Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial.

BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort. METHODS: In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters. RESULTS: This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters. CONCLUSIONS: Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency. TRIAL REGISTRATION: NCT00489697, registration number of the STIC-AVASTIN trial.

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.

Proton beam therapy outcomes for localized unresectable hepatocellular carcinoma.

BACKGROUND AND PURPOSE: This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC). METHODS AND METHODS: Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0-2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT. RESULTS: Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5-21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6-144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62% respectively; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED ≥90 GyE had a significantly better OS than those receiving BED <90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2-year LC improvement was observed in patients receiving BED ≥90 GyE compared with those receiving BED <90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity. CONCLUSIONS: High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes.

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.

Total Transthoracic Approach Facilitates Laparoscopic Hepatic Resection in Patients with Significant Prior Abdominal Surgery.

BACKGROUND: While the oncologic safety of minimally invasive hepatectomy for colorectal liver metastases (CLM) has been demonstrated, lesions in the postero-superior segments may be challenging.1 - 3 For these lesions, a transthoracic approach may be particularly helpful, especially in patients with a hostile/reoperative abdomen or morbid obesity.4 , 5 PATIENT: A 43-year-old man with a body mass index of 36.0 who had undergone rectosigmoid resection for primary cancer 5 years ago recurred with a solitary liver metastasis in SVIII. He had previously undergone the following resections for metachronous CLM: (i) partial resections of SV/VIII and SII/III; (ii) ablation for SVII; and (iii) left hepatectomy, common bile duct resection, and choledochojejunostomy. Following four cycles of FOLFIRI/panitumumab with good response, the patient was considered for his fourth abdominal cancer intervention via a thoracoscopic approach. TECHNIQUE: In a modified French position with left-lung ventilation, access to the right thoracic cavity was gained. Following thoracic adhesiolysis, transdiaphragmatic intraoperative ultrasonography (IOUS) was performed. To ensure optimal margins, IOUS-guided transthoracic hepatic resection with partial resection of the diaphragm was conducted. The diaphragm was reconstructed and a chest tube placed. Operative time was 247 min, with an estimated blood loss of 100 mL. Postoperative recovery was uneventful; pathology demonstrated no viable tumor, with the closest margin 5 mm from the necrotic area. CONCLUSION: Transthoracic hepatic resection of SVIII can optimize the port-target axis while minimizing morbidity. A systematic approach that includes precise port positioning, non-traumatic intrathoracic adhesiolysis, and meticulous transdiaphragmatic IOUS-guided parenchymal transection can optimize outcomes.

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases.

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.

Laparoscopic Management of Gallbladder Cancer: A Stepwise Approach.

BACKGROUND: In the era of laparoscopic cholecystectomy, incidentally discovered gallbladder cancer (IGBC) has become a common clinical presentation.1 A consensus exists that radical resection should be performed for IGBC patients with T1b or more advanced tumors.2 Although the oncologic safety of laparoscopic treatment for selected patients with gallbladder cancer (GBC) has been demonstrated, a laparoscopic approach for IGBC remains uncommonly practiced due to the technical challenge of the frequently reoperative cases.3 PATIENT: A 75-year-old man underwent laparoscopic cholecystectomy for the presumed diagnosis of chronic cholecystitis and sludge at an outside institution, and pathology showed a T3 gallbladder carcinoma with a positive margin at the cystic duct stump. Restaging computed tomography at the time of referral showed findings in the hepatoduodenal ligament and gallbladder fossa concerning residual tumor versus postoperative inflammation. After four cycles of gemcitabine and cisplatin, restaging showed interval resolution of the postoperative change, continued low tumor marker carbohydrate antigen 19-9, and no evidence of metastatic disease. Therefore, the decision was made to perform a laparoscopic radical resection TECHNIQUE: With the patient in French position, significant adhesions around the hepatoduodenal ligament had to be dissected. Lymph node stations 12 and 16 were removed after a Kocher maneuver and hepatoduodenal ligament lymphadenectomy, preserving an accessory right hepatic artery. The cystic duct stump was removed at the level of confluence with the common bile duct. The resulting defect was reconstructed with interrupted sutures. Using intraoperative ultrasonography (IOUS) guidance, an anatomic resection of segments 4b and 5 was performed. An alternative approach is a laparoscopic Glissonian approach that can facilitate a safe anatomic resection.4 An air cholangiogram detected no bile leak and confirmed biliary patency.5 The postoperative recovery was uneventful, and pathology showed residual adenocarcinoma in segments 4b, and 5 with 50 % tumor viability and negative margins. CONCLUSION: Because laparoscopic management of IGBC involves a challenging reoperative procedure, a systematic approach using accurate preoperative anatomic assessment, meticulous IOUS-guided surgery, and air cholangiogram is recommended to minimize the morbidity of this operation.

Evaluating the Clinical Applicability of the European Staging System for Perihilar Cholangiocarcinoma.

BACKGROUND: In 2011, a new European Staging System (ESS) for perihilar cholangiocarcinoma (PHC) was proposed with the expressed purpose of comparing treatment and outcomes data between institutions. The goal of this study was to evaluate the feasibility of ESS data capture. STUDY DESIGN: Forty-seven consecutive patients who underwent surgical resection for PHC between 1999 and 2013 were studied. Demographic variables, components of various staging systems (including the ESS), preoperative and perioperative details, pathology, and outcomes were recorded. RESULTS: The mean patient age was 63.2 and 62% were male. Preoperative imaging included high-resolution CT in all patients, MRI in 34%, and PET in 11%. R0 resection was accomplished in 80% of patients. Four patients (8.5%) and 18 patients (38.3%), respectively, received neoadjuvant or adjuvant therapy. During a mean follow-up of 36 months, recurrence rate was 51.3% and 2- and 5-year survival rates were 69.4 and 33.3%, respectively. Analysis of data capture found that tumor (T) classification was indeterminable in 7/47 patients (14.9%). For two patients, the form (F) designation had insufficient data. The extent of vascular involvement (PV/HA) was different compared to preoperative imaging in nine patients (19.1%). The liver remnant volume (V) was calculated in only 18 patients (38.3%). The liver disease (D) variable did not account for four patients with inflammation/cirrhosis. In total, only 15 patients (31.9%) had all required elements to complete the ESS. CONCLUSIONS: Without templated radiology, surgery, and pathology reports, the ESS cannot be applied to current clinical/research practice. Although resection continues to provide significant survival benefit to patients with perihilar cholangiocarcinoma, lack of an accurate prognostic tool for resectability and outcomes continues to be a major impediment to progress in the field.

Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.

An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.

(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.

Residual tumor thickness at the tumor-normal tissue interface predicts the recurrence-free survival in patients with liver metastasis of breast cancer.

Tumor response to neoadjuvant therapy is a significant predictive indicator of recurrence-free survival. We measured tumor response using residual tumor thickness at the tumor-normal tissue interface (TNI) and evaluated its association with outcome in patients with liver metastasis of breast cancer. We included 48 patients who underwent neoadjuvant therapy followed by partial liver resection at MD Anderson Cancer Center between 1997 and 2010. The hematoxylin-eosin-stained tumor sections were evaluated for both pathologic response and the residual tumor thickness at the TNI by 3 pathologists who were blinded to the clinical information, treatment regimen, and patient outcome. The residual tumor thickness at the TNI was correlated with recurrence-free survival using Kaplan-Meier method and log-rank test. Cox proportional hazard model was used to identify predictors of recurrence-free survival. All patients were women with a median age of 43 years. The median duration of follow-up was 52.1 months. Residual tumor thickness less than or equal to 3 mm at the TNI correlated with major pathologic response and was associated with longer recurrence-free survival in both univariate and multivariate analyses. Residual tumor thickness at the TNI predicts recurrence-free survival and provides an objective outcome end point in patients who underwent neoadjuvant therapy and liver resection of metastatic breast cancer. We suggest using both the pathologic response and the residual tumor thickness at the TNI to measure tumor response to therapy to improve accuracy.

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.