Related Articles

Background

A cohort of colorectal cancer (CRC) patients represents an opportunity to study missed opportunities for earlier diagnosis. Primary objective: To study the epidemiology of diagnostic delays and failures to offer/complete CRC screening. Secondary objective: To identify system- and patient-related factors that may contribute to diagnostic delays or failures to offer/complete CRC screening.

Methods

Setting: Rural Veterans Administration (VA) Healthcare system. Participants: CRC cases diagnosed within the VA between 1/1/2000 and 3/1/2007. Data sources: progress notes, orders, and pathology, laboratory, and imaging results obtained between 1/1/1995 and 12/31/2007. Completed CRC screening was defined as a fecal occult blood test or flexible sigmoidoscopy (both within five years), or colonoscopy (within 10 years); delayed diagnosis was defined as a gap of more than six months between an abnormal test result and evidence of clinician response. A summary abstract of the antecedent clinical care for each patient was created by a certified gastroenterologist (GI), who jointly reviewed and coded the abstracts with a general internist (TW).

Results

The study population consisted of 150 CRC cases that met the inclusion criteria. The mean age was 69.04 (range 35-91); 99 (66%) were diagnosed due to symptoms; 61 cases (46%) had delays associated with system factors; of them, 57 (38% of the total) had delayed responses to abnormal findings. Fifteen of the cases (10%) had prompt symptom evaluations but received no CRC screening; no patient factors were identified as potentially contributing to the failure to screen/offer to screen. In total, 97 (65%) of the cases had missed opportunities for early diagnosis and 57 (38%) had patient factors that likely contributed to the diagnostic delay or apparent failure to screen/offer to screen.

Conclusion

Missed opportunities for earlier CRC diagnosis were frequent. Additional studies of clinical data management, focusing on following up abnormal findings, and offering/completing CRC screening, are needed.

Objectives

Delays in colorectal cancer (CRC) diagnosis related to colonoscopy referrals are not well studied. We tested whether certain details of information transmitted through computerized provider order entry (CPOE)-based referrals affected timeliness of diagnostic colonoscopy for patients with newly diagnosed colorectal cancer (CRC).

Methods

We studied a 6-year cohort of all newly diagnosed patients with CRC at a large tertiary care Veterans Affairs hospital and its affiliated multispecialty clinics. Referring providers included primary care clinicians, resident trainees, and other specialists. From the colonoscopy referral preceding CRC diagnosis, we determined request date, type and frequency of diagnostic clues provided (symptoms, signs, test results), notation of urgency, and documented evidence of verbal contact between referring provider and consultant to expedite referral. We compared distributions of proportions of diagnostic clues between patients with > 60 and ≤ 60 day lag and examined predictors of lag time.

Results

Of 367 electronic referrals identified with a median lag of 57 days, 178 (48.5%) had lag > 60 days. Referrals associated with longer lag times included those with “positive fecal occult blood test” (92 days, P<0.0001), “hematochezia” (75 days, P=0.02), “history of polyps” (221 days, P=0.0006), and when “screening” (versus specific symptoms) was given as reason for diagnostic colonoscopy (203 days, P=0.002). Independent predictors of shorter wait times included 3 diagnostic clues, notation of urgency, and documentation of verbal contact.

Conclusions

Attention to certain details of diagnostic information provided to consultants through CPOE-based referrals may help reduce delays in CRC diagnosis.

Background Lagtimes to diagnostic colonoscopy have been used as practice performance measures.

Aim To evaluate the duration, determinants, and outcomes of lagtimes between referral for endoscopic evaluation and colorectal cancer (CRC) diagnosis.

Methods We examined the medical records of 289 patients with CRC and evaluated lagtimes, their potential determinants, and their association with CRC stage at diagnosis as well as overall survival.

Results Median lag between referral and CRC diagnosis was 41 days (41.5% >60 days, 30.1%>90 days). The only significant predictor of lagtime was the initiating event for referral: abnormal symptom, laboratory test, or imaging study was associated with shortest, and presence of family history was associated with longest lag times, respectively. Longer lagtimes were associated with lower mortality risk, but this was completely explained by earlier CRC stage. An analysis restricted to 100 patients referred for abnormal CRC screening tests found no association between duration of lag and CRC stage or mortality.

Conclusions There seems to be no meaningful association between mortality in patients with CRC and lagtimes between referral for colonoscopy and CRC diagnosis for periods up to 2-3 months. On the contrary, longer lagtimes were inversely associated with CRC stage at the time of diagnosis.

This study characterized patterns and costs of medical care by disease phase in patients with newly diagnosed mCRC using a large US national commercially insured claims database.

Purpose:

To characterize patterns of medical care by disease phase in patients with newly diagnosed metastatic colorectal cancer (mCRC).

Methods:

Patients with mCRC newly diagnosed between 2004 and 2008 were selected from a large US national commercially insured claims database and were observed from initial mCRC diagnosis to death, disenrollment, or end of study period (July 31, 2009), whichever occurred first. The observation period was divided into three distinct phases of disease: diagnostic, treatment, and death. Within each phase, patterns of medical care were examined by the mutually exclusive service categories of inpatient, emergency room (ER), outpatient office and facility, outpatient pharmacy, chemotherapy, and biologic therapy, as measured by estimation of aggregate and category costs per patient per month.

Results:

A total of 6,675 patients with newly diagnosed mCRC were analyzed. Mean age was 64.1 years; 55.5% were males. Mean costs per patient per month for diagnostic, treatment, and death phases were $16,895, $8,891, and $27,554, respectively. Inpatient care was the primary driver of medical care for both the diagnostic (41.7% of costs) and death (71.4% of costs) phases. The largest category of medical care for the treatment phase was outpatient care (45.0% of costs). Chemotherapy and biologic therapy accounted for 15.6% and 17.6% of costs in the treatment phase, respectively.

Conclusion:

Substantial differences in patterns of medical care were found between mCRC disease phases. Inpatient care was the key driver of medical care in the diagnostic and death phases compared with outpatient care in the treatment phase.

Background

Physicians’ cancer-related family history assessment for Lynch syndrome is often inadequate. Furthermore, the extent to which clinicians recognize non-family history-related clues for Lynch syndrome is unclear. We reviewed an integrated electronic health record (EHR) to determine diagnostic evaluation for Lynch syndrome in patients diagnosed with colorectal cancer (CRC).

Methods

We conducted a retrospective cohort study of consecutive patients with CRC, newly diagnosed at a tertiary care VA facility, between 1999 and 2007. A detailed review of the EHR was conducted to evaluate the presence of family-history and non-family history-related criteria of the Bethesda guidelines. Patient outcomes (identification in clinical practice and referral for genetic testing) were also determined.

Results

We identified a total of 499 patients (mean age=65.4 years, 98.6% male, 51.1% non-Hispanic white). At least 1 of the Bethesda criterion was met for 57 patients (11.4%); none were met for 198 (39.7%); and there was uncertainty for 244 (48.9%) because of inadequate family history documentation and/or the patient was unsure about their family history. Forty-nine patients met criteria unrelated to family history. Only 4 of 57 patients (7%) that met the Bethesda guidelines had documentation of counseling. Among 244 patients with uncertainty, a suspicion for Lynch syndrome was documented in the EHR of 6 patients (2.5%); 3 received counseling.

Conclusions

Lynch syndrome is under-recognized, even when patients have clear criteria unrelated to family history. Multifaceted strategies focused on reducing providers’ cognitive errors and harnessing EHR capabilities to improve recognition of Lynch syndrome are needed.

Background

The Two-Week Rule (TWR) was introduced to ensure that all patients with a suspected colorectal cancer (CRC) saw a hospital specialist within 14 days of an urgent GP referral. Guidelines were available to GPs to facilitate the appropriate TWR referral of patients exhibiting high-risk CRC symptoms.

Methods

We aimed to evaluate the TWR and its CRC detection rate on NHS CRC diagnostic services by performing a literature search and critically appraising the peer-reviewed studies. Only 12 studies were eligible for inclusion. Data was collected and overall results were given as weighted averages.

Results

The studies identified indicated that only 10.3% of patients referred by the TWR were eventually diagnosed with CRC. When examining the referral origin of all CRC patients diagnosed during the time of the studies, 24% had been referred using the TWR, 24.1% were referred as emergency cases, and 52.4% were referred using alternative routes. No evidence was found to indicate that the TWR had resulted in identifying CRC patients at an earlier, more treatable stage of their disease.

Conclusion

The TWR referral system needs to be improved to increase the number of CRC patients referred using this fast track method as they present to their GP. The TWR and new NICE Guidelines for the referral of patients with suspected cancer should be independently evaluated.

AIM: To assess the diagnostic yield and clinical value of early repeat colonoscopies for indications other than colorectal cancer (CRC) screening/surveillance.

METHODS: A retrospective review of patients who had more than one colonoscopy performed for the same indication within a three year time frame at our tertiary care referral hospital between January 1, 2000 and January 1, 2010 was conducted. Exclusion criteria included repeat colonoscopies performed for CRC screening/surveillance, poor bowel preparation, suspected complications from the index procedure, and incomplete initial procedure. Primary outcome was new endoscopic finding that led to an endoscopic therapeutic intervention or any change in clinical management. Clinical parameters including age, sex, race, interval between procedures, indication of the procedure, presenting symptoms, severity of symptoms, hemodynamic instability, duration between onset of symptoms and when the procedure was performed, change in endoscopist, withdrawal time, location of colonic lesions and improvement of quality of bowel preparation were analyzed using bivariate analysis and logistic regression analysis to examine correlation with this primary outcome.

RESULTS: Among 19  772 colonoscopies performed during the above mentioned period, 947 colonoscopies (4.79%) were repeat colonoscopies performed within 3 years from the index procedure. Out of these repeat colonoscopies, 139 patient pairs met the inclusion criteria. The majority of repeat colonoscopies were for lower gastrointestinal bleeding (88.4%), change in bowel habits (6.4%) and abdominal pain (5%). Among 139 eligible patient pairs of colonoscopies, only repeat colonoscopies that were done for lower gastrointestinal bleeding and abdominal pain produced endoscopic findings that led to a change in management [25 out of 123 (20.33%) and 2 out of 7 (28.57%), respectively]. When looking at only recurrent lower gastrointestinal bleeding cases, new endoscopic findings included 8 previously undetected hemorrhoid lesions (6.5%), 7 actively bleeding lesions requiring endoscopic intervention, which included 3 bleeding arterio-venous malformations (2.43%), 2 bleeding radiation colitis (1.6%), and 2 bleeding internal hemorrhoids (1.6%), 5 previously undetected tubular adenomas [4 were smaller than 1 cm (4.9%) and 1 was larger than 1 cm (0.8%)], 3 radiation colitis (2.43%), 1 rectal ulcer (0.8%), and 1 previously undetected right sided colon cancer (0.8%). Of the 25 new endoscopic findings, 18 (72%) were found when repeat colonoscopy was done within the first year after the index procedure. These findings were 1 rectal ulcer, 3 radiation colitis, 4 new hemorrhoid lesions, 3 previously undetected tubular adenomas, and 7 actively bleeding lesions requiring endoscopic intervention. Of all parameters analyzed, only the interval between procedures less than one year was associated with higher likelihood of finding a clinically significant change in repeat colonoscopy (odds ratios of interval between procedures of 1-2 year and 2-3 year compared to 0-1 year were 0.09; 95%CI 0.01-0.74, P = 0.025 and 0.26; 95%CI 0.09-0.72, P = 0.010 respectively). No complications were observed among all 139 colonoscopy pairs.

CONCLUSION: There is clinical value of repeating a colonoscopy for recurrent lower gastrointestinal bleeding, especially within the first year after the index procedure.

Purpose

Understanding delays in cancer diagnosis requires detailed information about timely recognition and follow-up of signs and symptoms. This information has been difficult to ascertain from paper-based records. We used an integrated electronic health record (EHR) to identify characteristics and predictors of missed opportunities for earlier diagnosis of lung cancer.

Methods

Using a retrospective cohort design, we evaluated 587 patients of primary lung cancer at two tertiary care facilities. Two physicians independently reviewed each case, and disagreements were resolved by consensus. Type I missed opportunities were defined as failure to recognize predefined clinical clues (ie, no documented follow-up) within 7 days. Type II missed opportunities were defined as failure to complete a requested follow-up action within 30 days.

Results

Reviewers identified missed opportunities in 222 (37.8%) of 587 patients. Median time to diagnosis in cases with and without missed opportunities was 132 days and 19 days, respectively (P < .001). Abnormal chest x-ray was the clue most frequently associated with type I missed opportunities (62%). Follow-up on abnormal chest x-ray (odds ratio [OR], 2.07; 95% CI, 1.04 to 4.13) and completion of first needle biopsy (OR, 3.02; 95% CI, 1.76 to 5.18) were associated with type II missed opportunities. Patient adherence contributed to 44% of patients with missed opportunities.

Conclusion

Preventable delays in lung cancer diagnosis arose mostly from failure to recognize documented abnormal imaging results and failure to complete key diagnostic procedures in a timely manner. Potential solutions include EHR-based strategies to improve recognition of abnormal imaging and track patients with suspected cancers.

Objective

The Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) seeks to develop partnerships between VA health services researchers and clinical managers, with the goal of designing and evaluating interventions to improve the quality of VA health care.

Methods

In the present report we describe one such initiative aimed at enhancing the continuum of colorectal cancer (CRC) care, including diagnosis, treatment and surveillance–the Colorectal Cancer Care Collaborative (C4).

Results

We describe the process and thinking that led to two parallel quality improvement “collaboratives” that addressed (1) CRC screening and diagnostic follow-up and (2) the guideline concordance and timeliness of CRC treatment. Additionally, we discuss ongoing effort to spread lessons learned during the first stages of the project, which initially occurred at only a subset of VA facilities, throughout the VA health care system. The description of this initiative is organized around key questions that must be answered when developing, sustaining and spreading multi-component quality improvement interventions.

Conclusion

We conclude with a discussion of lessons learned that we believe would apply to similar initiatives elsewhere, even if they address different clinical issues in health care settings with different organizational structures.

Background

Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.

Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC.

Methods

Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis.

Results

In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (p = 0.27).

In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank p = 0.93).

In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank p = 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (≤median) was 1.8 (95% confidence interval (CI) 1.1 to 3.0; p = 0.01). Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors.

Conclusion

In symptomatic CRC patients, a longer diagnostic and therapeutic delay in routine clinical practice was not associated with an adverse effect on survival. The time to CRC diagnosis and initiation of treatment did not differ between early stage and late stage colorectal cancer.

Multiple agents and combination therapies available to patients with advanced colorectal cancer have significantly improved survival and provided an opportunity for individualization of care, allowing clinicians and patients to prioritize risks and benefits of comparable regimens.

Purpose:

Patients with metastatic colorectal cancer (mCRC) are increasingly exposed to multiple chemotherapy regimens. Insight into patterns of care in mCRC is crucial to understanding physician and patient decision making.

Methods:

Patients with mCRC diagnosed between June 2003 and June 2006 were identified from one academic and nine community oncology practices in the southeastern United States. Demographic, disease, treatment, and toxicity data were abstracted by retrospective medical record review.

Results:

After screening 738 medical records, 110 patients were determined eligible. Of these, mean age was 58 years (standard deviation, 12 years), 74% had stage IV disease at diagnosis, 39% were male, 53% were white, 26% were black, and 13% were age 70 years or older. As part of first-line mCRC chemotherapy, 100% of patients received regimens containing fluorouracil (FU), 87% received oxaliplatin (95% CI, 81% to 93%), 12% received irinotecan (95% CI, 6% to 18%), and 74% received bevacizumab (95% CI, 66% to 82%). The proportions of patients receiving subsequent lines of chemotherapy were: second line, 48% (n = 53); third line, 26% (n = 29); fourth line, 14% (n = 15); and fifth line, 5% (n = 5). From first- to third-line therapy, use of oxaliplatin and bevacizumab decreased, whereas irinotecan use increased. Among patients for whom therapy was discontinued, 29% experienced disease progression (PD), and 19% experienced toxicity; for 27%, no reason for discontinuation was documented. Of regimens containing oxaliplatin and irinotecan, 22% (n = 25 of 114) and 34% (n = 20 of 59) were discontinued because of PD, respectively. Of the same regimens, 19% (n = 21 of 114) and 20% (n = 12 of 59) were discontinued because of toxicity, respectively.

Conclusion:

FU, oxaliplatin, and bevacizumab were most commonly used in first-line therapy for mCRC, despite data showing equivalency between regimens containing oxaliplatin and irinotecan. Use of oxaliplatin decreased and irinotecan use increased as treatment progressed beyond first-line therapy.

Background:

Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer.

Methods:

In a case–control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved – Fluorescence Immuno Assays (TR-FIA's).

Results:

All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I–III) P<0.0001 and suPAR(I–III)+(II–III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86–6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2–32.6) for suPAR(I–III) and 18.5% (95% CI:9.0–28.8) for suPAR(I–III)+(II–III) compared with subjects with non-malignant findings.

Conclusions:

The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest that uPAR expression could be useful in the early detection of CRC when combined with other markers and clinical variables.

AIM: To evaluate whether antiplatelet medication leads to an earlier stage colorectal cancer (CRC) diagnosis.

METHODS: From January 2002 until March 2010, patients that presented to our institution with the initial diagnosis of CRC and were submitted to an open curative CRC resection or a palliative procedure were retrospectively reviewed. Exclusion criteria were the use of antithrombotic medication, i.e., coumarins, and appendiceal malignancies. Data acquired from medical files included age, gender, past medical history, antithrombotic treatment received prior to endoscopic diagnosis, preoperative imaging staging, location of the tumor, surgical and final histopathological report. Patients that did not receive any antithrombotic medication prior to the endoscopic diagnosis comprised the control group of the study, while patients that were on antiplatelet medication comprised the antiplatelet group. Primary end point was a comparison of CRC stage in the two groups of the study. CRC presenting symptoms and the incidence of each cancer stage in the two groups were also evaluated.

RESULTS: A total of 387 patients with the diagnosis of CRC were submitted to our department for further surgical treatment. Ninety-eight patients (25.32%), with a median age of 71 years (range 52-91 years), were included in the antiplatelet group, while 289 (74.67%) patients, with a median age of 67 years (range 41-90 years), were not in any thrombosis prophylaxis medication (control group). Thirty-one patients were treated with some kind of palliative procedure, either endoscopic, such as endoscopic stent placement, or surgical, such as de-compressive colostomy or deviation. Coronary disease (77.55% - 76 patients), stroke recurrence prevention (14.28% - 14 patients) and peripheral arterial disease (8.16% - 8 patients) were the indications for the administration of antiplatelet treatment (aspirin, clopidogrel, ticlopidine or dipyridamole) in the antiplatelet group. All patients on aspirin treatment received a dosage of 100 mg/d, while the minimum prophylactic dosages were also used for the rest of the antiplatelet drugs. Investigation of an iron deficiency anemia (147 patients), per rectum blood loss (84 patients), bowel obstruction and/or perforation (81 patients), bowel habits alterations (32 patients), non-specific symptoms, such as weight loss, intermittent abdominal pain and fatigue, (22 patients) or population screening (21 patients) were the indications for the endoscopic investigation in both groups. Bleeding, either chronic presenting as anemia or acute was significantly higher (P = 0.002) for the antiplatelet arm of the study (71 patients - 72.4% of the antiplatelet group vs 160 patients - 55.3% of the control group). The mean tumor, node and metastasis stage was 2.57 ± 0.96 for the control group, 2.27 ± 0.93 for the antiplatelet group (P = 0.007) and 2.19 ± 0.92 for the subgroup of patients taking aspirin (P = 0.003). The incidence of advanced disease (stage IV) was lower for the antiplatelet group of the study (P = 0.033).

CONCLUSION: The adverse effect of bleeding that is justifiably attached to this drug category seems to have a favorable impact on the staging characteristics of CRC.

Although the quality of care delivered within the Florida Initiative for Quality Cancer Care practices seems to be high, several components of care were identified that warrant further scrutiny on a systemic level and at individual centers.

Purpose:

The Florida Initiative for Quality Cancer Care (FIQCC) was established to evaluate the quality of cancer care at the regional level across the state of Florida. This study assessed adherence to validated quality indicators in colorectal cancer (CRC) and the variability in adherence by practice site, volume, and patient age.

Methods:

The FIQCC is a consortium of 11 medical oncology practices in Florida. Medical record reviews were conducted for 507 patients diagnosed with CRC and seen as new medical oncology patients in 2006. Thirty-five indicators were evaluated individually and categorized across clinical domains and components of care.

Results:

The mean adherence for 19 of 35 individual indicators was > 85%. Pathology reports were compliant on reporting depth of tumor invasion (96%; range, 86% to 100%), grade (93%; range, 72% to 100%), and status of proximal and distal surgical resection margins (97%; range. 86% to 100%); however, documentation of lymphovascular and perineural invasion did not meet adherence standards (76%; range, 53% to 100% and 39%; range, 5% to 83%, respectively). Among patients with nonmetastatic rectal cancer, documentation of the status of surgical radial margins was consistently low across sites (42%; range, 0% to 100%; P = .19). Documentation of planned treatment regimens for adjuvant chemotherapy was noted in only 58% of eligible patients.

Conclusion:

In this large regional initiative, we found high levels of adherence to more than half of the established quality indicators. Although the quality of care delivered within FIQCC practices seems to be high, several components of care were identified that warrant further scrutiny on both a systemic level and at individual centers.

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is the most common hereditary colorectal cancer (CRC) syndrome, accounting for approximately 2–5% of all newly diagnosed cases of CRC. Patients with LS have an increased lifetime risk of colorectal (52.2% in women and 68.7% in men) and endometrial cancer (15–70%), as well as certain extra-colonic cancers. Germline mutations in one of several DNA mismatch repair genes underlie LS. Molecular testing has emerged as an indispensable strategy for the diagnosis of LS. The diagnostic work-up of at-risk individuals includes a careful family history evaluation, microsatellite instability, immunohistochemistry and germline DNA analysis. A positive test result can guide clinicians in formulating the appropriate screening, surveillance and management strategies. However, because of the absence of an overt phenotype, such as a diffuse polyposis, it is not always straightforward to recognize LS clinically.

We measured the financial consequences of new CRC treatment regimens. New regimens have increased cost directly through price and indirectly through nonstandard and second-line regimen use.

Purpose:

To compare medical expenditures of patients receiving old and new colorectal cancer (CRC) regimens.

Study Design:

Using claims data, we identified two cohorts of privately insured patients diagnosed with CRC: first, those diagnosed before new treatment introduction (January 1, 2002, to December 31, 2002), and second, those diagnosed after new treatment introduction (June 1, 2004, to May 31, 2005). CRC diagnosis was identified using International Classification of Diseases–9 codes 153.xx, 154.xx, and 159.0. First- and second-line chemotherapy regimens were identified. Treatments and expenditures were then observed for up to 2 years after initial diagnosis.

Methods:

We estimated multivariate models to measure changes in cost with changes in treatment regimen. Approval dates of new regimens were used as natural experiments.

Results:

New regimens, such as fluorouracil, leucovorin, and oxaliplatin (FOLFOX), have rapidly replaced the most prevalent preperiod product (ie, fluorouracil/leucovorin). Changes in treatment have caused large increases in total expenditure, primarily through increases in chemotherapy prices. FOLFOX alone has increased total average cost by 14%. New treatments have not substituted other medical services; rather, they have indirectly raised costs through nonstandard regimen use and increases in second-line treatment use. We found no evidence that expenditure effects were driven by changes in follow-up duration.

Conclusion:

New CRC treatments have increased both regimen choice and expenditures. New regimens have primarily increased expenditures through direct treatment costs; we observed no offsetting expenditure reductions.

Executive Summary

The colorectal cancer (CRC) screening project was undertaken by the Medical Advisory Secretariat (MAS) in collaboration with the Cancer Care Ontario (CCO).

In November 2007, the Ontario Health Technology Advisory Committee (OHTAC) MAS to conduct an evidence-based analysis of the available data with respect to colorectal cancer diagnosis and prevention. The general purpose of the project was to investigate the effectiveness, cost effectiveness, and safety of the various methods and techniques used for colorectal cancer screening in average risk people, 50 years of age and older.

The options currently offered for colorectal cancer screening were reviewed and five technologies were selected for review:

Computed tomographic (CT) colonography

Magnetic resonance (MR) colonography

Wireless capsule endoscopy (PillCam Colon)

Fecal occult blood test (FOBT)

Flexible sigmoidoscopy

In this review, colonoscopy was considered as the “gold standard” technique by which the effectiveness of all other modalities could be evaluated. An economic analysis was also conducted to determine cost-effectiveness of different screening modalities.

Evidence-based analyses have been prepared for each of these technologies, as well as summary document that includes an economic analysis, all of which are presented at the MAS Web site: http://www.health.gov.on.ca/english/providers/program/mas/tech/techmn.html

Objective

The objective of this evidence review is to examine the effectiveness and cost-effectiveness of fecal occult blood testing (FOBT), including guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT), for use in colorectal cancer (CRC) screening in asymptomatic, average-risk adults.

Specifically:

Is the use of gFOBT or iFOBT associated with a reduction in CRC and overall mortality?

What are the sensitivity and specificity of gFOBT and iFOBT for the detection of 1) CRC and 2) large polyps (≥ 1 cm)?

Clinical Need

CRC is the most common cause of non-tobacco related cancer death in Canada. It has been estimated that in 2007, 7,800 people were diagnosed with CRC in Ontario and 3,250 died from the disease, making the province’s incidence and mortality rate of CRC amongst the highest in the world.

Description of Technology/Therapy

There are two general types of FOBT that are categorized according to the analyte detected: guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT). Blood in the stool is a nonspecific finding but may originate from CRC or larger (>1 cm) polyps (small adenomatous polyps do not tend to bleed). Bleeding from cancers and larger polyps may be intermittent and not always detectable in a single sample. The FOBT thus requires regular testing that consists of collecting specimens from consecutive bowel movements. A positive gFOBT or iFOBT involves a diagnostic workup with colonoscopy to examine the entire colon in order to rule out the presence of cancer or advanced neoplasia.

Methods of Evidence-Based Analysis

A literature search was conducted from January 2003 to June 2008 that included OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment/Centre for Review and Dissemination.

Inclusion Criteria

Patients at average risk for CRC

All patients must be at least 50 years of age

Biennial FOBT as a screening modality and use of colonoscopy as the reference standard

Systematic reviews and randomized controlled trials (RCTs)

Outcomes: CRC mortality, overall mortality, sensitivity, specificity, adverse effects

Exclusion Criteria

Studies involving fewer than 100 patients

Studies that do not report sufficient data for analysis

Comparisons of Interest

Evidence exists for these comparisons of interest:

gFOBT compared with the reference “gold standard” colonoscopy (or double-contrast barium enema where colonoscopy is incomplete or contraindicated)

iFOBT compared with the reference gold standard colonoscopy (or DCBE where colonoscopy is incomplete or contraindicated)

gFOBT compared with iFOBT

The quality of the diagnostic studies was examined according to the ‘GRADE Working Group criteria’ for grading quality of evidence and strength of recommendations for diagnostic tests and strategies.

Summary of Findings

Single-Test Studies

There is limited direct/indirect evidence that iFOBT has sensitivity/specificity superior to that of unrehydrated gFOBT for CRC detection:

sensitivity for gFOBT:

pooled iFOBT sensitivity:

There is evidence that iFOBT and gFOBT have lower sensitivities for adenoma detection than for CRC detection:

sensitivity for rehydrated gFOBT

pooled iFOBT sensitivity

Repeated-Test Studies

No trials have examined CRC mortality outcomes after repeated testing of iFOBT.

Two RCTs from the United Kingdom and Denmark showed significant reduction in CRC mortality using unrehydrated gFOBT biennially

Relative risk reductions of 13% (UK trial) and 16% (Danish trial); absolute difference of 0.1% (UK trial) and 0.2% (Danish trial).

No significant reduction in overall mortality

Interval cancers (CRC that develop in the intervals between routine screening)

United Kingdom trial: 236 CRCs detected by positive test, 236 interval CRCs after negative test

Danish trial: 120 CRCs detected by positive test, 146 interval CRCs after negative test

Unrehydrated gFOBT has low sensitivity for CRC detection (45% in the UK trial and 54% in the Danish trial).

true positive rate

false positive rate

true negative rate

false negative rate

Guaiac FOBT – GRADE Quality of Evidence for Interventions

CRC indicates colorectal cancer; FOBT, fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation; RCT, randomized controlled trial.

Unlikely to be an important uncertainty.

GRADE Quality of Evidence for Diagnostic Tests: Implications of Testing Focusing on Accuracy

Benefit from diagnosis and treatment after confirmatory colonoscopy

Small risk of bowel perforation during colonoscopy

Benefit of reassurance

Anxiety/worry leading up to confirmatory colonoscopy

Small risk of bowel perforation during confirmatory colonoscopy

Detriment from delayed diagnosis

Some uncertainty (until after confirmatory colonoscopy)

No Uncertainty

Uncertainty

Uncertainty

FOBT indicates fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation.

Immunochemical FOBT – GRADE Quality of Evidence for Diagnostic Studies

FN indicates false negative; FOBT, fecal occult blood test; FP, false positive; Development and Evaluation; TN, true negative; TP, true positive.

Uncertainty until after confirmatory colonoscopy

Stress/worry for patient until confirmatory colonoscopy

Detrimental effects due to delayed diagnosis.

For these 3 reasons, downgrade quality from High to Moderate.

For these 3 reasons, downgrade quality from Moderate to Low.

Considerations for the Ontario Health System

Executive Summary Table 4 shows the potential system pressures and benefit/risk analysis for the use of FOBT and colonoscopy to screen for CRC in average-risk adults, ages 50 and over in Ontario.

Summary of Potential System Pressures for FOBT Screening

Prevent and detect

Detect

Every 10 years

Must repeat at regular intervals

Every 2 years

Must repeat at regular intervals

Observational studies

RCTs

Used as gold standard in studies

Intervention GRADE quality: High (gFOBT)

Diagnostic GRADE quality: Low (iFOBT)

No RCTs examining the effectiveness of repeated iFOBT on CRC mortality reduction were identified

Limited direct/indirect evidence that iFOBT has superior sensitivity/specificity to unrehydrated gFOBT for detection of CRC

0.1% risk of serious bleeding and perforation requiring surgery

0.3% risk of serious complications (stroke/bleeding requiring hospitalization/ myocardial infarction)

High interval cancer rate

The small benefit in CRC mortality reduction (absolute difference 0.1% to 0.2%) also coincides with a 0.3% risk of serious complications.

No food 1 day prior to exam

Office/hospital visit

Complete bowel preparation

Sedation

Eliminate citrus fruit and juices and vitamin C from diet for 3 days prior to/during stool collection.

Person applies 2 samples per bowel movement (each occurring on 3 different days) onto test areas of FOBT cards.

Increased demand for colonoscopies and colonoscopists or nurses who perform colonoscopies.

Patient receives kit from family physician, pharmacist

Patients mail completed FOBT kit to participating laboratory

Results sent back to patient

Increased demand for colonoscopies for positive patients

Removal of polyp during colonoscopy or surgery

Referral to colonoscopy

Cost-effective

Cost-effective

2nd of 5 choices in a patient survey study

5th of 5 choices in a patient survey study

FOBT indicates fecal occult blood test;; gFOBT, guaiac FOBT; GRADE, Grading of Recommendations Assessment, Development and Evaluation; iFOBT, immunochemical FOBT; RCT, randomized controlled trial.

Background

Data on clinical characteristics of patients with inflammatory bowel disease (IBD)-related colorectal cancer (CRC) are scarce and mainly originate from tertiary referral centres. We studied patient and disease characteristics of IBD-related CRC in a nationwide IBD cohort in general hospitals. Main outcome parameters were time to develop CRC, and factors associated with early CRC development.

Methods

All IBD patients diagnosed with CRC between 1 January 1990 and 1 July 2006 were identified using a nationwide automated pathology database (PALGA). Patient charts were assessed to confirm diagnosis and collect clinical data. Early CRC was defined as CRC diagnosed less than 8 years after IBD diagnosis. Statistical analysis was performed using descriptive statistics, independent t tests, binary logistic regression and Cox-regression analysis.

Results

Diagnosis of IBD-related CRC was confirmed in 251 patients (171 ulcerative colitis, 77 Crohn’s disease, 3 unclassified colitis), 161 males (64 %). Median time from IBD diagnosis to CRC diagnosis was 12 years (IQR 4–20); 89 patients (35 %) developed early CRC. Type of IBD, gender, concomitant PSC, pseudopolyps, extent of inflammation, and medication use were not related to early CRC (p > 0.05). IBD diagnosis at older age (HR for 10 years older age 2.25; 95 % CI 1.92–2.63) was related to early CRC. Twenty-three patients (12 %) had been included in a surveillance programme prior to CRC diagnosis. Patients in the surveillance group had a significantly better tumor stage (p = 0.004).

Conclusions

We emphasize the problem of a high proportion of IBD-associated CRCs developing before the recommended start of surveillance. Therefore, we suggest that older age at IBD onset could be an additional factor to start surveillance in IBD patients.

Background

The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease.

Methods

20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy.

Results

Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed.

Conclusion

This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC.

Background

Colorectal cancer (CRC) is the second most frequent tumor in developed countries. Since survival from CRC depends mostly on disease stage at the time of diagnosis, individuals with symptoms or signs suspicious of CRC should be examined without delay. Many factors, however, intervene between symptom onset and diagnosis. This study was designed to: 1) Describe the diagnostic process of CRC from the onset of first symptoms to diagnosis and treatment. 2) Establish the time interval from initial symptoms to diagnosis and treatment, globally and considering patient's and doctors' delay, with the latter due to family physician and/or hospital services. 3) Identify the factors related to defined types of delay. 4) Assess the concordance between information included in primary health care and hospital clinical records regarding onset of first symptoms.

Methods/Design

Descriptive study, coordinated, with 5 participant groups of 5 different Spanish regions (Balearic Islands, Galicia, Catalunya, Aragón and Valencia Health Districts), with a total of 8 acute public hospitals and 140 primary care centers.

Incident cases of CRC during the study period, as identified from pathology services at the involved hospitals. A sample size of 896 subjects has been estimated, 150 subjects for each participant group.

Information will be collected through patient interviews and primary health care and hospital clinical records. Patient variables will include sociodemographic variables, family history of cancer, symptom perception, and confidence in the family physician; tumor variables will include tumor site, histological type, grade and stage; symptom variables will include date of onset, type and number of symptoms; health system variables will include number of patient contacts with family physician, type and content of the referral, hospital services attending the patient, diagnostic modalities and results; and delay intervals, including global delays and delays attributed to the patient, family physician and hospital.

Discussion

To obtain a nonrestricted sample of patients with CRC we have minimized selection risk by identifying the patients from pathology services. A greater constraint may be associated with information sources based on clinical records. Due to inherent features of coordinated studies, it is important to standardize the collection of information.

Programs to increase colorectal cancer screening rates have seldom focused on improving patient care. To provide clinicians with methods for self-assessment and practice improvement, a national continuing medical education–certified performance improvement initiative was conceived.

Purpose:

In the United States, colorectal cancer (CRC) is the third leading cause of cancer after breast and prostate cancer. Numerous improvement programs have been implemented to increase CRC screening rates, but few have focused on improving the care and management of patients with a diagnosis of this malignancy. As national medical organizations focus on quality of care, efforts are necessary to provide clinicians the opportunity for self-assessment and methods for practice improvement. With this goal in mind, a national continuing medical education–certified performance improvement initiative was conceived.

Methods:

The initiative consisted of three stages: First, participants self-assessed their performance of predetermined topic measures through a review of patient charts. The topic areas included patient safety and supportive care, evidence-based surveillance, and evidenced-based treatment and were derived from current guidelines and other successful quality-improvement initiatives. Second, an actionable plan for practice improvement was developed in at least one of the three topic areas. Third, after a period of self-improvement, participants reassessed their performance of the same topic measures to determine tangible changes in patient care.

Results:

A total of 540 patient charts were reviewed by 27 clinicians. Notable results showed large gains in areas of supportive care, such as quantitative pain assessments and emotional well-being evaluations, which traditionally have been a minor focus of other quality-improvement initiatives. Participants also showed tangible improvements in the performance of leading measures of quality care.

Conclusion:

These findings support the need for continued efforts toward performance improvement in both established and emerging areas of CRC patient care.

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths in America. Nearly two thirds of newly diagnosed CRC cases include lymph node (LN) involvement, and LN metastasis is one of the strongest negative prognostic factors for CRC. It is thought that CRC tumors contain a small population of drug-resistant CRC tumor-initiating cells (Co-TICs) that may be responsible for cancer recurrence. To evaluate the effects of the LN stromal cells on Co-TICs, we established a unique xenoplant model using CRC cells isolated by enzymatic digestion from consented patient specimens, HT-29 cells, HCA-7 cells, and LN stromal cell line HK cells. We found that HK cells and HK cell-conditioned media enhanced CRC tumor formation and tumor angiogenesis. Cells expressing CD133+ and the stromal cell-derived factor 1α (SDF-1α) receptor CXCR4 were enriched in chemotherapeutic-resistant CRC cells. CD133+CXCR4+ Co-TICs isolated from patient specimens are more tumorigenic than unsorted tumor cells. Furthermore, the inhibitors specific to HK cell-derived SDF-1α reduced tumor formation and tumor angiogenesis. Our results have demonstrated a role for Co-TICs in tumor growth and defined the influence of LN stromal cells on Co-TICs. We have identified a major Co-TIC/LN microenvironment-specific mechanism for CRC resistance to chemotherapeutic agents and established experimental platforms for both in vitro and in vivo testing, indicating that SDF-1α and its receptor, CXCR4, may be targets for clinical therapy.

Abstract

Objective

To identify factors associated with delays to medical assessment and diagnosis for patients with colorectal cancer (CRC).

Design

Data were collected through a standardized questionnaire. Clinical records were also reviewed. When necessary, patients were contacted by a member of the study team to collect missing data and confirm information.

Setting

Cross Cancer Institute in Edmonton, Alta.

Participants

Patients newly diagnosed with a histologically proven colorectal adenocarcinoma were identified and eligible for the study.

Main outcome measures

Associations between symptoms, tumour stage at operation, symptom duration, and tumour location were sought to identify factors associated with a delay in diagnosis of CRC.

Results

Surveys were completed by 93 patients. A total of 49% of patients had symptoms of CRC present for 1 month or less before seeing a physician, and 51% had symptoms for longer than 1 month. Seventy-five (86%) patients initially presented to family physicians for assessment, while 12 (14%) patients presented to the emergency department for their first physician encounters. Only 33 (38%) patients had digital rectal examinations during their first visits. Women were more likely to present to physicians with longer than 1 month of symptoms, while men were more likely to present with less than 1 month of symptoms (P = .03). Abdominal pain, blood in the stool, and change in stool size were the most frequent symptoms encountered. Twenty-two (26%) patients delayed seeking treatment because they thought their symptoms were not serious and 12 (14%) believed that their family physicians had taken inappropriate action. Fifteen (18%) patients attributed their delays to waiting too long for specialist referral and diagnostic tests.

Conclusion

This study highlights the important role patients and physicians both play in delays in the diagnosis of CRC. Efforts to diminish future delays must focus on educating the public and practising physicians about important symptoms and signs of CRC. Additionally, the value of a digital rectal examination must be emphasized, along with continued promotion of CRC screening.

BACKGROUND:

There is a lack of data on familial aggregation of colorectal cancer (CRC) in Iran. We aimed to determine the frequency of hereditary nonpolyposis colorectal cancer (HNPCC) and familial colorectal cancer (FCC) and to determine the frequency of extracolonic cancers in these families in Isfahan.

METHODS:

We reviewed documents of all patients with a pathologically confirmed diagnosis of CRC admitted to Isfahan referral hospitals between 1995 and 2006. We also studied our CRC registry at Poursina Hakim Research Institute from 2003 to 2008. We found HNPCC and FCC families based on the Amsterdam II criteria and interviewed them for family history of CRC and extracolonic tumors. The family history was taken at least up to the second-degree relatives.

RESULTS:

During 1996 to 2008, a total of 2580 CRC cases have been diagnosed. We found 14 HNPCC and 53 FCC families. Mean age of CRC at diagnosis was 48.0 ± 14.6 and 49.0 ± 13.9 years in the HNPCC and FCC families, respectively (p > 0.05). The total numbers of observed extracolonic tumors were 70 (21.6%; mean age = 53.6 ± 11.0 years) and 157 (13.8%; mean age = 54.8 ± 18.0 years) in HNPCC and FCC families, respectively (p > 0.05). CRC was respectively found in 52 and 76 members of the HNPCC and FCC families, revealing the frequency of HNPCC and FCC as 2.0% (52/2580) and 2.9% (76/2580), respectively.

CONCLUSIONS:

We found a relative high frequency of HNPCC (2.0%) and FCC (2.9%) among CRC cases in our society and high incidence of extracolonic tumors in their families. Further studies focusing on molecular basis in this field and designing a specific screening and national cancer registry program for HNPCC and FCC families should be conducted.

Colorectal cancer (CRC) is the most common cause of non-tobacco-related cancer deaths in Canadian men and women, accounting for 10% of all cancer deaths. An estimated 7800 men and women will be diagnosed with CRC, and 3250 will die from the disease in Ontario in 2007. Given that CRC incidence and mortality rates in Ontario are among the highest in the world, the best opportunity to reduce this burden of disease would be through screening. The present report describes the findings and recommendations of Cancer Care Ontario’s Colonoscopy Standards Expert Panel, which was convened in March 2006 by the Program in Evidence-Based Care. The recommendations will form the basis of the quality assurance program for colonoscopy delivered in support of Ontario’s CRC screening program.