Yozo Sato

Neutropaenia as a prognostic factor in metastatic colorectal cancer patients undergoing chemotherapy with first-line FOLFOX

We retrospectively analysed 153 patients with metastatic colorectal cancer who received FOLFOX with or without bevacizumab as first-line chemotherapy. Several background characteristics and chemotherapy features (grade of neutropaenia, use of bevacizumab or irinotecan, re-introduction of FOLFOX, and tumour progression) as time-varying covariates were analysed as potential prognostic factors. Of the 153 patients, mild neutropaenia (grade 1-2) occurred in 60 patients (39%) and severe neutropaenia (grade 3-4) occurred in 46 patients (30%). The other 47 patients (31%) did not experience neutropaenia. According to a multivariate Cox model with time-varying covariates, hazard ratios (HRs) of death were 0.55 (95% confidence interval (CI), 0.31-0.98; P=0.044) for patients with mild neutropaenia and 0.35 (95% CI, 0.18-0.66; P=0.002) for those with severe neutropaenia. Both mild and severe neutropaenia during chemotherapy are associated with improved survival in patients with MCRC. Prospective trials are required to assess whether dosing adjustments based on neutropaenia may improve chemotherapy efficacy.

Embolization in a patient with ruptured anterior inferior pancreaticoduodenal arterial aneurysm with median arcuate ligament syndrome.

Abstract In median arcuate ligament syndrome, the root of the celiac artery is compressed and narrowed by the median arcuate ligament of the diaphragm during expiration, causing abdominal angina. Aneurysm may be formed in arteries of the pancreas and duodenum due to a chronic increase in blood flow from the superior mesenteric artery into the celiac arterial region. We report a patient saved by embolization with coils of ruptured aneurysm that developed with markedly dilated anterior inferior pancreaticoduodenal artery due to median arcuate ligament syndrome.

Clinical value of CT-guided needle biopsy for retroperitoneal lesions.

Objective The purpose of this study was to investigate retrospectively the clinical procedural performance of CT-guided needle biopsy for retroperitoneal lesions. Materials and Methods CT-guided needle biopsy was performed in 74 consecutive patients (M:F = 44:30; mean age, 59.7 years) with retroperitoneal lesions between April 1998 and June 2009. The target lesion ranged from 1.5 to 12.5 cm in size. The biopsy access path ranged from 3.5 to 11.5 cm in depth. A biopsy specimen was obtained using an 18-gauge core needle under a CT or CT-fluoroscopy guidance and with the patient under local anesthesia. The histopathological diagnoses from the biopsies were obtained. The diagnostic confirmation of the subtype of lymphoma was evaluated. Results Satisfactory biopsy samples were obtained in 73 (99%) of 74 patients and a pathological diagnosis was made in 70 (95%) of 74 patients. Sixty three lesions were malignant (45 lymphomas, nine primary tumors, nine lymph node metastases) and seven were benign. The subtype of lymphoma was specified in 43 (96%) of 45 patients who were diagnosed with lymphoma. Analysis of the value of CT-guided biopsy in this series indicated 63 true positives, zero false positive, six true negatives and five false negatives. This test had a sensitivity of 93%, a specificity of 100% and an accuracy of 93%. No major complications were seen and minor complications were noted in seven patients (five with local hematomas, two with transient pain at the puncture site). Conclusion CT-guided needle biopsy for retroperitoneal lesions is highly practical and useful, and particularly for determining the subtypes in patients with lymphoma.

Hepatic Arterial Infusion Chemotherapy through a Port-Catheter System as Preoperative Initial Therapy in Patients with Advanced Liver Dysfunction due to Synchronous and Unresectable Liver Metastases from Colorectal Cancer

PurposeWe retrospectively evaluated the safety and efficacy of preoperative initial hepatic arterial infusion chemotherapy (HAIC) through a port-catheter system in patients with liver dysfunction due to synchronous and unresectable liver metastases. The aim of HAIC was to improve patients’ clinical condition for later surgical removal of primary colorectal cancer.MethodsPort-catheter systems were placed radiologically in 21 patients (mean age 58.6 ± 8.1 years) with liver dysfunction due to synchronous liver metastases from colorectal cancer. Initial HAIC of 1,000 mg/m2 5-fluorouracil was administered weekly as a 5 hr continuous infusion through this system. Surgical removal of the primary lesion was planned after HAIC improved the liver function.ResultsPort-catheter system placement was successful in all patients without severe complications. Patients were followed up for a median of 309 days (range 51–998 days). After starting HAIC, no severe adverse events that caused drug loss and treatment postponement or suspension were observed in any of the patients. HAIC was performed a mean of 4.5 ± 3.0 times and the liver function improved in all patients. Curative (n = 18) or palliative (n = 1) surgical removal of the primary lesion was performed. The remaining 2 patients died because extrahepatic metastases developed and their performance status worsened; thus, surgery could not be performed. The median survival times of all patients and the operated patients were 309 and 386 days, respectively.ConclusionInitial HAIC administration is a safe and efficacious method for improving liver function prior to operative resection of primary colorectal cancer in patients with liver dysfunction due to synchronous and unresectable liver metastases.

Phase I/II Study of Radiologic Hepatic Arterial Infusion of Fluorouracil Plus Systemic Irinotecan for Unresectable Hepatic Metastases from Colorectal Cancer: Japan Clinical Oncology Group Trial 0208-DI

PURPOSE Treatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study. MATERIALS AND METHODS Twenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m(2)) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m(2). RESULTS No dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m(2). Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5-78.1 mo), respectively. CONCLUSIONS The combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.

Guidelines for the use of NBCA in vascular embolization devised by the Committee of Practice Guidelines of the Japanese Society of Interventional Radiology (CGJSIR), 2012 edition

Abstract Cyanoacrylates are a group of fast-acting adhesives. They form low viscosity liquids in the monomer state and instantly polymerize to become adhesive upon contact with ionic substances. Since the 1950s, they have been used around the world for industrial and household purposes. N-butyl cyanoacrylate (NBCA) is a cyanoacrylate that is commonly used for medical care, and the closure of skin wounds with NBCA has been found to promote hemostasis. However, in Japan, the intravascular injection of NBCA is considered to be off-label use, except during the treatment of gastric varices under endoscopy. The use of NBCA in embolotherapy is considered when the target vessels cannot be cannulated superselectively, for vascular diseases that require long segments of the target vessel to be embolized, or for patients in a hypocoagulable state. NBCA-based embolotherapy can be used to treat vascular malformations, acute hemorrhaging, tumors, and venous disease. The complications associated with NBCA-based embolotherapy include tissue ischemia, hemorrhaging, systemic or local reactions, and catheter adhesion to blood vessels. NBCA is mixed with Lipiodol to make it radiopaque and to adjust its polymerization time. Since there are various technical aspects to performing NBCA-based embolotherapy safely, it should be carried out by, or with the assistance of, proficient interventional radiologists.

Malignant Inferior Vena Cava Syndrome and Congestive Hepatic Failure Treated by Venous Stent Placement

A 65-year-old woman with liver metastases from colon cancer and tumor thrombus extending from the right hepatic vein (HV) to the right atrium (RA) presented with marked lower-extremity edema and massive ascites. Computed tomography showed tumor thrombus completely occluding the inferior vena cava (IVC) and HV ostia. Recanalization of the IVC and HVs was performed. Metallic stents were placed in tandem from the superior vena cava to the IVC through the RA, and additional metallic stents were placed in the left HV. The patients symptoms were relieved, and there was no recurrence of these symptoms for 19.5 months until death.

Visualization of liver uptake function using the uptake contrast-enhanced ratio in hepatobiliary phase imaging.

PURPOSE To visualize liver uptake function using the uptake contrast-enhanced ratio in hepatobiliary phase (uptake CERH) magnetic resonance imaging. MATERIALS AND METHODS Thirty-seven patients with hepatocellular carcinoma (HCC) and 23 with metastatic liver cancer were evaluated. Hepatobiliary phase images were acquired 20min after an intravenous bolus injection of gadoxetic acid disodium. We assumed that the contrast-enhanced ratio in the hepatobiliary phase (CERH) in the spleen was similar to the contrast-enhanced ratio in the extracellular matrix (CEREM). The Uptake CERH value was defined as the percentage signal gain between the precontrast and hepatobiliary phase images (without CEREM). The Uptake CERH value measured the tumor-free liver parenchyma. The association of the uptake CERH value with the biochemical liver function test results, and hepatocellular density in the liver parenchyma was assessed. Correlations were examined using Pearson correlation coefficient and the Mann-Whitney test. RESULTS The uptake CERH value was correlated with albumin, bilirubin, indocyanine green retention rate at 15min, prothrombin activity(%), platelet count, and cellular density in the liver parenchyma (p<0.01). CONCLUSIONS Uptake CERH images are useful for visualizing liver uptake function.

Preoperative Estimation of Future Remnant Liver Function Following Portal Vein Embolization Using Relative Enhancement on Gadoxetic Acid Disodium-Enhanced Magnetic Resonance Imaging

Objective To retrospectively evaluate relative enhancement (RE) in the hepatobiliary phase of gadoxetic acid disodium-enhanced magnetic resonance (MR) imaging as a preoperative estimation of future remnant liver (FRL) function in a patients who underwent portal vein embolization (PVE). Materials and Methods In 53 patients, the correlation between the indocyanine green clearance (ICG-K) and RE imaging was analyzed before hepatectomy (first analysis). Twenty-three of the 53 patients underwent PVE followed by a repeat RE imaging and ICG test before an extended hepatectomy and their results were further analyzed (second analysis). Whole liver function and FRL function were calculated on the MR imaging as follows: RE x total liver volume (RE Index) and FRL-RE x FRL volume (Rem RE Index), respectively. Regarding clinical outcome, posthepatectomy liver failure (PHLF) was evaluated in patients undergoing PVE. Results Indocyanine green clearance correlated with the RE Index (r = 0.365, p = 0.007), and ICG-K of FRL (ICG-Krem) strongly correlated with the Rem RE Index (r = 0.738, p < 0.001) in the first analysis. Both the ICG-Krem and the Rem RE Index were significantly correlated after PVE (r = 0.508, p = 0.013) at the second analysis. The rate of improvement of the Rem RE Index from before PVE to after PVE was significantly higher than that of ICG-Krem (p = 0.014). Patients with PHLF had a significantly lower Rem RE Index than patients without PHLF (p = 0.023). Conclusion Relative enhancement imaging can be used to estimate FRL function after PVE.

Phase I study of combination chemotherapy using sorafenib and transcatheter arterial infusion with cisplatin for advanced hepatocellular carcinoma

The aims of this study were to evaluate the frequency of dose‐limiting toxicities and to find the recommended dose of combination chemotherapy with sorafenib and transcatheter arterial infusion (TAI) using cisplatin for patients with advanced hepatocellular carcinoma (HCC), for whom surgical resection, local ablation therapy, or transcatheter arterial chemoembolization were not indicated. Patients received 800 mg sorafenib daily. Cisplatin was given at one of three dosages (level 1, 35 mg/m2/cycle; level 2, 50 mg/m2/cycle; and level 3, 65 mg/m2/cycle) from feeding arteries to the HCC. The treatment was repeated every 4–6 weeks up to a maximum of six cycles, until there were signs of tumor progression or unacceptable toxicity. The dose‐limiting toxicities experienced by the 20 enrolled patients were grade 4 increased aspartate aminotransferase at level 1, grade 3 gastrointestinal hemorrhaging at level 1, and grade 3 hypertension at level 3. The common drug‐related adverse events that were of severity grade 3 or 4 included the elevation of aspartate aminotransferase (30%), alanine aminotransferase (20%), amylase (30%), and lipase (30%). Partial response was seen in four patients (20%), and 13 patients (65%) had stable disease. The median overall survival and progression‐free survival were 9.1 and 3.3 months, respectively. The combination of sorafenib at 800 mg/day with TAI of cisplatin at 65 mg/m2/cycle was determined to be the recommended regimen. A randomized phase II trial of sorafenib alone versus sorafenib plus TAI of cisplatin is currently underway. This study was registered at UMIN as trial number UMIN000001496.