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Mutations in TP53 lead to a defective G1 checkpoint and the dependence on checkpoint kinase 1 (Chk1) for G2 or S phase arrest in response to DNA damage. In preclinical studies, Chk1 inhibition resulted in enhanced cytotoxicity of several chemotherapeutic agents. The high frequency of TP53 mutations in triple negative breast cancer (TNBC: negative for estrogen receptor, progesterone receptor, and HER2) make Chk1 an attractive therapeutic target. UCN-01, a non-selective Chk1 inhibitor, combined with irinotecan demonstrated activity in advanced TNBC in our Phase I study. The goal of this trial was to further evaluate this treatment in women with TNBC. Patients with metastatic TNBC previously treated with anthracyclines and taxanes received irinotecan (100-125 mg/m(2) IV days 1, 8, 15, 22) and UCN-01 (70 mg/m(2) IV day 2, 35 mg/m(2) day 23 and subsequent doses) every 42-day cycle. Peripheral blood mononuclear cells (PBMC) and tumor specimens were collected. Twenty five patients were enrolled. The overall response (complete response (CR) + partial response (PR)) rate was 4 %. The clinical benefit rate (CR + PR + stable disease ≥6 months) was 12 %. Since UCN-01 inhibits PDK1, phosphorylated ribosomal protein S6 (pS6) in PBMC was assessed. Although reduced 24 h post UCN-01, pS6 levels rose to baseline by day 8, indicating loss of UCN-01 bioavailability. Immunostains of γH2AX and pChk1(S296) on serial tumor biopsies from four patients demonstrated an induction of DNA damage and Chk1 activation following irinotecan. However, Chk1 inhibition by UCN-01 was not observed in all tumors. Most tumors were basal-like (69 %), and carried mutations in TP53 (53 %). Median overall survival in patients with TP53 mutant tumors was poor compared to wild type (5.5 vs. 20.3 months, p = 0.004). This regimen had limited activity in TNBC. Inconsistent Chk1 inhibition was likely due to the pharmacokinetics of UCN-01. TP53 mutations were associated with a poor prognosis in metastatic TNBC.

To explore the risk factors and prognostic impact of duodenal hepatic ligamentous lymph node (No.12 LN) metastasis in cases with curable advanced distal gastric cancer.The data of 379 cases with advanced distal gastric cancer undergoing radical resection were screened from the Database of Gastric Cancer Center of Sun Yat-sen University from January 1997 to December 2010. According to No.12 LN metastasis, they were divided into negative (n = 339) and positive (n = 40) groups. Their clinicopathological parameters and surgical regimens were compared. And the risk factors and prognostic impact of No.12 LN metastasis were analyzed.No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P0.05). In negative and positive groups, the percent of tumor size ≥ 5 cm was 30.1% (102/339) vs 55.0% (22/40), lymph node metastasis N3 stage 8.3% (28/339) vs 42.5% (17/40), other lymph nodes except for No.12 metastasis 70.2% (238/339) vs 92.5% (37/40), distal metastasis M1 10.9% (37/339) vs 32.5% (13/40), TNM stage IV 18.6% (63/339) vs 65.0% (26/40), infiltration Borrmann type 74.3% (252/339) vs 92.5% (37/40), non-adenocarcinoma 15.9% (54/339) vs 35.0% (14/40) and positive serum-carcinoembryonic antigen (S-CEA) 12.7% (43/339) vs 32.5% (13/40). There were all with significant difference (all P0.01). Logistic regression analysis showed tumor size ≥ 5 cm, lymph node (except for No.12) metastasis, distal metastasis and positive S-CEA were independent risk factors of No.12 LN metastasis (OR = 2.144, 3.581, 2.597, 2.552; P = 0.035, 0.042, 0.019, 0.022 respectively). Cox regression analysis showed lymph nodes (except for No.12) and No.12 metastasis, distal metastasis and Borrmann type were independent prognostic factors for all cases. In negative and positive groups, median survival time was 63.0 versus 12.0 months with significant difference (P = 0.000).For cases with curable advanced distal gastric cancer, No.12 LN metastasis was an independent prognostic factor. No.12 LN should be dissected thoroughly in cases with tumor size ≥ 5 cm, lymph nodes (except No.12) metastasis, distal metastasis and positive S-CEA.

Retroviral vectors can result in therapeutic and stable levels of expression of proteins from the liver. However, m ost retroviral vectors transduce only dividing cells, and hepatocytes are normally quiescent. The goal of this study was to determ ine if an adenoviral vector could transiently express hepatocyte growth factor (HG F) in order to induce hepatocyte replication and facilitate retroviral vector transduction of the liver. Intram uscular injection of an adenoviral vector that expressed human HGF from the cytomegalovirus promoter (Ad.C M V.HGF) resulted in m oderate levels of H GF in blood and liver, and replication of 3 to 12% of hepatocytes. No cytopathic effect was observed in the liver, and a control adenoviral vector induced no or lower levels of replication. W hen a retroviral vector expressing b -galactosidase cDNA was injected into a peripheral vein during the peak period of hepatocyte replication induced by intramuscularly adm inistered Ad.C M V.HG F, 8% of hepatocytes were transduced. W e conclude that intram uscular injection of Ad.C M V.HG F is a safe and effective way to induce transient systemic expression of HG F and hepatocyte replication, and to facilitate transduction of hepatocytes with a retroviral vector.

To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients.A total of 142 EGC cases screened from database of gastric cancer of Sun Yat-sen University, from Aug. 1994 to Jan. 2010, were included in this study. According to the lymph node metastasis status, they were divided into lymph node negative (n = 116) and lymph node positive (n = 26) groups. The clinicopathological features of the two groups and the impact of extent of lymph node dissection on the prognosis were analyzed.There were no significant differences in age, gender, tumor size and location, Borrmann typing, WHO TNM staging, histological typing, and CEA value between the two groups (P0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P0.001). Between the cases who underwent D1 (n = 21) and D2 (n = 121) dissection, there were no significant differences in postoperative hospital days, blood transfusion volume, and operation time (P0.05). The median numbers of LN dissected in D1 and D2 cases were 4 (0 to 16) and 20 (12 to 30), with a significant difference (P = 0.000), but the number of positive LN without significant difference (P = 0.502). The postoperative complication rates were 9.5% in the D1 and 3.3% in the D2 dissection groups, without a significant difference (P = 0.128). The median survival time of the lymph node negative and positive groups was 156 vs. 96 months (P = 0.010). In cases who received D2 and D1 lymph node dissection, the median survival time (MST) was 156 vs. 96 months (P = 0.0022). In the lymph node positive group, D2 dissection prolonged survival time significantly than D1 dissection (96 vs. 27months) (P = 0.001). Cox regression analysis showed that the extent of lymph node dissection and LN metastasis were independent prognostic factors for EGC patients.It is not able to accurately assess the LN metastasis status preoperatively according to the routine clinicopathological features. For the patients with unknown LN metastasis status, D2 dissection should be the first choice. Comparing with D1 dissection, the morbidity of D2 dissection are not increased, but survival time is prolonged.

To evaluate the impact of different gastrectomy and reconstruction method on prognosis and quality of life in proximal gastric cancer.The 265 cases of proximal gastric cancer received radical resection, according to gastrectomy or reconstruction method, were divided into proximal gastrectomy/gastroesophagostomy group (PG) (n = 63) and total gastrectomy/esophagojejunostomy group (TG) (n = 202). The clinical pathologic features, prognosis, postoperative quality of life in 2 groups were compared.There had no significant differences in age, gender, CEA value between two groups (all P0.05). In PG and TG group, tumor size (cm), ratio of organic invasion, lymph nodes metastasis, distal metastasis, TNM IV stage, Borrmann typing, poor or undifferentiated carcinoma was 2.9 ± 1.9 vs. 4.8 ± 2.8, 9.5% vs. 32.2%, 64.7% vs. 70.6%, 0 vs. 8.4%, 6.9% vs. 31.8%, 44.4% vs. 69.2%, 31.7% vs. 53.7%, respectively, all with significant difference (t = -6.260, χ(2) = 29.473, 14.559, 5.665, 32.483, 12.588, 10.954, all P0.05). In PG and TG group, the ratio of D3 and D3(+) resection, multi-visceral resection, complications was 0 vs. 13.8%, 9.5% vs. 38.6%, 7.9% vs. 1.5% respectively, showed increasing range of resection and decreasing complications significantly in TG group (all P0.05). The median survival time (months) was 62.5 vs. 78.9 in TG and PG group respectively, without significant difference (P0.05). In 2 groups, the evaluation index of post-operative quality of life without significant differences (P0.05).For proximal gastric cancer, although the cases received TG with worse clinicopathological features, which prognosis was similar to that received PG. The postoperative quality of life without significant difference between the cases received gastroesophagostomy and esophagojejunostomy.

To investigate the effects of fast track surgery on postoperative insulin sensitivity on the basis of clinical benefits in patients undergoing elective open colorectal resection.During May 2008 to December 2008, Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters, stress markers and insulin sensitivity were evaluated in both groups.The 62 patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. The speed of recovery of postoperative insulin sensitivity on 7 days postoperative in the fast-track group (97% ± 9%) was significantly faster than the conventional care group (88.5% ± 9.0%, t = 2.552, P = 0.016). The hospitalization days in the fast-track group was 6 days (M(50)), and it was significantly shorter than the conventional care group ((11.7 ± 3.8) days, Z = 4.360, P = 0.000). The time of recovery of bowel function were faster in the fast-track group (time to pass flatus was 2 days (M(50))) than the conventional care group (4 days, Z = 3.976, P = 0.000). The Infectious complication rate in the fast-track group (2/32) is lower than the other group (8/30, P = 0.040).Fast track surgery accelerates recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a lower rate of postoperative infectious complications and a shorter length of postoperative hospital stay.

To evaluate the impact of surgical modality for gastric cancer on operational trauma.A total of 1499 cases of gastric cancer undergoing surgical procedures were divided into the groups of radical resection (RR, n = 1344) and palliative resection group (NRR, n = 155) according to their surgical modalities. And they were further divided into sub-groups according to the profiles of gastrectomy, extent of lymphadenectomy and multi organic resection. The extent of operational trauma (as evaluated by operative duration, transfusion volume, postoperative hospital day and incidence of complications) was compared in different groups and subgroups.In RR and NRR groups, median transfusion volume (Q(1), Q(3)) was 0 (0, 600) vs 400 (0, 800) ml respectively. There was significant difference (P0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P0.05). In cases of distal gastrectomy, median transfusion volume was 0 (0, 400) vs 400 (200, 800) ml in RR and NRR groups (P0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P0.05). In cases of total gastrectomy, no significant difference existed in operative duration, postoperative hospital day, median transfusion volume or incidence of complications between two groups (all P0.05). In RR group, for the cases treated by D1, D2, D3 and paraaortic lymph node dissection (PAND), there were significant differences in operative duration ((248 ± 71), (271 ± 72), (309 ± 96), (351 ± 103) min), postoperative hospital day ((13 ± 4), (16 ± 12), (18 ± 11), (20 ± 19) days), median transfusion volume (0(0, 500), 0(0, 600), 400(0, 800), 600(200, 1000) ml) (all P0.05). But no significant difference existed in incidence of complications (P0.05). In RR group, operative duration, postoperative hospital day, median transfusion volume was (315 ± 96) vs (264 ± 66) min, (19 ± 15) vs (15 ± 11) days, 400 (0, 800) vs 0 (0, 400) ml in the patients with and without combined organic resection (all P0.05). But no significant difference existed in incidence of complications (P0.05).As compared with palliative resection, radical resection will not increase surgical trauma. For the cases of radical resection, extent of lymphadenectomy and organic resection increase surgical trauma.

To compare Borrmann type IV gastric cancer with other types of cancer and explore their clinicopathological features and prognostic factors.We retrospectively reviewed the medical records of 893 consecutive advanced gastric cancer patients. They were divided into 2 groups: Borrmann type IV (n = 139) and other macroscopic Borrmann types of cancer (n = 754). Their clinicopathologic characteristics and overall survival data were analyzed.Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features. The incidence of preoperative biopsy-negative rate of Borrmann type IV gastric cancer was much higher (15.9%) than other Borrmann types of gastric cancer. The 5-year survival rate of Borrmann type IV cancer patients was 9.9% and it was significantly lower than that of other types. Moreover, the 5-year survival rate was higher in the patients with curative resection (18.7%) (P0.05). Stratified analysis revealed that when the tumor TNM stages were of II, III, the survival data of Borrmann type IV cancer were worse than others. Multivariate analyses revealed distant metastasis and curability were independent prognostic factors for Borrmann type IV gastric cancer.Borrmann type IV carcinoma has poor clinicopathological features and survival rate compared with other types. An early detection and curative resection may improve the prognosis for the patients with Borrmann type IV cancer.

Pancreaticogastrostomy (PG) has been proposed as an alternative to pancreaticojejunostomy (PJ), assuming that postoperative complications are less frequent. The aim of this research was to compare the safety of PG with PJ reconstruction after pancreaticoduodenectomy.Articles of prospective controlled trials published until the end of December 2010 comparing PJ and PG after PD were searched by means of MEDLINE, EMBASE, Cochrane Controlled Trials Register databases, and Chinese Biomedical Database. After quality assessment of all included prospective controlled trials, meta-analysis was performed with Review Manager 5.0 for statistic analysis.Overall, six articles of prospective controlled trials were included. Of the 866 patients analyzed, 440 received PG and 426 were treated by PJ. Meta-analysis of six prospective controlled trials (including RCT and non-randomized prospective trial) revealed significant difference between PJ and PG regarding postoperative complication rates (OR, 0.53; 95%CI, 0.30 - 0.95; P = 0.03), pancreatic fistula (OR, 0.47; 95%CI, 0.22 - 0.97; P = 0.04), and intra-abdominal fluid collection (OR, 0.42; 95%CI, 0.25 - 0.72; P = 0.001). The difference in mortality was of no significance. Meta-analysis of four randomized controlled trials (RCT) revealed significant difference between PJ and PG regarding intra-abdominal fluid collection (OR, 0.46; 95% CI, 0.26 - 0.79; P = 0.005). The differences in pancreatic fistula, postoperative complications, delayed gastric emptying, and mortality were of no significance.Meta-analysis of six prospective controlled trials (including randomized controlled trials (RCT) and non-randomized prospective trial) revealed significant difference between PJ and PG regarding overall postoperative complications, pancreatic fistula, and intra-abdominal fluid collection. Meta-analysis of four RCT revealed significant difference between PJ and PG with regard to intra-abdominal fluid collection. The results suggest that PG may be as safe as PJ.

Few clinical studies or randomized clinical trial results have reported the impact of fast track surgery on postoperative insulin sensitivity. This study aimed to investigate the effects of fast track surgery on postoperative insulin sensitivity in patients undergoing elective open colorectal resection.Controlled, randomized clinical trial was conducted from November 2008 to January 2009 with one-month post-discharge follow-up. Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters (complication rates, return of gastrointestinal function and postoperative length of stay), stress index and insulin sensitivity were evaluated in both groups perioperatively.Sixty-two patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. Our findings revealed a significantly faster recovery of postoperative insulin sensitivity on postoperative day 7 in the fast-track group than that in the conventional care group. We also found a significantly shorter length of postoperative stay and a significantly faster return of gastrointestinal function in patients undergoing fast-track rehabilitation.Fast track surgery accelerates the recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection.Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into fast-track group (n = 35) and conventional care group (n = 35). The clinical parameters and markers of humeral immune function were evaluated in both groups postoperatively.Sixty-two patients finally completed the study, including 32 in the fast-track group and 30 in the conventional care group. There was a significantly faster recovery of postoperative humoral immunity: blood levels of globulin (24.1 ± 2.4 vs 22.1 ± 3.3 g/L, P = 0.025), immunoglobulin G (10.79 ± 2.39 vs 8.66 ± 2.09 g/L, P = 0.007) and complement 4 (0.24 ± 0.09 vs 0.17 ± 0.05 g/L, P = 0.035) at Day 3 postoperation were higher in the fast-track group than in the conventional care group. And there was also a significantly shorter length of postoperative stay (6.0 ± 1.0 vs 11.7 ± 3.8 d, P0.001) in patients undergoing fast-track rehabilitation.Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective surgery for colorectal carcinoma with a shorter length of postoperative hospital stay.

To compare the nutritional status between pancreaticojejunostomy(PJ) and pancreaticogastrostomy(PG) following pancreaticoduodenectomy.A retrospective clinical analysis was performed on 37 patients undergoing pancreaticoduodenectomy(PD) for duodenal carcinoma and pancreatic non-epithelial tumor with PG(n=19) and PJ(n=18) in the First Hospital of Sun Yat-sen University from April 2006 to December 2010. All the patients had a needle catheter jejunostomy inserted at the conclusion of laparotomy. Postoperative early enteral nutrition and parenteral nutrition was performed for all the patients. Nutritional status of two groups was compared in body mass index (BMI), serum nutritional parameters such as albumin, transferrin and prealbumin before surgery and on 1, 3, and 6 months postoperatively.There were no significant differences between PG and PJ groups in operative time, blood loss, pancreatic fistula, perioperative death, or postoperative length of hospital stay. One month after surgery, there were no significant differences in BMI [(17.1±7.0) vs. (19.0±4.8) kg/m(2), P0.05], albumin [(30.1±0.5) vs. (32.1±1.3) g/L, P0.05], transferrin [(1.89±0.57) vs. (2.01±0.61) g/L, P0.05] and prealbumin[(0.18±0.05) vs. (0.18±0.09) g/L, P0.05]. These parameters were decreased at 1 month after surgery, and gradually recovered to baseline or higher than the preoperative levels at 6 months after surgery. However, the differences were still not statistically significant between two groups.The influence of PJ and PG on the postoperative nutritional status are comparable.

To evaluate the efficacy and influencing factors of imatinib in patients with advanced gastrointestinal stromal tumor(GIST).From April 2004 to January 2010, clinicopathological data of 73 adult patients with advanced GIST treated with imatinib at the First Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The treatment outcomes and associated factors were investigated.Treatment outcomes included complete response in 1(1.4%) patients, partial response in 53(72.6%), stable disease in 14(19.2%), and primary resistant in 5(6.8%). All the patients had routine followed up, the length of which ranged from 12 to 76 (median 32) months. The median progression-free survival was 45.0 months(95% confidence interval, 34.2-55.8). The progression-free survival(PFS) rate was 87.7% in 1 year, 63.6% in 3 year, and 39.6% in 5 years. On multivariate analysis, both mutation status and patient performance were independent factors influencing the efficacy of imatinib treatment(both P0.01). PFS was significantly better in patients with c-kit exon 11 mutations than those with exon 9 mutations, and better in lower ECOG scales than in higher ones.Imatinib is effective in treating patients with advanced GIST, c-kit exon 9 mutations and poor performance status predict an adverse survival benefit of imatinib therapy.

The association of hepatitis B virus (HBV) infection and pancreatic cancer is still controversial. The purpose of this study is to determine whether chronic HBV infection increases the risk.In this case-control study, there were 1,066 patients recruited, with 533 in the study group and 533 controls, frequency-matched for age and sex. Blood samples were collected to detect hepatitis viral infection.Compared to 77 patients (14.4%) in the control group, 80 pancreatic cancer patients (15.0%) were seropositive for HBV surface antigen (not statistically significant, P=0.8). The prevalence of HBV e antigen was higher in study group than that of control group (P=0.03). Further analysis indicated that HBeAg was a risk factor for pancreatic cancer (OR=2.935, 95% CI: 1.048-8.220).In HBV endemic area of China, there appears to be no significant association between chronic HBV infection and pancreatic cancer, but the role of HBeAg needs further exploration.

Splenic cysts are unusual in daily surgical practice and less than 1000 cases have been reported. Primary, true or epithelial splenic cysts, are even rarer. Usually, most of the cysts are asymptomatic until of significant size, at which time they are then detected incidentally on ultrasonography or CT scan. We report a case of a 25-year-old woman with giant epithelial splenic cyst with about 3000 ml of clear-yellow fluid was collected from the cyst. The splenectomy specimen measured 205 mm × 192 mm × 137 mm and weighed 4000 g.

Distal pancreatectomy traditionally included splenectomy; the spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation. The aim of this research was to study the feasibility, safety and clinical effects of spleen and splenic vessel-preserving distal pancreatectomy.A retrospective review was performed for 26 patients undergoing distal pancreatectomy for benign or low grade malignant disease with splenectomy (n = 13) or splenic preservation (n = 13) at the First Hospital of Sun Yat-sen University and Guangdong General Hospital in Southern China from May 2002 to April 2009.All 26 pancreatectomies with splenectomy or splenic preservation were performed successfully. There was no statistically significant difference between two groups in mean operative time ((172 ± 47) minutes vs. (157 ± 52) minutes, P0.05), intraoperative estimated blood loss ((183 ± 68) ml vs. (160 ± 51) ml, P0.05), incidence of noninfectious and infection complication and mean length of postoperative hospital stay ((10.1 ± 2.2) days vs. (12.1 ± 4.6) days, P0.05). The platelet counts examined one week after operation were significantly higher in the distal pancreatectomy with splenectomy group than the other group ((37.3 ± 12.8) × 10(9)/L vs. (54.7 ± 13.2) × 10(9)/L, P0.05).Spleen-preserving distal pancreatectomy appears to be a feasible and safe procedure. In selected cases of benign or low-grade malignant disease, spleen-preserving distal pancreatectomy is recommended.

To investigate the clinicopathological characteristics between mucinous gastric cancer (MGC) and poorly differentiated gastric cancer(PDGC) and factors associated with prognosis.Medical records of 1016 consecutive patients with gastric cancer were retrospectively reviewed. Sixty-eight patients with MGC and 508 with PDGC were identified. Clinicopathologic characteristics and overall survival data were analyzed.As compared to PDGC patients, patients with MGC were significantly older [(59.2±11.9) years vs. (54.1±13.2) years], had significantly more distant metastasis(36.8% vs. 23.8%), more peritoneal seeding(29.4% vs. 16.9%), and less radical resection(60.3% vs. 76.6%). There were no significant differences in 5-year survival rate between MGC and PDGC patients(29.4% vs. 35.5%). However, for tumors in the middle third of the stomach, the survival rate of MGC patients was lower than that of PDGC. Using a Cox proportional hazard ratio model, lymph node involvement and radical resection were independent prognostic factors for survival of MGC patients, while tumor invasion, lymph node involvement, and radical resection were associated with survival in patients with PDGC.Although MGC and PDGC differ in age, frequencies of peritoneal seeding, distant metastasis, and rate of radical resection, overall survival is comparable.

Diabetes mellitus plays an important role in cancer prevalence and outcomes. The aim of this study was to evaluate the influence of DM on stages and outcomes among patients with colorectal cancer.The study enrolled 945 patients who were diagnosed as having colorectal carcinoma from August 1994 to December 2002. In the cohort, 26 patients were diagnosed as having DM. With a median follow-up of 45.8 months, differences in overall survival and disease-free survival between the diabetes and non-diabetes groups were analyzed.Kaplan and Meier analysis showed that there were no significant differences between the two groups in overall survival rates at 3 years or 5 years. At 5 years, patients with DM, compared with patients without diabetes, experienced a significantly lower disease-free survival rate (34.2% diabetics vs. 55.1% non-diabetics; P = 0.025).DM was associated with an increased risk of recurrence in patients with colorectal cancer.

To explore the clinical characteristics and the prognostic factors of patients with colorectal cancer.The data of 2042 cases of colorectal cancer, pathologically confirmed at our hospital from January 1995 to December 2007, were summarized and analyzed.The median age of all cases with colorectal cancer was 59 years old. The high-risk age ranged from 50 to 70 years old. The ratio of male and female was 1.4:1. The lesions located in rectum accounted for 46.2% and those for 22.0% in sigmoid. Patients under age 40 had a higher percentage of poor differentiation (33.5%) and mucinous carcinoma (16.7%). The cases with confirmed stage I, II, III and IV were 5.8%, 42.9%, 31.0% and 20.3% respectively. For all cases, the 1-, 3-, 5- and 10-year survival rates were 92.3%, 73.9%, 65.1% and 57.5% respectively. The independent risk factors for patient prognosis were age, gross type, differentiation, TNM staging and surgical type. Adjuvant chemotherapy was a protective factor. As compared with phase I (1995 - 2001), phase II (2002 - 2007) had a higher proportions of employing stapler, Dixon operation and adjuvant chemotherapy. The 1-, 3- and 5-year survival rates of phase II were higher than phase I (93.4%, 78.0% and 73.2% vs 90.6%, 69.2% and 58.8%).The prognostic factors of patients with colorectal cancer are age, gross type, differentiation, TNM staging, surgical type and adjuvant chemotherapy.

To explore the expression of serine protease Omi/HtrA2 in gastric carcinoma tissue and its association with clinicopathological features and prognosis.Omi/HtrA2 protein expression levels were detected by immunohistochemistry method in resected gastric carcinomas(n=68), adjacent noncancerous tissues(n=15), and normal tissues(n=15), and its association with clinicopathological features and prognosis were analyzed.Omi/HtrA2 expression was positive in 73.5%(50/68) of gastric cancer tissues, which was significantly higher than that in adjacent noncancerous tissues and normal tissues(P0.05). There were no significant differences in Omi/HtrA2 expression with respect to sex, age, tumor size, and depth of invasion(all P0.05). Omi/HtrA2 expression level was significantly associated with tumor differentiation, extent of lymph node metastasis, and tumor stage(all P0.05). Overall 5-year survival rate of patients with gastric carcinoma was 63.3%. Five-year survival rate was higher in Omi/HtrA2 positive cases than Omi/HtrA2 negative cases(72.0% vs. 61.1%), however the difference was not statistically significant.Omi/HtrA2 expression is more common in gastric carcinoma. Omi/HtrA2 expression is associated with tumor differentiation, extent of lymph node metastasis, and tumor stage.

To investigate the clinicopathologic features, diagnosis and treatment of neuroendocrine carcinoma (NEC) in the digestive system.Thirty-eight patients with NEC from Jan 1985 to Mar 2008 were analyzed retrospectively and the related literatures were reviewed.There were 29 males and 9 females. Common symptoms were melena or hematochezia (n=21, 55%), abdominal pain (n=19, 50%), abdominal mass (n=15, 39%), constipation (n=14, 37%), rectal mass (n=12, 32%), abdominal distention (n=11,29%) and diarrhea (n=7,18%). All the patients received surgical treatment including 1 esophagectomy, 5 radical total gastrectomies, 1 palliation proximal gastric resection, 2 local gastric resections, 6 pancreaticoduodenectomies, 1 distal pancreatectomies, 3 partial small intestine resections, 7 radical right hemicolectomies, 5 Dixon operations, 3 Miles operations, and 4 local resections of rectal tumor. Thirty-six patients received follow-up. The follow-up time ranged from 3 months to 144 months (median, 70 months). The 1-, 3- and 5-year survival rates were 94.7%, 86.8%, and 57.9% respectively. The median survival time was 62 months. The survival time of the patients with carcinoma infiltration exceeding bowel muscularis propria was (36+/-5) months, significantly shorter than that of patients without carcinoma infiltration exceeding the bowel muscularis propria [(73+/-5) months, P0.05]. The survival time of the patients with positive lymph node metastasis was (34+/-7) months, significantly shorter than that of patients with negative lymph node metastasis [(74+/-5) months, P0.05].Clinical symptoms, signs of neuroendocrine carcinoma in the digestive system are nonspecific. The correct diagnosis should depend on histopathologic examination. Systematic treatments including radical resection of NEC are the preferable treatment.

To investigate the clinical effect of surgery following systemic targeted therapy of tyrosine kinase inhibitors (TKIs) in patients with metastatic gastrointestinal stromal tumors (GIST).From June 2007 to December 2009, data of 15 consecutive patients with metastatic GIST treated with imatinib/sunitinib followed by surgery were retrospectively analyzed.Disease responses to TKI treatment was categorized into controlled disease (including partial response and stable disease) (6, 40.0%), limited progression (4, 26.7%), and generalized progression (5, 33.3%), respectively. Surgeries were performed after mean 12 months following TKI therapies. Gross complete resection or optimal debulking with minimal residual disease were managed to performed in 8/10 patients with disease controlled and limited progression, while optimal debulking only achieved in 2/5 patients with generalized progression. Surgical morbidity was 20.0% (3/15). After operation, patients with disease controlled and limited progression had a median progression-free survival of 25.0 months and 2-year overall survival rate of 100%. In contrast, for patients with generalized progression, the median progression- free survival was 3 months (P0.01), and median overall survival 10.5 months.Patients with metastatic GIST who have controlled disease or limited progression to TKI therapy can benefit from surgical resection. Surgery should be selective in patients with generalized progression since surgery hardly improves survival in these patients.

Purpose UCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase inhibitor that exhibits synergistic activity with DNA-damaging agents in preclinical studies. We conducted a Phase I study to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid tumors. Experimental design Patients received irinotecan (75–125 mg/m2 IV on days 1, 8, 15, 22) and UCN-01 (50–90 mg/m2 IV on day 2 and 25–45 mg/m2 on day 23 and subsequent doses) every 42 days. Blood for pharmacokinetics of UCN-01 and irinotecan, and blood, normal rectal mucosa, and tumor biopsies for pharmacodynamic studies were obtained. Results Twenty-five patients enrolled to 5 dose levels. The MTD was irinotecan 125 mg/m2 on days 1, 8, 15, 22 and UCN-01 70 mg/m2 on day 2 and 35 mg/m2 on day 23. DLTs included grade 3 diarrhea/dehydration and dyspnea. UCN-01 had a prolonged half-life and a low clearance rate. There was a significant reduction in SN-38 Cmax and aminopentanocarboxylic acid (APC) and SN-38 glucuronide half-lives. Phosphorylated ribosomal protein S6 was reduced in blood, normal rectal mucosa, and tumor biopsies at 24 h post-UCN-01. Two partial responses were observed in women with ER, PgR, and HER2-negative breast cancers (TBNC). Both tumors were defective for p53. Twelve patients had stable disease (mean duration 18 weeks, range 7–30 weeks). Conclusion UCN-01 and irinotecan demonstrated acceptable toxicity and target inhibition. Anti-tumor activity was observed and a study of this combination in women with TNBC is underway. Electronic supplementary material The online version of this article (doi:10.1007/s00280-010-1410-1) contains supplementary material, which is available to authorized users.

To investigate clinicopathological characteristics and the pattern of lymph node metastasis of patients with gastric remnant cancer.The data of the clinicopathological characteristics and the pattern of lymph node metastasis in 56 patients with gastric remnant cancer treated from March 1994 to December 2008 was investigated and compared with those in 1171 patients with primary gastric cancer treated over the same period.Fifty-six patients (4.6%) with gastric remnant cancer were enrolled in this study during the period. Compared with patients with primary gastric cancer, the age of cancer onset was older [(64.3+/-9.0) vs. (58.3+/-12.6) yrs], lymph node metastasis rate was higher (31.8% vs. 25.5%), Borrmann's classification was later and neighbor organ resection rate was higher (57.1% vs. 26.4%) in patients with gastric remnant cancer; the differences were all significant (chi2=18.800, 11.679, 9.177, 25.190; P0.05). Patients with gastric remnant cancer who underwent lymph node dissection tended to have a higher incidence of No.10 (splenic hilar lymph node) and No.11 (splenic artery lymph node) group lymph node metastasis than those in primary gastric cancer (chi2=5.558, 6.099; P0.05). In contrast, patients with primary gastric cancer had a higher incidence of No. 2 (left cardiac lymph node), No.3 (lesser curvature lymph node) and No.8 (common hepatic artery lymph node) group lymph node metastasis than those in gastric remnant cancer (chi2=15.508, 6.003, 4.084; P0.05). The jejunal mesentery lymph node metastasis was 24.0% (6/25) in patients with gastric remnant cancer and the peripheral connective tissue infiltration rate was 14.3% (8/56).It suggested that patients with gastric remnant cancer has different clinicopathologic characteristics and the pattern of lymph node metastasis from those with primary gastric cancer. D2 lymph node dissection of proximate gastric cancer and jejunal mesentery lymph node dissection should be the standard operation for these patients; but combined neighboring organ resection should be taken into consideration.

To evaluate the value of EUS and PET-CT in combination with spiral CT in preoperative assessment of gastric cancer invasion to the pancreas.Sixty advanced gastric cancer patients with suspected pancreatic invasion detected by spiral CT were selected in this study. All the 60 cases were then examined by EUS and 14 of them by PET-CT. The results were compared and evaluated with the findings during surgical operation and pathological results.The rate of correct preoperative diagnosis of pancreatic invasion by spiral CT in advanced gastric cancer patients was 63.3%, with an overdiagnosis rate of 36.7%. The diagnostic accuracy was increased to 87.8% and overdiagnosis reduced to 7.3%, when combined with EUS. There was a significant difference in diagnostic accuracy between spiral CT alone and spiral CT combined with EUS (P0.01), but no significant difference between spiral CT alone and spiral CT combined with PET-CT (P0.05). Spiral CT-EUS was more valuable in assessment of tumor location and invasion than PET-CT (P0.01).The accuracy of spiral CT alone in the preoperative assessment of advanced gastric cancer with invasion to the pancreas is not high enough yet at present. Spiral CT combined with EUS can provide more accurate information on the tumor location, invasion site and extent of gastric cancer invasion to the pancreas, and reduce the overstaging rate caused by spiral CT alone. However, spiral CT combined with PET-CT does not show such improvement significantly.

Mesh reconstruction has been proved to be an effective method in incisional hernia repairment. This study was designed to evaluate the effect of reconstructing the pelvic floor with the high-inlay expanded polytetrafluoroethylene (ePTFE) GORE-TEX Dual Mesh (WLGore And Associates, Flagstuff, USA) in abdominoperineal resection.Sixty patients who underwent abdominoperineal resection for rectal cancer were assigned to 2 groups. The pelvic peritoneum was closed by routine sutures in group 1 and reconstructed with ePTFE in group 2. Postoperative complications and related items were evaluated and the patients were followed up.Time of confining to bed, bowel function recovery, fasting, and detaining drainage were significantly different between two groups (P0.05). In group 1, three patients developed bowel obstruction (10%), while no bowel obstruction was observed in group 2.Reconstruction of the pelvic floor using ePTFE results in quicker postoperative recovery and could decrease the risk of postoperative intestinal obstruction.

To investigate the clinicopathological characteristics and prognosis of colorectal mucinous adenocarcinoma (MAC) and non-mucinous adenocarcinoma (NMAC).Clinical data of 2089 cases with colorectal cancer from 1994 to 2007 in our hospital, including 169 patients diagnosed as mucinous adenocarcinoma were analyzed retrospectively.As compared to NMAC, the tumor diameter of MAC was longer[(5.52+/-3.56) cm vs (4.62+/-2.68) cm, P0.01]; the age of MAC was younger [(52.3+/-16.5) vs (58.7+/-13.6) years, P0.01]. The rates of tumor location in colon (97 cases,57.4% vs 814 cases, 44.3%, in MAC and NMAC) were significantly different (P0.01). Compared with NMAC, MAC had more lymph node involvement (103 cases, 60.9% vs 929 cases, 50.1%), more often in serosa infiltration (116 cases, 68.7% vs 914 cases, 49.8%), more peritoneal dissemination (26 cases, 15.4% vs 125 cases, 6.8%), and adjacent organ invasion (44 cases, 26.0% vs 300 cases, 16.3%) (P0.01). The rate of radical resection (86.4% vs 91.5%), hepatic metastasis (5.3% vs 8.5%) and local recurrence had no significant difference between patients with mucinous and non-mucinous adenocarcinoma (P0.05). In comparison to NMAC patients, MAC patients were worse in long-term overall survival, the survival of receiving radical resection and of TNM stage (II+III) group (P0.01). Survivals were not significantly different in TNM stage I and IV groups between mucinous and non-mucinous adenocarcinoma (P0.05).Colorectal mucinous adenocarcinoma patients have worse outcome in comparison to non-mucinous adenocarcinoma patients. Mucinous adenocarcinoma may have special biological behavior, which is an independent prognostic factor for patients with colorectal cancer.

Previous studies have shown conflicting results on the relation between clinicopathologic features and prognosis of patients with colorectal mucinous, signet-ring cell, or non-mucinous adenocarcinoma; only few such studies have been performed in China. This retrospective study analyzed data from our department to investigate clinicopathologic characteristics, prognosis and possible correlations of three histologic types - colorectal mucinous, signet-ring cell, and non-mucinous adenocarcinoma, to clarify the bases for observed differences which may lead to development of targeted therapies.Of 2079 patients diagnosed with colorectal cancer between 1994 and 2007, 144 had mucinous, 25 had signet-ring cell, and 1837 had non-mucinous adenocarcinoma. Their clinicopathologic parameters and survival were analyzed using established statistical methodologies.Mucinous and signet-ring cell adenocarcinomas were common in younger patients (P0.001). Location, size and disease stage differed significantly among the three types. Signet-ring cell tumors were more commonly found in the rectum than mucinous and non-mucinous adenocarcinoma (P0.001). Mucinous and signet-ring cell tumors presented in a later stage in life more often than non-mucinous adenocarcinoma, with lymph node involvement, serosal infiltration, peritoneal dissemination, and adjacent organ invasion (P0.01). The rate of radical resection, hepatic metastasis and local recurrence did not differ among types (P0.05). Compared with patients with non-mucinous adenocarcinoma, patients with mucinous and signet-ring cell tumors who underwent potentially curative resections or stage II/III disease had poorer long-term overall survival. Survival did not differ by type for patients with either stage I or IV disease (P0.05).Mucinous and signet-ring cell adenocarcinoma have unique carcinogenesis and similar biologic behavior. Our study confirms that both histologic types, especially signet-ring cell tumors, are independent, negative prognostic factors for patients with colorectal cancer. Type does not appear to have a significant effect on survival when disease is either stage I or IV at presentation.

Although the indication and the timing for surgery in fulminant acute pancreatitis (FAP) are still controversial, our experience of surgical treatment for fulminant acute pancreatitis may help improve the outcome for patients.The clinical data of twenty-six patients with FAP from January 1, 2001 to October 1, 2005 were analyzed. The diagnostic criteria fitted the 2007 Guidelines for the Management of Severe Acute Pancreatitis by the Chinese Medical Association.Twenty-six patients with FAP received surgical debridement, with a mortality rate of 42.3% (11/26). The postoperative mortalities in the72 hour operation group and theor= 72 hour operation group were highly significantly different (7/8 vs 22.2% (4/18), respectively).Early surgery may reduce the intraabdominal pressure and prevent the deterioration of FAP. An operation within 72 hours from the onset of symptoms might decrease the mortality of the disease.

To evaluate and compare the results of vagina vasorum lymph node dissection (VLND) and non-vagina vasorum lymph node dissection (NVLND) in patients with gastric cancer after radical operation.A total of 759 cases of evaluable patients with gastric cancer, operated from June 1994 to April 2005, were retrospectively analyzed. Of which, 627 cases underwent radical gastrectomy: 215 patients received VLND and 412 cases received NVLND. The operation time, intraoperative blood loss, operative complications and survival rate were recorded and compared between the two groups.The 5- and 10-year overall accumulative survival rates of VLND group and NVLND group were 55.4% and 51.2%, 39.1%and 36.8%, respectively (all P0.05). No significant differences in intraoperative blood transfusion (loss), operation time, operative complication rate was found between the two groups. The 5- and 10-year accumulative survival in patients with a tumor of phase N0-N2, T2-T4, Ib-IV in VLND groups were all significant higher than those in NVLND group.VLND is a safe technique in advanced gastric cancer, it dose not prolong operation time or increase operative complications but improves survival.

To investigate whether albumin administration is beneficial in early stage of postoperative hypoalbuminemia after gastrointestinal surgery.A prospective randomized control trial was designed. One hundred and twenty-seven patients suffered from hypoalbuminemia after gastrointestinal surgery were randomly divided into albumin group (64 cases) and saline group (control group, 63 cases) by using random number form. The albumin group was given 100 ml 20% human albumin daily for 3 days; and in control group, saline 100 ml daily was administered for 3 days after the operation. The disease course of postoperative hypoalbuminemia, nutritional status, complications and hospital stay were compared between the two groups.Plasma albumin level in both groups decreased significantly after the operation (P0.05). No significant differences was found in the change of postoperative plasma albumin level between the two groups (P0.05). Postoperative plasma albumin, total protein and pre-albumin levels were similar in the two groups. Three-day and 5-day plasma albumin recovery ratios were similar in the two groups, and the 7-day recovery ratio was lower in the albumin group (P0.05). No significant difference was found in the incidence of postoperative complications between the two groups (23.4% vs. 12.7%, P = 0.116).Albumin administration in early stage of postoperative hypoalbuminemia following gastrointestinal surgery is not beneficial either in correcting hypoalbuminemia or in clinical outcomes.

To compare the clinicopathologic parameters of gastric carcinoma between different phases and to investigate the prognostic factors for gastric carcinoma.A total of 1016 consecutive gastric cancer patients were divided into two groups according to operating date, phase I (1994 - 1996) and phase II (2000 - 2006). The clinicopathologic parameters and prognosis were compared between the two phases. The prognostic factors were analyzed and compared.There were significant differences in the constituent ratio of male and female patients, the proportions of early gastric carcinoma, different TNM staged patients, specialized operation and adjuvant chemotherapy (all P0.05), but no significant differences in tumor location, peritoneal spread, lymph node metastasis and radical resection between the two phases. The overall 5-year survival rate and 5-year survival rate after curative resection were 48.1% and 61.5% respectively within phase II, significantly higher than 32.8% and 42.4% within phase I (all P0.01). Stratification analysis revealed that the survival rates of patients with curative resection, lymph node metastasis or not, advanced disease, different TNM stages, specialized operation, without adjuvant chemotherapy within phase II, were significantly higher than those within phase I (all P0.01). Multivariant regression analysis revealed that Borrmann type, histological type, depth of invasion, lymph node metastasis, curative resection, adjuvant chemotherapy and different phase were independent prognostic factors for gastric carcinoma.The therapeutic efficacy of gastric carcinoma within phase II was improved greatly as a result of elevated diagnostic rate of early gastric cancer, standardized radical operation and adjuvant chemotherapy. Gastric carcinoma within phase II was improved highly. It was elevated diagnostic rate of early gastric cancer, standardized radical operation, and adjuvant chemotherapy that contribute to such improvement.

To investigate the inhibitory effect of epigallocatechin-3-gallate (EGCG) on growth and angiogenesis of gastric cancer and to explore its molecular mechanism.Heterotopic tumor was established by subcutaneously injection with SGC-7901 cells in nude mice. Once the tumor was established, the mice were allocated randomly into two groups and received intraperitoneal injection of EGCG or phosphate buffered saline respectively. Tumor growth was measured by caliper in two dimensions, and angiogenesis was determined with tumor microvessel density (MVD) by immunohistochemistry. Protein levels of vascular endothelial growth factor (VEGF) and activation of signal transducer and activator of transcription 3(Stat3) in tumor cells and tumor tissues were examined by Western blot. VEGF release in tumor culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR.Intraperitoneal injection of EGCG significantly inhibited the growth of gastric cancer[(0.32+/-0.08) g vs(0.81+/-0.12) g, t=7.24, P0.01], and an average of 60.4% suppression of primary tumor growth was observed. Microvessel density in tumor tissues receiving EGCG treatment was also markedly reduced(15.2+/-4.3 vs 24.6+/-6.6,t=3.41,P0.01),and an average of 38.2% suppression was observed. EGCG treatment markedly reduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Stat3. Stat3 activation was dose-dependently suppressed by EGCG in tumor cells, and an average of 53.5% reduction was observed in tumor tissues, but EGCG treatment did not change total Stat3 expression.EGCG reduces expression of VEGF in gastric cancer by inhibiting activation of Stat3, thereby inhibits tumor growth and angiogenesis of gastric cancer.

To evaluate the efficacy of surgical treatment and the prognosis in gastric stump cancer patients.Between June 1994 and March 2004, 692 patients underwent radical operation for gastric cancer in our department. Among them, 22 cases were gastric stump cancer. Their surgical treatments, lymph node metastasis and survival were analyzed retrospectively.Gastric stump cancer accounted for 3.2 % of all the gastric cancer cases in the same period. There were 4 cases of stage I, 2 cases of stage II, 6 cases of stage III and 10 cases of stage IIII respectively. Radical excision was 77.3% and combined evisceration was 50.0%. Total gastrectomy were performed in 21 cases and exploratory laparotomy in 1 case. Digestive tract was reconstructed with Roux-en-Y pattern after total gastrectomy. Radical gastric stump cancer excisions were finished with abdominal incision in 18 cases and with thoraco-abdominal incision in 4 cases. Lymph node metastasis rate was 63.6 %, including pN(0) 8 cases, pN(1) 6 cases, pN(2) 7 cases and pN(3) 1 case respectively. Average survival time was(80.2+/-17.2) months in stage I( and II( gastric remnant cancer; average survival time was(31.2+/-9.2) months in stage III( gastric remnant cancer, average survival time was (23.6+/-6.1) months in stage IIII( gastric remnant cancer, which were significantly different(all P0.05). Between palliative operation group and standard radical excision, extended radical excision groups, well-moderate differentiated and poor differentiated adenocarcinoma groups, lymph node metastasis positive and negative groups, the differences were all significant.Total gastrectomy and D(2) lymph node dissection are imperative for radical excision of gastric remnant cancer. On this base, extended lymphectomy and combined evisceration should be performed appropriately. Tumor stage, procedure pattern, lymph node metastasis and tumor differentiation affect the prognosis of patients with gastric stump cancer.

To detect the expression of phosphatase of regenerating liver (PRL)-3 in primary gastric cancer tissues, evaluate its prognostic impact, and investigate the role of silencing PRL-3 expression by miRNA interference in gastric cancer growth.Immunohistochemistry was used to measure the expression of PRL-3 in 137 gastric tumor samples. The overall survival rates of the patients with different PRL-3 expression levels were compared. Recombinant lentivirus expressing artificial PRL-3 miRNA, Lent. rPRL3-miRs, was established. Human gastric cancer cells of the line SGC7901 were cultured and transfected with Lent. rPRL3-miRs or blank vector, Lenti.rPRL-miR-neg, respectively. Un-transfected progenitor cells were used as controls. MTT assay was used to examine the proliferation of these cells. RT-PCR and Western blotting were used to detect the RNA and protein expression of PRL-3 in the SGC7901 cells. Thirty BALB/c mice were divided into 3 equal groups to be inoculated subcutaneously with SGC7901 cells transfected with Lent. rPRL3-miRs or blank vector, and control SGC7901 cells respectively. The growth of tumor was observed and the tumor sizes were measured 21 days later.85 of the 137 gastric cancer samples (62%) showed high PRL-3 expression and 26 (19%) showed moderate and low PRL-3 expression. High PRL-3 expression was significantly correlated with tumor size (P0.01), infiltration depth (P0.01), lymph node metastasis (P0.01), hepatic metastasis (P0.01), adjacent organ invasion (P0.01), and TNM staging (P0.01). The median survival time of the patients with high PRL-3 expression in the primary tumor was 18.9 months, significantly shorter than those with moderate or low expression (39.1 and 74.3 months respectively, both P0.01). The growth rate of the SGC7901 cells transfected with the recombinant lentivirus expressing artificial PRL-3 miRNA was significantly lower than that of the blank vector-transfected group. The implanted tumor size of the Lenti. rPRL-3-miR-B transfection group was (1.92 +/- 0.18) cm(3), significantly smaller than those of the control and Lenti.rPRL-miR-neg groups [(4.86 +/- 0.38) and (4.74 +/- 0.39) cm(3) respectively, both P0.01].High PRL-3 expression is associated with gastric cancer progression. Silencing of PRL-3 significantly suppresses the proliferation of gastric cancer cells and tumor growth. PRL-3 plays a key role in the growth of gastric cancer. PRL-3 should be considered as a potential therapeutic target.

To observe the effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blocker (ARB) on tumor growth and angiogenesis in implanted gastric cancer mouse model, and to explore the probable mechanism of ACEI and ARB anticancer effect.Nude mouse model with human gastric cancer was established by subcutaneously inoculating human gastric cancer cell line SGC-7901. One week later, 60 mice were randomly divided into 5 groups: control group, perindopril group, captopril group, losartan group, and valsartan group. These groups respectively received the normal saline, perindopril (2 mg/kg), captopril (5 mg/kg), losartan (50 mg/kg), valsartan (40 mg/kg) by gavage once a day. Twenty-one days after treatment the tumors were removed and the tissues were stained by immunohistochemistry method to observe the expression of VEGF, MMP-7 and microvessel density (MVD).In all the ACEI and ARB groups, tumor volumes were significantly inhibited and MVD also decreased significantly as compared with control group (all P0.01). In captopril and perindopril groups, the expression of VEGF and MMP-7 decreased significantly as compared with control group(all P0.05). In losartan and valsartan group, the expressions of VEGF were significantly decreased as compared with control group (all P0.05). The expressions of MMP-7 between ARB groups and control group were not significantly different.ACEI and ARB can inhibit the tumor growth in gastric cancer model and suppress the angiogenesis of the tumor.

To investigate the effect of spleen preservation on the outcome of radical resection for cardia cancer.Data of 108 cardia cancer patients(Siewert types II and III ), undergone radical resection with D(2) or D(3) lymphadenectomy between July 1994 and December 2003 in our department, were analyzed retrospectively. Survival status was ascertained on December 2004. Of these 108 patients, 38 underwent splenectomy and 70 splenic preservation. Clinicopathological features and outcomes of the splenectomy and non-splenectomy groups were compared.Seventy-four patients (68.5%) had lymph node involvement; 18 patients (16.7%) had involvement of lymph nodes in the splenic hilus. Postoperative morbidity in two groups was similar. Overall 5-year survival rate in the non-splenectomy group was significantly higher than that of the splenectomy group (38.7% vs 16.9%, P=0.008). Multivariate regression analysis indicated that tumor invasion (P=0.009) and lymph node metastasis (P=0.001) were independent prognostic factors rather than splenectomy. Although splenectomy was associated with survival, it was not an independent prognostic factor (P= 0.085).Splenectomy does not improve survival of patients undergone curative resection for gastric cardia cancer. Thus, the spleen should be preserved in patients without direct cancer invasion of the spleen.

To explore the effect of advanced gastric cancer on vagniae vasorum of gastric vessels. To provide evidence for the surgical treatment of gastric cancer.The study included 107 specimens of left and right gastric arteries (55 left and 52 right ) from 59 patients who underwent radical gastrectomy for carcinoma. All specimens were dealt with frozen section method, then they were stained with HE, enzyme histochemical method and immunohistochemical method, respectively.Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage IV and III specimens. Cytokeratin positive of tumor cells in or on vagina vasorum was showed on 26 slices from 14 tumors. Among them, 4 slices from 2 tumors belonged to stage III, and 22 slices from 12 tumors belonged to stage IV. Observed under light microscope, the lymphatic capillaries within vagina vasorum were dark brown with 5'-nucleotidase staining in 107 specimens, the capillary tubes within vagina vasorum were blue with alkaline phosphatase staining in 101 specimens. The two structures changed with the development of gastric carcinoma. Average area and bulk density of lymphatic vessel vaginae vasorum were associated with TNM staging of gastric cancer (P=0.001 and P=0.004).Vaginae vasorum dissection, which may not be applied for early gastric cancer, is recommended when clearing lymph nodes around arteries in radical gastrectomy for carcinomas in stage II and above.

To analyze the relationships between smooth-muscle tumors of gastrointestinal (GI) tract and gastrointestinal stromal tumors (GISTs), and the efficacy of surgical management.The clinical and pathological data of 135 cases of GISTs were collected, including cases of leiomyomas/leiomyosarcoma between 1993 and 2003 and GIST between Jan. 2000 and Jul. 2005. The surgical outcomes were analyzed retrospectively.82.1% of former leiomyomas/leiomyosarcomas was corrected to GISTs. Overall 5-year survival rate was 79.7%. Univariate analysis revealed preoperative metastasis, tumor size, mitotic index, and postoperative metastasis or recurrence were correlated with overall survival in patients with completed resection. Multivariate analysis showed that only postoperative metastasis or recurrence were the indicators of poor prognosis, but without statistical significance (P=0.064). However, multivariate analysis for disease-free survival showed that preoperative metastasis and mitotic index were two independent predictors of poor prognosis (P=0.001 and P0.001).Most former leiomyomas/leiomyosarcomas of GI tract should be corrected to the diagnosis of GISTs. Complete surgical resection is the choice of treatment for GISTs. Preoperative metastasis and mitotic index are two independent predictors of poor prognosis.

To explore the factors affecting the long-term survival of patients with curative resection of gastric cardia cancer.The data of 108 patients who underwent radical resection of gastric cardia cancer from Jul. 1994 to Dec. 2003 in our hospital were investigated retrospectively. The Kaplan-Meier method and long-rank test were used for bivariate comparisons of survival. Multivariate analysis was done by the Cox regression model (Backward Wald).Survival status of the 108 patients was ascertained in Dec. 2004. Among them, 68 were Siewert type II and 40 were Siewert type III. Seventy-four patients had lymph node metastases (68.5%). The mean follow-up time was 37 months (95% CI: 29.3-44.7 months) and the middle follow-up time was 26.6 months (95% CI: 25.8-34.2 months). The 1-,3- and 5-year cumulative survival rates were 77.2%, 33.6% and 21.8%, respectively. According to the Kaplan-Meier and log-rank methods, splenectomy, lesion size, depth of tumor invasion and regional lymph node status were prognostic factors. Multivariate regression analysis indicated that only depth of tumor invasion (P=0.009) and lymph node metastases (P=0.001) were independent prognostic factors.Depth of tumor invasion and lymph node metastases have negative effects on the survival of patients with gastric cardia cancer undergoing curative resection. Splenectomy may only be appropriate for patients with direct tumor invasion to the spleen and the extent of gastric resection does not influence survival in patients with curative gastric cardia cancer.

To investigate the characteristics of lymph node metastases in advanced gastric cancer and its clinical significance.From April 2002 to July 2003, we studied 91 patients with advanced gastric cancer who underwent radical gastrectomy and lymphadenectomy from which specimens were obtained during surgery. Then, collection of dissected lymph node, histopathological and immunohistological studies were performed to detect the lymph node metastasis rates and calculation. In addition, to analyze the relationship between lymph node metastasis rates and tumor diameters, TNM classification, Borrmann analysis, tumor localization and the extent of lymph node resection.Among 91 patients with advanced gastric cancer, lymph node metastases were found in 63 patients (69.2%) with a total collection of 3149 lymph nodes and an average of 34.6 lymph nodes collected per patient. Lymph node metastasis rate was lower in tumor3 cm than that in tumor3 cm. About TNM classification, lymph node metastases in advanced gastric cancer among patients in stage IIIa and stage IV was 100%, with the lymph node metastasis rates varying from 30.3% to 58.4%, which were significantly higher than that among patients in stage I and II (P0.001). About Borrmann classification, lymph nodes metastasis in advanced gastric cancer among patients in Borrmann type III (79.6%) was higher than other Borrmann types, while in Borrmann type IV with the highest lymph node metastasis rate of 35.3% (P0.05). Patients undergone lymph node dissection D(3) had higher lymph node metastases among patients and higher lymph node metastasis rate (88.2%, 38.0%) than patients in the D(1) and D(2) (P0.05). Among 91 patients, 17 patients was found with micrometastasis (18.7%) from which 183 lymph nodes was collected, but no statistically significant difference between tumor location and micrometastasis was found (P0.05). For tumor localization, lymph node metastases in proximal gastric cancer were more shown in station 1, 2, 3, 5, 7, 8, 9, 12, 13 and 16, with the highest metastasis rate in station 8 (68.1%). Lymph node metastases in middle gastric cancer were more shown in station 1, 3, 7, 12, 13 and 16, with the highest metastasis rate in station 3 (47.6%). Lymph node metastases in distal gastric cancer were more shown in station 1, 2, 3, 5, 6, 12, 13, and 16, with the highest metastasis rate in station 16 (83.3%).Metastasis among patients and lymph node metastasis rates are significantly correlated with the severity of gastric malignancy and they may be valuable guideline to evaluate the extension of lymph nodes dissection in gastric cancer.

To investigate the related factors and prognosis of peritoneal dissemination and hepatic metastasis in gastric cancer, and the impact of palliative surgery on the prognosis.The clinicopathologic and follow-up data of the patients with gastric carcinoma treated in our hospital from Aug. 1994 to Jul. 2005 were analyzed retrospectively.The clinicopathologic factors correlated with peritoneal dissemination included serosal penetration, whole stomach cancer, undifferentiated type, female and hepatic metastasis, while those correlated with hepatic metastasis included Borrmann IV, lymph node metastasis and peritoneal dissemination (P0.05). The postoperative one-year survival rate of the patients with hepatic metastasis (H group) were lower than that of the patients with peritoneal dissemination (P group)(P0.05). The one- year survival rate of the patients with peritoneal dissemination undergoing palliative resection was significantly higher than that of the patients undergoing by-pass operation or feeding neostomy, and exploratory laparotomy (P0.05), while there was no significant difference among the three groups of the patients with hepatic metastasis.The short-term prognosis of the patients with hepatic metastasis is poorer than that of the patients with peritoneal dissemination. Palliative resection could improve the short-term survival rate of the patients with peritoneal dissemination, while it had no significant impact on the survival rate of the patients with hepatic metastasis.

To detect micrometastasis in regional lymph nodes using RT- PCR assay and evaluate the significance of the new assessment of nodal status in determining pN staging in gastric carcinoma.In addition to HE,RT- PCR assay for cytokeratin-20 gene marker was used to detect micrometastasis in 850 lymph nodes from 30 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy from Dec. 2003 to Apr. 2004.The detection rate of HE staining was 27.1% (233/850), the detection rate of RT-PCR assay was 36.5% (310/850) (Pa0.01). Lymph node micrometastasis was further detected in 77 nodes from 14 patients. The detection rate of RT- PCR assay from the routine negative lymph nodes was 12.5% (77/617). Seven of those patients were up- staged (from IB stage to II stage, from IB stage to III A stage, from I stage to III A stage, from III A stage to III B stage, from III A stage to IV stage in one patient respectively, and from III B stage to IV stage in 2 patients).RT- PCR assay can increase the detection rate of lymph node metastasis and have a significant impact on the staging system of gastric carcinoma.

To investigate the clinicopathologic features of the patients with node-negative metastasis (pN0) gastric carcinoma confirmed by routine pathologic examination (HaE staining),and their relationship with survival.The clinico-pathologic data of 87 pN0 gastric carcinoma patients were analyzed retrospectively. Kaplan-Meier (Log-rank) method was used to compare the survival rate,and Cox regression method was used to screen the independent prognosis factors for pN0 gastric cancer.There were 69 males and 18 females. D(2) lymphadenectomy was performed in 75 (86.2%), and D(3) in 13 cases (13.8%). Distal gastrectomy was performed in 59 (67.8%), total gastrectomy in 24 (27.6%) and proximal gastrectomy in l4 cases (4.6%). Twenty-three (26.4%) cases received postoperative chemotherapy and 64 (73.6% ) did not. The 5-year survival rate of the 87 pN0 gastric carcinoma patients was 56.5%. There were no differences in survival rate considering age, tumor location, gastrectomy, lymph nodes dissection, differentiation grade, and tumor-stroma relationship (P0.05), while the differences were significant in survival rate between the patients with postoperative chemotherapy,lymphatic invasion,venous invasion or not,and different pT staging (all Pa0.05). The Cox regression analysis revealed that pT staging and postoperative chemotherapy were independent prognostic factors.pT staging and postoperative chemotherapy are independent prognostic factors. It is necessary to develop a precise staging technique to select a suitable surgical therapy or confirm which patients should accept postoperative chemotherapy in pN0 gastric carcinoma patients.

To explore the patterns, intervals, risk factors of recurrent gastric cancer and provide evidences for predicting and prevention of recurrence after curative gastrectomy.Forty-eight patients with recurrent gastric cancer after curative gastrectomy for gastric cancer who were operated on in our department from August 1994 to August 1999 were enrolled in this study. Their recurrent patterns, intervals and clinicopathologic characters of primary tumors were analyzed retrospectively and compared with 48 cases without recurrence, who were treated homeochronously and chosen randomly. Risk factors correlated with tumor recurrence and recurrent intervals were studied by univariate and multivariate analysis.Univariate analysis showed that patients with metastases node in pelvic cavity, cancer invasion to serosa or more, Borrmann III or IV types were more occurred in recurrent group (P0.05). Multivariate analysis showed the depth of cancer invasion and Borrmann types were independently correlated with tumor recurrence after curative gastrectomy. COX regression analysis showed ascites and depth of cancer invasion were parameters dominating recurrent interval.Borrmann type is a risk factor of gastric cancer recurrence, while ascites is a parameter dominating recurrent interval, and the depth of cancer invasion is both risk factor of gastric cancer recurrence and parameter dominating recurrent interval.

To analyze the clinicopathological factors affecting synchronous liver metastasis in gastric cancer,and evaluate its surgical outcome.Clinical data of 44 patients with synchronous hepatic metastasis from gastric cancer from Aug. 1994 to Feb. 2004 were reviewed retrospectively, and compared with those of 576 gastric cancer patients without hepatic metastasis to analyze the clinicopathological factors affecting synchronous liver metastasis from gastric cancer. The survivals after radical resection, palliative and exploratory operation were compared.Univariate analysis revealed that ascites, pelvic and peritoneal seeding, serosal invasion, lymph node metastasis, involvement of neighboring organs, Borrmann types,depth of infiltration were correlated with synchronous hepatic metastasis from gastric cancer (P0.01). Logistic regression showed peritoneal seeding (P=0.003, OR=1.629), serosal infiltration (P=0.000, OR=3.000), lymph node metastasis (P=0.081, OR=1.689) were independent risk factors for synchronous hepatic metastasis from gastric cancer. Sixteen (36.4%) patients received radical excision, 15 (34.1%) patients palliative operation, and 13 (29.5 %) patients exploratory operation,and the median survival times were 19.5, 11.0 and 6.2 months respectively (P0.05).Peritoneal seeding,serosal infiltration, lymph node metastasis are most important risk factors for synchronous hepatic metastasis from gastric cancer. Radical resection of gastric primary lesion and hepatic metastases can significantly prolong survival time.

To investigate the disciplinarian of lymph node metastasis and evaluate the effect of paraaortic lymph nodes dissection on the clinical outcomes in advanced gastric carcinoma.One hundred and twenty-six patients who underwent D(3) (including D(3)(+)) radical resection (group D(3)) and 146 patients who underwent D(2) radical resection by the same surgical team (group D(2)) for advanced gastric cancer were enrolled in the present study. The dissected lymph nodes were grouped according to the definition of Japanese Research Society for the Study of Gastric Cancer (JRSGC) (Edition 13th). The lymph node metastasis was analyzed in group D(3). The clinicopathological characteristics and clinical outcomes were compared between the two groups.There were no differences in age, sex, tumor location, Borrman type, histological type and TNM stage between group D(2) and group D(3) (P0.05). The No16 lymph node metastatic rate was 3.8%, 22.3%, 46.8% and 32.1% in T(1), T(2), T(3), T(4) stage tumors respectively, 16.3% and 69.5% in the patients with negative and positive serosal invasion respectively; there were no differences in operative mortality (2/126 vs 2/146) and surgical complications (4/126 vs 6/146) between group D(2) and group D(3) (P0.05). The 5-year survival rate was 66.5% in group D(3) and 40.2% in group D(2) (P0.01). The 5-year survival rates of the patients with I, II, IIIa, IIIb and IV stage tumors who were No16 lymph nodes negative were 94.8%, 95.6%, 72.1%, 58.6%, 59% respectively in group D(3), and 42%, 36%, 27%, 35.6%, 16.3% respectively in group D(2). The 5-year survival rate of the patients with No16 (+) lymph nodes less than 3 was higher than that of the patients with No16(+) lymph nodes more than 3.No16a2 and No16b1 are the common locations of lymph node metastasis in advanced gastric cancer. The paraaortic lymph node metastasis closely is related with the depth of tumor invasion and serosal invasion. Paraaortic lymph nodes dissection (D(3) or D(3)(+) radical resection) improves the 5-year survival rate of the patients with No16 (-) and No16 (+) lymph nodes less than 3.

To analyze the relative risk factors of elderly patients with total gastrectomy for gastric cancer.The risk factors for hospital death and postoperative complications in 131 elderly patients undergoing total gastrectomy for gastric cancer from Aug. 1994 to Aug. 2004 were analyzed retrospectively.The risk factors for hospital death and postoperative complications included coexistent diseases, hemoglobin level less than 80 g/L, albumin level less than 35 g/L, body mass index(BMI) less than 18.5 kg/m (2), intraoperative blood loss more than 1000 ml, operating time longer than 5 h, combined resection of the spleen or pancreas. The relative risks were 1.57, 1.74, 2.97, 4.23, 2.21, 2.28, 3.80 respectively for hospital death, and 1.50, 1.90, 2.38, 2.12, 2.45, 1.66, 3.41 for postoperative complications.The risk factors of the elderly patients with total gastrectomy for gastric cancer should be considered carefully during the perioperative period. It can increase the security of the procedure to control these risk factors.

To investigate whether ulinastatin can alleviate the side effect in patients with gastrointestinal cancer undergoing adjuvant chemotherapy,and to explore the probable mechanism of its protective efficacy.Forty consecutive patients with gastrointestinal cancer who underwent surgical operations from May 2004 to October 2004 were recruited. The patients were randomly divided into therapeutic group and control group, receiving ulinastatin 150,000 U per day or 250 ml hydrochloric sodium before chemotherapy for 5 continuous days respectively. The prevalence of side effects and the levels IL-6 and TNF-alpha were compared between the two groups.There were no differences in the clinicopathological characteristics between the two groups. The prevalences of white blood cell decline (41.2% versus 13.1%), pigmentation (23.5% versus 4.3%), baldness (17.6% versus 4.3%) were higher in the control group than those in therapeutic group (all P0.05). In therapeutic group, IL-6 level was significantly decreased after ulinastatin treatment, but not in the control group while the levels of TNF-alpha were not changed in the both groups.Ulinastatin can reduce the common side effects of chemotherapy, and the mechanism may be associated with the decrease of IL-6.

To summarize the short-term outcomes of radical resection of gastric or colorectal carcinoma combined with liver transplantation for gastric or colorectal carcinoma with multiple hepatic metastases.Radical resection of gastric or colorectal carcinoma combined with liver transplantation were performed on one gastric carcinoma case and two rectal carcinoma cases with severe liver metastasis, and partial resection of left lung was performed in one of the two rectal cancer cases for pulmonary tuberculosis.There was no perioperative death. The gastric cancer patient died of recurrence 5 months after operation. The rectal cancer patient with pulmonary tuberculosis died of hepatic function failure 7 months after operation without recurrence. Another rectal cancer patient recovered well with normal liver functions, blood cells, without recurrence signs, and was back to work.Radical operation combined with liver transplantation may provide survival opportunity for some patients with gastric or colorectal carcinoma synchronous with severe liver metastasis, but the long-term outcome needs to be observed.