Comparison of outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal GIST: An inverse probability of treatment weighting analysis.

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. METHODS: Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. RESULTS: The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). CONCLUSIONS: In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

Usefulness of preoperative coronary computed tomography angiography in high risk non-cardiovascular surgery old patients with unknown or suspected coronary artery disease.

BACKGROUND: Cumulative evidence has shown that the non-invasive modality of coronary computed tomography angiography (CCTA) has evolved as an alternative to invasive coronary angiography, which can be used to quantify plaque burden and stenosis and identify vulnerable plaque, assisting in diagnosis, prognosis and treatment. With the increasing elderly population, many patients scheduled for non-cardiovascular surgery may have concomitant coronary artery disease (CAD). The aim of this study was to investigate the usefulness of preoperative CCTA to rule out or detect significant CAD in this cohort of patients and the impact of CCTA results to clinical decision-making. METHODS: 841 older patients (age 69.5 ± 5.8 years, 74.6% males) with high risk non-cardiovascular surgery including 771 patients with unknown CAD and 70 patients with suspected CAD who underwent preoperative CCTA were retrospectively enrolled. Multivariate logistic regression analysis was performed to determine predictors of significant CAD and the event of cancelling scheduled surgery in patients with significant CAD. RESULTS: 677 (80.5%) patients had non-significant CAD and 164 (19.5%) patients had significant CAD. Single-, 2-, and 3- vessel disease was found in 103 (12.2%), 45 (5.4%) and 16 (1.9%) patients, respectively. Multivariate analysis demonstrated that positive ECG analysis and Agatston score were independently associated with significant CAD, and the optimal cutoff of Agatston score was 195.9. The event of cancelling scheduled surgery was increased consistently according to the severity of stenosis and number of obstructive major coronary artery. Multivariate analysis showed that the degree of stenosis was the only independent predictor for cancelling scheduled surgery. In addition, medication using at perioperative period increased consistently according to the severity of stenosis. CONCLUSIONS: In older patients referred for high risk non-cardiovascular surgery, preoperative CCTA was useful to rule out or detect significant CAD and subsequently influence patient disposal. However, it might be unnecessary for patients with negative ECG and low Agatston score. Trial registration Retrospectively registered.

Efficacy and safety of endovascular thrombectomy in mild ischemic stroke: results from a retrospective study and meta-analysis of previous trials.

BACKGROUND: Mechanical thrombectomy has been proven as a standard care for moderate to severe ischemic stroke with anterior large vessel occlusion (LVO); however, whether it is equally effective in mild ischemic stroke (MIS) is controversial. METHODS: In this retrospective study, a total of 177 Chinese patients presenting with MIS (NIHSS ≤8) and LVO between January 2014 and September 2017 from seven comprehensive stroke centers were identified. Odds of good outcome with endovascular thrombectomy versus medical treatment were obtained by logistic regression analysis and propensity-score matching method, and a meta-analysis pooled results from six studies (n = 733). RESULTS: Good outcome (mRS: 0-1) was 58.2% (46/79) in the thrombectomy and 46.9% (46/98) in the medical group, which showed no statistical significance before adjustment (P = 0.13; OR = 1.57, 95% CI: 0.86 to 2.86). The adjusted ORs of thrombectomy versus medical group were 3.23 (95% CI, 1.35 to 7.73; P = 0.008) by multivariable logistic analysis, 2.78 (1.12 to 6.89; P = 0.02) by propensity score matching analysis, and 3.20 (1.22 to 8.37; P = 0.01) by propensity score matching analysis with additional adjustments, respectively. Thrombectomy treatment did not result in excessive mortality or symptomatic intracranial hemorrhage after adjustments. The meta-analysis did not confirm the associations between good outcome and endovascular treatment. CONCLUSIONS: The current study indicates that endovascular thrombectomy is associated with good functional outcome in MIS patients with LVO, and without additional risk of symptomatic intracranial hemorrhage and mortality. Although the meta-analysis failed to demonstrate its superiority compared to medical treatment, randomized clinical trials are needed.

EEG and ECG Power Spectrum Analysis of Sedative Effects on Propofol-Anesthetized Rats with Electroacupuncture.

Background: In previous studies, electroacupuncture (EA) with 2/15 Hz has been shown to enhance the sedative effects in general anesthesia patients. Central lateral thalamic stimulation of 50 Hz showed an arousal effect in macaques. Therefore, it is worth studying the sedative effect of EA at peripheral acupoints with different frequencies, especially the frequency of around 50 Hz. Methods: Rats were anesthetized under the constant infusion of propofol and EA at Zusanli (ST36) and Neiguan (PC6) locations. Electroencephalography (EEG) and heart rate were continuously recorded before and after the intervention by EA in the C group (control), LEA group (low-frequency group, 2/15 Hz diffuse/dense wave EA stimulation), and HEA group (high-frequency group, 50 Hz stimulation). Results: In the LEA group, a significant increase in the power of the delta component with a decrease in the alpha component (p < 0.05) was observed after EA stimulation. In the HEA group, significant increases in the powers of alpha and beta components of EEG (p < 0.05) and a decrease in the delta component of EEG were observed (p < 0.05). The phenomenon is also shown in full-frequency waves. In addition, a significant decrease in the low-frequency/high-frequency ratio parameter was observed in the LEA group. Conclusions: EA at bilateral ST36 and PC6 can enhance the sedative effects of propofol anesthesia in low-frequency stimulation but lighten the sedative effects in high-frequency (50 Hz) stimulation. The sympathetic-vagal balance was affected due to low-frequency EA.

UPF1: a potential biomarker in human cancers.

Recently, Up-frameshift protein 1 (UPF1) is reported to be downregulated in various cancers and its low expression is closely correlated with poor prognosis. UPF1 is well known as a master regulator of nonsense-mediated mRNA decay (NMD), which serves as a highly conserved mRNA surveillance process protecting cells from aberrant toxic transcripts. Due to dysfunction of UPF1, NMD fails to proceed, which contributes to tumor initiation and progression. This review shows a brief summary of the aberrant expression, functional roles and molecular mechanisms of UPF1 during tumorigenesis. Increasing evidence has indicated that UPF1 could serve as a potential biomarker for cancer diagnosis and treatment for future clinical applications in cancer.

Gunsight sutures significantly reduce surgical-site infection after ileostomy reversal compared with linear sutures.

BACKGROUND: Surgical-site infection (SSI) was one of the most common post-operative morbidities of ileostomy reversal. Although several skin-closure procedures had been developed to reduce the rate of SSI, the optimal procedure remains unclear. In this study, we compared the effect of two surgical techniques for wound closure following ileostomy reversal: gunsight suture (GS) and linear suture (LS). METHODS: A total of 233 patients who underwent loop ileostomy at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2017 were enrolled into our study. These patients were divided into two groups: the LS group and the GS group. We compared the clinical characteristics between the two groups and analyzed the data using IBM SPSS to identify risk factors for SSI. RESULTS: Both groups successfully underwent surgery. The rate of SSI was significantly lower in the GS group (n = 2, 0.02%) than in the LS group (n = 16, 12.00%, P = 0.007). The length of hospital stay after the operation in the GS group was significantly shorter than that in the LS group (8.1 ± 3.2 vs 10.8 ± 5.4 days, P < 0.001). Multivariate analysis showed that GS was an independent protective risk factor for SSI (odds ratio = 0.212, P = 0.048). CONCLUSIONS: Compared with the LS technique, the GS technique can significantly decrease the rate of SSI and shorten the length of hospital stay after surgery. The GS technique may be recommended for wound closure following ileostomy reversal.

To what extent should the intestinal be resected proximally after radiotherapy: hint from a pathological view.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown. METHODS: We evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, n = 21) or proximally extended resection (nCRT-E, n = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin. RESULTS: Compared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, P = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, P = 0.039) at the proximal margins compared with the nCRT-C group. CONCLUSIONS: The severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.

Diverting colostomy is an effective and reversible option for severe hemorrhagic radiation proctopathy.

BACKGROUND: Severe chronic radiation proctopathy (CRP) is difficult to treat. AIM: To evaluate the efficacy of colostomy and stoma reversal for CRP. METHODS: To assess the efficacy of colostomy in CRP, patients with severe hemorrhagic CRP who underwent colostomy or conservative treatment were enrolled. Patients with tumor recurrence, rectal-vaginal fistula or other types of rectal fistulas, or who were lost to follow-up were excluded. Rectal bleeding, hemoglobin (Hb), endoscopic features, endo-ultrasound, rectal manometry, and magnetic resonance imaging findings were recorded. Quality of life before stoma and after closure reversal was scored with questionnaires. Anorectal functions were assessed using the CRP symptom scale, which contains the following items: Watery stool, urgency, perianal pain, tenesmus, rectal bleeding, and fecal/gas incontinence. RESULTS: A total of 738 continual CRP patients were screened. After exclusion, 14 patients in the colostomy group and 25 in the conservative group were included in the final analysis. Preoperative Hb was only 63 g/L ± 17.8 g/L in the colostomy group compared to 88.2 g/L ± 19.3 g/L (P < 0.001) in the conservative group. All 14 patients in the former group achieved complete remission of bleeding, and the colostomy was successfully reversed in 13 of 14 (93%), excepting one very old patient. The median duration of stoma was 16 (range: 9-53) mo. The Hb level increased gradually from 75 g/L at 3 mo, 99 g/L at 6 mo, and 107 g/L at 9 mo to 111 g/L at 1 year and 117 g/L at 2 years after the stoma, but no bleeding cessation or significant increase in Hb levels was observed in the conservative group. Endoscopic telangiectasia and bleeding were greatly improved. Endo-ultrasound showed decreased vascularity, and magnetic resonance imaging revealed an increasing presarcal space and thickened rectal wall. Anorectal functions and quality of life were significantly improved after stoma reversal, when compared to those before stoma creation. CONCLUSION: Diverting colostomy is a very effective method in the remission of refractory hemorrhagic CRP. Stoma can be reversed, and anorectal functions can be recovered after reversal.

Efficacy and complications of argon plasma coagulation for hemorrhagic chronic radiation proctitis.

BACKGROUND: Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center. AIM: To assess the long-term efficacy and safety of APC for hemorrhagic CRP. METHODS: This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas. RESULTS: Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm2 (P = 0.035). CONCLUSION: The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm2.

Early predictors of hyperlipidemic acute pancreatitis.

The present study aimed to investigate early risk factors for hyperlipidemic acute pancreatitis (HLAP) in order to open up novel routes for its prevention and treatment. Demographics, laboratory data obtained within 48 h, enhanced computed tomography (CT) imaging data and the modified CT severity index (MCTSI) for 111 patients with HLAP who were assessed at Ordos Central Hospital (Ordos, China) between January 2015 and October 2017 were retrospectively analyzed. Of these, 17 patients progressed to infectious pancreatic necrosis (IPN) and 14 patients progressed to organ failure (OF), the occurrence of which were the study outcomes. The patients were divided into pairs groups: IPN and non-IPN, as well as OF and non-OF, and differences between the groups were determined regarding various clinicopathological parameters. Furthermore, univariate and multivariate regression analyses were performed to identify parameters associated with the risk of progression to IPN or OP. On univariate analysis, the following parameters were deemed as being significantly associated with the risk of IPN: Serum calcium ions, C-reactive protein (CRP), extent of necrosis, procalcitonin (PTC) and the MCTSI. Furthermore, calcium ions, red cell distribution width (RDW), extent of necrosis and the MCTSI were significantly associated with the risk of OF on univariate analysis. Multivariate logistic regression analysis for these parameters then indicated that CRP (P=0.014), RDW (P=0.025) and the extent of necrosis (P=0.022) were significant and independent predictors of progression; thus, these are early risk factors for patients with HLAP. Receiver operating characteristic curves were generated to evaluate the predictive value of these factors, and the area under the curve for the three parameters was 0.863 [95% confidence interval (CI), 0.646-0.886], 0.727 (95% CI, 0.651-0.803) and 0.833 (95% CI, 0.739-0.936), respectively. Therefore, CRP, RDW and the extent of necrosis are early predictive indexes for the risk of progression in HLAP.

Correlation between Disease Activity and Endorectal Ultrasound Findings of Chronic Radiation Proctitis.

The aim of this study was to summarize the imaging features of chronic radiation proctitis (CRP) on endorectal ultrasound (ERUS) and investigate the value of ERUS in the evaluation of disease activity. 40 CRP patients and 30 control patients were investigated by ERUS. Rectal wall thickness and layers, ulcers and rectovaginal fistulas were evaluated by B-mode ultrasound. Power Doppler imaging was used to evaluate the vascularity of the rectal wall using a semiquantitative score. Disease activity was calculated according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0). Imaging findings for patients with mild and severe CRP were compared. For 30 patients in the control group, the average maximum thickness of the rectal wall was 3.07 ± 0.73 mm, with all exhibiting typical wall stratification and level 0 vascularity. For the 40 CRP patients, there was marked thickening of the rectal wall (average thickness = 9.42 ± 1.94 mm), which was significantly thicker than in the control group (p < 0.05). The rectal walls of the mild group were significantly thinner than those of the severe group (8.71 ± 1.67 mm vs. 10.00 ± 2.00 mm, p < 0.05). Among the 22 severe cases, 19 cases (19/22, 86.4%) exhibited hyper-vascularity (level IV) or blurred wall stratification (including hypo-echoic submucosa, ulcer and fistula); 12 of the 18 mild cases (166.7%) exhibited a vascularity of level III and typical wall stratification. A significant association (p < 0.05) was observed between stratification and vascularity of the rectal wall and CRP activity. When ERUS findings of blurred rectal wall stratification or increasing vascularity (level IV) were used to evaluate CRP activity, the sensitivity was 86.4% (95% confidence interval: 64.0-96.4) and the specificity was 66.7% (95% confidence interval: 41.2-85.6). Thickening of the rectal wall, blurred wall stratification and increased vascularity are characteristic ERUS findings of CRP. ERUS is helpful in the comprehensive evaluation of disease activity and may provide objective evidence during treatment planning and follow-up.

Reduced NM23 Protein Level Correlates With Worse Clinicopathologic Features in Colorectal Cancers: A Meta-Analysis of Pooled Data.

The clinical value of a prominent metastasis suppressor, nonmetastatic protein 23 (NM23), remains controversial. In this study, we examined the correlation between NM23 protein levels and the clinicopathologic features of colorectal cancers (CRC), and assessed the overall prognostic value of NM23 for CRC. Embase, PubMed, Web of Science, and other scientific literature databases were exhaustively searched to identify relevant studies published prior to June 31, 2015. The methodological qualities of selected studies were scored based on the critical appraisal skills program (CASP) criteria, as independently assessed by 2 reviewers. NM23 protein levels in tumor tissues of CRC patients were examined in relation to Dukes stage, differentiation grade, T-stage, lymph node metastasis status, and overall survival (OS). STATA software version 12.0 (Stata Corp, College Station, TX) was used for statistical analysis of data pooled from selected studies. Nineteen cohort studies met the inclusion criteria for present study and contained a combined total of 2148 study subjects. Pooled odd ratios (ORs) for NM23 expression revealed that reduced NM23 protein levels in CRC tumor tissues correlated with Dukes stage C and D (OR = 1.89, 95% CI: 1.06-3.39, P = 0.032), poor differentiation grades (OR = 1.41, 95% CI: 1.03-1.94, P = 0.032), and positive lymph node metastasis status (OR = 3.21, 95% CI: 1.95-5.29, P < 0.001). On the other hand, no such correlations were evident with T-stage T3-4 (OR = 1.56, 95% CI: 0.60-4.06, P = 0.367) or OS (OR = 0.79, 95% CI: 0.58-1.08, P = 0.138). Our analysis of pooled data found that NM23 expression is reduced in CRC tissues and low NM23 levels tightly correlate with higher Dukes stages, poorer differentiation grade, and positive lymph node metastases. However, NM23 levels did not influence the OS in CRC patients.

Colostomy is a simple and effective procedure for severe chronic radiation proctitis.

AIM: To assess the efficacy and safety of diverting colostomy in treating severe hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with severe hemorrhagic CRP who were admitted from 2008 to 2014 were enrolled into this study. All CRP patients were diagnosed by a combination of pelvic radiation history, clinical rectal bleeding, and endoscopic findings. Inclusion criteria were CRP patients with refractory bleeding with moderate to severe anemia with a hemoglobin level < 90 g/L. The study group included patients who were treated by diverting colostomy, while the control group included patients who received conservative treatment. The remission of bleeding was defined as complete cessation or only occasional bleeding that needed no further treatment. The primary outcome was bleeding remission at 6 mo after treatment. Quality of life before treatment and at follow-up was evaluated according to EORTC QLQ C30. Severe CRP complications were recorded during follow-up. RESULTS: Forty-seven consecutive patients were enrolled, including 22 in the colostomy group and 27 in the conservative treatment group. When compared to conservative treatment, colostomy obtained a higher rate of bleeding remission (94% vs 12%), especially in control of transfusion-dependent bleeding (100% vs 0%), and offered a better control of refractory perianal pain (100% vs 0%), and a lower score of bleeding (P < 0.001) at 6 mo after treatment. At 1 year after treatment, colostomy achieved better remission of both moderate bleeding (100% vs 21.5%, P = 0.002) and severe bleeding (100% vs 0%, P < 0.001), obtained a lower score of bleeding (0.8 vs 2.0, P < 0.001), and achieved obvious elevated hemoglobin levels (P = 0.003), when compared to the conservative treatment group. The quality of life dramatically improved after colostomy, which included global health, function, and symptoms, but it was not improved in the control group. Pathological evaluation after colostomy found diffused chronic inflammation cells, and massive fibrosis collagen depositions under the rectal wall, which revealed potential fibrosis formation. CONCLUSION: Diverting colostomy is a simple, effective and safe procedure for severe hemorrhagic CRP. Colostomy can improve quality of life and reduce serious complications secondary to radiotherapy.

Novel and Effective Almagate Enema for Hemorrhagic Chronic Radiation Proctitis and Risk Factors for Fistula Development.

Radiation proctitis is a common complication after radiotherapy for pelvic malignant tumors. This study was conducted to assess the efficacy of novel almagate enemas in hemorrhagic chronic radiation proctitis (CRP) and evaluate risk factors related to rectal deep ulcer or fistula secondary to CRP. All patients underwent a colonoscopy to confirm the diagnosis of CRP and symptoms were graded. Typical endoscopic and pathological images, risk factors, and quality of life were also recorded. A total of 59 patients were enrolled. Gynecological cancers composed 93.1% of the primary malignancies. Complete or obvious reduction of bleeding was observed in 90% (53/59) patients after almagate enema. The mean score of bleeding improved from 2.17 to 0.83 (P<0.001) after the enemas. The mean response time was 12 days. No adverse effects were found. Moreover, long-term successful rate in controlling bleeding was 69% and the quality of life was dramatically improved (P=0.001). The efficacy was equivalent to rectal sucralfate, but the almagate with its antacid properties acted more rapidly than sucralfate. Furthermore, we firstly found that moderate to severe anemia was the risk factor of CRP patients who developed rectal deep ulcer or fistulas (P= 0.015). We also found abnormal hyaline-like thick wall vessels, which revealed endarteritis obliterans and the fibrosis underlying this disease. These findings indicate that almagate enema is a novel effective, rapid and well-tolerated method for hemorrhagic CRP. Moderate to severe anemia is a risk factor for deep ulceration or fistula.

Formalin irrigation for hemorrhagic chronic radiation proctitis.

AIM: To assess the efficacy and safety of a modified topical formalin irrigation method in refractory hemorrhagic chronic radiation proctitis (CRP). METHODS: Patients with CRP who did not respond to previous medical treatments and presented with grade II-III rectal bleeding according to the Common Terminology Criteria for Adverse Events were enrolled. Patients with anorectal strictures, deep ulcerations, and fistulas were excluded. All patients underwent flexible endoscopic evaluation before treatment. Patient demographics and clinical data, including primary tumor, radiotherapy and previous treatment options, were collected. Patients received topical 4% formalin irrigation in a clasp-knife position under spinal epidural anesthesia in the operating room. Remission of rectal bleeding and related complications were recorded. Defecation, remission of bleeding, and other symptoms were investigated at follow-up. Endoscopic findings in patients with rectovaginal fistulas were analyzed. RESULTS: Twenty-four patients (19 female, 5 male) with a mean age of 61.5 ± 9.5 years were enrolled. The mean time from the end of radiotherapy to the onset of bleeding was 11.1 ± 9.0 mo (range: 2-24 mo). Six patients (25.0%) were blood transfusion dependent. The median preoperative Vienna Rectoscopy Score (VRS) was 3 points. Nineteen patients (79.2%) received only one course of topical formalin irrigation, and five (20.8%) required a second course. No side effects were observed. One month after treatment, bleeding cessation was complete in five patients and obvious in 14; the effectiveness rate was 79.1% (19/24). For long-term efficacy, 5/16, 1/9 and 0/6 patients complained of persistent bleeding at 1, 2 and 5 years after treatment, respectively. Three rectovaginal fistulas were found at 1 mo, 3 mo and 2 years after treatment. Univariate analysis showed associations of higher endoscopic VRS and ulceration score with risk of developing rectovaginal fistula. CONCLUSION: Modified formalin irrigation is an effective and safe method for hemorrhagic CRP, but should be performed cautiously in patients with a high endoscopic VRS.

[Clinical analysis of acute heart failure's risk factor for chronic myelogenous leukemia patient during the early stage of allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: The study was to analyze the acute heart failure's risk factors and clinical characteristics for the patient with chronic myelogenous leukemia (CML) during the early stage (within 100 d) of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 106 cases of CML received allo-HSCT were retrospectively studied in Nanfang Hospital from May 2003 to May 2013. On the basis of existence or absence of acute heart failure during early stage of allo-HSCT (100 d), the patients were divided into heart failure (15 cases) and control group (91 cases). Using Logistic univariate analysis, Fisher' exact test and Pearson X(2) test, the acute heart failure's risk factors and clinical characteristics of both groups were analyzed. RESULTS: The median occurrence time of acute heart failure was 3 d (1 d before transplantation to 84 d after transplantation). Logistic univariate analysis indicated that the imatinib treatment history and time, and the prophylaxis regimens for GVHD with anti-thymocyte globulin (ATG) were all the poor prognostic factors for acute heart failure. Incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and adverse prognostic events including death in the heart failure group patients were statistically higher than that in control group (P < 0.05). CONCLUSION: Acute heart failure mostly happened in the early stage after allo-HSCT, imatinib treatment and GVHD prophylaxis regimens with ATG are the poor prognostic factors for acute heart failure. The patients of heart failure group seem to have higher incidence of hepatic veno-occlusive disease (HVOD), bacterial infection and deaths.

Effects of cobalt chloride on phenotypes of normal human saphenous vein smooth muscle cells.

To explore the cellular adaptations and responses to hypoxia in normal human saphenous vein smooth muscle cells (SMCs) and presume what roles phenotypic modulation of normal human saphenous vein SMCs would play in varicose vein of lower extremity, we used cobalt chloride (CoCl2), a hypoxia mimetic, to treat normal human saphenous vein SMCs in vitro. The proliferating ability of cells exposed to serial dilutions of CoCl2 (0, 200, 300, 400 and 500 µM) at 24 h, 48 h and 72 h respectively was detected by MTT assay. Wound healing assay was used to observe the migrating ability of cells under CoCl2 (200 µM) treatment for 8 days continuously. Hoechst 33258 stain was used to determine whether hypoxia induced by CoCl2 could cause apoptosis of normal human saphenous vein SMCs. We found that CoCl2 enhanced the proliferation and inhibited the migration of normal human saphenous vein SMCs. The apparent morphous of normal human saphenous vein SMCs under chronic CoCl2 treatment was significantly changed compared to no CoCl2 treated control, but this process did not relate to cell apoptosis. To conclude, our results support the concept that the phenotypes of normal human saphenous vein SMCs could be influenced by hypoxia stimulus. Cellular structural and functional changes under chronic hypoxia in normal human saphenous vein SMCs might play important roles in the development of varicose veins of lower extremity.

Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only endogenous NMDA receptor antagonist and could modulate neurotoxic effects of QA. We hypothesize that an activated kynurenine pathway induced by inflammatory cytokines would generate more neurotoxic metabolites, which could be closely related to the pathogenesis of AD in elderly patients. Moreover, some measures, which facilitate KA synthesis and reduce the formation of QA, may emerge as a new therapeutic strategy against AD.