Esophagectomy for locally advanced esophageal cancer, followed by chemoradiotherapy and adjuvant chemotherapy

AIM: To compare the efficacy and toxicity of a three-step combination therapy with post-operative radiation alone for locally advanced esophageal cancer.METHODS: Patients with T3-4 and N0-1 esophageal carcinoma from a number of institutions were non-randomly,prospectively enrolled in the study. All patients underwent single-stage curative en bloc esophagectomy. The patients were then assigned into one of two treatment groups based on treatment consisting of either post-operative concurrent chemoradiotherapy (CCRT) with weekly cisplatin 30 mg/m2 followed by systemic adjuvant chemotherapy (four monthly cycles of cisplatin 20 mg/m2 and 5-fiuorouracil 1 000 mg/m2 for five consecutive days),or, post-operative radiation alone. The radiotherapy dose was 55-60 Gy for all patients. Primary end-point of this study was to assess the per-protocol patients' improvement of overall survival benefit. Secondary end-point was designed to evaluate both the per-protocol and intent-to-treat patients' outcome of survival.RESULTS: A total of 60 patients (n = 30 per group) were enrolled in this study. The two groups were generally comparable for demographic characteristics and hematological and non-hematological toxicities. The CCRT with weekly cisplatin was well tolerated, with significantly better overall survival (30.9 mo vs 20.7 mo; 95% CI,27.5-36.4 vs15.2-26.1) and 3-year survival (70.0% vs 33.7%; P = 0.003). Low histological grade of tumor (P＜0.001) was associated with favorable survival in these locally advanced patients.CONCLUSION: For locally advanced esophageal cancer,the combination of esophagectomy, post-operative CCRT with weekly cisplatin and systemic adjuvant chemotherapy is well tolerated and effective. A large-scale, prospective randomized trial of this regimen is in progress.

Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation

AIM: We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells.METHODS: Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0, 1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis.RESULTS: Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively.G2/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL)nor with any dose after only 1 h of treatment.CONCLUSION: Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment.Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G2/M arrest. Further study is necessary to elucidate the mechanism.

Etoposide sensitizes CT26 colorectal adenocarcinoma to radiation therapy in BALB/c mice

AIM: To investigate the combined effect of etoposide and radiation on CT26 colorectal adenocarcinoma implanted into BALB/c mice.METHODS: We evaluated the radiosensitizing effect of etoposide on CT26 colorectal adenocarcinoma in a syngeneic animal model. BALB/c mice were subcutaneously implanted with CT26 cells and divided into four groups:control (intra-peritoneal salinex2) group, etoposide (5 mg/kgintra-peritoneallyx2) group, radiation therapy (RT 5 Gyx2fractions) group, and combination therapy with etoposide (5 mg/kg intra-peritoneally 1 h before radiation) group.RESULTS: Tumor growth was significantly inhibited by RT and combination therapy. The effect of combination therapy was better than that of RT. No significant changes were noted in body weight, plasma alanine aminotransferase,or creatinine in any group. The leukocyte count significantly but transiently decreased in the RT and combination therapy groups, but not in the etoposide and control groups. There was no skin change or hair loss in the RT and combination therapy groups.CONCLUSION: Etoposide can sensitize CT26 colorectal adenocarcinoma in BALB/c mice to RT without significant toxicity.

Chest pain in a heart transplant recipient:A case report

BACKGROUND Heart transplantation is recommended for the treatment of patients with refractory heart failure.Chest pain after heart transplantation is usually considered noncardiac owing to the denervated heart.However,data from case reports on tacrolimus-induced achalasia after heart transplantation are limited.We aimed to present a case of tacrolimus-induced achalasia that developed after heart tran-splantation,which was successfully relieved by laparoscopic Heller myotomy.CASE SUMMARY A 67-year-old man with a history of Type 2 diabetes mellitus,hyperlipidemia,and dilated cardiomyopathy had congestive heart failure following orthotopic heart transplantation with tacrolimus treatment 12 years ago.At the 10-year follow-up after the heart transplantation,the patient presented with persistent cough,dysphagia,heartburn,and retrosternal chest pain lasting for 2 wk.Upper endoscopy revealed no specific findings.Two years later,the patient experienced the same symptoms,including chest pain lasting for 4 wk.Esophagogram and manometry confirmed the presence of achalasia.Previous reports showed that discontinuing calcineurin inhibitor(CNI)treatment and endoscopic botulinum toxin injection could treat CNI-induced achalasia.Owing to the risk of rejection of the transplanted heart and considering the temporary benefits of botulinum toxin injection in achalasia,the patient underwent laparoscopic Heller myotomy.Dysphagia was relieved without complications.Eight months later,he had no signs of recurrence of the achalasia.CONCLUSION In transplant patients with chest pain and gastrointestinal symptoms, CNIinducedachalasia may be one of the differential diagnoses. Esophagogram/manometry is useful for diagnosis.

Modulation of Fatty Acid Oxidation and Glucose Uptake by Oxytocin in Adipocytes

Oxytocin (OT) is a hypothalamic neuropeptide synthesized and secreted by OT neurons. In addition to its conventional role in reproductive physiology, central OT also regulates various social behaviors, such as care, trust, and emotions. Central and subcutaneous OT infusions stimulate lipid metabolism in mice and rats when fed standard or high fat diets. Mice lacking the OT receptor (OTR) or OT peptide develop late-onset obesity with greater fat pad weights, larger adipocyte size and elevated plasma levels of leptin. To study the effects of OT on lipid metabolism, we examined the effects of serial OT doses (0, 10, 30, 100, 150, 300 nM) on 3T3L1 adipocytes, together with long (144 hours, 6 days) and short (24 hours, 1 day) term treatments. The short-term treatment with 150 nM OT increased triacylglycerol (TAG) accumulation and decreased mRNA expressions of carnitine palmitoyltransferase 1α (CPT-1α) and fatty acid binding protein 4 (FABP4). After long-term incubation with 150 nM OT, only the CPT-1α mRNA was decreased. In differentiated adipocytes derived from pig adipose tissue stem cells, only hormone sensitive lipase mRNA was decreased after short- or long-term treatment with OT. To obtain further insight into the underlying mechanism of OT induction, we tested the involvement of the AKT/PKB pathway;however, AKT phosphorylation was decreased after treatment with 150 nM OT, suggesting that OT effects may be independent from the AKT/PKB pathway. Taken together, OT effects on adipocyte glucose and lipid metabolism are probably through mechanisms other than the AKT/PKB pathway.

Computer Tomography and Ultrasonography Image Registration Based on the Cooperation of GPU and CPU

Image registration is wildly used in the biomedical image, but there are too many textures and noises in the biomedical image to get a precise image registration. In order to get the excellent registration performance, it needs more complex image processing, and it will spend expensive computation cost. For the real time issue, this paper proposes edge gradient direction image registration applied to Computer Tomography(CT) image and Ultrasonography (US) image based on the cooperation of Graphic Processor Unit (GPU) and Central Processor Unit (CPU). GPU can significantly reduce the computation time. First, the CT image slice is extracted from the CT volume by the region growing and the interpolation algorithm. Secondly, the image pre-processing is employed to reduce the image noises and enhance the image features. There are two kinds of the image pre-processing algorithms invoked in this paper: 1) median filtering and 2) anisotropic diffusion. Last but not least, the image edge gradient information is obtained by Canny operator, and the similarity measurement based on gradient direction is employed to evaluate the similarity between the CT and the US images. The experimental results show that the proposed architecture can distinctively improve the efficiency and are more suitably applied to the real world.