Enhancing the Efficiency of a Radiation Oncology Department Using Electronic Medical Records: Protocol for Preparing Radiotherapy.

BACKGROUND: Electronic medical records (EMRs) streamline medical processes, improve quality control, and facilitate data sharing among hospital departments. They also reduce maintenance costs and storage space needed for paper records, while saving time and providing structured data for future research. OBJECTIVE: This study aimed to investigate whether the integration of the radiation oncology information system and the hospital information system enhances the efficiency of the department of radiation oncology. METHODS: We held multidisciplinary discussions among physicians, physicists, medical radiation technologists, nurses, and engineers. We integrated paper records from the radiation oncology department into the existing hospital information system within the hospital. A new electronic interface was designed. A comparison was made between the time taken to retrieve information from either the paper records or the EMRs for radiation preparation. A total of 30 cases were randomly allocated in both the old paper-based system and the new EMR system. The time spent was calculated manually at every step during the process, and we performed an independent 1-tailed t test to evaluate the difference between the 2 systems. RESULTS: Since the system was launched in August 2020, more than 1000 medical records have been entered into the system, and this figure continues to increase. The total time needed for the radiation preparation process was reduced from 286.8 minutes to 154.3 minutes (P<.001)-a reduction of 46.2%. There was no longer any need to arrange for a nurse to organize the radiotherapy paper records, saving a workload of 16 hours per month. CONCLUSIONS: The implementation of the integrated EMR system has resulted in a significant reduction in the number of steps involved in radiotherapy preparation, as well as a decrease in the amount of time required for the process. The new EMR system has provided numerous benefits for the department, including a decrease in workload, a simplified workflow, and conserving more patient data within a confined space.

CircPTK2 inhibits the tumorigenesis and metastasis of gastric cancer by sponging miR-134-5p and activating CELF2/PTEN signaling.

BACKGROUND: CircRNAs are a new subset of noncoding RNAs formed by covalent closed loops and play crucial roles in the regulation of cancer gene expression. However, the roles and underlying mechanisms of circRNAs in gastric cancer (GC) remain indistinct. This study aimed to explore the role and mechanism of hsa_circ_0006421 (circPTK2) in GC. METHODS: The differential expression of circRNAs between GC tissues and adjacent normal tissues were identified by a circRNA expression profiling. Associations of circPTK2 or miR-134-5p expression with clinicopathological characteristics and prognosis of GC patients were analyzed by chi-square of Fisher's exact tests and Kaplan-Meier analysis. CCK8, colony formation, EdU assays and animal models were performed to assess the effects of circPTK2 on proliferation and invasion of GC cells. CircPTK2-specific probes were used to purify the RNA pulled down from the circPTK2, and enrichment of circPTK2 and miR-134-5p was detected by qRT-PCR. The effects of circPTK2 on miR-134-5p expression and CELF2/PTEN signaling were examined by qRT-PCR and Western blotting analysis. RESULTS: Low expression of circPTK2 and high expression of miR-134-5p were related to the poor survival, and high expression of miR-134-5p was related to the tumor recurrence in GC patients. Overexpressing circPTK2 suppressed the proliferation, colony formation, DNA synthesis and cell invasion as well as xenograft tumor growth and lung metastasis in vitro and in vivo, whereas silencing circPTK2 had the opposite effects. Moreover, circPTK2 was negatively correlated and co-localized with miR-134-5p in the cytoplasm of GC tissue cells. circPTK2 bound to and sponged miR-134-5p in GC cells, and miR-134-5p facilitated cell growth and invasion but attenuated circPTK2 induced tumor suppressive effects and CELF2/PTEN signaling activation in GC cells. CONCLUSIONS: circPTK2 functions as a tumor suppressor in GC by sponging miR-134-5p and activating the CELF2/PTEN axis.

CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway.

The increase in migratory ability of pancreatic ductal adenocarcinoma cells is a key event in the development of metastasis to the lymph nodes and distant organs. Although the C-C motif chemokine receptor 7 (CCR7) and its ligand, C-C motif chemokine ligand 21 (CCL21), have been revealed to serve an important role in tumor migration, their precise roles and potential underlying mechanisms remain largely unknown. The present study revealed that overexpression of CCR7 significantly promoted BxPC-3 cell migration, accompanied by the induction of anoctamin 6 (ANO6) expression, indicating that ANO6 is a downstream target of CCR7 signaling. Furthermore, the level of phosphorylated extracellular signal-regulated kinase (ERK) was significantly increased in CCR7-overexpressing BxPC-3 cells, indicating that ERK may be a potential mediator of CCR7-regulated ANO6 expression in BxPC-3 cells. To characterize the receptor-mediated pathway, a specific ERK inhibitor, U0126, was used, which reduced BxPC-3 cell migration and the expression of ANO6. In summary, the results of the present study demonstrate that CCR7 promoted BxPC-3 cell migration by regulating ANO6 expression perhaps via activation of the ERK signaling pathway.

Early prediction of persistent organ failure by serum apolipoprotein A-I and high-density lipoprotein cholesterol in patients with acute pancreatitis.

BACKGROUND: Early identification of acute pancreatitis (AP) patients at high-risk of developing persistent organ failure (persistent OF) is a vital clinical goal. This research intends to assess the ability of apolipoprotein A-I (APO A-I) and high-density lipoprotein cholesterol (HDL-C) to predict persistent OF. METHODS: Between January 2011 and September 2016, a total of 102 adult AP patients with organ failure, local complications or deterioration of former comorbidities disease during hospitalization were included in this study retrospectively. Serum lipids were tested and computed the correlation with clinical outcomes or scoring systems. The AUCs to predict persistent OF were also calculated and compared with each other. RESULTS: Serum APO A-I and HDL-C levels were negatively associated with scoring systems. Meanwhile, serum lipids were negatively correlated with poor clinical outcomes. The AUCs of APO A-I, HDL-C, the combination of APO A-I and BISAP, or the combination of APO A-I and MCTSI to predict persistent OF among Moderately severe acute pancreatitis (MSAP) and Severe acute pancreatitis (SAP) patients were 0.886, 0.811, 0.912, and 0.900 or among those with organ failure were 0.915, 0.859, 0.933, and 0.933, respectively. CONCLUSIONS: The concentrations of APO A-I, HDL-C, and the combinations of APO A-I and scoring systems have high predictive value to predict persistent OF.

[Retracted] Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo.

Following the publication of this article, an interested reader drew to the attention of the Editorial Board that the above article appeared to contain a series of Figures that featured duplicated data. Following an internal investigation, the Editorial Board reached the conclusion that the allegations of the reader were well-founded. Specifically, the GAPDH bands shown in Figs. 2 and 3 are identical with those in Figs. 4C and 5D, with the exception that the images have been reversed. Furthermore, certain data in Fig. 4C of this paper appeared to have been shared with Fig. 3 in the following article (albeit for purportedly different experiments): Zhang J, Zhu J, Zhou Z, Chen W and Chen N: Inhibitory effects of ethyl pyruvate on invasion and metastasis of human gastric cancer SGC-7901 cells via downregulation of Akt pathway. China J Cancer Prev Treat (Chin) 39: 776-779, 2012. Despite numerous attempts at doing so, we were unable to receive any response to our request for further information from the authors of this article. Given the extent of the anomalies with the data between the aforementioned papers, the Editorial Board has therefore decided to retract the article from Oncology Reports. We regret any inconvenience in this regard. [the original article was published in the Oncology Reports 27: 1511-1519, 2012; DOI: 10.3892/or.2012.1623].

Eriocalyxin B blocks human SW1116 colon cancer cell proliferation, migration, invasion, cell cycle progression and angiogenesis via the JAK2/STAT3 signaling pathway.

Eriocalyxin B, a natural ent-kaurene diterpene compound, has been shown to prevent carcinogenesis and tumor development. However, little is known regarding the mechanism underlying the antitumor activity of Eriocalyxin B in human colon cancer. The aim of the present study was to examine the role of Eriocalyxin B in SW1116 cells, and to verify the hypothesis that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway may serve as a therapeutic target in human colon cancer treatment. Cell proliferation was measured with a Cell Counting kit­8 assay, and the cell cycle was assessed by flow cytometry. Cell migration and invasion were measured by Transwell analysis. In addition, western blot analysis was performed to detect the protein expression levels in SW1116 cells treated with various concentrations of Eriocalyxin B. The results demonstrated that 1 µmol/l Eriocalyxin B was effective at inhibiting JAK2 and STAT3 phosphorylation, followed by the downregulation of JAK2 and STAT3 downstream target expression, which resulted in the inhibition of cell proliferation, migration, invasion and angiogenesis. Eriocalyxin B also suppressed the expression of proliferation­associated protein (proliferating cell nuclear antigen) and angiogenesis­associated proteins (vascular endothelial growth factor and vascular endothelial growth factor receptor 2), as well as that of migration- and invasion­associated proteins (matrix metalloproteinase 2 and 9). These results suggested that Eriocalyxin B may suppress JAK2/STAT3 signaling, and thus act as a therapeutic or preventive agent in the treatment of human colon cancer.

Endogenous hydrogen sulfide is associated with angiotensin II type 1 receptor in a rat model of carbon tetrachloride-induced hepatic fibrosis.

The present study aimed to investigate the effects of endogenous hydrogen sulfide (H2S) on the expression levels of angiotensin II type 1 receptor (AGTR1) in a rat model of carbon tetrachloride (CCl4)­induced hepatic fibrosis. A total of 56 Wistar rats were randomly divided into four groups: Normal control group, model group, sodium hydrosulfide (NaHS) group, and DL­propargylglycine (PAG) group. Hepatic fibrosis was induced by CCl4. The rats in the PAG group were intraperitoneally injected with PAG, an inhibitor of cystathionine­Î³­lyase (CSE). The rats in the NaHS group were intraperitoneally injected with NaHS. An equal volume of saline solution was intraperitoneally injected into both the control and model groups. All rats were sacrificed at week three or four following treatment. The serum levels of hyaluronidase (HA), laminin protein (LN), procollagen III (PcIII), and collagen IV (cIV) were detected using ELISA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin (ALB) were detected using an automatic biochemical analyzer. The liver mRNA expression levels of CSE were detected by reverse transcription­quantitative polymerase chain reaction. The liver expression levels of AGTR1 and the plasma expression levels of H2S were detected using western blot analyses. The results indicated that the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly higher in the PAG group, as compared with the model group (P<0.05). Conversely, the expression levels of ALB were significantly lower in the PAG group, as compared with the model group. In addition, the severity of hepatic fibrosis, the serum expression levels of HA, LN, PcIII, cIV, ALT, and AST, the liver expression levels of CSE and AGTR1, and the plasma expression levels of H2S were significantly lower in the NaHS group, as compared with the model group (P<0.05). These results suggest that endogenous H2S is associated with CCl4­induced hepatic fibrosis in rats, and may exhibit anti­fibrotic effects. Furthermore, H2S reduced the liver expression levels of AGTR1, which may be associated with the delayed progression of hepatic fibrosis.

Prediction of synchronous colorectal cancers by computed tomography in subjects receiving an incomplete colonoscopy: a single-center study.

AIM: To assess the value of computed tomography (CT) for diagnosis of synchronous colorectal cancers (SCRCs) involving incomplete colonoscopy. METHODS: A total of 2123 cases of colorectal cancer (CRC) were reviewed and divided into two groups according to whether a complete or incomplete colonoscopy was performed. CT results and final histological findings were compared to calculate the sensitivity and specificity associated with CT for detection of SCRCs following complete vs incomplete colonoscopy. Factors affecting the CT detection were also analyzed. RESULTS: Three hundred and seventy-four CRC patients underwent incomplete colonoscopy and 1749 received complete colonoscopy. Fifty-six cases of SCRCs were identified by CT, and 36 were missed. In the incomplete colonoscopy group, the sensitivity and specificity of CT were 44.8% and 93.6%, respectively. The positive and negative predictive values were 23.6% and 95.0%, respectively. In contrast, the sensitivity and specificity of CT for the complete colonoscopy group were 68.3% and 97.0%, while the positive and negative predictive values were 22.2% and 98.7%, respectively. In both groups, the mean maximum dimension of the concurrent cancers identified in the CT-negative cases was shorter than in the CT-positive cases (incomplete group: P = 0.02; complete group: P < 0.01) Topographical proximity to synchronous cancers was identified as a risk factor for missed diagnosis (P = 0.03). CONCLUSION: CT has limited sensitivity in detecting SCRCs in patients receiving incomplete colonoscopy. Patients with risk factors and negative CT results should be closely examined and monitored.

Inhibition of phosphoinositide 3-kinase/Akt pathway decreases hypoxia inducible factor-1α expression and increases therapeutic efficacy of paclitaxel in human hypoxic gastric cancer cells.

The phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway plays an important role in cell proliferation, transformation, apoptosis, tumor growth and angiogenesis. Paclitaxel is commonly used to treat multiple human malignancies; however, the underlying mechanisms of paclitaxel in gastric cancer (GC) have not been fully investigated. In the present study, specimens from 45 GC and 36 chronic gastritis patients were collected, and the correlations of PI3K, phosphorylated-Akt (p-Akt) and hypoxia-inducible factor-1α (HIF-1α) expression with the clinicopathological characteristics of GC were analyzed by immunohistochemistry. The human SGC-7901 GC cells under hypoxic conditions were pretreated with the PI3K inhibitor, LY294002 (40 µM), and paclitaxel (0.1 µM). The expression levels of PI3K, p-Akt and HIF-1α were detected by quantitative polymerase chain reaction and western blotting. Cell proliferative activity and apoptosis were evaluated by the Cell Counting Kit-8 assay and flow cytometry. As a result, the rates of positive expression of PI3K, p-Akt and HIF-1α were significantly higher in GC compared with chronic gastritis patients (each P<0.01), and were positively associated with the tumor-node-metastasis (TNM) staging, lymph node metastases, lymphatic infiltration and vascular infiltration (each P<0.01), but inversely correlated with tumor differentiation (P<0.01) in patients with GC. Under hypoxic conditions, the combined inhibition of the PI3K/Akt pathway with paclitaxel markedly reduced the proliferative activity and induced cell apoptosis in GC cells compared with the single treatment of PI3K inhibitor or paclitaxel (each P<0.01), and was accompanied by a decreased expression of HIF-1α. Overall, our findings indicate that the increased expression of the PI3K/Akt/HIF-1α pathway was closely correlated with tumor differentiation, TNM staging, lymph node metastases and lymphatic and vascular infiltration. The inhibition of the PI3K/Akt pathway enhanced the therapeutic efficacy of paclitaxel in GC cells under hypoxic conditions, suggesting that the PI3K/Akt/HIF-1α pathway may act as an important therapeutic target for paclitaxel treatment of GC.

Temporary placement of a paclitaxel or rapamycin-eluting stent is effective to reduce stenting induced inflammatory reaction and scaring in benign cardia stricture models.

BACKGROUND/AIMS: To investigate whether temporary placement of a paclitaxel or rapamycin eluting stent is more effective to reduce stenting induced inflammatory reaction and scaring than a bared stent in benign cardia stricture models. MATERIALS AND METHODS: Eighty dog models of stricture were randomly divided into a control group (CG, n=20, no stent insertion), a bare stent group (BSG, n=20), a paclitaxel eluting (Pacl-ESG, n=20) and a rapamycin eluting stent group (Rapa-ESG, n=20), with one-week stent retention. Lower-oesophageal-sphincter pressure (LOSP), 5-minute barium height (5-mBH) and cardia diameter were assessed before, immediately after the procedure, and regularly for 6 months. Five dogs in each group were euthanized for histological examination at each follow-up assessment. RESULTS: Stent insertion was well tolerated, with similar migration rates in three groups. At 6 months, LOSP and 5-mBH improved in Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with no difference between Pacl-ESG and Rapa-ESG (p>0.05). Cardia kept more patency in the Pacl-ESG and Rapa-ESG than in BSG (p<0.05). Reduced peak inflammatory reactions and scarring occurred in the Pacl-ESG and Rapa-ESG compared to BSG (p<0.05), with a similar outcome in the Pacl-ESG and Rapa-ESG (p>0.05). CONCLUSION: Paclitaxel or rapamycin-eluting stents insertion led to better outcomes than bare stents in benign cardia stricture models.

Inhibitory effects of ethyl pyruvate administration on human gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways in vitro and in vivo.

The high mobility group box-B1 (HMGB1)-receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. Ethyl pyruvate (EP), a potent inhibitor of HMGB1 release, can exert antitumor effects on the growth of gastric cancer. Therefore, it is necessary to observe the effects of EP on gastric cancer growth in vitro and in vivo. Human gastric adenocarcinoma tissues of different grades (N=45) were collected. The expression of HMGB1 and RAGE was evaluated immunohistochemically in biopsy samples. After SGC-7901 gastric cancer cells were treated with EP, the expression of HMGB1, RAGE, Akt, phosphorylated Akt (p-Akt) and some transcription factors was identified and the effects of EP on cell proliferation, invasion, cell cycle distribution and apoptosis were assessed. A subcutaneous xenograft tumor model was established, validating the effects of EP on tumor growth in vivo. The expression of HMGB1 and RAGE was respectively observed in 73.3 and 68.9% of the gastric adenocarcinoma tissues. The frequency of positive expression increased with the ascending grade of the tumor malignancy. EP decreased the expression of HMGB1, RAGE, Akt, p-Akt, Ki-67 and matrix metallopeptidase-9 (MMP­9), and increased the expression of p53. Moreover, EP could inhibit tumor cell proliferation and invasion, induce cell cycle arrest and apoptosis and slow the growth of xenograft tumors. In conclusion, HMGB1 and RAGE were strongly expressed in gastric adenocarcinoma, and EP administration inhibited gastric cancer growth via regulation of the HMGB1-RAGE and Akt pathways. EP may play a critical role in the treatment of cancer in conjunction with other therapeutic agents.

Application of the newly developed stents in the treatment of benign cardia stricture: an experimental comparative study.

BACKGROUND: Retrievable temporary stent placement has recently been suggested as a potential treatment for benign esophageal stricture. OBJECTIVE: To assess the efficacy of a newly designed cardia stent for the treatment of benign cardia stricture in a canine model compared with groups that received pneumatic dilation or standard esophageal stent insertion. DESIGN: Basic experimental study. SETTING: GI interventional center. PATIENTS: Forty-eight dog models were randomly divided into a control group (no stent insertion) (n=12), a pneumatic dilation group (PDG) (n=12), a standard esophageal stent group (SESG) (n=12), and a novel cardia stent group (NCSG) (n=12). INTERVENTIONS: Pneumatic dilation, standard esophagus stent, cardia stent. MAIN OUTCOME MEASUREMENTS: Lower esophageal sphincter pressures and the 5-minute barium height were assessed before and immediately after the procedure, after 1 week, and at 1-, 3-, and 6-month follow-up. Three dogs in each group were killed for histological examination. RESULTS: Stent insertion was tolerated by all dogs, with a lower migration rate in the NCSG (0% vs 41.7% in the SESG; P=.0373). At the 6-month follow-up, the lower esophageal sphincter pressure and 5-minute barium height values in the NCSG were still stable compared with those in the PDG and SESG (P<.05). Immunohistochemistry for mouse anti-proliferating cell nuclear antigen and α-smooth muscle actin revealed a stronger inflammatory reaction peak in the PDG than in the SESG and NCSG (P<.05). Collagen proliferation was most severe after 6 months in the PDG (P<.05). LIMITATIONS: Longer follow-up studies are required to assess whether the recurrence rate is lower because of less inflammation and scarring. CONCLUSIONS: The novel cardia stent was more effective than pneumatic dilation or a standard stent in this canine model.

13-year follow-up of a prospective comparison of the long-term clinical efficacy of temporary self-expanding metallic stents and pneumatic dilatation for the treatment of achalasia in 120 patients.

OBJECTIVE: The purpose of this article is to compare the efficacy of self-expanding metallic stents and pneumatic dilation for the long-term clinical treatment of achalasia. SUBJECTS AND METHODS: Patients diagnosed with achalasia (n = 120) were allocated for treatment with pneumatic dilation (n = 30; group A) or a temporary self-expanding metallic stent with a diameter of 20 mm (n = 30; group B), 25 mm (n = 30; group C), or 30 mm (n = 30; group D). Data on clinical symptoms, complications, and long-term clinical outcomes were collected, and follow-up was performed at 6 months and at 1, 3-5, 5-8, 8-10, and more than 10 years after surgery. RESULTS: Pneumatic dilation and stent placement were technically successful in all patients. The follow-up at more than 10 years revealed that the clinical remission rate in group D (83.3%) was higher than that in groups A (0%), B (0%), and C (28.6%), and the overall cumulative clinical failure rate in group D (13%) was lower than that in groups A (76.7%), B (53.3%), and C (26.7%). Patients in group D exhibited reduced dysphagia scores and lower esophageal sphincter pressures and had normal levels of barium height and width during the follow-up periods, whereas these markers increased with time in the other groups. The duration of primary patency in group D was also longer than that in groups A, B, and C. CONCLUSION: A temporary self-expanding metallic stent with a diameter of 30 mm has superior clinical efficacy for the treatment of achalasia compared with pneumatic dilation or self-expanding metallic stents with diameters of 20 or 25 mm.

Temporary self-expanding metallic stents for achalasia: a prospective study with a long-term follow-up.

AIM: To compare the efficacy of self-expanding metallic stents (SEMSs) for the long-term clinical treatment of achalasia. METHODS: Ninety achalasic patients were treated with a temporary SEMS with a diameter of 20 mm (n = 30, group A), 25 mm (n = 30, group B) or 30 mm (n = 30, group C). Data on clinical symptoms, complications and treatment outcomes were collected, and follow-up was made at 6 mo and at 1, 3-5, 5-8, 8-10 and > 10 years, postoperatively. RESULTS: Stent placement was successful in all patients. Although chest pain occurrence was high, stent migration was less in group C than in groups A and B. The clinical remission rate at 5-8, 8-10 and > 10 years in group C was higher than that in the other two groups. The treatment failure rate was lower in group C (13%) than in groups A (53%) and B (27%). SEMSs in group C resulted in reduced dysphagia scores and lowered esophageal sphincter pressures, as well as normal levels of barium height and width during all the follow-up time periods. Conversely, these parameters increased over time in groups A and B. The primary patency in group C was longer than in groups A and B. CONCLUSION: A temporary SEMS with a diameter of 30 mm is associated with a superior long-term clinical efficacy in the treatment of achalasia compared with a SEMS with a diameter of 20 mm or 25 mm.

Management of acute malignant colorectal obstruction with a novel self-expanding metallic stent as a bridge to surgery.

PURPOSE: To prospectively evaluate the safety and clinical efficacy of a newly designed self-expandable metallic stent (SEMS) in the treatment of patients with acute malignant colorectal obstruction. METHODS: Between April 2001 and October 2007, 52 patients with acute malignant colorectal obstruction were treated with a new designed SEMS as an investigational bridge to surgery. Patients were prospectively followed and relevant data collection was collected, including details regarding technique, clinical symptoms, complications, need for elective surgery, and overall survival. RESULTS: Stent placement was technically successful in all but two patients (due to complete obstruction) with no procedure-related complications. Complications included stent migration (n=4), anal pain (n=2) and stool impaction (n=1). Clinical success was achieved in 49 (98%) of 50 patients with resolution of bowel obstruction within 2 days of stent placement. In one patient with stool impaction 2 days after stent placement, endoscopic disimpaction was successfully performed. An elective one-stage surgical procedure was performed in all 50 patients who successfully received a SEMS as a bridge to surgery within a mean of 8+/-2 days (range: 4-11 days) after stent placement. Mean follow-up time was 36+/-12 months (range 3-70 months), and all patients remained alive at the time of this report. CONCLUSION: The newly designed SEMS placement as a bridge to surgery was a safe and effective intervention for colonic decompression in patients with acute malignant colorectal obstruction and allowed a high proportion of patients to be successfully proceeded to elective surgery.

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience.

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4-5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1-3, 3-5, 5-8, 8-10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 +/- 0.28 years (95% CI: 2.25-3.35) and 4.28 +/- 0.40 years (95% CI: 3.51-5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate.

[Inhibition of bFGF gene expression and tumor angiogenesis of orthotopic implantation of human gastric carcinoma by N-desulfated heparin].

OBJECTIVE: To investigate the effect of N-desulfated heparin on tumor metastasis, tumor angiogenesis and basic fibroblast growth factor(bFGF) gene expression of orthotopically implanted human gastric carcinoma in NOD-SCID mice. METHODS: Human gastric cancer SGC-7901 tissues were orthotopically implanted into the stomach of the NOD-SCID mice. Twenty mice were randomly divided into two groups which received either intravenous injection of 0.9% NaCl solution(0.9%NaCl solution group) or 10 mg/kg N-desulfated heparin (N-desulfated heparin group) twice a week for three weeks. Mice were sacrificed six weeks after tumor implantation. Tissues from stomach and other organs were obtained for histopathological evaluation. The intratumoral microvessel density (MVD) in tumor was evaluated immunohistochemically. Real time PCR was used to detect bFGF mRNA expression. RESULTS: The tumor metastasis rates were 9/10 in 0.9% NaCl solution group and 2/10 in N-desulfated heparin group(P<0.05).MVD was 9.1+/-3.4 in 0.9% NaCl solution group and 4.7+/-1.8 in N-desulfated heparin group (t=3.617,P<0.05). bFGF mRNA expression was lower in N-desulfated heparin group(2.60+/-0.56%)than that in 0.9% NaCl solution group(30.65+/-6.84%). CONCLUSION: N-desulfated heparin can inhibit the metastasis of gastric cancer through inhibiting tumor bFGF gene expression and tumor angiogenesis with no obvious anticoagulant activity.

Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo.

AIM: To investigate the effects of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue. METHODS: Human gastric cancer SGC-7901 tissues were implanted into the dorsal subcutis of nude mice. One week after tumors reached to a volume of 50-100 mm(3) for around 1 wk, these mice were randomly divided into 8 groups (n = 10). NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin (5 mg/kg) every third day for 4 wk. As controls of combined treatment, another 4 groups of mice were injected with either NM-3 at 10 mg/kg, 20 mg/kg or 40 mg/kg, or with carboplatin alone (5 mg/kg). The control mice received normal saline. Tumor weight, tumor growth inhibition (TGI), and intratumoral microvessel density (MVD) were evaluated. Apoptosis of human gastric cancer was detected by TUNEL method and flow cytometry analysis, respectively. RESULTS: The mean tumor volume (692.40 +/- 58.43 mm(3), 548.30 +/- 66.02 mm(3), 382.13 +/- 43.52 mm(3)) after treatment with carboplatin combined NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg was lower than that after treatment with either NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg or with carboplatin alone. Compared with the normal saline group, NM-3 administered at 10 mg/kg, 20 mg/kg or 40 mg/kg significantly reduced the tumor weight in these groups (P < 0.05). Carboplatin used alone at 5 mg/kg showed minimal effects. But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone. NM-3 alone at the dose 10 mg/kg or in combination with carboplatin had no obvious effects on body changes. Two mice died of diarrhea in each of the two groups treated with 40 mg/kg NM-3 or with 40 mg/kg NM-3 in combination with carboplatin. A significant increase in apoptosis was observed in the NM-3 treated groups, and the effect was more significant in the groups treated with carboplatin in combination with NM-3 at 10 mg/kg, 20 mg/kg and 40 mg/kg, than in the control group. The induction of apoptosis was positively associated with the dose of NM-3. NM-3 significantly reduced the neo-microvascular formation of gastric cancer. The MVD was lower in the groups treated with NM-3 or with NM-3 in combination with carboplatin than in the group treated with carboplatin or in the normal saline group (P < 0.05). CONCLUSION: The results suggest that the inhibitory effect of NM-3 on gastric cancer growth is mediated through decreased angiogenesis and the increased induction of apoptosis. Furthermore, NM-3 alone at the dose of 10 mg/kg or in combination with carboplatin has no obvious effects on body changes, indicating that NM-3 in combination with carboplatin may be effective in the treatment of gastric cancer. The toxicity of NM-3 needs further studies.

Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma.

AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice. METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SCID mice. The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group received i.v. injections of N-desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline (100 microL) twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluated histologically for metastasis under microscope. Intratumoral microvessel density (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SCID mice was detected by real time PCR. RESULTS: The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group (P < 0.05). MVD was 8.0 +/- 3.1 in normal saline group and 4.3 +/- 1.8 in N-desulfated heparin group (P < 0.05). VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated heparin treated group (90% vs 20%, P < 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.51 +/- 1.01 vs 22.55 +/- 1.36, P < 0.05). N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group. CONCLUSION: N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious anticoagulant activity.