Effects of anti-histamine treatment on liver injury triggered by small intestinal ischemia reperfusion in rats.

Mast cell (MC) degranulation has been implicated in small intestinal ischemia reperfusion (IIR) injury, therein, inhibiting overproduction of histamine released from activated MC may provide promising strategies against IIR-mediated liver injuries. The aim of the present study was to explore whether anti-histamine treatment contribute to attenuating IIR-mediated liver injury. Adult SD rats were randomized into sham-operated group (S group), sole IIR group (IIR group), and IIR treated with Ketotifen, a histamine antagonist (IIR+K group), Cromolyn Sodium, a MC stabilizer (IIR+C group), and Compound 48/80, a MC degranulator (IIR+CP group), respectively. IIR was induced by superior mesenteric artery occlusion for 75 min followed by 4 h of reperfusion. The agents were intravenously administrated 5 min before reperfusion to induce different levels of histamine. Subsequently, serum concentrations of ALT, AST and histamine; levels of LDH,TNF-α, IL-8 and MDA as well as SOD activities in the liver were assessed. Histopathologic changes were also evaluated. IIR resulted in severe liver injury as demonstrated by significant increases in injury scores, with concomitant significant increases in serum ALT, AST and histamine levels, as well as LDH, TNF-α, IL-8, and MDA levels in the liver, accompanied by reduction in SOD activities (all P < 0.05, IIR vs. S). Treatments by Ketotifen and Cromolyn Sodium similarly markedly alleviated IIR-mediated liver injury as confirmed by significant reduction of the above biomedical changes whereas Compound 48/80 further aggravated IIR-mediated liver injury by dramatically enhancing the above biomedical changes. Data of our study suggest that anti-histamine treatments may provide promising benefits in alleviating liver injury triggered by IIR.

[Surgical treatment for endoscopically unresectable polyps of colon and rectum].

OBJECTIVE: To explore the characteristics and risks of cancer in endoscopically unresectable polyps and compare the surgical outcomes of different operations. METHODS: A retrospective review of 40 patients undergoing surgical operations for polyps unresectable at colonoscopy between August 2006 and July 2012 from Department of Gastrointestinal Surgery was performed. The follow-up period was 3 to 72 months (median: 24.5 months). RESULTS: The rate of endoscopically unresectable polyps with invasive cancer was 67.5% (27/40). And it was significantly influenced by patient age and number of polyps (both P < 0.01). Perioperative volume of blood loss ((86 ± 58) ml vs (44 ± 32) ml, P = 0.0066), time to first flatus ((2.7 ± 1.3) d vs (1.7 ± 0.6) d, P = 0.0018), incidence of complication (2 cases vs 0, P = 0.0365) and hospital stay ((11.2 ± 1.0) d vs (15.0 ± 5.0) d, P = 0.0164) were significantly different between open colectomy and laparoscopic group. And the long-term survival outcomes were similar in both groups (90.9% (10/11) vs 100.0% (27/27), 90.9% (10/11) vs 96.3% (26/27), both P > 0.05). CONCLUSIONS: Endoscopically unresectable polyps of colon and rectum have high malignancy rate. Polyps in elderly patients and multiple polyps are more likely to develop invasive cancer. Long-term outcomes are similar between open colectomy and laparoscopic colectomy groups, but laparoscopic group has better short-term outcomes. For endoscopically unresectable polyps, laparoscopic colectomy may be the first choice.

Celecoxib increases retinoid sensitivity in human colon cancer cell lines.

Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE(2) production was measured with the ELISA assay. The expression of RARbeta was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE(2) did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE(2) did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARbeta and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

[Expression and its significance of retinoic acid receptor-beta in colorectal cancer].

OBJECTIVE: To investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer. METHODS: RAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer. RESULTS: The expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%). CONCLUSIONS: The expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer.

Risk factors analysis for surgical site infection following elective colorectal resection: a retrospective regression analysis.

BACKGROUND: A surgical site infection (SSI) is a major post-operative complication from elective colorectal surgery; however, few studies have focused on evaluating the risk factors for SSI. This study aimed to analyze the relative correlation of medical and environmental factors as well as patient-related factors that contribute to the incidence of all types of SSI. METHODS: A retrospective search for eligible patients was conducted using the patient database of the Gastrointestinal Surgery Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2011 to August 2017. Pre-operative demographic and surgical data were extracted and recoded according to the study protocol. Univariate and multivariate analyses were performed to clarify factors affecting the incidence of SSI. Propensity analysis was conducted to minimize bias in the demographic characteristics to explore the prophylactic effect of pre-operative administration of oral antibiotics. RESULTS: Univariate analysis of the baseline characteristics revealed that younger age (odds ratio [OR]: 0.378; 95% confidence interval [CI]: 0.218-0.657) and pre-operative oral antibiotic use (OR: 0.465; 95% CI: 0.255-0.850) were protective factors, while pre-operative anemia (OR: 4.591; 95% CI: 2.567-8.211), neoadjuvant chemotherapy history (OR: 2.398; 95% CI: 1.094-5.256), and longer surgical duration (OR: 2.393; 95% CI: 1.349-4.246; P = 0.002) were identified as risk factors for SSI. Multivariate analysis indicated that age (P = 0.003), surgical duration (P = 0.001), and pre-operative oral antibiotic use (P < 0.001) were independent factors that affect the incidence of SSI. Furthermore, a propensity-matched analysis confirmed the protective effect of oral antibiotic use, with a 1-day course of oral antibiotic producing a similar effect to a 3-day course. CONCLUSIONS: Age, surgical duration, and pre-operative oral antibiotic use were associated with the incidence of SSI. However, pre-operative oral antibiotic use was the only controllable factor. From the results of our study, pre-operative oral antibiotic use is recommended before elective colorectal surgery and a 1-day course is enough to provide the protective effect.

[Celecoxib increased cellular ATRA sensitivity of human colon cancer cell lines through COX-2-independent mechanisms].

Retinoid resistance has limited clinical activity of retinoids as differentiation-inducing and apoptosis-inducing drugs. The present study was designed to investigate whether celecoxib (selective COX-2 inhibitor) has effects on cellular retinoid sensitivity of human colon cancer cell lines and its possible mechanism. Cell viability was measured by MTT assay. Apoptosis was detected by Annexin-V/PI staining and flow cytometry assay. PGE2 production was measured by ELISA assay. Expression of RARbeta was assayed by Western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, and the addition of PGE2 did not affect the number of apoptotic cells induced by the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA on both cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines increased in celecoxib group and combination group. And the addition of PGE2 did not affect the expression of RARbeta induced by celecoxib either. In conclusion, celecoxib increased expression of RARbeta and cellular ATRA sensitivity through COX-2-independent mechanisms, which may provide a potential strategy for combination therapy.

The implication of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously inflammatory infiltration compared with EBV-negative gastric carcinoma. To date, the local immune status in EBVaGC and its relationship with patient prognosis and apoptosis of tumor cells are largely unknown. In this study, we evaluated the density of different types of tumor-infiltrating lymphocytes (TILs) in 53 EBVaGCs and 67 EBV-negative gastric carcinomas and analyzed its relationship with patient outcomes and apoptosis of tumor cells in EBVaGC. The average number of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, CD56+ natural killer cells, Fascin+ dendritic cells (DCs), and FoxP3+ Tregs and the average proportions of Ki-67, interleukin 1ß, granzyme B, interferon γ, and interleukin 10 in TILs were higher in EBVaGC, and CD8+ T cells were the predominant constituent cells of TILs in EBVaGC. Patients with higher numbers of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs survived longer in EBVaGC, and CD8+ T cells and Fascin+ DCs were independent prognostic factors for patient survival. Besides, CD8+ T cells were positively correlated with apoptotic index of tumor cells. However, the apoptosis of tumor cells was lower, and the expression of survivin and NF-κBp65 in tumor cells was up-regulated in EBVaGC. These findings suggested that CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs predict a better prognosis in EBVaGC; CD8+ T cells might through a nonapoptotic pathway eliminate tumor cells, thereby improving the patient prognosis.

Endoscopy-Assisted Laparoscopic Resections for Gastric Gastrointestinal Stromal Tumors: A Retrospective Study.

OBJECTIVE: To explore the safety, feasibility, and clinical curative effect of endoscopy-assisted laparoscopic resections for gastric gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: We retrospectively compared the general condition of 41 GIST patients undergoing endoscopy-assisted laparoscopic resections (n = 41, combined group) with those undergoing traditional open gastrectomy (n = 43, open surgery group). RESULTS: All patients survived during the surgery. The average operation time of the combined group and the open surgery group was 90 ± 40 minutes and 120 ± 60 minutes, respectively, and no significant difference (P = .088) was observed. Bleeding volume during operation was significantly lower [(50 ± 20 versus 150 ± 40) mL, P < .001] and recovery time of the gastrointestinal function was significantly shorter in the combined group [(2.02 ± 0.99) days versus (3.02 ± 1) days, P < .001]. No statistical difference was found in the postoperative complications (5% versus 12%, P = .442) or GIST recurrence (2.44% versus 2.33%, P = 1.000) between the two groups. Follow-up visit showed no death. CONCLUSION: For GIST patients who attempted to receive gastrectomy, endoscopy-assisted laparoscopic resections showed advantages on the operation time, bleeding volume, and recovery time and are suggested as a better alternative for GISTs.

Comparison of laparoscopic versus open complete mesocolic excision for right colon cancer.

AIM: To explore the feasibility, safety, efficacy, and short-term oncologic outcomes of laparoscopic-assisted complete mesocolic excision (CME) for right colon cancer. METHODS: The clinical data from 102 patients with right colon cancer who underwent laparoscopic CME (n = 53; LS group) and open CME (n = 49; OS group) from June 2012 to December 2013 were retrospectively reviewed. Outcomes of the two groups were compared. RESULTS: There were no conversions to open surgery in the LS group. The operative time in the LS group was similar to that in the OS group (194 ± 57 vs. 177 ± 51 min, respectively, p = 0.118). Intraoperative blood loss was significantly less in the LS group compared with the OS group (94 ± 56 vs. 118 ± 60 ml, respectively, p = 0.039). There was no difference in the total number of harvested lymph nodes (14 ± 6 vs. 13 ± 5, respectively, p = 0.313). The time to resume liquid diet (3 ± 2 vs. 5 ± 2 d, p < 0.001) and length of hospital stay (11 ± 4 vs. 14 ± 6 d, p = 0.002) were significantly shorter in the LS group. The rate of complications was similar between the groups (4% vs. 12%, respectively, p = 0.222). No recurrences were noted in either group during follow-up (range, 6-24 months). CONCLUSION: Laparoscopic CME is a safe, feasible, and effective minimally invasive procedure for right colon cancer.

Adult congenital intestinal malrotation accompanied by midgut volvulus: report of eight cases.

Congenital midgut malrotation is a complex gastrointestinal anomaly, which could easily lead to midgut volvulus and gastrointestinal obstruction. Large studies on congenital midgut malrotation in adults are rarely investigated. The current study aimed to explore the clinical profile and diagnostic modalities of congenital midgut malrotation in Chinese adult patients. Clinical and radiological data of eight adult patients with intestinal malrotation were retrospectively analyzed and related literatures were simultaneously reviewed. Mean age of patients was 41.25 years range, 14 to 63 years. Abdominal radiography and computerized tomography (CT) were conducted for all studied patients prior to surgery, and the diagnosis of congenital midgut malrotation was confirmed during surgery. All patients underwent volvulus reduction, Ladd's band loosening, and stage I appendectomy. In addition, three patients received additional extensive intestinal adhesion loosening, and one patient received resection of bowel up to 50 cm. All patients recovered well after surgery, and no recurrence and adhesive intestinal obstruction were reported. All three patients with malnutrition prior to surgery had gained significant weight. Thus, we consider that adult congenital intestinal malrotation accompanied with midgut volvulus should be treated with surgery as soon as possible. Preoperative colour ultrasonography and CT are helpful for definitive diagnosis.