Recommendations for the Management of Incidental Pancreatic Findings in Adults by the Canadian Association of Radiologists Incidental Findings Working Group.

The Canadian Association of Radiologists Incidental Findings Working Group consists of both academic subspecialty and general radiologists and is tasked with adapting and expanding upon the American College of Radiology incidental findings white papers to more closely apply to Canadian practice patterns, particularly more comprehensively dealing with the role of ultrasound and pursuing more cost-effective approaches to the workup of incidental findings without compromising patient care. Presented here are the 2021 Canadian guidelines for the management of pancreatic incidental findings. Topics covered include anatomic variants, fatty atrophy, pancreatic calcifications, ductal ectasia, and management of incidental pancreatic cysts.

The sensitivity and specificity of guaiac and immunochemical fecal occult blood tests for the detection of advanced colonic adenomas and cancer.

PURPOSE: Fecal immunochemical tests (FITs) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests (g-FOBTs). Our aim was to compare the performance characteristics of one g-FOBT (Hemoccult II) and two FITs (the Hemoccult ICT and MagStream HemSp) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions. We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance. METHODS: We used a prospective observational cohort design in a Canadian population eligible for screening. All participants received colonoscopy after performing the occult blood tests. RESULTS: One thousand seventy-five individuals were enrolled (mean age 56.3 years, 53.8 % females). Using colonoscopy as the gold standard, the sensitivity for screen-relevant neoplasm was determined for Hemoccult II (7.2, 95 % CI: 1.1-13.4), Hemoccult ICT (23.2 %: 13.2-33.1), and MagStream HemSp using 67 µg/gram stool as the cut-off (23.2 %: 13.2-33.1). The Magstream HemSp, using a cut-off threshold of 30 µg/gram stool, had the lowest specificity at 87.6 % (85.4-89.6), while the Hemoccult II had the highest at 98.8 % (98.1-99.5). Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity. CONCLUSION: We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold standard. Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate. Single-day testing with an FIT may be an option to enhance population compliance with screening.

Practices in peptic ulcer bleeding controversies among university- versus nonuniversity-affiliated gastroenterologists.

BACKGROUND: Practices relating to acute peptic ulcer bleeding (APUB) outside of guideline recommendations are unknown. OBJECTIVE: To evaluate the practices of university-affiliated (UA) versus nonuniversity-affiliated (non-UA) gastroenterologists in controversial APUB issues. METHODS: Gastroenterologists in Canada were mailed an anonymous questionnaire (January 2008) regarding APUB management. RESULTS: Responses were received for 281 of the 530 questionnaires mailed (53%). There were no differences between the UA versus non-UA gastroenterologists regarding acid suppression medication and route of administration pre- and postendoscopy (all P>0.05). There were no differences in endoscopic practices between groups regarding large versus small volume injection, endoclip versus combination injection plus coagulation, endoclip versus endoclip plus injection, and management of adherent clots (all P>0.05). There was variability within each group regarding optimal empirical acid suppression pre- and postendoscopy, volume of injection therapy and endoclip use. The non-UA group had longer delays before restarting acetylsalicyclic acid (P=0.08) and warfarin (P=0.02) post-APUB. CONCLUSIONS: UA and non-UA gastroenterologists have similar practices in acid suppression and endoscopic therapy for controversial APUB issues; however, non-UA gastroenterologists appear more cautious in restarting acetylsalicylic acid and warfarin. Further studies are needed to address the optimal empirical acid suppression pre- and postendoscopy, injection therapy volume, endoclip use, and timing of restarting antiplatelet and anticoagulation therapy.

Synergistic activity of troxacitabine (Troxatyl) and gemcitabine in pancreatic cancer.

BACKGROUND: Gemcitabine, a deoxycytidine nucleoside analog, is the current standard chemotherapy used as first-line treatment for patients with locally advanced or metastatic cancer of the pancreas, and extends life survival by 5.7 months. Advanced pancreatic cancer thus remains a highly unmet medical need and new therapeutic agents are required for this patient population. Troxacitabine (Troxatyl) is the first unnatural L-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. Troxacitabine was recently evaluated as a first-line therapy in 54 patients with advanced adenocarcinoma of the pancreas and gave comparable overall results to those reported with gemcitabine in recently published randomized trials. METHODS: The human pancreatic adenocarcinoma cell lines, AsPC-1, Capan-2, MIA PaCa-2 and Panc-1, were exposed to troxacitabine or gemcitabine alone or in combination, for 72 h, and the effects on cell growth were determined by electronic particle counting. Synergistic efficacy was determined by the isobologram and combination-index methods of Chou and Talalay. Mechanistic studies addressed incorporation of troxacitabine into DNA and intracellular levels of troxacitabine and gemcitabine metabolites. For in vivo studies, we evaluated the effect of both drugs, alone and in combination, on the growth of established human pancreatic (AsPC-1) tumors implanted subcutaneously in nude mice. Statistical analysis was calculated by a one-way ANOVA with Dunnett as a post-test and the two-tailed unpaired t test using GraphPad prism software. RESULTS: Synergy, evaluated using the CalcuSyn Software, was observed in all four cell-lines at multiple drug concentrations resulting in combination indices under 0.7 at Fa of 0.5 (50% reduction of cell growth). The effects of drug exposures on troxacitabine and gemcitabine nucleotide pools were analyzed, and although gemcitabine reduced phosphorylation of troxacitabine when cells were exposed at equal drug concentrations, there was no effect on phosphorylated pools at drug combinations that were synergistic. The amount of troxacitabine incorporated into DNA was also not affected by the presence of gemcitabine. In vivo testing against a human pancreatic (AsPC-1) xenograft mouse tumor model indicated that both drugs were more than additive at well-tolerated doses and schedule. The biological basis for this synergy is unclear as we did not observe changes in apoptosis, DNA repair, troxacitabine incorporation into DNA or troxacitabine metabolism in the presence of gemcitabine. CONCLUSION: These data, together with phase I clinical data showing tolerability of both agents when combined, suggest combination therapy with troxacitabine and gemcitabine warrants further evaluation in advanced pancreatic cancer patients.

Increased risk of colorectal cancer in ulcerative colitis patients diagnosed after 40 years of age.

BACKGROUND: The association between ulcerative colitis (UC) and colorectal cancer (CRC) is well established. Retrospective data show a 5.4% CRC incidence rate among patients with pancolitis and suggest that cancer surveillance should be provided to patients following eight to 10 years of extensive UC. AIM: To identify premalignant risk factors for UC patients and to determine whether current recommendations for cancer surveillance need reviewing. PATIENTS AND METHODS: A retrospective audit was conducted of adult patients with UC who were diagnosed with CRC between 1991 and 2002 in five hospitals in Edmonton, Alberta. RESULTS: Thirty-one cases of CRC (68% male) were identified. In this group, the mean ages at diagnosis were 44.4 years for UC patients and 60.1 years for CRC patients. For patients in whom the initial data of diagnosis of UC could be determined (n=29), the median duration of UC at the time of CRC diagnosis was 16 years. Patients diagnosed with UC after 40 years of age (n=15, mean age 64 years) progressed more rapidly to CRC than patients diagnosed before 40 years of age (n=14, mean age 23 years). The median durations of UC before development of CRC were 22 years and 10 years, respectively, for patients with a diagnosis of UC before and after 40 years of age (OR 11.5, 95% CI 2.41 to 20.16; P=0.00029). Only four patients (13%) were enrolled in an appropriate cancer-screening program. Nine of these UC patients (29%) who were older than 40 years of age developed CRC before the 10-year point. CONCLUSIONS: In the present study, patients diagnosed with UC after 40 years of age developed CRC more rapidly than those diagnosed before 40 years of age. This finding suggests that patients who are diagnosed with UC after 40 years of age should undergo CRC surveillance earlier than current recommendations.

Prospective Study of the Quality of Colonoscopies Performed by Primary Care Physicians: The Alberta Primary Care Endoscopy (APC-Endo) Study.

BACKGROUND: The quality of colonoscopies performed by primary care physicians (PCPs) is unknown. OBJECTIVE: To determine whether PCP colonoscopists achieve colonoscopy quality benchmarks, and patient satisfaction with having their colonoscopy performed by a primary care physician. DESIGN: Prospective multi-center, multi-physician observational study. Colonoscopic quality data collection occurred via completion of case report forms and pathological confirmation of lesions. Patient satisfaction was captured by a telephone survey. SETTING: Thirteen rural and suburban hospitals in Alberta, Canada. MEASUREMENTS: Proportion of successful cecal intubations, average number of adenomas detected per colonoscopy, proportion of patients with at least one adenoma, and serious adverse event rates; patient satisfaction with their wait time and procedure, as well as willingness to have a repeat colonoscopy performed by their primary care endoscopist. RESULTS: In the two-month study period, 10 study physicians performed 577 colonoscopies. The overall adjusted proportion of successful cecal intubations was 96.5% (95% CI 94.6-97.8), and all physicians achieved the adjusted cecal intubation target of ≥90%. The average number of ademonas detected per colonoscopy was 0.62 (95% CI 0.5-0.74). 46.4% (95% CI 38.5-54.3) of males and 30.2% (95% CI 22.3-38.2) of females ≥50 years of age having their first colonoscopy, had at least one adenoma. Four serious adverse events occurred (three post polypectomy bleeds and one perforation) and 99.3% of patients were willing to have a repeat colonoscopy performed by their primary care colonoscopist. LIMITATIONS: Two-month study length and non-universal participation by Alberta primary care endoscopists. CONCLUSIONS: Primary care physician colonoscopists can achieve quality benchmarks in colonoscopy. Training additional primary care physicians in endoscopy may improve patient access and decrease endoscopic wait times, especially in rural settings.

Argon plasma coagulation for the treatment of hemorrhagic radiation colitis.

Radiation colitis is a common consequence of pelvic radiation. Its complications may include anemia due to chronic bleeding requiring transfusions. Many of these patients are managed with rectal medications which are often inadequate for control. Argon plasma coagulation (APC) has been well described for its efficacy in treating radiation proctitis. Here we present two cases in whom APC therapy was used to treat severe radiation colitis. We reviewed two cases originally seen at the regional cancer center (Cross Cancer Institute) in Edmonton, Alberta, Canada. Both patients received pelvic radiation for recurrent endometrial cancers and were referred for active bleeding secondary to radiation colitis that had required numerous transfusions. Radiation-induced telangiectasias were found from 10-50 cm in the sigmoid colon. Both patients had significant improvement of symptoms after one session of APC treatment set at 40-60 W and gas flow of 2.0 l/min. There were no complications from the procedures. Neither patient required blood transfusions after the treatment with improvement in their hemoglobin levels and were doing well at 3- and 6-month follow-up. APC can be used effectively to provide immediate and sustained resolution of symptoms in patients with radiation colitis.