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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.

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 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.

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 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.

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.

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 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 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 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 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 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 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 explore the prevalence, clinical features and prognosis of multiple primary neoplasms in patients with colorectal carcinoma (CRC).Data of colorectal cancer patients admitted to our hospital from June 1994 to June 2002 were analyzed retrospectively. Patients were divided into multiple-cancer group (MCG) and single- cancer group (SCG). Clinical features and prognosis were compared between two groups.The incidence of multiple cancers was 7.4 % (83/ 1125). Forty- seven patients had multiple colorectal cancers metachronous CRC(S) in 12 and synchronous CRC(S) in 35. Thirty- six patients 5 patients with synchronous cancers had malignant tumors outside colorectal tract,12 of whom were gastric carcinomas. No significant differences were found between MCG and SCG regarding gender, onset age, Dukes stage and differentiation of index CRC. Cancer family history (P=0.002) and colorectal adenoma (P=0.036) were significantly more common in MCG than those in SCG. The local recurrence or distant metastasis in MCG was significantly higher than that in SCG (P=0.047), though there was no significant difference in survival between the two groups. Forty- one percent of index tumors were located in right colon in MCG, significantly higher than that in SCG (P=0.048). The secondary tumors were mainly adenoma cancerization in MCG.Cancer family history and colorectal adenoma seems to be at high risk for developing multiple cancers in CRC patients. Gastric cancer and colorectal adenoma cancerization were common secondary tumors of multiple primary neoplasms in patients with colorectal carcinoma.

To explore the relationship between heparanase mRNA expression and clinicopathological parameters in human gastric cancer.RT-PCR was used to detect the expression of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues.Heparanase mRNA was expressed in 29 of the 43 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than that in adjacent normal gastric tissues (P = 0.013). The expression level was higher in late-stage tumors (stage III and IV) than in early-stage tumors (stage I and II) (P = 0.001), in tumors with invasion to serosa than those without serosal invasion (P = 0.009), in tumors with lymph node metastasis than those without lymph node metastasis (P = 0.018), and in large-sized tumors than in small-sized ones (P = 0.009). The expression was not correlated with patients' age, sex, tumor location, histologic types, differentiation, peritoneal dissemination and liver metastasis (P0.05).Heparanase might play an important role in the development of invasion and metastasis of gastric cancer.

To investigate the clinical importance of palliative gastrectomy for late-staged gastric cancer.From June 1994 to October 2001, 95 patients with late-staged gastric cancer underwent palliative operation. Clinicopathological and prognostic parameters between 64 patients with palliative gastrectomy (PG group) and 31 patients with unresectable operation (UO group) was compared retrospectively.The age and gender ratios were not different between the two groups. The incidence of large volume (diameteror = 8 cm), serosal invasion (T(4)) and late TNM stage (IV stage) were significantly higher in the UO group than that in the PG group. There was no difference in peritoneal dissemination, distant lymph node and hepatic metastasis, and tumor location between the two groups. The one- and two-year survival of the patients in the PG group was 48.1% and 23.1%, and significantly better than 13.5% and 0 in the UO group.Palliative gastrectomy, compared with unresectable operation, can improve the prognosis of the patients with late-staged gastric cancer even with peritoneal dissemination, distant lymph node and hepatic metastasis, and surrounding organ invasion.