A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer.

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.

[Impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer patients].

OBJECTIVE: To explore the impact of clinicopathological features and extent of lymph node dissection on the prognosis in early gastric cancer (EGC) patients. METHODS: 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. RESULTS: 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 (P > 0.05). The TNM stages in the lymph node positive group were higher than that in the lymph node negative group (P < 0.001). 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 (P > 0.05). 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. CONCLUSIONS: 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.

[Effects of inhibition of Hedgehog signaling pathway for transforming growth factor-ß-induced epithelial-mesenchymal transition].

OBJECTIVE: To elucidate the mechanism of Hedgehog pathway in the metastasis of gastric cancer and examine particularly the effect on epithelial-mesenchymal transition (EMT). METHODS: Using pharmacological and siRNA knockdown approach, the Hedgehog pathway was inhibited. The cellular morphology, protein level, invasion and metastatic abilities were measured by microscope, Western blot, Transwell invasion assay and Transwell migration assay. RESULTS: Under the inhibition of Hedgehog pathway, the invasive and migration abilities of gastric cancer decreased. The transforming growth factor (TGF) -ß could induce spindle-like-shaped morphological changes with a down-regulation of epithelial characteristic (decreased E-cadherin protein level) and an up-regulation of mesenchymal characteristics (increased Vimentin protein level). There were concurrent increases of invasive and migration potentials by 3 and 4 folds respectively.However, under the continuous stimulation of TGF-ß, the inhibition of Hedgehog pathway could reverse the EMT changes, lower the expression of vimentin and reduce the invasion and metastatic abilities by 3 and 2 folds respectively. CONCLUSIONS: The inhibition of Hedgehog pathway can decrease the TGF-ß-inducing EMT.It suggests that Hedgehog pathway may play a critical role in the metastasis of gastric cancer.

[Risk factors and prognostic impact of No.12 lymph node metastasis in cases with curable advanced distal gastric cancer].

OBJECTIVE: 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. METHODS: 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. RESULTS: No significant inter-group difference existed in gender, age, infiltration depth or differentiation degree (all P > 0.05). 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 P < 0.01). 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). CONCLUSIONS: 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.

Abnormal expression of E-cadherin in tumor cells is associated with poor prognosis of gastric carcinoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to clarify the relationship of hepatocyte growth factor (HGF), c-Met, and E-cadherin with clinicopathological parameters and prognosis in gastric carcinoma (GC). METHODS: 114 specimens were collected from GC patients and expression of HGF, c-Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, follow-up data of patients, was analyzed statistically. RESULTS: Abnormal E-cadherin expression was found in 60.5% (69/114) and associated with tumor depth (P = 0.003), lymph node metastasis (P = 0.001) and advanced clinical stage (P = 0.001). High-expression of HGF and c-Met were found in 64.0% (73/114) and 82.4% (94/114), respectively. High c-Met expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.011) of GC. In univariate survival analysis, high-expression of HGF and c-Met, and abnormal E-cadherin were significantly associated with poor prognosis of GC patients. However, only abnormal E-cadherin expression (P = 0.001) and tumor depth (P = 0.010) emerged as strong independent prognostic factors for overall survival of GC patients. CONCLUSION: We found significant correlation among HGF/c-Met, E-cadherin expression and worse prognosis of patients with GC. Abnormal E-cadherin expression may serve as an independent predictive factor for prognosis of GC patients.

Tumor-associated macrophages promote angiogenesis and lymphangiogenesis of gastric cancer.

BACKGROUND AND OBJECTIVES: This study was conducted to investigate whether and how macrophages recruited to tumor microenvironments (tumor-associated macrophages, TAMs) were involved in angiogenesis and lymphangiogenesis of gastric cancer (GC). METHODS: TAMs, microvessel density (MVD), and lymphatic vessel density (LVD) in 115 cases of GC tissue were assessed by immunohistochemistry (IHC) staining of CD68, CD34, and D2-40, respectively. Preoperative blood samples from 43 patients were obtained to detect serum levels of vascular endothelial growth factor (VEGF) and VEGF-C. A co-culture system was also developed to study effects and underlying mechanisms of THP-1 macrophages on SGC7901 GC cells. RESULTS: TAMs numbers were closely related to serosa invasion, lymph node metastasis and tumor, nodes, and metastases stage and a positive correlation existed between the TAMs count and MVD and LVD. Additionally, TAMs were associated with preoperative serum levels of VEGF and VEGF-C, the expression of VEGF and VEGF-C protein in macrophages was up-regulated in the co-culture system, and inhibition of the NF-κB pathway in macrophages induced a significant reduction in the expression of VEGF and VEGF-C in both macrophages and GC cells (all P<0.05). CONCLUSIONS: TAMs may promote angiogenesis and lymphangiogenesis of GC, possibly by enhancing VEGF and VEGF-C expression.

[Clinicopathologic features and prognostic analyses of Borrmann type IV gastric cancer].

OBJECTIVE: To compare Borrmann type IV gastric cancer with other types of cancer and explore their clinicopathological features and prognostic factors. METHODS: 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. RESULTS: 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%) (P < 0.05). 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. CONCLUSIONS: 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.

[Selection of radical operative modalities for proximal gastric cancer].

OBJECTIVE: To evaluate the rationality of different radical operative modalities for proximal gastric cancer. METHODS: A total of 366 cases of proximal gastric cancer undergoing radical dissection were screened from data base. According to the operative modalities, they were divided into proximal gastrectomy group (PG) (n = 77) and total gastrectomy group (TG) (n = 289). Through the comparisons of clinical pathologic features, surgical profiles, postoperative complications, postoperative quality-of-life and prognosis in two groups, the rationality of different operative modalities was evaluated. RESULTS: No significant differences existed in age, gender or carcinoembryonic antigen (CEA) value between two groups (all P > 0.05). The rates of tumor diameter ≥ 5 cm, organic infiltration, lymph nodes metastasis, distal organs metastasis, infiltrative type, poorly differentiated tumor in PG and TG groups were 15.6% (12/77) vs 49.8% (144/289), 16.9% (13/77) vs 37.7% (109/289), 67.5% (52/77) vs 79.9% (231/289), 3.9% (3/77) vs 11.4% (33/289), 45.5% (35/77) vs 68.9% (199/289), 32.5% (25/77) vs 57.8% (167/289) respectively (all P < 0.05). Operative duration, volume of blood transfusion, number of dissected lymph nodes and positive lymph nodes, rate of combined organic resection and complications in groups of PG and TG were (256 ± 83) vs (298 ± 86)min, 0 vs 400 ml, 15 ± 12 vs 26 ± 15, 0 vs 3, 15.6% (12/77) vs 43.2% (125/289), 14.3% (11/77) vs 7.6% (22/289) respectively (all P < 0.05). In two groups, the evaluating indices of postoperative quality-of-life showed no significant differences (P > 0.05). In two groups, the median survival time of the cases with tumor diameter < 5 cm, no-organic infiltration, no-peri-tumor lymph nodes metastasis, no-distal organic metastasis had no significant difference (all P > 0.05). However, in groups of PG and TG, the median survival time of the cases with tumor diameter ≥ 5 cm, organic infiltration, peri-tumor lymph nodes metastasis and distal organic metastasis was 15.0 months vs 29.0 months, 15.0 months vs 30.0 months, 34.0 months vs 45.0 months, 4.0 months vs 18.0 months respectively(all P < 0.05). CONCLUSION: As compared with radical proximal gastrectomy, radical total gastrectomy improves significantly the prognosis of patients of proximal gastric cancer with organic infiltration, peri-tumor lymph nodes metastasis, distal organic metastasis and tumor diameter ≥ 5 cm.

[Impact of surgical modalities for gastric cancer on operational trauma].

OBJECTIVE: To evaluate the impact of surgical modality for gastric cancer on operational trauma. METHODS: 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. RESULTS: 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 (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). In cases of distal gastrectomy, median transfusion volume was 0 (0, 400) vs 400 (200, 800) ml in RR and NRR groups (P < 0.05). No significant difference existed in operative duration, postoperative hospital day or incidence of complications between two groups (all P > 0.05). 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 P > 0.05). 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 P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). 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 P < 0.05). But no significant difference existed in incidence of complications (P > 0.05). CONCLUSIONS: 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.

[Fast-track surgery accelerates the recovery of postoperative humoral immune function in elective operation for colorectal carcinoma: a randomized controlled clinical trial].

OBJECTIVE: To explore the effects of fast-track surgery on postoperative humoral immune function in patients undergoing elective colorectal resection. METHODS: 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. RESULTS: 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, P < 0.001) in patients undergoing fast-track rehabilitation. CONCLUSION: 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.

[Fast track surgery accelerates the postoperative rehabilitation and recovery of insulin sensitivity in elective operation for colorectal carcinoma: a randomized controlled clinical trial].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Impact of different gastrectomy and reconstruction methods on prognosis and quality of life in proximal gastric cancer].

OBJECTIVE: To evaluate the impact of different gastrectomy and reconstruction method on prognosis and quality of life in proximal gastric cancer. METHODS: 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. RESULTS: There had no significant differences in age, gender, CEA value between two groups (all P > 0.05). 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 P < 0.05). 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 P < 0.05). The median survival time (months) was 62.5 vs. 78.9 in TG and PG group respectively, without significant difference (P > 0.05). In 2 groups, the evaluation index of post-operative quality of life without significant differences (P > 0.05). CONCLUSIONS: 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.

[Comparison of clinical outcomes between laparoscopic-assisted and hand-assisted laparoscopic operations in colorectal cancer].

OBJECTIVE: To compare the clinical outcomes of laparoscopic-assisted versus hand-assisted laparoscopic radical operations in colorectal cancer and evaluate the safety and indications of hand-assisted laparoscopic operations. METHODS: A total of 64 consecutive colorectal cancer patients enrolled from November 2009 to December 2011 at our hospital were randomly and prospectively divided into 2 groups: hand-assisted laparoscopic operation (HALS) (n = 32) and laparoscopic-assisted operation (n = 32). And such clinicopathologic features as safety, operative curability and postoperative recovery were compared between two groups. RESULTS: Neither death nor conversion-to-open-surgery was reported among all patients. There were no statistical differences in such clinicopathologic features as age, gender, body mass index, mass size and location (all P > 0.05). There were statistically a shorter operation time [(127 ± 31) min vs (184 ± 71) min, P = 0.022] and a smaller number of Trocar (2.4 vs 5.0, P = 0.015) in the HALS group. However, the laparoscopic-assisted group had a lesser volume of blood loss [(82 ± 31) ml vs (150 ± 42) ml, P = 0.008] and a smaller postoperative 48 h drainage flow [(170 ± 52) ml vs (208 ± 58) ml, P = 0.020]. Moreover, no statistical differences existed in the length of bowel resection [(19 ± 5) cm vs (18 ± 4) cm], amount of lymph nodes dissection (16 ± 4 vs 16 ± 3), postoperative complications [12.5% (4/32) vs 25.0% (8/32)], time of intestinal function recovery [(1.7 ± 0.9) d vs (1.8 ± 0.7) d], time of semifluid tolerance [(2.9 ± 1.3) vs (2.8 ± 1.2) d], hospitalization expenses [(4.8 ± 0.6) 10 000 yuan vs (4.9 ± 0.4) 10 000 yuan] and postoperative hospital stay [(6.7 ± 2.3) d vs (6.6 ± 2.3) d] (all P > 0.05). CONCLUSION: HALS is both safe and efficacious for colorectal cancer patients.

[Reconstruction of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy: a meta-analysis of prospectively controlled trials].

OBJECTIVE: To compare the reconstructing safety of pancreaticogastrostomy (PG) versus pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD). METHODS: The articles of prospectively controlled trials published until late December 2010 comparing PJ and PG after PD were searched by the means of MEDLINE, EMBASE, Cochrane Controlled Trials Register databases and Chinese Biomedical Database. After quality assessment of all included prospective controlled trials, a meta-analysis was performed with Review Manager 5.0 for statistic analysis. RESULTS: A total of 6 prospective controlled trials were included. Among 867 patients analyzed, 440 underwent PG and 426 PJ. A meta-analysis of 6 prospective controlled trials (including randomized control trial (RCT) and non-randomized prospective trial) revealed significant differences between PJ and PG regarding the overall 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 differences in biliary fistula, intra-abdominal (IAC) complications and mortality were of no significance. Meta-analysis of 4 RCTs revealed significant differences 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, overall postoperative complications, biliary fistula, intra-abdominal complications and mortality were of no statistical significance. CONCLUSION: Through a meta-analysis of 6 prospective controlled trials, there are significant differences between PJ and PG regarding overall postoperative complications, pancreatic fistula and intra-abdominal fluid collection. Significant differences exist between PJ and PG regarding intra-abdominal fluid collection. The safety profiles of PG and PJ are comparable.

A Substage Increase in The AJCC Classification System Improves Prognostic Prediction in Stage III Gastric Cancer With Insufficient Lymph Nodes Removed.

BACKGROUND: The impact of lymph nodes (LNs) removed on the survivals of patients with stage III gastric cancer, especially on that of those who undergo the adjuvant chemotherapy as a compensation for a possibly insufficient lymphadenectomy, is still unclear. METHODS: Consecutive patients (n = 488) with stage III gastric cancer under R0 curative resection followed by adjuvant chemotherapy were analyzed. The overall survival (OS) was compared between patients with insufficient LNs removed (ILNr, <16 LNs) and sufficient LNs removed (SLNr, ≥16 LNs). Performance of the prediction systems was evaluated using the Likelihood ratio χ2 test, Akaike information criterion (AIC), Harrell's concordance index (C-index), and area under the receiver operating characteristic curves (AUC). RESULTS: The OS of patients were significantly longer in those with SLNr relative to those with ILNr (for stage IIIA, 68.2 vs. 43.2 months, P = 0.042; for stage IIIB, 43.7 vs. 24.9 months, P < 0.001; for stage IIIC, 23.9 vs. 8.3 months, P < 0.001; and for total stage III, 37.7 vs. 21.7 months, P < 0.001). However, the OS were similar between stage IIIA patients with ILNr and stage IIIB patients with SLNr (P = 0.928), between IIIB patients with ILNr and IIIC patients with SLNr (P = 0.962), and IIIC patients with ILNr and stage IV (P = 0.668), respectively. A substage increase in the AJCC classification system, from IIIA to IIIB, from IIIB to IIIC, and from IIIC to IV in patients with ILNr, enhanced the accuracy of prognostic prediction in patients with stage III gastric cancer compared to the current TNM system (Likelihood ratio χ2, 188.6 vs. 184.8; AIC, 4336.4 vs. 4340.6; C-index, 0.695 vs. 0.679, P = 0.002). The ROC curves revealed that the performance of prognostic prediction was better in the new prediction system (AUC = 0.699) compared with the current TNM system (AUC = 0.676). CONCLUSIONS: ILNr (LNs <16) impairs the long-term outcomes of stage III gastric cancer underwent adjuvant chemotherapy. The status of LNs removal adds values to the current TNM system in prognostic prediction of stage III gastric cancer.

[Regression analysis of the characteristics and outcome of colorectal cancer 1995 - 2007].

OBJECTIVE: To explore the clinical characteristics and the prognostic factors of patients with colorectal cancer. METHODS: The data of 2042 cases of colorectal cancer, pathologically confirmed at our hospital from January 1995 to December 2007, were summarized and analyzed. RESULTS: 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%). CONCLUSION: The prognostic factors of patients with colorectal cancer are age, gross type, differentiation, TNM staging, surgical type and adjuvant chemotherapy.

Anti-EGFR therapy in metastatic colorectal cancer: mechanisms and potential regimens of drug resistance.

Cetuximab and panitumumab, as the highly effective antibodies targeting epidermal growth factor receptor (EGFR), have clinical activity in the patients with metastatic colorectal cancer (mCRC). These agents have good curative efficacy, but drug resistance also exists at the same time. The effects of KRAS, NRAS, and BRAF mutations and HER2 amplification on the treatment of refractory mCRC have been elucidated and the corresponding countermeasures have been put forward. However, the changes in EGFR and its ligands, the mutations or amplifications of PIK3CA, PTEN, TP53, MET, HER3, IRS2, FGFR1, and MAP2K1, the overexpression of insulin growth factor-1, the low expression of Bcl-2-interacting mediator of cell death, mismatch repair-deficient, and epigenetic instability may also lead to drug resistance in mCRC. Although the emergence of drug resistance has genetic or epigenetic heterogeneity, most of these molecular changes relating to it are focused on the key signaling pathways, such as the RAS/RAF/mitogen-activated protein kinase or phosphatidylinositol 3-kinase/Akt/mammalian target of the rapamycin pathway. Accordingly, numerous efforts to target these signaling pathways and develop the novel therapeutic regimens have been carried out. Herein, we have reviewed the underlying mechanisms of the resistance to anti-EGFR therapy and the possible implications in clinical practice.

High expression of PRL-3 can promote growth of gastric cancer and exhibits a poor prognostic impact on patients.

High expression of PRL-3 had been implicated in lymph node metastasis of gastric cancer. In the present study, we detected the expression of PRL-3 in primary gastric cancer tissue, and evaluated its role in gastric cancer growth and the prognostic impact on patients. PRL-3 phosphatase expression was measured in 137 gastric tumor samples by using the immunohistochemistry method, and the overall survival rate was compared between the patients with high PRL-3 expression (n = 85) and those with moderate or low PRL-3 expression (n = 52). RNA interference, mediated by recombinant lentivirus expressing artificial PRL-3 miRNA, was used to knockdown PRL-3 expression in SGC7901 cell line. MTT assay and animal experiment were conducted to determine the role of PRL-3 in the proliferation of SGC7901 cells and tumor growth. PRL-3 expression was more frequently detected in tumors with a diameter >40 mm and in advanced stages. Furthermore, the overall survival rate of high PRL-3 expression was significantly lower than that of moderate or low PRL-3 expression (P < 0.001), and multivariate analysis showed that PRL-3 expression level independently influences the survival of patients (P = 0.024). Importantly, knockdown of PRL-3 significantly suppressed the proliferation of SGC7901 cells and slowed the tumor growth compared with controls (P < 0.05). PRL-3 is associated with gastric cancer progression. High PRL-3 expression in the primary lesion had a negative impact on prognosis. PRL-3 plays a key role in the control of gastric cancer growth. PRL-3 should be considered as a potential therapeutic target and a prognostic factor.

[Value of spiral CT plus endoscopic ultrasonography (EUS) and spiral CT plus PET-CT in the preoperative assessment of gastric cancer invasion to the pancreas].

OBJECTIVE: To evaluate the value of EUS and PET-CT in combination with spiral CT in preoperative assessment of gastric cancer invasion to the pancreas. METHODS: 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. 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 (P<0.01), but no significant difference between spiral CT alone and spiral CT combined with PET-CT (P>0.05). Spiral CT-EUS was more valuable in assessment of tumor location and invasion than PET-CT (P<0.01). CONCLUSION: 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.

[Comparison of clinicopathologic parameters and prognosis of gastric carcinoma between different phases].

OBJECTIVE: To compare the clinicopathologic parameters of gastric carcinoma between different phases and to investigate the prognostic factors for gastric carcinoma. METHODS: 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. RESULTS: 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 P < 0.05), 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 P < 0.01). 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 P < 0.01). 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. CONCLUSION: 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.