The effect of anti-spasmodic administration on the accuracy of magnetic resonance imaging staging of rectal cancer.

BACKGROUNDS: Magnetic resonance imaging is the primary method for local staging in rectal cancer patients. Administration of intravenous (IV) hyoscine butylbromide is thought to improve accuracy, but there are contraindications and potential adverse effects. The aim was to assess the efficacy of IV hyoscine butylbromide on the accuracy of MRI rectal cancer staging of T2 and T3 rectal cancers. METHODS: A retrospective cohort study was carried out on patients prospectively recorded on the Cabrini Monash colorectal neoplasia database. A total of 74 patients (53 males, 21 females) MRI pelvis and rectums with antispasmodics were performed at multiple centres in the pre-operative setting between 2010 and 2016. Each patient underwent total mesorectal excision of rectal cancer. The excision specimens were assessed and given a pathological TNM stage, which was considered the reference standard. RESULTS: There was no statistically significant impact on the overall accuracy of MRI rectal cancer staging between patient groups who received IV hyoscine butylbromide and groups who did not receive IV hyoscine butylbromide. The accuracy of T2 and T3 staged rectal cancers was more likely to be correct (compared with T1 cancers) with the administration of IV hyoscine butylbromide. Still, there was no improvement in the accuracy of N-staging. CONCLUSION: Given the potential side effects and adverse outcomes of IV anti-spasmodic agents, department protocols may need to be re-assessed regarding the prescription of these medications for MRI rectal cancer staging.

Modeling colorectal cancer: A bio-resource of 50 patient-derived organoid lines.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. To improve outcomes for these patients, we need to develop new treatment strategies. Personalized cancer medicine, where patients are treated based on the characteristics of their own tumor, has gained significant interest for its promise to improve outcomes and reduce unnecessary side effects. The purpose of this study was to examine the potential utility of patient-derived colorectal cancer organoids (PDCOs) in a personalized cancer medicine setting. METHODS: Patient-derived colorectal cancer organoids were derived from tissue obtained from treatment-naïve patients undergoing surgical resection for the treatment of CRC. We examined the recapitulation of key histopathological, molecular, and phenotypic characteristics of the primary tumor. RESULTS: We created a bio-resource of PDCOs from primary and metastatic CRCs. Key histopathological features were retained in PDCOs when compared with the primary tumor. Additionally, a cohort of 12 PDCOs, and their corresponding primary tumors and normal sample, were characterized through whole exome sequencing and somatic variant calling. These PDCOs exhibited a high level of concordance in key driver mutations when compared with the primary tumor. CONCLUSIONS: Patient-derived colorectal cancer organoids recapitulate characteristics of the tissue from which they are derived and are a powerful tool for cancer research. Further research will determine their utility for predicting patient outcomes in a personalized cancer medicine setting.

Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon cancer: A cohort study of two cancer centres.

BACKGROUND/OBJECTIVES: Adjuvant chemotherapy for Stage II colon cancer offers a small (2-3%) overall survival benefit and is not universally recommended. Mismatch repair deficiency (dMMR) confers an improved prognosis identifying patients unlikely to benefit from adjuvant chemotherapy. The aim of this study was to investigate the use of dMMR immunohistochemistry in two major cancer treatment centres. METHODS: Prospective data were collected on all patients with resected Stage II colon cancer between 2010 and 2015 across two large Australian hospitals. Data collected included patient demographics, tumour histology, dMMR immunohistochemistry, chemotherapy use, and outcomes. RESULTS: All 355 patients (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to the surgical database were included in this analysis. MMR testing was performed on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients). dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient >80 years receiving treatment. Presence of ≥2 high-risk feature increased the likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients (with follow up) relapsed, with 7 disease-free post-resection of metastatic disease, 9 are alive with metastatic disease, and 11 deceased. CONCLUSIONS: Unlike clinical trial populations, Stage 2 colon cancer patients are often elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet still have excellent outcomes. dMMR immunohistochemistry is being increasingly used to identify Stage 2 patients who do not require chemotherapy.

Familial adenomatous polyposis-related desmoids presenting with air-fluid level: a clinical review and management algorithm.

BACKGROUND: Familial adenomatous polyposis-related desmoid tumors can present with a liquefied center containing gas, accompanied by abdominal pain and sepsis. To date the optimal management of such patients has not been documented. OBJECTIVE: The aim of this study was to review our experience of managing these desmoids grouped together as "intra-abdominal desmoids with air-fluid level" and present a management algorithm. DESIGN: This is a retrospective study of prospectively maintained polyposis registry database. SETTING: This study was conducted at a tertiary referral center specializing in familial adenomatous polyposis and desmoid disease. PATIENTS: Nine patients with intra-abdominal desmoid and air-fluid level were analyzed for the purpose of this study. RESULTS: Two hundred and forty-six patients were identified with desmoid tumor. Of these, a total of 9 patients had an intra-abdominal desmoid with air-fluid level; 7 were women. Age range at diagnosis was 20 to 41 years. The median time from primary surgery to desmoid tumor development was 24 months (range, 0-48 months), and the median time for further progression to air-fluid level was 24 months (range, 0-226 months). Desmoid tumor size ranged from 10 cm to greater than 20 cm in diameter. Two patients were successfully managed with antibiotics alone, and 2 patients were managed with percutaneous drainage and antibiotics. The other 5 patients required surgical intervention involving either excision or drainage with or without proximal defunctioning/exclusion. There was a single 30-day mortality. LIMITATION: This study was limited by the small number of patients. CONCLUSIONS: The majority of intra-abdominal desmoids with an air-fluid level require surgical intervention. Antibiotics and percutaneous drainage are only successful in a limited number of patients. We present our current treatment algorithm based on this experience.