Surgical Management of Epiphrenic Diverticula in the Minimally Invasive Era

Background:

Epiphrenic diverticula are rare outpouchings of the distal esophagus that infrequently require surgical intervention for the treatment of symptoms. In cases where surgical therapy is indicated, the traditional approach is through a thoracotomy. Advances in minimally invasive techniques have led to thoracoscopic and more recently laparoscopic management of epiphrenic diverticula. The purpose of this article is to review the literature on minimally invasive surgery for epiphrenic diverticula with particular attention to the operative approach and technique, surgical mortality and morbidity, and symptomatic outcomes.

Methods:

A review of the literature limited to studies in the English language and performed on humans was conducted on PubMed using the following key words: “esophageal diverticula” and “epiphrenic”. Articles retrieved by the PubMed search were reviewed.

Conclusions:

A minimally invasive approach to epiphrenic diverticula offers reduced operative mortality, decreased length of stay, and similar symptom relief compared with open surgery in the hands of experienced laparoscopic surgeons.     

Lack of KIR3DS1 binding to MHC class I Bw4 tetramers in complex with CD8+ T cell epitopes

In HIV-1 infection, the synergistic association of a subset of Bw4 MHC class I molecules and the activating killer inhibitory receptor (KIR), KIR3DS1, with prolonged AIDS-free survival has been reported. As KIRs represent a diverse group of MHC class I receptors, we questioned whether Bw4 MHC class I molecules expressing isoleucine at position 80 (Bw4Ile80) and in complex with HIV-1-derived T cell epitopes represented KIR3DS1 ligands. MHC class I tetramers are powerful tools for the detection of T cell receptor-MHC class I interactions, and have recently been used to evaluate KIR-MHC class I binding ex vivo. Specifically, this approach has been successfully utilized to assess binding of Bw4 MHC class I tetramers to KIR3DL1, an inhibitory KIR and allele of KIR3DS1. In this study we generated a diverse panel of HIV-1-specific Bw4Ile80 MHC class I tetramers and tested its ability to bind transiently expressed KIR3DS1 on 293-T cells. Using flow cytometry analysis, the expression of KIR3DS1 on 293-T cells was confirmed by anti-FLAG BioM2 staining, prior to incubation with PE-conjugated MHC class I tetramers. Despite choosing a broad array of peptide epitopes and diverse Bw4Ile80 MHC class I molecules, we were unable to detect tetramer binding to KIR3DS1. We speculate that our negative finding may be a consequence of the MHC class I molecules and peptide epitopes chosen, but could also relate to key amino acid differences that distinguish KIR3DS1 from KIR3DL1.     

Influence of fatigue, depression, and demographic, socioeconomic, and clinical variables on quality of life of patients with epilepsy

The purpose of this study was to define the influence of fatigue, depression, and clinical, demographic, and socioeconomic factors on the quality of life of patients with epilepsy. The study was performed on 103 adult patients who visited Erciyes University Epilepsy Outpatient Clinic between 2004 and 2005. Patients were evaluated with the Form of Negotiation, Quality of Life in Epilepsy Inventory (QOLIE-89), Beck Depression Inventory, and Fatigue Severity Scale. Mean age of the patients was 34.3+/-12.6, and mean duration of disease was 12.6+/-9.3 years. Among these patients, 52.4% were men, 49.5% were married, 15.5% had a university education, 53.4% had low incomes, 45.6% had generalized seizures, and 35.0% had experienced one or more seizures per month during the preceding year. The most significant variables in the domain of Overall quality of life were seizure frequency (P<0.001), depression (P<0.001), and fatigue (P<0.001); the variables in the domain of Mental Health were seizure frequency (P<0.001) and fatigue (P<0.001); the variable in the Cognitive domain was fatigue (P<0.001); the variables in the domain of Physical Health were social insurance coverage (P<0.01), fatigue (P<0.01), and age (P<0.01); the variables in the Epilepsy Targeted domain were depression (P<0.001), seizure frequency (P<0.001), and fatigue (P<0.01). Although quality of life has multiple determinants, seizure frequency, fatigue, and depression are the most important factors affecting quality of life in patients with epilepsy. One or more seizures per month, severe fatigue, and depression are associated with lower quality of life in some but not all domains. Partial correlations demonstrated that fatigue was a significant independent predictor of quality of life. The present study confirms that fatigue can be a powerful predictor of quality of life.     

Incorporation and immunogenicity of cleaned bovine bone in a sheep model

This study was conducted to determine if a novel cleaning process could extract antigenic material from bovine bone thereby improving incorporation. Cleaned bovine xenograft, untreated bovine xenograft and sheep allograft were implanted into the tibia of mature sheep for 12 and 24 weeks. Inflammation, bone integration and immunological reactions were evaluated via standardized assays. Cleaned bovine bone dowels induced significantly lower inflammatory responses (p < 50.05) when compared to traditionally processed xenograft. Bone integration, measured by in situ biomechanics, was not different between cleaned bovine bone and allograft controls (p = 0.96). A transient antibody response was observed for non-treated xenografts although this response abated by 3 months.     

Unravelling the complexity of metastasis - molecular understanding and targeted therapies

Despite recognizing the devastating consequences of metastasis, we are not yet able to effectively treat cancer that has spread to vital organs. The inherent complexity of genomic alterations in late-stage cancers, coupled with numerous heterotypic interactions that occur between tumour and stromal cells, represent fundamental challenges in our quest to understand and control metastatic disease. The incorporation of genomic and other systems level approaches, as well as technological breakthroughs in imaging and animal modelling, have galvanized the effort to overcome gaps in our understanding of metastasis. Future research carries with it the potential to translate the wealth of new knowledge and conceptual advances into effective targeted therapies.     

Classification and toxicities of vascular disrupting agents

Vascular disrupting agents (VDAs) are an exciting new group of targeted therapies under active clinical research in many solid tumors, in particular, lung cancer. Small-molecule VDAs are the focus of current clinical research, and consist of the flavonoids and the tubulin-binding agents. Toxicities of single-agent VDAs are characterized by acute, transient, and generally noncumulative side effects including headaches, nausea and vomiting, tumor pain, hypertension, and tachycardia. Flavonoid agents can also cause infusion site pain, visual disturbances, electrocardiac abnormalities, and symptoms consistent with an acute release of serotonin. Tubulin-binding agents can result in cardiac ischemia, abdominal pain, neuromotor abnormalities and cerebellar ataxia, and acute hemodynamic changes. Clinical trials investigating VDAs in combination with traditional chemotherapy have also shown the potential for significant pharmacologic and adverse toxicity interactions. Further research will need to focus on pharmacokinetic and pharmacodynamic parameters to optimize dosing schedules, determine effective combinations with chemotherapy, and minimize toxicities associated with VDAs.     

Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells

Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway's contribution to metastasis remains unknown. Here, we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of bone metastasis by activating the Notch pathway in bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the bone metastasis cytokine TGFβ that is released during bone destruction. Importantly, γ-secretase inhibitor treatment reduces Jagged1-mediated bone metastasis by disrupting the Notch pathway in stromal bone cells. These findings elucidate a stroma-dependent mechanism for Notch signaling in breast cancer and provide rationale for using γ-secretase inhibitors for the treatment of bone metastasis.     

Secondary cold agglutinin disease associated with Hashimoto disease

Our case involves a 53 year old woman. Three years ago, she was investigated because of normal hemoglobin levels despite very a low erythrocyte count, which was revealed during the preoperative evaluation for ovarian cyst operation. The Direct Coombs test was found to be positive against complement and negative against IgG. Cold agglutinin titer was 1/448 (+). Due to the polyclonal IgM increase, secondary cold agglutinin disease (CAD) was considered but no factor could be found that would lead to cold agglutinin disease. During the post-operative follow-up, cold agglutinin titers increased with fluctuations in the patient. Twenty-four months after transabdominal hysterectomy and bilateral salpingooopherectomy operation, diagnosis of Hashimoto disease was made upon detection of subclinical hypothyroidism. No case of Hashimoto disease associated with CAD caused by polyclonal IgM has been reported until the present time.