Optimizing cytological specimens of EUS-FNA of solid pancreatic lesions: A pilot study to the effect of a smear preparation training for endoscopy personnel on sample quality and accuracy.

BACKGROUND: In the absence of rapid on-side pathological evaluation, endoscopy staff generally "smears" endoscopic ultrasound guided fine needle aspiration (EUS-FNA) specimens on a glass slide. As this technique is vulnerable to preparation artifacts, we assessed if its quality could be improved through a smear-preparation-training for endoscopy staff. METHODS: In this prospective pilot study, 10 endosonographers and 12 endoscopy nurses from seven regional EUS-centers in the Netherlands were invited to participate in a EUS-FNA smear-preparation-training. Subsequently, post training slides derived from solid pancreatic lesions were compared to pre-training "control" slides. Primary outcome was to assess if the training positively affects smear quality and, consequently, diagnostic accuracy of EUS-FNA of solid pancreatic lesions. RESULTS: Participants collected and prepared 71 cases, mostly pancreatic head lesions (48%). Sixty-eight controls were selected from the pretraining period. The presence of artifacts was comparable for smears performed before and after training (76% vs 82%, P = .36). Likewise, smear cellularity (≥50% target cells) before and after training did not differ (44% (30/68) vs 49% (35/71), P = .48). Similar, no difference in diagnostic accuracy for malignancy was detected (P = .10). CONCLUSION: In this pilot EUS-FNA smear-preparation-training for endoscopy personnel, smear quality and diagnostic accuracy were not improved after the training. Based on these results, we plan to further study other training programs and possibilities.

Diagnostic yield and agreement on fine-needle specimens from solid pancreatic lesions : comparing the smear technique to liquid-based cytology.

Background and study aims The traditional "smear technique" for processing and assessing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is sensitive to artifacts. Processing and evaluation of specimens collected in a liquid medium, liquid-based cytology (LBC) may be a solution. We compared the diagnostic value of EUS-FNA smears to LBC in pancreatic solid lesions in the absence of rapid on-site evaluation (ROSE). Patients and methods Consecutive patients who required EUS-FNA of a solid pancreatic lesion were included in seven hospitals in the Netherlands and followed for at least 12 months. Specimens from the first pass were split into two smears and a vial for LBC (using ThinPrep and/or Cell block). Smear and LBC were compared in terms of diagnostic accuracy for malignancy, sample quality, and diagnostic agreement between three cytopathologists. Results Diagnostic accuracy for malignancy was higher for LBC (82 % (58/71)) than for smear (66 % (47/71), P  = 0.04), but did not differ when smears were compared to ThinPrep (71 % (30/42), P  = 0.56) or Cell block (62 % (39/63), P  = 0.61) individually. Artifacts were less often present in ThinPrep (57 % (24/42), P  = 0.02) or Cell block samples (40 % (25/63), P  < 0.001) than smears (76 % (54/71)). Agreement on malignancy was equally good for smears and LBC (ĸ = 0.71 versus ĸ = 0.70, P  = 0.98), but lower for ThinPrep (ĸ = 0.26, P  = 0.01) than smears. Conclusion After a single pass, LBC provides higher diagnostic accuracy than the conventional smear technique for EUS-FNA of solid pancreatic lesions in the absence of ROSE. Therefore, LBC, may be an alternative to the conventional smear technique, especially in centers lacking ROSE.

The incidence and risk factors of metachronous colorectal cancer: an indication for follow-up.

BACKGROUND: Patients with colorectal cancer are at risk for developing metachronous colorectal cancer. The purpose of posttreatment surveillance is to detect and remove premalignant lesions to prevent metachronous colorectal cancer. OBJECTIVE: The aim of this study was to investigate the incidence of and predictive factors for metachronous colorectal cancer in patients with newly diagnosed colorectal cancer. DESIGN AND PATIENTS: The data on all patients with newly diagnosed colorectal cancer between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands and studied for metachronous colorectal cancer. MAIN OUTCOME MEASURES: The annual incidence rate and the standardized incidence ratios were calculated. RESULTS: In total, colorectal cancer was diagnosed in 10,283 patients; there were 39,974 person-years of follow-up. The mean annual incidence rate of metachronous colorectal cancer was 314/100,000 person-years at risk during 10 years of follow-up, corresponding with a mean annual incidence of 0.3% and a cumulative incidence of 1.1% at 3 years, 2.0% at 6 years, and 3.1% at 10 years. The incidence of metachronous colorectal cancer after resection of a first colorectal cancer is significantly higher than the incidence of colorectal cancer in an age- and sex-matched general population (standardized incidence ratio 1.3, 95% CI 1.1-1.5). This difference is especially seen during the first 3 years after first colorectal cancer diagnosis (standardized incidence ratio 1.4, 95% CI 1.1-1.8). The presence of synchronous colorectal cancer was the only significant risk factor for developing metachronous colorectal cancer (relative risk 13.9, 95% CI 4.7-41.0). CONCLUSIONS: Despite the availability of colonoscopy, metachronous colorectal cancer is still seen during follow-up in patients with colorectal cancer; the highest risk is during the first 3 years after initial diagnosis. For this reason, a follow-up colonoscopy is useful at a short-term interval after colorectal cancer diagnosis. The presence of synchronous colorectal cancer at the time of first colorectal cancer diagnosis is the only predictive risk factor for developing metachronous colorectal cancer. Tailored surveillance programs may be considered in patients with a diagnosis of synchronous tumors.

Prevalence and prognosis of synchronous colorectal cancer: a Dutch population-based study.

BACKGROUND: A noticeable proportion of colorectal cancer (CRC) patients are diagnosed with synchronous CRC. Large population-based studies on the incidence, risk factors and prognosis of synchronous CRC are, however, scarce, and are needed for better determination of risks of synchronous CRC in patients diagnosed with colonic neoplasia. METHODS: All newly diagnosed CRC between 1995 and 2006 were obtained from the Rotterdam Cancer Registry in The Netherlands, and studied for synchronous CRC. RESULTS: Of the 13,683 patients diagnosed with CRC, 534 patients (3.9%) were diagnosed with synchronous CRC. The risk of having synchronous CRC was significantly higher in men (OR 1.54, 95% CI 1.29-1.84) and in patients aged >70 years (OR 1.83, 95% CI 1.39-2.40). Synchronous CRC patients had a significantly higher risk of distant metastases (OR 1.69, 95% CI 1.27-2.26). In 34% (184/534) the two tumours were located in different surgical segments. Five-year relative survival of synchronous CRC was similar to patients with solitary CRC after multivariate adjustment for the presence of distant metastases. CONCLUSION: One out of 25 patients diagnosed with CRC presents with synchronous CRC. In the multivariate analysis, survival of patients with synchronous CRC was similar to patients with solitary CRC, when corrected for the presence of distant metastases at first presentation. One third of the synchronous CRC were located in different surgical segments, which stresses the importance of performing total colon examination preferably prior to surgery.

Exposure to colorectal examinations before a colorectal cancer diagnosis: a case-control study.

OBJECTIVES: To assess the prior exposure to colorectal examinations between colorectal cancer (CRC) patients and matched control participants to estimate the effect of these examinations on the development of CRC and to obtain insight into the background incidence of colorectal examinations. METHODS: A population-based case-control study was conducted within the Dutch Integrated Primary Care Information database over the period 1996-2005. All incident CRC cases were matched with up to 18 controls (n=7,790) for age, sex, index date (date of CRC diagnosis) and follow-up before diagnosis. All colorectal examinations performed in symptomatic participants in the period 0.5-5 years before index date were considered in the analyses. RESULTS: Within the source population of 457 024 persons, we identified 594 incident cases of CRC. In the period 0.5-5 years before index date 2.9% (17 of 594) of the CRC cases had undergone colorectal examinations, compared with 4.4% (346 of 7790) in the control population [odds ratio (ORadj): 0.56, 95% confidence interval (CI): 0.33-0.94]. For left-sided CRC, significantly more controls than cases had undergone a colorectal examination (4.7 vs. 2.0%, respectively, ORadj: 0.36, 95% CI: 0.17-0.76), which was not seen for right-sided CRCs (3.3 vs. 3.9%, respectively, ORadj: 0.98, 95% CI: 0.42-2.25). CONCLUSION: Patients diagnosed with CRC were less likely than controls to have had a colorectal examination in previous years, being more pronounced in patients diagnosed with left-sided CRCs. If diagnostic examinations have a similar protective effect as screening examinations, this finding supports the concept that colorectal examination can have a major impact on the reduction of CRC risk.

Risk analyses for screening sigmoidoscopy based on a colorectal cancer (CRC) population.

OBJECTIVE: Although colonoscopy can be effective in the prevention of colorectal cancer (CRC), it requires many endoscopic facilities, has a high patient burden and risk of complications, and it is expensive. The aim of this study was to determine the risk for proximal CRC and to identify subgroups in which screening sigmoidoscopy can be effective. MATERIAL AND METHODS: A database search was carried out on all patients who underwent endoscopy of the lower gastrointestinal (GI) tract between 1997 and 2005. All patients diagnosed with CRC were included. Variables including age, gender and the presence of distal colonic neoplasia were used for risk analyses. RESULTS: In total, 783 patients were diagnosed with CRC. Tumour was located in the proximal colon in 68/255 (27%) of the patients <65 years. Of the patients <65 years, 22% (57/255) had proximal CRC without synchronous distal lesions and would thus have been missed by sigmoidoscopy screening. Among patients >65 years, 41% (216/528) were diagnosed with proximal CRC, significantly more often in women than in men (p <0.001). In 35% of patients (185/528) proximal CRC without distal colonic neoplasia was found, significantly more than in those under 65 years of age (p <0.001). CONCLUSIONS: Significantly more proximal localized CRC would have been missed by sigmoidoscopy screening in elderly patients, especially in women. In subjects <65 years of age, sigmoidoscopy screening allows detection of almost 80% of CRC cases and might suffice as a screening method.

A nationwide survey evaluating adherence to guidelines for follow-up after polypectomy or treatment for colorectal cancer.

BACKGROUND: Endoscopic follow-up (FU) in patients treated for colorectal adenomas or cancer (CRC) is intended to reduce the incidence of CRC. In the Dutch postpolypectomy guidelines, the FU interval is solely determined by the number of previous adenomas, whereas in other countries size and histology are also taken into account. Whether this difference in policy is also reflected in clinical practice is unknown. Furthermore, FU guidelines after CRC are not standardized in The Netherlands, even though national recommendations are available. GOAL: To assess the adherence to the current Dutch postpolypectomy guidelines and to evaluate the FU policy after CRC resection. STUDY: A survey was sent to all Gastrointestinal Departments in The Netherlands. The survey consisted of questions on logistic organization of FU, postpolypectomy FU intervals, and FU after CRC. RESULTS: The response rate was 85%. In contrast to the national guidelines, size and histology of the adenomas were often taken into account, leading to shortening of the FU interval. With respect to the CRC cases, 52% of the respondents advised shorter FU intervals than advised by the national recommendations. CONCLUSIONS: Despite recent Dutch postpolypectomy guidelines, clinicians incorporate histology and size into their clinical strategy. Either further education on the guidelines is needed, or the guidelines need to be reconsidered. Furthermore, evidence-based guidelines for FU after CRC should be formulated.

Tumor pyruvate kinase isoenzyme type M2 and immunochemical fecal occult blood test: performance in screening for colorectal cancer.

OBJECTIVES: Immunochemical fecal occult blood test (FOBT) and determination of tumor pyruvate kinase isoenzyme type M2 (TuM2-PK) in stool samples may be valuable new screening tools for colorectal cancer (CRC). The aim of this study was to compare the accuracy of fecal TuM2-PK testing with immunochemical FOBT in patients with CRC or adenomas. METHODS: A total of 52 patients with CRC were analyzed, 47 with colorectal adenomas, and 63 matched controls with a normal colonoscopy. Nineteen additional patients with inflammatory bowel disease were tested to determine influence of inflammation. Stool samples were analyzed with two immunochemical FOBTs, Immo-care and OC-Light, and with a commercial enzyme-linked immunosorbent assay for TuM2-PK. RESULTS: In patients with CRC, the sensitivity of TuM2-PK, Immo-care and OC-Light was respectively 85, 92 and 94%. In patients with adenomas, the sensitivity was respectively 28, 40 and 34%. Specificity for these tests was 90% for TuM2-PK and 97% for both immunochemical FOBTs. All tests showed a high positivity rate in patients with inflammatory bowel disease (79% for TuM2-PK and Immo-care, and 89% for OC-Light). CONCLUSION: Both immunochemical FOBTs appear valuable and are sensitive tests for CRC screening. TuM2-PK does not have supplemental value for screening for CRC because of a lower sensitivity and specificity. None of these tests is sensitive enough for detection of advanced adenomas. Patients with inflammatory bowel disease should be excluded from CRC screening when using immunochemical FOBT or TuM2-PK.

Attendance at surveillance endoscopy of patients with adenoma or colorectal cancer.

OBJECTIVE: Surveillance of patients treated for adenoma or colorectal cancer (CRC) is intended to reduce the incidence of CRC. Responsibility for the adherence to surveillance advice is often left to the patients and family physician. It is not known whether this type of passive policy affects the efficacy of surveillance. The aim of this study was to determine the yield of surveillance without active invitation to follow-up endoscopy. MATERIAL AND METHODS: The study comprised a cohort follow-up of patients under 75 years of age with adenomas or CRC at index endoscopy in the period 1997-99. Adherence and intervals of follow-up endoscopy were determined up to December 2004. RESULTS: During the inclusion period 2946 patients underwent lower endoscopy. In total, 393 patients were newly diagnosed with colorectal polyps (n=280) or CRC (n=113). Polyps were classified as adenomas in 167/280 (61%) patients. Forty-five (27%) of the adenoma patients underwent surveillance endoscopy within the guideline interval, 63 (38%) underwent delayed endoscopy, and 59 (35%) did not have any follow-up at all. CRC was diagnosed in 113 patients. Thirty-six patients who died during the first year or were diagnosed with metastases were excluded from the analysis. Twenty-three (30%) of the remaining 77 patients underwent endoscopic surveillance according to the guidelines, 40 (52%) had delayed surveillance endoscopy, and 14/77 (18%) did not undergo surveillance endoscopy at all. CONCLUSIONS: In surveillance for colorectal neoplasia, active follow-up invitation is important. Given the low follow-up rate in our series, passive follow-up policies may lead to under-performance of surveillance programs. An active and controlled follow-up is advisable.