Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer

AIM:To investigate human epidermal growth factor receptor 2(HER2) gene amplification and protein expression in Chinese patients with resectable gastric cancer and the association with clinicopathological characteristics and survival.METHODS:One hundred and ninety-seven gastric cancer patients who underwent curative surgery procedures were enrolled into this study.HER2 gene amplification and protein expression were examined using fluorescence in-situ hybridization(FISH) and immunohistochemistry(IHC) analysis on formalin-fixed paraffinembedded gastric cancer samples from all patients.For scoring,Hofmann’s HER2 gastric cancer scoring system was adopted.All cases showing IHC3+ or FISH positiv-ity were defined as HER2 positive.Patient clinicopathological data and survival information were collected.Finally,χ 2 statistical analysis was performed to analyze the HER2 positivity rate amongst the subgroups with different clinicopathological characteristics including;gender,age,tumor location,Lauren classification,differentiation,TNM staging,depth of invasion,lymph node metastases and distant metastasis.The probability of survival for different subgroups with different clinicopathological characteristics was calculated using the Kaplan-Meier method and survival curves plotted using log rank inspection.RESULTS:According to Hofmann’s HER2 gastric cancer scoring criteria,31 cases(15.74%) were identified as HER2 gene amplified and 19 cases(9.64%) were scored as strongly positive for HER2 membrane staining(3+),25 cases(12.69%) were moderately positive(2+) and 153 cases(77.66%) were HER2 negative(0/1+).The concordance rate between IHC and FISH analyses was 88.83%(175/197).Thirty-six cases were defined as positive for HER2 gene amplification and/or protein expression,with 24 of these cases being eligible for Herceptin treatment according to United States recommendations,and 29 of these cases eligible according to EU recommendations.Highly consistent results were detected between IHC3+,IHC0/1 and FISH(73.68% and 95.42%),but l     

Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer

AIM: To evaluate the expression of galectin-1 and vascular endothelial growth factor (VEGF) in gastric cancer and investigate their relationships with clinicopathologic factors and prognostic significance. METHODS: Galectin-1 and VEGF were immunohistochemically investigated in tumor samples obtained from 214 gastric cancer patients with all tumor stages. Immunohistochemical analyses for galectin-1 and VEGF expression were performed on formalin-fixed, paraffin-embedded sections of surgical specimens. The relationship between the expression and staining intensity of galectin-1 and VEGF, clinicopathologic variables, and patient survival were analyzed. All patients underwent follow-up until cancer-related death or more than five years after tumor resection. P values < 0.05 were considered statistically significant.RESULTS: Immunohistochemical staining demonstrated that 138 of 214 gastric cancer samples (64.5%) were positive for galectin-1, and 116 out of 214 gastric cancer samples (54.2%) were positive for VEGF. There was a significant association between galectin-1 and VEGF expression; VEGF was detected in 60.1% of galectin-1-positive samples and 43.4% of galectin-1-negative samples (P < 0.05). Galectin-1 expression was associated with tumor size, tumor location, stage, lymph node metastases, and VEGF expression (all P < 0.05). VEGF expression was related to tumor size, stage, and lymph node metastases (all P < 0.05). The 5-year survival rate was 56.6% for galectin-1-positive patients and 69.2% for galectin-1-negative patients, and the prognosis for galectin-1-positive patients was significantly poorer compared with galectin-1-negative patients (χ 2 = 13.880, P = 0.000). The 5-year survival rates for VEGF-positive and VEGF-negative patients were 53.4% and 70.5%, respectively (χ2 = 4.619, P = 0.032). The overall survival rate of patients with both galectin-1 and VEGF overexpression in gastric cancer tissue samples was significantly poorer than other groups (both P < 0.05).CONCLUSION: Galectin-1 expr     

Clinical role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in post-operative follow up of gastric cancer： Initial results

AIM： To evaluate the clinical role of 18F-fluorodeo-xyglucose positron emission and computed tomography （18F-FDG PET/CT） in detection of gastric cancer recurrence after initial surgical resection. METHODS： In the period from January 2007 to May 2008, 23 patients who had previous surgical resection of histopathologically diagnosed gastric cancer underwent a total of 25 18F-FDG PET/CT scans as follow-up visits in our center. The standard of reference for tumor recurrence consisted of histopathologic confirmation or clinical follow-up information for at least 5 mo after PET/CT examinations. RESULTS： PET/CT was positive in 14 patients （61%） and negative in 9 （39%）. When correlated with final diagnosis, which was confirmed by histopathologic evidence of tumor recurrence in 8 of the 23 patients （35%） and by clinical follow-up in 15 （65%）, PET/CT was true positive in 12 patients, false positive in 2, true negative in 8 and false negative in 2. Overall, the accuracy of PET/CT was 82.6%, the negative predictive value （NPV） was 77.7%, and the positive predictive value （PPV） was 85.7%. The 2 false positive PET/CT findings were actually chronic inflammatory tissue lesions. For the two patients with false negativePET/CT, the f inal diagnosis was recurrence of mucinous adenocarcinoma in the anastomosis in one patient and abdominal wall metastasis in the other. Importantly, PET/CT revealed true-positive findings in 11 （47.8%） patients who had negative or no definite findings by CT. PET/CT revealed extra-abdominal metastases in 7 patients and additional esophageal carcinoma in one patient. Clinical treatment decisions were changed in 7 （30.4%） patients after introducing PET/CT into their conventional post-operative follow-up program. CONCLUSION： Whole body 18F-FDG PET/CT was highly effective in discriminating true recurrence in post-operative patients with gastric cancer and had important impacts on clinical decisions in a considerable portion of patients.     

Vascular resection in pancreatic adenocarcinoma with portal or superior mesenteric vein invasion

AIM:To evaluate long-term survival after the Whipple operation with superior mesenteric vein/portal vein resection(SMV/PVR)in relation to resection length.METHODS:We evaluated 118 patients who underwent the Whipple operation for pancreatic adenocarcinoma at our Department of Hepatobiliary Pancreatic Surgery between 2005 and 2010.Fifty-eight of these patients were diagnosed with microscopic PV/SMV invasion by frozen-section examination and underwent SMV/PVR.In 28 patients,the length of SMV/PVR was≤3 cm.In the other 30 patients,the length of SMV/PVR was>3cm.Clinical and survival data were analyzed.RESULTS:SMV/PVR was performed successfully in 58patients.There was a significant difference between the two groups(SMV/PVR≤3 cm and SMV/PVR>3 cm)in terms of the mean survival time(18 mo vs 11 mo)and the overall 1-and 3-year survival rates(67.9%and14.3%vs 41.3%and 5.7%,P<0.02).However,there was no significant difference in age(64 years vs 58years,P=0.06),operative time(435 min vs 477 min,P=0.063),blood loss(300 mL vs 383 mL,P=0.071)and transfusion volume(85.7 mL vs 166.7 mL,P=0.084)between the two groups.CONCLUSION:Patients who underwent the Whipple operation with SMV/PVR≤3 cm had better long-term survival than those with>3 cm resection.     

&beta;-elemene enhances the radiosensitivity of gastric cancer cells by inhibiting Pak1 activation

AIM: To explore the potential of β-elemene as a radiosensitizer for gastric cancer cells and the underlying mechanisms. METHODS: SGC7901, MKN45, MKN28, N87, and AGS human gastric cancer cell lines were used to screen for radioresistant gastric cancer cell lines. A 3-(4,5-dimeth-ylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was used to determine the effects of β-elemene and IPA-3 on cell viability in MKN45 and SGC7901 gastric cancer cell lines. A clonogenic survival assay and annexin V-FITC/PI apoptosis detection assay were used to evaluate cellular radiosensitivity and radiation-induced cell death, respectively. A proteomic method, isobaric tags for relative and absolute quantitation (iTRAQ), was employed to screen the proteins regulated by β-elemene pretreatment prior to ionizing radiation (IR) in SGC7901 gastric cancer cell line. IPA-3 was used as a specific small molecule inhibitor of p21-activated protein kinase 1 (Pak1) to target Pak1 signaling. Protein levels of PAK1IP1 (p21-activated protein kinase-interacting protein 1), total Pak1 (t-Pak1), phospho-Pak1 (T423), phospho-ERK1/2 (Thr202/Tyr204), and cleaved caspase-3 (17 kDa) were assessed by western blotting. RESULTS: MKN45 and SGC7901 gastric cancer cell lines were relatively more resistant to IR. β-elemene pretreatment decreased clonogenic survival following IR in MKN45 and SGC7901 gastric cancer cell lines. Additionally, β-elemene pretreatment prior to IR increased radiation-induced cell death compared with IR alone in MKN45 (10.4% ± 0.9% vs 34.8% ± 2.8%, P < 0.05) and SGC7901 (11.6% ± 0.9% vs 46.7% ± 5.2%, P < 0.05) human gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Through iTRAQ analysis and western blot validation, we found that β-elemene upregulated PAK1IP1 and downregulated phospho-Pak1 (T423) and phospho-ERK1/2 in SGC7901 gastric cancer cells. IR increased the level of phospho-Pak1 (T423). Pretreatment with β-elemene decreased radiation-induced Pak1 and ERK1/2 phosphorylation. Inhibition of Pak1 using IPA-3 decreased clonogenic survival following IR. In addition, IPA-3 increased radiation-induced cell death in MKN45 (13.4% ± 0.3% vs 26.6% ± 1.0%, P < 0.05) and SGC7901 (16.0% ± 0.6% vs 37.3% ± 1.7%, P < 0.05) gastric cancer cell lines, respectively, consistent with the level of cleaved caspase-3 (17 kDa). Western blotting showed that IPA-3 decreased radiation-induced Pak1 and ERK1/2 phosphorylation. CONCLUSION: This is the first demonstration that β-elemene enhances radiosensitivity of gastric cancer cells, and that the mechanism involves inhibition of Pak1 signaling.     

Short-term outcomes of laparoscopic total mesorectal excision compared to open surgery

AIM:To investigate the short-term outcome of laparoscopic total mesorectal excision(TME) in patients with mid and low rectal cancers.METHODS:A consecutive series of 138 patients with middle and low rectal cancer were randomly assigned to either the laparoscopic TME(LTME) group or the open TME(OTME) group between September 2008 and July 2011 at the Department of Colorectal Cancer of Shanghai Cancer Center,Fudan University and pathological data,as well as surgical technique were reviewed retrospectively.Short-term clinical and oncological outcome were compared in these two groups.Patients were followed in the outpatient clinic 2 wk after the surgery and then every 3 mo in the first year if no adjuvant chemoradiation was indicated.Statistical analysis was performed using SPSS 13.0 software.RESULTS:Sixty-seven patients were treated with LTME and 71 patients were treated with OTME(sex ratio 1.3:1vs 1.29:1,age 58.4 ± 13.6 years vs 59.6 ± 9.4 years,respectively).The resection was considered curative in all cases.The sphincter-preserving rate was 65.7%(44/67) vs 60.6%(43/71),P = 0.046;mean blood loss was 86.9 ± 37.6 mL vs 119.1 ± 32.7 mL,P = 0.018;postoperative analgesia was 2.1 ± 0.6 d vs 3.9 ± 1.8 d,P = 0.008;duration of urinary drainage was 4.7 ± 1.8 d vs 6.9 ± 3.4 d,P = 0.016,respectively.The conversion rate was 2.99%.The complication rate,circumferential margin involvement,distal margins and lymph node yield were similar for both procedures.No port site recurrence,anastomotic recurrence or mortality was observed during a median follow-up period of 21 mo(range:9-56 mo).CONCLUSION:Laparoscopic TME is safe and feasible,with an oncological adequacy comparable to the open approach.Further studies with more patients and longer follow-up are needed to confirm the present results.     

Substance P,vasoactive intestinal peptide,and leu-enkephalin in plasma and gastric juice of patients with precancerous lesions and gastric cancer

AIM: To investigate the changes of the brain-gut-peptide concentrations in the plasma and gastric juice and their relations to gastric diseases. METHODS: A total of 83 subjects were part of the study. Of those, 28 had chronic atrophic gastritis with precancerous lesions, 22 had gastric cancer in an advanced stage, and 33 were healthy subjects for a control group. Samples of fasting blood and gastric juice were collected. Levels of substance P (SP), vasoactive intestinal peptide (VIP) and leu-enkephalin (LEK) in plasma and gastric juice were measured with radioimmunoassay kits expressed as ng/L. RESULTS: In patients with gastric cancer, the SP levels (83.7 ± 11.0 vs 39.6 ± 4.5, P < 0.01; 24.0 ± 1.6 vs 17.8 ± 1.5, P < 0.05) and LEK in plasma and gastric juice (226.2 ± 15.4 vs 180.3 ± 13.1, P < 0.01; 55.0 ± 3.4 vs 30.7 ± 2.4, P < 0.05), and VIP of gastric juice (80.5 ± 2.9 vs 64.3 ± 4.1, P < 0.05) were higher than those in the controls. The SP and LEK levels of plasma correlated with those of gastric juice (r = 0.432 and 0.516, P < 0.05). In the post-surgical gastric cancer, plasma levels of SP and gastric juice LEK were lower than the pre-surgical levels (P < 0.05). In the precancerous lesions, plasma and gastric juice LEK levels and gastric juice VIP levels were increased (P < 0.05), and the plasma LEK level correlated with the gastric juice LEK level (r = 0.398, P < 0.05). CONCLUSION: Measurement of concentrations of SP, VIP, and LEK in plasma and gastric juice is of clinical significance in detecting certain stomach diseases.     

Alcohol,postprandial plasma glucose,and prognosis of hepatocellular carcinoma

AIM:To identify factors associated with prognosis of hepatocellular carcinoma(HCC) after initial therapy.METHODS:A total of 377 HCC patients who were newly treated at Katsushika Medical Center,Japan from January 2000 to December 2009 and followed up for > 2 years,or died during follow-up,were enrolled.The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis.A similar analysis was performed in 282 patients with tumor stage T1-T3.Additionally,factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence.Finally,214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels,and differences in their causes of death were examined.RESULTS:On multivariate Cox proportional hazards regression analysis,the following were significantly associated with survival:underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C,hazard ratio(HR):0.603,95% CI:0.417-0.874,P = 0.0079],HCC stage(T1/T2 vs T3/T4,HR:0.447,95% CI:0.347-0.576,P < 0.0001),and mean postprandial plasma glucose after initial therapy(< 200 vs ≥ 200 mg/dL,HR:0.181,95% CI:0.067-0.488,P = 0.0008).In T1-T3 patients,uninterrupted alcohol consumption after initial therapy(no vs yes,HR:0.641,95% CI:0.469-0.877,P = 0.0055) was significant in addition to underlying liver disease stage(non-cirrhosis/Child-Pugh A vs B/C,HR:0649,95% CI:0.476-0.885,P = 0.0068),HCC stage(T1 vs T2/T3,HR:0.788,95% CI:0.653-0.945,P = 0.0108),and mean postprandial plasma glucose after initial therapy(< 200 mg/dL vs ≥ 200 mg/dL,HR:0.502,95% CI:0.337-0.747,P = 0.0005).In patients without local recurrence,time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group"(l     

Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells

AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.     

Changes in patients&rsquo; symptoms and gastric emptying after Helicobacter pylori treatment

AIM: To investigate the changes in clinical symptoms and gastric emptying and their association in functional dyspepsia (FD) patients. METHODS: Seventy FD patients were enrolled and divided into 2 groups Helicobacter pylori (H. pylori)-negative group (28 patients), and H. pylori-positive group (42 patients). Patients in the H. pylori-positive group were further randomly divided into groups: H. pylori-treatment group (21 patients) and conventional treatment group (21 patients). Seventy two healthy subjects were selected as the control group. The proximal and distal stomach area was measured by ultrasound immediately after patients took the test meal, and at 20, 40, 60 and 90 min; then, gastric half-emptying time was calculated. The incidence of symptoms and gastric half-emptying time between the FD and control groups were compared. The H. pylori-negative and conventional treatment groups were given conventional treatment: domperidone 0.6 mg/(kg/d) for 1 mo. The H. pylori-treatment group was given H. pylori eradication treatment + conventional treatment: lansoprazole 30 mg once daily, clarithromycin 0.5 g twice daily and amoxicillin 1.0 g twice daily for 1 wk, then domperidone 0.6 mg/(kg/d) for 1 mo. The incidence of symptoms and gastric emptying were compared between the FD and control groups. The relationship between dyspeptic symptoms and gastric half-emptying time in the FD and control groups were analyzed. Then total symptom scores before and after treatment and gastric half-emptying time were compared among the 3 groups. RESULTS: The incidence of abdominal pain, epigastric burning sensation, abdominal distension, nausea, belching, and early satiety symptoms in the FD group were significantly higher than in the control group (50.0% vs 20.8%; 37.1% vs 12.5%; 78.6% vs 44.4%; 45.7% vs 22.2%; 52.9% vs 15.3%; 57.1% vs 19.4%; all P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the FD group were slower than in the control group (93.7 ± 26.2 vs 72.0 ± 14.3; 102.2 ± 26.4 vs 87.5 ± 18.2; 102.1 ± 28.6 vs 78.3 ± 14.1; all P < 0.05). Abdominal distension, belching and early satiety had an effect on distal gastric half-emptying time (P < 0.05). Abdominal distension and abdominal pain had an effect on the gastric half-emptying time of the whole stomach (P < 0.05). All were risk factors (odds ratio > 1). The total symptom score of the 3 groups after treatment was lower than before treatment (P < 0.05). Total symptom scores after treatment in the H. pylori-treatment group and H. pylori-negative group were lower than in the conventional treatment group (5.15 ± 2.27 vs 7.02 ± 3.04, 4.93 ± 3.22 vs 7.02 ± 3.04, All P < 0.05). The gastric half-emptying times of the proximal end, distal end, and the whole stomach in the H. pylori-negative and H. pylori-treatment groups were shorter than in the conventional treatment group (P < 0.05). CONCLUSION: FD patients have delayed gastric emptying. H. pylori infection treatment helps to improve symptoms of dyspepsia and is a reasonable choice for treatment in clinical practice.     

Clinical implication of FDG uptake of bone marrow on PET/CT in gastric cancer patients with surgical resection

AIM To determine the relationship between F-18 fluorodeoxyglucose(FDG) uptake of bone marrow(BM) on positron emission tomography/computed tomography(PET/CT) and clinical factors and to assess the prognostic value of FDG uptake of BM in gastric carcinoma.METHODS We retrospectively enrolled 309 gastric cancer patients who underwent staging FDG PET/CT and curative surgical resection. FDG uptake of primary tumor was visually classified as positive or negative FDG uptake. Mean FDG uptake of BM(BM SUV) and BM-to-liver uptake ratio(BLR) were measured. The relationships of BM SUV or BLR with clinical factors were evaluated. The prognostic values of BM SUV, BLR, and other clinical factors for predicting recurrence-free survival(RFS) and overall survival(OS) were assessed.RESULTS Of 309 patients, 38 patients(12.3%) experienced cancer recurrence and 18 patients(5.8%) died. Patients with advanced gastric cancer, positive FDG uptake, and recurrence had higher values of BM SUV and BLR than those with early gastric cancer, negative FDG uptake, and no recurrence(P 0.05). BM SUV and BLR were significantly correlated with hemoglobin level, neutrophil-to-lymphocyte ratio, and platelet-tolymphocyte ratio(P 0.05). On multivariate analysis, multiple tumors, T stage, lymph node metastasis, tumor involvement of resection margin, and BLR were significantly associated with RFS(P 0.05). T stage, lymph node metastasis, hemoglobin level, and BLR were significantly associated with OS(P 0.05). CONCLUSION BLR on PET/CT was an independent prognostic factor for RFS and OS in gastric cancer patients with curative surgical resection.     

Ex-situ liver surgery without veno-venous bypass

AIM:To evaluate the results of hepatic resection with ex-situ hypothermic perfusion and without veno-venous bypass.METHODS:In 3 patients with liver tumor,the degree of the inferior vena cava and/or main hepatic vein involvement was verified when the liver was dissociated in the operation.It was impossible to resect the tumors by the routine hepatectomy,so the patients underwent ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.All surgical procedures were carried out or supervised by a senior surgeon.A retrospective analysis was performed for the prospectively collected data from patients with liver tumor undergoing ex-situ liver surgery,vein cava replacement and hepatic autotransplantation without veno-venous bypass.We also compared our data with the 9 cases of Pichlmayr's group.RESULTS:Three patients with liver tumor were analysed.The first case was a 60-year-old female with a huge haemangioma located in S1,S4,S5,S6,S7 and S8 of liver;the second was a 64-year-old man with cholangiocarcinoma in S1,S2,S3 and S4 and the third one was a 55-year-old man with a huge cholangiocarcinoma in S1,S5,S7 and S8.The operation time for the three patients were 6.6,6.4 and 7.3 h,respectively.The anhepatic phases were 3.8,2.8 and 4.0 h.The volume of blood loss during operation were 1200,3100,2000 mL in the three patients,respectively.The survival periods without recurrence were 22 and 17 mo in the first two cases.As for the third case complicated with postoperative hepatic vein outflow obstruction,emergency hepatic vein outflow extending operation and assistant living donor liver transplantation were performed the next day,and finally died of liver and renal failure on the third day.Operation time(6.7 ± 0.47 h vs 13.7 ± 2.6 h) and anhepatic phase(3.5 ± 0.64 h vs 5.7 ± 1.7 h) were compared between Pichlmayr's group and our series(P = 0.78).CONCLUSION:Ex-situ liver resection and liver autotransplantation has shown a potential for treatment of complicated hepatic neoplasms that are unresectable by traditional procedures.     

Improvement of prognosis for unresectable biliary tract cancer

AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan,were retrospectively analyzed.These patients were divided into three groups based on the year beginning chemotherapy:Group A(2000-2003),Group B(2004-2006),and Group C(2007-2009).The data were fixed at the end of December 2011.Overall survival and time-to-progression were analyzed and compared chronologically.RESULTS:No patient characteristics were significantly different among the three groups.The gallbladder was involved in about half of the patients in each group,and metastatic biliary tract cancer was present in three quarters of the enrollees.In Group A,5-fluorouracilbased chemotherapies were primarily selected as firstline chemotherapy,and only 24% were treated with second-line chemotherapy.In Group B,gemcitabine or S-1 monotherapy was mainly introduced as firstline chemotherapy,and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy.In Group C,the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy,and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy.The median timeto-progressions were 4.4 mo,3.5 mo and 5.9 mo in Groups A,B and C,respectively(4.4 mo vs 3.5 mo vs 5.9 mo,P < 0.01).The median overall survivals were 7.1,7.3,and 11.7 mo in Groups A,B and C(7.1 mo vs 7.3 mo vs 11.7 mo,P = 0.03).Induction rates of all three drugs(gemcitabine,platinum analogs,and fluoropyrimidine) in Groups A,B and C were 4%,2% and 27%(4% vs 2% vs 27%,P < 0.01).CONCLUSION:The prognosis of unresectable biliary tract cancer has improved recently.Using three effective drugs(gemcitabine,platinum analogs,and fluoropyrimidine) may     

应用米兰标准微波消融治疗肝细胞癌患者预后及其影响因素分析*

目的 探讨应用米兰标准施行微波消融术(MWA)治疗肝细胞癌(HCC)患者影响生存的因素。方法 2013年1月～2016年12月我院消化内科住院的94例直径≤5 cm的HCC患者接受超声引导下MWA治疗,随访5年。分析不同HCC结节个数和不同肿瘤直径对总生存率(OS)和无进展生存率(PFS)的影响。结果 随访5年,本组HCC患者OS为64.9%,1 a和2 a 肿瘤复发率分别为12.8%和53.2%;HCC直径> 3 cm患者的PFS显著短于直径≤3 cm的患者(P=0.005),PFS≤2年的HCC患者OS显著低于PFS> 2年的患者(48.0%对 84.1%,P<0.001);多因素回归分析显示HCC直径> 3 cm (HR=0.42,95%CI:0.21～0.83,P=0.01)是MWA术后肿瘤复发的独立危险因素,而白细胞计数< 4.0×10⁹ /L (HR=0.38, 95%CI:0.18～0.84,P=0.017)和PFS≤2 年(HR=0.24, 95%CI:0.10～0.56,P=0.001)是影响HCC患者OS的独立危险因素。结论 直径> 3 cm的HCC患者PFS较短,但似乎不影响OS,因为大多数肝内复发的HCC患者仍然可进行重复MWA治疗。     

Preoperative defining system for pancreatic head cancer considering surgical resection

AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members. METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing "resectability- tumor location- vascular relationship- adjacent organ involvement- preoperative CA19-9(initial bilirubin level)- vascular anomaly". The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients(66.4%) with resectable, 34 patients(30.1%) with borderline resectable, and 4 patients(3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo(95%CI: 19.6-30.1) with a 5-year diseasefree survival rate of 13.5%. Pretreatment tumor size ≥ 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatichead cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 ≥ 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence. CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.     

Long-term outcomes and prognostic factors of patients with obstructive colorectal cancer: A multicenter retrospective cohort study

AIM: To investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive colorectal cancer(CRC) at multiple Japanese institutions.METHODS: We identified 362 patients diagnosed with obstructive colorectal cancer from January 1, 2002 to December 31, 2012 in Yokohama Clinical Oncology Group's department of gastroenterological surgery. Among them, 234 patients with stage Ⅱ/Ⅲ disease who had undergone surgical resection of their primary lesions were analyzed, retrospectively. We report the long-term outcomes, the risk factors for recurrence, and the prognostic factors.RESULTS: The five-year disease free survival and cancer-specific survival were 50.6% and 80.3%, respectively. A multivariate analysis showed the ASAPS(HR = 2.23, P = 0.026), serum Albumin ≤ 4.0 g/d L(HR = 2.96, P = 0.007), T4 tumor(HR = 2.73, P = 0.002) and R1 resection(HR = 6.56, P = 0.02) to be independent risk factors for recurrence. Furthermore, poorly differentiated cancers(HR = 6.28, P = 0.009), a T4 tumor(HR = 3.46, P = 0.011) and R1 resection(HR = 6.16, P = 0.006) were independent prognostic factors in patients with obstructive CRC.CONCLUSION: The outcomes of patients with obstructive CRC was poor. T4 tumor and R1 resection were found to be independent prognostic factors for both recurrence and survival in patients with obstructive CRC.     

A case of small bowel adenocarcinoma in a patient with Crohn's disease detected by PET/CT and double-balloon enteroscopy

Small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) is quite rare, difficult to diagnose without surgery, and has a poor prognosis. Here, we report a 48-year-old man with SBA and a 21-year history of CD who was diagnosed by a combination of positron emission tomography/computed tomography (PET/CT) and double-balloon enteroscopy (DBE). Since the age of 27 years, the patient had been treated for ileal CD and was referred to our hospital with persistent melena. Multiple hepatic tumors were found by CT. PET/CT detected an accumulation spot in the small bowel. DBE revealed an ulcerative tumor in the ileum about 100 cm from the ileocecal valve. An endoscopic forceps biopsy specimen showed poorly differentiated adenocarcinoma. There were some longitudinal ulcer scars near the tumor, and the chronic inflammation in the small bowel appeared to be associated with the cancer development. Previous reports suggest the risk of SBA in patients with CD is higher than in the overall population. Since early diagnosis is extremely difficult in these cases, novel techniques, such as PET/CT and DBE, may be expected to help in making a preoperative diagnosis of the development of SBA in CD.     

Standard triple versus levofloxacin based regimen for eradication of Helicobacter pylori

AIM: To compare the eradication rates for Helicobacter pylori (H. pylori) and ulcer recurrence of standard triple therapy (STT) and levofloxacin based therapy (LBT). METHODS: Seventy-four patients with perforated duodenal ulcer treated with simple closure and found to be H. pylori infected on 3 mo follow up were randomized to receive either the STT group comprising of amoxicillin 1 g bid, clarithromycin 500 mg bid and omeprazole 20 mg bid or the LBT group comprising of amoxicillin 1 g bid, levofloxacin 500 mg bid and omeprazole 20 mg bid for 10 d each. The H. pylori eradication rates, side effects, compliance and the recurrence of ulcer were assessed in the two groups at 3 mo follow up. RESULTS: Thirty-four patients in the STT group and 32 patients in the levofloxacin group presented at 3 mo follow up. H. pylori eradication rates were similar with STT and the LBT groups on intention-to-treat (ITT) analysis (69% vs 80%, P = 0.425) and (79% vs 87%, P = 0.513) by per-protocol (PP) analysis respectively. Ulcer recurrence in the STT and LBT groups on ITT analysis was (20% vs 14%, P = 0.551) and (9% vs 6%, P = 1.00) by PP analysis. Compliance and side effects were also comparable between the groups. A complete course of STT costs Indian Rupees (INR) 1060.00, while LBT costs only INR 360.00. CONCLUSION: H. pylori eradication rates and the rate of ulcer recurrence were similar between the STT and LBT. The LBT is a more economical option compared to STT.     

18氟-脱氧葡萄糖正电子发射计算机断层摄影诊断胃恶性肿瘤

目的 探讨18氟-脱氧葡萄糖正电子发射计算机断层摄影(18F-FDG PET/CT)判断胃恶性肿瘤的临床应用价值.方法 2007年5至7月对24例临床疑诊胃恶性肿瘤患者进行18F-FDGPET/CT显像检查,根据初次胃镜及病理活检结果将患者分为确诊组(胃镜和病理检查均提示恶性,9例)和未确诊组(胃镜下疑似恶性但病理检查提示良性,15例).确诊组行PET/CT以助术前评估,之后行手术治疗.未确诊组行PET/CT以判断病灶良恶性,之后再行胃镜和活检病理复查,符合手术指征者行手术治疗,无手术指征者临床随访.最终诊断以手术病理或临床随访结果为准.分析18F-FDG PET/CT对胃恶性肿瘤的诊断灵敏度、特异度、阳性预测值、阴性预测值及对腺癌患者l临床分期的作用.结果 18F-FDG PET/CT检出胃恶性肿瘤患者16例(确诊组9例、未确诊组7例),胃部原发灶16处,腔外增殖性病灶1处侵犯肝脏、胰腺及腹膜,肝转移1处,肺转移1处,空回肠病变3处,累及淋巴结13处,均获术后病理确诊.另有1例未确诊组患者PET/CT疑似恶性病变,术后病理确诊为良性间质瘤;1例未确诊组腺癌患者PET/CT漏诊.PET/CT诊断胃恶性肿瘤的灵敏度为16/17,特异度为6/7,阳性预测值16/17,阴性预测值6/7.对Ⅲ、Ⅳ期胃癌患者的分期正确率为6/6.结论 18F-FDG PET/CT为简单易行、安全、无创及有前景的检查方法,对胃恶性肿瘤的检出及良恶性肿瘤的鉴别有较高的临床应用价值,可作为胃镜检查的补充手段和制定手术方案的辅助工具.     

Conservative treatment of early postoperative small bowel obstruction with obliterative peritonitis

AIM:To investigate the effect of somatostatin and dexamethasone on early postoperative small bowel obstruction with obliterative peritonitis(EPSBO-OP).METHODS:This prospective randomized study included 70 patients diagnosed with EPSBO-OP from June2002 to January 2009.Patients were randomized into two groups:a control group received total parenteral nutrition and nasogastric(NG)tube feeding;and an intervention group received,in addition,somatostatin and dexamethasone treatment.The primary endpoints were time to resolution of bowel obstruction and length of hospital stay,and the secondary endpoints were daily NG output and NG feeding duration,treatment-related complications,postoperative obstruction relapse,and patient satisfaction.RESULTS:Thirty-six patients were allocated to the intervention group and 34 to the control group.No patient needed to undergo surgery.Patients in the intervention group had an earlier resolution of bowel obstruction(22.4±9.1 vs 29.9±10.1 d,P=0.002).Lower daily NG output(583±208 vs 922±399 mL/d,P<0.001),shorter duration of NG tube use(16.7±8.8vs 27.7±9.9 d,P<0.001),and shorter length of hospital stay(25.8 vs 34.9 d,P=0.001)were observed in the intervention group.The rate of treatment-related complications(P=0.770)and relapse of obstruction(P=0.357)were comparable between the two groups.There were no significant differences in postoperative satisfaction at 1,2 and 3 years between the two groups.CONCLUSION:Somatostatin and dexamethasone for EPSBO-OP promote resolution of obstruction and shorten hospital stay,and are safe for symptom control without increasing obstruction relapse.