ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.     

Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer.

PURPOSE: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) has recently been implicated in cancer development and progression. This study was performed to assess whether CEACAM-1 expression in primary tumors is correlated to long-term survival in patients with operable non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Primary tumors of 145 consecutive patients with completely resected NSCLC (pT(1-4) pN(0-2) M(0) R(0)) were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2. The prognostic relevance of CEACAM-1 expression was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 72 months (range, 10-130 months). RESULTS: Normal bronchiolar epithelium present in all sections exhibited no immunostaining. In contrast, 73 tumors (50.4%) showed between 1 and 66% CEACAM-1 positive tumor cells, and 72 tumors (49.6%) exhibited even a higher percentage of positive tumor cells. A high CEACAM-1 expression rate (i.e., >/=66% positive tumor cells) was more frequent in adenocarcinomas than in squamous cell carcinomas (61.9 versus 35.7%, respectively). Multivariate Cox regression analysis demonstrated that CEACAM-1 represents an independent prognosticator for cancer-related survival (P = 0.018; relative risk, 1.8; 95% confidence interval, 1.1-2.8). Subgroup analysis revealed that a high CEACAM-1 expression rate was of significant prognostic impact in pN(1)-pN(2) patients (n = 60; P = 0.024), pT(3)-pT(4) patients (n = 22; P = 0.009), and stage IIa-IIIa patients (n = 69; P = 0.012). CONCLUSIONS: The absence of CEACAM-1 in normal lung tissue and its expression in tumor cells argues against a tumor-suppressive role of CEACAM-1 in NSCLC. The correlation between elevated CEACAM-1 expression and an unfavorable prognosis indicates rather that CEACAM-1 might promote lung cancer progression.     

Asparaginase‐associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

L‐asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re‐exposure to L‐asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase‐intensive protocol has been poorly reported. Children (1–17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase‐associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L‐asparginase (PEG‐asparaginase) 1000 iu/m²/dose at 2–6 weeks intervals, with a total of 30 weeks of exposure to PEG‐asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1–13), and 11 d (median) from the latest administration of PEG‐Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re‐exposed to L‐asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re‐exposure to PEG‐asparaginase in ALL patients with mild AAP seems safe.     

Removal of Protein‐Bound,Hydrophobic Uremic Toxins by a Combined Fractionated Plasma Separation and Adsorption Technique

Protein‐bound uremic toxins, such as phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate, contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, based on their protein binding, these hydrophobic uremic toxins are poorly cleared during conventional dialysis and thus accumulate in CKD‐5D patients. Therefore, we investigated whether hydrophobic and cationic adsorbers are more effective for removal of protein‐bound, hydrophobic uremic toxins than conventional high‐flux hemodialyzer. Five CKD‐5D patients were treated using the fractionated plasma separation, adsorption, and dialysis (FPAD) system for 5 h. A control group of five CKD patients was treated with conventional high‐flux hemodialysis. Plasma concentrations of phenylacetic acid, indoxyl sulfate, and p‐cresyl sulfate were measured. Removal rates of FPAD treatment in comparison to conventional high‐flux hemodialysis were increased by 130% for phenylacetic acid, 187% for indoxyl sulfate, and 127% for p‐cresol. FPAD treatment was tolerated well in terms of clinically relevant biochemical parameters. However, patients suffered from mild nausea 2 h after the start of the treatment, which persisted until the end of treatment. Due to the high impact of protein‐bound, hydrophobic uremic toxins on progression of CKD and CVD in CKD‐5D patients, the use of an adsorber in combination with dialysis membranes may be a new therapeutic option to increase the removal rate of these uremic toxins. However, larger, long‐term prospective clinical trials are needed to demonstrate the impact on clinical outcome.     

Cardiac catheterisation in nonagenarians: Single center experience

Objective To explore the treatment, procedure related risks, and outcomes of patients older than 90 years of age undergoing cardiac catheterization. Methods We retrospectively studied 32 patients ≥ 90 years (93.0 ± 1.2 years) who underwent cardiac catheterisation in a tertiary specialist hospital (0.2% of 14,892 procedures during three years). The results were compared to a patient cohort younger than 90 years of age. Results Baseline characteristics revealed a higher prevalence of diabetes (P < 0.001), chronic obstructive pulmonary disease (P < 0.04), previous myocardial infarction (P < 0.02), and complex coronary anatomy (SYNTAX score 33 vs. 19) in nonagenarians. Patients < 90 years of age showed more hyperlipidemia (P < 0.01) and previous percutaneous coronary interventions (P < 0.015). Nonagenarians underwent coronary angiography more often for acute coronary syndrome (ACS) (P < 0.003), were presented more often in cardiogenic shock (P < 0.003), and were transferred faster to coronary angiography in cases of ACS (P < 0.0001). The observed in-hospital mortality rate (13% study group vs. 1% control group; P < 0.003) in nonagenarians was lower than the calculated rate of thrombolysis in myocardial infarction (TIMI) and global registry of acute cardiac events (GRACE) mortality and strongly influenced by the severity of clinical presentation and the presence of co-morbidities. Conclusions Despite the common scepticism that cardiac catheterisation exposes patients ≥ 90 years to an unwarranted risk, our data demonstrate an acceptable incidence of complications and mortality in this group of patients.     

Influence of residual stenosis after percutaneous coronary intervention with stent implantation on development of restenosis and stent thrombosis

The aim of this study was to assess the effects of residual stenosis after single-stent implantation on the rate of stent thrombosis, as well as restenosis within a 6-month follow-up period. Coronary angiograms of 2,157 patients with 2,523 lesions treated with a single stent were analyzed by quantitative coronary angiography before, immediately after stent implantation, and at a planned 6-month follow-up. Lesions were classified into 4 subgroups according to the degree of residual stenosis after stent implantation: group 1, gross oversizing <-15%; group 2, slight oversizing -15% to <0%; group 3, mild residual 0% to <15%; group 4, moderate residual 15% to <30%. Stent thrombosis rates were not significantly different among the 4 subgroups (group 1: 0 of 60 [0%]; group 2: 2 of 388 [0.5%]; group 3: 8 of 1,370 [0.6%]; group 4: 8 of 705 [1.1%]; p = NS for all). An adequate dosage of ticlopidine (250 mg twice daily) and aspirin (100 mg/day) led to a lower rate of stent thrombosis (6 of 2,189 cases) than inadequate dosages or missing therapy (12 of 343 cases). In 1,882 stenoses with angiographic follow-up (77.7%), gross oversizing of stents lead to a significantly higher increase of percent stenosis (p <0.001) associated with a higher restenosis rate (group 1: 34.7% vs groups 2, 3, and 4: 32.5%, 28.2%, and 29.6%, respectively). A multiple regression analysis was performed. Optimal results with regard to stent thrombosis and restenosis were achieved with mild residual stenoses between 0% and 15% after stent implantation. Oversizing of stents is no longer necessary with an adequate dosage of ticlopidine and aspirin.     

Effect of Aspiration Thrombectomy on Microvascular Obstruction in NSTEMI Patients : The TATORT-NSTEMI Trial

Background

Aspiration thrombectomy in ST-segment elevation myocardial infarction is recommended by current guidelines based on several randomized trials. There are no trials assessing thrombectomy in non–ST-segment elevation myocardial infarction (NSTEMI) patients.

Objectives

The TATORT-NSTEMI (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non–ST-Elevation Myocardial Infarction) trial sought to assess the effect of aspiration thrombectomy on microvascular injury in patients with NSTEMI compared with standard percutaneous coronary intervention (PCI).

Methods

This prospective, controlled, multicenter study randomized 440 patients to adjunctive thrombectomy (n = 221) compared with conventional PCI (n = 219) in NSTEMI patients with thrombus-containing lesions. The primary endpoint of the extent of microvascular obstruction (MO) in the percentage of left ventricular mass (%LV) was assessed by cardiac magnetic resonance imaging within 4 days. Secondary endpoints included infarct size, myocardial salvage index, and angiographic parameters including myocardial blush grade and Thrombolysis In Myocardial Infarction flow grade. The combined clinical endpoint consisted of death, reinfarction, target vessel revascularization, and new congestive heart failure within 6 months.

Results

The primary endpoint of MO was not different between the thrombectomy and the standard PCI group with 2.0%LV (interquartile range [IQR]: 0.8 to 4.1) versus 1.4%LV (IQR: 0.7 to 2.6) (p = 0.17). Similarly, no significant differences were observed for infarct size (8.6%LV; IQR: 4.0 to 14.7 vs. 7.4%LV; IQR: 4.1 to 13.1; p = 0.46), myocardial salvage index (63.3; IQR: 35.4 to 87.2 vs. 65.6; IQR: 46.9 to 82.6; p = 0.45), or angiographic parameters such as blush grade (p = 0.63) and Thrombolysis In Myocardial Infarction flow grade (p = 0.66). Clinical follow-up at 6 months revealed no differences in the combined clinical endpoints (p = 0.22).

Conclusions

Aspiration thrombectomy in conjunction with PCI in NSTEMI with a thrombus-containing lesion does not lead to a reduction in MO. (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction [TATORT-NSTEMI]; NCT01612312).