Rethinking of neoadjuvant therapy for patients with initially resectable colorectal cancer liver metastases / 中华肝胆外科杂志

Surgical resection is the best method for patients with colorectal cancer liver metastases. However, tumor recurrence rate is still high after surgery. Preoperative chemotherapy can help shrink the tumor, test biological behavior, and reduce recurrence rate; but it may also cause liver injury and delay surgery. There is still controversy whether neoadjuvant chemotherapy should be performed and how to select patients from chemotherapy before surgery. Thus, in this article, combined the research progress and the clinical experience of author's center, we discuss this issue in 4 aspects: the development of neoadjuvant chemotherapy; the indications and guideline recommendation for neoadjuvant chemotherapy; the selection of neoadjuvant chemotherapy regimens; common problems in neoadjuvant chemotherapy.

Mid-term outcomes of a prospective phase Ⅱ trial of preoperative sandwich-like neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective To evaluate the mid-to long-term survival benefits of preoperative sandwich-like neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC).Methods A total of 45 LARC patients who underwent neoadjuvant sandwich CRT in the form of XELOX regimen prior to,concurrently with,and following volumetric modulated arc radiotherapy (VMAT) in 2012 were enrolled in this study.VMAT was given at a gross tumor volume dose of 50 Gy in 25 fractions,and a clinical target volume dose of 45-46 Gy in 25 fractions.Total mesorectal excision was performed 6 to 8 weeks after completion of VMAT.The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method,and survival comparison and univariate prognostic analysis were performed using the log-rank test.Results The median follow-up time was 46.7 months.There was no local recurrence detected among the patients.The 3-year distant metastasis (DM) rate was 18%,and the 3-year OS and DFS were 96% and 84%,respectively.Univariate analysis indicated that perineural invasion,N1-N2 pathology (pathological stage Ⅲ),and Ca-199>35 U/ml before treatment were risk factors for DM (P=0.000,0.000,and 0.013,respectively).Conclusions The significant short-term efficacy of preoperative sandwich-like neoadjuvant CRT can be extended to a positive mid-term survival in LARC patients.However,further phase Ⅲ clinical studies will be needed to confirm this finding.

Surgical treatment and prognostic analysis for 57 patients with gastrointestinal lymphoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore clinicopathologic characteristics, surgical features and prognostic factors in patients with primary gastrointestinal lymphoma(PGIL) in order to provide evidence for optimizing surgical treatment.</p><p><b>METHODS</b>Clinicopathological data of 57 PGIL patients undergoing abdominal surgery in Sun Yat-sen University Cancer Center between October 1990 and January 2015 were retrospectively collected. The survival rates were compared among patients with different clinicopathologic characteristics by Kaplan-Meier method, while Cox regression model was employed to analyze the prognostic factors.</p><p><b>RESULTS</b>Among 57 patients, 43 were male and 14 were female, with a median age of 48 (range 16 to 80) years. Seventeen (29.8%) cases were classified as Musshoff I( stage, 19 (33.3%) cases as II( stage, 9 (15.8%) cases as III( stage, and 12(21.1%) cases as IIII( stage. Forty-four (77.2%) cases underwent selective operation, 13(22.8%) cases underwent emergent operation due to acute abdomen. Thirty-two(56.1%) cases had radical resection, 18 (31.6%) cases had partial resection and the rest 7(12.3%) cases failed to perform resection. Four (7.0%) cases received simple surgical operation, and 53 (93.0%) cases received comprehensive treatment, including 5(8.8%) cases with preoperative chemotherapy and surgery, 40 (70.2%) cases with surgery and postoperative chemotherapy, and 8 (14.0%) cases with surgery and perioperative chemotherapy. Stage III( and IIII( accounted for 76.9%(10/13) in patients undergoing emergent operation and accounted for 25.0%(11/44) in patients undergoing selective operation, whose difference was statistically significant (χ=9.503, P=0.002). Univariate prognostic analysis showed that T lymphocyte source pathological cell phenotype (P=0.000), clinical Musshoff stage III( and IIII((P=0.001), emergent operation (P=0.000) and incomplete tumor resection(P=0.007) had worse 5-year overall survival. Multivariate Cox regression analysis indicated that tumor pathological cell phenotype (HR=13.75, 95%CI:3.546-53.308, P=0.000) and surgical timing (HR=7.497, 95%CI:1.163-48.313, P=0.034) were independent prognostic risk factors of patients with stage I( and II(.</p><p><b>CONCLUSIONS</b>Surgical operation is an important part of comprehensive treatment for PGIL. T lymphocyte source and ulcerative lymphoma indicates poorer prognosis.</p>

Clinical study on locally advanced rectal cancer patients with pathological complete response after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the efficacy prediction of the locally advanced rectal cancer patients, especially those with pathological complete response(pCR), receiving neoadjuvant chemoradiotherapy in order to execute precise preoperative neoadjuvant chemoradiotherapy.</p><p><b>METHODS</b>From January 2000 to January 2011, 125 patients diagnosed as locally advanced rectal cancer receiving preoperative neoadjuvant chemoradiotherapy in our department with complete data were enrolled in this study, including 85 males and 40 females with mean age of 54(15 to 77) years old. All the patients received radiotherapy with 46 Gy(23 times) and administered XELOX regimen (oxaliplatin 100 mg/m(2) plus capecitabine 2 000 mg/m(2)) for 2 courses simultaneously, and underwent radical operation 6 to 8 weeks after chemoradiotherapy. The data of these patients were analyzed retrospectively. Pathological remission was divided into 4 grades. Patients achieving grade 4 were defined as pCR, and those achieving above grade 2 were defined as better response. Logistic regression analysis was used to identify significant predictors of pCR.</p><p><b>RESULTS</b>Among 125 patients, 16(12.8%) achieved pCR status, and 90(72.0%) had better response to the neoadjuvant chemoradiotherapy. Logistic regression analysis showed that age(OR:1.060, P=0.037) and preoperative positive lymph nodes detected by endorectal ultrasonography (OR:0.059, P=0.006) were independent predictors of pCR after neoadjuvant chemoradiotherapy.</p><p><b>CONCLUSIONS</b>Preoperative existence of lymph node metastasis around bowel indicates the poor response to neoadjuvant chemoradiotherapy. Age is associated with pCR in patients receiving neoadjuvant chemoradiotherapy.</p>

Impact of macroscopic enlarged lymph node on stage II colorectal cancer prognosis and its potential mechanism / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of macroscopic enlarged lymph node on the clinicopathological characteristics of stage II colorectal cancer, and to explore the potential mechanism.</p><p><b>METHODS</b>Clinicopathological data of 116 consecutive patients with stage II colorectal cancer, who underwent colorectal radical resection and were identified as stage II colorectal cancer without mesenteric metastasis by postoperative pathology, in our department between December 2001 and December 2002 were analyzed retrospectively. All the patients were examined by the surgeons with gross appearance to decide the enlarged lymph nodes as metastasis during operation. There were 43 patients with macroscopic enlarged lymph nodes and 73 without such lymph nodes. Survival rate was compared between the two groups. Impact of macroscopic enlarged lymph node on the prognosis of stage II colorectal cancer was analyzed. Structure of macroscopic enlarged lymph node was observed. CK expression in 107 macroscopic enlarged lymph nodes from 43 cases was examined by immunohistochemistry.</p><p><b>RESULTS</b>The 10-year disease-free survival (DFS) of the whole group was 83.5%. The 10-year DFS of patients with macroscopic enlarged lymph nodes was 75.9%, which was significantly lower than 89.3% (P=0.038) of patients without macroscopic enlarged lymph nodes. Univariate analysis showed that macroscopical enlarged lymph node (P=0.038), perioperative blood transfusion (P=0.004), number of retrieved lymph nodes (P=0.016), concomitant disease (P=0.003), and preoperative serum carcinoembryonic antigen (CEA) level (P=0.050) were related to the prognosis of all the 116 patients. Multivariate analysis showed that macroscopical enlarged lymph node (P=0.044), number of retrieved lymph nodes (P=0.021), and perioperative blood transfusion (P=0.032) were independent prognostic factors. Haematoxylin and eosin (HE) staining indicated that enlarged lymph nodes had hyperplasia reaction. Immunohistochemistry showed that among 107 enlarged lymph nodes, 1 had macrometastases, 1 micrometastasis, 4 isolated tumor cell (ITC), and the rest 101 had no positive CK expression.</p><p><b>CONCLUSION</b>Macroscopic enlarged lymph node indicates a poor prognosis in patients with stage II colorectal cancer.</p>

Clinicopathological analysis of 61 patients with rectal gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with rectal gastrointestinal stromal tumor(GIST).</p><p><b>METHODS</b>Clinicopathological and follow-up data of 61 patients with rectal GIST in our department from January 1990 to October 2012 were analyzed retrospectively and pathology specimens were reviewed. Kaplan-Meier method was used to calculate the survival. Univariate analysis and multivariate analysis were performed to investigate the influencing factors of prognosis with Log-rank test and Cox regression model.</p><p><b>RESULTS</b>There were 42 male and 19 female patients with a median age of 59 years old. Eighteen cases(29.5%) were confirmed preoperatively as GIST by biopsy and 46 cases were diagnosed as GIST by first pathological examination. Fifteen cases(24.6%) were revised as GIST after re-examination of specimes among whom 14 cases had been diagnosed as leiomyoma or sarcoma, and 1 as neurolemmoma. Tumor location was above peritoneal reflection in 12 cases(19.7%) and below peritoneal reflection in 49(80.3%). Fifty-two patients underwent surgery, including 21 extended resections(lymph nodes clearance and combined organs resection simultaneously) and 31 local resections(tumor rejection or partial resection of rectal wall). Eleven patients received preoperative imatinib(400 mg/d). Forty-one cases received imatinib therapy after operation or biopsy diagnosis, including 25 cases who received palliative treatment for postoperative recurrence. Median follow-up time was 55(6 to 391) months and follow-up longer than 2 years was carried out in 46 patients. Overall survival rates of 1-, 2-, 3- , 5-year were 98%, 95.6%, 86.0% and 73.7% respectively. There were no significant differences between local resection group(96.4%, 92%, 83.3% and 77.3%) and extended resection group (100%, 94.7%, 89.50% and 82.6%)(χ(2)=0.004, P=0.947). Univariate analysis showed that survival was only associated with recurrence and metastasis (χ(2)=4.292, P=0.038). Multivariate Cox analysis showed postoperative survival was not associated with any factors(all P>0.05). The 3-year survival rate of patients with postoperative recurrence or metastasis receiving imatinib therapy was better as compared to those who did not received imatinib(82.7% vs. 71.4%).</p><p><b>CONCLUSIONS</b>Rectal GIST are more common in the lower rectum. Surgery is the main treatment for rectal GIST. Local complete resection is the mainstay treatment. Extensive resection and lymph node clearance may not improve survival. Imatinib can improve the prognosis of patients with recurrence or metastasis.</p>

The 13th world congress on gastrointestinal cancer: new progress of bevacizumab in treating colorectal carcinoma / 肿瘤研究与临床

To summarize the latest study results about anti-angiogenic therapy for colorectal cancer (CRC) reported in the 13th world congress on gastrointestinal cancer, and review the latest progress of bevacizumab in treating colorectal carcinoma combined with related literatures.From the internal medicine point of view, bevacizumab is emphasized that to be applied earlier would gain benefit as soon as possible,and to be applied continuously would gain more benefit.The curative effect of second-line therapy has been confirmed renewedly.In the surgery point, bevacizumab neoadjuvant treating liver metastases in metastatic colorectal carcinoma (mCRC) can improve the disease-free rate and the operable rate significantly, and has favorable tolerance.In addition,bevacizumab can decrease the hepatic injury induced by chemotherapy safely and effectively.

Distal spread of low and middle rectal cancer in mesorectum and rectal wall found by large slices stained with CK20 / 中华普通外科杂志

Objective To examine the frequency and mode of distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Methods Thirty-four specimens from low and middle rectal cancer were collected between August 2004 and December 2005 in Cancer Center of Sun Yat-sen University. Twenty-eight specimens of low and middle rectal cancer were collected between October 2006 and October 2007 in Shandong Provincial Hospital of Shandong University. All 62 specimens were studied using large slices stained with CK20. Logistic regression was used to analyze clinicopathologic factors related to distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Results Two types of distal spread of the tumor were observed in rectal wall: submucosa invasion and muscularis propria invasion. Distal spread in rectal wall was observed in 16% (10/62) of the patients. The length of distal spread in rectal wall was found from O. 5 cm to 1.0 cm. Four types of distal spread of the tumor were observed in mesorectum: lymph node invasion, blood and lymphatic vessel invasion, perineural invasion, isolated neoplastic microfoci. Distal spread in mesorectum was observed in 24% (15/62) of the patients. The length of distal spread in mesorectum was found from 0. 5 cm to 4. 0 cm. Three more cases with microcapillary invasion in distal mesorectum was observed by immunohistochemical technique, which was difficult to identify by conventional HE staining. Univariate analysis showed that serum CEA , lymph node invasion, CMI and TNM stage were correlated with distal spread of low and middle rectal cancer in the mesorectum and rectal wall. TNM stage was shown to be independent impact factor by multivariate analysis( Wald = 9. 567, P =0. 002). Conclusion TNM stage is an independent impact factor for distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Resection of 1.5 cm for distal rectal wall is necessary for a curative intention, but it must be emphasized that the clearance for distal mesorectum should be 5 cm at least.

A study on distal spread of low and middle rectal cancer in mesorectum and rectal wall / 中华普通外科杂志

Objective To examine the frequency and mode of distal spread of low and middle rectal cancer in the mesorectum and rectal wall to determine the optimal distal clearance in situ. Methods Thirty-four specimens with low and middle rectal cancer were collected in the pathologic study between August 2004 and December 2005 in Cancer Center of Sun Yat-sen University,Twenty-eight specimens with low and middle rectal cancer were enrolled in the pathologic study between October 2006 and October 2007 in Shandong Provincial Hospital of Shandong University.Logistic regression wag used to analyze clinicopathoiogic factors related to distal spread of low and middle rectal cancer in the mesorectum and rectal wall. Results Two types of disial spread of the tumor were identified in rectal wall:submucosa invasion and muscularis propda invasion.Distal spread in rectal wall was observed in 16%(10/62)of the patients.The length of distal spread in rectal wall was found from 0.5 cm to 1.0 cm.Four types of distal spread of the tumor were identified in mesorectum:lymph node invasion,blood and lymphatic vessel invasion,perineural invasion,isolated neoplastic microfoci.Distal spread in mesorectum was observed in 19%(12/62)of the patients.The length of distal spread in mesorectum was found from 0.5 cm to 4.0 cm.Univariate analysis showed that serum CEA,lymph node invasion.circumferential margin involvemenl and Dukes stage were correlated with distal spread of low and middle rectal cancer in the mesorectum and rectal wall.Dukes stage was shown to be independent impact factor by multivariate analysis(Wald=8.386,P=0.004).Conclusion Dukes stage is an independent impaet factor for distal spread of low and middle rectal cancer in the mesorectum and rectal wall.Resection of 1.5 cm for distal rectal wall mandatory for a curative resection,provided that the clearance for distal mesorectum is no less than 5.0 cm.

Recent advances of surgical treatment for rectal cancer / 中国癌症杂志

Incidence and mortality of colorectal cancer(CRC) are rising.There were one million and twenty-three thousand new cases and five hundred and twenty-nine thousand deaths in 2002,which were 8.3% and 7.5% more than that in 2000,respectively.Incidence and mortality of CRC take the third and forth place in all cancers.Mortality in China has increased by 70.7% since 1991,by 4.71% per year in average.Therefore,CRC is one of the heat points in cancer research.In this paper,we focused on the progress in treatment for rectal cancer.Sphincter-preserved resection has an increasing proportion in surgical procedures,owing to improvement of technique,TME and the staplers.Above all,the most important reason seems to be the popular opinion that distal margin of 1 to 2 centimeters is safe enough.TME acts as a "gold standard" in rectal cancer resection,due to its magnificent potential in controlling local recurrence which had decreased from 35%-45% to 3%-11%.Microsurgery is a band-new technique.Laparoscopic colon resection is satisfactory with selective cases.Extended resection results in improving 5-year survival of advanced rectal cancer distal to the reflection to 68%.Further improvement of the outcome depends on multiple modality regimens.Neoadjuvant chemoradiotherapyshows an exciting prospect in some trials.But more multicenter clinical trials are needed to solve the remaining problems.

Multiple factors analysis on liver metastasis from colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical factors related with liver metastasis from colorectal cancer.</p><p><b>METHODS</b>1 312 colorectal cancer patients treated from 1988 to 1997 were collected to set up the database. Binary and multinomial logistic regression (SPSS 10.0 for windows) and then correlation analysis were used to evaluate the factors concerned.</p><p><b>RESULTS</b>Sex, disease course, gross tumor type, differentiation degree, pathological grade, infiltration depth and lymph node metastasis were related with liver metastasis by single factor analysis. Only sex, infiltration depth and lymph node metastasis were related with liver metastasis by multiple factor analysis. More male than female were observed in patients with liver metastasis from colorectal cancer (1.9:1, P = 0.006). Liver metastasis in colorectal cancer was positively related to the infiltration depth into the intestine wall (r = 0.926, P = 0.024). However, the correlation between the distance of lymph node metastasis and liver metastasis in colorectal cancer had no statistical significance (r = 0.748, P = 0.252).</p><p><b>CONCLUSION</b>Sex, depth of infiltration and lymph node metastasis are the main clinical factors related with liver metastasis from colorectal cancer. Male colorectal cancer patients are apt to develop liver metastasis. The deeper the tumor infiltrates, the more the liver metastasis. Age, blood type, symptoms, course, complications, tumor size and site are not related with liver metastasis in colorectal carcinoma.</p>

The evidence-based adjuvant chemotherapy for colon cancer / 中国癌症杂志

Fluoropyrimidines are still the basic agents for adjuvant chemotherapy of colon cancer,a regimen containing 5-FU/LV/oxaliplatin (FOLFOX or FLOX) is the new standard for adjuvant settings,and FU/LV alone (Mayo,Roswell Park or LV5FU2) or single agent of capecitabine should be a choice of treatment for some particular patients; irinotecan should not be used for the adjuvant setting of colon cancer,because currently there is no evidence to show additional survival benefi t with addition of irinotecan to the adjuvant treatment,but increased risk of chemotherapy-related toxicity. Stage Ⅲ colon cancer is the main and defi nite indication for adjuvant chemotherapy,while adjuvant chemotherapy should not be routinely considered for stage Ⅱ colon cancer,except those with high risk factors including T4 tumor,obstruction,perforation,poor differentiation,invasion to nerve or vessels,and less than 12 examined lymph nodes. The age should not exclude the adjuvant chemotherapy if there is an adequate performance status. Adjuvant chemotherapy should be started within 8 weeks after surgery,and the current optimal duration for adjuvant chemotherapy of colon cancer should be six months.