Lynch syndrome testing of colorectal cancer patients in a high-income country with universal healthcare: a retrospective study of current practice and gaps in seven australian hospitals.

BACKGROUND: To inform effective genomic medicine strategies, it is important to examine current approaches and gaps in well-established applications. Lynch syndrome (LS) causes 3-5% of colorectal cancers (CRCs). While guidelines commonly recommend LS tumour testing of all CRC patients, implementation in health systems is known to be highly variable. To provide insights on the heterogeneity in practice and current bottlenecks in a high-income country with universal healthcare, we characterise the approaches and gaps in LS testing and referral in seven Australian hospitals across three states. METHODS: We obtained surgery, pathology, and genetics services data for 1,624 patients who underwent CRC resections from 01/01/2017 to 31/12/2018 in the included hospitals. RESULTS: Tumour testing approaches differed between hospitals, with 0-19% of patients missing mismatch repair deficiency test results (total 211/1,624 patients). Tumour tests to exclude somatic MLH1 loss were incomplete at five hospitals (42/187 patients). Of 74 patients with tumour tests completed appropriately and indicating high risk of LS, 36 (49%) were missing a record of referral to genetics services for diagnostic testing, with higher missingness for older patients (0% of patients aged ≤ 40 years, 76% of patients aged > 70 years). Of 38 patients with high-risk tumour test results and genetics services referral, diagnostic testing was carried out for 25 (89%) and identified a LS pathogenic/likely pathogenic variant for 11 patients (44% of 25; 0.7% of 1,624 patients). CONCLUSIONS: Given the LS testing and referral gaps, further work is needed to identify strategies for successful integration of LS testing into clinical care, and provide a model for hereditary cancers and broader genomic medicine. Standardised reporting may help clinicians interpret tumour test results and initiate further actions.

Ileocolonic End-to-End Anastomoses in Crohn's Disease Increase the Risk of Early Post-operative Endoscopic Recurrence in Those Undergoing an Emergency Resection.

BACKGROUND AND AIM: Several risk factors affecting post-operative recurrence in Crohn's disease patients have been studied, and of these, the role of the anastomosis remains contentious. We aimed to compare the risk of developing early post-operative endoscopic recurrence (EPER), in resections that had an end-to-end anastomosis (ETEA) to a side-to-side anastomosis (STSA). METHODS: All Crohn's disease patients that underwent an ileocolic or small bowel resection between January 2012 and June 2017 at two tertiary IBD centres were reviewed retrospectively. Included patients had a minimum of 12-month clinical follow-up and a colonoscopy within 12 months of the resection or stoma reversal. Univariate and multivariate binary logistic regression analyses determined the independent risk factors for early post-operative endoscopic recurrence, defined as a Rutgeerts score of ≥ i2b. RESULTS: Ninety-two resections associated with an ETEA or a STSA were included for analysis. The ETEA was the most common anastomosis, constructed in 55 patients (59.8%). Forty-nine operations (53.3%) resulted in a ≥ i2b recurrence at the first surveillance colonoscopy. The multivariate analysis showed that there was no difference between the ETEA and STSA in determining the odds ratio (OR) for developing EPER (OR = 2.41 (0.95-6.05), P = 0.06). In those that underwent a resection emergently however, the significant determinants of EPER were as follows: having an ETEA (OR = 38.12 (2.44-595.87), P = 0.01), failing to commence a biologic and/or an immunosuppressant early (OR = 24.21 (1.69, 347.81), P = 0.02), and active smoking (OR = 7.19 (1.12-46.21), P = 0.04). CONCLUSION: The ETEA is best avoided in those undergoing an emergency resection. The early commencement of a biologic and/or an immunosuppressant and smoking cessation is imperative this high-risk group of patients.

Emergency left colonic resections on an acute surgical unit: does subspecialization improve outcomes?

BACKGROUND: Left-sided colonic pathologies requiring emergency resection are commonly encountered on an acute surgical unit. Subspecialist colorectal (CR) management of these patients may result in decreased morbidity, mortality and stoma rates. This study is the first of its kind comparing outcomes between CR surgeons and general surgeons on an acute surgical unit. METHODS: This is a retrospective review of 196 consecutive patients who underwent emergency left colonic resection on an acute surgical unit between January 2009 and July 2014. Patients were divided into two groups dependent on whether their surgery was managed by a CR specialist or general surgeon. Primary outcome measures were 30-day mortality, rate of primary anastomosis and overall stoma rate. RESULTS: Patients in the two groups were comparable for age, sex, American Society for Anesthesiologists score as well as CR POSSUM scores. Rates of primary anastomosis were significantly higher in the CR group compared with the acute surgical unit group (85.5 versus 28.7%, P ≤ 0.001). Overall stoma rates were significantly lower in the CR group (40.4 versus 88.8%, P = 0.0001). Thirty-day mortality was similar in both groups. Other secondary markers of morbidity including length of stay, return to theatre, anastomotic leak rate, wound problems and systemic complications had no significant difference between the two groups. CONCLUSION: Subspecialist CR management of patients undergoing emergency left-sided colonic resection on an acute surgical unit is associated with a similar level of morbidity and mortality while safely achieving significantly higher rates of primary anastomosis and lower stoma rates.

First report of the stapled mesh stoma reinforcement technique in a urologic context.

Parastomal hernia is a common complication of ileal conduit formation. Mesh repair of parastomal hernia has lower rate of recurrence than nonmesh techniques but can be time-consuming to perform. The stapled mesh stoma reinforcement technique (SMART) is a novel method of rapidly constructing a reinforced stapled stoma. We report the first case utilising this technique in a urologic context. The procedure was performed on a middle-aged female with recurrent parastomal hernia of her ileal conduit. There were no perioperative complications. The resited stoma remained healthy and functioned normally. Longer term data is clearly desirable though this technique deserves consideration in the treatment of urologic parastomal hernias. This case demonstrates that SMART is an easy and convenient procedure for parastomal hernia repair.

Population-based screening for Lynch syndrome in Western Australia.

We showed earlier that routine screening for microsatellite instability (MSI) and loss of mismatch repair (MMR) protein expression in colorectal cancer (CRC) led to the identification of previously unrecognized cases of Lynch syndrome (LS). We report here the results of screening for LS in Western Australia (WA) during 1994-2012. Immunohistochemistry (IHC) for loss of MMR protein expression was performed in routine pathology laboratories, while MSI was detected in a reference molecular pathology laboratory. Information on germline mutations in MMR genes was obtained from the state's single familial cancer registry. Prior to the introduction of routine laboratory-based screening, an average of 2-3 cases of LS were diagnosed each year amongst WA CRC patients. Following the implementation of IHC and/or MSI screening for all younger (<60 years) CRC patients, this has increased to an average of 8 LS cases diagnosed annually. Based on our experience in WA, we propose three key elements for successful population-based screening of LS. First, for all younger CRC patients, reflex IHC testing should be carried out in accredited pathology services with ongoing quality control. Second, a state- or region-wide reference laboratory for MSI testing should be established to confirm abnormal or suspicious IHC test results and to exclude sporadic cases by carrying out BRAF mutation or MLH1 methylation testing. Finally, a state or regional LS coordinator is essential to ensure that all appropriate cases identified by laboratory testing are referred to and attend a Familial Cancer Clinic for follow-up and germline testing.

The acute surgical unit: improving emergency care.

BACKGROUND: Acute care surgical teams are a new concept in the provision of emergency general surgery. Juggling emergency patients around the surgeons' and staffs' elective commitments resulted in semi-emergency procedures routinely being delayed. In an era of increasing financial pressure and the recent introduction of 'safe work hours' practices, the need for a new system which optimized available resources became apparent. METHODS: At Fremantle Hospital we developed a new system in a concerted effort to minimize the waiting time for general surgical referrals in the Emergency Department, as well as to move semi-urgent operating from the afterhours to the daytime. To analyse the impact of the ASU, data were collected during February, March, and April 2009 and compared with data from the same period in 2008. RESULTS: Although most referrals were received afterhours, over 85% of operations were performed during working hours compared with 72% in the 2008 period. The time from referral to review decreased from an average of 3.2 h in 2008 to 2.1 h. The mean duration of stay in 2009 was 3 days, which was a reduction from 4.2 days in 2008. An increase in weekend discharge rates was seen after the introduction of the ASU. CONCLUSION: Despite an increased workload, more referrals were seen and more operations performed during working hours and the time from referral to review was reduced. Higher discharge rates and reduced length of stays increased the availability of beds. We have demonstrated a successful new model which continues to evolve.

Can histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival?

PURPOSE: This study set out to determine the impact of a positive circumferential resection margin (CRM) (R1-R2) and pathologic downstaging on local recurrence and survival in patients with borderline resectable or unresectable rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 150 patients with locally advanced rectal cancer were treated with long-course neoadjuvant CRT using low-dose folinic acid and 5-fluorouracil. CRT was followed 6-12 weeks later by surgical excision. The CRM rate and incidence, site, and pattern of local and systemic recurrences were recorded. The median follow-up was 25 months. RESULTS: The overall median survival was 37 months, with a 5-year overall survival rate of 34%. Of the 150 patients, 122 underwent curative resection; 12% had a complete pathologic response, and downstaging to pT1-T2 occurred in an additional 16%. A negative CRM (R0) was achieved in 65% overall (98 of 150). Local recurrence occurred in 10% of those with R0 resection and 62% of those with R1-R2 resections. Distant metastases occurred in 29% of those with R0 resections and 75% of those with R1-R2 resections. The 3-year disease-free and 3-year overall survival rate was 9% and 25% and 52% and 64%, respectively, for patients with and without a histologically positive CRM. CONCLUSION: After 5-fluorouracil-based CRT, a positive CRM predicted for a high risk of subsequent local recurrence and a 3-year disease-free survival rate of only 9%. For this reason, the CRM should be considered a major prognostic factor and should be validated in future trials as an early alternative clinical endpoint.