Faculty Bibliography

PURPOSE: To assess the relationship between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM)-derived quantitative parameters (apparent diffusion coefficient [ADC], perfusion fraction [f], Dslow , diffusion coefficient [D], and Dfast , pseudodiffusion coefficient [D*]) and histopathology in pancreatic adenocarcinoma (PAC). MATERIALS AND METHODS: Subjects with suspected surgically resectable PAC were prospectively enrolled in this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board-approved study. Imaging was performed at 1.5T with a respiratory-triggered echo planar DWI sequence using 10 b values. Two readers drew regions of interest (ROIs) over the tumor and adjacent nontumoral tissue. Monoexponential and biexponential fits were used to derive ADC2b , ADCall , f, D, and D*, which were compared to quantitative histopathology of fibrosis, mean vascular density, and cellularity. Two biexponential IVIM models were investigated and compared: 1) nonlinear least-square fitting based on the Levenberg-Marquardt algorithm, and 2) linear fit using a fixed D* (20 mm2 /s). Statistical analysis included Student's t-test, Pearson correlation (P < 0.05 was considered significant), intraclass correlation, and coefficients of variance. RESULTS: Twenty subjects with PAC were included in the final cohort. Negative correlation between D and fibrosis (Reader 2: r = -0.57 P = 0.01; pooled P = -0.46, P = 0.04) was observed with a trend toward positive correlation between f and fibrosis (r = 0.44, P = 0.05). ADC2b was significantly lower in PAC with dense fibrosis than with loose fibrosis ADC2b (P = 0.03). Inter- and intrareader variability was excellent for ADC, D, and f. CONCLUSION: In PAC, D negatively correlates with fibrosis, with a trend toward positive correlation with f suggesting both perfusion and diffusion effects contribute to stromal desmoplasia. ADC2b is significantly lower in tumors with dense fibrosis and may serve as a biomarker of fibrosis architecture. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017.

BACKGROUND:The Barcelona Clinic Liver Cancer staging system recommends radiofrequency ablation as treatment of choice for patients with "small" (up to 2 cm in size) hepatocellular carcinoma. AIMS/OBJECTIVE:Aim of the study was to assess whether laparoscopic ablation therapies or hepatic resection could be proposed as alternative option if percutaneous approach is not feasible. METHODS:Overall survival and tumour recurrence rate were compared in a retrospective cohort of 176 consecutive patients with small hepatocellular carcinoma on cirrhosis treated by laparoscopic ablation therapies or surgery. To balance the covariates between the two groups, a propensity case-matched analysis was developed to generate a matched sample, which included 76 patients in each arm. RESULTS:Local tumour progression (p=0.005), intra-segmental recurrence (p=0.0001), and 5-year recurrence rates (80% vs. 60%; p=0.0014) were significantly higher in the ablation therapies group. The 5-year survival rate were 48% after ablation therapies and 69% after hepatic resection (p=0.0006). Multivariate analysis showed that MELD score, alpha-fetoprotein value, procedure category and intraoperative restaging were associated with survival, while the surgery was the only independent predictor of intra-hepatic recurrence. CONCLUSIONS:The present study suggests that, if percutaneous ablation is not feasible, hepatic resection may be considered as a sound option in the treatment of small hepatocellular carcinoma.

BACKGROUND:Hepatocellular adenoma (HCA) is the second most common benign liver neoplasm and occurs predominantly in women in their reproductive years. Positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) is commonly used in cancer staging, surveillance and evaluation of treatment response. PET-avid HCA are rare and can be falsely interpreted as malignancies. METHODS:A retrospective review of four institutions' database was performed to identify the PET-avid HCAs with clinico-pathological correlation. RESULTS:Nine patients with histological proven PET-avid HCA was identified. Eight out of 9 patients were female with a median age at diagnosis of 44 years. All patients' tumors with available histological subtyping (8/8) were HNF1-α mutated and had no inflammatory changes; 6 out the 9 lesions had prominent (>50%) steatotic changes. CONCLUSION/CONCLUSIONS:Hepatocellular adenomas, specifically the HNF1-α subtype, can cause false-positive PET findings when seeking to identify malignancy. Concomitantly, PET-CT may have the potential to identify the HCA histopathologic variant with the lowest malignant and hemorrhagic potential.

INTRODUCTION/BACKGROUND:Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignancy with a poor prognosis when treated with systemic therapy. Cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) is considered the best therapy in DMPM, but a high risk of locoregional recurrence remains. AREAS COVERED/METHODS:This review describes patient selection and operative goals with CRS and IPC, the reported outcomes with this approach, and the data supporting platinum-based IPC. We assess the pharmacokinetics supporting the use of dwell IPC. We outline clinical, imaging and laboratory surveillance for recurrence. In addition, we highlight the role of re-operation, both as a planned second procedure and in the context of disease recurrence. Literature review was performed via Medline search. Expert commentary: CRS/IPC offers survival benefit in selected patients with DMPM, but given the high rate of recurrence, close surveillance is needed post-operatively. Strategies to prevent and treat recurrent disease include dwell IPC and second CRS/IPC.

New surgical procedures taking advantage of the regenerative abilities of the liver are being introduced as potential curative therapies to these patients either to provide auxiliary support while the native liver recovers or undergoes hypertrophy. For patients with hepatocellular carcinoma outside of the Milan criteria or bilobar colorectal metastases liver transplantation is not an option. Fulminant hepatic failure can be treated but requires life-long immunosuppression. These complex surgical procedures require high quality and directed imaging.

BACKGROUND:Irreversible electroporation (IRE) for treatment of locally advanced pancreatic tumors is garnering increasing attention. This study was conducted to determine perioperative morbidity and mortality for locally advanced pancreatic cancer. METHODS:Prospective data of 50 consecutive patients receiving IRE for T4 lesions at a single tertiary center were analyzed. The primary end point was Clavien-Dindo complications at 90 days, and the secondary outcomes were survival and recurrence. RESULTS:A total of 50 patients underwent 53 IRE procedures for primary treatment (n = 29) or margin extension (n = 24), and 47 patients had adenocarcinoma. Six patients died within 90 days after the procedure (5 in the primary control group). Mortality occurred a median of 26 days (range, 8-42 days) after the procedure. Five patients in both the margin-extension and primary control groups experienced grade 3 or 4 morbidity (p = 0.739). The incidences of grades 3 to 5 complications did not differ significantly based on the adjustable parameters of IRE, tumor size, or primary treatment versus margin extension. After a median follow-up period of 8.69 months [interquartile range (IQR), 0.26-16.26 months], the median overall survival period for the primary control group was 7.71 months [95 % confidence interval (CI), 6.03-12.0 months) and was not reached in the margin-extension group (p = 0.01, log-rank). CONCLUSIONS:At the authors' center, the mortality rate after IRE was higher than reported in other series, with the majority occurring in the primary control group. Major morbidity trended around upper gastrointestinal bleeding, visceral ulcerations/perforations, and portal vein thromboses. This favors further investigation of the safety and efficacy of IRE.

BACKGROUND & AIMS/OBJECTIVE:Treatment decisions for hepatocellular carcinoma are mostly guided by tumor size. The aim of this study was to analyze resection outcomes according to tumor size and characterize prognostic factors. METHODS:Patients resected at a Western center between 1989 and 2010 were grouped by largest tumor size: <50mm, 50-100mm, and >100mm. The primary end points were overall- and recurrence-free survival. Univariate associations with primary endpoints were entered into a Cox proportional hazard regression model. RESULTS:Three hundred thirteen patients underwent resection: 111 (36%) had tumors <50mm, 113 (36%) had tumors between 50 and 100mm, and 89 (28%) had tumors >100mm. Five-year overall and disease-free survival rates for the three groups were 67%, 46%, and 34%, and 32%, 27%, and 27%, respectively. Thirty-five patients, mostly from <50mm group, underwent transplantation which was associated with a 91% 5 year survival rate. Tumor size was not an independent predictor of overall or recurrence-free survival on multivariate analyses. Independent predictors of decreased overall survival were: intraoperative transfusion (HR=2.60), cirrhosis (HR=2.42), poorly differentiated tumor (HR=2.04), satellite lesions (HR=1.69), alpha-fetoprotein >200 (HR=1.53), and microvascular invasion (HR=1.48). The use of salvage transplantation was an independent predictor of improved survival (HR=0.21). Recurrence-free survival was predicted by intraoperative transfusion (HR=2.15), poorly differentiated tumor (HR=1.87), microvascular invasion (HR=1.71) and cirrhosis (HR=1.69). CONCLUSION/CONCLUSIONS:By studying a large group of patients across a distribution of tumor sizes and background liver diseases, it is demonstrated that size alone is a limited prognostic factor. Tumor biology and condition of the underlying liver are better prognosticators and should be given closer attention. Although hampered by recurrence rates, resection is safe and offers good overall survival. In addition, it may allow for better selection for salvage transplantation after consideration of histopathological risk factors.

Surgery remains the only curative treatment for pancreaticobiliary tumors. These patients typically present in a malnourished state. Various screening tools have been employed to help with preoperative risk stratification. Examples include the subjective global assessment (SGA), malnutrition universal screening tool (MUST), and nutritional risk index (NRI). Adequate studies have not been performed to determine if perioperative interventions, based on nutrition risk assessment, result in less morbidity and mortality. The routine use of gastric decompression with nasogastric sump tubes may be unnecessary following elective pancreatic resections. Instead, placement should be selective and employed on a case-by-case basis. A wide variety of feeding modalities are available, oral nutrition being the most effective. Artificial nutrition may be provided by temporary nasal tube (nasogastric, nasojejunal, or combined nasogastrojejunal tube) or surgically placed tube [gastrostomy (GT), jejunostomy (JT), gastrojejunostomy tubes (GJT)], and intravenously (parenteral nutrition, PN). The optimal tube for enteral feeding cannot be determined based on current data. Each is associated with a specific set of complications. Dual lumen tubes may be useful in the presence of delayed gastric emptying (DGE) as the stomach may be decompressed while feeds are delivered to the jejunum. However, all feeding tubes placed in the small intestine, except direct jejunostomies, commonly dislodge and retroflex into the stomach. Jejunostomies are associated with less frequent, but more serious complications. These include intestinal torsion and bowel necrosis. PN is associated with septic, metabolic, and access-related complications and should be the feeding strategy of last-resort. Enteral feeds are clearly preferred over parental nutrition. A sound understanding of perioperative nutrition may improve patient outcomes. Patients undergoing pancreatic cancer surgery should undergo multidisciplinary nutrition screening and intervention, and the surgical/oncological team should include nutrition professionals in managing these patients in the perioperative period.

Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis.

BACKGROUND:Hepatocellular adenoma (HCA) is the second most common benign liver neoplasm and occurs predominantly in women in their reproductive years. Positron-emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) is commonly used in cancer staging, surveillance and evaluation of the treatment response. PET-avid HCA is rare and can be falsely interpreted as malignancies. METHODS:A retrospective review of four institutions' database was performed to identify the PET-avid HCAs with clinico-pathological correlation. RESULTS:Nine patients with histological proven PET-avid HCA was identified. Eight out of nine patients were female with a median age at diagnosis of 44 years. All patients' tumours with available histological subtyping (8/8) were HNF1-α mutated and had no inflammatory changes; six out the nine lesions had prominent (>50%) steatotic changes. CONCLUSION/CONCLUSIONS:Hepatocellular adenomas, specifically the HNF1-α subtype, can cause false-positive PET findings when seeking to identify malignancy. Concomitantly, PET-CT may have the potential to identify the HCA histopathological variant with the lowest malignant and haemorrhagic potential.