Huaier Granule Combined with Tegafur Gimeracil Oteracil Potassium Promotes Stage IIb Gastric Cancer Prognosis and Induces Gastric Cancer Cell Apoptosis by Regulating Livin.

Gastric cancer is one of the most common malignancies worldwide, with high morbidity and poor survival rate. Its prognosis remains unsatisfactory, with a 5-year survival rate of <30%. Studies have indicated that Huaier granules have good antitumor efficacy and safety in several solid malignant tumors. Recent studies have also found that Huaier polysaccharides can promote apoptosis in numerous tumor cells, although only few studies have focused on the effects of Huaier granules on gastric cancers and the mechanisms underlying their antitumor role. We retrospectively evaluated stage IIb gastric cancer patients at Xiangya Hospital, Central South University, through our outpatient system from January 2013 to December 2015. Fifty-four patients were in the Huaier+Tegafur Gimeracil Oteracil Potassium (TGOP) group and 72 in the TGOP group. Further, we conducted CCK8, colony formation, Annexin V-FITC/PI, Western blot, RT-PCR, and plasmid transfection assays to analyze the mechanism by which Huaier polysaccharides play an antitumor role. We confirmed that Huaier granules combined with Tegafur Gimeracil Oteracil Potassium could promote patient prognosis, with a better disease-free survival rate (51.32 ± 2.23 vs. 44.19 ± 2.26, p = 0.034) and overall survival rate (56.81 ± 1.32 vs. 51.32 ± 1.69, p = 0.020). Moreover, through cell proliferation assays, Western blot, RT-PCR, and detection of Livin expression at the mRNA and protein levels, we found that Huaier polysaccharides could promote gastric cancer cell apoptosis and inhibit gastric cancer cell proliferation in a time- and dose-dependent manner. Finally, we demonstrated that Huaier polysaccharides promote gastric cancer cell apoptosis through the regulation of Livin expression. Overexpression of Livin reversed the gastric cell apoptosis induced by Huaier polysaccharides. Huaier granules combined with Tegafur Gimeracil Oteracil Potassium ameliorated stage IIb gastric cancer prognosis and induced gastric cancer cell apoptosis by regulating Livin.

Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study.

BACKGROUND: Preoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs. METHODS: We retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded. RESULTS: A total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%. CONCLUSION: Preoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.

Hand-assisted laparoscopic surgery versus open surgery for colorectal disease: a systematic review and meta-analysis.

BACKGROUND: Laparoscopic colorectal surgery remains one of the most challenging techniques to learn. METHODS: The authors collected studies that have compared hand-assisted laparoscopic surgery (HALS) and open surgery for the treatment of colorectal disease over the past 17 years. Data of interest for HALS and open surgery were subjected to meta-analysis. RESULTS: Twelve studies that included 1,362 patients were studied. In total, 2.66% of HALS procedures were converted to laparotomy. Compared with the open surgery group, blood loss, rate of wound infection, and ileus in the HALS group decreased, and incision length, recovery of gastrointestinal function, and hospitalization period were shorter. There were no significant differences in operating time, hospitalization costs, mortality, and complications, including urinary tract infection, pneumonia, and anastomotic leak, between the groups. CONCLUSIONS: HALS has the advantages of minimal invasion, lower blood loss, shorter incision length, and faster recovery, and it can shorten the length of hospitalization without an increase in costs. The drawbacks are that a small number of patients who undergo HALS may need to be converted to laparotomy, and the oncologic safety and long-term prognosis are not clear.

Single-incision versus conventional three-incision laparoscopic appendicectomy for appendicitis: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was designed to investigate the safety and efficacy of single-incision laparoscopic appendicectomy (SILA) and three-incision laparoscopic appendicectomy (TILA) in the treatment of appendicitis. MATERIALS AND METHODS: Studies published since 1992 that compared SILA versus TILA in laparoscopic appendicectomy were collected. Data on operative parameters, postoperative recovery, postoperative pain and complications, and hospitalization costs for SILA and TILA were meta-analyzed using fixed-effect and random-effect models. RESULTS: Seventeen studies (1 randomized controlled trial and 16 retrospective studies) that included 1809 patients were studied. Of these patients, 793 and 1016 had undergone SILA and TILA, respectively. There was significantly shorter length of hospital stay; however, there were evidently higher conversion rate, and perhaps higher surgical difficulty and hospitalization costs for SILA compared with TILA. Other outcome variables such as operative time, blood loss, time to first oral intake, postoperative pain and complications were not found to be statistically significant for either group. CONCLUSIONS: Compared with TILA, SILA has the advantage of shorter hospital stay, and it can achieve comparable operative time, blood loss, postoperative recovery, postoperative pain and complications with TILA. The drawback is that SILA is associated with higher conversion rate, and perhaps higher surgical difficulty and hospitalization costs. Whether it can achieve improvement in cosmesis remains to be confirmed.

Laparoscopic versus open right hemicolectomy for colon cancer: a meta-analysis.

OBJECTIVE: This meta-analysis was designed to assess the feasibility and safety of laparoscopic right hemicolectomy for colon cancer. RESEARCH DESIGN: A systematic search of the MEDLINE, EMBASE, and Cochrane databases identified 12 studies that met the inclusion criteria for data extraction. Publications that compared laparoscopic right hemicolectomy and open right hemicolectomy for treatment of colon cancer in the past 20 years were collected for review. The primary outcomes used for meta-analysis were operating time, blood loss, number of harvested lymph nodes, time to first flatus, postoperative hospital stay, postoperative complications, mortality, and rate of recurrence. RESULTS: Twelve studies that included 1057 patients were examined. Of these patients, 475 and 582 had undergone laparoscopic right hemicolectomy and open right hemicolectomy, respectively. There were significant reductions in blood loss, time to first flatus, postoperative hospital stay, and rate of wound but a operating time for laparoscopic right hemicolectomy compared with open right hemicolectomy. Other outcome variables such as number of harvested lymph nodes, postoperative complications except wound infection, mortality, and rate of recurrence were not found to be statistically significant for either group. CONCLUSIONS: Compared with open right hemicolectomy, laparoscopic right hemicolectomy has the advantages of minimal invasion, faster recovery, and a lower rate of wound infection, and it can achieve the same degree of radicality and short-term prognosis as open right hemicolectomy. The drawback is that the operative time is longer.

Medial versus lateral approach in laparoscopic colorectal resection: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to investigate the safety and efficacy of the medial approach (MA) and the lateral approach (LA) in the treatment of colorectal disease. METHODS: Studies published since 1994 that compared MA versus LA in laparoscopic colorectal resection were collected. Data on conversion rate, operative time, blood loss, number of harvested lymph nodes, hospital stay, complications, mortality, rate of recurrence, and hospitalization costs for MA and LA were meta-analyzed using fixed-effect and random-effect models. RESULTS: Five cohort studies (2 randomized controlled trials and 3 retrospective studies) that included 881 patients were studied. Of these patients, 475 and 582 had undergone laparoscopic colorectal resection via MA and LA, respectively. There were significant reductions in conversion rate and operative time and possible reductions in blood loss and hospitalization costs for MA compared to LA; however, there were fewer harvested lymph nodes for MA compared with LA, which remains to be further studied. Other outcome variables such as postoperative complications, postoperative immune function, mortality, and rate of recurrence were not found to be statistically significant for either group. Sensitivity analysis on the pooled data from randomized controlled trials showed that the conversion rates were not significantly different between MA and LA. CONCLUSIONS: Compared with the lateral approach, the medial approach has the advantages of shorter operative time and possibly lower conversion rate; it also can be as safe as the lateral approach. Whether the MA has less blood loss and lower hospitalization costs remains to be confirmed, and its oncological safety and long-term prognosis are not clear. Due to insufficient data from a limited number of studies, inadequate assessment of the results may arise.

An integrated genome-wide approach to discover tumor-specific antigens as potential immunologic and clinical targets in cancer.

Tumor-specific antigens (TSA) are central elements in the immune control of cancers. To systematically explore the TSA genome, we developed a computational technology called heterogeneous expression profile analysis (HEPA), which can identify genes relatively uniquely expressed in cancer cells in contrast to normal somatic tissues. Rating human genes by their HEPA score enriched for clinically useful TSA genes, nominating candidate targets whose tumor-specific expression was verified by reverse transcription PCR (RT-PCR). Coupled with HEPA, we designed a novel assay termed protein A/G-based reverse serological evaluation (PARSE) for quick detection of serum autoantibodies against an array of putative TSA genes. Remarkably, highly tumor-specific autoantibody responses against seven candidate targets were detected in 4% to 11% of patients, resulting in distinctive autoantibody signatures in lung and stomach cancers. Interrogation of a larger cohort of 149 patients and 123 healthy individuals validated the predictive value of the autoantibody signature for lung cancer. Together, our results establish an integrated technology to uncover a cancer-specific antigen genome offering a reservoir of novel immunologic and clinical targets.

[Expression and significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors].

OBJECTIVE: To explore the expression and clinical significance of Slug, E-cadherin and N-cadherin in gastrointestinal stromal tumors (GIST). METHODS: Seventy eight GIST specimens removed surgically from 2004 to 2007 were collected from the Department of Gastrointestinal Surgery at Guizhou Provincial People's Hospital. There were 48 males and 30 females with an age range of 28 - 87 years old. The expressions of Slug, E-cadherin and N-cadherin in GIST were determined by immunohistochemistry. And the correlations with their clinicopathologic characteristics were analyzed. RESULTS: The positive rates of Slug, E-cadherin and N-cadherin in GIST were 53.8% (42/78), 35.9% (28/78) and 75.6% (59/78) respectively. And the differences were statistically significant (χ(2) = 24.98, P < 0.05). Slug was expressed markedly higher in the cases of GIST with distant metastasis or distant metastasis and local invasion: 75% (18/24) vs 44.4% (24/54), 63.6% (28/44) vs 41.2% (14/34), both P < 0.05. And E-cadherin was expressed markedly lower in the cases of GIST with distant metastasis: 16.7% (4/24) vs 44.4% (24/54), P < 0.05. The expression of N-cadherin was not significantly different between its clinicopathological characteristics (allP > 0.05). The expression of Slug correlated negatively with that of E-cadherin (r(s) = -0.267, P = 0.018). But it had no correlation with that of N-cadherin (r(s) = 0.056, P = 0.625). CONCLUSION: Slug is expressed markedly higher while E-cadherin markedly lower in metastatic GIST, and both are closely correlated with the metastasis of GIST.

Meta-analysis of laparoscopy-assisted distal gastrectomy with D2 lymph node dissection for gastric cancer.

BACKGROUND: To assess the value of laparoscopy-assisted distal gastrectomy with D2 dissection for treatment of gastric cancer. METHODS: We collected studies that have compared laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 dissection for treatment of gastric cancer in the past 15 years. Data of interest for LADG and ODG were subjected to meta-analysis using a fixed-effect and random-effect model. RESULTS: We analyzed 8 studies that included 1,065 patients. There were significant differences in operating time, blood loss, time to first flatus and first eating, postoperative hospital stay, and postoperative complications between the LADG and ODG groups. Compared with the ODG group, blood loss and complications in the LADG group decreased, time to recovery of gastrointestinal function and hospitalization period were shorter, but operating time was longer. There were no significant differences in the number of harvested lymph nodes, mortality, and rate of recurrence between the groups. CONCLUSIONS: Compared with ODG, LADG with D2 dissection has the advantages of minimal invasion, faster recovery, and fewer complications, and it can achieve the same degree of radicality and short-term prognosis as ODG. The drawbacks are that the operating time is slightly longer and long-term prognosis is not clear.

Sonographically guided transthoracic biopsy of peripheral lung and mediastinal lesions: role of contrast-enhanced sonography.

OBJECTIVES: The purpose of this study was to assess the impact of contrast-enhanced sonography on sonographically guided transthoracic needle biopsy of lung lesions. METHODS: A total of 121 patients underwent sonographically guided transthoracic needle cutting biopsy. Of the 121 patients, 62 (contrast-enhanced sonography group) underwent contrast-enhanced sonography before biopsy, and the information from contrast-enhanced sonography was used to optimize the biopsy procedure. The remaining 59 patients constituted the non-contrast-enhanced sonography group. The enhancement patterns and echogenicity were evaluated by the consensus of 2 sonographers. The diagnostic efficacy was compared between the contrast-enhanced and non-contrast-enhanced sonography groups. RESULTS: The enhancement intensity and extent varied greatly among different thoracic lesions, and an anechoic area (necrosis) was revealed in 26 of 62 lesions (41.9%) lesions after administration of the contrast agent. The overall diagnostic accuracy of sonographically guided transthoracic biopsy in this study was 85.9% (104 of 121). In the contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 58 of 62 lesions (93.6%). In the non-contrast-enhanced sonography group, the initial biopsy led to correct diagnosis in 46 of 59 lesions (78.0%). The difference in the diagnostic accuracy between the contrast-enhanced and non-contrast-enhanced sonography groups was statistically significant (P < .05). CONCLUSIONS: Contrast-enhanced sonography enables differentiation of viable from necrotic portions of thoracic lesions and has a positive impact on the diagnostic efficacy of sonographically guided transthoracic needle biopsy.

[Meta-analysis of laparoscopic and open repair of perforated peptic ulcer].

OBJECTIVE: To assess the safety and feasibility of laparoscopic and open repair of perforated peptic ulcer. METHODS: Studies on comparison between laparoscopic repair(LR) and open repair(OR) of perforated peptic ulcer were collected. Data of operating time, blood loss, time to first flatus, postoperative hospital stay, postoperative complications and mortality between LR group and OR group were meta-analyzed using fixed effect model and random effect model. RESULTS: Nineteen studies including 1507 patients were selected for this study,including laparoscopic surgery(n=673) and open surgery(n=834). There were significant differences in blood loss, time to first flatus, postoperative hospital stay, wound infection rate and mortality between LR group and OR group. However, no significant differences existed in operative time, postoperative sepsis, pulmonary infection, abdominal abscess, and suture leakage between the two groups. CONCLUSIONS: Laparoscopic repair of perforated peptic ulcer is associated with improved outcomes in terms of less blood loss, quicker recovery, and lower rates of wound infection and mortality. Laparoscopic repair of perforated peptic ulcer is safe and feasible.

Radiotherapy of unicentric mediastinal Castleman's disease.

Castleman's disease is a slowly progressive and rare lymphoproliferative disorder. Here, we report a 55-year-old woman with superior mediastinal Castleman's disease being misdiagnosed for a long term. We found a 4.3 cm mass localized in the superior mediastinum accompanied with severe clinical symptoms. The patient underwent an exploratory laparotomy, but the mass failed to be totally excised. Pathologic examination revealed a mediastinal mass of Castleman's disease. After radiotherapy of 30 Gy by 15 fractions, the patient no longer presented previous symptoms. At 3 months after radiotherapy of 60 Gy by 30 fractions, Computed tomography of the chest showed significantly smaller mass, indicating partial remission. Upon a 10-month follow-up, the patient was alive and free of symptoms.

[Necessity of splenectomy in radical resection of gastric cancer: a meta-analysis].

OBJECTIVE: To evaluate the necessity of splenectomy in radical resection of gastric cancer. METHODS: Twelve studies comparing outcomes after radical resection of gastric cancer with or without splenectomy were identified. Both fixed effect model and random effect model were used. RESULTS: There were 2628 patients in total. There were significant differences in complications between splenectomy group and spleen-preserving group(OR=1.91, 95% CI:1.28-2.87, P<0.05), while no significant difference in 5-year survival rate was noticed(HR=0.90, 95% CI:0.73-1.11, P>0.05). CONCLUSION: Radical resection of gastric cancer combined with splenectomy is not associated with improved survival but increased postoperative complications.

[Clinical significance of expressions of tumor markers in peripheral blood in non-small cell lung cancer].

OBJECTIVE: To investigate the expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in peripheral blood from the patients with non-small cell lung cancer and analyze their correlations with non-small cell lung cancer. METHODS: The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA were detected by nested reverse transcription-PCR assay in peripheral blood from the patients with non-small cell lung cancer (n = 120), benign pulmonary disease (n = 106) and from healthy subjects (n = 80) so as to further investigate their relationship with clinicopathological features and prognosis. Meantime we also examined the sensitivity, specificity and accuracy of combination detection. RESULTS: The expressions of BJ-TSA-9, CK19 and Pre-proGRP mRNA in non-small cell lung cancer patients were 56.7%, 57.5%, 35.0%, higher than that of benign pulmonary disease (0.9%, 6.6%, 5.7%) and healthy groups (0, 3.8%, 0, all P < 0.05). The ROC curves indicated the sensitivity of combined detection was 84.3% and the specificity of combined detection was 94.6%. Univariate analysis revealed that the clinical stage, the ECOG score and the number of positive marker had significant association with overall survival (OS) (χ(2) = 67.928, 95.981, 60.285, all P = 0.000). Multivariate analysis indicated that the clinical stage, ECOG score and the number of positive marker was an independent prognostic factor each (HR = 2.866, 4.251, 1.845, all P = 0.000). CONCLUSION: BJ-TSA-9, CK19 and Pre-proGRP mRNA may be the specific and sensitive markers to detect circulating tumor cells in the peripheral blood of non-small cell lung cancer patients.

Detection of circulating cancer cells in lung cancer patients with a panel of marker genes.

The current study was undertaken to examine the circulating cancer cells of lung cancer patients using a panel of markers and to evaluate the clinical significance of such tests. Peripheral blood mononuclear cells (PBMCs) from 134 lung cancer patients, 106 benign pulmonary disease, and 80 healthy individuals were isolated and assessed by nested reverse transcription-PCR assay for the expression of three different tumor markers, including tumor specific antigen 9 (TSA-9), Keratin 19 (KRT-19), and Pre-progastrin-releasing peptide (Pre-proGRP). Receiver operating characteristic curve (ROC) analysis showed that the combination of these markers was highly sensitive and specific in differentiating cancer patients from healthy and benign pulmonary disease controls. Of the 134 lung cancer patient blood samples, 84.3% expressed at least one tumor marker. A significant correlation was observed between the number of positive markers and disease stage and progression. Positivity of more than one marker predicted a poor response to therapy and short survival time in non-small cell lung cancer patients.

Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma.

AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma. METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300. RESULTS: The replicative multiples in Hep3B and HepG II after 48 h of CNHK300 proliferation were 40625 and 65326 fold, respectively, similar to that of wtAd5. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. CONCLUSION: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

[Androgen receptor and SMRT].

OBJECTIVE: To explore the interaction between androgen receptor (AR) and silencing mediator for retinoid and thyroid hormone receptor (SMRT) and their interaction site. Methods We recombined and constructed AR, SMRT gene and gene fragments, in vitro translated 35S fusion proteins to investigate the relationship between AR and SMRT using transient transfection, mammalian two-hybrid test, GST pull-down assay, and indirect immunofluorescence staining. Results AR possessed an intrinsic transcriptional repression activity and AR interacted directly with SMRT. One interactive surface on AR was mapped to the ligand-binding domain (LBD), and the presence of DNA binding domain enhanced this interaction. The binding surface on SMRT was mapped to the carboxyl-terminal nuclear receptor interacting domain (ID), and mutation of the LXXXIXXXI/L corepressor motif within this domain interferred with the interaction. CONCLUSION: LBD domain on the AR can interact with ID2 motif on the SMRT.