Long-term outcomes of the australasian randomized clinical trial comparing laparoscopic and conventional open surgical treatments for colon cancer: the Australasian Laparoscopic Colon Cancer Study trial.

OBJECTIVE: : We report a multicentered randomized controlled trial across Australia and New Zealand comparing laparoscopic-assisted colon resection (LCR) with open colon resection (OCR) for colon cancer. BACKGROUND: : Colon cancer is a significant worldwide health issue. This trial investigated whether the short-term benefits associated with LCR for colon cancer could be achieved safely, without survival disadvantages, in our region. METHODS: : A total of 601 patients with potentially curable colon cancer were randomized to receive LCR or OCR. Primary endpoints were 5-year overall survival, recurrence-free survival, and freedom from recurrence rates, compared using an intention-to-treat analysis. RESULTS: : On April 5, 2010, 587 eligible patients were followed for a median of 5.2 years (range, 1 week-11.4 years) with 5-year confirmed follow-up data for survival and recurrence on 567 (96.6%). Significant differences between the 2 trial groups were as follows: LCR patients were older at randomization, and their pathology specimens showed smaller distal resection margins; OCR patients had some worse pathology parameters, but there were no differences in disease stages. There were no significant differences between the LCR and OCR groups in 5-year follow-up of overall survival (77.7% vs 76.0%, P = 0.64), recurrence-free survival (72.7% vs 71.2%, P = 0.70), or freedom from recurrence (86.2% vs 85.6%, P = 0.85). CONCLUSIONS: : In spite of some differences in short-term surrogate oncological markers, LCR was not inferior to OCR in direct measures of survival and disease recurrence. These findings emphasize the importance of long-term data in formulating evidence-based practice guidelines.

Ethical issues with the disclosure of surgical trial short-term data.

BACKGROUND: This paper describes the distinctions between major surgical and pharmaceutical trials and questions the application of a common ethical paradigm to guide their conduct and reporting. METHODS: Surgical trials differ from other trials in cumulative therapeutic effects, operator dependence, the clinical setting, interdependence of short- and long-term outcomes, and equipoise. A principal tenant of randomized controlled trial management is the maintenance of interim data confidentiality. Its application to complete surgical short-term data is examined across a variety of common clinical trial circumstances that influence data integrity and the reliability of conclusions regarding the benefit-to-risk profile of experimental interventions. RESULTS: Complete perioperative results describe important treatment ends that cannot influence primary outcomes. These short-term results may inform patient consent, teaching and provide valuable procedural insights to surgeons outside trial precincts. CONCLUSION: Structured experimentation standards are necessary. But, the common paradigm applied across all clinical trials and the prohibition on short term data reporting may not serve the achievement of safe and effective advancements in surgery.

Factors influencing medical oncology referral in Dukes' C colonic cancer.

AIM: Colorectal cancer (CRC) is one of the most common malignancies worldwide and adjuvant chemotherapy is proven to improve survival in patients with Dukes' C CRC. The purpose of this study was to analyze factors influencing referral to medical oncology in patients with Dukes' C colonic cancer in our institutions. METHODS: Patients who underwent resection for Dukes' C colonic cancer were assessed for factors that influence the pattern of postoperative referral to the medical oncology department, including demographic and perioperative data. RESULTS: Overall, 466 patients were identified to have Dukes' C colonic cancer, with 53.9% of these being female. Referral to medical oncology occurred for 58.4% patients. Multivariable logistic regression modeling identified age, elective admission and resection in private hospitals as factors. The likelihood of medical oncology referral in patients who had elective resection was 63% versus 41% in those who had emergency resection and resection in private hospitals was 69% versus 50% in public hospitals. CONCLUSION: Referral to a postoperative medical oncology clinic for adjuvant chemotherapy in Dukes' C colonic cancer was more likely in younger patients, those who underwent elective resection and those treated in private hospitals.

Implantation of ethylene vinyl alcohol copolymer for faecal incontinence management.

PURPOSE: The primary objectives of this trial were to evaluate the safety and feasibility of treatment and to gain a preliminary indication of the effectiveness of ethylene vinyl alcohol injections into the anal sphincters of faecally incontinent patients. METHODS: Between April 2004 and February 2006, we conducted a prospective, single-arm, procedure optimization study of ethylene vinyl alcohol injections in 21 subjects with well-characterized faecal incontinence and an intact external anal sphincter at two Australian hospitals. RESULTS: There was a significant decrease in the Cleveland Clinic Florida Faecal Incontinence Score (CCFFIS) (P= 0.0005) and the Faecal Incontinence Severity Index score (P= 0.005) after treatment. At 12 months post-treatment, the mean CCFFIS had decreased by 37% (P= 0.0021), and 47% of subjects had a > or =50% improvement in CCFFIS. There were significant improvements in embarrassment (P= 0.0455) and coping/behaviour (P= 0.0056) domains of the Faecal Incontinence Quality of Life. At 12 months, the mean anal canal length had increased by 29% (P= 0.066), with 40% of patients demonstrating increases of 50% or more. There were no further improvements following retreatment. CONCLUSIONS: Ethylene vinyl alcohol injection into the anal intersphincteric plane is feasible and well tolerated. Improvement in faecal incontinence compared with baseline was seen. Retreating initial non-responders was not successful.

Single-incision laparoscopically assisted colectomy using standard laparoscopic instrumentation.

BACKGROUND: A prospective case series of transumbilical single-incision laparoscopic colectomies using conventional laparoscopic trocars and instruments is described. METHODS: Seven selected patients with colonic neoplasm underwent transumbilical SIL colectomy between November 2008 and March 2009. Three trocars via a single small umbilical incision were used. The bowel was mobilized and the vessels ligated intracorporeally with an extracorporeal anastomosis. RESULTS: This series of seven patients (6 men and 1 woman) had no conversion to standard multiport laparoscopy or open surgery. Six of the patients had pathology in the right colon, and one had a carcinoma at the splenic flexure. The patients had an average age of 71 years (range, 63-83 years) and an average body mass index (BMI) of 24.3 kg/m(2) (range, 21-28 kg/m(2)). The average operating time was 89 min (range, 75-115 min). No significant blood loss or complications occurred. The average length of hospital stay was 5.4 days (range, 4-11 days). The average incision length was 3.1 cm (range, 2.5-4.5 cm). Histopathology showed adequate tumor excision margins and an average lymph node yield of 15 nodes (range, 7-26 nodes). CONCLUSIONS: Single-incision laparoscopic surgery for colectomy is feasible. It can be performed without specialized instrumentation and at no extra cost. Further evaluation is required.

Initial impact of Australia's National Bowel Cancer Screening Program.

OBJECTIVE: To examine the initial impact of the National Bowel Cancer Screening Program (NBCSP), which was launched in May 2006 and offers faecal occult blood testing to Australians aged 55 or 65 years. DESIGN AND SETTING: Review of data on colorectal cancer (CRC) cases diagnosed between May 2006 and June 2008 from a prospective database used at 19 Australian hospitals, linked and analysed by BioGrid Australia. MAIN OUTCOME MEASURES: Number of CRC cases detected through the NBCSP or symptomatic presentation, and differences by sex, stage at diagnosis, tumour location and level of socioeconomic disadvantage. RESULTS: 1628 cases of CRC were identified; 1268 had information on the patients' test status as part of the NBCSP, and 40 of these (3.2%) were recorded as being detected by the NBCSP. Of 75 CRC cases in patients aged 55 or 65 at diagnosis, 22 were NBCSP-detected. Overall, there was no difference in NBCSP-detected cases by sex. The distribution of tumour locations was similar between NBCSP-detected cases and symptomatic cases, but NBCSP-detected cancers were diagnosed at an earlier stage than symptomatic cancers (stage I, 40% v 14%; stage IV, 3% v 15%, respectively). Of patients diagnosed through the NBCSP, 63% were from areas of least socioeconomic disadvantage (deciles 8-10) and 18% were from the most disadvantaged areas (deciles 1-4) (P=0.0375). CONCLUSION: Initiation of the Australian NBCSP has had a measurable impact on CRC stage at diagnosis, and an improvement in survival would be anticipated. The lower uptake among people from disadvantaged areas is of concern.

Complete pathologic response after preoperative rectal cancer chemoradiotherapy.

BACKGROUND: Following preoperative treatment of rectal cancer with chemoradiotherapy (CRT), a complete pathological response (CPR) can be seen in the surgical specimen. The aim of this study was to assess the outcome of these patients as compared with those who did not have a complete response. METHODS: A retrospective study of the outcome of patients managed with preoperative CRT for their rectal cancer was conducted. RESULTS: Between November 1998 and July 2004, there were 530 new presentations of rectal cancer at The Queen Elizabeth and Royal Adelaide hospitals. Forty of these patients (7.5%) were treated with long-course preoperative CRT. After resection, a CPR was seen in seven patients (17.5%). These patients were all disease free at January 2006 after a median follow-up of 6.0 years (range 1.42-7.02 years). One patient had died from non-tumour-/surgery-related causes. Tumour recurrence, but not mortality, in this group was superior to the comparison group of patients without a CPR. CONCLUSIONS: None of our patients who had a CPR after preoperative CRT have recurred or died from their disease.

Australian and New Zealand study comparing laparoscopic and open surgeries for colon cancer in adults: organization and conduct.

This article describes the initiation and implementation of the multicentre Australia and New Zealand prospective randomized controlled clinical study comparing laparoscopic and conventional open surgical treatments of right-sided and left-sided potentially curable colon cancer (Australasian Laparoscopic Colon Cancer Study). Six hundred and one adult patients were admitted with a clinical diagnosis of a single adenocarcinoma based on a physical examination and colonoscopy, barium enema or computed tomography scan and randomly allocated to either laparoscopic or open surgery. The primary aim of the study is to compare 5-year mortality and tumour recurrence rates between the two groups. Secondary aims include comparisons of safety (intraoperative and early postoperative complications, wound site recurrence, postoperative recovery and 30-day mortality), quality of life, in-hospital costs and short-term mortality and tumour recurrence. The data for 592 patients have been collected. There are currently 3141 person years of follow up. In all 370 patients have been assessed at 5 years. This study shows that large cooperative Australia-New Zealand surgical trials can and should be carried out to address significant clinical issues. When possible, coherence with similar, concurrent international trial protocols ensures broader analyses and applicability of results. It is important to recognize that special attention to sustained funding, surgeon credentialing, clinical protocol standardization, data management, publication policy and the protection of study credibility is required from the outset. The Australasian Laparoscopic Colon Cancer Study will achieve its aims with 5-year assessments of all entered patients in March 2010.

Short-term outcomes of the Australasian randomized clinical study comparing laparoscopic and conventional open surgical treatments for colon cancer: the ALCCaS trial.

BACKGROUND: Laparoscopy has revolutionized many abdominal surgical procedures. Laparoscopic colectomy has become increasingly popular. The short- and long-term benefits and satisfactory surgical oncological treatment of colorectal cancer by laparoscopic-assisted resection remain topical. The long-term outcomes of all international randomized controlled trials are still awaited, and short-term outcomes are important in the interim. METHODS: Between January 1998 and April 2005, a multicenter, prospective, randomized clinical trial in patients with colon cancer was conducted. Six hundred and one eligible patients were recruited by 33 surgeons from 31 Australian and New Zealand centers. Patients were allocated to colectomy by either laparoscopic-assisted surgery (n = 294) or open surgery (n = 298). Patient demographics and secondary end-points, such as operative and postoperative complications, length of hospital stay, and histopathological data, will be presented in this article. Analysis was by intention-to-treat. Survival will be reported only as the study matures. RESULTS: Histopathological parameters were similar between the two groups, except in regard to distal resection margins. There was no statistically significant difference found in postoperative complications, reoperation rate, or perioperative mortality. Statistically significant differences in quicker return of gastrointestinal function and shorter hospital stay were identified in favor of laparoscopic-assisted resection. A statistically significant increased rate of infective complications was seen in cases converted from laparoscopic-assisted to open procedures but with no difference in reoperation or in-hospital mortality. CONCLUSIONS: Laparoscopic-assisted colonic resection gives significant improvements in return of gastrointestinal function and length of stay, with an increased operative time and no difference in the postoperative complication rate.

Six-year prospective analysis of the rectal bleeding clinic at the Queen Elizabeth Hospital, Adelaide, South Australia.

BACKGROUND: One-stop rectal bleeding clinics (RBC) are designed to diagnose and treat colorectal diseases that present with rectal bleeding. The Queen Elizabeth Hospital RBC is an open access clinic and is unique in South Australia. It offers flexible sigmoidoscopy and facilities for treating common anorectal conditions. METHODS: Data of all patients presenting to the RBC were prospectively recorded into a database. Data were collected on the patient details, presentation, medical history, physical examination, treatment and intended follow-up. RESULTS: A total of 1539 cases was seen in the clinic between March 2000 and February 2006. Flexible sigmoidoscopy was carried out in 1145 cases (75.03%). Banding or injection of haemorrhoids was carried out in 383 cases. A total of 590 patients was referred for colonoscopy and of these, 27 were diagnosed with colorectal adenocarcinoma or squamous cell cancer of the anus. Most of these patients were more than 50 years old (26 of 27; 96.30%) and had associated symptoms, such as weight loss or altered bowel habit with their rectal bleeding (23 of 27; 85.19%). CONCLUSION: Rectal bleeding clinics can facilitate early diagnosis of colorectal malignancy and can also provide a 'one-stop shop' for treating benign anorectal conditions.

Self-expanding metallic stents for relieving malignant colorectal obstruction: a systematic review.

OBJECTIVE: To assess the safety and efficacy of self-expanding metallic stents (SEMS) placement for the relief of malignant colorectal obstruction in comparison to surgical procedures through a systematic review of the literature. SUMMARY BACKGROUND DATA: Conventional therapies for relieving colorectal obstructions caused by cancer have high rates of morbidity and mortality, particularly when performed under emergency conditions, and palliative procedures resulting in colostomy creation can be a burden for patients and caregivers. METHODS: A systematic search strategy was used to retrieve relevant studies. Inclusion of papers was established through application of a predetermined protocol, independent assessment by 2 reviewers, and a final consensus decision. Eighty-eight articles, 15 of which were comparative, formed the evidence base for this review. RESULTS: Little high-level evidence was available. However, the data suggested that SEMS placement was safe and effective in overcoming left-sided malignant colorectal obstructions, regardless of the indication for stent placement or the etiology of the obstruction. Additionally, SEMS placement had positive outcomes when compared with surgery, including overall shorter hospital stays, and a lower rate of serious adverse events. Postoperative mortality appeared comparable between the 2 interventions. Combining SEMS placement with elective surgery also appeared safer and more effective than emergency surgery, with higher rates of primary anastomosis, lower rates of colostomy, shorter hospital stays, and lower overall complication rates. CONCLUSIONS: Stenting appears to be a safe and effective addition to the armamentarium of treatment options for colorectal obstructions. However, the small sample sizes of the included studies limited the validity of the findings of this review. The results of additional comparative studies currently being undertaken will add to the certainty of the conclusions that can be drawn.

Endosonographic imaging of anal sphincter injury: does the size of the tear correlate with the degree of dysfunction?

PURPOSE: This study was designed to test the hypothesis that the extent of anal sphincter muscle injury as graded at endosonography correlates with the degree of functional impairment. METHODS: Three hundred and thirty adults presenting for evaluation of fecal incontinence were recruited. Ultrasound was performed with a 7.5-MHz radial rotating axial endoprobe in the left lateral position. Anal sphincter muscle tears were graded on the basis of the degree of circumferential involvement (< or >25 percent) and by an assessment of the superoinferior longitudinal extent of an external anal sphincter tear. Muscles that demonstrated multiple tears, poor visualization, or fragmentation were classed as fragmented. Sphincter injuries were correlated with basal and squeeze pressures at manometry, pudendal nerve terminal latencies, and the severity of symptoms using the Parks-Browning clinical score. RESULTS: Patients with an intact external anal sphincter had a higher squeeze pressure (mean, 162.6 cm H(2)O) than those with a partial- (mean, 125.7 cm H(2)O) or full-length tear (mean, 124.9 cm H(2)O; P < 0.0001). There was no significant difference in squeeze pressure between those with partial- vs. full-length external anal sphincter tears nor between circumference tears < or >25 percent. Basal pressure was significantly lower in those with a full-length external anal sphincter tear (47.8 cm H(2)O) vs. an intact external anal sphincter (65.7 cm H(2)O; P < 0.001). The basal pressure in those with an intact internal anal sphincter was not significantly different from those with clearly defined internal anal sphincter tears, and the degree of circumferential involvement was also not important in this regard. However, those with a fragmented internal anal sphincter had a significantly lower basal pressure than other subgroups of internal anal sphincter injuries (P < 0.001). There was no association between external or internal anal sphincter status and the mean pudendal nerve terminal motor latency, suggesting the patient groups were neurologically similar. There was no significant association between external or internal anal sphincter status and the severity of reported symptoms. CONCLUSION: Correlations between the presence or absence of muscle tears and reduced manometric function have been identified. Further grading of tears was of less importance. No relationship between muscle injuries and the severity of clinical symptoms could be elicited.