Tertiary Lymphoid Structures, Immune Response, and Prognostic Relevance in Non-Small Cell Lung Cancer.

We assessed the presence of 'tertiary lymphoid structures' (TLS) in a series of surgically treated non-small cell lung carcinomas (NSCLC). The TLS-density in the tumor periphery (pTLS) ranged from 0 to 1.8 (median 0.45), while in inner tumor areas (iTLS) ranged from 0 to 1.0 (median 0); (p < 0.0001). High pTLS-density was linked with early stage of the disease. Glycolysis-related enzyme expression (MCT1, Hexokinase 2) was linked with high pTLS-density (p < 0.05). High pTLS and iTLS densities were linked with better postoperative prognosis (p = 0.02 and p = 0.01, respectively). Assessment of TLS is a useful prognostic marker in NSCLC.

Carbonic anhydrase 9 (CA9) expression in non-small-cell lung cancer: correlation with regulatory FOXP3+T-cell tumour stroma infiltration.

BACKGROUND: Low pH suppresses the proliferation and cytotoxic activity of CD8+ cytotoxic and natural killer lymphocytes. The hypoxia-regulated transmembrane protein, carbonic anhydrase CA9, converts carbon dioxide produced by the Krebs cycle to bicarbonate and protons that acidify the extracellular milieu. We examined whether CA9 is also involved in intratumoural immunosuppression pathways. METHODS: A series of 98 tissue samples of primary non-small-cell lung carcinomas (NSCLC) from patients treated with surgery were analysed for the expression of CA9 and programmed-death ligand PD-L1 by cancer cells, and of FOXP3 by tumour-infiltrating lymphocytes (TILs). RESULTS: There was no direct association of CA9 with PD-L1 expression or the density of TILs in the tumour stroma, but CA9 was directly related to the extent of FOXP3+ TIL density (p = 0.008). Double-stratification survival analysis showed that patients with high CA9 expression and low TIL score had significantly poorer survival compared with all other groups (p < 0.04). In a multivariate analysis stage (p < 0.0001, HR 1.95, 95% CI: 1.3-2.7), TIL score (p = 0.05, HR 0.55, 95% CI: 0.2-1.0) was an independent prognostic variable of death events. CA9 expression by cancer cells is associated significantly with FOXP3+ regulatory T-cell abundance in the tumour stroma of NSCLC. CONCLUSION: The study provides a basis for testing CA9 as a marker of resistance to immune-checkpoint inhibitors and as a therapeutic target to enhance the efficacy of immunotherapy.

Situs Inversus Totalis: Single-Stage Anatomic Repair of Complex Congenital Heart Disease.

Transposition of the great arteries occurs rarely in patients with mirror image dextrocardia and situs inversus, while the combination with severe coarctation of the descending aorta (CoA) makes the anatomy even more unusual. Therefore, it is not surprising that a case with such unusual and complicated anatomy presents unique problems when a primary definitive correction is attempted. We report a patient with situs inversus totalis and complex congenital heart disease including transposition of the great arteries and severe CoA who underwent successful complete, single-stage, anatomic correction.

Postcardiotomy mechanical circulatory support in two infants with williams' syndrome.

Supravalvar aortic stenosis (SVAS) in patients with Williams' syndrome is often accompanied by coronary, pulmonary, and even myocardial lesions and therefore associated with increased perioperative morbidity and mortality. Extracorporeal membrane oxygenation (ECMO) provides reliable short-term mechanical circulatory support to patients, especially young, in acute postoperative cardiac failure when conventional means are ineffective. The incorporation of centrifugal pumps in these systems has made their use more efficient and less traumatic. We describe our experience of using the Levitronix CentriMag pump in two patients with Williams' syndrome who underwent surgical correction of supravalvular aortic stenosis.

Hybrid procedures for complex congenital cardiac lesions.

BACKGROUND: We present an alternative treatment employing a hybrid approach used in 3 patients with congenital heart disease. The goal was to provide optimal therapy by minimizing the potentially harmful effects of methods that accompany conventional surgical procedures. METHODS: Two patients aged 4 and 6 months underwent beating-heart closure of a muscular ventricular septal defect (VSD) with an occluding device. In addition, an 8-year-old patient with supraaortic, main, and branch pulmonary artery (PA) stenosis underwent conventional surgical patch augmentation of the ascending aorta and the main PA and intraoperative stenting of the branch PA stenoses. RESULTS: No patient deaths occurred. One patient developed a postoperative pneumothorax. Median intensive care unit and hospital stays for the VSD patients were 1 and 5 days and for the other patients 2 and 20 days, respectively. At median follow-up of 25 months, all patients were well and had required no further interventions. CONCLUSIONS: Patients with muscular VSD can currently be treated with the hybrid approach. Intraoperative PA stenting in addition to conventional surgical repair can be performed safely and may be complementary in patients with complex lesions.

Mid-term results following surgical treatment of congenital cardiac malformations in adults.

The long term consequences of untreated of residual or recurrent lesions pose unique challenges in the growing population of adults with congenitally malformed hearts. In our unit, 335 patients aged from 18 to 72 years, with a mean age of 35 plus or minus 14 years, presented for correction of congenital cardiac disease from September, 1997, through December, 2006. Of the group, 42 (12.5%) had undergone one or more prior surgical procedures, 3 were admitted as emergencies, and a further 10 (3%) had suffered prior cardiac related complications. Symptoms had been noted by 181 patients (54%), and 42 (12.5%) had an established arrhythmia. Chromosomal anomalies were identified in 13 (3.8%), and diagnostic catheterisation was required in 201 (60%) patients. Of the overall group, 2 patients died early (0.6%). Complications occurred in 61 patients (18%), including atrial fibrillation, pneumothorax, postoperative haemorrhage, pericardial or pleural effusions requiring drainage, stroke, complete heart block, endocarditis, wound dehiscence, and peripheral neuropathy. The median length of stay in the intensive care unit and hospital were 2 and 7 days, respectively. Death occurred later in 2 further patients (0.6%), due to atrial fibrillation and pulmonary hypertension. At mean follow-up of 63 plus or minus 30 months, the majority of the remaining patients are well with resolution or significant improvement in their symptoms. Despite the long term deleterious effects of untreated, residual or recurrent congenital cardiac lesions in adults, therefore, we conclude that surgical correction can be achieved with low mortality and acceptable morbidity. Most significant complications are related to arrhythmias.

Partial right-sided pericardial defect associated with congenital aortic valve disease.

Partial right-sided pericardial defect is an extremely rare congenital anomaly and is often associated with other congenital abnormalities. We describe a unique case of congenital aortic valve disease associated with right-sided pericardial defect. The clinical implications are discussed and a review of the literature is presented.

Emergency surgery for embolisation of Amplatzer device into the left atrium.

Occlusion of secundum atrial septal defects (ASD) by means of percutaneous transcatheter systems is increasingly used in clinical practice. A variety of different types and models of septal occluder devices are available nowadays, amongst which the Amplatzer device (Amplatzer Medical, Golden Valley, MN, U.S.A.), is regarded as one of increasing popularity. We report a case of attempted percutaneous transcatheter closure of a large ASD in an 11-year-old boy, complicated by device embolisation to the left atrium necessitating emergency surgery.

Early left ventricular function recovery after trap-door coronary transfer repair of ALCAPA in an adult patient.

Anomalous origin of the left coronary from the pulmonary artery (ALCAPA) is a rare congenital malformation, which may result in myocardial infarction, congestive heart failure, and sudden death if left untreated. Despite frequently advanced pathologic changes, there seems to be significant potential for the recovery of myocardial function in individuals with left ventricular dysfunction after the establishment of physiologic coronary circulation, particularly in the pediatric population. Reports of ALCAPA repair in adulthood are scarce and little information exists regarding the response of the left ventricle to revascularization in this age group. In this report, repair of ALCAPA in a significantly symptomatic adult patient with ventricular dysfunction is described, leading to an early recovery of left ventricular function.