The Effectiveness of Postoperative Chemotherapyon pT1bN0 and pT2N0 Gastric Cancer Patients withRisk Factors: An International Dual-Center Analysis

Purpose@#This study aimed to investigate the effectiveness of postoperative chemotherapy in pT1bN0 and pT2N0 gastric cancer patients with high risk factors. @*Materials and Methods@#Clinicopathological data of gastric cancer patients, who had undergone gastrectomy in high volume centers in Korea and China and were finally diagnosed with pT1bN0 and pT2N0 between 2006 and 2010, were analyzed retrospectively. Survival analyses stratified by risk factors and multivariable analyses were performed. @*Results@#A total of 1509 patients were enrolled, with 41 (2.7%) patients receiving adjuvant chemotherapy after gastrectomy and 1468 (97.3%) patients undergoing surgery alone. The adjuvant chemotherapy group showed higher percentages of tumor with maximal diameter >3 cm (51.2% vs. 25.8%), poor differentiation (68.3% vs. 49.8%), and less harvested lymph nodes (17.1% vs. 5.2%) compared to the surgery alone group. The overall survival rates were 95.1% in the adjuvant chemotherapy group and 93.3% in the surgery alone group, without significant difference. In multivariable analysis, age was found to be an independent prognostic factor. However, there were no difference in the overall survival between patients with risk factors and those without risk factors, even in terms of age. Meanwhile, patients with more than two risk factors who received chemotherapy showed better survival trend, especially for pT2N0 patients, compared to the surgery alone group, although no significant differences were observed. @*Conclusion@#In pT1bN0 and pT2N0 patients, age was found to be an independent prognostic factor. However, adjuvant chemotherapy seemed to be unnecessary, while postoperative chemotherapy might offer survival benefits to pT2N0 patients with more than two risk factors.

Down-regulation of Notch1 by small interfering RNA enhances chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of down-regulation of Notch1 by Notch1 small interfering RNA (siRNA) on chemosensitivity to gemcitabine in pancreatic cancer cells and its mechanism.</p><p><b>METHODS</b>Notch1 siRNA was transfected to pancreatic cancer cell lines AsPC-1, BxPC-3, MIAPaCa-2 and Panc-1. The transfected pancreatic cancer cells were treated with 10 μmol/L gemcitabine in vitro. The relative quantity of Notch1 mRNA of pancreatic cancer cells was detected by real-time PCR. The inhibition rates of gemcitabine-treated cells were evaluated by CCK-8 method. The expression of Bax protein was examined by Western blot, and the caspase 3 activity was detected by CaspACETM assay system kit.</p><p><b>RESULTS</b>The relative quantity of Notch1 mRNA was the highest in BxPC-3 cell line and the lowest in Panc-1 cells. The inhibition rates of gemcitabine treated-cells were significantly higher in Notch1 siRNA transfection groups than in corresponding siRNA control groups (AsPC-1: 67.5±6.7 vs 47.5±6.8; BxPC-3: 90.5±4.4 vs 70.2±4.2; MIAPaCa-2: 80.9±5.7 vs 58.1±6.0; Ps<0.05), with the overexpression of protein Bax. The activity of caspase 3 was also significantly increased in Notch1 siRNA transfection groups compared with corresponding siRNA control groups (AsPC-1: 28.90±2.70 vs 12.82±3.44; BxPC-3: 59.87±6.77 vs 27.27±11.88; MIAPaCa-2: 29.34±4.06 vs 14.59±4.25; P<0.05).</p><p><b>CONCLUSION</b>Inhibition of Notch signaling pathway by Notch1 siRNA can enhance chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity．</p>

Neo-adjuvant therapy for locally advanced low rectal cancer / 中华胃肠外科杂志

Rectal cancer is one of the most malignant tumors in gastrointestinal tract, while low rectal cancer with locally advanced stage is the most common type in China. The concept of neo-adjuvant therapy has challenged the traditional treatment strategy for rectal cancer, and has showed encouraging effects in local relapse control, radical resection and sphincter preservation. However, some important issues still remain controversial, including course and dose of radiotherapy, choice of chemotherapy regimen, long-term benefits. This article aims to review and discuss related issues of neo-adjuvant therapy.

Delayed presentation of colonic perforation after abdominal impalement trauma by sewing needle: a case report and review of literature

Post-traumatic, delayed colonic perforation is a rare but life-threatening cause of acute abdomen. Delayed presentation of colonic perforation is extremely rare, being observed only in patients after blunt abdominal trauma. We encountered an unusual case of delayed colonic perforation in a patient after abdominal impalement trauma. A 45-year-old man sustained abdominal impalement trauma by sewing needle 12 months ago, without getting timely management, and had a delayed perforation of sigmoid colon later. This case reminds surgeons not to overlook the delayed colonic perforation after abdominal impalement trauma

Laparoscopic transhiatal extended gastrectomy for type II, III esophagogastric junction cancer: a preliminary report of 55 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the feasibility and safety of laparoscopic extended gastrectomy through the transhiatal approach in patients with esophagogastric junction cancer.</p><p><b>METHODS</b>From Feb 2008 to May 2010, 55 cases with Siewert type II or III esophagogastric junction cancer underwent laparoscopic transhiatal extended gastrectomy at the West China hospital. Clinical data were analyzed retrospectively.</p><p><b>RESULTS</b>Esophagogastric junction cancer was Siewert type II in 36 patients and Siewert type III in 19. Thirty-five cases underwent proximal gastrectomy, 20 total gastrectomy. There were 53 D2 lymph node excisions and 2 palliative resections. Fifty patients underwent laparoscopic extended gastrectomy successfully, with 5 converted to open operations. A safe anastomosis between inferior pulmonary vein and pulmonary hilum was achieved in the majority of patients. The mean operative time was(236.2±35.5) min and the mean estimated blood loss was(60.6±33.9) ml. There were no postoperative mortalities or anastomotic leakage/stenosis. No reoperations were required. Pleural laceration occurred in 11 cases during operation, of whom 10 were repaired intraoperatively and one was managed with drainage postoperatively. There were 3 patients developed pulmonary infection and one wound infection. Postoperative recovery was uneventful in other patients.</p><p><b>CONCLUSION</b>Laparoscopic transhiatal extended gastrectomy is feasible and safe for patients with esophagogastric junction cancer.</p>

Expression of AIF and caspase-3 in colorectal carcinoma, adenoma, and normal mucosa and its correlation / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression differences of apoptosis-inducing factor (AIF) and caspase-3 among colorectal carcinoma, adenoma and normal mucosa, and to identify the relationship between AIF and caspase-3 expression in colorectal adenoma-carcinoma sequence.</p><p><b>METHODS</b>Formalin-fixed paraffin embedded colorectal tissues from 174 cases, including 84 adenomas, 72 carcinomas, and 18 normal mucosa, were examined for expression of AIF and caspase-3 by streptavidin-peroxidase (SP) immunohistochemistry.</p><p><b>RESULTS</b>The positive rates of AIF and caspase-3 in colorectal adenoma were higher than those in normal mucosa (P <0.05). The positive rate of AIF in adenoma showed no significant difference compared to colorectal carcinoma (P >0.05). However, caspase-3 expression in adenomas was significantly higher than that in carcinoma (P <0.05). The positive rate of AIF in tubular adenoma was significantly higher than that in villous adenoma (P <0.05), while the positive expression rate of caspase-3 in the two types of adenoma showed no significant difference (P >0.05). AIF expression had no prominent correlation with the caspase-3 expression (P >0.05).</p><p><b>CONCLUSIONS</b>The dysregulation of caspase-independent pathway of apoptosis may be an early event in the development of colorectal carcinogenesis, while the dysregulation of the caspase-dependent pathway of apoptosis may be one of contributing factors of colorectal carcinogenesis. The caspase-independent pathway of apoptosis and the caspase-dependent pathway of apoptosis are two relatively independent pathways in colorectal carcinogenesis.</p>

Clinicopathological significance of microRNA-21 and miR-125 expression in colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of microRNA(miR)-21 and miR-125 in colorectal cancer (CRC) and its relationship with clinicopathological features.</p><p><b>METHODS</b>Quantitative real-time PCR was applied to examine the expression of miR-21 and miR-125 in 100 primary CRC specimens which were diagnosed and operated in West China Hospital between 2006 and 2007, in comparison with the corresponding normal mucosa specimens. The relationship between the expression of miRNAs and clinicopathological features was analyzed.</p><p><b>RESULTS</b>The expression of miR-21 in CRC was up-regulated by 2.3 times compared to normal mucosa (P =0.025), while the expression of miR-125 was down-regulated by 3.3 times in comparison with normal mucosa (P =0.005). Furthermore, the expression of miR-21 was related to TNM stage (P =0.028) and local invasion (P =0.023). On the other hand, no significant relationship was found between the expression of miR-125 and clinicopathological features (P >0.05).</p><p><b>CONCLUSION</b>The over-expression of miR-21 may play a role in the development and progression of CRC, while miR-125 may not be related to the pathogenesis of CRC.</p>

Expression of minichromosome maintenance protein 2 in colonic adenocarcinoma, adenoma and normal colonic mucosa and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression differences of minichromosome maintenance 2 (MCM2) mRNA and protein among colon adenocarcinoma, colon adenoma and normal mucosa, and among different clinicopathological types of adenomas.</p><p><b>METHODS</b>Fifty specimens, including 33 colonic adenomas, 12 colonic adenocarcinomas and 5 normal colonic mucosa were selected. Each specimen was divided into two parts, one for immunohistochemistry and the other for real-time RT-PCR. Expression differences of MCM2 mRNA among the colonic adenocarcinoma, adenoma and normal colonic mucosa were evaluated by REST-XL software.</p><p><b>RESULTS</b>The expression of MCM2 was observed in the basal third to half of the colonic crypts in normal mucosa, while throughout the epithelium in the colonic adenocarcinomas and adenomas. However, the expression of MCM2 mRNA in the adenocarcinomas was significantly higher than that in the adenomas(P=0.001). The MCM2 mRNA expression was elevated in the adenoma with villous type, in the conditions of high-grade dysplasia, larger size, sessile morphology and in patients of older ages, but the difference was not significant by REST-XL (P>0.05).</p><p><b>CONCLUSION</b>The difference of MCM2 expression between the adenoma and the adenocarcinoma indicates its potential value in the early diagnosis of colonic cancer.</p>

Expression of phosphatase of regeneration liver-3 in human colorectal carcinoma and its prognosis value / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of phosphatase of regeneration liver-3(PRL-3) protein and its relationship with tumor invasion and metastasis in human colorectal carcinoma,and elucidate prognostic value.</p><p><b>METHODS</b>Immunohistochemistry method was applied to detect the PRL-3 expression in the primary tumor specimens and paired paratumor normal tissues from 46 colorectal carcinoma patients, the adenoma tissues from 6 patients with colorectal adenoma, all the metastatic lymph nodes from 29 cases and the metastatic liver lesions from 6 cases. The relationship between PRL-3 expression and clinicopathologic parameters was analyzed and a survival curve was achieved according to Kaplan-Meier method.</p><p><b>RESULTS</b>No or weak PRL-3 protein expression was detected in normal colorectal mucosa and colorectal adenoma. In colorectal carcinoma tissues, PRL-3 expression was confirmed in 26 of 46 cases (56.5%) of primary colorectal carcinomas (with lymph node metastasis 63.0%, without lymph node metastasis 37.0%, P=0.001), 26 of 29 (89.7%) lymph node metastases, and 5 of 6 liver metastases. The expression of PRL-3 was assembled in the cytoplasm of carcinoma cells and more intensively on the cell membrane.Analysis of the relationship between PRL-3 expression and the clinicopathologic features showed that PRL-3 expression was closely associated with tumor stage (P=0.019), lymph node metastasis (P=0.026), but no relationship with age, sex, tumor size, degree of differentiation was founded (P<0.05). The mean follow-up time was 41.4 months and results showed that patients with positive expression of PRL-3 had a significantly poorer prognosis than those with negative PRL-3 expression group(P=0.032).</p><p><b>CONCLUSIONS</b>PRL-3 protein plays a novel role in tumor progression and metastasis of colorectal carcinoma. PRL-3 can be expected to be a potential predictive biomarker for identifying the prognosis in colorectal carcinoma patients.</p>

Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP).</p><p><b>METHODS</b>Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-alpha) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-kappaB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-alpha concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-alpha concentrations.</p><p><b>CONCLUSIONS</b>The results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome (SIRS)-like response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.</p>

Lateral pelvic metastasis and micrometastasis in low rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study lateral pelvic metastasis and micrometastasis of low rectal cancer and elucidate their prognostic value.</p><p><b>METHODS</b>Whole-mount slice and tissue microarray of dissected lateral pelvic specimen from 67 cases of low rectal cancer were examined, and the included cases were followed up.</p><p><b>RESULTS</b>Twelve specimens were diagnosed as lateral metastasis, while another 10 were proved to bear micrometastasis. Most of the involved metastatic lymph nodes (82.9%) were smaller than 5 mm in diameter. Internal iliac, obturator regions and middle rectal root were more likely to be involved by tumors. Patients with lateral metastasis suffered more recurrence and poorer survival.</p><p><b>CONCLUSIONS</b>Lateral pelvic metastasis could be observed in low rectal cancer and its incidence differed among lateral pelvic regions. Patients with lateral spread predisposed poor prognosis, thus underlies the value of pre/postoperative adjuvant therapy.</p>

Effect of curved cutter stapler in the ultra low anterior resection for low rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the curative effect of curved cutter stapler (Contour, Ethicon Endo-Surgery, Inc) in the ultra low anterior resection for low rectal cancer.</p><p><b>METHODS</b>Clinic data of 56 patients with low rectal cancer from Dec. 2005 to Sep. 2006 were reviewed retrospectively. After total mesorectal excision (TME) and lateral lymph node dissection (LLD) in 56 cases, the rectal (anal) remnant was cut and closed with curved cutter stapler (Contour), and preserved for ultra low colo-rectal (anal) anastomoses with 33 mm straight intraluminal stapler.</p><p><b>RESULTS</b>There was no operational death and the mean hospitalization time was (11.2+/-3.2) days. The incidence rate of postoperative complications in 1 month was 3.57% (2/65). Both of the cases were anastomotic leakage. One was cured by surgical drainage, the other combining with rectal vaginal fistula was cured by transverse colostomy.</p><p><b>CONCLUSION</b>Curved cutter stapler has the advantages of complete cutting, safe closure and low anastomotic leakage rate in the process of ultra low anterior resection for low rectal cancer.</p>

E1AF gene expression and its clinical significance in human rectal cancer / 肿瘤研究与临床

Objective To detect EIA factor expression in human rectal cancer and normal tissue and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods Real- time RT-PCR was used to detect E1AF expression in matched rectal cancers and normal tissues from g6 in- patients.Results Among the 86 rectal cancer samples tested,55 cases E1AF mRNA overexpression was ob- served. The mRNA expression of E1AF in the sample group was remarkably different from that in the control group.In carcinomas,E1AF mRNA expression correlated significantly with histological type,depth of inva- sion,lymph node and distant metastasis and advanced Duke stage.Conclusion E1AF is correlated signifi- cantly with invasion and metastasis of human rectal cancer and may be an important factor in the invasion and metastasis.

Distribution of micrometastatic nodules of low rectal cancer in mesorectum: a pathological study using whole-mount sections / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the regional spread of micrometastatic nodules in the mesorectum from low rectal cancer, and provide further pathological evidence to optimize radical resection procedure for rectal cancer.</p><p><b>METHODS</b>A total of 62 patients with low rectal cancer underwent low anterior resection and total mesorectal excision (TME) was included in this study. Surgical specimens were sliced transversely and serial embedded blocks were made at 2.5 mm interval, and paraffin sections were stained with hematoxylin and eosin. The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic spread were examined microscopically on the sections for the distribution in different mesorectal regions, frequency, types, involvement of lymphatic system and correlation with the primary tumor.</p><p><b>RESULTS</b>Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) involved by microscopic tumor foci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involvement was recorded in 6.5% (4/62) with a spread extent within 3 cm of distal border of the main lesions. Most (20/24) of the patients with microscopic spread in mesorectum were in TNM stage III.</p><p><b>CONCLUSION</b>Results of the present study support that complete excision of mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, and an optimal DMR clearance resection margin should not be less than 4 cm.</p>

Patterns and prognostic value of resection margin involvement and lateral pelvic metastases for patients with rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the patterns and prognostic value of resection margin involvement and lateral pelvic metastases, providing surgeons with pathologic proofs of tumor spread within the studied areas.</p><p><b>METHODS</b>Large tissue slices of 62 specimens from patients with rectal cancer were used in the pathologic study and the outcomes were followed.</p><p><b>RESULTS</b>Compared with patients without margin involvement, patients with circumferential margin involvement (CMI), seen in 8 cases (12.9%), had poorer postoperative survival (P=0.003). The 12 patients (19.4%) with lateral pelvic metastases suffered poorer survival, compared with those without lateral pelvic metastases (P=0.026). Eight patients (66.7%) were diagnosed to have single lateral pelvic region involved, while the other 4 had multiple regions involved. The incidence of lateral metastases differed among regions, with higher occurrence in the root of middle rectal artery (6/12, 50.0%), area of the internal iliac artery (4/12, 33.3%) and the obturator region (3/12, 25.0%).</p><p><b>CONCLUSION</b>Occurrence of CMI or lateral metastases in rectal cancer patients predispose poor survival, thus a more radical clearance and postoperative adjuvant therapy are recommended.</p>

Study with large slice technique and tissue microarray on lymph node involvement and micro-metastasis of rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study lymph node involvement and micro-metastasis of rectal cancer with large slice technique and tissue microarray.</p><p><b>METHODS</b>Large slice technique, combined with tissue microarray,was used in pathologic study of 31 patients after total mesorectal excision (TME) for rectal cancer.</p><p><b>RESULTS</b>Nine hundred and ninety- two lymph nodes were harvested and 148 were positive. More than 40% of positive lymph nodes were located in the outer layer of the mesorectum and in the same side of the mesorectum as the primary tumor was. Circumferential margin involvement was observed in 12 cases and correlated with the numbers of metastatic lymph nodes (Beta =1.166, P=0.041). Micrometastasis was found in 9 cases with negative pathological lymph nodes, but not correlated with tumor differentiation and stage (P> 0.05).</p><p><b>CONCLUSION</b>Large slice technique combined with tissue microarray facilitates the detection of lymph node involvement and micrometastasis. There is a predominance of lymph node metastasis in the outer layer and the same side of the mesorectum. Micrometastasis can be discovered in different stages of rectal cancer.</p>

Expression of phosphatase of regenerating liver-3 mRNA and its clinical implications in human colorectal carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of phosphatase of regenerating liver-3 (PRL- 3) mRNA and evaluate its relationship with tumor invasion and metastasis in human colorectal carcinoma.</p><p><b>METHODS</b>The expression level of PRL-3 mRNA was examined semi-quantitatively in surgically resected tumor specimens, paired paratumor normal tissues from 46 CRC patients, metastatic lymph nodes and liver metastases from 18 cases with metastasis,adenoma tissues from 6 patients with colorectal adenoma (CRA). In addition,the mutation of PRL-3 gene was examined by PCR-SSCP.</p><p><b>RESULTS</b>The PRL-3 mRNA level was increased in primary CRC tissues as compared with paired paratumor normal tissues (1.6+/- 0.7 vs. 0.4+/- 0.1, P< 0.01), while no significant difference of its expression was found between CRA tissues and their adjacent normal mucosae (P> 0.05). However,the PRL-3 mRNA levels of liver metastases (2.1+/- 0.8) in 12 cases and metastatic lymph nodes (3.3+/- 1.0) in 6 cases were significantly higher compared with the matched primary lesions, normal tissues and negative-lymph nodes (P< 0.01). There was significant relation of the expression of PRL-3 mRNA with the clinicopathological features including Dukes stage, invasion depth and metastasis (P< 0.05), but no relation with sex,tumor size,degree of differentiation was found (P> 0.05). Abnormal electrolysis band was found in 1 of 6 cases with liver metastasis by PCR-SSCP analysis.</p><p><b>CONCLUSION</b>PRL-3 gene plays an important role in tumor invasion and metastasis and may associated with carcinogenesis and development of CRC. There might exist some unknown mechanisms of overexpression and mutation of PRL-3 gene in CRC.</p>