Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited.
In this ...prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival.
Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates.
Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
Currently, mercury has been identified as a risk factor of cardiovascular diseases among humans. Here, the authors tested the hypothesis that mercury modulates the activity of the endothelial lipid ...signaling enzyme, phospholipase D (PLD), which is an important player in the endothelial cell (EC) barrier functions. Monolayers of bovine pulmonary artery ECs (BPAECs) in culture, following labeling of membrane phospholipids with 32Porthophosphate, were exposed to mercuric chloride (inorganic form), methylmercury chloride (environmental form), and thimerosal (pharmaceutical form), and the formation of phosphatidylbutanol as an index of PLD activity was determined by thin-layer chromatography and liquid scintillation counting. All three forms of mercury significantly activated PLD in BPAECs in a dose-dependent (0 to 50 μM) and time-dependent (0 to 60 min) fashion. Metal chelators significantly attenuated mercury-induced PLD activation, suggesting that cellular mercury-ligand interaction(s) is required for the enzyme activation and that chelators are suitable blockers for mercury-induced PLD activation. Sulfhydryl (thiol-protective) agents and antioxidants also significantly attenuated the mercury-induced PLD activation in BPAECs. Enhanced reactive oxygen species generation, as an index of oxidative stress, was observed in BPAECs treated with methylmercury that was attenuated by antioxidants. All the three different forms of mercury significantly induced the decrease of levels of total cellular thiols. For the first time, this study revealed that mercury induced the activation of PLD in the vascular ECs wherein cellular thiols and oxidative stress acted as signal mediators for the enzyme activation. The results underscore the importance of PLD signaling in mercury-induced endothelial dysfunctions ultimately leading to cardiovascular diseases.
JCO
To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with ...stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (
= .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (
= .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% 95% CI, 53 to 78) and patients in WW who underwent TME after regrowth (64% 95% CI, 53 to 78;
= .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.
Spontaneous diabetes mellitus was blocked in nonobese diabetic mice by treatment with a monoclonal antibody against the L3T4 determinant present on the surface of T-helper lymphocytes. Sustained ...treatment with the monoclonal antibody led to cessation of the lymphocytic infiltration associated with the destruction of the insulin-producing $\beta $ cells. Moreover, the mice remained normoglycemic after the antibody therapy was stopped. These studies indicate that immunotherapy with monoclonal antibodies to the lymphocyte subset may not only halt the progression of diabetes, but may lead to long-term reversal of the disease after therapy has ended.
Allografts of pancreatic islets of Langerhans were induced to survive for an indefinite period in diabetic mice if, at the time of engraftment, the mice received a single course of treatment with a ...monoclonal antibody directed against the L3T4 determinant, a nonpolymorphic cell surface glycoprotein present on the cell surface of the murine T helper-inducer lymphocyte subset. This treatment allowed the survival of islets of Langerhans transplanted across a major histocompatibility barrier without additional immunosuppression. The results demonstrate that the lymphocyte subset defined by the expression of the L3T4 molecules is central to the induction of allograft rejection and provides a model for tolerance induction for organ allograft transplantation.
A case of massive thymolipoma Gregory, Anita K; Connery, Cliff P; Resta-Flarer, Franco ...
Journal of pediatric surgery,
12/1997, Volume:
32, Issue:
12
Journal Article
Peer reviewed
Open access
A massive anterior mediastinal tumor was discovered in a 9-year-old girl with long-standing symptoms of asthma. Preoperative computed tomography (CT) scan and magnetic resonance imaging (MRI) results ...suggested the presence of a thymolipoma, a rare benign tumor of the thymus. Few cases have been reported in the literature, although the histological and radiographic features have been well described. This case confirms previously reported characteristics and also illuminates new aspects of clinical presentation and perioperative management.
Tuberculous pericarditis is estimated to occur in 1% to 2% of cases of pulmonary tuberculosis. Despite adequate therapy, a subset of patients may eventually require pericardiectomy. Incomplete ...pericardial resections are associated with an increased incidence of late complications. We report a cutaneous sinus tract communicating with residual pericardium and a retrosternal abscess cavity 11 years after partial pericardial resection.
Interferon-gamma (IFN-gamma) is produced during the response to infection and participates in immunostimulatory events. We have previously reported the induction of diabetes in transgenic mice ...(ins-IFN-gamma) in which the expression of the lymphokine IFN-gamma is directed by the insulin promoter. This diabetes is a result of the progressive destruction of pancreatic islets that occurs with the influx of inflammatory cells. Here we demonstrate that this islet cell loss is mediated by lymphocytes, that engrafted histocompatible islets are destroyed, and that lymphocytes from the transgenic mice are cytotoxic to normal islets in vitro. These results indicate that the pancreatic expression of IFN-gamma can result in a loss of tolerance to normal islets, consistent with its role as an inducer of costimulatory activity, which is essential for lymphocyte activation during an immune response.
The purpose of this study was to describe levels of satisfaction of the adjunct faculty who teach in online modalities of instruction at a private evangelical university located in the southern ...United States. The three faculty groups included in the study were (a) online adjunct faculty (independent contractors), (b) adjunct faculty (university full time staff and administrators teaching part-time in the online program) and (c) full-time residential faculty who teach online courses in the distance format. The abridged Job Descriptive Index and the abridged Job in General index were chosen to survey respondents regarding satisfaction levels. The results of the study found that in general, all faculty groups who taught in the online environment were satisfied with the work itself, supervision, staff, and the job in general. Full-time faculty were neither satisfied nor dissatisfied with pay and opportunities for improvement. Part-time faculty and full-time staff and administration who taught in the online programs scored in the neutral area of satisfaction regarding opportunities for promotion. In general, none of the faculty groups was dissatisfied with any of the job facets examined during the study.
Previous work has revealed that nonspecific abdominal aortic aneurysms (AAAs) have a prominent infiltration of inflammatory cells and that soluble extracts of AAA tissue are rich in immunoglobulins. ...These observations raise the question whether autoimmune mechanisms play a role in the pathogenesis or progression of AAA disease. The hypothesis of this investigation was that IgG purified from aneurysmal specimens would be immunoreactive with normal components of the aortic wall (by means of immunohistochemistry) and with soluble proteins extracted from normal aortic tissue (by Western immunoblotting methods).
Immunoglobulin G extracted from AAA homogenates was used to detect immunohistochemical reactivity to connective tissue components in fixed sections of normal aorta obtained from an organ donor. Immunoblotting techniques were used to compare the reactivity of IgG (detected with secondary goat antihuman antibody) from 14 patients with AAA with soluble proteins extracted from normal and aneurysmal aortas. Immunoglobulins G purified from extracts obtained from nine patients with no AAA were used for control experiments.
A unique band at approximately 80 kd was visualized when the filters were probed with IgG from 11 (79%) of 14 patients with AAA compared with only one (11%) of nine control subjects (P = .002 by Fisher's exact test). Immunoglobulins G from patients with AAA codistributed with matrix fibers in normal aortic sections, particularly in the adventitia (suggestive of a microfibrillar component).
Our findings suggest that there are autoimmune features of AAA disease that might not only be informative in terms of AAA origin but also lead to more precise forms of pharmacologic down-regulation of disease progression.
