Comparison of virtual to true unenhanced abdominal computed tomography images acquired using rapid kV-switching dual energy imaging.

OBJECTIVE: To compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages. METHODS: VUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling. RESULTS: Quantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney. CONCLUSIONS: Significant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.

Tumor thrombus in the venous drainage pathways of primary, recurrent and metastatic disease on routine oncologic imaging studies: beyond hepatocellular and renal cell carcinomas.

Radiologists routinely evaluate for tumor thrombus in the portal and hepatic veins in patients with hepatocellular carcinoma and in the renal vein and inferior vena cava in patients with renal cell carcinoma. However, tumor thrombus occurs in association with numerous other tumor types, e.g. colorectal carcinoma and pancreatic neuroendocrine tumor. Furthermore tumor thrombi are not limited to the primary tumor but also seen with local recurrence and metastatic disease. While less recognized, these thrombi nevertheless affect patterns of recurrence and prognosis. Their detection is critical for accurate local staging and early detection of local recurrence and metastatic disease. The purpose of this pictorial review is to draw the attention of radiologists to the less familiar manifestations of tumor thrombus, review the imaging findings and illustrate the clinical significance of these thrombi.

Intrahepatic Recurrence Patterns Predict Survival After Resection of Colorectal Liver Metastases.

BACKGROUND: After resection of colorectal liver metastases (CLM), up to 40% of patients will develop intrahepatic recurrence. This study aims to identify patterns of intrahepatic recurrence and their impact on survival after preoperative chemotherapy and CLM resection. METHODS: A retrospective review was performed of patients developing intrahepatic recurrence after CLM resection following preoperative chemotherapy. Prechemotherapy, preoperative, and postoperative computed tomography scans were reviewed. Recurrences were classified as in situ, de novo, or both in situ and de novo. Median follow-up was 42 months (range 2-144 months). RESULTS: Among 223 patients meeting study criteria, intrahepatic recurrence was identified a median of 9 months after hepatectomy. Isolated de novo or in situ recurrence developed in 105 (47%) and 86 (39%) patients, respectively. Thirty-two patients (14%) developed both in situ and de novo recurrence, which was associated with significantly lower median overall survival of 33 months compared with 49 and 45 months with isolated in situ or de novo recurrence, respectively (p = 0.048). Among 118 patients (53%) who developed in situ recurrence as a component of disease relapse, recurrences resulted from disappearing or missed liver metastases in 47 patients (40%). CONCLUSIONS: An intrahepatic recurrence pattern of both in situ and de novo metastases after CLM resection following preoperative chemotherapy predicts significantly worse overall survival compared with isolated in situ or de novo recurrence.

Comparison of early radiological predictors of outcome in patients with colorectal cancer with unresectable hepatic metastases treated with bevacizumab.

OBJECTIVE: The purpose was to validate the prognostic value of an early optimal morphological response on CT in patients treated with bevacizumab-containing chemotherapy for unresectable colorectal cancer liver metastases (CLM). It also evaluated the prognostic value of size-based criteria and the association of optimal morphological response with the receipt of bevacizumab. DESIGN: 141 patients treated first using bevacizumab and 142 patients from a randomised study evaluating the addition of bevacizumab to oxaliplatin-based chemotherapy were retrospectively analysed. Radiologists evaluated pretreatment and restaging CT scans using morphological response criteria. Responses were also assessed with size-based criteria: Response Evaluation Criteria in Solid Tumors (RECIST), early tumour shrinkage (ETS) and deepness of response (DpR). The ability of each criterion to predict progression-free survival (PFS), overall survival (OS) and postprogression survival (PPS) was determined using a univariate Cox proportional hazards model. RESULTS: In both populations, median PFS was significantly longer for patients achieving an optimal morphological response (10.4 vs 6.8 months, p=0.03; and 8.3 vs 4.9 months, p<00001, respectively). Neither RECIST nor ETS responses were associated with a prolonged PFS. Median OS was longer for those with an optimal morphological response but only at second restaging in the first population (n=141, 20.8 vs 12.3 months, p=0.002). DpR but not optimal morphological response was associated with PPS. In the randomised study, an optimal morphological response was 6.2 times more likely among patients receiving bevacizumab (p<0.0001). CONCLUSION: In patients with unresectable CLM, early morphological response may be a better predictor of PFS than size-based response. The addition of bevacizumab improves morphological response rate.

Radiofrequency Ablation of Hepatic Tumor: Subjective Assessment of the Perilesional Vascular Network on Contrast-Enhanced Computed Tomography Before and After Ablation Can Reliably Predict the Risk of Local Recurrence.

OBJECTIVE: To determine whether simple, subjective analysis of the perilesional vascular network can predict the risk of local recurrence after radiofrequency ablation (RFA) of liver malignancies on contrast-enhanced computed tomography (CECT). METHODS: Contrast-enhanced computed tomography's 103 patients (59 men and 44 women; mean age, 63 years (range, 31-84 years) with 134 lesions who underwent RFA between 2000 and 2010 were retrospectively analyzed. The primary tumors include colorectal carcinoma (58 patients), hepatocellular carcinoma (n = 13), breast carcinoma (n = 8), neuroendocrine tumor (n = 5), and others (n = 19). Three blinded radiologists independently reviewed the CECT (a triple phase liver protocol for hypervascular tumors and a single phase for the hypovascular tumors) before and 6 weeks after RFA and subjectively estimated the width of the ablative margin on a 3-point scale (optimal, 1; suboptimal, 2; and residual tumor, 3). Local recurrence was determined on follow-up CECT. RESULTS: The consensus score was 1 in 94, 2 in 28, and 3 in 12 lesions. κ among readers was 0.75. Local recurrence occurred in 3 lesions with a score of 1 and 12 lesions with a score of 2. The consensus score was a significant univariate predictor of local recurrence. CONCLUSIONS: Subjective estimation of the width of ablative margin can reliably predict the risk of local recurrence.

Quantitation of clinical feedback on image quality differences between two CT scanner models.

The aim of this work was to quantitate differences in image quality between two GE CT scanner models - the LightSpeed VCT ("VCT") and Discovery HD750 ("HD") - based upon feedback from radiologists at our institution. First, 3 yrs of daily QC images of the manufacturer-provided QC phantom from 10 scanners - five of each model - were analyzed for both noise magnitude, measured as CT-number standard deviation, and noise power spectrum within the uniform water section. The same phantom was then scanned on four of each model and analyzed for low contrast detectability (LCD) using a built-in LCD tool at the scanner console. An anthropomorphic phantom was scanned using the same eight scanners. A slice within the abdomen section was chosen and three ROIs were placed in regions representing liver, stomach, and spleen. Both standard deviation of CT-number and LCD value was calculated for each image. Noise magnitude was 8.5% higher in HD scanners compared to VCT scanners. An associated increase in the magnitude of the noise power spectra were also found, but both peak and mean NPS frequency were not different between the two models. VCT scanners outperformed HD scanners with respect to LCD by an average of 13.1% across all scanners and phantoms. Our results agree with radiologist feedback, and necessitate a closer look at our body CT protocols among different scanner models at our institution.

(18)F-FDG Uptake at the Surgical Margin after Hepatic Resection: Patterns of Uptake and Differential Diagnosis.

OBJECTIVE: To evaluate the patterns of (18)F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. METHODS: Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. RESULTS: There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100 % sensitivity, 87 % specificity, 37 % false positive rate. As expected, SUVmax was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. CONCLUSION: F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. KEY POINTS: • Marginal uptake exposes patients to the risk of false positive diagnosis of recurrence. • Benign and malignant patterns of marginal uptake overlap. • Diffuse marginal uptake in our experience, has a high chance to be inflammatory. • Focal marginal uptake can be due to recurrent tumour or inflammation. • Contrast-enhanced CT or MR allows the differentiation between benign and malignant uptake.

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases.

BACKGROUND: RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. METHODS: RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2). RESULTS: Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy. CONCLUSIONS: RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.

Efficacy and safety of portal vein embolization for two-stage hepatectomy in patients with colorectal liver metastasis.

PURPOSE: To examine the efficacy and safety of portal vein embolization (PVE) when used during two-stage hepatectomy for bilobar colorectal liver metastases (CLM). MATERIALS AND METHODS: PVE was performed as an adjunct to two-stage hepatectomy in 56 patients with CLM. Absolute future liver remnant (FLR) volumes, standardized FLR ratios, degree of hypertrophy (DH), and complications were analyzed. Segment II and III volumes and DH were also measured separately. All volumetric measurements were compared with a cohort of 96 patients (n = 37 right portal vein embolization [RPVE], n = 59 right portal vein embolization extended to segment IV portal veins [RPVE+4]) in whom PVE was performed before single-stage hepatectomy. RESULTS: For patients who completed RPVE during two-stage hepatectomy (n = 17 of 17), mean absolute FLR volume increased from 272.1 cm(3) to 427.0 cm(3) (P < .0001), mean standardized FLR ratio increased from 0.17 to 0.26 (P < .0001), and mean DH was 0.094. For patients who completed RPVE+4 during two-stage hepatectomy (n = 38 of 39), mean FLR volume increased from 288.7 cm(3) to 424.8 cm(3) (P < .0001), mean standardized FLR increased from 0.18 to 0.26 (P < .0001), and mean DH was 0.083. DH of the FLR was not significantly different between two-stage hepatectomy and single-stage hepatectomy. Complications after PVE occurred in five (8.9%) patients undergoing two-stage hepatectomy. CONCLUSIONS: PVE effectively and safely induced a significant DH in the FLR during two-stage hepatectomy in patients with CLM.

Intrabiliary growth of colorectal liver metastasis: spectrum of imaging findings and implications for surgical management.

OBJECTIVE: The propensity for colorectal liver metastasis to invade the biliary tree is increasingly recognized, placing particular emphasis on the risk of postoperative recurrence. This article illustrates the spectrum of imaging findings when colorectal metastasis invades the biliary tree. CONCLUSION: Knowledge of the imaging features of intrabiliary invasion by colorectal liver metastasis improves the quality of preoperative staging and is crucial in an era in which nonanatomic wedge resection and radiofrequency ablation are routinely performed.

Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction.

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case-control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68-6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13-71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05-5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26-3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.

Evaluation of cancer treatment in the abdomen: Trends and advances.

Response evaluation in Oncology has relied primarily on change in tumor size. Inconsistent results in the prediction of clinical outcome when size based criteria are used and the increasing role of targeted and loco-regional therapies have led to the development of new methods of response evaluation that are unrelated to change in tumor size. The goals of this review are to expose briefly the size based criteria and to present the non-size based approaches that are currently applicable in the clinical setting. Other paths that are still being explored are not discussed in details.

Non-size-based response criteria to preoperative chemotherapy in patients with colorectal liver metastases: the morphologic response criteria.

Since the introduction of biologic agents, increasing data have suggested that conventional size-based RECIST criteria are not accurate in the assessment of response to therapy and non-size-based changes in tumor morphology can be a surrogate marker for assessment of chemotherapeutic effect. The morphologic response criteria are recently introduced, non-size-based criteria for patients undergoing chemotherapy for colorectal liver metastases (CLM). These novel criteria predict pathologic response and long-term survival of patients treated with preoperative chemotherapy, with or without bevacizumab, independent of their RECIST response. They have been validated in patients with resectable and unresectable CLM. These criteria are difficult to apply in small metastases and can be used as an adjunct to RECIST in the assessment of response to preoperative chemotherapy.

Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy.

OBJECTIVE: To determine the impact of surgical margin status on overall survival (OS) of patients undergoing hepatectomy for colorectal liver metastases after modern preoperative chemotherapy. BACKGROUND: In the era of effective chemotherapy for colorectal liver metastases, the association between surgical margin status and survival has become controversial. METHODS: Clinicopathologic data and outcomes for 378 patients treated with modern preoperative chemotherapy and hepatectomy were analyzed. The effect of positive margins on OS was analyzed in relation to pathologic and computed tomography-based morphologic response to chemotherapy. RESULTS: Fifty-two of 378 resections (14%) were R1 resections (tumor-free margin <1 mm). The 5-year OS rates for patients with R0 resection (margin ≥1 mm) and R1 resection were 55% and 26%, respectively (P = 0.017). Multivariate analysis identified R1 resection (P = 0.03) and a minor pathologic response to chemotherapy (P = 0.002) as the 2 factors independently associated with worse survival. The survival benefit associated with negative margins (R0 vs R1 resection) was greater in patients with suboptimal morphologic response (5-year OS rate: 62% vs 11%; P = 0.007) than in patients with optimal response (3-year OS rate: 92% vs 88%; P = 0.917) and greater in patients with a minor pathologic response (5-year OS rate: 46% vs 0%; P = 0.002) than in patients with a major response (5-year OS rate: 63% vs 67%; P = 0.587). CONCLUSIONS: In the era of modern chemotherapy, negative margins remain an important determinant of survival and should be the primary goal of surgical therapy. The impact of positive margins is most pronounced in patients with suboptimal response to systemic therapy.

Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases.

PURPOSE: The purposes of this study were to confirm the prognostic value of an optimal morphologic response to preoperative chemotherapy in patients undergoing chemotherapy with or without bevacizumab before resection of colorectal liver metastases (CLM) and to identify predictors of the optimal morphologic response. PATIENTS AND METHODS: The study included 209 patients who underwent resection of CLM after preoperative chemotherapy with oxaliplatin- or irinotecan-based regimens with or without bevacizumab. Radiologic responses were classified as optimal or suboptimal according to the morphologic response criteria. Overall survival (OS) was determined, and prognostic factors associated with an optimal response were identified in multivariate analysis. RESULTS: An optimal morphologic response was observed in 47% of patients treated with bevacizumab and 12% of patients treated without bevacizumab (P < .001). The 3- and 5-year OS rates were higher in the optimal response group (82% and 74%, respectively) compared with the suboptimal response group (60% and 45%, respectively; P < .001). On multivariate analysis, suboptimal morphologic response was an independent predictor of worse OS (hazard ratio, 2.09; P = .007). Receipt of bevacizumab (odds ratio, 6.71; P < .001) and largest metastasis before chemotherapy of ≤ 3 cm (odds ratio, 2.12; P = .025) were significantly associated with optimal morphologic response. The morphologic response showed no specific correlation with conventional size-based RECIST criteria, and it was superior to RECIST in predicting major pathologic response. CONCLUSION: Independent of preoperative chemotherapy regimen, optimal morphologic response is sufficiently correlated with OS to be considered a surrogate therapeutic end point for patients with CLM.

CT findings of response and recurrence, independent of change in tumor size, in colorectal liver metastasis treated with bevacizumab.

OBJECTIVE: The purpose of this article is to provide a practical review of newly established morphologic tumor response criteria for hepatic colorectal metastasis treated with bevacizumab-containing chemotherapy and a description of the patterns of early recurrence. We also discuss the respective value of these criteria and the Response Evaluation Criteria in Solid Tumors (RECIST). CONCLUSION: RECIST alone are not sufficient to assess response after bevacizumab-containing chemotherapy for hepatic colorectal metastasis. The combined use of RECIST and morphologic criteria is mandatory for optimal evaluation in this population.

Planning and follow-up after ablation of hepatic tumors: imaging evaluation.

CTs or MRIs are essential for preablative therapy planning of hepatic tumors to identify accurate size, number, and location of tumors. Tumors larger than 5 cm and located near the major branches of the portal vein and hepatic vein have a higher potential for incomplete ablation. Postablative imaging studies are needed to determine if the entire tumors are included in the treatment zone to minimize the risk of local tumor recurrences. Complications of ablative therapy can be identified on post-treatment imaging studies.

Is resection of colorectal liver metastases after a second-line chemotherapy regimen justified?

BACKGROUND: Patient outcomes following resection of colorectal liver metastases (CLM) after second-line chemotherapy regimen is unknown. METHODS: From August 1998 to June 2009, data from 1099 patients with CLM were collected prospectively. We retrospectively analyzed outcomes of patients who underwent resection of CLM after second-line (2 or more) chemotherapy regimens. RESULTS: Sixty patients underwent resection of CLM after 2 or more chemotherapy regimens. Patients had advanced CLM (mean number of CLM ± standard deviation, 4 ± 3.5; mean maximum size of CLM, 5 ± 3.2 cm) and had received 17 ± 8 cycles of preoperative chemotherapy. In 54 (90%) patients, the switch from the first regimen to another regimen was motivated by tumor progression or suboptimal radiographic response. All patients received irinotecan or oxaliplatin, and the majority (42/60 [70%]) received a monoclonal antibody (bevacizumab or cetuximab) as part of the last preoperative regimen. Postoperative morbidity and mortality rates were 33% and 3%, respectively. At a median follow-up of 32 months, 1-year, 3-year, and 5-year overall survival rates were 83%, 41%, and 22%, respectively. Median chemotherapy-free survival after resection or completion of additional chemotherapy administered after resection was 9 months (95% confidence interval, 4-14 months). Synchronous (vs metachronous) CLM and minor (vs major) pathologic response were independently associated with worse survival. CONCLUSIONS: Resection of CLM after a second-line chemotherapy regimen was found to be safe and was associated with a modest hope for definitive cure. This approach represents a viable option in patients with advanced CLM.