Mandeep Sawhney

Quality Indicators for Colonoscopy

Colonoscopy is widely used for the diagnosis and treatment of colonic disorders. Properly performed, colonoscopy is generally safe, accurate, and well tolerated by most patients. Visualization of the mucosa of the entire large intestine and distal terminal ileum is usually possible at colonoscopy. In patients with chronic diarrhea, biopsy specimens can help diagnose the underlying condition. Polyps can be identified and removed during colonoscopy, thereby reducing the risk of colon cancer. Colonoscopy is the preferred method to evaluate the colon in most adult patients with bowel symptoms, iron deficiency anemia, abnormal radiographic studies of the colon, positive colorectal cancer screening tests, postpolypectomy and postcancer resection surveillance, surveillance in inflammatory bowel disease, and in those with suspected masses. The use of colonoscopy has become accepted as the most effective method of screening the colon for neoplasia in patients over the age of 50 years and in younger patients at increased risk (1). The effectiveness of colonoscopy in reducing colon cancer incidence depends on adequate visualization of the entire colon, diligence in examining the mucosa, and patient acceptance of the procedure. Preparation quality affects the ability to perform a complete examination, the duration the procedure, and the need to cancel or reschedule procedures (2, 3). Ineffective preparation is a major contributor to costs (4). Longer withdrawal times have been demonstrated to improve polyp detection rates, (5‐7) and conversely, rapid withdrawal may miss lesions and reduce the effectiveness of colon cancer prevention by colonoscopy. The miss rates of colonoscopy for large (≥1 cm) adenomas may be higher than previously thought (8, 9) Thus, careful examinations are necessary to optimize the effectiveness of recommended intervals between screening and surveillance examinations. Finally, technical expertise will help prevent complications that can offset any cost benefit ratio gained by removing neoplastic lesions. The following quality indicators have been selected to establish competence in performing colonoscopy and help define areas for continuous quality improvement. The levels of evidence supporting these quality indicators were graded according to Table 1. PREPROCEDURE The preprocedure period encompasses the time from first contact by the patient until administration of sedation or instrument insertion. The aspects of patient care addressed in prior documents apply here as well, including timely scheduling, patient preparation, identification, history and physical examination, appropriate choice of sedation and analgesia, evaluation of bleeding risk, etc. Because many examinations are currently being performed for colon cancer screening and are elective, care must be taken to be certain that all potential risks have been reduced to as low as practically achievable. The American Society for Gastrointestinal Endoscopy (ASGE) (10) and the U.S. Multi-Society Task Force on Colon Cancer have published appropriate indications for colonoscopy (11) (Tables 2 and 3).

CIMP Status of Interval Colon Cancers: Another Piece to the Puzzle

OBJECTIVES:Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to the development of new tumors, possibly reflecting molecular and environmental differences in tumorigenesis resulting in rapid tumor growth. In a previous study from our group, interval cancers (colon cancers diagnosed within 5 years of a complete colonoscopy) were almost four times more likely to demonstrate microsatellite instability (MSI) than non-interval cancers. In this study we extended our molecular analysis to compare the CpG island methylator phenotype (CIMP) status of interval and non-interval colorectal cancers and investigate the relationship between the CIMP and MSI pathways in the pathogenesis of interval cancers.METHODS:We searched our institutions cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with non-interval cancers (defined as colon cancers diagnosed on a patients first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for CIMP gene markers. The MSI status of subjects identified between 1989 and 2004 was known from our previous study. Tissue specimens of newly identified cases and controls (between 2005 and 2006) were tested for MSI.RESULTS:There were 1,323 cases of colon cancer diagnosed over the 17-year study period, of which 63 were identified as having interval cancer and matched to 131 subjects with non-interval cancer. Study subjects were almost all Caucasian men. CIMP was present in 57% of interval cancers compared to 33% of non-interval cancers (P=0.004). As shown previously, interval cancers were more likely than non-interval cancers to occur in the proximal colon (63% vs. 39%; P=0.002), and have MSI 29% vs. 11%, P=0.004). In multivariable logistic regression model, proximal location (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.01–3.8), MSI (OR 2.7; 95% CI 1.1–6.8) and CIMP (OR 2.41; 95% CI 1.2–4.9) were independently associated with interval cancers. CIMP was associated with interval cancers independent of MSI status. There was no difference in 5-year survival between the two groups.CONCLUSIONS:Interval cancers are more likely to arise in the proximal colon and demonstrate CIMP, which suggests there may be differences in biology between these and non-interval CRC. Additional studies are needed to determine whether interval cancers arise as a result of missed lesions or accelerated neoplastic progression.

Risk factors for severe delayed postpolypectomy bleeding

BACKGROUND AND STUDY AIMS Postpolypectomy bleeding is a rare but serious adverse event. The aim of this study was to identify factors associated with the risk of severe delayed postpolypectomy bleeding. PATIENTS AND METHODS This was a case-control study, comparing cases who developed hematochezia and required medical evaluation 6 hours to 14 days after colonoscopic polypectomy, and control patients who underwent polypectomy without delayed bleeding, and who were selected in approximately a 3 : 1 ratio. The following risk factors were specified a priori: resuming anticoagulation (within 1 week following polypectomy), aspirin use, hypertension, and polyp diameter. RESULTS Of the 4592 patients who underwent colonoscopy with polypectomy, 41 patients (0.9 %) developed delayed postpolypectomy bleeding (cases), and 132 patients were selected as controls. The mean age was 64.3 years for cases and 65.4 years for controls. Cases presented on average 6 days after polypectomy (range 1 - 14 days), and 48 % required blood transfusion (average 4.2 units, range 0 - 17). Two patients required surgery. Anticoagulation was resumed following polypectomy in 34 % of cases compared with 9 % of controls (OR 5.2; 95 % CI 2.2 - 12.5; P < 0.001). For every 1 mm increase in polyp diameter, the risk of hemorrhage increased by 9 % (OR 1.09; 95 % CI 1.0 - 1.2; P = 0.008). Hypertension (OR 1.1) and aspirin use (OR 1.1) did not increase the risk of postpolypectomy bleeding. In exploratory analysis, diabetes (OR 2.5) and coronary artery disease (OR 3.0) were associated with postpolypectomy hemorrhage, but the association was no longer statistically significant once adjusted for the use of anticoagulation. CONCLUSIONS Resuming anticoagulation following polypectomy and polyp diameter were strongly associated with increased risk of severe delayed postpolypectomy bleeding.

Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

PURPOSE Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. PATIENTS AND METHODS A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with ≥12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. RESULTS With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. CONCLUSION Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

Effect of Institution-Wide Policy of Colonoscopy Withdrawal Time ≥7 Minutes on Polyp Detection

BACKGROUND & AIMS Practice guidelines recommend that endoscopists spend at least 7 minutes examining the colonic mucosa during colonoscopy withdrawal to optimize polyp yield. The aim of this study was to determine if the implementation of an institution-wide policy of colonoscopy withdrawal time > or = 7 minutes was associated with an increase in colon polyp detection. METHODS All 42 endoscopists at our institute were asked to attain a colonoscopy withdrawal time of at least 7 minutes. Compliance with 7-minute withdrawal time was recorded for all nontherapeutic colonoscopies. Polyp detection ratio (number of polyps detected divided by number of colonoscopies performed) was computed. Regression models were used to assess the association between compliance with 7-minute withdrawal time and polyp detection. RESULTS During the study period, 23,910 colonoscopies were performed. The average age of patients was 56.8 years, and 54% were female. Colon cancer screening or surveillance was the indication for 42.5% of colonoscopies. At the beginning of the study, the polyp detection ratio was 0.48. Compliance with 7-minute withdrawal time for nontherapeutic procedures increased from 65% at the beginning of the initiative to almost 100%. However, no increase in polyp detection ratio was noted over the same period for all polyps (slope, 0.0006; P = .45) or for polyps 1-5 mm (slope, 0.001; P = .26), 6-9 mm (slope, 0.002; P = .43), or > or = 10 mm (slope, 0.006; P = .13). No association was detected when only colonoscopies performed for screening or surveillance were analyzed. CONCLUSIONS An institution-wide policy of colonoscopy withdrawal time > or = 7 minutes had no effect on colon polyp detection.

Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer.

PURPOSE Stereotactic body radiotherapy (SBRT) has been used successfully to treat patients with locally advanced pancreas cancer. However, many patients develop metastatic disease soon after diagnosis and may receive little benefit from such therapy. We therefore retrospectively analyzed a planned strategy of initial chemotherapy with restaging and then treatment for those patients with no evidence of metastatic progression with SBRT. METHODS AND MATERIALS Forty-seven patients received gemcitabine (1,000 mg/m(2) per week for 3 weeks then 1 week off) until tolerance, at least six cycles, or progression. Patients without metastases after two cycles were treated with SBRT (tolerance-based dose of 24-36 Gy in 3 fractions) between the third and fourth cycles without interrupting the chemotherapy cycles. RESULTS Eight of the 47 patients (17%) were found to have metastatic disease after two cycles of gemcitabine; the remaining 39 patients received SBRT. The median follow-up for survivors was 21 months (range, 6-36 months). The median overall survival for all patients who received SBRT was 20 months, and the median progression-free survival was 15 months. The local control rate was 85% (33 of 39 patients); and 54% of patients (21 of 39) developed metastases. Late Grade III toxicities such as GI bleeding and obstruction were observed in 9% (3/39) of patients. CONCLUSION For patients with locally advanced pancreas cancer, this strategy uses local therapy for those who are most likely to benefit from it and spares those patients with early metastatic progression from treatment. SBRT delivers such local therapy safely with minimal interruption to systemic chemotherapy, thereby potentially improving the outcome in these patients.

Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid

BACKGROUND Pancreatic-cyst fluid carcinoembryonic antigen (CEA) levels and molecular analysis are useful diagnostic tests in differentiating mucinous from nonmucinous cysts. OBJECTIVE To assess agreement between CEA and molecular analysis for differentiating mucinous from nonmucinous cysts. DESIGN Retrospective analysis. SETTING Academic medical center. METHODS Patients who underwent EUS-guided FNA for evaluation of pancreatic cysts were identified. The following information was used to designate a cyst mucinous: the CEA criterion was CEA level >or=192 ng/mL and the molecular analysis criteria were DNA quantity >or=40 ng/microL and/or k-ras 2-point mutation and/or >or=2 allelic imbalance mutations. Pathologic analysis of cysts served as the criterion standard. RESULTS From 2006 to 2007, 100 patients met the study criteria. The average age of the patients was 63 years, 65% were women, and 30% were symptomatic. The mean diameter of pancreatic cysts was 2.5 cm. The median CEA value was 83 ng/mL (range 1-50,000 ng/mL), the mean DNA content was 16 ng/microL (range 1-212 ng/microL), 11% had K-ras mutations, and 43% had >or=2 allelic imbalance mutations. When using prespecified criteria, there was poor agreement between CEA and molecular analysis for the classification of mucinous cysts (kappa = 0.2). Poor agreement existed between CEA and DNA quantity (Spearman correlation = 0.2; P = .1), K-ras mutation (kappa = 0.3), and >or=2 allelic imbalance mutations (kappa = 0.1). Of the 19 patients for whom a final pathologic diagnosis was available, CEA had a sensitivity of 82% compared with 77% for molecular analysis. When CEA and molecular analysis were combined, 100% sensitivity was achieved. LIMITATIONS Retrospective analysis and small sample size. CONCLUSION There was poor agreement between CEA levels and molecular analysis for diagnosis of mucinous cysts. Diagnostic sensitivity was improved when results of CEA levels and molecular analysis were combined.

The Incidence and Cost of Unexpected Hospital Use After Scheduled Outpatient Endoscopy

BACKGROUND Data on complications of gastrointestinal endoscopic procedures are limited. We evaluated prospectively the incidence and cost of hospital visits resulting from outpatient endoscopy. METHODS We developed an electronic medical record-based system to record automatically admissions to the emergency department (ED) within 14 days after endoscopy. Physicians evaluated all reported cases for relatedness of the ED visit to the prior endoscopy based on predetermined criteria. RESULTS We evaluated 6383 esophagogastroduodenoscopies (EGDs) and 11 632 colonoscopies (7392 for screening and surveillance). Among these, 419 ED visits and 266 hospitalizations occurred within 14 days after the procedure. One hundred thirty-four (32%) of the ED visits and 76 (29%) of the hospitalizations were procedure related, whereas 31 complications were recorded by standard physician reporting (P < .001). Procedure-related hospital visits occurred in 1.07%, 0.84%, and 0.95% of all EGDs, all colonoscopies, and screening colonoscopies, respectively. The mean costs were

Quality Indicators for ERCP

1403 per ED visit and

International consensus guidelines for surgical resection of mucinous neoplasms cannot be applied to all cystic lesions of the pancreas.

10 123 per hospitalization based on Medicare standardized rates. Across the overall screening/surveillance colonoscopy program, these episodes added