Purpose: Adenosine is a ubiquitous nucleoside that accumulates at high levels in hypoxic regions of solid tumors, and A 3 adenosine receptors have been recently demonstrated to play a pivotal role in the adenosine-mediated inhibition of tumor cell proliferation. In the present work, we addressed the question of the putative relevance of A 3 subtypes in colorectal adenocarcinomas.Experimental Design: Seventy-three paired samples of tumor and surrounding peritumoral normal mucosa at a distance of 2 and 10 cm from the tumor and blood samples obtained from a cohort of 30 patients with colorectal cancer were investigated to determine the presence of A 3 receptors by means of binding, immunocytochemistry, and real-time reverse transcription-polymerase chain reaction studies.Results: As measured by receptor binding assays, the density of A 3 receptor was higher in colon carcinomas as compared with normal mucosa originating from the same individuals (P < 0.05). Overexpression of A 3 receptors at the protein level was confirmed by immunohistochemical studies, whereas no changes in A 3 mRNA accumulation in tumors as compared with the corresponding normal tissue were revealed. The overexpression of A 3 receptors in tumors was reflected in peripheral blood cells, where the density was approximately 3-fold higher compared with healthy subjects (P < 0.01). In a cohort of 10 patients studied longitudinally, expression of A 3 receptors in circulating blood cells returned to normal after surgical resection for colorectal cancer.Conclusions: This study provides the first evidence that A 3 receptor plays a role in colon tumorigenesis and, more importantly, can potentially be used as a diagnostic marker or a therapeutic target for colon cancer.
BackgroundColorectal cancer (CRC) is the second most prevalent type of cancer in the world. Surgery is the only curative option. However, postoperative complications occur in up to 50% of patients and are associated with higher morbidity and mortality rates, lower health related quality of life (HRQoL) and increased expenditure in health care. The number and severity of complications are closely related to preoperative functional capacity, nutritional state, psychological state, and smoking behavior. Traditional approaches have targeted the postoperative period for rehabilitation and lifestyle changes. However, recent evidence shows that the preoperative period might be the optimal moment for intervention. This study will determine the impact of multimodal prehabilitation on patients’ functional capacity and postoperative complications.Methods/designThis international multicenter, prospective, randomized controlled trial will include 714 patients undergoing colorectal surgery for cancer. Patients will be allocated to the intervention group, which will receive 4 weeks of prehabilitation (group 1, prehab), or the control group, which will receive no prehabilitation (group 2, no prehab). Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. The primary outcomes for measurement will be functional capacity (as assessed using the six-minute walk test (6MWT)) and postoperative status determined with the Comprehensive Complication Index (CCI). Secondary outcomes will include HRQoL, length of hospital stay (LOS) and a cost-effectiveness analysis.DiscussionMultimodal prehabilitation is expected to enhance patients’ functional capacity and to reduce postoperative complications. It may therefore result in increased survival and improved HRQoL. This is the first international multicenter study investigating multimodal prehabilitation for patients undergoing colorectal surgery for cancer.Trial registrationTrial Registry: NTR5947 – date of registration: 1 August 2016.
Adenosine may affect several pathophysiological processes, including cellular proliferation, through interaction with A(1), A(2A), A(2B), and A(3) receptors. In this study we characterized adenosine receptors in human colon cancer tissues and in colon cancer cell lines Caco2, DLD1, HT29. mRNA of all adenosine subtypes was detected in cancer tissues and cell lines. At a protein levels low amount of A(1), A(2A), and A(2B) receptors were detected, whilst the A(3) was the most abundant subtype in both cancer tissues and cells, with a pharmacological profile typical of the A(3) subtype. All the receptors were coupled to stimulation/inhibition of adenylyl-cyclase in cancer cells, with the exception of A(1) subtype. Adenosine increased cell proliferation with an EC(50) of 3-12 microM in cancer cells. This effect was not essentially reduced by adenosine receptor antagonists. However dypiridamol, an adenosine transport inhibitor, increased the stimulatory effect induced by adenosine, suggesting an action at the cell surface. Addition of adenosine deaminase makes the A(3) agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (Cl-IB-MECA) able to stimulate cell proliferation with an EC(50) of 0.5-0.9 nM in cancer cells, suggesting a tonic proliferative effect induced by endogenous adenosine. This effect was antagonized by 5-N-(4-methoxyphenyl-carbamoyl)amino-8-propyl-2(2furyl)-pyrazolo-[4,3e]-1,2,4-triazolo [1,5-c] pyrimidine (MRE 3008F20) 10 nM. Cl-IB-MECA-stimulated cell proliferation involved extracellular-signal-regulated-kinases (ERK1/2) pathway, as demonstrated by reduction of proliferation with 1,4-diamino-2,3-dicyano-1,4-bis-[2-amino-phenylthio]-butadiene (U0126) and by ERK1/2 phosphorylation. In conclusion this study indicates for the first time that in colon cancer cell lines endogenous adenosine, through the interaction with A(3) receptors, mediates a tonic proliferative effect.
Patients undergoing elective colorectal resection can be managed without postoperative NG catheters, starting oral feeding on the first postoperative day. Albeit, no reduction in postoperative hospital stay or patients' well being could be detected, abolition of postoperative NG intubation with early oral feeding was a safe approach, with only 20% of patients requiring NG decompression because of repeated episodes of vomiting.
In patients with achalasia who have esophageal dilation, a laparoscopic Heller myotomy and Dor fundoplication (a) took no longer and was no more difficult, (b) was associated with no more postoperative complications, and (c) gave just as good relief of dysphagia. We conclude that esophageal dilation by itself should rarely serve as an indication for esophagectomy rather than myotomy as the initial surgical treatment.
Background: Better understanding of the pathogenesis of gastroesophageal reflux disease in recent years has not been accompanied by appreciable advances in the design of antireflux operations. In many cases, operations are still being performed just as they were described 30 years ago. It is important now to go beyond the eponymous procedures traditionally associated with antireflux operations and to identify the technical elements that contribute to effective and durable fundoplications. Objectives: To compare antireflux operations and identify the important technical elements. Design and Setting: Retrospective study in a universitybased tertiary care center. RESULTS The operating time for groups A, B, and C was 193 (±45), 150 (±50), and 161 (±47) minutes, respectively. The hospital PAPER
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