Efficacy of artificial intelligence in reducing miss rates of GI adenomas, polyps, and sessile serrated lesions: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The aim of this study was to determine if utilization of artificial intelligence (AI) in the course of endoscopic procedures can significantly diminish both the adenoma miss rate (AMR) and the polyp miss rate (PMR) compared with standard endoscopy. METHODS: We performed an extensive search of various databases, encompassing PubMed, Embase, Cochrane Library, Web of Science, and Scopus, until June 2023. The search terms used were artificial intelligence, machine learning, deep learning, transfer machine learning, computer-assisted diagnosis, convolutional neural networks, gastrointestinal (GI) endoscopy, endoscopic image analysis, polyp, adenoma, and neoplasms. The main study aim was to explore the impact of AI on the AMR, PMR, and sessile serrated lesion miss rate. RESULTS: A total of 7 randomized controlled trials were included in this meta-analysis. Pooled AMR was markedly lower in the AI group versus the non-AI group (pooled relative risk [RR], .46; 95% confidence interval [CI], .36-.59; P < .001). PMR was also reduced in the AI group in contrast with the non-AI control (pooled RR, .43; 95% CI, .27-.69; P < .001). The results showed that AI decreased the miss rate of sessile serrated lesions (pooled RR, .43; 95% CI, .20 to .92; P < .05) and diminutive adenomas (pooled RR, .49; 95% CI, .26-.93) during endoscopy, but no significant effect was observed for advanced adenomas (pooled RR, .48; 95% CI, .17-1.37; P = .17). The average number of polyps (Hedges' g = -.486; 95% CI, -.697 to -.274; P = .000) and adenomas (Hedges' g = -.312; 95% CI, -.551 to -.074; P = .01) detected during the second procedure also favored AI. However, AI implementation did not lead to a prolonged withdrawal time (P > .05). CONCLUSIONS: This meta-analysis suggests that AI technology leads to significant reduction of miss rates for GI adenomas, polyps, and sessile serrated lesions during endoscopic surveillance. These results underscore the potential of AI to improve the accuracy and efficiency of GI endoscopic procedures.

Antitumoral Activity of the MEK Inhibitor Trametinib (TMT212) Alone and in Combination with the CDK4/6 Inhibitor Ribociclib (LEE011) in Neuroendocrine Tumor Cells In Vitro.

OBJECTIVES: This study assessed the antitumoral activity of the MEK inhibitor trametinib (TMT212) and the ERK1/2 inhibitor SCH772984, alone and in combination with the CDK4/6 inhibitor ribociclib (LEE011) in human neuroendocrine tumor (NET) cell lines in vitro. METHODS: Human NET cell lines BON1, QGP-1, and NCI-H727 were treated with trametinib or SCH772984, alone and in combination with ribociclib, to assess cell proliferation, cell cycle distribution, and protein signaling using cell proliferation, flow cytometry, and Western blot assays, respectively. RESULTS: Trametinib and SCH772984, alone and in combination with ribociclib, significantly reduced NET cell viability and arrested NET cells at the G1 phase of the cell cycle in all three cell lines tested. In addition, trametinib also caused subG1 events and apoptotic PARP cleavage in QGP1 and NCI-H727 cells. A western blot analysis demonstrated the use of trametinib alone and trametinib in combination with ribociclib to decrease the expression of pERK, cMyc, Chk1, pChk2, pCDK1, CyclinD1, and c-myc in a time-dependent manner in NCI-H727 and QGP-1 cells. CONCLUSIONS: MEK and ERK inhibition causes antiproliferative effects in human NET cell lines in vitro. The combination of the MEK inhibitor trametinib (TMT212) with the CDK4/6 inhibitor ribociclib (LEE011) causes additive antiproliferative effects. Future preclinical and clinical studies of MEK inhibition in NETs should be performed.

Inhibition of Wnt/ß-Catenin Signaling in Neuroendocrine Tumors in vitro: Antitumoral Effects.

BACKGROUND AND AIMS: Inhibition of Wnt/ß-catenin signaling by specific inhibitors is currently being investigated as an antitumoral strategy for various cancers. The role of Wnt/ß-catenin signaling in neuroendocrine tumors still needs to be further investigated. METHODS: This study investigated the antitumor activity of the porcupine (PORCN) inhibitor WNT974 and the ß-catenin inhibitor PRI-724 in human neuroendocrine tumor (NET) cell lines BON1, QGP-1, and NCI-H727 in vitro. NET cells were treated with WNT974, PRI-724, or small interfering ribonucleic acids against ß-catenin, and subsequent analyses included cell viability assays, flow cytometric cell cycle analysis, caspase3/7 assays and Western blot analysis. RESULTS: Treatment of NET cells with WNT974 significantly reduced NET cell viability in a dose- and time-dependent manner by inducing NET cell cycle arrest at the G1 and G2/M phases without inducing apoptosis. WNT974 primarily blocked Wnt/ß-catenin signaling by the dose- and time-dependent downregulation of low-density lipoprotein receptor-related protein 6 (LRP6) phosphorylation and non-phosphorylated ß-catenin and total ß-catenin, as well as the genes targeting the latter (c-Myc and cyclinD1). Furthermore, the WNT974-induced reduction of NET cell viability occurred through the inhibition of GSK-3-dependent or independent signaling (including pAKT/mTOR, pEGFR and pIGFR signaling). Similarly, treatment of NET cells with the ß-catenin inhibitor PRI-724 caused significant growth inhibition, while the knockdown of ß-catenin expression by siRNA reduced NET tumor cell viability of BON1 cells but not of NCI-H727 cells. CONCLUSIONS: The PORCN inhibitor WNT974 possesses antitumor properties in NET cell lines by inhibiting Wnt and related signaling. In addition, the ß-catenin inhibitor PRI-724 possesses antitumor properties in NET cell lines. Future studies are needed to determine the role of Wnt/ß-catenin signaling in NET as a potential therapeutic target.

Multiband mucosectomy versus endoscopic submucosal dissection and endoscopic submucosal excavation for GI submucosal tumors: short and long term follow-up.

AIMS: To evaluate the short- and long-term outcomes of 3 different endoscopic dissection techniques for upper gastrointestinal (GI) submucosal tumours (SMTs). METHODS: Data for 135 patients withGI SMTs who underwent multiband mucosectomy (MBM), endoscopic submucosal dissection (ESD), or endoscopic submucosal excavation (ESE) were retrospectively assessed. The en bloc resection rate, endoscopic complete resection rate, operation time, potential complications and local recurrence rate were compared. RESULTS: No significant differences were observed in the rate of endoscopic complete resections and pathologic complete resections among the three groups. For SMTs > 15 mm in width, the lowest en bloc resection rate was found for MBM (P = 0.000). MBM was also associated with the shortest procedure time, lowest perforation rate and lowest rate of major bleeding. ESE was the most effective procedure for muscularis propria (MP) lesions but was associated with the longest operation time (P < 0.01). The ESD and ESE groups had similar perforation rates (P > 0.05). No differences were observed in 4-year local recurrence rates among the groups (P = 0.945). CONCLUSIONS: MBM is a simple and effective method for the treatment of small SMTs and achieves clinical success rates similar to those of ESD and ESE. However, ESD and ESE are preferable for larger and deep lesions and are associated with a longer operation time. Nonetheless, all 3 techniques resulted in a low 4-year local recurrence rate. Large-scale randomized clinical trials are needed to further investigate these results.

Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro.

Peptide receptor radionuclide therapy in advanced neuroendocrine tumors (NETs) demonstrates a limited objective response rate. The therapeutic efficacy might be further increased by peptide receptor chemoradionuclide therapy. In this preclinical study, we explored the effects of 5-fluorouracil plus the DNA methyltransferase inhibitor decitabine or the histone deacetylase inhibitor tacedinaline on NET cells in vitro. Methods: Human NET cell lines BON1 and QGP1 were treated with 5-fluorouracil alone or in combination with decitabine or tacedinaline, respectively. Radiosensitivity was tested in combination with γ-irradiation at doses of 0, 2, 4, or 6 Gy by colony formation assay. Somatostatin receptor type 2 (SSTR2) expression and 68Ga-DOTATOC uptake by human NET cell lines were investigated by Western blot analysis and by a radioligand binding assay. Results: Treatment with 5-fluorouracil alone or in combination with decitabine or tacedinaline reduced tumor cell viability and induced apoptosis, enhanced radiosensitivity in BON1 and QGP1 cells, induced SSTR2 expression, and resulted in increased radioligand binding of 68Ga-DOTATOC in NET cells. Conclusion: This preclinical study demonstrated that 5-fluorouracil alone or in combination with decitabine or tacedinaline caused radiosensitization of tumor cells, upregulation of SSTR2 expression in tumor cells, and increased radioligand binding of 68Ga-DOTATOC to these tumor cells. These preclinical in vitro findings indicate that 5-fluorouracil in combination with epigenetic modifiers might be a putative strategy to improve the treatment efficacy of peptide receptor chemoradionuclide therapy in NET.

Efficacy of narrow-band imaging in detecting early esophageal cancer and risk factors for its occurrence.

OBJECTIVE: The aim of this study is to evaluate the efficacy of narrow-band imaging (NBI) in the detecting early esophageal cancer and precancerous lesions and to investigate the risk factors for its occurrence. METHODS: The esophagus was examined with ordinary endoscopy, NBI, and iodine staining. All the lesions were confirmed by histopathologically as the gold standard; NBI and intrapapillary capillary scale (IPCL) scale were compared with pathologic diagnosis. The accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated. Subgroup analysis was performed between the elderly vs. younger group, and head and neck squamous cell cancer (HNSCC) vs. non-HNSCC patients. RESULTS: Ninety lesions were detected with ordinary endoscopy, 108 with NBI, and 120 with iodine staining. All esophageal cancers were detected both by NBI and by iodine staining. Accuracy, sensitivity, and specificity for esophageal cancer and precancerous lesion were 67.8%, 58.1%, and 76.6%; 92%, 89.7%, and 96%; 93.4%, 93.4%, and 93.2%, respectively. NBI endoscopy and iodine staining were superior to ordinary endoscopy for detecting esophageal cancer and precancerous lesions (p < 0.05). NBI showed better detection of esophageal neoplasms in the elderly patients (p < 0.001). The incidence of multiple squamous cell cancers (SCCs) was significantly higher in non-elderly group (p = 0.009). NBI can also detect more esophageal neoplastic lesions in patients with head and neck cancers (p = 0.003). CONCLUSIONS: NBI endoscopy appears as effective as Lugol staining to detect and screen the early esophageal cancer. NBI shows better detection of esophageal neoplasms in the elderly patients. The incidence of multiple SCCs was much higher in non-elderly patients.

Supportive therapy in gastroenteropancreatic neuroendocrine tumors: Often forgotten but important.

Neuroendocrine tumors (NETs) are a group of rare and heterogeneous malignancies that can develop in various organs. A significant number of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is functionally active and presents with symptoms related to the secretion of biologically active substances, leading to the development of distinct clinical syndromes. There are various therapeutic approaches for GEP-NETs, including curative surgery, palliative surgery, local-ablative and loco-regional therapies as well as systemic therapeutic options including peptide receptor radionuclide therapy, cytotoxic therapy, and molecularly targeted therapies. Specific supportive therapy of patients with NETs includes management or prevention of hormone-related clinical syndromes and paraneoplastic states. Supportive therapy plays a key role in NET treatment. Supportive therapy includes debulking surgery and interventional radiologic techniques to reduce tumour bulk or load, as well as systemic medical treatment options to manage or prevent hypersecretion syndromes and treatment-related side effects. Supportive therapies are a type of of comprehensive treatment addressing the patient as a whole person throughout the process of NET treatment. Therefore, supportive therapy also encompasses psychosocial support, expert nursing, nutritional support and management of cancer related pain.

Simultaneous endoscopic submucosal dissection for multiple early gastric cancers in a low volume center.

The aim of the study is to evaluate the safety and efficacy of simultaneous endoscopic submucosal dissection (ESD) for multiple early gastric cancers.A total of 70 solitary early gastric cancers from 70 patients and 20 multiple early gastric cancers from 10 patients were included in this retrospective study. The curative resection rate, en bloc resection rate, procedure-related complications, and local recurrence were compared between the 2 groups.There was no statistical difference in the rate of complete resection, en bloc resection, and curative resection between the 2 groups (P > .05). No significant difference was found with respect to the occurrence of postoperative bleeding (P > .05). Procedure time was significantly longer in the simultaneous group than that in the single group (87.6 ±â€Š25.1 min vs 54.6 ±â€Š22.0 min, P = .004). The overall incidence of synchronous early gastric cancer was 7.5%.Simultaneous ESD for multiple early gastric cancers is a safe and feasible choice in low-volume hospital. The entire stomach should be examined meticulously during and after ESD. Larger randomized studies are needed to validate our results.

Comparison of Endoscopic Resection and Minimally Invasive Esophagectomy in Patients With Early Esophageal Cancer.

OBJECTIVE: To determine whether endoscopic resection (ER) and minimally invasive esophagectomy (MIE) are safe and effective for treating squamous intraepithelial neoplasia of the esophagus. MATERIALS AND METHODS: This study retrospectively analyzed a total of 99 consecutive patients with pathologically confirmed early esophageal cancer between December 2007 and 2011. ER was performed in 59 patients, whereas MIE was performed in 40 patients. We compared the 2 groups according to R0 resection rates, treatment-related complications, mean hospital stay, local recurrence rates, and 3- and 4-year overall survival. RESULTS: No significant differences were found in the R0 resection rates between ER and MIE (94.9% vs. 97.5%, P>0.05). The occurrence rate of minor complications in the ER group was significantly lower than that in the thoracoscopic esophagectomy group (11.8% vs. 32.5%, P>0.05). The mean operative time in the ER group was 74±23 minutes, which was significantly shorter than that in the MIE group (298±46 min). The average length of hospital stay in the ER group was significantly shorter than that in the MIE group (P<0.001). No significant differences were observed in the local recurrence rates between the 2 groups (P>0.05). Similarly, no differences were found in the 3-year survival rate (ER: 96.6%, vs. MIE: 97.5%, P>0.05) and 4-year survival rate (ER: 91.5% vs. MIE: 90%, P>0.05) between the 2 groups. CONCLUSIONS: ER achieves the same positive results as MIE in the treatment of early esophageal cancer and is associated with a lower complication rate, a shorter recovery time, and a similar survival rate. However, multiple ER procedures were required for several patients in this study.

Multiband Mucosectomy Versus Endoscopic Submucosal Dissection for Treatment of Squamous Intraepithelial Neoplasia of the Esophagus.

BACKGROUND & AIMS: We compared the efficacy and safety of multiband mucosectomy (MBM) vs endoscopic submucosal dissection (ESD) for the treatment of squamous intraepithelial neoplasia of the esophagus. METHODS: We performed a retrospective study of 78 patients with squamous intraepithelial neoplasia of the esophagus who received either ESD or MBM between January 2009 and January 2011 at the Tengzhou Central People's Hospital in China. We compared rates of bloc resection and curative resection, as well as complications and local recurrence, between groups. RESULTS: Overall, there was no statistical difference in the rate of complete resection between patients who received ESD (95.8%) vs MBM (93%) (P > .05). For tumors less than 15 mm in width, ESD produced a significantly higher rate of en bloc resection (100%) and curative resection (92.3%) than MBM (44.8% and 41%; P < .05). No significant differences were found between lesions less than 15 mm. MBM had a significantly shorter procedure time (38 ± 11 min) than ESD (84 ± 35 min) (P < .05). Major bleeding occurred in 1.85% of MBM procedures and in 16.7% of ESD procedures (P > .05). ESD led to perforations in 8.3% of cases, whereas MBM did not lead to any perforations (P < .05). No significant differences were found between groups in proportions of cases with postoperative esophageal strictures (16.7% vs 14.8%; P > .05) or the 3-year rate of local recurrence (P > .05). CONCLUSIONS: Based on a retrospective comparison of patients who underwent ESD vs MBM for squamous intraepithelial neoplasia of the esophagus, ESD should be reserved for patients with larger neoplastic lesions (>15 mm), with respect to the success of attempted en bloc resection and the number of curative resections achieved. However, ESD has longer procedure times and higher rates of complication. MBM allows for safe and easy piecemeal resections, and is associated with similar levels of clinical success as ESD for lesions less than 15 mm. Large, randomized, controlled studies are needed to determine which endoscopic resection modality is superior for patients with high-grade intraepithelia neoplasms.

A tandem trial of HD-NBI versus HD-WL to compare neoplasia miss rates in esophageal squamous cell carcinoma.

BACKGROUND/AIMS: To determine whether the use of narrow-band imaging (NBI) system could enhance the detection rate of esophageal squamous cell carcinoma and precancerous lesions during endoscopic examination of the esophagus. METHODOLOGY: 113 patients were randomized to undergo endoscopic examination using high definition television (HDTV) narrow band imaging (NBI) endoscopy or HDTV WL endoscopy. The primary endpoint was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate. RESULTS: The number of esophageal cancer and high grade intraepithelial neoplasia lesions detected by HD-NBI and HD-WL was 45 and 21, respectively. The neoplasm miss rate per lesion and per patient with HD-NBI showed significant difference compared with that of HD-WL (P <0.05). Characteristics of lesions missed by use of HD-NBI were similar to those missed by use of HD-WL; all missed lesions were high grade intraepithelial neoplasia lesions. Significant difference was observed between NBI and WL in adenoma detection rate (70.2% vs. 35.7%, P < 0.01). CONCLUSIONS: Endoscopy with HD-NBI seems to improve the detection of esophageal cancer and precancerous lesions, high definition may be tested for its effect on detection of esophageal cancer and precancerous lesions in the future. These results indicate that endoscopy routinely using the NBI system for the surveillance of esophageal cancer and precancerous lesions may be recommended.

Clinical value of multiband mucosectomy for the treatment of squamous intraepithelial neoplasia of the esophagus.

BACKGROUND AND AIM: To evaluate the clinical value of multiband mucosectomy (MBM) for the treatment of squamous intraepithelial neoplasia of the esophagus. METHODS: A total of 51 lesions located at esophagus from 43 patients were treated with MBM, among which 11 were diagnosed as middle-grade intraepithelial neoplasia, 25 as high-grade intraepithelial neoplasia, and 15 as early esophageal cancer pathologically. Primary end-points were the rate of complete endoscopic resection and the mean operation time; the second end-points were the postoperative local recurrence rate and acute plus early complications. The histopathological results were compared between pre-MBM biopsy and MBM specimens. All patients were followed up endoscopically. RESULTS: A total of 52 MBM procedures with 180 resections were performed in 43 patients. The complete endoscopic resection was achieved in 92.3% (95% confidence interval [CI] 81.8-96.9%). The sizes of the lesions ranged from 10 × 8 mm to 25 × 23 mm. The mean operation time is 37 ± 5 min. The operative acute bleeding complication was 7.6% (95% CI 3-18.1%); no perforations occurred. Early complications consisted of delayed bleeding (one patient 1.9%; 95% CI 0.3-10.1%) and slight esophageal stenosis (one patient). The histopathological diagnosis of 26 cases (51%) was consistent between biopsy and MBM samples, while 20 lesions exhibited higher grade dysplasia. The local recurrence rate was 6.9% (3/43) at 1 year, 9.3% (4/43) at 2 years, and 9.3% at 2.5 years. No death occurred during follow-up. CONCLUSIONS: MBM is a safe and effective technique for the treatment of early esophageal cancer and precancerous lesions.

Meta-analysis for evaluating the accuracy of endoscopy with narrow band imaging in detecting colorectal adenomas.

BACKGROUND AND AIM: The aim of this study was to determine whether the use of the narrow band imaging (NBI) system could enhance the accuracy of adenoma detection during an endoscopic examination of the colon and rectum. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched along with a hand search of abstracts from relevant conferences up to June 2011. The rates of adenoma and flat adenoma detection, and withdrawal time were analyzed using Review Manager 4.2. RESULTS: A total of 3049 subjects in eight trials were included. Meta-analysis revealed that there was no statistically significant difference in the rates of adenoma detection between the NBI group and the white light colonoscopy group (pooled relative risk [RR]: 1.09, 95% confidence interval [CI]: 1.00-1.19, P = 0.05). However, after exclusion of high-definition television modalities, the rate of adenoma detection by NBI was significantly higher than that by white light, particularly for patients with one adenoma (pooled RR 1.36, 95%CI 1.07-1.71, P = 0.02). Endoscopy with the NBI system significantly increased the rate of flat adenoma detection (pooled RR 1.96, 95%CI 1.09-3.52, P = 0.02). However, endoscopy with NBI had longer withdrawal time than that with white light (pooled weighted mean difference: 0.90, 95%CI: 0.38-1.42, P = 0.0006). CONCLUSIONS: Endoscopy with NBI seems to improve the detection of flat adenomas, particularly with high-definition technology, but prolongs the withdrawal time. These results indicate that endoscopy routinely using the NBI system for the surveillance of adenomas may be recommended after the technique is further modified.

Chemopreventive effect of epigallocatechin-3-gallate (EGCG) and folic acid on the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rat model.

OBJECTIVE: To investigate the chemopreventive effect and mechanisms of epigallocatechin-3-gallate (EGCG) and folic acid on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis. METHODS: A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG+folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki-67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase-mediated nick-end labeling (TUNEL) assay, respectively. RESULTS: The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P=0.011). Ki-67 expression in cancerous tissues of group ME and MEF also decreased significantly (P=0.038, P=0.009), while apoptosis of group ME, MF and MEF increased significantly (P=0.000, P=0.003, P=0.000). CONCLUSION: EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.

[Selective cyclooxygenase-2 inhibitors for the prevention of colorectal adenomas: a meta-analysis].

OBJECTIVE: To determine the validity and safety of selective cyclooxygenase (COX)-2 inhibitors for the prevention of colorectal adenomas. METHODS: The relevant data were retrieved from Medline (1966 to 2006), OVID (1996 to January 2007), EMBASE (1980 to January 2007), Chinese Cochrane Centre databases (up to January 2007) and Chinese Biological Medicine Disk (CBM disk, 1997 to 2007). Methodological quality assessment was based on the Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan4.2 was used for meta-analysis. RESULTS: Six randomized clinical trials (5708 patients) were included in the study. Compared with placebo, selective COX-2 inhibitors lowered the detection rates of both adenomas and advanced adenomas (RR: 0.70, 95% CI: 0.55 - 0.88, P = 0.0003 and RR: 0.69, 95% CI: 0.53 - 0.89, P = 0.005). No significant difference was observed in the number of adverse events between patients taking selective COX-2 inhibitors and those taking placebo (RR: 1.07, 95% CI: 0.98 - 1.17, P = 0.11). Compared with placebo, selective COX-2 inhibitors increased the risk of cardiovascular events (RR: 1.21, 95% CI: 1.09 - 1.33, P = 0.0002). CONCLUSION: Selective COX-2 inhibitors can induce sufficient regression of colorectal adenomatous polyps and thus be used for chemoprevention of colorectal neoplasms. However, because of the potential cardiovascular events, it is not routinely recommended for this indication.

[Chemopreventive effect of oxymatrine on N-methyl-N'-nitro-N-nitrosoguanidine induced gastrointestinal cancer: experiment with rats].

OBJECTIVE: To investigate the chemopreventive effect of oxymatrine on the N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer. METHODS: Ninety-nine male Wistar rats were randomly allocated into four groups: MNNG treated group (36 rats, fed with MNNG for 28 weeks so as to establish rat model of gastrointestinal cancer), oxymatrine intervention group (n = 23, fed with MNNG and oxymatrine), negative control group (20 rats, fed with mixed feed), and oxymatrine control group (20 rats. fed with normal food and oxymatrine). 28 weeks later all the rats began to be fed with normal food for 4 weeks. two rats in the MNNG treated group were killed at the 28 th, 32 nd, and 40 th weeks of the experiment respectively to observe the tumor growth in the gastrointestinal tract. At the 44 th week all the rats were sacrificed and assessed for the presence of gastrointestinal tumor. Immunohistochemistry was used to detect the expression of Ki67, an antigen associated to the proliferation of nucleus. The cell apoptosis rate in the tumor tissue was detected by TUNEL method. RESULTS: Experiment was completed in 92 rats (92.93%). The incidence of gastrointestinal tumor in the MNNG treated group was 58.62% (17/29), significantly higher than that in the oxymatrine treated group (30.43%, 7/23, P < 0.05). Duodenum tumor was found in 1 rat of the negative control group and no tumor was found in the oxymatrine control group. The average volume of tumor in the MNNG treated group was 2.56 (full range 49.5) cm(3), significantly larger than those of the oxymatrine treated group [0.03 (full range 0.009) cm(3)], and negative control group (0.5 cm(3)) (both P < 0.05). The incidence rates of gastrointestinal mucosal ulceration and dysplasia of the MNNG treated group were higher than those of the oxymatrine treated group (both P < 0.05). The expression rate of Ki67 in the tumor tissue of the MNNG treated group was (48 +/- 18)%, significantly higher than that of the oxymatrine treated group [(25 +/- 24)%, P < 0.05]. The apoptotic rate of tumor cell in the MNNG treated group was (11 +/- 7)%, significantly lower than that in the oxymatrine treated group [(30 +/- 16)%, P = 0.002]. CONCLUSION: Inhibiting the development and inducing the apoptosis of gastrointestinal tumor induced by MNNG, oxymatrine can be used as a chemopreventive agent against gastrointestinal tumor.