Facilitating the drug repurposing with iC/E strategy: A practice on novel nNOS inhibitor discovery.

Over the past decades, many existing drugs and clinical/preclinical compounds have been repositioned as new therapeutic indication from which they were originally intended and to treat off-target diseases by targeting their noncognate protein receptors, such as Sildenafil and Paxlovid, termed drug repurposing (DRP). Despite its significant attraction in the current medicinal community, the DRP is usually considered as a matter of accidents that cannot be fulfilled reliably by traditional drug discovery protocol. In this study, we proposed an integrated computational/experimental (iC/E) strategy to facilitate the DRP within a framework of rational drug design, which was practiced on the identification of new neuronal nitric oxide synthase (nNOS) inhibitors from a structurally diverse, functionally distinct drug pool. We demonstrated that the iC/E strategy is very efficient and readily feasible, which confirmed that the phosphodiesterase inhibitor DB06237 showed a high inhibitory potency against nNOS synthase domain, while other two general drugs, i.e. DB02302 and DB08258, can also inhibit the synthase at nanomolar level. Structural bioinformatics analysis revealed diverse noncovalent interactions such as hydrogen bonds, hydrophobic forces and van der Waals contacts across the complex interface of nNOS active site with these identified drugs, conferring both stability and specificity for the complex recognition and association.

Preliminary investigation into the prediction of indicators of beef spoilage using Raman and Fourier transform infrared spectroscopy.

The objective of this study was to assess the potential to predict the microbial beef spoilage indicators by Raman and Fourier transform infrared (FT-IR) spectroscopies. Vacuum skin packaged (VSP) beef steaks were stored at 0 °C, 4 °C, 8 °C and under a dynamic temperature condition (0 °C âˆ¼ 4 °C âˆ¼ 8 °C, for 36 d). Total viable count (TVC) and total volatile basic nitrogen (TVB-N) were obtained during the storage period along with spectroscopic data. The Raman and FTIR spectra were baseline corrected, pre-processed using Savitzky-Golay smoothing and normalized. Subsequently partial least squares regression (PLSR) models of TVC and TVB-N were developed and evaluated. The root mean squared error (RMSE) ranged from 0.81 to1.59 (log CFU/g or mg/100 g) and the determination coefficient (R2) from 0.54 to 0.75. The performance of PLSR model based on data fusion (combination of Raman and FT-IR data) is better than that based on Raman spectra and similar to that of FT-IR. Overall, Raman spectroscopy, FT-IR spectroscopy, and a combination of both exhibited a potential for the prediction of the beef spoilage.

Local injection of botulinum toxin type A (BTX-A) prevents scarring esophageal stricture caused by electrocautery in rabbit models.

Background: Benign esophageal strictures are common in clinical practice. The commonly used methods for preventing benign esophageal strictures still have many shortcomings. In this study, we investigated the preventive effect and possible mechanism of endoscopic local injection of botulinum toxin type A (BTX-A) on scarring esophageal stricture caused by electrocautery in rabbit models, with an attempt to provide a theoretical basis for the clinical application of BTX-A in the prevention of benign esophageal stricture. Methods: Adult male New Zealand rabbits were randomly divided into 4 groups: cautery group (cauterized with 30 W electrocoagulation power without other intervention), saline group (injected with normal saline at 4 spots in the local esophagus after modeling), BTX-A I group (injected with 10 U of BTX-A after modeling), and BTX-A II group (injected with 20 U of BTX-A after modeling). Body weight was measured at postoperative weeks 1, 2, and 4. Esophagography was performed, and the internal diameter of the esophagus was measured. The esophageal tissues were harvested for hematoxylin and eosin (HE) staining and Masson staining. Type I, type III collagen levels and the mRNA expression of transforming growth factor ß1 (TGF-ß1) in esophageal tissues were detected. Results: Compared with the cautery and saline groups, the BTX-A I and BTX-A II groups had significantly higher body weight, larger esophageal internal diameter, lower type I and type III collagen levels, and lower TGF-ß1 mRNA expression levels in esophageal tissues at postoperative week 4. Comparisons between the BTX-A I and BTX-A II groups showed no significant differences in terms of body weight, esophageal internal diameter, and type I collagen level at postoperative week 4. However, the BTX-A II group had a significantly lower type III collagen level and TGF-ß1 mRNA expression level than the BTX-A I group. Conclusions: Local injection of BTX-A can alleviate esophageal stricture after electrocautery and has a preventive effect on benign esophageal stricture caused by electrocautery in rabbits. The mechanism may be that BTX-A down-regulates the expression of TGF-ß1 in the esophageal tissue at the burn site and reduces the deposition of collagen.

Risk Factors and Clinical Outcomes of 54 Cases of Rectal Neuroendocrine Tumors with Incomplete Resection: A Retrospective Single-Center Study.

OBJECTIVE: The present study aimed to analyze the risk factors and clinical outcomes of the incomplete endoscopic resection of rectal neuroendocrine tumors (rNETs). METHODS: This study retrospectively analyzed the cases of 428 patients with rNETs who had undergone endoscopic treatment in the Department of Gastroenterology at the PLA General Hospital, China, between January 2010 and September 2019. RESULTS: Of the 428 patients with rNETs, 266 were men (62.1%) and 162 were women (37.9%). Of these, 54 had been pathologically diagnosed with positive incisal margins without lymphatic vessel invasion, and the incomplete resection (R1) rate was 12.6%. Among the R1 patients, 28 had received endoscopic submucosal dissection, 22 had received endoscopic mucosal resection, two had received snare resection, and two had undergone removal with forceps. In addition, there were 31 cases of grade G1 R1 resection (11.2%; 31/277), 13 cases of grade G2 R1 resection (23.2%; 13/56), and 10 cases whose grading was not described. The univariate analysis showed the pathological grade was statistically correlated with R1 resection (P < 0.05), and the grade G2 R1 resection rate was higher than that of grade G1. The multivariate logistic regression analysis showed that grade G2 was an independent risk factor leading to R1 resection (P = 0.02). All patients with R1 resection were followed up for 10-110 months, with an average of 38 months. No salvage treatment was performed. The endoscopic monitoring showed there were no recurrences during the follow-up period. CONCLUSION: Endoscopic resection is a good option for rNETs, with a high complete resection rate and good prognosis, with rare recurrence even if endoscopic resection is not complete.

Vascular-targeted photodynamic therapy of gastric antral vascular ectasia (GAVE).

BACKGROUND AND STUDY AIM: Vascular-targeted photodynamic therapy (V-PDT) has been used for several benign vascular diseases. The aim of this pilot study was to demonstrate the potential benefits of VPDT in the treatment of gastric antral vascular ectasia (GAVE). PATIENTS AND METHODS: Data from patients with GAVE (n=5) who underwent endoscopic V-PDT were analyzed retrospectively. Pre- and post-V-PDT clinical and endoscopic features, hemoglobin levels, and transfusion requirement were compared. RESULTS: The five GAVE patients received one to four sessions of V-PDT. The hemoglobin levels of all five patients increased steadily following V-PDT. Within 6-48months of follow-up, gastrointestinal bleeding and melena disappeared in all five patients and none of the patients needed a transfusion. Endoscopy examinations showed that the dilated vessels had disappeared without scar formation. No significant side effects or adverse reactions were reported. CONCLUSION: This preliminary study indicates the good selectivity, safety, and efficacy of V-PDT in the treatment of patients with GAVE. Larger prospective studies are needed to further confirm the feasibility of using V-PDT to treat patients with GAVE.

Prevention of esophageal strictures after endoscopic submucosal dissection with the injection of botulinum toxin type A.

BACKGROUND AND AIMS: The use of endoscopic submucosal dissection (ESD) for management of widespread superficial esophageal squamous carcinoma is closely associated with esophageal stenosis. We investigated the efficacy and feasibility of endoscopic injection of botulinum toxin type A (BTX-A) for preventing esophageal strictures after ESD for superficial esophageal squamous carcinoma. METHODS: Sixty-seven patients with superficial esophageal squamous cell carcinomas with mucosal defects that exceeded one half of the circumference of the esophagus after ESD treatment were enrolled and randomly divided into 2 groups (group A, n = 33; group B, n = 34). Patients in group A (BTX-A group) were immediately injected with BTX-A after ESD, whereas patients in group B (control group) received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in both groups received bougie dilation. RESULTS: The number of patients who experienced esophageal strictures in group A (per protocol analysis, 6.1%, 2/33; intention to treat analysis, 11.4%, 4/35) was significantly less than that seen in group B (per protocol analysis, 32.4%, 11/34; intention to treat analysis, 37.8%, 14/37) (P < .05). Moreover, the number of bougie dilation procedures was significantly lower in group A (mean, 1.5; range, 0-2) than in group B (mean, 2.8; range, 0-5) (P < .05). CONCLUSIONS: Endoscopic injection of BTX-A was effective in preventing post-ESD esophageal strictures and decreasing the times of bougie dilation procedures. ( CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-12003188.).

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].

OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours. RESULTS: The average disease duration of 7 patients with UC was (9.1 ± 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 ± 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found. CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.

Associated risk factor analysis for positive resection margins after endoscopic submucosal dissection in early-stage gastric cancer.

PURPOSE: To investigate the associated risk factors and the prognostic impact of positive resection margins after endoscopic submucosal dissection (ESD) of early-stage gastric cancer. METHODS: A retrospective analysis of prospectively collected data was performed on 319 consecutive lesions in 316 patients who underwent ESD. Age, gender, surgeons, lesion location, maximum diameter of resected specimens, macroscopic type, depth of tumor invasion and tumor differentiation were evaluated as potential risk factors. RESULTS: A total of 27 (8.5%) patients exhibited positive resection margins after ESD. Among 25 successfully followed-up patients 13 were subjected to gastrectomy, 1 was administered chemotherapy, 2 underwent additional endoscopic resection and 9, who were initially followed-up during a median period of 11.7 months (range 1-40), had neither recurrence nor metastasis. Univariate analysis revealed that age, lesion location, depth of tumor invasion, macroscopic type and tumor differentiation were correlated with positive resection margin. By contrast, multivariate logistic regression analysis showed that only age, tumor differentiation and depth of tumor invasion were independent risk factors of positive resection margins. CONCLUSION: Age, tumor differentiation and depth of tumor invasion were independent risk factors for post-ESD positive resection margins. This result suggests that older patients, undifferentiated lesions and a greater depth of invasion increase the risk for post-ESD positive resection margins.

Risk Factors Associated with Mortality and Increased Drug Costs in Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND/AIMS: To determine risk factors associated with mortality and increased drug costs in patients with nonvariceal upper gastrointestinal bleeding. METHODOLOGY: We retrospectively analyzed data from patients hospitalized with nonvariceal upper gastrointestinal bleeding between January 2001-December 2011. Demographic and clinical characteristics and drug costs were documented. Univariate analysis determined possible risk factors for mortality. Statistically significant variables were analyzed using a logistic regression model. Multiple linear regression analyzed factors influencing drug costs. p < 0.05 was considered statistically significant. RESULTS: The study included data from 627 patients. Risk factors associated with increased mortality were age > 60, systolic blood pressure<100 mmHg, lack of endoscopic examination, comorbidities, blood transfusion, and rebleeding. Drug costs were higher in patients with rebleeding, blood transfusion, and prolonged hospital stay. CONCLUSION: In this patient cohort, re-bleeding rate is 11.20% and mortality is 5.74%. The mortality risk in patients with comorbidities was higher than in patients without comorbidities, and was higher in patients requiring blood transfusion than in patients not requiring transfusion. Rebleeding was associ-ated with mortality. Rebleeding, blood transfusion, and prolonged hospital stay were associated with increased drug costs, whereas bleeding from lesions in the esophagus and duodenum was associated with lower drug costs.

Prevention and treatment of esophageal stenosis after endoscopic submucosal dissection for early esophageal cancer.

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward.

The potential of photodynamic therapy to treat esophageal candidiasis coexisting with esophageal cancer.

BACKGROUND: Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis. METHODS: Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation. RESULTS: The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases. CONCLUSION: Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis.

Effectiveness and safety of endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction.

BACKGROUND: Endoscopic submucosal dissection of the esophagogastric junction is the most difficult gastric and esophageal dissection procedure. No reports of endoscopic submucosal dissection for Siewert type II carcinoma of the esophagogastric junction have compared the outcomes of endoscopic submucosal dissection for all three Siewert types of adenocarcinoma. This study aimed to evaluate the efficacy and safety of endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction. METHODS: From October 2008 to June 2013, 73 patients underwent endoscopic submucosal dissection for intraepithelial neoplasia of the esophagogastric junction. The patients were prospectively evaluated regarding the executability of the technique, short-term results of the procedure, en bloc resection rate, curative resection rate, complications and additional treatment after endoscopic submucosal dissection, and follow-up outcomes. RESULTS: Sixty-eight of the 73 patients (93.2%) underwent en bloc resection; the mean maximum specimen diameter was 33.7 mm. Fifty-seven of 61 patients (93.4%) who underwent curative resection were successfully followed-up for 1.0 to 56.0 months (average, 24.1 months). Local recurrence developed in one patient with high-grade intraepithelial neoplasm. Twelve patients underwent noncurative resection, including lateral resection margin residues in three, vertical resection margin residues in one, signet ring cell carcinoma or undifferentiated adenocarcinoma in four, lymphatic or vessel invasion in one, vertical residual margin residues combined with signet ring cell carcinoma in one, and undifferentiated adenocarcinoma with lymphatic or vessel invasion in two. In the noncurative resection group, one patient was lost to follow-up, seven underwent additional surgery, and the remaining four were periodically followed up; none had local recurrence or distant metastases. The only complication was delayed bleeding in three patients, which was successfully controlled by conservative treatment or endoscopic therapy. CONCLUSIONS: Endoscopic submucosal dissection is safe and effective for intraepithelial neoplasia of the esophagogastric junction. R0 en bloc resection is possible and can avoid the risk of local recurrence.

Relevant risk factors and prognostic impact of positive resection margins after endoscopic submucosal dissection of superficial esophageal squamous cell neoplasia.

BACKGROUND: Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions has a risk of resection margin residues. The related risk factors and prognosis of post-ESD resection margin residues have not been fully evaluated. The aim of this study was to investigate the associated risk factors and the prognostic impact of resection margin residues after ESD of superficial esophageal squamous cell neoplasia. METHODS: We conducted a retrospective analysis of medical records at our hospital, including the clinical, endoscopic, and pathological data from patients who underwent ESD for the treatment of superficial esophageal squamous cell neoplasia from January 2008 to December 2012. In addition, we conducted a statistical analysis of the following factors: sex, age, location, the proportion of circumferential extension, the maximum diameter of the resected specimen, macroscopic type, the depth of invasion, and the endoscopists. RESULTS: A total of 145 patients were included in the study. Overall, 148 lesions were completely resected. There were 17 patients (17 lesions) presenting with positive resection margin after ESD and the positive rate was 11.5 %. A total of 16 patients were followed-up. Among the patients who had resection margin residues, three underwent surgical esophageal resection, one underwent radiotherapy, two received ESD, and one received endoscopic mucosal resection. The remaining nine patients were periodically followed-up, and no recurrences were found. The results of a one-dimensional analysis suggested that there were significant differences in the maximum diameters of the resected specimens, macroscopic type, and the depth of invasion between the positive resection margin group and the negative resection margin group. The results of a multivariate regression analysis suggested that the maximum diameter of the resected specimens and the depth of invasion were risk factors for resection margin residues. CONCLUSIONS: The maximum diameter of the resected specimens and the depth of tumor invasion are risk factors for post-ESD positive resection margins, which suggests that larger lesions and a greater depth of invasion increases the chance of residual tumor after ESD.

Preventing stricture formation by covered esophageal stent placement after endoscopic submucosal dissection for early esophageal cancer.

OBJECTIVE: We aimed to evaluate the efficacy and safety of fully covered esophageal stent placement for preventing esophageal strictures after endoscopic submucosal dissection (ESD). METHODS: Twenty-two patients with a mucosal defects that exceeded 75 % of the circumference of the esophagus after ESD treatment for superficial esophageal squamous cell carcinomas were grouped according to the type of mucosal defect and randomized to undergo fully covered esophageal stent placement post-ESD (group A, n = 11) or no stent placement (group B, n = 11). In group A, the esophageal stents were removed 8 weeks post-ESD. Endoscopy was performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms. Savary-Gilliard dilators were used for bougie dilation in patients experiencing esophageal stricture in both groups, and we compared the rates of post-ESD strictures and the need for bougie dilation procedures. RESULTS: The proportion of patients who developed a stricture was significantly lower in group A (18.2 %, n = 2) than in group B (72.7 %, n = 8) (P < 0.05). Moreover, the number of bougie dilation procedures was significantly lower in group A (mean 0.45, range 0-3) than in group B (mean 3.9, range 0-17) (P < 0.05). The two patients in group A who experienced stricture also had stent displacement. CONCLUSIONS: Esophageal stents are a safe and effective method of preventing esophageal strictures in cases where >75 % of the circumference of the esophagus has mucosal defects after ESD treatment for early esophageal cancer.

Endoscopic lithotripsy for gastric bezoars by Nd:YAG laser-ignited mini-explosive technique.

Until now, there still has no standard treatment option to deal with gastric bezoars. This respective study was conducted to evaluate the safety and efficiency of Nd:YAG laser-ignited mini-explosive technique for the treatment of gastric bezoars. Two hundred sixty patients with 285 gastric bezoars were treated by endoscopic lithotripsy with Nd:YAG laser-ignited mini-explosive technique. Among the 260 patients, the 284 gastric bezoars of the 259 patients completely disappeared, with the cure rate of 99.6% after 1-2 treatments at 2-4 weeks follow-up. Only one patient, who was cured by surgery, had gastric perforation during the explosion. No intraoperative or delayed complications was found in the other 259 patients. The endoscopic lithotripsy with Nd:YAG laser-ignited mini-explosive technique is an effective, safe, and promising alternative for gastric bezoars.

[The difference in diagnosis rate of different diagnostic criteria of autoimmune pancreatitis and its major influential factors].

OBJECTIVE: To discuss the difference in diagnostic criteria of autoimmune pancreatitis(AIP) and its major influential factors, so as to provide guidance for AIP diagnosis and treatment. METHODS: The clinical data of 561 cases of chronic pancreatitis admitted to PLA General Hospital from June, 2008 to January, 2013 were retrospectively reviewed and analyzed. Data were extracted and analyzed to summarize the reasons of the differences in AIP diagnosis rate diagnosed by different diagnostic criteria. RESULTS: A total of 34 cases were eligible for the 2006 American HISORt criteria of AIP of whom, 5, 10 and 26 met the criteria of histology, pancreatic imaging findings and increasing serum IgG4 levels, and response to steroids and increasing serum IgG4 levels, respectively. Seven AIP patients met the latter two criteria. Fifteen patients were eligible for the 2008 Asian diagnostic criteria for AIP, of which, 10 met the two necessary imaging findings and 5 met the criteria of pathology of lymphoplasmacytic sclerosing pancreatitis (LPSP) after surgical resection. CONCLUSIONS: AIP is characterized by autoimmune inflammatory process, and is easy to be misdiagnosed as pancreatic cancer or cholangiocarcinoma etc. As a few sets of criteria issued from different countries, the 2008 Asian diagnostic criterion is more suitable with Chinese population. We should pay full attention to the importance of imaging examination of the diagnosis of AIP on the base of the detection of immune parameters, pathological examination and response to steroids.

A systematic analysis of pneumatosis cystoids intestinalis.

AIM: To increase the understanding, diagnosis and treatment of pneumatosis cystoides intestinalis (PCI) and to find the characteristics and potential cause of the disease in China. METHODS: We report here one case of PCI in a 70-year-old male patient who received a variety of treatment methods. Then, we systematically searched the PCI eligible literature published from an available Chinese database from May 2002 to May 2012, including CBM, CBMDisc, CMCC, VIP, Wanfang, and CNKI. The key words were pneumatosis cystoides intestinalis, pneumatosis, pneumatosis intestinalis, pneumatosis coli and mucosal gas. The patients' information, histories, therapies, courses, and outcomes were reviewed. RESULTS: The study group consisted of 239 PCI cases (male:female = 2.4:1) from 77 reported incidents. The mean age was 45.3 ± 15.6 years, and the median illness course was 6 mo. One hundred and sixty patients (66.9%) were in high altitude areas. In addition, 43.5% (104/239) of the patients had potential PCI-related disease, and 16.3% had complications with intestinal obstruction and perforation. The most common symptom was abdominal pain (53.9%), followed by diarrhea (53.0%), distention (42.4%), nausea and vomiting (14.3%), bloody stool (12.9%), mucous stool (12.0%) and constipation (7.8%). Most multiple pneumocysts developed in the submucosa of the colon (69.9%). The efficacy of the treatments by combined modalities, surgery, endoscopic treatment, conservative approach, oxygen, and antibiotics were 100%, 100%, 100%, 93.3%, 68.3% and 26.3%, respectively. CONCLUSION: PCI can be safely managed by conservative treatments, presents more frequently in males, in the large bowel and submucosa, than in females, in the small intestine and subserosa. High altitude residence maybe associated with the PCI etiology.

Lactulose is highly potential in prophylaxis of hepatic encephalopathy in patients with cirrhosis and upper gastrointestinal bleeding: results of a controlled randomized trial.

BACKGROUND AND AIMS: Upper gastrointestinal bleeding (UGB) is an important precipitating factor for the development of hepatic encephalopathy (HE) in cirrhotic patients. The aim of this study was to evaluate the efficacy of lactulose in a controlled randomized trial for prophylaxis of HE after UGB. PATIENTS AND METHODS: 128 cirrhotic patients with UGB were consecutively classified according to Child-Pugh criteria and randomized to receive lactulose (group A, n = 63) or no lactulose (group B, n = 65) treatment after the symptoms of active bleeding disappeared. Curative effects were observed for 6 days. RESULTS: Two patients in group A and 11 in group B had developed HE; the incidence rates were 3.2 and 16.9% (χ(2) 5.2061, p < 0.05). After treatment, a significant increase in ammonia level and higher number connection test (NCT) in the non-lactulose group, median blood ammonia levels (60.0 vs. 52.0), p < 0.05, and median NCT (43 vs. 38), p < 0.05, were observed. Patients who had developed HE had a significantly higher baseline Child-Turcotte-Pugh score (10.15 ±1.82 vs. 6.35 ± 1.60, p < 0.05), alanine aminotransferase (111.25 ± 91.62 vs. 48.32 ± 47.45, p < 0.05), aspartate aminotransferase (171.42 ± 142.68 vs. 46.33 ± 42.68, p < 0.05), total bilirubin (73.44 ± 47.20 vs. 29.75 ± 22.08, p < 0.05), serum albumin (24.65 ± 5.04 vs. 33.43 ± 6.49, p < 0.05), plasma prothrombin time (22.18 ± 4.60 vs. 17.12 ± 4.62, p < 0.05), and lower hemoglobin level (72.31 ± 15.15 vs. 87.45 ± 19.79, p < 0.05) as compared to patients who did not develop HE. On unconditional logistic regression analysis, patients who had developed HE were significantly associated with a higher baseline Child-Turcotte-Pugh score (OR 9.92, 95% CI 1.94-50.63, p < 0.05) and lactulose therapy (OR 0.02, 95% CI 0-0.74, p < 0.05) but were not associated with other parameters. CONCLUSIONS: Lactulose is an effective prophylaxis agent of HE for cirrhotic patients who had developed UGB.

Endoscopic holmium:YAG laser ablation of early gastrointestinal intramucosal cancer.

Various endoscopic techniques are being increasingly used in early gastrointestinal (GI) cancer. The holmium: yttrium-aluminum-garnet (Ho:YAG) laser has precise tissue cutting ability and good hemostatic properties and has been widely applicated to soft tissue, but the use of endoscopic Ho:YAG laser ablation for early gastrointestinal cancer has not been reported. Twenty patients with biopsy-proven early GI cancer who had a high surgical risk or refused surgery were treated by endoscopic Ho:YAG laser ablation. The tumors of all patients were confined to the mucosal layer without ulceration and without lymph node metastasis. The tumor diameter was not more than 2.5 cm. Endoscopy, endoscopic ultrasound, and computed tomography scan were performed 1-3 months after the treatment, and a biopsy was performed to evaluate the effects of the therapy. Long-term endoscopic follow-up was maintained. Complete eradication was achieved in all the 20 patients, including four patients with high-grade dysplasia associated with focal canceration, seven patients with well-differentiated squamous cell cancer, and nine patients with well-differentiated adenocarcinoma, resulting in a complete response rate of 100% at 1-3 months after treatment. No recurrence was found during 36-73 months of follow-up in all 20 patients. No operative or delayed complications were observed in any of the 20 patients. Preliminary study shows that endoscopic Ho:YAG laser ablation may be an effective, safe, and minimally invasive method for selected patients with early GI intramucosal cancer. Further research is required to confirm the safety and efficacy of this technique compared to its alternative techniques in a multicenter randomized controlled trial.

Prior peritoneal lavage with hot 0.9 % saline induces HSP70 expression and protects against cerulein-induced acute pancreatitis in rats.

Recent studies have indicated that pre-induction of heat shock protein 70 (HSP70) expression in the pancreas protects against secretagogue-induced pancreatitis. In those studies, the HSP70 was mostly induced by unfeasible conditions. The aim of this current study was to investigate the effect of peritoneal lavage with hot 0.9 % saline (42 °C) on the pancreatic expression of HSP70 and its protective effect on cerulein-induced acute pancreatitis in rats. Male Wistar rats were peritoneally lavaged with 0.9 % saline at 42 °C for 30 min. HSP70 expression was evaluated by western blotting analysis. Prior peritoneal lavages with hot and warm saline were performed. Acute pancreatitis was induced by administration of intraperitoneal injection of cerulein (20 µg/kg) four times, and its severity was assessed by measuring serum amylase, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and trypsinogen activation peptide (TAP) levels. Pancreatic sections were stained with hematoxylin and eosin for histological evaluation. Peritoneal lavage with hot 0.9 % saline increased intrapancreatic HSP70 expression and ameliorated the cerulein-induced pancreatitis in rats, judged by the significantly reduced serum amylase, TNF-α, and IL-6 concentrations; histopathological scores, and serum TAP levels. Peritoneal lavage with hot 0.9 % saline can induce HSP70 expression and prevent cerulein-induced acute pancreatitis in rats. The results suggest that HSP70 protects against cerulein-induced pancreatitis by preventing proinflammatory cytokine synthesis and trypsinogen activation during acute pancreatitis.