Raymond Y. C. Yiu

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.

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.

Mechanisms of Microsatellite Instability in Colorectal Cancer Patients in Different Age Groups

PURPOSEThe proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers.METHODSA representative sample of 230 colorectal cancers from three age groups (<45 years, 60–70 years, >87 years) was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay.RESULTSThe proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent).CONCLUSIONThe age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.

Pelvic wall involvement denotes a poor prognosis in T4 rectal cancer

PURPOSE: An aggressive surgical approach with en bloc resection of involved structures is often possible with anterior rectal cancers that invade adjacent visceral organs, but is rarely possible in tumors that invade the pelvic wall. However, most staging systems include both situations in the same group of T4 rectal cancers. We performed a retrospective study of patients with stage T4 rectal cancer undergoing surgery to assess the influence of different organ involvement on resectability and survival. METHODS: A retrospective review was conducted of 84 patients with T4 rectal cancer treated at the University of Minnesota and affiliated hospitals over a ten-year period. Forty-seven patients (56 percent) were staged for local invasion on the basis of final pathology, 19 (23 percent) on the basis of operative findings, and 18 (21 percent) on the basis of ultrasound images. Patients were divided into two groups, those with or without pelvic wall involvement. Resectability, local control, and overall survival were compared between groups. Survival curves were estimated by the Kaplan-Meier method and compared by log-rank test. Multivariate analysis was performed with Cox proportional and logistic regression. RESULTS: Thirty-one patients (37 percent) had involvement of the pelvic wall, whereas 53 patients (63 percent) had visceral involvement only. All 29 patients with distant metastasis died of their disease. Forty-seven of the 55 patients without distant metastasis underwent tumor resection. Age and pelvic wall involvement were the only two factors independently associated with the probability of resection in logistic regression analysis (P=0.0067 andP=0.037, respectively). The only factor that affected median survival in patients without distant metastasis was tumor resection (49.1 months for resectionvs. 6.1 months for no resection,P=0.017). Patients with visceral involvement had a longer median survival (49.2 months) than those with pelvic wall involvement (13.2 months), but the difference did not reach statistical significance (P=0.058). CONCLUSION: Rectal cancers with pelvic and visceral involvement have different rates of resectability and median survival. These differences should be reflected in the TNM classification system.

The mechanism of microsatellite instability is different in synchronous and metachronous colorectal cancer.

MLH1 promoter hypermethylation has been described as the primary mechanism for high-frequency microsatellite instability (MSI-H) in sporadic colorectal cancers (CRCs). The underlying molecular mechanism for microsatellite instability (MSI) in synchronous and metachronous CRCs is not well described. A total of 33 metachronous CRC patients and 77 synchronous CRC patients were identified from 2884 consecutive patients undergoing cancer surgery in an academic center. Evaluable tumors were tested for MSI, immunohistochemistry for MLH1 and MSH2 protein expression, and hypermethylation of the MLH1 promoter. MSI-H tumors were found in 12 (36%) metachronous CRC patients and 29 (38%) synchronous CRC patients. MSI-H metachronous CRC patients were younger at index cancer diagnosis (64 vs. 76 years, P = 0.01) and more often were diagnosed before 50 years of age (4 of 12 vs. 0 of 29, P = 0.005). Loss of MLH1 expression associated with promoter hypermethylation was common in all patients, although more common in MSI-H synchronous patients (50% metachronous vs. 83% synchronous, P = 0.03). Overall, MLH1 promoter hypermethylation was seen in 7 of 17 (41%) metachronous and 44 of 54 (81%) synchronous MSI-H CRCs tested (P = 0.004). Although MSI occurred with equal frequency among patients with synchronous and metachronous CRCs, the underlying mechanism for MSI was different. Observed differences in MLH1 promoter hypermethylation and patient characteristics suggest most MSI-H synchronous CRCs in our population were sporadic in origin. In contrast, more MSI-H metachronous CRCs were associated with patient and tumor characteristics suggestive of underlying hereditary nonpolyposis CRC.

Emergency Laparoscopic-Assisted Versus Open Right Hemicolectomy for Complicated Cecal Diverticulitis: A Comparative Study

BACKGROUND Emergency open colectomy is generally agreed, by most surgeons, to be the treatment of choice for complicated cecal diverticulitis. However, the literature on the use of laparoscopy in treating this surgical emergency is scanty. This study aimed to evaluate the feasibility and safety of emergency laparoscopic-assisted right hemicolectomy for complicated cecal diverticulitis and to compare its operative and short-term clinical outcomes with the open approach. PATIENTS AND METHODS Between September 2001 and June 2006, 18 consecutive patients with an intraoperative diagnosis of complicated cecal diverticulitis underwent emergency right hemicolectomy at our institution, 6 with the laparoscopic-assisted approach and 12 with the open approach. Clinical data were retrospectively collected and compared between the two groups. RESULTS The demographic data of the two groups were comparable. The operative time was similar between the two groups, but the laparoscopic-assisted group had significantly less blood loss (35 vs. 100 mL; P = 0.041). Although the time to first bowel motion was significantly shorter in the laparoscopic-assisted group (3.5 vs. 5 days; P = 0.041), the time to full ambulation and the duration of hospital stay were not different between the two groups. More patients in the open group developed postoperative complications (50 vs. 33.3%), but the difference was not statistically significant. CONCLUSIONS With the availability of experienced laparoscopic surgeons, emergency laparoscopic-assisted right hemicolectomy can be safely performed in patients with complicated cecal diverticulitis. Compared with the open approach, the laparoscopic-assisted approach is associated with less blood loss and earlier return of bowel function.

Synchronous laparoscopic resection of colorectal and renal/adrenal neoplasms.

Synchronous laparoscopic resections of coexisting abdominal diseases are shown to be feasible without additional postoperative morbidity. We report our experience with synchronous laparoscopic resection of colorectal carcinoma and renal/adrenal neoplasms with an emphasis on surgical and oncologic outcomes. Five patients diagnosed to have synchronous colorectal carcinoma and renal/adrenal neoplasms (renal cell carcinoma in 2 patients, adrenal cortical adenoma in 2 patients, and adrenal metastasis in 1 patient) underwent synchronous laparoscopic resection. The median operative time was 420 minutes and the median operative blood loss was 1000 mL. Three patients developed minor complications, including wound infection in 2 patients and retention of urine in 1 patient. There was no operative mortality. The median duration of hospital stay was 11 days. At a median follow-up of 17.6 months, no patient developed recurrence of disease. Synchronous laparoscopic resection of colorectal and renal/adrenal neoplasms is technically feasible and safe.