metastases. A minimum of 5 years of follow-up was possible for all long-term survivors. Patients having preoperative bone scans, brain imaging, and abdominal imaging had no increased survival over those without such evaluation (using Kaplan-Meier survival curves). Additionally, no difference was found in the time to first recurrence between these groups, and the site of recurrence was independent of a negative preoperative scan for that location. These data, using patient outcome as the basis of our conclusion, support a policy of reserving expensive preoperative metastatic evaluations only for those patients with clinical evidence of metastatic disease.

Biopsy first: Lessons learned from Cancer and Leukemia Group B (CALGB) 140503

Objective: Cancer and Leukemia Group B 140503 is an ongoing, multicenter randomized trial assessing whether sublobar resection is equivalent to lobectomy for the treatment of stage I A non−small cell lung cancer (NSCLC) ≤2 cm in diameter. The objective of this report is to determine the reasons precluding intraoperative randomization. Methods: From June 15, 2007, to March 22, 2013, 637 patients were preregistered to the trial. Three hundred eighty‐nine were randomized successfully (61%), and 248 patients were not randomized (39%). We analyzed the reasons for nonrandomization among a subset of the nonrandomized patients (208) for whom additional data were available. Results: Of these 208 patients, undiagnosed benign nodules (n =104, 16% of all registered patients) and understaging of NSCLC (n =45, 7% of all registered patients) were the dominant reasons precluding randomization. Granulomas represent one‐quarter of the benign nodules. The understaged patients had unsuspected nodal metastases (n =28) or other more advanced NSCLC. The rate of randomization was significantly greater in those patients who had a preoperative biopsy (P <.001). Conclusions: In a carefully monitored cohort of patients with suspected small NSCLC ≤2 cm, a substantial number are misdiagnosed (benign nodules) or understaged. These patients may not have benefited from a thoracic surgical procedure. Preoperative biopsy significantly increased the rate of correct diagnosis. Preoperative biopsy of small suspected NSCLC will reduce the number of nontherapeutic or unnecessary thoracic procedures. Accuracy in preoperative diagnosis is increasingly important as more such small nodules are discovered through lung cancer screening.

Single-dose versus multidose cardioplegia in neonatal hearts

We designed an experiment to compare single-dose versus multidose cardioplegia (calcium 0.3 mmol/L) in neonatal rabbit hearts 1, 4 and 6 weeks of age at 25 degrees C and 32 degrees C. Isolated hearts had a stabilization period of retrograde perfusion, a working period, a period of ischemia with single or multidose cardioplegia, reperfusion, and a final working period. We measured hemodynamic recovery, creatine kinase during reperfusion, and coronary vascular resistance during administration of the cardioplegic solution. One-week and 4-week-old hearts exhibited better recovery with single-dose than with multidose cardioplegia. Six-week-old hearts, on the other hand, showed better recovery with multidose cardioplegia. Four-week-old hearts at 25 degrees C showed increased creatine kinase release with multidose cardioplegia. The 6-week-old hearts tended toward lower creatine kinase release with multidose cardioplegia. Coronary vascular resistance rose with subsequent administrations in 1-week and 4-week-old hearts at 25 degrees C but did not rise in 1- and 4-week-old hearts at 32 degrees C or in 6-week-old hearts at either temperature. On the basis of hemodynamic recovery, single-dose cardioplegia appears to provide better protection than multidose cardioplegia to 1- and 4-week-old isolated rabbit hearts. Once the rabbit has reached 6 weeks of age, multidose cardioplegia has some advantage over single-dose cardioplegia, similar to the findings in adult hearts. Creatine kinase release and coronary vascular resistance data corroborate the hemodynamic findings.

Recovery of hypoxic neonatal hearts after cardioplegic arrest

OBJECTIVES Surgery for repair of congenital heart defects in the infant may be affected by hypoxia associated with the defect. The effects of chronic hypoxia on systemic ventricular function are not well characterised and few studies have considered myocardial preservation in the hypoxic neonatal heart. The aim was to determine how chronic hypoxia would affect left ventricular function in neonatal rabbit hearts subjected to global ischaemia. METHODS Hearts from rabbits one, four, and six weeks of age and raised at 9% O2 were compared with hearts from rabbits raised in ambient air. Haemodynamic variables were measured with an isolated heart preparation before and after cardioplegic arrest. Creatine kinase was measured during reperfusion and myocardial oxygen consumption (MVO2) during ischaemia. RESULTS At all ages, hypoxic hearts had significantly lower peak dP/dt and contractility index (dP/dt/left ventricular pressure (LVP)) than normoxic controls. After ischaemia and reperfusion, one week hypoxic hearts did not differ significantly in recovery from controls. Four week hypoxic hearts had significantly higher stroke volume and aortic flow, and six week hearts had significantly higher coronary flow than age matched controls. Contractility index did not show significant differences between hypoxic and control animals at any age. Hypoxic hearts released less creatine kinase in the coronary effluent during reperfusion than did control hearts of similar age. Six week hypoxic hearts had significantly higher MVO2 measured during the second administration of cardioplegia compared with six week control hearts but MVO2 did not differ significantly at one and four weeks of age. CONCLUSIONS Despite reduced baseline function, chronically hypoxic immature rabbit hearts can recover from an ischaemic insult as well as age matched controls, with less evidence of myocardial necrosis. This parallels clinical findings in cyanotic infants.

Neonatal myocardium resists reperfusion injury

The response of neonatal myocardium to ischemia and reperfusion was observed in an isolated working heart model using neonatal rabbits and compared to that of the adult rabbit heart. Lipid peroxidation occurring during ischemia and that occurring during reperfusion were evaluated separately. Malondialdehyde (MDA) in heart tissue was measured as an index of lipid peroxidation, and the occurrence of oxygen free radical damage was assessed by the effects of the scavengers, superoxide dismutase and catalase, on MDA production. Baseline MDA levels were similar in neonatal and adult hearts, were changed little by treatment with normoxic cardioplegia, and were elevated in both groups by treatment with hyperoxic cardioplegia. Thus, the degree of lipid peroxidation during ischemia is similar in neonatal and adult hearts. After 10 min of retrograde reperfusion subsequent to treatment with anoxic cardioplegia, the MDA content of adult hearts was significantly greater than that of similarly treated neonatal hearts. Addition of free radical scavengers to the reperfusion medium lowered the MDA content of adult hearts significantly, but not to the level of neonatal hearts. After 60 min of reperfusion subsequent to hyperoxic cardioplegia, adult hearts had higher MDA than neonates; addition of scavengers to the cardioplegia did not lower the MDA significantly in either group. Only 5 of 12 adult hearts recovered function after hyperoxic cardioplegia, while all 12 neonatal hearts recovered. Our results indicate that neonatal myocardium suffers less damage from oxygen-centered free radicals during reperfusion than does adult myocardium.

The relationship of iron and glycogen to the in vitro, ultraweak chemiluminescent analysis of lipid peroxidation in rabbit hearts of varying ages

Oxidative stress, which occurs when prooxidants overwhelm antioxidants, has been implicated as a cause of tissue damage related to ischemia and reperfusion. Neonatal animal and human hearts have been shown to differ in their response to oxidative stress, but the mechanism for this difference is unclear. To study this phenomena, crude homogenates of hearts from 4-day, 4-week, and adult (> 6 months) New Zealand rabbits were studied by chemiluminescence after exposure to O2/CO2 (95/5) or tert-butyl hydroperoxide (TBHP). Loosely bound iron and glycogen concentrations were also determined. The 4-day hearts exhibited more chemiluminescence after both oxygen and TBHP-driven stress. When exposed to O2, they reached a maximum rate of chemiluminescence in one-third less time and exhibited a 22% higher count rate. Likewise, when stimulated by TBHP, their rate was 44% higher than the hearts of both older groups. The 4-day hearts also had a 40% greater content of loosely bound iron that may, in part, explain their greater susceptibility to oxidative stress. Although the youngest hearts had the highest glycogen content, that did not offer protection against oxidative stress, as has been previously reported for liver.