Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer / 中华胃肠外科杂志

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial / 癌症

<p><b>INTRODUCTION</b>Multimodality therapy, including preoperative chemoradiotherapy (CRT) and total mesorectal excision (TME), has effectively reduced local recurrence rates of rectal cancer over the past decade. However, the benefits and risks of the addition of neoadjuvant CRT to surgery need to be evaluated. This study was to compare the efficacy of TME with versus without preoperative concurrent chemoradiotherapy (CCRT) involving XELOX regimen (oxaliplatin plus capecitabine) in Chinese patients with stages II and III mid/low rectal adenocarcinoma.</p><p><b>METHODS</b>We randomly assigned patients to the TME group (TME without preoperative CCRT) or CCRT + TME group (TME with preoperative CCRT). The primary endpoint was disease-free survival (DFS); the secondary endpoints were overall survival (OS), local and distant recurrence, tumor response to CRT, toxicity, sphincter preservation, and surgical complications. An interim analysis of the potential inferiority of DFS in the CCRT + TME group was planned when the first 180 patients had been followed up for at least 6 months.</p><p><b>RESULTS</b>A total of 94 patients in the TME group and 90 patients in the CCRT + TME group were able to be evaluated. The 3-year DFS and OS rates were 86.3 % and 91.5 % in the whole cohort, respectively. The 3-year DFS rates of the TME and CCRT + TME groups were 85.7% and 87.9 % (P = 0.766), respectively, and the 3-year OS rates were 90.7 % and 92.3 % (P = 0.855), respectively. The functional sphincter preservation rates of the TME and CCRT + TME groups were 71.3 % and 70.0 % (P = 0.849), respectively. In the TME group, 16 (17.0 %) patients were proven to have pTNM stage I disease after surgery. In the CCRT + TME group, 32 (35.6 %) patients achieved a pathologic complete response (pCR).</p><p><b>CONCLUSIONS</b>Preliminary results indicated no significant differences in the DFS, OS, or functional sphincter preservation rates between the TME and CCRT + TME groups. However, preoperative CCRT with XELOX yielded a high pCR rate. Newer techniques are needed to improve the staging accuracy, and further investigation is warranted.</p><p><b>CLINICAL TRIAL REGISTRATION NUMBER</b>Chi CTR-TRC-08000122.</p>

Expression of molecular markers detected by immunohistochemistry and risk of lymph node metastasis in stage T1 and T2 colorecrectal cancers / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the molecular risk factors of lymph node metastasis in stage T1 and T2 colorectal cancers by tissue microarray and immunohistochemistry techniques.</p><p><b>METHODS</b>Two hundred and three patients with stage T1 and T2 colorectal carcinoma who underwent radical surgery from 1999 to 2010 in our department were included in this study. Their clinicopathological data were retrospectively analyzed. Expression of the following 14 molecular markers were selected and assayed by tissue microarray and immunohistochemistry: VEGFR-3, HER2, CD44v6, CXCR4, TIMP-1, EGFR, IGF-1R, IGF-2, IGFBP-1, ECAD, MMP-9, RKIP, CD133, MSI. Chi-squared test and logistic regression were used to evaluate the variables as potential risk factors for lymph node metastasis.</p><p><b>RESULTS</b>The positive expression rates of biomarkers were as following: VEGFR-3 (44.3%), EGFR (30.5%), HER-2 (28.1%), IGF-1R (63.5%), IGF-2 (44.8%), IGFBP-1 (70.9%), ECAD (45.8%), CD44v6 (51.2%), MMP-9 (44.3%), TIMP-1 (41.4%), RKIP (45.3%), CXCR4 (40.9%), and CD133 (49.8%). The positive rate of MSI expression was 22.2%. Both univariate and multivariate analyses showed that VEGFR-3, HER-2, and TIMP-1 were significant predictors of lymph node metastasis. Univariate analysis showed that CD44v6 and CXCR4 were significant significant predictors of lymph node metastasis.</p><p><b>CONCLUSIONS</b>VEGFR-3, HER2 and TIMP-1 are independent factors for lymph node metastasis in stage T1 and T2 colorectal cancers.</p>

Compliance and associated factors of postoperative chemotherapy for elderly patients with colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the compliance and associated factors of postoperative chemotherapy for elderly patients with colorectal cancer.</p><p><b>METHODS</b>A total of 386 elderly patients (>70 years old) with stage II(-IIII( colorectal cancer underwent surgery between January 2000 and January 2010. The clinicopathological data were retrospectively reviewed. There were 226 patients received postoperative chemotherapy and 160(41.4%) refused. Logistic regression model was used to analyze factors associated with patients compliance to chemotherapy. Patients were followed up by phone call regarding the reason for refusal.</p><p><b>RESULTS</b>Multivariate analysis showed that gender, body mass index (BMI), body surface area (BSA), age, and complication were independent risk factors associated with chemotherapy compliance(All P<0.05). Follow-up phone questionnaire showed that 63.8%(51/80) of patients with stage II( cancer did not received chemotherapy because of the doctor's uncertainty of chemotherapy benefit. For stage III( patients, fear of chemotherapy (31.2%, 15/48), feeling uncomfortable (18.8%, 9/48), and financial issues(18.8%, 9/48) were the main factors. The desperate feeling was the predominant reason for stage IIII( patients(56.2%, 18/32).</p><p><b>CONCLUSIONS</b>Gender, BSA, age, and postoperative complication are the main factors associated with compliance to postoperative chemotherapy. Doctors' recommendation should be emphasized for stage II( patients. For stage III( patients, treatment recommendation should be enthusiastic.</p>

Surgical treatment and prognosis of gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the outcome of surgical treatment for gastrointestinal stromal tumor(GIST) and the associated factors.</p><p><b>METHODS</b>A total of 277 patients with GIST underwent primary surgical treatment from January 1990 to February 2010 at the Cancer Center of Sun Yat-sen University. The clinical data were retrospectively reviewed and the pathological examination was reviewed. Follow-up was performed.</p><p><b>RESULTS</b>There were 176 males and 101 females. The age ranged from 20 to 81 years old (median,57). Location of the tumor included colorectum (n=28),small bowel(n=76), stomach(n=173). All the patients had en bloc resection, including local excision in 98 patients, organ resection in 64, and extended resection in 115. The 5-year survival rates were 83.5%, 71.9%, and 61.9% in the three different procedures, respectively, and the difference was not statistically significant(P>0.05). Cox model showed that the tumor size, recurrence and metastasis were independent risk factors associated with the prognosis in GIST patients(P<0.05).</p><p><b>CONCLUSIONS</b>Surgery remains the major approach for gastrointestinal GIST. Complete resection is the principal treatment. Extensive resection or extended lymph nodes dissection is not associated with improved survival.</p>

Surgical treatment for 140 patients with gastric stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the outcome of the patients with gastric gastrointestinal stromal tumor(GIST) after surgical treatment and identify the associated risk factors.</p><p><b>METHODS</b>Clinical data and the tissue slices including immunohistochemistry staining of 140 patients with gastric GIST from January 1990 to December 2008 were retrospectively reviewed. SPSS 16.0 for Windows software package was used for statistical analysis.</p><p><b>RESULTS</b>The overall survival rates of 1-, 3-, 5-year were 96.8%, 86.7% and 79.3%, respectively. The survival rates of 1-, 3-, 5-year were 98.1%, 90.0% and 85.4% in patients who underwent complete tumor resection. But the survival rates of 1-, 3-, 5-year were 38.1%, 0 and 0 in patients with incomplete tumor resection. The differences were statistically significant (P<0.05). Gender, preoperative metastasis, tumor size,pathology type,karyokinesis, recurrence and metastasis were associated with survival rates in patients with complete tumor resection by univariate analysis. However, only tumor size, karyokinesis, recurrence and metastasis were associated with survival rates by Cox regression multivariable analysis(P<0.05).</p><p><b>CONCLUSION</b>Surgery remains the main treatment for gastric GIST. Local complete resection is the principal treatment.</p>

Surgical treatment for gastrointestinal stromal tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To analyze the effects of surgical treatment for gastrointestinal stromal tumors (GISTs) and influential factors of survival.</p><p><b>METHODS</b>The clinical data and the tissue slices including immunohistochemical staining of 153 cases of GISTs from January 1990 to March 2006 were rechecked retrospectively. All patients were followed up carefully. More attention was paid to the surgical effects and the influential factors of survival.</p><p><b>RESULTS</b>The overall survival rates at 1-, 2-, 3-, 4- and 5-year were 94.9%, 83.3%, 73.3%, 70.5% and 64.3%, respectively. The median survival time for patients with tumor resected completely was 66.0 months, and the 2- and 5-year survival rate were 89.4% and 70.9% respectively. The median survival time was 23.8 months for the patients with tumor resected partly, and only two of these patients survived over 2 years. Gender, tumor sites, preoperative metastasis, tumor size, pathological type, karyokinesis and recurrence and metastasis were related with survival rates for the patients with tumor resected completely on univariate analysis, but tumor size, pathology type, recurrence and metastasis were related with survival rates on Cox regression multivariate analysis (P < 0.05).</p><p><b>CONCLUSIONS</b>Surgery should still be the main therapy for GISTs. Local complete resection is the principal treatment. The survival cannot be improved by extensive resection and lymph nodes clearance.</p>

Inhibitory effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the effect of angiogenesis inhibitor YH-16 in combination with 5-FU on liver metastasis of colorectal cancer.</p><p><b>METHODS</b>In vitro, the inhibitory effects of YH-16 and 5-FU on the growth of vascular endothelial cells and colorectal cancer cells were examined by MTT assay. In vivo, colorectal cancer cells were transplanted into BALB/c mice, and the mice were divided into six groups randomly:control group, low-dose YH-16 group, middle-dose YH-16 group, high-dose YH-16 group, 5-FU group and combination group. The number of liver metastases, the size of primary tumor and the toxicity were examined after 2 weeks postoperatively. The expression of vascular endothelial growth factor (VEGF) in liver metastases was detected by immunohistochemistry, and tumor microvessel density (MVD) was measured by immunostaining with CD34 and factor VIII (monoclonal antibodies.</p><p><b>RESULTS</b>In vitro, YH-16 inhibited the growth of colon cancer cells and vascular endothelial cells, with the IC50 at (2.16+/-0.28) microg/ml and (0.64+/-0.10) microg/ml respectively. In vivo high-dose YH-16 and 5-FU had a remarkable inhibitory effect on liver metastasis, and the combination group showed significant enhancement on this effect (P< 0.05). The combination group and 5-FU group could inhibit the growth of primary tumor, but not found in YH-16 group. The toxicity of YH-16 was lower than that of 5-FU (P< 0.05), and the difference was not found in the toxicity between combination group and 5-FU group (P > 0.05). Expression of VEGF in liver metastases was clearly inhibited by YH-16 in combination with 5-FU or 5-FU alone compared to the control group, and MVD in middle-dose and high-dose YH-16 group, 5-FU group and combination group was lower than that in control group (P< 0.05).</p><p><b>CONCLUSIONS</b>The angiogenesis inhibitor YH-16 can inhibit liver metastasis of colorectal cancer through inhibiting the growth of vascular endothelial cells. YH-16 in combination with 5-FU has additive effect on inhibitory activity against liver metastasis.</p>

Clinical features and treatment of 49 patients with anal canal adenocarcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and treatment of anal canal adenocarcinoma.</p><p><b>METHODS</b>Clinical data of 49 patients with anal canal adenocarcinoma treated in our hospital from January 1965 to March 2002 were analyzed retrospectively.</p><p><b>RESULTS</b>The ratio of male to female was 1.3. The median age was 56 years old. Anal bleeding, tapering stool and anal lump were the most common symptoms. Chronic perianal diseases were complicated in 36.7% of the cases. The median follow-up was 66 months. Local recurrence and inguinal lymph node metastasis were found in 7 cases respectively, lung metastasis in 2, supraclavicular and mediastinal metastasis in 1 respectively. The 3-year survival rates in the patients with resection alone, radiochemotherapy alone, resection combined with radiochemotherapy, and without any treatment were 41.3%, 20.0%, 56.3% and 15.0%, respectively, and the 5-year survival rates were 34.4%, 0, 37.5%, 0, respectively.</p><p><b>CONCLUSIONS</b>Anal canal adenocarcinoma is a rare and fatal malignancy. Abdomino-perineal resection combined with postoperative radiochemotherapy is the principal treatment.</p>

Long- term results after radical resection in patients with rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the long- term results of radical resection for rectal cancer and the factors influencing the operative results.</p><p><b>METHODS</b>From January 1990 to December 1999, clinical data of 689 patients who underwent radical resection for rectal cancer were analyzed retrospectively.</p><p><b>RESULTS</b>The overall operative mortality was 0.7%, the follow- up rate was 96.7%, the median survival rate was 67.4 months. The 1-, 3-, 5- and 10-year survival rate after operation was 89.9%, 77.3%, 69.6% and 63.3% respectively. Univariate analysis showed that the survival rate was related with the first onset symptom, tumor location, infiltrated circumference of intestine, T staging, Dukes staging, histological type, extent of lymph node metastasis and operative approaches. Multivariate analysis showed that tumor location, histological type, invasive depth and Dukes staging were independent prognostic factors.</p><p><b>CONCLUSIONS</b>The long-term efficacy after radical resection for rectal cancer is correlated with tumor location, histological type, invasive depth and Dukes staging.</p>

Comparing the effect of adjuvant chemotherapy by portal vein infusion with intraluminal chemotherapy for colorectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the effect of 5-fluorouracil (5-FU) portal vein infusion (PVI) for 7 days after radical resection, with intraluminal chemotherapy during operation for eliminating liver metastasis and elevating long-term prognosis in colorectal cancer.</p><p><b>METHODS</b>162 colorectal cancer patients with radical resection were divided into portal vein chemotherapy group (group A, 82 cases) and intraluminal chemotherapy group (group B, 80 cases) randomly. In group A, 5-fluorouracil were infused with 1g per day constantly for 7 days after operation through portal vein catheters, which placed into greater omental vein and fixed on the abdominal wall. In group B, intraluminal chemotherapy was given and 5-fluorouracil 0.5 g was injected into the greater omental vein during operation.</p><p><b>RESULTS</b>The short-term complications and long-term effect in the two groups were compared by statistical software SPSS 8.0. Group A had more operative complications, and no statistical differences was found in hospital time and survival rate of the two groups. The 5-year survival rate is 76.7% (group A: 74.3%, group B: 79.2%), and the liver metastasis rate is 19.8%. There is no significant difference between the two group-survival curves. Multiple variable analysis suggested that Dukes' stage was the prognosis factor (P < 0.05).</p><p><b>CONCLUSIONS</b>The present study demonstrated that the two chemotherapy methods play an important role in preventing liver metastasis and improving the survival rate, and the intraluminal chemotherapy would be easier and simpler. The result should be further improved by using combined chemotherapy.</p>