Philip F. Bagshaw

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.

Tumor cell distribution following laparoscopic colectomy in a porcine model.

PURPOSE: A clinically relevant, laparoscopic colectomy model has been developed to quantify surgical practices that may affect the incidence of port wound tumor implantation. METHODS: Suspended51Cr-labeled, fixed HeLa cells were injected intraperitoneally into pigs before laparoscopic colectomies were performed with or without insufflation. Tumor cell contamination of instruments, ports, stability threads, and excised port wound margins was determined by gamma counting. RESULTS: Tumor cells were distributed throughout the peritoneal cavity, and the number detected at wound sites was directly related to number injected. Ports used by the operating surgeon had more cells than those used by the camera operator or assistant surgeon. Postoperative withdrawal of contaminated ports through abdominal wound was associated with an increase in port site contamination. Although the port site distribution of tumor cells was affected, mechanical elevation of abdominal wall did not eliminate contamination at any site. CONCLUSION: These results demonstrate application of the porcine model to test current surgical practices and measures that might be used perioperatively to reduce the numbers of intraperitoneal tumor cells or their distribution to specific sites during laparoscopic or open surgery.

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.

Operative factors affecting tumor cell distribution following laparoscopic colectomy in a porcine model

BACKGROUND: An increased risk of laparoscopic port wound tumor implantation in the presence of overt or covert abdominal malignancy has been identified. PURPOSE: A porcine laparoscopic colectomy model has been used to quantify the influence surgical practices may have on tumor cell implantation. METHODS:51Cr-labeled, fixed HeLa cells were injected intraperitoneally before surgery. Tumor cell contamination of instruments, ports, security threads, and excised wound margins was assessed by gamma counting. RESULTS: Greatest contamination occurred in ports used by the operating surgeon under pneumoperitoneum (64 percent of all port wound tumor cells) and mechanical elevation (76 percent). Gasless surgery in patients in the head-down position increased the rostral accumulation of tumor cells in the abdomen and right upper quadrant port wound by 330 and 176 percent, respectively. Under pneumoperitoneum, port movement was the major contributor to port leakage and wound contamination (21 percent of total recovered wound tumor cells per port). Tumor cells were not carried in aerosol form. Instrument passage and the withdrawal of security threads through the abdominal wall increased port wound contamination 430 and 263 percent, respectively, over pneumoperitoneum control ports. Preoperative lavage reduced by 61 percent, but did not eliminate, wound contamination. CONCLUSION: This porcine model may be used to evaluate surgical factors for the impact on port wound contamination.

DIAPHRAGMATIC HERNIAS COMPLICATING PREGNANCY

Background:  Diaphragmatic hernias complicating pregnancy are not a common problem but they can have catastrophic consequences. They can present to the surgeon as a life‐threatening emergency or pose a management dilemma when detected incidentally. In this paper, recommendations for the management of non‐hiatal maternal diaphragmatic hernias are made based on our experience and the available published reports.

Dual silver staining to characterise Helicobacter spp. outer membrane components.

Helicobacter pylori is a bacterial pathogen, estimated to infect half the worlds population. The bacterium is the aetiological cause of gastritis, the common precursor for peptic ulcer disease and gastric cancer. Immunisation of at-risk individuals is the most cost-effective means of dealing with such a widespread pathogen. Potential vaccine candidates need to be identified and characterised. Conventional silver staining is commonly used for the sensitive detection of bacterial protein components separated by SDS-PAGE. Modified silver stains employing periodate oxidation have also been developed for the analysis of purified bacterial lipopolysaccharide. By using these methods in parallel, as a dual silver stain, bacterial fractions can be characterised in terms of protein and LPS content. Strain differences can also be readily identified by comparing protein and LPS profiles. When combined with differential immunoblotting, the dual silver stain is a useful analytical tool for characterising potential vaccine candidate antigens.

Protective effect of appendectomy on the development of ulcerative colitis: matched, case-control study.

PURPOSE: Appendectomy and cigarette smoking have been suggested to reduce the chance of developing ulcerative colitis. A case-control study was undertaken to determine the relative incidence of appendectomy in patients with ulcerative colitis. METHODS: This case-control study examined the incidence of appendectomy in patients with ulcerative colitis and patients attending an orthopedic outpatient clinic. RESULTS: Of 100 patients with ulcerative colitis, 75 pairs were matched for age, gender, and cigarette smoking. The ulcerative colitis group had an appendectomy rate of 8 percent (6/75), compared with 21 percent in the control group (P=0.018). The odds ratio was 3.5 (95 percent confidence interval, 1.15–10.6). CONCLUSIONS: No previous study has examined the effect of appendectomy, controlling for cigarette smoking. This study confirms that appendectomy protects against or reduces the chance of development of ulcerative colitis. A possible immunological explanation for this effect is advanced.

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.

TREATMENT OF DUODENAL ADENOMAS WITH ENDOSCOPIC ARGON PLASMA COAGULATION

Background:  Surgical resection has been the standard treatment for duodenal adenomas. It has a high associated morbidity rate and a significant recurrence rate. The aim of this study was to evaluate endoscopic treatment of these lesions with argon plasma coagulation.

THE AUSTRALASIAN LAPARAOSCOPIC COLON CANCER STUDY

The Australasian Laparoscopic Colon Cancer Study (ALCCaS) is a non-inferiority randomized controlled trial (RCT) comparing laparoscopic and open surgical treatments of right-sided and left-sided potentially curable colon cancer. It is not often that large and complex multicentre surgical trials are jointly undertaken between Australia and New Zealand and ALCCaS methodological coherence with other major international trials adds an unprecedented analytical dimension. This paper emphasizes some of the implications and issues that transcend the nuts, bolts and results of ALCCaS. Similar international studies (e.g., Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection, Conventional versus Laparoscopic-Assisted Surgery in Patients with Colorectal Cancer (CLASICC) and ALCCaS) set against different economic and cultural backgrounds achieve clinical consensus by reducing both acknowledged and unrecognized regional variables. These related studies also allow economic, social and clinical variables to be identified and their contributions to outcomes assessed. In addition, close alignment of methods and outcomes between important RCT increases the evidence base and statistical power to assess combined data that can be stratified beyond the primary and secondary clinical outcomes and quality of life assessments of any single trial. The original accrual target of 1260 patients proved unattainable within a practical time frame. An adjustment to 600, to detect a mortality difference of 11% at 5 years, was approved by the Health Research Council of New Zealand-appointed international Data Monitoring Committee (DMC) and was attained in March 2005 in the expectation of combining ALCCaS with other RCT outcome data. Patient recruitment to surgical trials is a problem that is not confined to ALCCaS. Both the COST and CLASICC trials were required to reduce their accrual targets to provide timely operative and teaching guidance.1,2 The chief factors limiting accrual were the number of surgeons enrolled and their patient recruitment to ALCCaS. This was influenced by the stringent credentialing criteria, surgeon and/or patient preference for a procedure,3 increased laparoscopic colonic resection (LCR) time and reluctance to randomize private patients. There were also delays in gaining ethics approval in individual centres that could have been improved by centralization of the process. Surgeon credentialing, as specified in the COST protocol, was based on an audited videotape of an LCR and 20 operative reports describing oncologically appropriate laparoscopic procedures. It must be said that, at the outset of the COST study (from which ALCCaS derived its protocols) the criteria on which qualified participation and learning curve prediction were based may have been arbitrary and unproved. Whatever criteria are appropriate may not be a simple matter to decide, but arguably what was done for ALCCaS seemed to work. Procedure credentialing and the achievement of short-term results similar to other important RCT raise several points. First, the willingness to undergo close peer scrutiny illustrates the integrity of surgeons and their desire to achieve excellence. Some may also think that it emphasizes the potential for the future adoption of video evidence in vocational examinations and staff appointments. Moreover, the amalgamation of coherent international RCT trial data provides not only information about new therapies, but also gives an historical perspective on well-defined, conventional therapies and outcomes for comparison by surgeons in the future. With regard for that perspective the question might be put: if all the compatible RCT show equivalence or non-inferiority for survival and recurrence and the benefits of minimally invasive surgery are modest and largely subjective, what is the ‘gold standard’? Is it LCR or open colon resection (OCR)? Are the level 1 data to be considered together or separately? In practice, future open operations might be judged against OCR results, whereas new minimally invasive techniques would be judged against LCR with two separate, but statistically equivalent, ‘gold standard’ constructs because the results of each new treatment could be expected to influence both short-term and long-term outcomes differently. The overall results attained in this RCT may prove to be better than ‘real life’ because of credentialing, patient selection, treatment standardization and possibly better care of patients included in high-quality clinical research.4 It is not possible to quantify the individual or combined effects of these factors. It is also difficult to assess the impact of changing practice. For example, the length of stay following open operations may be more influenced by experience of laparoscopic patients and fasttrack recovery technique changes than by the method of removal of the cancer.5,6 Acknowledgement, however, that a higher standard is attainable may be required for the future advancement of safe laparoscopic surgery as well as the adoption of other new procedures. Although a voluntary moratorium on LCR for malignant disease outside ALCCaS was recommended,7,8 it was not the case in practice. There was a surge in LCR before and less so since RCT short-term data papers were released. Are RCT needed to introduce new procedures? This probably depends on the type of procedure and information to be gained. Learning new techniques, operations and the use of equipment are technical objectives (e.g., harmonic scalpel) and could be taught traditionally or using a variety of virtual, remote or ‘hand-in-hand’ robotic formats. Biological outcome assessments and comparisons are different and require the full suite comprising procedure standardization, operator competence, unbiased data collection and the analysis of actual rather than surrogate end-points that are encompassed in the RCT trial model.8 The present process for clinical introduction of new operations involves an initial audit of the outcomes and issues surrounding a procedure, so that surgeons know what the questions are and whether they can be answered. Once a procedure has been developed to a point where it has reproducible outcomes, an RCT can help define the way ahead and a temporary moratorium constraining surgical practice can provide a means of mitigating surgical enthusiasm for new techniques with unexpected, undesirable outcomes.9 However, the point at which surgeons believe they have enough conclusive information from short-term or long-term outcome publications from international trials that are published asynchronously remains undetermined and unaddressed. ANZ J. Surg. 2008; 78: 832–833 doi: 10.1111/j.1445-2197.2008.04673.x