Clinical research progress on disappearing colorectal liver metastases / 中华胃肠外科杂志

Colorectal cancer is currently one of the most common digestive system tumors, and the liver is the most common metastatic site of colorectal cancer. In recent years, with the continuous development of the multidisciplinary treatment for colorectal cancer patients, there are quite a few cases of disappearing liver metastases (DLM) after receiving preoperative chemotherapy (or combined targeted drug therapy), and the diagnosis and treatment of DLM is currently still a very challenging and controversial topic. This article sorts out the related researches on DLM in recent years, mainly including the following 4 aspects: (1) The factors associated with DLM, including the size and number of liver metastases, chemotherapy regimens and cycles, targeted therapy drugs, and the pattern of liver metastases, Ras/Braf status and the location of the primary lesion. (2) The relationship between DLM and true complete response (pathological complete response and persistent clinical complete response), and the related predictive factors of pathological complete response. (3) Clinical evaluation of DLM: preoperative evaluation includes ultrasound, CT, MRI, and PET, while intraoperative evaluation includes intraoperative exploration, intraoperative ultrasound, and augmented reality. (4) DLM treatment strategies, including surgical treatment, local treatment, non-surgical treatment and individualized treatment.

Research progress of conversion therapy in colorectal cancer liver metastases / 中华胃肠外科杂志

The probability of developing liver metastases in patients with colorectal cancer is 40%-50%. Liver metastases remain an important adverse factor affecting long-term prognosis of colorectal cancer patients. Surgical resection of liver metastases is the only potentially curative treatment option. After comprehensive treatment, initially unresectable liver metastases might be converted to resectable tumors. This concept is known as conversion therapy. In this review, research status of conversion therapy in colorectal cancer liver metastases was summarized, providing updated concept of resectability, discussions on the assessment of tumor response and timing of operation, debates on the influence on tumor sidedness, and latest advancement in the treatment strategy of conversion therapy. Through analyzing existing problems, we hope to offer insights into possible progress in the future and provide references for the development of clinical practice.

Therapy progression in surgery of inflammatory bowel diseases / 中华胃肠外科杂志

The inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are characterized by idiopathic, chronic inflammation of the gastrointestinal tract. The overall incidence of IBDs is constantly increasing in eastern countries. In comparison with the data from western nations, in China, the incidence of male IBDs is relatively higher, the onset age is older. The severity of most cases is mild to moderate. The occurrence of fistula and peri-anal involvement are rare. Although significant improvements of IBDs therapy have been achieved in recent years, there are still over 30% UC and 70% CD cases need at least one surgery throughout their life span. Here we review the literatures published in recent years about the surgical management of IBDs.

Factors associated with complications in patients undergoing surgery for obstructing colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate risk factors associated with morbidity and mortality in patients undergoing surgery for obstructing colorectal cancer.</p><p><b>METHODS</b>One hundred and eleven patients who underwent emergency surgery for obstructing colorectal cancer from January 2001 to December 2009 were retrospectively reviewed.</p><p><b>RESULTS</b>Forty-nine patients had obstruction proximal to the splenic flexure and 62 patients at or distal to the splenic flexure. The morbidity and mortality rates of the emergency surgery for malignant obstruction were 21.6% and 5.4%, respectively. Twenty-three patients received resection with primary anastomosis with intraoperative lavage for left-sided lesions. There was no difference in morbidity between right-sided cancer and left-sided cancer(P>0.05). Univariable analysis showed that complications rate was higher in patients with higher ASA score (3-4) and in those aged over 60 years. Multivariate logistic regression analysis revealed that ASA score(3-4) was an independent risk factor.</p><p><b>CONCLUSIONS</b>Emergency surgery for obstructing colorectal cancer is associated with high rates of morbidity and mortality. Selection of the proper operation and intensive treatment after surgery are recommended in high risk patients.</p>

Surgical outcomes for 187 patients with locally recurrent rectal cancer and analysis of prognostic factors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the surgical outcomes for patients with locally recurrent rectal cancer (LRRC) and to analyze the prognostic factors.</p><p><b>METHODS</b>Clinical data of 187 patients with LRRC undergoing surgery at the First Hospital of peking University from January 1985 to December 2009 were retrospectively reviewed.</p><p><b>RESULTS</b>Procedures performed included local resection(n=34), abdominoperineal resection (n=35), posterior pelvic exenteration (n=17), total pelvic exenteration(TPE, n=98), TPE with sacrectomy (n=2), and TPE with internal hemipelvectomy (n=1). The operation was R0 in 87 patients, R1 in 60, and R2 in 40. The degree of radical resection was associated with the initial surgery and the degree of pelvic fixation (P<0.05). The pelvic recurrence rate was 44.4%(64/144). The operative morbidity and mortality were 47.5%(89/187) and 2.7%(5/187), respectively. The overall 3- and 5-year survival rates were 42.2% and 30.7%, respectively. The degree of radical resection and lymph node metastasis were independent risk factors associated with prognosis. The 5-year survival rates of R0, R1 and R2 were 42.6%, 17.2% and 0, respectively(P<0.01). The 5-year survival rates of patients with and without lymph node metastasis were 5.6% and 40.5%(P<0.01) respectively.</p><p><b>CONCLUSION</b>Accurate evaluation of extent of pelvic fixation and achievement of R0 resection are critical to improve the surgical outcomes for LRRC.</p>

Extrahepatic synthesis of coagulation factor VII by colorectal cancer cells promotes tumor invasion and metastasis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Blood coagulation factor VII (FVII) is physiologically synthesized in the liver and released into the blood. Binding of FVII to tissue factor (TF) is related to the metastatic potential of tumor cells, also a significant risk factor in the development of hepatic metastasis in patients with colorectal cancer (CRC). It has been found that some cancer cells can produce FVII extrahepatically. However, little is known about FVII and CRC. We therefore hypothesized that CRC cells may synthese FVII, leading to tumor invasion and metastasis.</p><p><b>METHODS</b>We detected the expression of FVII protein in 55 CRC specimens by immunohistochemical staining. The FVII mRNA in 45 of 55 CRC cases, 6 colon cancer cell lines and one hepatoma cell line was measured by real-time reverse transcription-PCR (RT-PCR). Transwell invasion assays were performed to evaluate the changes of cell migration and invasion of LoVo cancer cells in vitro. We further observed the likely effectors regulated by the TF/FVIIa complex Western blotting assay.</p><p><b>RESULTS</b>Extrahepatic synthesis of FVII was detected in the cytoplasm of 32 (58.2%) CRC specimens by immunohistochemistry, but not in normal mucosa. Liver metastasis (P = 0.003) and TNM staging (P = 0.005) were significantly correlated with FVII antigen expression. The positive ratios in stages I, II, III and IV were 33.3%, 40.0%, 52.4% and 87.5%, respectively. The expression of FVII mRNA in CRC with hepatic metastasis was significantly higher than CRC without hepatic metastasis (5.33 ± 2.88 vs. 1.47 ± 0.51, P = 0.03). Ectopic FVIIa induced a slight increase (1.34-fold) in the number of migrating cells, which was inhibited by the specific TF antibody. The formation of TF/FVIIa complex resulted in a marked increase in the expression of matrix metalloproteinases (MMP)-2 (3.5-fold) and MMP-9 (4.7-fold) in a time-dependent and dose-dependent manner.</p><p><b>CONCLUSIONS</b>Extrahepatic synthesis of FVII by CRC cells may promote tumor invasion and metastasis. MMPs, as downstream effectors of TF/FVIIa signaling, facilitate the development of metastasis in colon cancer.</p>

Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of lateral pelvic lymph node metastasis on low rectal cancer.</p><p><b>METHODS</b>One hundred and seventy-six patients with low rectal cancer who underwent radical resection combined with lateral pelvic lymph node dissection between 1994 and 2005 were reviewed. The data of the cases was investigated to define the prognostic value of lateral pelvic lymph node metastasis on the patients.</p><p><b>RESULTS</b>Lateral node metastasis occurred in 33 patients (18.8%), and 51.5% of the metastasis occurred in internal iliac nodes or nodes at middle rectal roots and 39.4% in obturator nodes. Age < or =40 years, infiltrative cancer, T34 tumor, upward lymph node metastasis were risk factors for lateral node metastasis in low rectal cancer (P < 0.05). The overall 5-year survival rate was 64.1%, and it was 94.1%, 79.1%, 42.1% for patients with TNM stage I, II, III cancer, respectively. Tumor size, depth of infiltration, upward lymph node metastasis, lateral node metastasis was correlated significantly with prognosis (P < 0.05). The 5-year survival rate of the patients without lateral metastasis was 73.6%, which was significant higher than that of patients with lateral metastasis (21.4%, P < 0.05).</p><p><b>CONCLUSION</b>Lateral pelvic lymph node metastasis is an important prognostic factor for low rectal cancer.</p>

Expression of proline-rich tyrosine kinase-2 in human primary colorectal carcinoma and its prognostic implication / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of proline-rich tyrosine kinase-2 (Pyk2) in human primary colorectal carcinoma (CRC) and it's prognostic significance.</p><p><b>METHODS</b>The expression of Pyk2 was retrospectively examined with immunohistochemistry (IHC) in 108 tissues of primary CRC. The correlation of Pyk2 expression to prognosis and relevant clinical factors were analyzed.</p><p><b>RESULTS</b>The rate of Pyk2 low-expression in CRC was 56.5% (61/108). The expression of Pyk2 correlated significantly to the histological grade (P < 0.05) and the TNM stage (P < 0.05), while no correlation between Pyk2 expression and age, tumor size (P > 0.05). Patients with Pyk2 over-expression had significantly higher 5-year survival rate (66.0%) than those with Pyk2 low-expression (31.4%). Pyk2 expression, together with carcinoma histologic grade and TNM stage were prognostic factors to CRC on the multivariate analysis.</p><p><b>CONCLUSIONS</b>Pyk2 expression can be a prognostic factor to the CRC patients together with other predictors.</p>

Hic-5/ARA55 inhibits the growth of Lovo cells by up-regulating the expression of P27 / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of Hic-5/ARA55 on the growth of the human colorectal cancer cells (Lovo cells) and its mechanism.</p><p><b>METHOD</b>Flow cytometry (FCM) was used to study the cell cycle of Lovo cells (Lovo group), Lovo cells stably transfected with empty vector (Lovo-Vector group) and the Lovo cells stably transfected with vector containing Hic-5/ARA55 (Lovo-Hic-5/ARA55 group). Western blot assay was used to detect the principal cyclins in the three groups, and Luciferase assay was used to study the mechanism between Hic-5/ARA55 and the only target cyclin. The cells from the three groups were inoculated subcutaneously into 7 nude mice (Balb/c nu/nu) respectively to observe the effects of Hic-5/ARA55 on the growth of the cells in vivo. Seven weeks later, the subcutaneous tumors were harvested and weighed. Then immunohistochemistry assay was used to detect Hic-5/ARA55 and the target cyclin in the tumors.</p><p><b>RESULTS</b>The cell cycle was obviously delayed from G0/G1 to S stage in Lovo-Hic-5/ARA55 cells. A significantly higher expression of P27 was found in Lovo-Hic-5/ARA55 cells than in the other two groups. The weight of the subcutaneous tumors of Lovo-Hic-5/ARA55 cells, Lovo cells and Lovo-Vector cells were (0.33 +/- 0.23) g, (1.20 +/- 0.39) g and (1.30 +/- 0.49) g, respectively; the tumors of Lovo-Hic-5/ARA55 cells was significantly lighter than those of the other two groups (P<0.05). Hic-5/ARA55 and P27 were both over-expressed in implanted tumors of Lovo-Hic-5/ARA55 cells, while were both expressed lower or not expressed in the other two groups. And the expressions of Hic-5/ARA55 and P27 were highly positive correlated (r=0.816, P<0.05).</p><p><b>CONCLUSION</b>Hic-5/ARA55 could inhibit the growth of Lovo cells both in vitro and in vivo by up-regulating the transcription of P27.</p>

TGF-beta1/SMAD signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To determine whether transforming growth factor betal (TGF-beta1)/Smad signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.</p><p><b>METHODS</b>Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines was analyzed using TUNEL assay. For identifying the mechanism of apoptosis induced by TGF-beta1, cell lines were transfected with a TGF-beta1-inducible luciferase reportor plasmid containing Smad4 binding elements. After transfection, cells were treated with TGF-beta1, then assayed for luciferase activity.</p><p><b>RESULTS</b>The apoptosis rate of HepG2 cell lines (48.51% +/- 8.21%) was significantly higher than control (12.72% +/- 2.18%, P <0.05). But TGF-beta1 was not able to induce apoptosis of Huh-7 and Hep3B cell lines. The relative luciferase activity of TGF-beta1-treated HepG2 cell lines (4.38) was significantly higher than control (1.00, P < 0.05). But the relative luciferase activity of TGF-beta1-treated Huh-7 and Hep3B cell lines less increased compared with control.</p><p><b>CONCLUSIONS</b>HepG2 cells seem to be highly susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 is a central mediator of TGF-beta1 signaling transdution pathway. TGF-beta1/Smad signaling pathway might mediate p53-dependent apoptosis in hepatoma cell lines.</p>

The role of tissue factor in the invasion and metastasis of colorectal carcinoma cells / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of tissue factor (TF) in the invasion and hematogenous metastasis of human colorectal carcinoma cells.</p><p><b>METHODS</b>The eukaryotic expression vectors pcDNA3.1/Zeo bearing either sense or antisense TFcDNA were transfected into HT-29 and LoVo cells by the way of lipofactamine 2000. TF proteins in transfected cells were detected by Western Blot. Then the transfected and un-transfected tumor cells were implanted into nude mice (Balb/c Nu/Nu) to produce primary tumor, lung metastasis and liver metastasis respectively.</p><p><b>RESULTS</b>HT-29 and LoVo cells with sense-TFcDNA transfection showed increased TF expression compared with the cells without transfection, but the cells with antisense-TFcDNA transfection got the contrary change. The primary tumor growth and invasive range, lung metastasis and live metastasis all increased in sense transfectants but reduced in antisense transfectants.</p><p><b>CONCLUSIONS</b>TF can increase the invasion and hematogenous metastatic ability of human colorectal carcinoma cells.</p>

Role of tissue factor in lung metastasis of colorectal carcinoma cells in vivo / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the role of tissue factor(TF) in hematogenous metastasis of human colorectal carcinoma cells (LOVO) in vivo.</p><p><b>METHODS</b>The eukaryotic expression vectors pcDNA3.1/Zeo bearing either sense or antisense TFc DNA were transfected into LOVO cells by lipofectamine 2000. TF protein expression in the transfected cells was detected by Western blot. Eighteen nude mice (Babl/c nu/nu) were randomly divided into three groups, and then transfected and untransfected LOVO cells were implanted via tail vein respectively. The nude mice were sacrificed 8 weeks after implantation, and the number of metastatic nodules in the lung was used to assess the metastatic ability of LOVO cells.</p><p><b>RESULTS</b>Compared with the untransfected group, TF expression of LOVO cells and the numbers of metastatic nodules in the lung increased in sense-TF cDNA transfection group (P< 0.05, P< 0.01, respectively), whereas decreased in antisense-TF cDNA transfection group (P< 0.05, P< 0.01, respectively).</p><p><b>CONCLUSION</b>TF can increase the hematogenous metastatic ability of human colorectal carcinoma cells (LOVO) in vivo.</p>

Rectal stromal tumors: a clinicopathological study of 16 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical diagnosis, treatment and immunohistochemical characteristics of rectal stromal tumors.</p><p><b>METHODS</b>Immunohistochemical expression of CD117 was retrieved in 20 cases of mesenchymal tumors of the rectum. And we analyzed the immunohistochemical characteristics, clinical data of rectal stromal tumors, and the results retrospectively.</p><p><b>RESULTS</b>Sixteen cases of rectal stromal tumors, 3 cases of leiomyosarcomas and 1 case of schwannoma were diagnosed. Histologically, 2 cases of GISTs were classified as benign, 1 as borderline and 13 as malignant. All of rectal stromal tumors (100%) were strongly positive for CD117, and 14 cases (88%) positive for CD34. The demographic profile of rectal stromal tumors showed a male predominance with average age of 60 years old. The main symptoms were urinary retention, constipation and abdominal pain. 14 cases were positive in digital rectal examination. The recurrence rate of local and radical resection in malignant stromal tumors was 4/4 and 3/6. 1, 3, 5-year survival rates were 89%, 64%, 48%, respectively. After operation mean survival time of was 47 months.</p><p><b>CONCLUSIONS</b>The specific GIST constituted the majority of mesenchymal tumors in rectum. It usually showed malignant biological behavior. Invasion and recurrence were common. Earlier diagnosis and radical resection had better prognosis. Periodically following up can help to detect the recurrence timely.</p>

The role of tissue factor expression in the invasive and metastatic ability of colorectal carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of tissue factor (TF) expression in the invasive and metastatic ability of colorectal carcinoma and explore the influence of TF on the invasive ability of HT-29 cells.</p><p><b>METHODS</b>TF expression of specimens from 85 colorectal carcinomas and 6 colorectal adenomas was observed by immunohistochemistry. The role of TF expression in prognosis and tumor invasion and metastasis was analyzed. The plasmids pcDNA3.1/Zeo bearing either sense or antisense-TFcDNA were transfected into HT-29 cells by the way of Lipofectamine 2000. TF proteins in transfected and untransfected HT-29cells were detected by Western blot. In vitro Matrigel invasion assays were performed to show the invasive ability of those cells.</p><p><b>RESULTS</b>TF expression was positive in 40 (47.1%) of 85 colorectal carcinoma specimens, but negative in normal mucosa and adenoma specimens. TF expression showed significant correlation with tumor invasive depth (r = 0.895, P < 0.01). TF expression showed significant correlation with synchronous and metachronous hepatic metastasis (r = 0.974, P < 0.01 and r = 0.963, P < 0.01 respectively). TF expression was a significant risk factor for hepatic metastasis (P < 0.01) and prognosis (P < 0.01). TF expression in HT-29 cells with sense/antisense-TFcDNA transfection was more/less than that of the cells without transfection. The invasive ability of HT-29 cells with sense-TFcDNA transfection was increased in vitro compared with the untransfected cells, but HT-29 cells with antisense-TFcDNA transfection got the contrary change.</p><p><b>CONCLUSIONS</b>TF may take part in the invasive and metastatic process of primary colorectal carcinoma, and TF expression may be an indicator of hepatic metastasis and prognosis for colorectal carcinoma patients. TF expression may increase the invasive ability of HT-29 cell in vitro.</p>

Clinical analysis of combined resection for T4 gastric cancer: report of 69 cases / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of combined resection for the treatment of T(4) gastric cancer and to refine the indication for en bloc dissection.</p><p><b>METHODS</b>Clinical data of 69 cases receiving combined resection were analyzed retrospectively, and compared with those of 45 cases undergoing palliative gastrectomy.</p><p><b>RESULTS</b>Of 69 cases, 54 patients underwent curative combined resection, 15 patients underwent palliative combined resection, including 24 with transverse colectomy, 22 with pancreatico-splenectomy, 8 with left lateral lobectomy of liver, 6 with pancreatico-splenectomy and transverse colectomy, 5 with pancreaticoduodenectomy, 2 with cholecystectomy, 1 with splenectomy, 1 with phrenectomy. The total rate of lymph node metastasis was 88.4%; the operative mortality rate was 4.3%; the morbidity rate was 14.5%. The postoperatively 1-, 3-, 5-year survival rates of CR group and NCR group were 66.9%, 39.1%, 26.8% and 33.4%, 7.4%, 0% respectively (P < 0.01). The five year survival rate of curative resection group was 34.1%.</p><p><b>CONCLUSIONS</b>An en bloc combined resection can cure some T(4) patients, and improve the five-year survival rate.</p>

TF/F Ⅶa complex induce the expression of MMP-7mRNA via P38 signal pathway in LOVO cells of colon cancer in vitro / 中国普通外科杂志

Objective To investigate the expression of matrix metalloproteinase 7(MMP-7) mRNA in LOVO cells of colon cancer induced by TF/F Ⅶ a and its signal pathway.Methods We transfected LOVO cells stably with RNAi plasmid targeting to tissue factor to get TFRNAi LOVO cells and detected efficiency of interference in TFRNAi LOVO cells based on Western blot analysis;Expression of MMP-7 was evaluated in LOVO cells treated with 100 nmol/L FⅦa in 0 h、4 h、8 h、12 h、24 h based on RT-PCR and Northern blot.Expression of MMP-7mRNA was determined in quiescent LOVO cells treated with different doses of FⅦa(0 nmol/L、10nmol/L、50 nmol/L、100 nmol/L、200 nmol/L)for 8 h based on Northern blot.Quiescent LOVO cells were treated for 0 h、4 h、8 h、12 h、16 h、24 h with 100 nmol/L FⅦa to evaluate the expression of p-P38;The expression level of MMP-7mRNA induced by 100 nmol/L FⅦa for 8 h in LOVO cells blocked by 10retool SB203580 0.5 h previously and in TFRNAi LOVO cells were measured by Northern blot.Results Northern blot analysis revealed that FⅦa markedly increased the expression of MMP-7mRNA in a time-and dose-dependent manner.Western blot analysis confirmed that FⅦa stimulates p-P38 in a time-dependent manner.SB203580 block 59.2% expression of MMP-7mRNA in LOVO cells induced by TF/FⅦa.In TFRNAi LOVO cells,the expression of MMP-7mRNA induced by TF/FⅦa was 48% less than that in normal LOVO cells.Conclusions TF/FⅦa Complex induces the expression of MMP-7mRNA in LOVO cells in vitro,possibly through P38 pathway.