Intensified Total Neoadjuvant Therapy in Patients With Locally Advanced Rectal Cancer: A Phase II Trial.

AIMS: We assessed the efficacy and safety of total neoadjuvant therapy, including targeted agent plus FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) induction chemotherapy followed by intensified chemoradiotherapy (CRT) and surgical resection, in patients with locally advanced rectal cancer. MATERIALS AND METHODS: This was a single-arm, single-centre phase II trial. Eligible patients had non-metastatic locally advanced rectal adenocarcinoma. Based on Ras-BRAF status, patients were treated with bevacizumab (mutated Ras-BRAF) or panitumumab/cetuximab (wild-type Ras-BRAF) plus FOLFOXIRI regimen followed by oxaliplatin-5-fluorouracil-based CRT and surgery. The primary end point was pathological complete response rate. Secondary end points were toxicity, compliance, tumour downstaging, complete resection, surgical complications, local and distant failures and overall survival. The sample size was planned to expect an absolute 20% improvement in pathological complete response rate over historical literature data with an α error of 0.05 and a power of 80%. RESULTS: Between October 2015 and September 2019, 28 patients (median age 66 years) were enrolled. All patients had regional lymph node involvement at diagnosis. FOLFOXIRI plus bevacizumab was administered in 11 mutated Ras-BRAF patients, whereas the 17 wild-type Ras-BRAF patients received FOLFOXIRI plus panitumumab/cetuximab. Overall, total neoadjuvant therapy was well tolerated and 26 patients (92.9%) completed the programmed strategy. A complete response was achieved in nine cases (32.1%) and a nearly pathological complete response (ypT1 ypN0) in two patients (7.2%). There was no evidence of febrile neutropenia and no grade 4 adverse events were recorded. Radical resection was achieved in all cases. CONCLUSION: FOLFOXIRI plus targeted agent-based induction chemotherapy and intensified CRT before surgery showed promising clinical activity and was well tolerated in locally advanced rectal cancer patients. This phase II trial provides a strong rationale for phase III studies.

Bowel cleansing before CT colonography: comparison between two minimal-preparation regimens.

AIM: To compare two regimens of reduced bowel preparation and faecal tagging for CT colonography. MATERIALS AND METHODS: Single centre, prospective, randomized, noninferiority study, in which 52 consecutive adults underwent routine CT colonography. Patients, following a three-day low-fibre diet, received one of the two reduced preparations: 1-L polyethylene glycol and four tablets of bisacodyl in association with 90 mL of Iopamidol for faecal tagging administered on the same day as CTC examination (group 1); or a standard "iodine-only" preparation, consisting in 180 ml of Iopamidol the day before the examination (group 2). Primary outcome was the overall quality of bowel preparation. RESULTS: Twenty-six patients per group were included. Per segment analysis showed preparation of diagnostic quality in 97.4% of segments in group 1 and in 95.5% in group 2 (p = ns). Per-patient analysis showed optimal quality of preparation in 76.9% of patients in group 1 and in 84.6% in group 2 (p = ns). Patient tolerability to both preparations was not different. CONCLUSION: A limited bowel preparation consisting of 1-L PEG and four tablets of bisacodyl in association with 90 mL of Iodine for faecal tagging administered on the same day as CTC examination is feasible and offers bowel cleansing comparable to "iodine-only" preparation. KEY POINTS: • Low-dose PEG bisacodyl and Iopamidol preparation is feasible, providing adequate bowel cleansing. • Faecal tagging is not different from the two limited preparations. • Patient tolerability to the two colon cleansing regimens is similar.

Gallbladder and muscular endometriosis: a case report.

A 55-year-old woman referred to Radiology Department, with abdominal mass and chronic indefinite and vague abdominal pain, most severe in right hypochondrium and accentuated during menstruation. A history of two cesarean sections was revealed. The patient underwent an ultrasound and Computed Tomography with intravenous contrast media revealing the presence of gallbladder and abdominal wall hyperenhancing masses. Finally, Magnetic Resonance study with intravenous administration of paramagnetic contrast media confirmed the involvement of gallbladder by a solid tissue and the presence of a solid nodule on the abdominal wall. Considering imaging features and the contrast enhancement of the nodules, the patient was sent to surgery. Surgical removal of both gallbladder and abdominal solid implant was performed and histology confirmed the diagnosis of gallbladder and abdominal wall endometriosis.

Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion-weighted imaging.

Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment.

High positive predictive value of CT colonography in a referral centre.

AIM: To assess the positive predictive value (PPV) of CTC in the clinical routine of a dedicated referral centre. MATERIAL AND METHODS: All consecutive patients referred for CTC between May 2009 and May 2010 were considered for inclusion in this study. All the patients who, following the diagnosis of a>6 mm polyp or mass at CTC, underwent a post-CTC colonoscopy within eight weeks from diagnosis were included. Per patient PPV for lesions, adenomas and advanced neoplasia was calculated. Chi-square test was used for statistical comparison, and a p value<0.05 was considered to be statistically significant. RESULTS: 516 patients were included in the study. Of them, 76 (14%) patients had at least one lesion≥6 mm on CTC. Overall, 59 (11%) patients were diagnosed at CTC with at least one polyp, 12 (2%) with a flat lesions, and 5 (1%) with a mass. Per-patient PPVs for any lesion>6 mm, neoplasia, and advanced neoplasia were 96% (95% CI: 92-100%), 68.4% (95% CI: 58-79%), and 30% (95% CI: 20-41%), respectively. PPV for neoplasia and advanced neoplasia was substantially higher for >10 mm lesions. CONCLUSION: In dedicated centers, CTC appears to be a highly specific procedure, characterized by a very low rate of false-positive results for >6 mm lesions.

Diagnostic accuracy of translucency rendering to differentiate polyps from pseudopolyps at 3D endoluminal CT colonography: a feasibility study.

PURPOSE: The aim of this study was to assess the accuracy of translucency rendering (TR) in computed tomographic (CT) colonography without cathartic preparation using primary 3D reading. MATERIALS AND METHODS: From 350 patients with 482 endoscopically verified polyps, 50 pathologically proven polyps and 50 pseudopolyps were retrospectively examined. For faecal tagging, all patients ingested 140 ml of orally administered iodinated contrast agent (diatrizoate meglumine and diatrizoate sodium) at meals 48 h prior to CT colonography examination and two h prior to scanning. CT colonography was performed using a 64-section CT scanner. Colonoscopy with segmental unblinding was performed within 2 weeks after CT. Three independent radiologists retrospectively evaluated TRCT clonographic images using a dedicated software package (V3D-Colon System). To enable size-dependent statistical analysis, lesions were stratified into the following size categories: small (< or =5 mm), intermediate (6-9 mm), and large (> or =10 mm). RESULTS: Overall average TR sensitivity for polyp characterisation was 96.6%, and overall average specificity for pseudopolyp characterisation was 91.3%. Overall average diagnostic accuracy (area under the curve) of TR for characterising colonic lesions was 0.97. CONCLUSIONS: TR is an accurate tool that facilitates interpretation of images obtained with a primary 3D analysis, thus enabling easy differentiation of polyps from pseudopolyps.

Systematic review: distribution of advanced neoplasia according to polyp size at screening colonoscopy.

BACKGROUND: The impact of not referring sub-centimetre polyps identified at CT colonography upon the efficacy of colorectal cancer screening remains uncertain. AIM: To determine the distribution of advanced neoplasia according to polyp size in a screening setting. METHODS: Published studies reporting the distribution of advanced adenomas in asymptomatic screening cohorts according to polyp size were identified by MEDLINE and EMBASE searches. Predefined outputs were the screening rates of advanced adenomas represented by diminutive (< or =5 mm), small (6-9 mm), sub-centimetre (<10 mm) and large (> or =10 mm) polyp sizes. RESULTS: Data from four studies with 20 562 screening subjects met the primary inclusion criteria. Advanced adenomas were detected in 1155 (5.6%) subjects (95% CI = 5.3-5.9), corresponding to diminutive, small and large polyps in 4.6% (95% CI = 3.4-5.8), 7.9% (95% CI = 6.3-9.4) and 87.5% (95% CI = 86-89.4) of cases respectively. The frequency of advanced lesions among patients whose largest polyp was diminutive, small, sub-centimetre and large in size was 0.9%, 4.9%, 1.7% and 73.5% respectively. CONCLUSIONS: Based on this systematic review, a 6-mm polyp size threshold for polypectomy referral would identify over 95% of subjects with advanced adenomas, whereas a 10-mm threshold would identify 88% of cases.

Cost-effectiveness of early colonoscopy surveillance after cancer resection.

BACKGROUND: Short-interval surveillance colonoscopy at 1 year has been recently recommended following curative-intent surgery for colorectal cancer. However, the efficacy and cost-effectiveness of this endoscopic strategy is largely unknown. AIM: To assess the clinical and economic impact of early surveillance post-surgical colonoscopy at 1 year in relation to the detection of metachronous colorectal cancer. METHODS: A decision analysis model was constructed in order to compare a strategy of 1-year endoscopic surveillance versus no early endoscopy following surgical resection for colorectal cancer. A 2-year cancer upstaging was modelled in order to simulate cancer progression in patients with metachronous colorectal cancer who were not referred to early endoscopy. Endoscopic prevalence of metachronous colorectal cancer was estimated from a previous pooled data analysis based on systematic review of the literature. Costs of colonoscopy and cancer care were estimated from Medicare reimbursement data. Outcome measures were the number of early colonoscopies needed to detect one case of cancer or to prevent one cancer-related death and the incremental cost-effectiveness ratio. RESULTS: The number of early 1-year colonoscopies needed to detect one colorectal cancer and to prevent one colorectal cancer-related death was 143 and 926, respectively. The incremental cost-effectiveness ratio of the early 1-year colonoscopy as compared to a policy of not performing it was $40,313 per life-year gained. The incremental cost-effectiveness ratio of performing early surveillance colonoscopy was sensitive to the changes in cancer prevalence. However, only a reduction from the baseline value of 0.7% to 0.19% was associated with an incremental cost-effectiveness ratio higher than $150,000. Other assumptions about cancer upstaging, initial distribution of cancer, and costs had a lesser influence on incremental cost-effectiveness ratio differences. CONCLUSIONS: Our study shows that the recently recommended short-interval 1-year surveillance colonoscopy following colorectal cancer resection is a clinically efficient and cost-effective strategy in terms of cancer detection and cancer-specific death prevention.

CT colonography with reduced bowel preparation after incomplete colonoscopy in the elderly.

We prospectively assessed the feasibility and acceptance of computerized tomographic colonography (CTC) without bowel cathartic preparation in elderly patients after incomplete colonoscopy. A total of 136 patients underwent CTC without cathartic preparation. The time delay between conventional colonoscopy and CTC ranged between 3 and 20 days, depending on the clinical situation. Before CTC, fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals. CTCs were interpreted using a primary two-dimensional (2D) approach and 3D images for further characterization. Patients were interviewed before and 2 weeks after CTC to assess preparation acceptance. CTC was feasible and technically successful in all the 136 patients. Fecal tagging was judged as excellent in 113 (83%) patients and sufficient in 23 (17%). Average CT image interpretation time was 14.8 min. Six (4.4%) cases of colorectal cancer and nine (6.6%) large polyps were detected, as well as 23 (11.3%) extracolonic findings of high clinical importance. No major side effect occurred, although 25% patients reported minor side effects, especially diarrhea. Overall, 76/98 patients replied that they would be willing to repeat the test if necessary. CTC without cathartic preparation is a technically feasible and safe procedure to complete a colonic study in the elderly, prompting its use in clinical practice.

Q&A on diagnosis, screening and follow-up of colorectal neoplasia.

The impressive and brisk evolution of medical science prevents many physicians from a thorough update on all the research fields. Colorectal cancer diagnosis, screening and follow-up is well known to require a multi-disciplinary approach, as it is faced by several specialties such as primary care physicians, gastroenterologists, non-gastroenterologist internists, radiologists and surgeons. To address this issue in a mutual perspective, we focused on the main points of the epidemiology, diagnosis, screening and follow-up of colorectal neoplasia by using a simple "Question & Answers" structure.

Projected impact of colorectal cancer screening with computerized tomographic colonography on current radiological capacity in Europe.

BACKGROUND: The impact of a primary colorectal cancer screening with computerized tomographic colonography on current radiological capacity is unknown. The multispecialty needs for computerized tomographic examinations raise some doubts on the feasibility of a mass colorectal cancer screening with computerized tomographic colonography. AIM: To assess whether the number of available computerized tomographic units in Europe is adequate to cover population screening with computerized tomographic colonography. METHODS: A mathematical and a Markov model were, respectively, used to assess the number of computerized tomographic colonography procedures needed to be performed each day in the start-up and in the steady-state phases of a colorectal cancer screening programme in Europe. Such outcome was divided for the total number of computerized tomographic machines aged <10 years estimated to be present in the European hospitals. RESULTS: At a simulated 30% compliance, 28 760 130 European people would need to be screened by the 3482 available computerized tomographic units in a 5-year start-up period, corresponding to 6.6 CTC/CT unit/day. Assuming a 10-year repetition of computerized tomographic colonography between 50 and 80 years, the number of computerized tomographic colonography needed to be performed in the steady-state period appeared to be 4.3/CT unit/day. CONCLUSIONS: The current radiological capacity may cover the need for a primary colorectal cancer screening with computerized tomographic colonography in a steady state. On the other hand, a substantial implementation of the current computerized tomographic capacity or a synergistic approach with other techniques seems to be necessary for the start-up period.

Anatomical variations of the coeliac trunk and the mesenteric arteries evaluated with 64-row CT angiography.

PURPOSE: This study was undertaken to evaluate the accuracy of 64-row computed tomography angiography (CTA) in the study of vascular anatomy by assessing the incidence of anatomical variations of the origin of the coeliac trunk, mesenteric arteries and collateral branches. MATERIALS AND METHODS: Sixty patients were evaluated with 64-row CTA (VCT, General Electric Healthcare, Milwaukee, WI, USA) with a collimation of 0.625 mm after the injection of iodinated nonionic contrast material (4 ml/s). Exclusion criteria were the presence of any pathological condition likely to affect normal vascular anatomy. RESULTS: The coeliac trunk had a normal trifurcation in 56.7% of cases. The common hepatic artery was normal in 60% of patients. The inferior pancreaticoduodenal arteries were either absent or not assessable in 8.3% of cases and there was a double trunk in 5%, a common trunk in 83.3% and a single vessel in 3.3%. The number of jejunal and ileal arteries ranged from a minimum of six to a maximum of 13 (mean value 8.7+/-1.34). The Riolan arcade was assessable in 31.7% and developed in 68.4% of these. CONCLUSIONS: The 64-row CTA enables visualisation of small vessels and accessory arteries that are difficult to identify with other techniques. The technique's high sensitivity allowed us to observe that the prevalence of vascular abnormalities is higher than that reported in the literature.

Colon cancer prevention in Italy: cost-effectiveness analysis with CT colonography and endoscopy.

BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality in Italy. Although prevention of CRC is possible, its cost-effectiveness when applied to the Italian population is unknown. Recently, computerized tomographic colonography (CTC) has been proposed for CRC screening. AIM: To compare the efficacy and cost-effectiveness of CTC screening in a simulated Italian population with those of colonoscopy and flexible sigmoidoscopy (FS). METHODS: The cost-effectiveness of different screening strategies was compared using a Markov process computer model, in which in a hypothetical population of 100,000 50 year-olds were investigated by CTC, colonoscopy or FS every decade. Outcomes were projected to the Italian national level. RESULTS: CRC incidence reduction was calculated at 40.9%, 38.2%, and 31.8% with colonoscopy, CTC and FS, respectively. As compared to no screening, all screening programs were shown to be cost-saving, allowing a saving of 11 Euro, 17 Euro, and 48 Euro per person with colonoscopy, FS and CTC, respectively. FS appeared to be less cost-effective than CTC, whilst colonoscopy appeared to be an expensive option as compared to CTC. Undiscounted national expenditure was calculated to be 1,042,489,512 Euro, 1,093,268,285 Euro, and 1,198,783,428 Euro for FS, CTC and colonoscopy, respectively, as compared to 695,818,078 Euro without screening. CONCLUSION: CRC screening is cost-saving in Italy, irrespective of the technique applied. CTC appeared to be more cost-effective than FS, and it may also become a valid alternative to colonoscopy.

3D CT protocol in the assessment of the esophageal neoplastic lesions: can it improve TNM staging?

The purpose of this prospective observational study was the evaluation of the usefulness of MPR reconstructions and virtual endoscopy in the study of the esophageal carcinoma. Thirty-nine patients with esophageal cancer proved by means of endoscopy, underwent preoperative TNM staging with dynamic CT of the chest and abdomen with the aid of 3D rendering. Twenty-six patients underwent surgery, and the CT results were compared with histopathologic findings. In staging the T parameter, the CT with 3D reconstructions and virtual endoscopy, showed a sensitivity of 92% and an accuracy of 88%. In staging lymph nodes, the sensitivity in our study was 85%, the specificity 58%, and the accuracy 69%. Our protocol of the study of the esophageal cancer with 3D CT and virtual endoscopy, demonstrated a high concordance with the surgical and pathologic findings. The 3D reconstructed images were very helpful to the surgeons regarding preoperative planning. We performed an observational enquiry, and although this was a small study, it has, however, confirmed that the 3D imaging of the esophagus represents a valuable advantage to conventional imaging. Further studies with a larger number of patients are needed to prove its superiority to traditional CT imaging of the esophagus.

Pre-operative assessment of extramural invasion and sphincteral involvement in rectal cancer by magnetic resonance imaging with phased-array coil.

OBJECTIVE: Pre-operative staging of rectal cancer should identify patients with extrarectal spread, who might benefit from pre-operative radiotherapy, and patients with minimal sphincteral involvement, who can avoid permanent colostomy. The aim of this study was to assess the accuracy of Magnetic Resonance Imaging (MRI) to predict tumour stage and sphincter status. PATIENTS AND METHODS: Thirty-three patients with a rectal tumour were pre-operatively assessed by MRI with a phased-array coil. Imaging results were correlated with the final pathological findings. RESULTS: The overall accuracy of pre-operative staging with MRI was 88% (k = 0.75) for extramural tumour invasion and 59% (k = 0.26) for lymph node metastases. MRI correctly evaluated the infiltration of the anal sphincters in 87% of patients (7 of 8 patients with low rectal tumour). CONCLUSION: MRI provides the surgeon with valuable information regarding extramural tumour spread and sphincteral involvement, enabling appropriate selection of patients for pre-operative adjuvant therapy or sphincter-saving surgery.

Magnetic Resonance Imaging of the anal canal using high resolution sequences and phased array coil: visualization of anal sphincter complex.

PURPOSE: To assess the normal anatomy of the anal sphincter complex using high-resolution MR imaging with phased -array coil. MATERIAL AND METHODS: Twenty patients, 13 males and 7 females, ranging in age between 27 and 56 years underwent MRI evaluation of the pelvic region, using a superconductive 1.5 T magnet (maximum gradient strength, 25 mT/m; minimum rise time 600 microseconds, equipped with phased-array coil. High-resolution T2-weighted Turbo Spin Echo sequences (TR, 4055 ms; TE, 132 ms; matrix 390x512; in-plane resolution, 0.67x0.57 mm) were acquired on multiple axial, sagittal and coronal planes. Images were reviewed by two experienced gastrointestinal radiologists in order to evaluate the normal anal sphincter complex. RESULTS: Optimal image quality of the anal sphincter complex was obtained in all cases. Different muscular layers were observed between the upper and lower aspects of the anal canal. In the lower part of the anal canal, internal and external sphincter muscles could be observed; in the upper part, puborectal and internal sphincter muscles were depicted. Good visualization of intersphincteric space, levator ani muscle and ischioanal space was also obtained in all cases. CONCLUSIONS: High-resolution MR images with phased-array coil provide optimal depiction of the anal canal and the anal sphincter complex.