Janet F. Y. Lee

Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial

BACKGROUND Although laparoscopic resection of colorectal carcinoma improves post-operative recovery, long-term survival and disease control are the determining factors for its application. We aimed to test the null hypothesis that there was no difference in survival after laparoscopic and open resection for rectosigmoid cancer. METHODS From Sept 21, 1993, to Oct 21, 2002, 403 patients with rectosigmoid carcinoma were randomised to receive either laparoscopic assisted (n=203) or conventional open (n=200) resection of the tumour. Survival and disease-free interval were the main endpoints. Patients were last followed-up in March, 2003. Perioperative data were recorded and direct cost of operation estimated. Data were analysed by intention to treat. FINDINGS The demographic data of the two groups were similar. After curative resection, the probabilities of survival at 5 years of the laparoscopic and open resection groups were 76.1% (SE 3.7%) and 72.9% (4.0%) respectively. The probabilities of being disease free at 5 years were 75.3% (3.7%) and 78.3% (3.7%), respectively. The operative time of the laparoscopic group was significantly longer, whereas postoperative recovery was significantly better than for the open resection group, but these benefits were at the expense of higher direct cost. The distal margin, the number of lymph nodes found in the resected specimen, overall morbidity and operative mortality did not differ between groups. INTERPRETATION Laparoscopic resection of rectosigmoid carcinoma does not jeopardise survival and disease control of patients. The justification for adoption of laparoscopic technique would depend on the perceived value of its effectiveness in improving short-term post-operative outcomes.

Systemic Cytokine Response After Laparoscopic-Assisted Resection of Rectosigmoid Carcinoma: A Prospective Randomized Trial

OBJECTIVE To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma. SUMMARY BACKGROUND DATA Laparoscopic resection of colorectal carcinoma is technically feasible, but objective evidence of its benefit is scarce. Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response. METHODS Thirty-four patients with rectosigmoid carcinoma, without evidence of metastatic disease and suitable for laparoscopic resection, were randomized to undergo either laparoscopic (n = 17) or conventional open (n = 17) resection of the tumor. Clinical parameters were recorded. Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein. The primary end points were the cytokine and C-reactive protein levels. Data were analyzed by intention to treat. RESULTS The demographic data of the two groups were comparable. The clinical outcome of both groups was satisfactory, with no surgical deaths and a reasonable complication rate. Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery, with the responses in the laparoscopic group significantly less than those in the open group. C-reactive protein levels peaked at 48 hours, and the difference was also statistically significant. Levels of tumor necrosis factor-alpha were not elevated after surgery, and there was no difference between the groups. CONCLUSIONS Tissue trauma, as reflected by systemic cytokine response, was less after laparoscopic resection than after open resection of rectosigmoid carcinoma. The difference in the systemic cytokine response may have implications on the long-term survival.

Long-term morbidity and oncologic outcomes of laparoscopic-assisted anterior resection for upper rectal cancer: ten-year results of a prospective, randomized trial.

PURPOSE: We have previously reported the five-year results of a randomized trial comparing laparoscopic and open resection for cancer of the upper rectum and rectosigmoid junction. The aim of this follow-up study is to report on the long-term morbidity and ten-year oncologic outcomes among the subgroup of patients with upper rectal cancer. METHODS: From September 1993 to October 2002, 153 patients with upper rectal cancer were randomly assigned to receive either laparoscopic-assisted (n = 76) or open (n = 77) anterior resection. Patients were last followed up in December 2007. Long-term morbidity, survival, and disease-free interval were prospectively recorded. Data were analyzed by intention-to-treat principle. RESULTS: The demographic data of the two groups were comparable. More patients in the open group developed adhesion-related bowel obstruction requiring hospitalization (P = 0.001) and intervention. The overall long-term morbidity rate was also significantly higher in the open group (P = 0.012). After curative resection, the probabilities of cancer-specific survival at ten years of the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent, respectively (P = 0.595), and their probabilities of being disease-free at ten years were 82.9 percent and 80.4 percent, respectively (P = 0.698). CONCLUSION: Laparoscopic-assisted anterior resection for upper rectal cancer is associated with fewer long-term complications and similar ten-year oncologic outcomes when compared with open surgery.

Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and Nf-kB in human colon cancer

Peroxisome-proliferator activated receptor-gamma (PPARgamma) has been demonstrated to exert an inhibitory effect on cell growth in most cell types studied, but its role in colon cancer is still uncertain. The molecular mechanism between the activation of PPARgamma and its consequence is unknown. In the present report, we show that the expression of PPARgamma was significantly increased in tumor tissues from human colon cancer compared with non-tumor tissues and that PPARgamma ligands, 15-Deoxy-delta(12,14)prostaglandin J2 or ciglitizone, induced apoptosis in HT-29 cells, a human colon cancer cell line. The occurrence of apoptosis induced by PPARgamma ligands was sequentially accompanied by reduced levels of NF-kappaB and Bcl-2. Over-expression of Bcl-2 significantly protected the cells from apoptosis. This study suggested that a PPARgamma-Bcl-2 feedback loop may function to control the life-death continuum in colonic cells and that a deficiency in generation of PPARgamma ligands may precede the development of human colon cancer.

Promoter hypermethylation of tumor‐related genes in the progression of colorectal neoplasia

Gene promoter hypermethylation is increasingly recognized to play an important role in cancer development through silencing of gene transcription. This study determined the methylation profiles of primary colorectal cancers and adenomas to elucidate the role of epigenetic changes in different stages of colorectal carcinogenesis. We examined the methylation profiles of 47 sporadic colorectal cancers, 36 colonic adenomas from patients without cancer and 34 colonic biopsies from patients without colonic lesions. Paired adjacent dysplasia tissues obtained from 17 cancer patients were also examined. Promoter hypermethylation in 10 tumor‐related genes (APC, ATM, GSTP1, HLTF, MGMT, hMLH1, p14, p15, SOCS‐1 and TIMP‐3) were studied by methylation‐specific PCR. Promoter hypermethylation was frequently detected in more than 40% of colonic cancers and adenomas in APC, ATM, HLTF, MGMT and hMLH1 genes (p < 0.0001 vs. normal). While low level of methylation was detected in p14, p15 and TIMP‐3, there was no methylation detected in GSTP1 and SOCS‐1. The frequencies of methylation were comparable between tumors and adenomas, and advanced and nonadvanced adenoma. In contrast, K‐ras mutation was only detected in advanced adenomas and cancers. Concurrent methylation in ≥ 3 genes was found in 66.7% adenomas and 68.1% cancers but not in normal colonic tissues. Methylation was associated with reduced protein expressions in colorectal adenomas and cancers. Moreover, methylation in ATM was more common in older cancer patients (p = 0.002), but there was no significant association between promoter hypermethylation and other clinicopathologic characteristics of cancer. Our study demonstrated the early and specific involvement of promoter hypermethylation in the colorectal adenoma‐carcinoma sequence.

Laparoscopic-assisted resection of right-sided colonic carcinoma: a case-control study.

Laparoscopic‐assisted resection of colorectal carcinoma is technically feasible. Whether it is beneficial to patients is uncertain. This study reviewed the results of laparoscopic‐assisted resection in patients with right‐sided colonic adenocarcinoma.

15-hydroxy-eicosatetraenoic acid arrests growth of colorectal cancer cells via a peroxisome proliferator-activated receptor gamma-dependent pathway.

Peroxisome proliferator‐activated receptor gamma (PPARγ) inhibits cell growth via promoting apoptosis. Human colorectal cancer tissues had abundant PPARγ but the incidence of apoptosis was very low, suggesting a defect in the PPARγ pathway. Here, we found that 15‐hydroxy‐eicosatetraenoic acid (15S‐HETE), an endogenous ligand for PPARγ, was significantly decreased in the serum of patients with colorectal cancer. Treatment of colon cancer cells with 15S‐HETE inhibited cell proliferation and induced apoptosis, which was preceded by an increase in TGF‐β‐inducible early gene (TIEG) and a decrease in Bcl‐2. The action of 15S‐HETE could be blocked when PPARγ was suppressed. Overexpression of Bcl‐2 prevented the apoptosis. The levels of TIEG and 15‐lipoxygenase (15‐LOX), the enzyme responsible for 15S‐HETE production, was decreased in colorectal cancer. Therefore, colorectal cancer is associated with decreased 15S‐HETE. Treatment of colon cancer cells with 15S‐HETE inhibits cell proliferation and induces apoptosis in a PPARγ‐dependent pathway involving augmentation of TIEG and reduction of Bcl‐2 expression.

Electroacupuncture Reduces Duration of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer

BACKGROUND & AIMS We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. METHODS We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. RESULTS Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P < .001) and length of hospital stay (6.5 ± 2.2 vs 8.5 ± 4.8 days; P = .007). Patients who received electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. CONCLUSIONS In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425.

Long-term oncologic outcomes of laparoscopic versus open surgery for rectal cancer: a pooled analysis of 3 randomized controlled trials.

Objective:To compare long-term oncologic outcomes between laparoscopic and open surgery for rectal cancer and to identify independent predictors of survival. Background:Few randomized trials comparing laparoscopic and open surgery for rectal cancer have reported long-term survival data. Methods:Data from the 3 randomized controlled trials comparing curative laparoscopic (n = 136) and open surgery (n = 142) for upper, mid, and low rectal cancer conducted at the Prince of Wales Hospital, Hong Kong, between September 1993 and August 2007 were pooled together for this analysis. Survival and disease status were updated to February 2012. Survival was calculated using the Kaplan-Meier method, and independent predictors of survival were determined using the Cox regression analysis. Results:The demographic data of the 2 groups were comparable. The median follow-up time of living patients was 124.5 months in the laparoscopic group and 136.6 months in the open group. At 10 years, there were no significant differences in locoregional recurrence (5.5% vs. 9.3%; P = 0.296), cancer-specific survival (82.5% vs. 77.6%; P = 0.443), and overall survival (63.0% vs. 61.1%; P = 0.505) between the laparoscopic and open groups. There was a trend toward lower recurrence rate at 10 years in the laparoscopic group than in the open group among patients with stage III cancer (P = 0.078). The Cox regression analysis showed that stage III cancer, lymphovascular permeation, and blood transfusion, but not the operative approach, were independent predictors of poorer cancer-specific survival. Conclusions:This pooled analysis with a follow-up of more than 10 years confirms the long-term oncologic safety of laparoscopic surgery for rectal cancer.

Increased Risk of Advanced Neoplasms Among Asymptomatic Siblings of Patients With Colorectal Cancer

BACKGROUND & AIMS Colorectal cancer (CRC) is the second-most common cancer in Hong Kong. Relatives of patients with CRC have an increased risk of colorectal neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC. METHODS Patients with CRC were identified from the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011. Colonoscopies were performed for 374 siblings of patients (age, 52.6 ± 7.4 y) and 374 age- and sex-matched siblings of healthy subjects who had normal colonoscopies and did not have a family history of CRC (controls, 52.7 ± 7.4 y). We identified individuals with advanced neoplasms (defined as cancers or adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or tubulovillous characteristics). RESULTS The prevalence of advanced neoplasms was 7.5% among siblings of patients and 2.9% among controls (matched odds ratio [mOR], 3.07; 95% confidence interval [CI], 1.5-6.3; P = .002). The prevalence of adenomas larger than 10 mm was higher among siblings of patients than in controls (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45-7.66; P = .004), as was the presence of colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52-3.17; P < .001). Six cancers were detected among siblings of patients; no cancers were detected in controls. The prevalence of advanced neoplasms among siblings of patients was higher when their index case was female (mOR, 4.95; 95% CI, 1.81-13.55) and had distally located CRC (mOR, 3.10; 95% CI, 1.34-7.14). CONCLUSIONS In Hong Kong, siblings of patients with CRC have a higher prevalence of advanced neoplasms, including CRC, than siblings of healthy individuals. Screening is indicated in this high-risk population. ClinicalTrials.gov number: NCT00164944.