Traditional Serrated Adenomas on CT Colonography: International Multicenter Experience With This Rare Colorectal Neoplasm.

OBJECTIVE. Serrated polyps include hyperplastic polyps, sessile serrated polyps, and traditional serrated adenomas (TSAs). Hyperplastic polyps and sessile serrated polyps account for approximately 99% of all serrated lesions; TSAs are rare. However, both sessile serrated polyps and TSAs are now recognized as precursor lesions to carcinogenesis, representing approximately one-fourth of all sporadic colorectal cancers. We report what is, to our knowledge, the first series describing the characteristics of CTAs on CT colonography (CTC). MATERIALS AND METHODS. An international, multicenter, retrospective review of CT colonography-detected TSAs diagnosed between 2008 and 2018 was conducted. Data collected included patient demographics and data from CTC, optical colonoscopy, and pathologic analysis. RESULTS. A total of 67 proven TSAs in 58 patients (mean age, 67 years) were identified. The majority (66%) were located in the distal colon (descending colon, sigmoid colon, and rectum), and their mean size was 19 mm (range, 3-80 mm). Small (< 10 mm) TSAs typically had a simple sessile or pedunculated morphologic appearance, whereas large (≥ 10 mm) TSAs tended to be more lobulated and irregular, pedunculated, or carpetlike. The majority (88%) showed at least some contrast medium surface coating. CONCLUSION. We report what we believe to be the first multicenter experience describing the characteristics of TSAs on CTC. Unlike sessile serrated lesions, TSAs are more often left-sided and tend to be more lobulated and irregular. However, like sessile serrated polyps, most TSAs show contrast medium surface coating. Detection of these rare lesions on CTC is important, given their malignant potential.

Validation of a motion-robust 2D sequential technique for quantification of hepatic proton density fat fraction during free breathing.

BACKGROUND: Current chemical-shift-encoded (CSE) MRI techniques for measuring hepatic proton density fat fraction (PDFF) are sensitive to motion artifacts. PURPOSE: Initial validation of a motion-robust 2D-sequential CSE-MRI technique for quantification of hepatic PDFF. STUDY TYPE: Phantom study and prospective in vivo cohort. POPULATION: Fifty adult patients (27 women, 23 men, mean age 57.2 years). FIELD STRENGTH/SEQUENCE: 3D, 2D-interleaved, and 2D-sequential CSE-MRI acquisitions at 1.5T. ASSESSMENT: Three CSE-MRI techniques (3D, 2D-interleaved, 2D-sequential) were performed in a PDFF phantom and in vivo. Reference standards were 3D CSE-MRI PDFF measurements for the phantom study and single-voxel MR spectroscopy hepatic PDFF measurements (MRS-PDFF) in vivo. In vivo hepatic MRI-PDFF measurements were performed during a single breath-hold (BH) and free breathing (FB), and were repeated by a second reader for the FB 2D-sequential sequence to assess interreader variability. STATISTICAL TESTS: Correlation plots to validate the 2D-sequential CSE-MRI against the phantom and in vivo reference standards. Bland-Altman analysis of FB versus BH CSE-MRI acquisitions to evaluate robustness to motion. Bland-Altman analysis to assess interreader variability. RESULTS: Phantom 2D-sequential CSE-MRI PDFF measurements demonstrated excellent agreement and correlation (R2 > 0.99) with 3D CSE-MRI. In vivo, the mean (±SD) hepatic PDFF was 8.8 ± 8.7% (range 0.6-28.5%). Compared with BH acquisitions, FB hepatic PDFF measurements demonstrated bias of +0.15% for 2D-sequential compared with + 0.53% for 3D and +0.94% for 2D-interleaved. 95% limits of agreement (LOA) were narrower for 2D-sequential (±0.99%), compared with 3D (±3.72%) and 2D-interleaved (±3.10%). All CSE-MRI techniques had excellent correlation with MRS (R2 > 0.97). The FB 2D-sequential acquisition demonstrated little interreader variability, with mean bias of +0.07% and 95% LOA of ± 1.53%. DATA CONCLUSION: This motion-robust 2D-sequential CSE-MRI can accurately measure hepatic PDFF during free breathing in a patient population with a range of PDFF values of 0.6-28.5%, permitting accurate quantification of liver fat content without the need for suspended respiration. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1578-1585.

Neither FDG-PET Nor CT can distinguish between a pathological complete response and an incomplete response after neoadjuvant chemoradiation in locally advanced rectal cancer: a prospective study.

OBJECTIVE: To prospectively compare the ability of flourodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) to identify a pathological complete response (pCR) in patients with rectal cancer treated by chemoradiation. BACKGROUND: A major obstacle in pursuing nonoperative management in patients with rectal cancer after chemoradiation is the inability to identify a pCR preoperatively. METHODS: A total of 121 patients with rectal cancer were prospectively enrolled. FDG-PET scans and helical CT scans were obtained before and after neoadjuvant chemoradiation. Consensus readings of PET and CT scans were used to classify certainty of disease (5-point confidence rating scale). The ability of PET and CT scans to accurately distinguish a pCR (ypT0) from an incomplete response (ypT1-4) was estimated using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 121 patients, 26 (21%) had a pCR. PET and CT scans were equally inadequate at distinguishing a pCR from an incomplete response (AUC = 0.64 for both, P = 0.97). Among the 26 patients with a pCR, 14 (54%) and 5 (19%) were classified as complete responders on PET and CT scans, respectively. Among the 95 patients with an incomplete pathological response, 63 (66%) and 90 (95%) were classified as incomplete responders on PET and CT scans, respectively. None of the individual PET parameters, including visual response score, mean standard uptake value (SUVmean), maximum SUV (SUVmax), and total lesion glycolysis, accurately distinguished a pCR (AUCs = 0.57-0.73). CONCLUSIONS: Neither PET nor CT scans have adequate predictive value to be clinically useful in distinguishing a pCR from an incomplete response and, therefore, should not be obtained for the purpose of attempting to predict a pCR after neoadjuvant chemoradiation for rectal cancer.

Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy.

INTRODUCTION: Nonoperative management (NOM) of rectal cancer after a complete clinical response (cCR) to neoadjuvant therapy is controversial. In this article, we retrospectively reviewed the outcomes of patients managed with selective NOM after a cCR to neoadjuvant treatment and compared these with patients who underwent standard rectal resection with a pathological complete response (pCR). METHODS: Patients completing neoadjuvant chemoradiotherapy (CRT) for stage I to III rectal cancer between January 2006 and August 2010 were retrospectively reviewed. Median follow-up was calculated in months after completion of CRT. RESULTS: Thirty-two patients (median follow-up 28 months) were treated by NOM after a cCR. Among 265 treated by CRT and rectal resection, 57 patients (22%) had a pCR and formed the control group (median follow-up 43 months). Factors associated with selective use of NOM included lower pretreatment stage, older age, and distal tumor location (P < 0.05). In the NOM group, 6 recurred locally (median 11 months, range 7-14), 3 of whom also had concurrent distant recurrence. All 6 local failures were controlled by salvage rectal resection with no further local recurrence of disease (median follow-up 17 months). In the rectal resection/pCR group, there were no local failures. The 2-year distant disease-free survival (88% vs 98%, P = 0.27) and overall survival (96% vs 100%, P = 0.56) were similar for NOM and rectal resection/pCR groups. CONCLUSIONS: Rectal resection was successfully avoided in 81% of patients selected for NOM. When combined with salvage surgery, NOM appears to achieve similar local and distant disease control compared with patients with a pCR treated by rectal resection. Longer follow-up and prospective trials are warranted to evaluate this promising treatment option.

Hypoxia-related proteins in patients with rectal cancer undergoing neoadjuvant combined modality therapy.

BACKGROUND: We have previously demonstrated the prognostic significance of rectal cancer pathologic response to neoadjuvant chemoradiation. Recent studies in other cancers have reported that hypoxia influences response to neoadjuvant chemoradiation. OBJECTIVE: This study aimed to 1) characterize hypoxia-related protein expression in locally advanced rectal cancer before neoadjuvant chemoradiation, 2) determine the comodulation of hypoxia-related protein expression, and 3) evaluate the relationship between hypoxia-related protein expression and overall survival, time to recurrence, and tumor regression grade. DESIGN: Immunohistochemical analysis of 4 hypoxia-related proteins (HIF-1α, CA-IX, VEGF, and GLUT-1) was performed on archival pretreatment rectal cancer biopsies. PATIENTS: : Eighty-five patients with locally advanced rectal cancer treated with neoadjuvant radiation and 5-fluorouracil-based chemotherapy were included. MAIN OUTCOME MEASURES: The impact of hypoxia-related protein expression on outcome was evaluated by use of Cox proportional hazards model. Hypoxia-related protein expression was correlated with tumor regression grade by use of Spearman correlation coefficients. RESULTS: Median follow-up was 54 months. CA-IX expression was associated with overall survival (p = 0.01). HIF-1α expression was weakly correlated with VEGF (r = 0.26, p = 0.02) and GLUT-1 (r = 0.35, p = 0.001). Hypoxia-related protein expression was not associated with time to recurrence or Mandard tumor regression grade. CONCLUSIONS: Elevated CA-IX expression may be associated with poorer overall survival in locally advanced rectal cancer treated by neoadjuvant chemoradiation and resection. The expression of the hypoxia-related proteins HIF-1α, VEGF, and GLUT-1 may be comodulated in locally advanced rectal cancer. Further studies are needed to evaluate the mechanisms governing hypoxia regulation and the role of hypoxia in rectal cancer response to neoadjuvant chemoradiation.

FDG-PET assessment of rectal cancer response to neoadjuvant chemoradiotherapy is not associated with long-term prognosis: a prospective evaluation.

BACKGROUND: At present there is no defined role for routine FDG-PET in the preoperative evaluation of nonmetastatic rectal cancer. OBJECTIVE: The primary objective of this study was to evaluate the ability of FDG-PET to predict long-term prognosis based on the response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. DESIGN: This was a prospective study. SETTINGS: This study was performed at an academic, tertiary care, comprehensive cancer center. PATIENTS: One hundred twenty-seven patients with locally advanced rectal cancer were enrolled between September 1999 and December 2005. INTERVENTIONS: All patients underwent FDG-PET scans before and after neoadjuvant chemoradiotherapy. MAIN OUTCOME MEASURES: FDG-PET parameters were evaluated by at least 2 study board-certified nuclear medicine physicians, and included mean standard uptake value, maximum standard uptake value, total lesion glycolysis, and visual response score. The main outcome measures were time to recurrence and disease-specific survival. RESULTS: Of 127 patients, 82 (65%) were men, the median age was 60 years (range, 27-82), 110 patients had stage II/III disease, and 17 patients had stage IV disease. Median follow-up among survivors was 77 months (range, 1-115 months). Nine patients had unresectable metastatic disease and were excluded from the time-to-recurrence analysis. At 5 years, 74% (95% CI = 66%-81%) of patients had not had recurrences (locally and/or distantly). The 5-year disease-specific survival was 89% (95% CI = 81%-93%). On univariate analysis, visual response score and time to recurrence came closest to having an association (HR = 0.83, 95% CI = 0.68-1.01, p = 0.06). On multivariate analysis, the visual response score was not significant (p = 0.85). No FDG-PET parameter was associated with disease-specific survival. CONCLUSIONS: Assessment of rectal cancer response to neoadjuvant chemoradiotherapy by FDG-PET provides no prognostic information. Therefore, serial FDG-PET before and after neoadjuvant chemoradiotherapy should not be performed for this purpose.

p27 expression in post-treatment rectal cancer: a potential novel approach for predicting residual nodal disease.

BACKGROUND: Expression profiles of p21, p27, p53, Ki-67, and thymidylate synthase may be associated with response to neoadjuvant chemoradiation. The relationship between post-treatment protein expression and regional lymph node involvement has not been fully explored. METHODS: Tumor cores from 126 rectal cancer patients underwent immunohistochemical analysis for the aforementioned proteins. Staining indices (SIs) using percentage of stained cells and staining intensity were calculated for 10 tumor cores per patient. SI for each marker was compared between node negative and node positive patients. RESULTS: Twenty-six (20.6%) cancer patients had a pathologic complete response and 37 had inadequate tissue or cancer cells, leaving 63 for analysis. Thirty-seven (58.7%) cancer patients were node negative and 26 (41.3%) were node positive. There was an association between increased p27 SI and nodal positivity (P = .04). CONCLUSION: Increased p27 expression in post-treatment rectal cancer is associated with nodal positivity and may determine which patients are suitable for local excision.

Pilot study of PET imaging of 124I-iodoazomycin galactopyranoside (IAZGP), a putative hypoxia imaging agent, in patients with colorectal cancer and head and neck cancer.

BACKGROUND: Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging. METHODS: Ten patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake. RESULTS: There were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake. CONCLUSIONS: It is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00588276.

Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective.

This review contains a surgical perspective on the evolution of the nonoperative approach to patients with locally advanced rectal cancer who have a clinical complete response after neoadjuvant combined modality therapy, including accuracy of pathologic complete response identification, the timing between neoadjuvant combined modality therapy and assessment of response, the extent of long-term follow-up, and the likelihood of surgical salvage after an initial nonoperative approach.

Protein intake compliance of morbidly obese patients undergoing bariatric surgery and its effect on weight loss and biochemical parameters.

BACKGROUND: Grade D evidence supports a daily protein intake (DPI) of >60 g/d after Roux-en-Y gastric bypass. However, the physiologic effects of this recommendation have yet to be elucidated. The primary aim of the present study was to assess the effects of DPI after laparoscopic Roux-en-Y gastric bypass on weight loss, leptin levels, and albumin levels. The setting was a 617-acute inpatient bed university-affiliated teaching hospital. METHODS: The data from 427 consecutive bariatric surgery patients were prospectively collected from December 2007 to April 2011. The data were analyzed using Pearson's correlation, the chi-square test, the paired t test, analysis of covariance, and hierarchical linear regression analysis. RESULTS: Of the 427 patients, 167 (39.1%) had complete data at 3, 6, and 12 months of follow-up and were used for the present analysis. Of the 427 patients, 140 (83.8%) were women with a mean age and preoperative body mass index (BMI) of 42.7 ± 11 years and 47.3 ± 8.1 kg/m(2), respectively. Of the 427 patients, 71.3% were compliant with a DPI of ≥1 g/kg/d at 12 months postoperatively. The patients had a mean percentage of excess weight loss of 74.9% ± 16.7% and a mean BMI of 29.4 ± 5.4 kg/m2 at 12 months. When controlling for the preoperative BMI, carbohydrate violations, and exercise increase, DPI was associated with a greater percentage of excess weight loss (P = .001), BMI change (P < .0001), and percentage of lean mass (P = .003), and a lower percentage of body fat (P < .0001) at 12 months. CONCLUSION: Excellent compliance with a DPI of ≥1 g/kg/d at 12 months after laparoscopic Roux-en-Y gastric bypass is feasible and might result in the benefits of increased weight loss, a decreased percentage of body fat, and improved percentage of lean mass.