Lapo Sali

Efficacy of Computer-aided Detection as a Second Reader for 6–9-mm Lesions at CT Colonography: Multicenter Prospective Trial

PURPOSE To assess the effect of computer-aided detection (CAD) as a second reader on the sensitivity and specificity of computed tomographic (CT) colonography in detecting 6-9-mm colorectal cancer (CRC) lesions. MATERIALS AND METHODS Individuals with clinical indications for colonoscopy--either for symptoms or as part of participating in a surveillance program or CRC screening--were prospectively enrolled at one of 10 academic centers between July 2007 and May 2009. Institutional review board approval was obtained at each clinical site, and all participants provided written informed consent. All participants underwent CT colonography and colonoscopy on the same day. Experienced readers interpreted the CT colonography images unassisted and then reviewed all colorectal lesion-like structures pinpointed by the CAD algorithm. Segmental unblinding of CT colonoscopy findings at colonoscopy was utilized. The sensitivity and specificity of unassisted and CAD-assisted reading in identifying individuals with 6-9-mm lesions were calculated and compared by means of pairwise analysis. RESULTS A total of 618 participants (mean age, 57.9 years; 54.5% male) were included in the final analysis. Of these participants, 464 (75.1%) had no lesions 6 mm or larger, and 52 (8.4%) had 6-9-mm lesions. The sensitivity of CT colonography with unassisted reading and that with CAD-assisted reading in identifying individuals with 6-9-mm lesions was 65.4% (95% confidence interval [CI]: 50.9%, 78.0%) and 76.9% (95% CI: 63.2%, 87.5%; P = .016), respectively. No significant change in specificity was observed: The specificity of CT colonography with unassisted and that with CAD-assisted reading was 91.8% (95% CI: 88.9%, 94.1%) and 90.9% (95% CI: 88.0%, 93.4%; P = .063), respectively. Evaluation of CAD candidates required an additional 1.6 minutes (25th-75th percentile: 1.0 minute to 3.4 minutes). CONCLUSION The addition of CAD to reading performed by experienced readers resulted in a significant benefit in the detection of 6-9-mm polyps at CT colonography in this cohort. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120376/-/DC1.

Reduced and Full-Preparation CT Colonography, Fecal Immunochemical Test, and Colonoscopy for Population Screening of Colorectal Cancer: A Randomized Trial

BACKGROUND Population screening for colorectal cancer (CRC) is widely adopted, but the preferred strategy is still under debate. We aimed to compare reduced (r-CTC) and full cathartic preparation CT colonography (f-CTC), fecal immunochemical test (FIT), and optical colonoscopy (OC) as primary screening tests for CRC. METHODS Citizens of a district of Florence, Italy, age 54 to 65 years, were allocated (8:2.5:2.5:1) with simple randomization to be invited by mail to one of four screening interventions: 1) biennial FIT for three rounds, 2) r-CTC, 3) f-CTC, 4) OC. Patients tested positive to FIT or CTC (at least one polyp ≥6mm) were referred to OC work-up. The primary outcomes were participation rate and detection rate (DR) for cancer or advanced adenoma (advanced neoplasia). All statistical tests were two-sided. RESULTS Sixteen thousand eighty-seven randomly assigned subjects were invited to the assigned screening test. Participation rates were 50.4% (4677/9288) for first-round FIT, 28.1% (674/2395) for r-CTC, 25.2% (612/2430) for f-CTC, and 14.8% (153/1036) for OC. All differences between groups were statistically significant (P = .047 for r-CTC vs f-CTC; P < .001 for all others). DRs for advanced neoplasia were 1.7% (79/4677) for first-round FIT, 5.5% (37/674) for r-CTC, 4.9% (30/612) for f-CTC, and 7.2% (11/153) for OC. Differences in DR between CTC groups and FIT were statistically significant (P < .001), but not between r-CTC and f-CTC (P = .65). CONCLUSIONS Reduced preparation increases participation in CTC. Lower attendance and higher DR of CTC as compared with FIT are key factors for the optimization of its role in population screening of CRC.

Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study)

BackgroundColorectal cancer (CRC) is the most frequent cancer in Europe. Randomized clinical trials demonstrated that screening with fecal occult blood test (FOBT) reduces mortality from CRC. Accordingly, the European Community currently recommends population-based screening with FOBT. Other screening tests, such as computed tomography colonography (CTC) and optical colonoscopy (OC), are highly accurate for examining the entire colon for adenomas and CRC. Acceptability represents a critical determinant of the impact of a screening program. We designed a randomized controlled trial to compare participation rate and diagnostic yield of FOBT, CTC with computer-aided diagnosis, and OC as primary tests for population-based screening.Methods/DesignA total of 14,000 subjects aged 55 to 64 years, living in the Florence district and never screened for CRC, will be randomized in three arms: group 1 (5,000 persons) invited to undergo CTC (divided into: subgroup 1A with reduced cathartic preparation and subgroup 1B with standard bowel preparation); group 2 (8,000 persons) invited to undergo a biannual FOBT for three rounds; and group 3 (1,000 persons) invited to undergo OC. Subjects of each group will be invited by mail to undergo the selected test. All subjects with a positive FOBT or CTC test (that is, mass or at least one polyp ≥6 mm) will be invited to undergo a second-level OC. Primary objectives of the study are to compare the participation rate to FOBT, CTC and OC; to compare the detection rate for cancer or advanced adenomas of CTC versus three rounds of biannual FOBT; to evaluate referral rate for OC induced by primary CTC versus three rounds of FOBT; and to estimate costs of the three screening strategies. A secondary objective of the study is to create a biological bank of blood and stool specimens from subjects undergoing CTC and OC.DiscussionThis study will provide information about participation/acceptability, diagnostic yield and costs of screening with CTC in comparison with the recommended test (FOBT) and OC.Trial registrationClinicalTrials.gov Identifier: NCT01651624.

Computed tomographic colonography in subjects with positive faecal occult blood test refusing optical colonoscopy.

BACKGROUND Refusal of colonoscopy is a drawback of colorectal cancer screening programmes based on faecal occult blood test. Computed-tomographic-colonography is generally more accepted than colonoscopy. AIM To compare adherence to computed-tomographic-colonography and second-invitation colonoscopy in subjects with positive faecal test refusing colonoscopy. METHODS We performed a prospective study in 198 subjects with positive faecal test who refused first referral to colonoscopy in one endoscopy service of the Florence screening programme. Subjects were randomly invited to computed-tomographic-colonography (n = 100) or re-invited to colonoscopy (n = 98). Mail invitation was followed by a questionnaire administered by phone. Computed-tomographic-colonography findings were verified with colonoscopy. RESULTS 32 subjects could not be reached, 71 (35.9%) had undergone colonoscopy on their own; 4 were excluded for contraindications; 30/48 (62.5%) in the computed-tomographic-colonography arm and 11/43 (25.6%) in the colonoscopy arm accepted the proposed examinations (p < 0.001). Four advanced adenomas and 1 cancer were found in the 28 subjects who ultimately underwent computed-tomographic-colonography and 2 advanced adenomas and 2 cancers in the 9 subjects who ultimately underwent second-invitation colonoscopy. CONCLUSION Subjects with positive faecal occult blood test refusing colonoscopy show a higher adherence to computed-tomographic-colonography than to second invitation colonoscopy.

CT colonography before colonoscopy in subjects with positive faecal occult blood test. Preliminary experience.

PurposeWe report a preliminary evaluation of the performance of computed tomography colonography (CTC) systematically obtained before optical colonoscopy (OC) in subjects with positive faecal occult blood test (FOBT) within a population-based screening programme for colorectal cancer (CRC).Materials and methodsSeventy-nine subjects with positive FOBT from a regional screening programme were invited to perform same day CTC and OC. CTC was performed with standard bowel preparation. OC with segmental unblinding was the reference standard. A perpatient per-adenoma analysis was performed.ResultsForty-nine of 79 subjects (62%) with positive FOBT adhered to the study and completed both examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma ≥6 mm. Per-patient sensitivity, specificity, negative predictive value and positive predictive value for cancer or adenoma ≥6 mm were 95.5% (95%CI:77.2%–99.9%), 51.9% (95%CI:32.0%–71.3%), 93.3% (95%CI:68.1%–99.8%) and 61.8% (95%CI:43.6%–77.8%).ConclusionsIn the setting of a FOBT-based screening programme for CRC, CTC showed a high sensitivity, but relatively low specificity and positive predictive value, for cancer and adenoma ≥6 mm. Probably performing CTC without faecal tagging as second line test after a positive FOBT is not a cost-effective strategy.RiassuntoObiettivoValutare la performance della colongrafia TC (CTC) eseguita sistematicamente prima della colonscopia ottica (CO) in soggetti con test del sangue occulto fecale (FOBT) positivo nell’ambito di un programma di screening di popolazione per il cancro colorettale.Materiali e metodiSettantanove soggetti FOBT positivi del programma di screening della regione Toscana sono stati invitati ad eseguire nello stesso giorno la CTC e la CO dopo preparazione intestinale standard (polietilenglicole). Come standard di riferimento è stata utilizzata la CO effettuata con la tecnica del “segmental unblinding”. Sono stati calcolati i valori di sensibilità, specificità, valore predittivo negativo (VPN) e positivo (VPP) per-paziente per-adenoma.RisultatiSu 79 soggetti invitati 49 (62%) hanno accettato di partecipare allo studio. Ventidue soggetti (44,9%) su 49 hanno presentato un cancro o un adenoma ≥6 mm. I valori di sensibilità, specificità, VPN e VPP per-paziente nella detezione di cancri o adenomi ≥6 mm sono risultati rispettivamente del 95,5% (95%CI:77,2%‐99,9%), 51,9% (95%CI:32,0%–71,3%), 93,3% (95%CI:68,1%–99,8%) e del 61,8% (95%CI:43,6%–77,8%).ConclusioniNel contesto di un programma di screening basato sul FOBT, la CTC ha mostrato elevata sensibilità ma bassi valori di specificità e valore predittivo positivo. Probabilmente utilizzare la CTC come test di secondo livello nei soggetti FOBT positivi non è una strategia costo-efficace.

Screen-detected multiple primary lung cancers in the ITALUNG trial

Occurrence of multiple primary lung cancers (MPLC) in individuals undergoing low-dose computed tomography (LDCT) screening has not been thoroughly addressed. We investigated MPLC in subjects recruited in the ITALUNG randomized clinical trial. Cases of cytologically/histologically proven MPLC detected at screening LDCT or follow-up CT were selected and pathologically re-evaluated according to the WHO 2015 classification. Overall 16 MPLC were diagnosed at screening LDCT (n=14, all present at baseline) or follow-up CT (n=2) in six subjects (4 in one subject, 3 in two and 2 in three subjects), representing 0.43% of the 1,406 screenees and 15.8% of the 38 subjects with at least one screen-detected primary lung cancer. MPLC included 9 adenocarcinomas in three subjects and a combination of 7 different tumour histotypes in three subjects. MPLC, mostly adenocarcinomas, are not uncommon in smokers and ex-smokers with at least one LDCT screen detected primary lung cancer.

Circulating tumor cells and microemboli can differentiate malignant and benign pulmonary lesions

The presence of circulating tumor cells (CTC) or microemboli (CTM) in the peripheral blood can theoretically anticipate malignancy of solid lesions in a variety of organs. We aimed to preliminarily assess this capability in patients with pulmonary lesions of suspected malignant nature. We used a cell-size filtration method (ScreenCell) and cytomorphometric criteria to detect CTC/CTM in a 3 mL sample of peripheral blood that was taken just before diagnostic percutaneous CT-guided fine needle aspiration (FNA) or core biopsy of the suspicious lung lesion. At least one CTC/CTM was found in 47 of 67 (70%) patients with final diagnoses of lung malignancy and in none of 8 patients with benign pulmonary nodules. In particular they were detected in 38 (69%) of 55 primary lung cancers and in 9 (75%) of 12 lung metastases from extra-pulmonary cancers. Sensitivity of CTC/CTM presence for malignancy was 70.1% (95%CI: 56.9-83.1%), specificity 100%, positive predictive value 100% and negative predictive value 28.6% (95%CI: 11.9-45.3%). Remarkably, the presence of CTC/CTM anticipated the diagnosis of primary lung cancer in 3 of 5 patients with non-diagnostic or inconclusive results of FNA or core biopsy, whereas CTC/CTM were not observed in 1 patient with sarcoidosis and 1 with amarthocondroma. These results suggest that presently, due to the low sensitivity, the search of CTC/CTM cannot replace CT guided percutaneous FNA or core biopsy in the diagnostic work-up of patients with suspicious malignant lung lesions. However, the high specificity may as yet indicate a role in cases with non-diagnostic or inconclusive FNA or core biopsy results that warrants to be further investigated.

Diffuse Brain Hypoperfusion in Advanced Leukoencephalopathy with Calcifications and Cysts

Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon condition of unknown etiology occurring in children and adults. Pathological findings include obliterative hyalinosis of the small vessels, myelin loss, intense gliosis, Rosenthal fiber formation, microcalcifications, and hemosiderin deposits. Herein we report a 55-year-old man with LCC documented 10 years ago, in whom we examined brain perfusion by pseudocontinuous arterial spin labeling technique. We demonstrated diffused hypoperfusion of the affected white matter (WM) and of the subcortical gray matter (GM) and cortical GM in the patient in comparison to a group of healthy control subjects, using both qualitative evaluation and region of interest analysis. WM and subcortical GM hypoperfusion reflects the known distribution of LCC microangiopathy. We speculate that cortical hypoperfusion may be related to cerebral atrophy or may reflect deafferentation secondary to severe leukoencephalopathy, and may possibly contribute to severe motor and cognitive impairment. Further studies addressing cerebral blood flow in LCC are necessary.

Faecal immunochemical test in subjects not attending screening computed tomography colonography and colonoscopy in a randomized trial

The aim of this study was to evaluate the participation and yield of the faecal immunochemical test (FIT) in nonattendees for computed tomography colonography (CTC) or optical colonoscopy (OC) screening, in the setting of a randomized trial. In the SAVE trial, 16087 individuals were randomly assigned and invited to one of four interventions for colorectal cancer screening: (i) biennial FIT for three rounds; (ii) reduced-preparation CTC; (iii) full-preparation CTC; and (iv) OC. Nonattendees of reduced-preparation CTC, full-preparation CTC and OC groups were invited to FIT. Here, we analysed the participation rate and the detection rate for cancer or advanced adenoma (advanced neoplasia) of FIT among nonattendees for reduced-preparation CTC, full-preparation CTC and OC. Nonattendees were 1721 of 2395 (71.9%) eligible invitees in the reduced-preparation CTC group, 1818 of 2430 (74.8%) in the full-preparation CTC group and 883 of 1036 (85.2%) in the OC group. Participation rates for FIT were 20.2% (347/1721) in nonattendees for reduced-preparation CTC, 21.4% (389/1818) in nonattendees for full-preparation CTC and 25.8% (228/883) in nonattendees for OC. Differences between both CTC groups and the OC group were statistically significant (P⩽0.01), whereas the difference between reduced-preparation and full-preparation CTC groups was not statistically significant (P=0.38). The detection rate of FIT was not statistically significantly different among nonattendees for reduced-preparation CTC (0.9%; 3/347), nonattendees for full-preparation CTC (1.8%; 7/389) and nonattendees for OC (1.3%; 3/228) (P>0.05). Offering FIT to nonattendees for CTC or OC increases the overall participation in colorectal cancer screening and enables the detection of additional advanced neoplasia.

Computer-based self-training for CT colonography with and without CAD

ObjectivesTo determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning.MethodsInstitutional review board approval and patients’ informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres. After an introductory course, readers performed a baseline assessment test (37 cases) using CAD as second reader. Then they were randomized (1:1) to perform either a computer-based self-training (150 cases verified at colonoscopy) with CAD as second reader or the same training without CAD. The same assessment test was repeated after completion of the training programs. Main outcome was per lesion sensitivity (≥ 6 mm). A generalized estimating equation model was applied to evaluate readers’ performance and the impact of CAD use during training.ResultsAfter training, there was a significant improvement in average per lesion sensitivity in the unassisted phase, from 74% (356/480) to 83% (396/480) (p < 0.001), and in the CAD-assisted phase, from 83% (399/480) to 87% (417/480) (p = 0.021), but not in average per patient sensitivity, from 93% (390/420) to 94% (395/420) (p = 0.41), and specificity, from 81% (260/320) to 86% (276/320) (p = 0.15). No significant effect of CAD use during training was observed on per patient sensitivity and specificity, nor on per lesion sensitivity.ConclusionsA computer-based self-training program for CTC improves readers’ per lesion sensitivity. CAD as second reader does not have a significant impact on learning if used during training.Key Points• Computer-based self-training for CT colonography improves per lesion sensitivity of novice readers.• Self-training program does not increase per patient specificity of novice readers.• CAD used during training does not have significant impact on learning.