An Alternative Approach for Selective Lung Ventilation.

Single lung ventilation (SLV) with the double lumen tube (DLT) has been an effective process for providing surgical exposure in the thoracic cavity and has been applied effectively in the operating room. SLV also aids in protecting a healthy lung from the ill effects of fluid from an unhealthy lung, which may be blood, lavage fluid, or malignant or purulent secretions. Ensure correct placement, which is required and confirmed by a fiberoptic bronchoscope (FOB). The use of the DLT has been proven to be effective, but it has its challenges and drawbacks. This article proposes an alternative technique to the DLT in SLV without the use of a FOB. We have implemented this technique in 14 cases, however, we would like to discuss two challenging cases that have highlighted the advantages of this new technique.

Novel Sequence of Endoscopic Therapy for the Management of Colonic Adenocarcinoma and Surrounding Adenoma.

An 80-year-old man with a history of an orthotopic heart transplant was found to have a 25 × 40 mm centrally ulcerated mass at the hepatic flexure during evaluation of anemia. Owing to comorbidities, the patient was deemed to be a poor surgical candidate and was referred to the advanced endoscopy team to explore palliative and potentially curative options. We present a novel sequence of intervention involving full-thickness resection with subsequent morcellation clean-up to achieve complete endoscopic removal of a neoplastic lesion.

Foreign Body in the Glottis.

This case report highlights some of the anesthetic challenges of an airway foreign body removal. We present a case report of foreign body removal in a 50-year-old male with an oxtail bone lodged between the vocal cords. We used face mask general anesthesia with sevoflurane.

Exosomal integrins and their influence on pancreatic cancer progression and metastasis.

As one of the most lethal and untreatable types of cancer so far, pancreatic cancer is not benefitting from advancements in research. Despite all the efforts, this malignancy is still very difficult to diagnose in time, resistant to treatments, and prone to relapses. The appearance of metastasis-notoriously difficult to fight and a signal of unfortunate prognosis-is the event most dreaded by every cancer patient, especially by those with pancreatic cancer. Strategies for early detection and treatment of metastases are limited, and new action plans are desperately awaited. Recently, the importance of cell-secreted vesicles, or exosomes, in cell-cell communication and, particularly, their key role in promoting pathological conditions, such as infectious diseases and cancer, have attracted the attention of the scientific community. The discovery of some exosome membrane components, such as adhesion receptors and integrins, and their ability to influence cancer cell functions and metastasis progression, has added some important understanding of the metastatic process and will hopefully open the door to the development of new tools for identifying and targeting metastases. The aim of this review is to discuss the role played by integrins in exosomal-mediated pancreatic cancer progression and metastasis.

Exosomal long non-coding RNAs in the diagnosis and oncogenesis of pancreatic cancer.

Extracellular vesicles, specifically exosomes, play a significant role as an extracellular messenger through their transporting cargo. Of particular interest are the potential roles they play in pancreatic cancer, one of the leading causes of cancer-related mortality worldwide. Pancreatic Ductal Adenocarcinoma displays high chemo-resistance and metastatic ability, which may be influenced by cancer-derived exosomes carrying proteins, lipids and RNA. To date, among the most extensively examined exosomal molecular cargo there are long non-coding RNAs (lncRNAs) that, despite the increasing interest in their role and functions, are relatively poorly understood compared to other RNA transcripts. Nevertheless, we have witnessed an increasing interest for lncRNAs roles and functions in the past decade. For example, lncRNAs have been investigated as potential biomarkers for diagnosing pancreatic cancer and may have a role as therapeutics targets for precision medicine, but may also directly intervene in tumour progression features such as metastasis, epithelial to mesenchymal transition and resistance of cancer cells towards chemotherapy agents. The function of lncRNAs within various cancer exosomes is still undefined. In this review, we summarize the current knowledge on pancreatic cancer-derived exosome specific lncRNAs having prominent roles in genome integrity, pancreatic cancer progression and in other oncogenic hallmarks.

Stress responses, M2 macrophages, and a distinct microbial signature in fatal intestinal acute graft-versus-host disease.

Steroid-refractory intestinal acute graft-versus-host disease (aGVHD) is a frequently fatal condition with little known about mechanisms driving failed steroid responses in gut mucosa. To uncover novel molecular insights in steroid-refractory aGVHD, we compared gene expression profiles of rectosigmoid biopsies from patients at diagnosis of clinical stage 3-4 lower intestinal aGVHD (N=22), to repeat biopsies when the patients became steroid refractory (N=22), and normal controls (N=10). We also performed single gene analyses of factors associated with tolerance (programmed death ligand-1 [PDL1], indoleamine 2,3 dioxygenase [IDO1], and T cell immunoreceptor with Ig and ITIM domains [TIGIT]) and found that significantly higher expression levels of these aGVHD inhibitory genes (PDL1, IDO1, TIGIT) at aGVHD onset became decreased in the steroid-refractory state. We examined genes triggered by microbial ligands to stimulate gut repair, amphiregulin (AREG) and the aryl hydrocarbon receptor (AhR), and found that both AREG and AhR gene expression levels were increased at aGVHD onset and remained elevated in steroid-refractory aGVHD. We also identified higher expression levels of metallothioneines, metal-binding enzymes induced in stress responses, and M2 macrophage genes in steroid-refractory aGVHD. We observed no differences in T-cell subsets between onset and steroid-refractory aGVHD. Patients with a rapidly fatal course showed greater DNA damage and a distinct microbial signature at aGVHD onset, whereas patients with more prolonged survival exhibited a gene expression profile consistent with activation of Smoothened. Our results extend the paradigm beyond T cell-centric therapies for steroid-refractory GI aGVHD and highlight new mechanisms for therapeutic exploration.

Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.

Amphiregulin, a weak epidermal growth factor receptor agonist, is elevated, while epidermal growth factor, a strong epidermal growth factor receptor agonist, is low in the blood of patients with severe acute graft-versus-host disease. However, the tissue expression and function of these epidermal growth factor receptor ligands in acute graft-versus-host disease target organs is unknown. We compared by immunohistochemistry expression of amphiregulin and epidermal growth factor in archived, formalin-fixed, paraffin-embedded intestinal tissues of 48 patients with biopsy-proven gastrointestinal acute graft-versus-host disease to 3 groups: (1) 10 non-hematopoietic cell transplant normal controls, (2) 11 patients with newly diagnosed ulcerative colitis (ulcerative colitis), (3) 8 patients with a clinical diagnosis of acute graft-versus-host disease despite pathologically non-diagnostic biopsies, (4) and 10 cases of cytomegalovirus colitis. We used a semi-quantitative score of 0 (absent) through 3 (strong) to describe the intensity of immunohistochemical staining. We correlated serum and tissue amphiregulin and epidermal growth factor in patients with acute graft-versus-host disease. Gastrointestinal amphiregulin was significantly lower in acute graft-versus-host disease biopsies (median score 1), ulcerative colitis (median score 1.5), and cytomegalovirus colitis (median score 1) than in normal colon (median score 2, p = 0.004, p = 0.03, p = 0.009 respectively). Amphiregulin expression in was low in 74% of acute graft-versus-host disease cases with or without significant apoptosis. Patients with acute graft-versus-host disease exhibiting the pattern of high gastrointestinal amphiregulin but low serum amphiregulin (n = 14) had the best 1-year survival at 71%, but patients with high serum amphiregulin had poorer survival (<30%) regardless of gastrointestinal amphiregulin expression. Overall, our results lead to the hypothesis that amphiregulin is released into the circulation from damaged intestinal epithelium and stroma, although contributions from other cellular sources are likely. Low gastrointestinal amphiregulin expression by immunohistochemistry may be further studied for its utility in the pathologic acute graft-versus-host disease diagnosis without classic apoptotic changes.