Morbidity, mortality, and long-term survival after sleeve lobectomy for non-small cell lung cancer.

OBJECTIVE: Sleeve lobectomy is a widely accepted procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study is to assess operative mortality, morbidity, and long-term results of sleeve lobectomies performed for non-small cell lung carcinoma (NSCLC). METHODS: A retrospective review of 218 patients who underwent sleeve lobectomy for NSCLC between 1981 and 2005 was undertaken. There were 186 (85%) men and 32 women with a mean age of 61.9 years (range, 19-82 years). Eighty patients (36.6%) had a preoperative contraindication to pneumonectomy. Right upper lobectomy was the most common operation (45.4%). Vascular sleeve resection was performed in 28 patients (12.8%) and was commonly associated with left upper lobectomy (n=20; 9.1%; p=0.0001). The histologic type was predominantly squamous cell carcinoma (n=164; 75%), followed by adenocarcinoma (n=46; 21%). Resection was incomplete in nine (4.1%) patients. RESULTS: There were nine operative deaths; the operative mortality and the morbidity rates were 4.1% and 22.9%, respectively. A total of 14 (6.4%) patients presented with bronchial anastomotic complications: two were fatal postoperatively, seven patients required reoperation, three required a stent insertion, and two were managed conservatively. Multivariate analysis showed that compromised patients (p=0.001), current smoking (p=0.01), right sided resections (p=0.003), bilobectomy (p=0.03), squamous cell carcinoma (p=0.03), and presence of N1 or N2 disease (p=0.01) were risk factors for mortality and morbidity. Follow-up was complete in 208 patients (95.4%). Overall 5-year and 10-year survival rates were 53% and 28.6%, respectively. After complete resection, recurrence was local in 10 patients, mediastinal in 20, and distant in 25. By multivariate analysis, two factors significantly and independently influenced survival: nodal status (N0-N1 vs N2; p=0.01) and the stage of the lung cancer (stage I-II vs III, p=0.02). CONCLUSIONS: For patients with NSCLC, sleeve lobectomy achieves local tumor control, even in patients with preoperative contraindication to pneumonectomy and is associated with low mortality and bronchial anastomotic complication rates. Postoperative complications are higher in compromised patients, smokers, N disease, right sided resections, bilobectomies, and squamous cell cancers. The presence of N2 disease and stage III significantly worsen the prognosis.     

The temporal dynamics of postanoxic burst-suppression EEG.

Burst-suppression EEG (BS-EEG) after cardiopulmonary resuscitation implies a bad prognosis, but little is known of the temporal dynamics of postanoxic BS-EEG. The authors studied 24 consecutive patients who developed BS-EEG within 24 hours after cardiopulmonary resuscitation, and followed 20 of these patients with serial EEGs. Except for one patient, BS-EEG was followed by another EEG pattern within 1 day, mainly areactive alpha EEG (n = 6), isoelectric EEG (n = 5), generalized continuous epileptiform discharges (n = 4), or theta; EEG (n = 3). The coexistence of different EEG patterns in the same recording was seen in 10 patients. Serial recordings disclosed a variety of EEG sequences with (often subtle) transitions between the different EEG patterns, including reappearance of BS-EEG. Postanoxic BS-EEG is followed by a variety of EEG sequences composed of different EEG patterns, each of which is recognized as an unfavorable sign in and of itself. The coexistence of different unfavorable EEG patterns in the same recording, and transitions between these EEG patterns in subsequent recordings, are common in patients with postanoxic BS-EEG. It seems reasonable to speculate that BS-EEG and subsequently evolving EEG patterns in anoxic encephalopathy reflect different forms of neocortical dysfunction, which occur at different stages of a dynamic process, leading ultimately to severe neuronal loss.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

Comparative genomic indexing reveals the phylogenomics of Escherichia coli pathogens

The Escherichia coli O26 serogroup includes important food-borne pathogens associated with human and animal diarrheal disease. Current typing methods have revealed great genetic heterogeneity within the O26 group; the data are often inconsistent and focus only on verotoxin (VT)-positive O26 isolates. To improve current understanding of diversity within this serogroup, the genomic relatedness of VT-positive and -negative O26 strains was assessed by comparative genomic indexing. Our results clearly demonstrate that irrespective of virulence characteristics and pathotype designation, the O26 strains show greater genomic similarity to each other than to any other strain included in this study. Our data suggest that enteropathogenic and VT-expressing E. coli O26 strains represent the same clonal lineage and that VT-expressing E. coli O26 strains have gained additional virulence characteristics. Using this approach, we established the core genes which are central to the E. coli species and identified regions of variation from the E. coli K-12 chromosomal backbone.     

Monitoring CD4+ T cell responses against viral and tumor antigens using T cells as novel target APC

CD4+ T cells play an important role in the induction and maintenance of an effective antiviral and antitumor immune response. However, standardized monitoring of antigen-specific CD4+ T cells has not been established at the single-cell level. We now present a sensitive, specific, and simple methodology in which purified memory CD4+ T cells are expanded from PBMC in a single cycle of antigen-driven stimulation and quantitatively assayed by interferon-gamma ELISPOT. Issues of nonspecific background in assays were resolved with the use of innovative target cells, autologous PHA-expanded CD4+ T cells (T-APC). Remarkably, T-APC could not only present peptide epitopes from model antigens NY-ESO-1 and influenza nucleoprotein, but could also process full-length antigen endogenously expressed from recombinant fowlpox vector. This approach makes it possible to monitor CD4+ T cells in large series of patients, regardless of HLA haplotype, against the full peptide repertoire of a given antigen.     

Methylation status of immunoglobulin x e segments correlates with their recombination potential

We have previously shown that unlike endogenous ? genes, unrearranged ? transgenes undergo V?-J? recombination in T as well as B cells of transgenic mice. To determine whether the difference in recombination specificity of the transgenic and endogenous ? genes is associated with differences in DNA structure, the methylation status of the endogenous genes and three unrearranged ? transgenes was compared. The J?-C? locus of the transgenes was found to be hypomethylated in all tissues of the transgenic mice. In contrast, methylation of the endogenous ? genes was tissue and developmentally regulated. Hypomethylation of the endogenous J?-C? region occurs only in cells of the B lineage undergoing, or having completed ? gene recombination. Transfection of fibroblasts from transgenic and control mice with the recombination activating genes, Rag1 and Rag2, led to a high level of rearrangement of the hypomethylated transgenic, but not the endogenous ? genes. These results suggest that hypomethylation defines an accessible state of the ? locus and that methylation/demethylation could be involved in the control of ? gene rearrangement during lymphocyte differentiation.     

Mapping and ranking of potential cytotoxic T epitopes in the p53 protein: effect of mutations and polymorphism on peptide binding to purified and refolded HLA molecules

In many cancer cells, the p53 gene displays point mutations that result in stabilization and accumulation of the p53 protein. Therefore, p53 peptides could be presented to the immune system by tumor cells; thus, p53 might be a suitable target antigen for developing an immunotherapy against tumors using cytotoxic T lymphocytes (CTL). To map candidate CTL epitopes, we synthesized 150 peptides of 8–11 residues that contained putative anchor motifs required for binding to common HLA class I molecules. They were tested for their capacity to promote the assembly of purified and refolded HLA-A1, A2, B7 and B8 molecules. The following wild-type p53 peptides were found to be reactive with the HLA molecules tested: 196–205 and 226–234 bound moderately to HLA-A1; 25–35, 65–73, 129–137, 187–197, 263–272 and 264–272 bound strongly, and 187–195 and 256–264 moderately to HLA-A2; 26–35, 63–73, 189–197, 249–257 and 321–330 bound strongly to HLA-B7; and 135–143, 210–218 and 375–383 bound weakly to HLA-B8. We also analyzed the effects of p53 mutations occurring naturally in tumors on peptide/HLA assembly. We found substitutions that enhanced, diminished or had no effect on the peptide binding to HLA molecules. Polymorphism at position 72 mainly affected peptide/HLA-B7 binding, the proline allele P72 giving a less-reactive peptide (63–73) than the arginine allele R72. We have ranked potential p53 epitopes according to their reactivity for purified HLA molecules, allowing the selection of appropriate peptides and HLA molecules to attempt CTL induction in vitro.     

Treating acute colonic diverticulitis with extraluminal pericolic air: An Acute Care Surgery in the Netherlands (ACCSENT) multicenter retrospective cohort study

BackgroundOwing to improved quality of computed tomography, a new category of complicated acute diverticulitis, including patients with pericolic air but without abscess formation, can be defined (Hinchey 1a). Recent studies question whether this new category of acute diverticulitis could be treated as uncomplicated cases. The aim of our study is to report on the clinical course of acute diverticulitis Hinchey 1a in current clinical practice.MethodsFor this multicenter retrospective cohort study, patients presenting at the emergency department with Hinchey 1a acute diverticulitis as demonstrated by computed tomography scan, were identified. The primary outcome measure was successful conservative treatment with observation alone, antibiotics, and/or hospital admission. Readmissions, percutaneous drainage of abscesses, and emergency operations were considered as failure.ResultsBetween October 2016 and October 2018, 1,199 patients were clinically suspected for acute diverticulitis, of whom 101 (8.4%) were radiologically diagnosed to have type 1a acute diverticulitis (average age 57 (±13) years, 45% female) and started with conservative treatment. This was successful in 86 (85%) patients. One of the 15 unsuccessfully treated patients (1%) received percutaneous drainage of an abdominal abscess. Surgery was required in 9 cases (9%) after a median time of 6 days (range, 3 to 69 days). Although a difference in the volume of extraluminal air on computed tomography scan was found, this was not shown to be a risk factor for the clinical course.ConclusionPatients with type 1a acute diverticulitis can be treated successfully by conservative therapy in the majority of cases (85%). More research is required to define predictive factors for successful conservative management.