Value of multidetector-row CT in the preoperative prediction of peritoneal metastasis from gastric cancer: a single-center and large-scale study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the value of multidetector-row computed tomography (MDCT) in preoperatively predicting peritoneal metastasis of gastric cancer and to evaluate the indication for laparoscopic staging of gastric cancer on the basis of MDCT features.</p><p><b>METHODS</b>Six hundred and forty gastric cancer patients underwent preoperative MDCT examination, and the results of MDCT were compared with surgical and pathological findings. In addition, the relationship between MDCT features (depth of invasion, lymph node metastasis status, tumor size, and thickness of tumor) and peritoneal metastasis of gastric cancer was analyzed.</p><p><b>RESULTS</b>The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MDCT in predicting peritoneal metastasis of gastric cancer were 51.0% (25/49), 99.3% (587/591), 86.2% (25/29), 96.1% (587/611), and 95.6% (612/640), respectively. Univariable analysis showed that all the four MDCT features (depth of invasion, lymph node metastasis status, tumor size, and tumor thickness) of gastric cancer were significantly correlated with the peritoneal metastasis of gastric cancer. None of the patients diagnosed with stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer by MDCT were found to have peritoneal metastasis. Receiver operating characteristic (ROC) analysis showed that the accuracy of the tumor size and thickness of gastric cancer in determining peritoneal metastasis was high(area under ROC curve was 0.83 and 0.75, respectively). Multivariable analysis showed that only tumor size was significantly correlated with the peritoneal metastasis from gastric cancer.</p><p><b>CONCLUSIONS</b>The clinical value of MDCT in preoperative prediction of peritoneal metastasis from gastric cancer is favorable. Laparoscopy can be avoided in patients with small tumor size or stage T(0~2)N(x)M(0) or T(x)N(0)M(0) gastric cancer diagnosed by MDCT due to lower incidence of peritoneal metastasis.</p>

A comparative study on the efficacy of spleen-preserving modified D2 radical gastrectomy and D2 radical gastrectomy with splenectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the efficacy of modified D(2) radical total gastrectomy with spleen-preserving and D(2) radical total gastrectomy with splenectomy in patients with gastric cancer located in the upper third, upper and middle third and entire stomach.</p><p><b>METHODS</b>One hundred and twelve patients with gastric cancer in the upper third, upper and middle third, or entire stomach underwent radical total gastrectomy between January 1989 and December 1994. Modified D(2) total radical gastrectomy with spleen-preserving (spleen-preservation group) was performed in 61 patients, and 51 underwent D(2) total radical gastrectomy with splenectomy (splenectomy group). The differences in clinicopathological characteristics,5-year survival rate, incidence of postoperative complication and hospital stay between the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>There were no significant differences between the spleen-preservation group and the splenectomy group in gender, age, tumor size, T stage, N stage and TNM stage. The overall 5-year survival rate was 41.0% in the spleen-preservation group and 39.2% in the splenectomy group (P>0.05). The 5-year survival rates of patients with stage I, II, III and IIII were 100%, 66.7%, 27.8% and 17.4% in the spleen-preservation group, respectively, and were 100%, 70.0%, 26.7% and 5.6% in the splenectomy group, respectively (all P>0.05). The incidence of postoperative complication was lower in the spleen-preservation group (11.5% vs 27.5%, P<0.05). The mean hospital stay was longer in the splenectomy group (27.3 d vs 20.3 d, P=0.057).</p><p><b>CONCLUSION</b>The efficacy of modified D(2) radical total gastrectomy with spleen-preserving for patients with gastric cancer in the upper third, upper and middle third or entire stomach is similar to that of D(2) radical total gastrectomy with splenectomy, and the spleen-preserving procedure is associated with decreased postoperative complication and improved survival.</p>

Capecitabine combined with cisplatin as first-line therapy in Chinese patients with advanced gastric carcinoma-a phase II clinical study / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness and safety of the combination chemotherapy of capecitabine (X) with fractionated administration of cisplatin (C) in Chinese patients with advanced gastric cancer (AGC).</p><p><b>METHODS</b>141 patients with AGC were enrolled between July 2002 and August 2004. All patients had measurable tumor according to the criteria of RECIST, Karnofsky performance status > or = 60, adequate bone marrow, renal and hepatic functions. Prior radiotherapy or adjuvant chemotherapy was not permitted. Patients received oral administration of capecitabine at a dose of 1000 mg/m(2) twice a day on D1-D14, and intravenous infusion of fractionated cisplatin at a dose of 20 mg/m(2)/day on D1-D5. The regimen was repeated every 3 weeks, totally for 6 cycles.</p><p><b>RESULTS</b>Of the 141 evaluable patients, there were 104 men and 37 women, with a median age of 54 years (range, 23 - 80 years). Metastases before chemotherapy were detected in lymph nodes (46.8%), liver (40.4%), lung (5.7%) and other area (10.6%). The median treatment duration was 6 cycles (range, 3 - 6 cycles). The objective response rate (RR) was 36.2% (51/141). The median follow-up period was 17.5 months. The median time to progress (TTP) was 9.0 months, and the median overall survival (OS) was 12.0 months. The most common treatment-related adverse events (grade 3/4) were: hand-foot syndrome (HFS) (2.1%), leucopenia (0.7%), abnormal alanine transaminase elevation (2.8%). There was no treatment-related death.</p><p><b>CONCLUSION</b>Capecitabine combined with fractionated cisplatin is highly effective and well tolerated as a first-line treatment for advanced gastric cancer, with comparable results to 5-Fu plus cisplatin combination therapy.</p>

Chromosomal alterations analyzed by comparative genomic hybridization in primary gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To identify genetic abnormalities in primary gastric carcinoma.</p><p><b>METHODS</b>Comparative genomic hybridization (CGH) was used in screening DNA copy number changes along all chromosomes in 23 cases of primary gastric cancer.</p><p><b>RESULTS</b>Twenty-one out of 23 cases showed chromosomal losses and gains for at least one of the chromosomal arms in primary gastric cancer. The mean number of chromosomal alterations was 7.52. Chromosomal gains predominated over chromosomal losses in a ratio of 5.38:2.14. The most often involved chromosomal gains were observed in 8q (9/21, 42.9%), 20q (9/21, 42.9%), 17q (8/21, 38.1%), 3q (7/21, 33.3%), 7q (7/21, 33.3%), 11q (6/21, 28.6%), 13q (6/21, 28.6%), 1q (5/21, 23.8%) and 20p (5/21, 23.8%). The chromosomal arms with frequent losses were 17p (7/21, 33.3%), 18q (6/21, 28.6%), 5q (5/21, 23.8%), 8p (5/21, 23.8%), and 9p (5/21, 23.8%).</p><p><b>CONCLUSIONS</b>The phenomenon of gain and loss of chromosomal regions is observed in primary gastric cancer, which may induce the amplification of oncogenes and the loss of tumor suppressor genes to regulate the development and progression of gastric cancer.</p>

Prognostic significance of metastatic lymph nodes ratio in patients with T2-T3 stage gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic significance of metastatic lymph nodes ratio in patients with T(2)~T(3) stage gastric cancer.</p><p><b>METHODS</b>Clinical data of 238 patients with T(2)-T(3) stage gastric cancer undergone radical gastrectomy and D(2) lymphadenectomy, at least 15 lymph nodes was dissected per patient, were analyzed retrospectively. Spearman correlation analysis was used to determine the correlation coefficient. Survival was determined by the Kaplan-Meier method and differences were assessed by the Log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients 5 years postoperatively and that of metastatic lymph nodes number.</p><p><b>RESULTS</b>The metastatic lymph nodes ratio didn't correlate with the total number of dissected lymph nodes, whereas metastatic lymph nodes number did. Kaplan-Meier survival analysis demonstrated the metastatic lymph nodes ratio significantly influenced the postoperative survival time and Cox proportional hazard regression model analysis showed the metastatic lymph nodes ratio was an independent poor prognostic factor. There was no significant difference between the area under the receiver working characteristic curve of metastatic lymph nodes ratio and metastatic lymph nodes number in predicting the death of patients 5 years postoperatively.</p><p><b>CONCLUSIONS</b>The metastatic lymph nodes ratio in T(2)-T(3) stage gastric cancer patients is not correlated with the total number of dissected lymph nodes if at least 15 lymph nodes are dissected. The metastatic lymph nodes ratio is a major independent poor prognostic factor of the patients of T(2)-T(3) stage gastric cancer. The ability of the metastatic lymph nodes ratio in predicting the death of T(2)-T(3) stage gastric cancer patients 5 years postoperatively is the same as that of metastatic lymph nodes number.</p>

The relationship between frameshift mutations of transforming growth factor-beta type II receptor, insulin growth factor II receptor, bcl-2 associated X protein, E2F4 and microsatellite instability in gastric carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To determine the microsatellite instability in gastric carcinomas, examine the frameshift mutations of transforming growth factor-beta type II receptor (TGFbetaRII), insulin growth factor II receptor (IGFIIR), bcl-2 associated X protein (BAX) and E2F4, and investigate whether or how alterations of the TGFbetaRII, IGFIIR, BAX and E2F4 gene are associated with MSI in gastric cancer.</p><p><b>METHODS</b>Formalin-fixed, paraffin-embedded gastrectomy specimens and matching normal tissues of 65 cases of gastric carcinomas were retrieved from shanghai Ruijin Hospital and Shanghai East Hospital. DNA was extracted from tissue sections using phenol chloral isoamyl alcohol. Sections with no more than 50% of tumor cell areas were isolated by microdissection. DNA was amplified by PCR-based single strand conformation polymorphism (SSCP) for microsatellite analysis and was sequenced directly. Frameshift mutations in the coding regions, repetitive mononucleotide tracts of (A)10 for TGFbetaRII, (G)8 for IGFIIR, (G)8 for BAX, and trinucleotide repeats of (AGC)13 for transcription factors E2F4 were detected using PCR. Tumors were classified as being microsatellite stable (MSS) or having a low frequency of MSI (MSI-L, one of markers different in the tumor) or a high frequency of MSI (MSI-H, two or more of markers different).</p><p><b>RESULTS</b>Eleven cases (18.0%) showed MSI-L, 12 (19.7%) showed MSI-H and 38 (62.3%) cases showed MSS. The mutation rates of TGFbetaRII, IGFIIR, BAX and E2F4 gene were 19.7%, 4.9%, 6.6% and 16.4% respectively. Among the 12 MSI-H gastric cancers, there were 10 TGFbetaRII mutations, 3 IGFIIR mutations, 4 BAX mutations and 10 E2F4 gene mutations. The alterations in the repeats of the related genes presented polymorphisms. Associations of MSI-H status and mutations of the 4 genes were highly significant (P < 0.01, respectively). No repeat tracts mutations in TGFbetaRII, IGFIIR, BAX and E2F4 gene were found in MSS tumors.</p><p><b>CONCLUSIONS</b>The repeat coding regions within TGFbetaRII, IGFIIR, BAX and E2F4 gene are the targets of microsatellite instability. Frameshift mutations of the 4 genes play an important role in the development and progression of gastric cancers with microsatellite instability.</p>

Clinical effect of intraoperative peritoneal hyperthermic chemotherapy for advanced gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical effect of intraoperative peritoneal hyperthermic chemotherapy (IPHC) for advanced gastric cancer (AGC).</p><p><b>METHODS</b>A total of 118 AGC patients with serosal invasion were enrolled in this study from 1998 to 2001. Among these cases, 96 patients without macroscopic peritoneal metastases were selected for prophylactic study, including 42 cases with IPHC and 54 cases without IPHC as control. Other 22 patients with macroscopic peritoneal metastases were selected for therapeutic study, including 10 cases with IPHC and 12 without IPHC. Postoperative survival rate and peritoneal recurrence were compared.</p><p><b>RESULTS</b>For prophylactic study, the 1, 2 and 4 years survival rates were 85.7%, 81.0% and 63.9% respectively in the patients with IPHC,significantly higher than 77.3%, 61.0% and 50.8% in the patients without IPHC. Cox ratio hazard model revealed that IPHC procedure was an independent prognostic factor. More patients in the control group suffered from peritoneal recurrence than those in IPHC group (34.7% vs 10.3%). For therapeutic study,the median survival period of the patients with IPHC was 10 months, higher than 5 months in the patients without IPHC. The overall 1, 2, 4 year survival rates were 76.9%, 69.2%, 55.2% respectively in all cases with IPHC, higher than 66.2%, 49.7%, 41.4% in the cases without IPHC.</p><p><b>CONCLUSION</b>IPHC procedure can improve the prognosis of AGC patients with serosal invasion, reduce the risk for peritoneal recurrence, and is an independent prognostic factor.</p>

Study on amplification of ZNF217 in primary gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate amplification of zinc finger protein 217(ZNF217) and its association with clinicopathologic parameters in primary gastric carcinoma.</p><p><b>METHODS</b>Semiquantitative polymerase chain reaction (PCR) was used to determine DNA copies of ZNF217 in the specimens from forty- seven cases with primary gastric carcinoma.</p><p><b>RESULTS</b>There was no difference in DNA copies between tumor specimens and paratumor normal tissues. The incidence of ZNF217 amplification was 11.36% in gastric cancer. The amplification of ZNF217 was significantly associated with tumor size(P< 0.01) and intestinal type of stomach cancer(P< 0.05).</p><p><b>CONCLUSION</b>Oncogene ZNF217 may play a role in specific tumor types or subtypes of gastric cancer. There may be other oncogenes associated with gastric carcinoma in 20(q)13.</p>

Study of hepatic injury during stop-flow chemotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the hepatic injury following stop- flow chemotherapy and investigate the potential mechanisms.</p><p><b>METHODS</b>Twelve healthy hybrid female pigs were randomly divided into two groups as stop- flow group (SF) and stop- flow chemotherapy (SFC) group. The expression of IL- 8 and ICAM- 1 mRNA in hepatic biopsies was detected by RT- PCR, and the expression of NF- kappa B P65 subunit in nuclei was assessed by Western blot analysis. The levels of ALT and AST, and histopathologic alterations were examined to evaluate the hepatic function at different time before and after stop- flow procedure.</p><p><b>RESULTS</b>The expression of NF- kappa B P65 subunit, IL- 8 and ICAM- 1mRNA increased at 30 min after stop- flow procedure, and gradually decreased at 3 h and 6 h after stop- flow procedure. The levels of ALT and AST decreased after reaching the peak at 24 h after stop- flow procedure, but removed one week after stop- flow procedure. Cytoplasmic microvascular steatosis developed with appreciable neutrophils infiltration after early stop- flow procedure without significant destroy occurred in the structure of hepatic lobule. No significant difference of various parameters above occurred between SF and SFC groups.</p><p><b>CONCLUSION</b>The hepatic injury following stop- flow procedure was self-limited and reversible. There is no severe destroy of hepatic structure and disfunction during stop- flow chemotherapy.</p>

Value of transabdominal ultrasonography in preoperative assessment of gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the value of transabdominal ultrasonography (TAUS) in preoperative assessment of TNM stage and tumor angiogenesis for patients with gastric carcinoma.</p><p><b>METHODS</b>Sixty- four patients with gastric carcinoma preoperatively underwent TAUS, in whom transabdominal color Doppler ultrasonography was used for measuring color Doppler vascularity index (CDVI) of each tumor in 37 cases and microvessel density (MVD) was evaluated by using immunohistochemical staining of surgical specimens with anti- CD34 antibody.</p><p><b>RESULTS</b>The overall accuracy rate was 56.0% for T staging of gastric carcinoma (T (1) 2/3 cases, T (2) 28.6% , T (3) 73.1% , T (4) 50.0% , respectively) by TAUS. The diagnostic accuracy rate was 63.3% for lymph node status of gastric carcinoma. The diagnostic sensitivity and specificity for lymph node metastasis was 37.9% and 100% respectively. The overall accuracy for N staging of gastric carcinoma was 57.1% (N (0) 100% , N (1) 16.7% , N (2) 35.3% , respectively). The diagnostic sensitivity and specificity for determining distant metastases was 58.3% and 100% respectively. The CDVI of gastric carcinoma determined by color Doppler ultrasonography was significantly correlated to vascular invasion (P=0.0418), a linear correlation between CDVI and MVD was determined by logistic regression analysis (r=0.5628, P< 0.01).</p><p><b>CONCLUSION</b>TAUS can be a routine diagnostic approach for preoperative gastric carcinoma patients.</p>

Transcription factor Sp1 expression in gastric cancer and its prognostic value / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of transcription factor Sp1 in human gastric cancer tissues and normal gastric mucosa, and its prognostic significance.</p><p><b>METHODS</b>By using immunohistochemistry, we studied the Sp1 expression patterns in 65 cases of gastric cancer with various clinico-pathologic characteristics, and 40 normal gastric mucosa specimens obtained from patients who underwent partial gastrectomy for benign gastric diseases. The significance of Sp1 expression on the survival of patients was evaluated.</p><p><b>RESULTS</b>The expression rate of Sp1 in normal gastric mucosa was 12.5% (5/40). The positively stained glandular cells were mainly limited to those in the neck region. Cells at the basal portion of the gland were essentially negative. In sharp contrast, Sp1 expression rate in gastric cancer lesions was 53.8% (35/65). The medium survival time in patients who had a tumor with negative, weak and strong Sp1 expression was 1700, 1560 and 1026 days, respectively (P = 0.036). Sp1 protein expression was closely related to the depth of tumor invasion and TNM stage (P = 0.001, P = 0.026), but not related to the number of metastatic lymph nodes and Lauren's classification (P = 0.306, P = 0.667).</p><p><b>CONCLUSION</b>Normal and malignant gastric tissues have unique Sp1 expression patterns. Sp1 might be served as an independent prognostic factor.</p>

COX- 2 expression in gastric cancer and its relationship with lymphangiogenesis and lymph node metastasis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) in human gastric cancer, the relationship between their expression and the clinicopathological features,as well as the relationship between these two parameter expression and lymphangiogenesis and lymph node metastasis.</p><p><b>METHODS</b>COX-2 and VEGF-C expressions were detected in 63 gastric cancer samples by immunostaining. Lymphangiogenesis was evaluated by immunostaining with the specific antibody LYVE-1.</p><p><b>RESULTS</b>The expression rates of COX-2 and VEGF-C were 66.7% (42/63), 52.4% (33/63), respectively in 63 gastric cancer specimens. LYVE-1 was positive in 35 cases (35/63), which indicated lymphangiogenesis in the tumors. The expression of COX-2 was significantly correlated with the expression of VEGF-C, tumor lymphangiogenesis and lymphatic metastasis (P< 0.05), however not gender, tumor size, tumor location, Lauren classification and serosa invasion (P< 0.05).</p><p><b>CONCLUSIONS</b>In gastric cancer, the expression of COX-2 is significantly associated with VEGF-C expression, lymphangiogenesis and lymphatic metastasis. COX-2 may up-regulate the expression of VEGF-C, which induces lymphangiogenesis and accordingly contributes to lymphatic metastasis.</p>

A preliminary study of endoscopic ultrasonography in the preoperative staging of early gastric carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinical value of endoscopic ultrasonography (EUS) in the preoperative staging of early gastric carcinoma.</p><p><b>METHODS</b>EUS was performed in 149 gastric carcinoma patients proved by biopsy (including 33 patients with early gastric cancer), of which the results were compared with postoperative pathologic findings.</p><p><b>RESULTS</b>The accuracy of EUS in determining the T stage of gastric carcinoma was 80.3% (T1 81.8%, T2 70.4%, T3 88.9%, T4 71.4%). The accuracy of EUS in differentiating early gastric carcinoma from advanced ones was 95.1%, and the accuracy of EUS in differentiating mucosal cancer from submucosal cancer was only 63.6%. The diagnostic accuracy of EUS for mucosal and submucosal cancer was 52.9% and 75%, with positive predictive value of 90% and 70.6%, respectively. The accuracy of invasion depth of EUS for the bulging and flat type of early gastric carcinoma was 100%, whereas the accuracy was only 58.6% for the depressed type. The accuracy of invasion depth of the differentiated and undifferentiated early cancer was 71.4%and 57.9%, without any significant difference (P > 0.05). The accuracy of invasion depth of EUS for early gastric carcinoma decreased as tumor size increased. The diagnostic accuracy of lymph node status of early gastric carcinoma by EUS was 90.9%, and the sensitivity and specificity of lymph node metastasis was 66.7% and 96.3%, respectively.</p><p><b>CONCLUSION</b>The clinical value of endoscopic ultrasonography in the preoperative staging of early gastric carcinoma is relatively high.</p>