Surgical Treatment of Colorectal Cancer with Peritoneal and Liver Metastases Using Combined Liver and Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Report from a Single-Centre Experience.

BACKGROUND: Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer. OBJECTIVES: The aims of this study were to evaluate the safety of combining liver surgery (LS) with HIPEC and CRS (which remains controversial) and its impact on overall survival (OS) rates. METHODS: From 2007 to 2015, a total of 77 patients underwent CRS/HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. Twenty-five of these patients underwent concomitant LS for suspicion of liver metastases (LM; group 2), and were compared with patients who underwent CRS/HIPEC only (group 1). Demographic and clinical data were reviewed retrospectively. RESULTS: Among the group 2 patients, two underwent major hepatectomies, six underwent multiple wedge resections, 16 underwent single wedge resections (one with radiofrequency ablation), and one underwent radiofrequency ablation alone. For groups 1 and 2, median peritoneal cancer index was 6 and 10 (range 0-26; p = 0.08), complication rates were 15.4 and 32.0 % (Dindo-Clavien ≥3; p = 0.15), and median follow-up was 34.2 and 25.5 months (range 0-75 and 3-97), respectively. One group 2 patient died of septic shock after 66 days. Pathology confirmed LM in 21 patients in group 2 (four with benign hepatic lesions were excluded from long-term outcome analysis). Two-year OS rates were 89.5 and 70.2 % (p = 0.04), and 2-year recurrence-free survival rates were 38.3 and 13.4 % (p = 0.01) in groups 1 and 2, respectively. CONCLUSIONS: Simultaneous surgery for colorectal LM and PC is both feasible and safe, with low postoperative morbidity. Further longer-term studies would help determine its impact on patient survival.

To chew or not to chew: that's the question.

A 25-year-old Somalian man was referred to the department of internal medicine because of nausea, vomiting and jaundice of recent onset. On physical examination, he was frankly icteric without clinical signs of chronic liver disease. Laboratory data showed evidence of acute hepatitis. Viral serologic tests for hepatitis A, B, C and E were negative. Antinuclear antibodies (ANA) were positive (titre 1 : 1280; speckled pattern, NV < 1 : 40) as well anti-actin antibodies (titre 75 UA, NV < 20). A liver biopsy was performed and showed a feature compatible with toxic hepatitis. On further questioning, the patient admitted to daily chew Khat when he was living in Somalia. We concluded to Khat-induced toxic hepatitis together with high-titre anti-nuclear antibody mimicking serologic patterns of auto-immune hepatitis.

Chemoembolization for hepatocellular carcinoma: 1-month response determined with apparent diffusion coefficient is an independent predictor of outcome.

PURPOSE: To evaluate the predictive utility of apparent diffusion coefficient (ADC) changes at diffusion-weighted (DW) magnetic resonance (MR) imaging 1 month after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) compared with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, European Association for the Study of the Liver (EASL) criteria, and modified RECIST (mRECIST). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this prospective study. Thirty-eight patients with inoperable HCC underwent 1.5-T MR imaging, including DW imaging, before and 1 month after TACE. Responses 1 month after TACE were assessed with the ADC change relative to baseline (ADC ratio), RECIST, EASL criteria, and mRECIST. Eight patients underwent transplantation 4 months after TACE, allowing the association between response and histopathologic necrosis ratio to be determined. In 30 patients, Kaplan-Meier and log-rank tests were used to correlate the response variables with progression-free and overall survival. RESULTS: Median progression-free survival (PFS) was 5 months, and overall survival was 17.5 months. Survival analyses showed significant effects of pretreatment α-fetoprotein level (P = .03) and ADC ratio (P < .0001) on PFS and substantial effects of mRECIST, RECIST, and EASL criteria (.05 < P < .1). ADC ratio was a significant predictor of 5-month PFS (P < .001), with an accuracy of 93.3% compared with 53.3% with mRECIST and EASL criteria and 66.7% with RECIST. No response variables correlated with overall survival. Only the ADC ratio was significantly associated with histopathologic tumor necrosis (P = .03). CONCLUSION: The ADC ratio 1 month after TACE was an independent predictor of PFS, which showed stronger association with tumor response than did RECIST, EASL criteria, or mRECIST.

Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats.

UNLABELLED: The farnesoid X receptor (FXR) is a nuclear bile acid receptor involved in bile acid homeostasis, hepatic and intestinal inflammation, liver fibrosis, and cardiovascular disease. We studied the effect of short-term treatment with obeticholic acid (INT-747), a potent selective FXR agonist, on intrahepatic hemodynamic dysfunction and signaling pathways in different rat models of cirrhotic portal hypertension (PHT). For this, thioacetamide (TAA)-intoxicated and bile-duct-ligated (BDL) rats were used as models. After gavage of two doses of 30 mg/kg of INT-747 or vehicle within 24 hours, in vivo hemodynamics were assessed. Additionally, we evaluated the direct effect of INT-747 on total intrahepatic vascular resistance (IHVR) and intrahepatic vascular tone (endothelial dysfunction and hyperresponsiveness to methoxamine) by means of an in situ liver perfusion system and on hepatic stellate cell contraction in vitro. FXR expression and involved intrahepatic vasoactive pathways (e.g., endothelial nitric oxide synthase [eNOS], Rho-kinase, and dimethylarginine dimethylaminohydrolase [DDAH]) were analyzed by immunohistochemistry, reverse-transcriptase polymerase chain reaction, or western blotting. In both cirrhotic models, FXR expression was decreased. Treatment with INT-747 in TAA and BDL reactivated the FXR downstream signaling pathway and decreased portal pressure by lowering total IHVR without deleterious systemic hypotension. In the perfused TAA and BDL cirrhotic liver, INT-747 improved endothelial vasorelaxation capacity, but not hyperresponsiveness. In both groups, this was associated with an increased eNOS activity, which, in TAA, related to down-regulation of Rho-kinase and in BDL to up-regulation of DDAH-2. CONCLUSION: FXR agonist INT-747 improves PHT in two different rat models of cirrhosis by decreasing IHVR. This hemodynamic effect relates to increased intrahepatic eNOS activity by pathways that differ depending on the etiology of cirrhosis.