The role of percutaneous endoscopic gastrostomy(PEG)in palliative care

The role of percutaneous endoscopic gastrostomy(PEG)in palliative care has not been well discussed. With the evolution of endoscopic techniques and PEG devices, we can perform PEG more safely, even in difficult cases. Actually, PEG is very useful in home care of cancer patients. We should discuss the indications of PEG in the field of palliative medicine. We suggest the following indications for PEG: 1.Difficulty in ingestion of sufficient quantities of food and water because of pain on swallowing, or an obstruction caused by cancer. 2.Normal gastrointestinal function. 3.Expected survival time of more than four weeks in addition to absence of cachexia. 4.Patient's consent for PEG.     

Treatment for gastric carcinoma in the oldest old patients

Background

The strategy for treating extremely aged patients with gastric carcinoma is controversial. This study reviews the prognoses of patients aged 85?years and older who were diagnosed with gastric carcinoma.

Methods

One hundred seventeen patients aged 85?years and older were diagnosed as having gastric carcinoma after 1969 in our institution. After excluding those at stage IV, 36 cases underwent curative resection and 30 cases received best supportive care (BSC), which we reviewed retrospectively.

Results

Surgical methods included distal gastrectomy for 28 cases, total gastrectomy for five cases, and other procedures for three cases. Postoperatively, pneumonia developed in four cases, anastomotic leakage in two cases, and pancreatic fistula in one case. Two patients died of pneumonia within 1?month of surgery. Univariate analysis demonstrated that age, surgery, performance status, and sodium level were statistically significant prognostic factors. Multivariate analysis demonstrated that surgery was the only independent prognostic factor. When patients with a performance status of 4 were excluded, the clinical characteristics of the surgery group (n?=?36) and BSC group (n?=?20) were statistically identical, and the overall survival was significantly better in the surgery group (p?=?0.0078).

Conclusions

Postoperative outcomes were relatively acceptable. Surgery may be feasible and beneficial even for extremely aged patients 85?years and older, except for those with a performance status of 4.     

Long-term ventilation for high-level tetraplegia: a report of 2 cases of noninvasive positive-pressure ventilation

Toki A, Tamura R, Sumida M. Long-term ventilation for high-level tetraplegia: a report of 2 cases of noninvasive positive-pressure ventilation.Ventilator-dependent patients with tetraplegia rarely use noninvasive positive-pressure ventilation (NPPV) for long-term ventilation. We report 2 patients with high-level traumatic tetraplegia who were able to return home after being changed from traditional ventilation to NPPV. When they were referred to our hospital from acute care hospitals 2 to 6 months after injury, both were on tracheostomy ventilation with a cuff inflated 24 hours a day, and tidal volume (Vt) settings were low. In case 1, a man with complete C1 tetraplegia was admitted to our hospital 6 months after injury. We changed ventilator settings to high Vt and introduced NPPV. He was discharged home with NPPV with a volume-setting ventilator. Case 2 involved a man in his late twenties with complete C1 tetraplegia who was discharged home with NPPV. After discharge, he trained in glossopharyngeal breathing by himself, enabling him to breathe up to 1900mL of maximum insufflation capacity. Both have lived nearly 1 year without pulmonary complications in the community. They use visiting nurses 3 times a week and services of visiting caregivers. Further study is needed to determine the usefulness of NPPV for long-term ventilatory management.     

Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes

Translocation of inhaled ultrafine particles from the lungs into the blood may impair cardiovascular function. We administered ultrafine (20-nm) and fine (200-nm) gold colloid or fluorescein-labeled polystyrene particles to mice intratracheally and examined their localization in the lung and extrapulmonary organs. Fifteen minutes after instillation, dispersed and agglomerated 20-nm gold colloid particles were observed on the surface of endothelial cells, on the alveolar surface, in endocytotic vesicles of alveolar epithelial cells, and in the basement membrane of the lung. A small but noteworthy amount of gold was detected in the liver, kidney, spleen, and heart by inductively coupled plasma-mass spectrometry. After administration of 20- or 200-nm fluorescent particles, free particles were detected infrequently in blood vessels, on the endocardial surface, and in the kidney and liver only in the mice that received 20-nm particles, whereas phagocytes containing 20- or 200-nm particles were found in the extrapulmonary tissues. Fluorescent particle-laden alveolar macrophages administered intratracheally translocated from alveoli to extrapulmonary organs via the blood circulation. Thus, small amounts of ultrafine particles are transported across the alveolar wall into the blood circulation via endocytotic pathways, but particle-laden alveolar macrophages translocate both ultrafine and fine particles from the lungs to the extrapulmonary organs.     

The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity

Adrenomedullin (AM) is a peptide involved both in the pathogenesis of cardiovascular diseases and in circulatory homeostasis. The high-affinity AM receptor is composed of receptor activity-modifying protein 2 or 3 (RAMP2 or -3) and the GPCR calcitonin receptor-like receptor. Testing our hypothesis that RAMP2 is a key determinant of the effects of AM on the vasculature, we generated and analyzed mice lacking RAMP2. Similar to AM-/- embryos, RAMP2-/- embryos died in utero at midgestation due to vascular fragility that led to severe edema and hemorrhage. Vascular ECs in RAMP2-/- embryos were severely deformed and detached from the basement membrane. In addition, the abnormally thin arterial walls of these mice had a severe disruption of their typically multilayer structure. Expression of tight junction, adherence junction, and basement membrane molecules by ECs was diminished in RAMP2-/- embryos, leading to paracellular leakage and likely contributing to the severe edema observed. In adult RAMP2+/- mice, reduced RAMP2 expression led to vascular hyperpermeability and impaired neovascularization. Conversely, ECs overexpressing RAMP2 had enhanced capillary formation, firmer tight junctions, and reduced vascular permeability. Our findings in human cells and in mice demonstrate that RAMP2 is a key determinant of the effects of AM on the vasculature and is essential for angiogenesis and vascular integrity.     

Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sj?gren's syndrome–like autoimmune exocrinopathy

Although several autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. Recently, we found that retinoblastoma-associated protein 48 (RbAp48) induces tissue-specific apoptosis in the exocrine glands depending on the level of estrogen deficiency. In this study, we report that transgenic (Tg) expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjögren''s syndrome. CD4⁺ T cell–mediated autoimmune lesions were aggravated with age, in association with autoantibody productions. Surprisingly, we obtained evidence that salivary and lacrimal epithelial cells can produce interferon-γ (IFN-γ) in addition to interleukin-18, which activates IFN regulatory factor-1 and class II transactivator. Indeed, autoimmune lesions in Rag2^−/− mice were induced by the adoptive transfer of lymph node T cells from RbAp48-Tg mice. These results indicate a novel immunocompetent role of epithelial cells that can produce IFN-γ, resulting in loss of local tolerance before developing gender-based autoimmunity.Autoimmune disease is controlled by environments that include gene variants or various cytokines (1, 2). It can increase susceptibility to autoimmunity by affecting the overall reactivity and quality of the cells of the immune system. There is an autoimmune disease specific for certain organs in the body, involving a response to an antigen expressed only in those organs. Antigen/organ specificity is affected by antigen presentation and recognition, antigen expression, and the state and response of the target organs (3, 4), which are maintained by a local immune system termed here “local tolerance.”Many mechanisms protect tissues from autoimmune damage. These include relative isolation from the immune system and inhibition of the function of invading lymphocytes. For example, the eye has barriers to T cell infiltration and produces immunosuppressive cytokines, such as TGF-β (5). Constitutive expression of Fas ligand within the privileged site might also prevent immune-mediated damage by eliminating Fas-expressing T cells (6). Although they have yet to be well demonstrated in spontaneous animal models or human disease, genetic effects at the level of tissue protection are therefore to be expected. Autoimmune organ damage can be mediated by CD4⁺ T cells, which play a crucial role in the development of autoimmunity (7–9). MHC class II alleles are probably involved in autoimmune disease because different alleles have different abilities to present peptides from target cells to autoreactive CD4⁺ T cells (10, 11). Certain class II alleles might predispose to autoimmunity by increasing positive selection or decreasing negative selection of autoreactive T cells in the thymus. They might also act by inhibiting selection in the thymus of the regulatory CD4⁺ T cells that are thought to prevent autoantigen-specific responses. Evidence for the local tolerance hypothesis is provided by the observation that autoimmune diseases are often tissue specific and sometimes involve antibodies against a restricted set of antigens, thereby prompting us to accept this most simple explanation for the initiation of autoimmunity. The loss of local tolerance is considered to result from the combined effect of different environmental factors. MHC class II genes are constitutively expressed only on hematopoietic cells involved in antigen presentation (dendritic cells, macrophages, B cells, and cortical thymic epithelial cells), but can be aberrantly induced by inflammatory stimuli on many other cell types (such as endothelial cells, hepatocytes, β cells of the pancreas, and thyrocytes) (12, 13). Although it has been implicated in allograft rejection (14), and subsequently in autoimmunity, it is still unknown whether to initiate autoimmunity class II molecules have to be expressed on professional APCs within secondary lymphoid organs or on nonhematopoietic cells of the target organ itself.It has been suggested that estrogenic action is responsible for the strong female preponderance of many autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren''s syndrome (SS) (15, 16). Recent evidence suggests that apoptosis plays a key role in the physiology and pathogenesis of various autoimmune diseases, including SS (17–21). We have demonstrated that estrogenic action influences target epithelial cells through Fas-mediated apoptosis in a murine model for SS (21). Recently, we found that tissue-specific apoptosis in the exocrine glands spontaneously occurring in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy (22). Searching for the role of estrogen deficiency in the development of autoimmunity, we have recently identified retinoblastoma-associated protein 48 (RbAp48) gene specific for estrogen deficiency–dependent apoptosis in the exocrine glands, and transgenic expression of RbAp48 gene induced tissue-specific apoptosis in the exocrine glands (23). In this transgenic mouse model, we propose a possible clear and defined ab initio relationship between aberrant exposure of MHC class II molecules on IFN-γ–producing epithelial cells and disease development (i.e., autoimmune exocrinopathy).