Initial treatment is associated with improved survival and end-of-life outcomes for patients with pancreatic cancer: a cohort study.

BACKGROUND: We describe the association between initial treatment and end-of-life (EOL) outcomes among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This population-based cohort study included patients with PDAC who died from April 2010-December 2017 in Ontario, Canada using administrative databases. We used multivariable models to explore the association between index cancer treatment (no cancer-directed therapy, radiation, chemotherapy, surgery alone, and surgery and chemotherapy), and primary (mortality, healthcare encounters and palliative care) and secondary outcomes (location of death, hospitalizations, and receipt of chemotherapy within the last 30 days of life). RESULTS: In our cohort (N = 9950), 56% received no cancer-directed therapy, 5% underwent radiation, 27% underwent chemotherapy, 7% underwent surgery alone, and 6% underwent surgery and chemotherapy. Compared to no cancer-directed therapy, radiation therapy (HR = 0.63), chemotherapy (HR = 0.43) surgery alone (HR = 0.32), and surgery and chemotherapy (HR = 0.23) were all associated with decreased mortality. Radiation (AMD = - 3.64), chemotherapy (AMD = -6.35), surgery alone (AMD = -6.91), and surgery and chemotherapy (AMD = -6.74) were all associated with fewer healthcare encounters per 30 days in the last 6 months of life. Chemotherapy (AMD = -1.57), surgery alone (AMD = -1.65), and surgery and chemotherapy (AMD = -1.67) were associated with fewer palliative care visits (all p-values for estimates above < 0.05). Treatment groups were associated with lower odds of institutional death and hospitalization at EOL, and higher odds of chemotherapy at EOL. CONCLUSIONS: Receiving cancer-directed therapies was associated with higher survival, fewer healthcare visits, lower odds of dying in an institution and hospitalization at EOL, fewer palliative care visits, and higher odds of receiving chemotherapy at EOL.

High Diagnostic Yield of Endoscopic Retrograde Cholangiopancreatography Brush Cytology for Indeterminate Strictures.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) brush cytology is used frequently for sampling indeterminate biliary strictures. Studies have demonstrated that the diagnostic yield of brush cytology for malignant strictures is estimated to be 6%-70%. With improved diagnostic tools, sampling techniques and specimen processing, the yield of ERCP brush cytology may be higher. This study aimed to assess the yield of brush cytology and determine factors associated with a positive diagnosis. Methods: This was a cohort study of patients who underwent ERCP brush cytology from October 2017 to May 2020. Patient demographics, clinical, procedural and pathological data were collected using chart review. Sampling data were captured up to 3 months post-index ERCP to capture repeat brushings, biopsies or surgical resections. Outcomes included the diagnostic yield, true/false positive values and true/false negative values of malignancy detection using ERCP brush cytology. Results: A total of 126 patients underwent a brush cytology, 58% were male and 79% had a stricture in the extrahepatic region. Ninety-three patients were diagnosed with a malignancy, of which 78 had positive brush cytology results and 15 had a negative brush cytology result. The diagnostic yield, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 84%, 83%, 97%, 99%, 68% and 87% respectively. Conclusion: ERCP brush cytology performed using updated sampling technique is associated with high diagnostic yield. This allows for earlier malignancy diagnosis, timely treatment and decreased need for further investigation.

Patient-centered outcomes for gastrointestinal cancer care: a scoping review protocol.

INTRODUCTION: Following a cancer diagnosis, patients and their caregivers face crucial decisions regarding goals of care and treatment, which have consequences that can persist throughout their cancer journey. To foster informed and value-driven treatment choices, evidence-based information on outcomes relevant to patients is needed. Traditionally, clinical studies have largely focused on a few concrete and easily measurable outcomes such as survival, disease progression and immediate treatment toxicities. These outcomes do not capture other important factors that patients consider when making treatment decisions. Patient-centred outcomes (PCOs) reflect the patients' individual values, preferences, needs and circumstances that are essential to directing meaningful and informed healthcare discussions. Often, however, these outcomes are not included in research protocols in a standardised and practical fashion. This scoping review will summarise the existing literature on PCOs in gastrointestinal (GI) cancer care as well as the tools used to assess these outcomes. A comprehensive list of these PCOs will be generated for future efforts to develop a core outcome set. METHODS AND ANALYSIS: This scoping review will follow Arksey and O'Malley's expanded framework for scoping reviews. We will systematically search Medline, Embase, CINAHL, Cochrane Library and APA PsycINFO databases for studies examining PCOs in the context of GI cancer. We will include studies published in or after the year 2000 up to the date of the final searches, with no language restrictions. Studies involving adult patients with GI cancers and discussion of any PCOs will be included. Opinion pieces, protocols, case reports and abstracts will be excluded. Two authors will independently perform two rounds of screening to select studies for inclusion. The data from full texts will be extracted, charted and summarised both quantitatively and qualitatively. ETHICS AND DISSEMINATION: No ethics approval is required for this scoping review. Results will be disseminated through scientific publication and presentation at relevant conferences.

The Bowel CLEANsing National Initiative: High-Volume Split-Dose Vs Low-Volume Split-Dose Polyethylene Glycol Preparations: A Randomized Controlled Trial.

BACKGROUND & AIMS: The aim of this study was to compare high-volume polyethylene glycol (PEG) with low-volume PEG with bisacodyl split-dosing regimens. METHODS: Adult outpatients in 10 Canadian tertiary hospitals were randomized, stratified by morning or afternoon colonoscopy, to high-volume split-dose PEG (2 L + 2 L) (High-SD) or low volume (1 L + 1 L) + bisacodyl (15 mg) PEG (Low-SD), with a second randomization to liquid or low-residue diets. The primary end point, using noninferiority hypothesis testing, was adequate bowel cleansing (Boston Bowel Preparation Scale total score of ≥6, with each of 3 colonic segments subscores ≥2). Secondary objectives were willingness to repeat the preparation, withdrawal time, cecal intubation, and polyp detection rates. RESULTS: Over 29 months, 2314 subjects were randomized to High-SD (N = 1157) or Low-SD (N = 1157) (mean age, 56.2 ± 13.4 y; 52.1% women). Colonoscopy indications were 38.2% diagnostic, 36.8% screening, and 25.0% surveillance, with no between-group imbalances in patient characteristics. Low-SD satisfied noninferiority criteria vs High-SD for adequate bowel cleanliness with only marginally inferior results (90.1% vs 88.1%; P = .02; difference, 2.0%; 95% CI [0.0%; 4.5%]). High-SD was associated with lower willingness to repeat (66.9% vs 91.9%; P < .01), was less well tolerated (7.3 ± 2.3 vs 8.1 ± 1.9; P < .01), causing more symptoms. No differences in procedural outcomes were noted except for more frequent cecal intubation rates after High-SD (97.4% vs 95.6%; P = .02). Among the High-SD group, adequate bowel preparation was greater after a clear liquid diet (93.6% vs 87.9%; P < .01), a finding not seen in the Low-SD group. CONCLUSIONS: Low-SD is noninferior to High-SD in providing adequate bowel preparation. Low-SD results in fewer symptoms, with greater willingness to repeat and tolerability. The overall impact of diet was modest.The study was approved by the research ethic boards from all sites and was registered at ClinicalTrials.gov (NCT02547571).

The Bowel CLEANsing National Initiative: A Low-Volume Same-Day Polyethylene Glycol (PEG) Preparation vs Low-Volume Split-Dose PEG With Bisacodyl or High-Volume Split-Dose PEG Preparations-A Randomized Controlled Trial.

INTRODUCTION: Bowel cleanliness has been shown to be superior with split-dose vs nonsplit preparations; we aimed to directly assess the poorly characterized comparative efficacies of split-dose vs same-day polyethylene glycol (PEG) regimens. METHODS: In this study, one of a series of randomized trials performed across 10 Canadian endoscopy units, patients undergoing colonoscopies between 10:30 and 16:30 were allocated to PEG low-volume same-day (15 mg bisacodyl the day before, 2 L the morning of the procedure), low-volume split-dose (15 mg bisacodyl the day before, 1 L + 1 L), or high-volume split-dose (2 L + 2 L). Coprimary endpoints were adequate bowel cleansing based on the Boston Bowel Preparation Scale using in turn different threshold cutoffs. RESULTS: Overall, 1,750 subjects were randomized equally across the 3 groups, with no differences in adequate bowel cleanliness rates (low-volume same-day, 90.5%; high-volume split-dose, 92.2%; P = 0.34; and low-volume split-dose, 87.9%; P = 0.17) for the Boston Bowel Preparation Scale ≥6 and 2 for each segment. Willingness to repeat the preparation was not significantly different between low-volume same-day (91.0%) and low-volume split-dose (92.5%; P = 0.40) but was greater than the high-volume split-dose (68.9%; P < 0.01). No significant differences were noted for withdrawal time, cecal intubation, or polyp detection rates. DISCUSSION: In this large randomized trial of PEG regimens, low-volume same-day resulted in similar bowel cleanliness compared with high-volume or low-volume split-dosing. Willingness to repeat and tolerability were superior with low-volume same-day compared with high-volume split-dose and similar to low-volume split-dose.

Long-Term Effectiveness, Safety and Mortality Associated with the Use of TC-325 for Malignancy-Related Upper Gastrointestinal Bleeds: A Multicentre Retrospective Study.

BACKGROUND AND STUDY AIMS: Malignant-related upper gastrointestinal bleeding (MRUGIB) is difficult to treat by conventional endoscopic methods. We sought to determine the efficacy, safety and mortality associated with the use of TC-325 for the treatment of MUGIB. PATIENTS AND METHODS: This is a multicentre, retrospective study at the University of Calgary and University of Ottawa performed between January 1, 2010, and July 30, 2016. TC-325 use was identified via staff polling, product order forms and endoscopic records review. Once identified, patient charts and online records were examined to identify MRUGIB cases and to assess our primary and secondary endpoints. OUTCOMES: The primary outcome was hemostasis at seven days. Secondary outcomes include immediate hemostasis, early hemostasis, hemostasis at 14 days, 30-day mortality, adverse events related to TC-325 therapy and the need for repeat endoscopic intervention, surgery or transarterial embolization. RESULTS: Twenty-five patients were identified. The median age was 62 years (interquartile range [IQR] 52.5-76), and most were male (64%). TC-325 was the primary treatment modality in 20 patients (80%). Hemostasis was 88%, 89%, 58% and 50% at 24 hours, 72 hours, 7 days and 14 days, respectively. Five patients underwent repeat endoscopy, two patients required surgical intervention, and transarterial embolization was not required. Twelve patients died by 30 days (48%). There were no complications directly attributed to the use of TC-325. CONCLUSIONS: TC-325 is effective for achieving and maintaining hemostasis in patients with malignancy-related upper gastrointestinal bleeding, and most patients do not require additional interventions. The 30-day mortality risk in this group of patients is high.

History of malignancy and relevant symptoms may predict a positive computed tomography enterography in obscure gastrointestinal bleeds.

BACKGROUND AND AIM: This study aimed to assess the clinical utility of computed tomography enterography (CTE) and identify factors associated with a diagnostic CTE for patients with obscure gastrointestinal bleeding (OGIB). METHODS: A retrospective observational study was performed at a Canadian tertiary care center from 2005 to 2015. A total of 138 patients underwent a CTE for OGIB. Univariate and multivariate logistic regressions were performed to determine factors associated with a diagnostic CTE. A highly sensitive clinical rule was then developed to help identify OGIB patients for whom a CTE may be beneficial in their clinical work-up. RESULTS: A possible bleeding source was identified in 30 (22%) cases. The presence of abdominal or constitutional symptoms as well as history of colorectal cancer was significantly associated with a positive CTE in univariate and multivariate analyses (P < 0.05). A positive CTE could be predicted based on the presence of abdominal or constitutional symptoms and history of colorectal cancer with 90% sensitivity (95% CI 74-98%) in our population. CONCLUSION: CTE identified a possible source of OGIB in one in five cases. In patients with the presence of abdominal or constitutional symptoms and a personal history of colorectal cancer, CTE may contribute to their diagnostic work-up.

Temporal trends in postcolonoscopy colorectal cancer rates in 50- to 74-year-old persons: a population-based study.

BACKGROUND AND AIMS: Colorectal cancers (CRCs) diagnosed between 6 and 36 months after colonoscopy, termed postcolonoscopy CRCs (PCCRCs), arise primarily due to missed or inadequately treated neoplasms during colonoscopy. Introduction of multiple quality indicators and technological advances to colonoscopy practice should have reduced the PCCRC rate over time. We assessed temporal trends in the population rate of PCCRC as a measure of changing colonoscopy quality. METHODS: We conducted a population-based retrospective cohort study of persons aged 50 to 74 years without advanced risk factors for CRC who underwent complete colonoscopy in Ontario, Canada between 1996 and 2010. We defined the PCCRC rate as the proportion of individuals diagnosed with CRC within 36 months of colonoscopy that had PCCRC. We compared age-adjusted and sex-adjusted rates of PCCRC over time based on 3 periods (1996-2001, 2001-2006 and 2006-2010) and assessed the independent association between time period and PCCRC risk through multivariable regression, with respect to all PCCRCs, proximal PCCRC and distal PCCRC. RESULTS: There was a marked increase in colonoscopy volumes over the study period, particularly in younger age groups and non-hospital settings. Among 1,093,658 eligible persons the PCCRC rate remained stable at approximately 8% over the 15-year study period. The adjusted odds of PCCRC, distal PCCRC and proximal PCCRC, comparing the 2006 to 2010 period with the 1996 to 2001 period, were 1.14 (95% confidence interval [CI], 1.0-1.31), 1.11 (95% CI, 0.91-1.34), and 1.14 (95% CI, 0.94-1.38), respectively. Temporal trends in PCCRC risk did not differ by endoscopist specialty or institutional setting after covariate adjustment. CONCLUSION: The PCCRC rate in Ontario has remained consistently high over time. Widespread initiatives are needed to improve colonoscopy quality.

Repeated faecal occult blood testing is associated with decreased advanced colorectal cancer risk: A population-based study.

OBJECTIVE: To evaluate the association between repeated faecal occult blood testing and advanced colorectal cancer risk at population level in Canada. METHODS: A retrospective cohort study of all Ontario residents aged 56-74 diagnosed with colorectal cancer from 1 April 2007 to 31 March 2010, identified using health administrative data. The primary outcome was stage IV colorectal cancer, and primary exposure was faecal occult blood testing use within five years prior to colorectal cancer diagnosis. Patients were categorized into four mutually exclusive groups based on their exposure to faecal occult blood testing in the five years prior to colorectal cancer diagnosis: none, pre-diagnostic, repeated, and sporadic. Logistic regression was utilized to adjust for confounders. RESULTS: Of 7753 patients (median age 66, interquartile range 61-70, 62% male) identified, 1694 (22%) presented with stage I, 2056 (27%) with stage II, 2428 (31%) with stage III, and 1575 (20%) with stage IV colorectal cancer. There were 4092 (53%) with no record of prior faecal occult blood testing, 1485 (19%) classified as pre-diagnostic, 1693 (22%) as sporadic, and 483 (6%) as repeated faecal occult blood testing. After adjusting for confounders, patients who had repeated faecal occult blood testing were significantly less likely to present with stage IV colorectal cancer at diagnosis (Odds ratio 0.46, 95% Confidence Interval 0.34-0.62) than those with no prior faecal occult blood testing. CONCLUSIONS: Repeated faecal occult blood testing is associated with a decreased risk of advanced colorectal cancer. Our findings support the use of organized screening programmes that employ repeated faecal occult blood testing to improve colorectal cancer outcomes at population level.

Paraduodenal pancreatitis as an uncommon cause of gastric outlet obstruction: A case report and review of the literature.

INTRODUCTION: Paraduodenal pancreatitis (PP) is an under-recognized form of focal chronic or recurrent pancreatitis. Since PP presents with non-specific symptoms and shares radiological and histopathological features with other entities, it can be challenging to diagnose. PRESENTATION OF CASE REPORT: Herein, a case of a 64 year-old Caucasian male with PP presenting with recurrent gastric outlet obstruction (GOO) is detailed. Over the course of two years, he underwent multiple balloon dilatations for symptom management. His diagnostic course was complicated by inconclusive and misleading biopsies. CONCLUSION: PP can rarely present as GOO in otherwise asymptomatic patients. A preoperative pathologic diagnosis can be difficult to obtain, and in this case delayed definitive surgical management. The case is discussed in detail, and a concise review the current literature was undertaken.

Regional differences in use of endoscopic ultrasonography in Ontario: a population-based retrospective cohort study.

BACKGROUND: Endoscopic ultrasonography is a safe and accurate modality for evaluating and managing hepatobiliary and gastrointestinal conditions (malignant and nonmalignant); its use is increasing. The aim of this study was to describe regional trends in the use of endoscopic ultrasonography in Ontario. METHODS: We conducted a population-based retrospective cohort study using health administrative databases. We identified all patients who underwent an endoscopic ultrasound procedure in Ontario from 2003 to 2011 using physician billing data. Patient, physician and institution characteristics were examined. The primary outcome was use of endoscopic ultrasonography. RESULTS: We identified 9076 endoscopic ultrasound procedures performed in 8001 patients (3858 women [48.2%]; median patient age at first procedure 59 years). A total of 3066 procedures (33.8%) involved fine-needle aspiration. Use of endoscopic ultrasonography increased 17-fold over the study period. In 2011, people living in the health region with the highest rate of use of endoscopic ultrasonography were more than 4 times more likely to undergo the procedure than people living in the health region with the lowest rate of use (standardized rate 61.6 v. 12.9 per 100 000). About 7 in 10 endoscopic ultrasound procedures were performed in an academic institution or regional cancer centre. All 17 endoscopists performing endoscopic ultrasonography during the study period practised in urban areas. INTERPRETATION: Although the use of endoscopic ultrasonography increased over time in Ontario, there were marked regional differences in use. Provincial needs- and evidence-based initiatives may be needed to narrow the regional gaps in provision of endoscopic ultrasound services in the province.

The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis.

BACKGROUND AND STUDY AIMS: It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. PATIENTS AND METHODS: We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. RESULTS: Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10-33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8-24%) after a CT scan was performed. LIMITATIONS: The majority of the included studies were retrospective. CONCLUSIONS: EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma.

Clinical prediction rule to determine the need for repeat ERCP after endoscopic treatment of postsurgical bile leaks.

BACKGROUND AND AIMS: In patients who have undergone ERCP with biliary stenting for postsurgical bile leaks, the optimal method (ERCP or gastroscopy) and timing of stent removal is controversial. We developed a clinical prediction rule to identify cases in which a repeat ERCP is unnecessary. METHODS: Population-based study of all patients who underwent ERCP for management of surgically induced bile leaks between 2000 and 2012. Multivariate and binary recursive partitioning analyses were performed to generate a rule predicting the absence of biliary pathology on repeat endoscopic evaluation. RESULTS: A total of 259 patients were included. On multivariate analysis, postsurgical normal alkaline phosphatase (ALP; OR, 2.26; 95% CI, 1.03-4.99), time from surgery to first ERCP < 8 days (OR, 2.47; 95% CI, 1.15-5.31), and minor leak with no other pathology on initial ERCP (OR, 6.74; 95% CI, 1.75-25.89) were independently associated with the absence of persistent bile leak and other pathology on repeat ERCP. The derived rule included laparoscopic cholecystectomy, normal postsurgical ALP, minor leak with no other pathology on initial ERCP, and an interval from initial to repeat ERCP between 4 and 8 weeks. When all 4 criteria were met, the rule had a sensitivity of 94% (95% CI, 83%-99%) and a negative predictive value of 93% (95% CI, 81%-99%). Optimism-adjusted sensitivity and negative predictive value were 88% (95% CI, 76%-96%) and 86% (95% CI, 73%-96%), respectively. CONCLUSIONS: This clinical decision rule identifies patients who can have their biliary stents removed via gastroscopy, which may improve patient safety and healthcare utilization.

Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis.

BACKGROUND: Current guidelines recommend CT scan or magnetic resonance imaging as the initial imaging modalities for the work-up of suspected pancreatic neuroendocrine tumors (PNETs). OBJECTIVE: To determine the incremental benefit of preoperative EUS (IBEUS) for the detection of suspected PNETs after other investigative modalities have been attempted. DESIGN: This systematic review searched MEDLINE, EMBASE, bibliographies of included articles, and conference proceedings for studies reporting original data regarding the preoperative detection of PNETs. Pooled IBEUS was calculated by using random effects models. Heterogeneity was explored by using stratified meta-analysis and meta-regression. Evidence of small-study effects was assessed by using funnel plots and the Begg test. PATIENTS: Patients with suspected PNETs. INTERVENTIONS: EUS evaluation. MAIN OUTCOME MEASUREMENTS: The pooled IBEUS for the detection of PNETs after CT scan, with or without additional investigative modalities. RESULTS: Among 4505 citations identified, we included 17 cohort studies (612 patients). EUS identified PNETs in 97% of cases. Improved PNET identification with EUS was observed in all of the studies. After adjusting for small-study effects, meta-analysis showed that EUS alone could identify PNETs in approximately 1 in 4 patients (adjusted IBEUS 26%; 95% confidence interval, 17%-37%). The pooled IBEUS varied based on the study design, study size, type of CT scan used, and the number of modalities used prior to EUS. LIMITATIONS: The majority of included studies were retrospective. Small-study effects were observed. CONCLUSION: Preoperative EUS is associated with an increase in PNET detection after other modalities are attempted.

Avoidable mortality across Canada from 1975 to 1999.

BACKGROUND: The concept of 'avoidable' mortality (AM) has been proposed as a performance measure of health care systems. In this study we examined mortality in five geographic regions of Canada from 1975 to 1999 for previously defined avoidable disease groups that are amenable to medical care and public health. These trends were compared to mortality from other causes. METHODS: National and regional age-standardized mortality rates for ages less than 65 years were estimated for avoidable and other causes of death for consecutive periods (1975-1979, 1980-1985, 1985-1989, 1990-1994, and 1995-1999). The proportion of all-cause mortality attributable to avoidable causes was also determined. RESULTS: From 1975-1979 to 1995-1999, the AM decrease (46.9%) was more pronounced compared to mortality from other causes (24.9%). There were persistent regional AM differences, with consistently lower AM in Ontario and British Columbia compared to the Atlantic, Quebec, and Prairies regions. This trend was not apparent when mortality from other causes was examined. Injuries, ischaemic heart disease, and lung cancer strongly influenced the overall AM trends. CONCLUSION: The regional differences in mortality for ages less than 65 years was attributable to causes of death amenable to medical care and public health, especially from causes responsive to public health.