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To evaluate the clinical utility of bland arterial embolization using microspheres in patients with hypervascular liver metastases refractory to standard treatments. Primary endpoints of this prospective single-arm non-comparative study were objective response and disease control rates (ORR and DCR), based on the modified Response Evaluation Criteria in Solid Tumors at 4 weeks after embolization. Secondary endpoints were ORR according to primary tumor, overall survival, progression-free survival (PFS), and safety. Twenty-five patients with a median age of 66 years (range, 40–95 years) were enrolled in this study. The median maximum diameter of liver metastasis was 3.7 cm (range, 2.0–15.2 cm). Primary lesions were colorectal cancer in 12 patients (48%, 12/25), other cancer in 7 (28%, 7/25), neuroendocrine tumor in 4 (16%, 4/25), and sarcoma in 2 (8%, 2/25). ORR and DCR were 52% (13/25) and 72% (18/25) in all patients, 42% (5/12) and 75% (9/12) in colorectal cancer patients, and 62% (8/13) and 69% (9/13) in other malignant tumor patients (p = 0.43, p > 0.99). Median survival time was 19 months in all patients, 19 months in colorectal cancer patients, and 8 months (p = 0.16) in other malignant tumor patients. Median PFS time was 4 months in all patients, 4 months in colorectal cancer patients, and 6 months (p = 0.0085) in other malignant tumor patients. There were no grade-3 or -4 adverse events. Microsphere embolization appears to be an effective and safe treatment for hypervascular liver metastases refractory to standard treatments.

We reported consecutive five patients with BRAF V600E-mutant recurrent or advanced non-small cell lung cancer who were identified between April 2016 and June 2019. All five patients had high programmed death ligand 1 (PD-L1) tumor proportion scores (50, 55, 75, 95 and 100%). Four of the five patients received regimens including pembrolizumab. Of them, one patient experienced a partial response, but two patients experienced progressive disease and one patient was not evaluable. Three of the four patients received regimens including pemetrexed were able to continue long-term treatment. The presence of a BRAF mutation may be associated with higher levels of PD-L1 expression. The effect of immune checkpoint inhibitors therapy in patients with BRAF mutation was similar to the previous reports in patients with previously treated advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥50%. Chemotherapy regimens including pemetrexed may have a positive effect in patients with BRAF V600E-mutant lung adenocarcinoma. Accumulation of additional Case series is necessary to confirm our results.

To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid’s secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

This study aimed to compare the efficacy and safety of image-guided core needle biopsy (CNB) with those of surgical excision biopsy (SEB) for the diagnosis of lymphoma, and to clarify the indication of CNB in clinical practice.This retrospective study included 263 image-guided CNB cases and 108 SEB cases that were performed at our institution between January 2014 and December 2018. The rate of patients with performance status of grade 1-4 was higher in the CNB group than in the SEB group (43.7% vs. 24.1%, P 0.01). Waiting time to biopsy and diagnosis was shorter for CNB group than for SEB group (4 days vs. 7 days, 13 days vs. 15 days, P 0.01). The rate of biopsy at the deep sites was higher in the CNB group than in the SEB group (53.2% vs. 8.3%, P 0.01). Successful biopsy and complication rates were compared between the 2 groups.There were no significant differences between the CNB and SEB groups in successful biopsy rates (89.0% vs. 93.5%, P = 0.25). The grade 3 complication rate was significantly lower for CNB group than for SEB group (0% vs. 4.6%, P 0.01), although there was no significant difference in overall complication rates (4.9% vs. 6.5%, respectively, P = 0.61).CNB showed high diagnostic yield comparable to SEB for suspected lymphoma. CNB was especially recommended to the cases with low-PS, lesions in the deep sites, and requiring early pathological diagnosis.

Background Postoperative bleeding originating from pseudoaneurysms after radical gastrectomy is not common, but it can be fatal. In particular, delayed bleeding that occurs after the seventh postoperative day is rare. Case presentation A 54-year-old man underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Roux en-Y reconstruction for duodenal neuroendocrine tumors. Drainage was performed for a postoperative pancreatic fistula and abdominal abscess. On the 28th postoperative day, he passed a large amount of bloody stool; therefore, emergency esophagogastroduodenoscopy (EGD) and angiography were performed. However, neither examination demonstrated any bleeding foci or pseudoaneurysm. He was conservatively observed and discharged on the 50th postoperative day. Approximately 1 year after the surgery, he passed a bloody stool and experienced hemorrhagic shock. An EGD revealed exposed blood vessels at the duodenal blind end. His condition was diagnosed as a pseudoaneurysm arising from gastroduodenal artery, which ruptured into the duodenum, based on abdominal contrast-enhanced computed tomography findings. Emergency angiography was performed, and the pseudoaneurysm and artery were successfully embolized. Conclusions This case illustrates that there is a possibility of delayed bleeding even 1 year after gastrectomy. Such cases may be serious and require immediate and careful management.

Background Although radiofrequency ablation (RFA) is widely performed for the treatment of colorectal cancer (CRC) lung metastases, its efficacy for candidates with surgically resectable disease is unclear. Purpose To evaluate the prognosis after RFA in participants with resectable CRC lung metastases. Materials and Methods For this prospective multicenter study (ClinicalTrials.gov identifier: NCT00776399), participants with five or fewer surgically resectable lung metastases measuring 3 cm or less were included. Participants with CRC and a total of 100 lung metastases measuring 0.4-2.8 cm (mean, 1.0 cm ± 0.5) were chosen and treated with 88 sessions of RFA from January 2008 to April 2014. The primary end point was the 3-year overall survival (OS) rate, with an expected rate of 55%. The local tumor progression rate and safety were evaluated as secondary end points. The OS rates were generated by using the Kaplan-Meier method. Log-rank tests and Cox proportional regression models were used to identify the prognostic factors by means of univariable and multivariable analyses. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Results Seventy participants with CRC (mean age, 66 years ± 10; 49 men) were evaluated. The 3-year OS rate was 84% (59 of 70 participants; 95% confidence interval [CI]: 76%, 93%). In multivariable analysis, factors associated with worse OS included rectal rather than colon location (hazard ratio [HR] = 7.7; 95% CI: 2.6, 22.6; P < .001), positive carcinoembryonic antigen (HR = 5.8; 95% CI: 2.0, 16.9; P = .001), and absence of previous chemotherapy (HR = 9.8; 95% CI: 2.5, 38.0; P < .001). Local tumor progression was found in six of the 70 participants (9%). A grade 5 adverse event was seen in one of the 88 RFA sessions (1%), and grade 2 adverse events were seen in 18 (20%). Conclusion Lung radiofrequency ablation provided a favorable 3-year overall survival rate of 84% for resectable colorectal lung metastases measuring 3 cm or smaller. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Gemmete in this issue.

Background Chylothorax is the accumulation of chyle within the pleural space. Chylothorax can occur as a complication after multiple different types of surgery, most frequently after thoracic surgery, albeit with an incidence rate of less than 1%. Chylothorax after abdominal surgery is extremely rare, and there are only a few case reports. Case presentation A 74-year-old Japanese woman presented with jaundice. She was diagnosed as having hilar cholangiocarcinoma and underwent right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and lymph node dissection after preoperative percutaneous transhepatic portal vein embolization. Postoperative liver function was normal. She developed chylous ascites on postoperative day 5, for which conservative treatment was initially effective. Dyspnea developed suddenly on postoperative day 42, and she had a massive right pleural effusion and a small amount of ascites. Management with pleural drainage, total parenteral nutrition, and octreotide injections decreased the chylothorax. However, the chylous effusion reaccumulated on postoperative day 57. As conservative treatments ultimately failed, lymphangiography was performed on postoperative day 62. Lymphangiography with Lipiodol (ethiodized oil) revealed extravasation into the pleural space, but the location of the leak was not identified. There was neither obstruction nor dilation of the thoracic duct. A lymphatic leak in her abdominal cavity was not demonstrated. A chest tube was placed after lymphangiography, and the chylothorax was diminished by postoperative day 71. She was discharged on postoperative day 72. Two and a half years after surgery, she is doing well with no evidence of recurrence of either chylothorax or cancer. Conclusions Chylothorax can occur after hepatectomy and pleural effusion should raise suspicion for chylothorax. Lymphangiography may be effective for both diagnosis and treatment in the case of chylothorax after hepatectomy.

Purpose To evaluate safety and efficacy of combining sorafenib with transarterial chemoembolization in patients with advanced stage hepatocellular carcinomas (HCCs). Materials and Methods Systemic chemotherapy–naive patients with a Child-Pugh class A liver profile and advanced stage HCCs were enrolled. Sorafenib therapy (daily dose 800 mg) was initiated within 4 weeks after initial conventional transarterial chemoembolization with an allowance of subsequent on-demand conventional chemoembolization. The primary endpoint was rate of protocol treatment completion, which was defined as sorafenib administration for at least 2 months. Secondary endpoints included objective response rate, disease control rate, overall survival, progression-free survival, and incidence of adverse events. Thirty-one patients (24 men, 7 women; median age, 75 years; vascular invasion, n = 19; extrahepatic metastases, n = 18; both, n = 6) who met the inclusion criteria were enrolled. Results Protocol treatment was completed in 28 patients (90.3%, 28/31) with median protocol treatment duration of 7.0 months (range, 0.5–30 months) and median of 2 (range, 1–4) transarterial chemoembolization sessions. Objective response rate was 77.4% with median overall and progression-free survival of 17.3 months (95% confidence interval, 11.9–22.6 months) and 5.4 months (95% confidence interval, 4.6–6.2 months), respectively. The most common grade 3 or 4 adverse events were self-limiting elevation of aspartate aminotransferase (54.8%, 17/31) and alanine aminotransferase (45.2%, 14/31). Conclusions This combination therapy is feasible and promising in patients with advanced stage HCCs.

This study aimed to predict the treatment response for colorectal liver metastases (CLM) using relative tumor enhancement (RTE) of the hepatobiliary phase (HBP) for patients with no history of chemotherapy. In this retrospective study, we enrolled 26 patients [14 males, 12 females; median age: 58 years (range 37–82 years)] with CLM and no history of chemotherapy between December 2011 and May 2017. Gadoxetic acid-enhanced magnetic resonance imaging was performed before starting chemotherapy and RTE of HBP. The response was evaluated using RECIST ver.1.1, and progression-free survival (PFS) was estimated. Based on the RECIST ver.1.1, there were 15 responders and 11 non-responders. In the tumor, the mean pretreatment RTE values were significantly higher in the responders group than in the non-responders group (37.2% ± 10.9% vs. 17.9% ± 10.5%, respectively; P = 0.0006). When the threshold values of parameters for detecting responders comprised the RTE value of 24.2% (area under the curve value, 0.90), the sensitivity and specificity were 93.3% and 72.7%, respectively. The median follow-up period for 26 patients was 602 days (range 160–1971 days). Although no significant differences were observed in PFS between the groups, the high RTE group tended to take longer to progress than the low RTE group (PFS of the high RTE group did not reach the median). This study suggests that the RTE value of CLM could be a potential biomarker to predict early treatment response.

Introduction An Amplatzer Vascular Plug (AVP), which was designed as a permanent occluding device derived from the Amplatzer Septal Occluder and Amplatzer Duct Occluder, is a useful embolic device that can be precisely deployed in medium to large vessels with high resistance to migration. However, migration of these Amplatzer devices has been reported as a relatively rare but major complication. Case report A 59-year-old woman was referred for the treatment of advanced pancreatic body cancer; after systemic chemotherapy, distal pancreatectomy with en bloc celiac axis resection (DP-CAR) was planned as curative treatment. Therefore, preoperative embolisation of the common hepatic artery (CHA) for arterial redistribution was performed. Although a 6-mm AVP II was deployed at the mid-portion of the CHA, the AVP migrated to the proper hepatic artery. Although migrated AVP retrieval using a goose neck snare was attempted, it was impossible to retrieve it into the 5-F guiding sheath. Therefore, the AVP was delivered to the splenic artery, which was planned to be resected in DP-CAR. Finally, a 10-mm AVP II was redeployed at the proximal portion of the CHA, and complete occlusion was achieved. Conclusions When AVP retrieval is not possible, delivery to the other arteries having lesser influence might be an alternate technique.

Acute colorectal obstruction has been often reported as a secondary outcome of left-colonic malignancy. It is considered as a common emergency condition. Self-expandable metallic stent (SEMS) placement is widely used as a palliative treatment for the management of malignant colorectal obstruction (MCRO). SEMS placement is also deliberated as a bridge to surgery. With advances in technology, several recent studies of SEMS placement for MCRO indicated high technical (94–98%) and clinical (91–93%) success rates. The complication rate associated with SEMS is quite acceptable. However, long-term outcomes are still unclear. The symptoms should be carefully monitored before application of SEMS, particularly in patients who are eligible for systemic chemotherapy and in patients with a long life expectancy because of late complications such as reobstruction, stent migration, and perforation. Appropriate patient selection and placement technique are keys for the successful implementation of SEMS.

Proton beam therapy is a type of radiation therapy and a promising modality for cancer management because it involves few adverse effects and high therapeutic efficacy. However, there are reports of acute and late complications because of normal tissue damage. Hemobilia, known as bleeding from the biliary tree, is observed in various conditions, and it can also be of iatrogenic origin such as due to percutaneous hepatobiliary interventions. In most cases, it can be managed conservatively without significant hemorrhage. However, in a few cases with massive hemobilia, further intervention is necessary. We report the successful use of a stent-graft in the portal vein to treat massive hemobilia with porto-biliary fistula that was caused by previous proton beam therapy.

Superior mesenteric artery (SMA) pseudoaneurysms are rare but fatal. Surgical repair is an ideal treatment; however, it is inappropriate in patients with SMA pseudoaneurysm due to advanced cancer, and endovascular therapy is an alternative treatment for nonsurgical candidates. Here, we report a case of SMA pseudoaneurysm in a patient with advanced pancreatic cancer, which was successfully treated with the placement of a biliary covered stent. Keywords: Superior mesenteric artery, Pseudoaneurysm, Covered stent, Pancreatic cancer, Angiography

To evaluate the possibility of pathologic diagnosis and genetic analysis of percutaneous core-needle biopsy (CNB) lung tumor specimens obtained immediately after radiofrequency ablation (RFA). Patients who underwent CNB of lung tumors immediately after RFA from May 2013 to May 2016 were analyzed. There were 19 patients (8 men and 11 women; median age, 69 years; range, 52–88 years) and 19 lung tumors measuring 0.5–2.6 cm (median, 1.6 cm). Thirteen tumors were solid, and 6 were predominantly ground-glass opacity (GGO) on computed tomography. All specimens were pathologically examined using hematoxylin and eosin (H&E) staining and additional immunostaining, as necessary. The specimens were analyzed for EGFR and KRAS genetic mutations. The safety and technical success rate of the procedure and the possibility of pathologic diagnosis and genetic mutation analysis were evaluated. Major and minor complication rates were 11% (2/19) and 53% (10/19), respectively. Tumor cells were successfully obtained in 16 cases (84%, 16/19), and technical success rate was significantly lower for GGO-dominant tumors (50%, 3/6) compared with solid lesions (100%, 13/13, p = 0.02). Pathologic diagnosis was possible in 79% (15/19) of cases based on H&E staining alone (n = 12) and with additional immunostaining (n = 3). Although atypical cells were obtained, pathologic diagnosis could not be achieved in 1 case (5%, 1/19). Both EGFR and KRAS mutations could be analyzed in 74% (14/19) of the specimens. Pathologic diagnosis and genetic analysis could be performed even for lung tumor specimens obtained immediately after RFA.

Summary Background Unresectable advanced hepatocellular carcinoma is a heterogeneous disease, for which sorafenib is the first targeted agent approved for first-line therapy, and treatment options for patients with sorafenib-refractory advanced hepatocellular carcinoma are limited. We assessed the efficacy and safety of S-1, a chemotherapeutic agent based on fluorouracil, in patients with sorafenib-refractory advanced hepatocellular carcinoma. Methods We did a randomised, double-blind, placebo-controlled, phase 3 study done at 57 sites in Japan. Patients with advanced hepatocellular carcinoma who were ineligible for surgical or local-regional therapy and judged refractory to sorafenib (ie, had progressed on sorafenib or had discontinued sorafenib because of adverse events) were randomly assigned (2:1) to receive oral S-1 (weight-banded 80 mg/m 2 [80–120 mg per day]), or placebo, twice per day for 28 days consecutively, followed by a minimum 14 day drug-free period. This cycle was repeated until disease progression or the patient became intolerant to the study treatment. Patients were stratified by site and presence or absence of extrahepatic metastasis or vascular invasion. The primary endpoint was overall survival, assessed in the full analysis set (ie, all patients who were treated with study drug except any individuals who were found not to have hepatocellular carcinoma or who were found to have active double cancer). Patients, medical staff, investigators, and the sponsor were masked to treatment assignment. Blinding was maintained even after study treatment concluded. This study is registered with JapicCTI, number JapicCTI-090920, and has been completed. Findings Between Oct 26, 2009, and Aug 22, 2012, we screened 399 patients. 65 patients were excluded due to not meeting criteria (n=61), declining to participate (n=3), or other reasons (n=1). 334 patients were randomly assigned to receive either S-1 (n=223) or placebo (n=111). One patient in the S-1 group did not receive treatment, and was thus excluded from analyses. At data cutoff, median follow-up was 32·4 months (IQR 24·0–34·7) in the S-1 group and 32·9 months (23·7–39·5) in the placebo group. Median overall survival was 11·1 months (95% CI 9·7–13·1) in the S-1 group and 11·2 months (9·2–12·8) in the placebo group (hazard ratio 0·86, 95% CI 0·67–1·10; p=0·220). The most frequently reported adverse events were skin hyperpigmentation (123 [55%] of 222 patients in the S-1 group vs nine [8%] of 111 patients in the placebo group), decreased appetite (104 [47%] vs 21 [19%]), fatigue (102 [46%] vs 20 [18%]), diarrhoea (77 [35%] vs 14 [13%]), and increased blood bilirubin (77 [35%] vs 14 [13%]). Serious adverse events were reported in 90 (41%) of 222 patients in the S-1 group and 24 (22%) of 111 patients in the placebo group. Five treatment-related deaths were reported in the S-1 group. Interpretation S-1 did not prolong overall survival in patients with sorafenib-refractory advanced hepatocellular carcinoma. Further research is needed to identify subgroups of patients who might benefit from S-1. Funding Taiho Pharmaceuticals.

Background The aim of this study was to investigate the dose-limiting toxicities (DLTs) and determine the recommended doses in the Phase I part of the study, and to evaluate the efficacy and toxicity in the Phase II part, of continuous hepatic intra-arterial infusion therapy with 5-fluorouracil, mitoxantrone and cisplatin (FMP therapy) in patients with advanced hepatocellular carcinoma (HCC). Methods Forty-five patients with advanced HCC were enrolled. The therapy consisted of continuous intra-arterial infusion of 5-fluorouracil from Day 1 through Day 5, and intra-arterial administration of mitoxantrone and cisplatin on Day 1 [5-fluorouracil/mitoxantrone/cisplatin (mg/m2): Level 1; 400/4/60, Level 2; 400/6/60, Level 3; 500/6/60]. Results In the Phase I part of the study, one of the six patients at Level 1 developed DLTs, including Grade 3 pulmonary embolism, while none of the patients at either Level 2 or Level 3 exhibited any DLTs. In the Phase II part, at Level 3, 36 patients were enrolled. Nine patients (25%) showed partial response, representing a response rate of 25% (95% confidence interval: 12-42%). The overall median survival time, 1-year survival rate and median progression-free survival time were 11.3 months, 46.9% and 7.0 months, respectively. The main Grade 3 or 4 hematological and non-hematological toxicities were leukopenia (36%), neutropenia (39%), thrombocytopenia (19%), and elevated serum aspartate aminotransferase (22%), elevated serum alanine aminotransferase (14%) and occlusion of hepatic artery (22%), respectively. Conclusion Hepatic intra-arterial infusion therapy of FMP could not demonstrate a favorable tumor response and overall survival in patients with advanced HCC.

The purpose of this study was to assess hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous 5-fluorouracil (5-FU) and l-leucovorin (l-LV) in colorectal cancer (CRC) patients with systemic chemotherapy failure in a phase I/II trial. CRC patients with unresectable liver metastases following standard systemic chemotherapy failure were eligible. A catheter-port system for HAI was placed using interventional radiology. In phase I, escalating doses of oxaliplatin for levels 1 and 2 were set at 50 and 100 mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200 mg/m2 bolus and 2400 mg/m2/46-h continuous infusion) and l-LV (200 mg/m2). The dose-limiting toxicity (DLT) was assessed, and the recommended dose (RD) was estimated. In phase II, patients receiving RD were included to assess the 6-month survival rate (the expected rate 80%), overall survival time, tumor response, and toxicity. In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100 mg/m2. In phase II, seven additional patients were enrolled. In patients receiving RD (n = 10), the disease control rates for total lesions and liver lesions were 30 and 70%, respectively. The 6-month survival rate and the overall survival time were 53.3% and 6.9 months, respectively. There were no adverse reactions equivalent to DLT in any of the patients. The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100 mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.

BACKGROUND The prevalence of chronic obstructive pulmonary disease (COPD) is 8.6% in Japan and 10% worldwide. Unfortunately, many patients with COPD are not correctly identified and appropriately educated regarding the condition. In this paper, we demonstrate that some citizens of Ebina City with symptoms suspicious for COPD, such as cough, sputum production, and shortness of breath, have undiagnosed COPD. We describe our activities to raise awareness of COPD through a 10-year campaign. METHODS From 2006 to 2015, we developed activities to raise awareness of COPD, including public lectures, utilization of pulmonary function tests, and questionnaires on subjective symptoms and knowledge of COPD. RESULTS Among 1,206 participants aged>40 years, COPD was suspected in 5.6%, as indicated by airway obstruction (i.e. forced expiratory volume in 1 second (FEV1)/forced vital capacity ratio (FVC)

Herein, we report the case of an 84-year-old woman with epidermal growth factor receptor (EGFR) mutation exon 19 deletion postoperative recurrent lung adenocarcinoma. Osimertinib was administered as a first-line treatment; however, she was urgently admitted to our hospital due to dyspnea on the 46th day. Chest computed tomography revealed bilateral diffuse ground-glass opacities (GGOs) suggestive of grade 3 osimertinib-induced interstitial lung disease (ILD). After discontinuation of osimertinib in combination with short-term corticosteroid therapy, widespread GGOs were promptly resolved. As the disease gradually deteriorated after discontinuation of osimertinib, we administered osimertinib (80 mg every other day) followed by careful observation. However, bilateral GGOs re-appeared on the 15th day, and the diagnosis of osimertinib-induced ILD was established. After the improvement in ILD following corticosteroid therapy, afatinib was administered as salvage therapy, resulting in desirable control of lung cancer without any relapse of ILD. Our results indicate that afatinib would be a promising alternative treatment option even in patients who develop osimertinib-induced ILD and experience failure of osimertinib rechallenge.

A 65-year-old man with hepatocellular carcinoma (HCC) due to alcohol-related liver cirrhosis had undergone transarterial chemoembolization 11 times. However, treatment for HCC was difficult to continue, due to episodic hepatic encephalopathy. He was referred to our hospital for treatment of hepatic encephalopathy, showing a Child-Pugh score of 8 despite medical therapy. Abdominal computed tomography revealed intrahepatic portosystemic venous shunt comprising two shunt tracts from the right posterior portal vein to the inferior vena cava via the right adrenal vein. The larger tract was occluded using an Amplatzer Vascular Plug (AVP) II, and the smaller tract was occluded using an original AVP. The postembolization course was uneventful. Hepatic encephalopathy improved after shunt occlusion and no recurrence had occurred as of one year after the procedure.

A panel of Japanese experts on tumor ablation therapy gathered to reach a general consensus on topics surrounding ablation therapy. Questionnaires relating to ablation protocols for radiofrequency ablation (RFA) and cryoablation, as well as ancillary procedures required for safe and secure ablation therapy, were sent to seven institutions. Experts from these institutions discussed each topic based on the evidence and the questionnaire data, and a consensus was reached at an annual meeting of the Japan Image-guided Ablation Group in Maebashi, Japan, in October 2015. A consensus was reached on each of six topics, including “management of antiplatelet and anticoagulation drug therapy”; “pain control in the perioperative period”; “arterial embolization combined with ablation therapy”; “protection of non-target organs”; “RFA and cryoablation protocols”; and “ablative margins.” The consensus achieved here will serve as the framework for tumor ablation therapies in Japan.

In the palliative setting, the necessity of biliary drainage of both liver lobes for malignant hilar biliary obstruction remains controversial. However, bilateral biliary drainage is a reasonable option to prevent cholangitis of the undrained lobe and to preserve liver function during the course of chemotherapy. Bilateral biliary drainage can be accomplished by the percutaneous or endoscopic placement of multiple self-expandable metallic stents (SEMS). Although SEMS placement via bilateral (multiple) percutaneous routes is technically simple, multiple percutaneous transhepatic biliary drainage (PTBD) may lead to additional morbidity. SEMS placement via a single percutaneous route is a useful method; however, negotiation of a guidewire into the contralateral bile duct is occasionally impossible if the hilar angle between the right hepatic duct and left hepatic duct is acute. Percutaneous dual SEMS placement is generally performed using the stent-in-stent technique (T configuration or Y configuration) or the side-by-side technique. In addition, the crisscross technique has been reported as being a useful method for trisegmental drainage. The side-to-end technique is also useful for multiple SEMS placement. In the future, the combination of percutaneous intervention and endoscopic ultrasonography-guided procedures may be effective in the management of malignant hilar biliary obstruction.

Purpose: To evaluate posthepatectomy liver failure (PHLF) using gadoxetic acid-enhanced magnetic resonance imaging (MRI) with a measure of relative liver enhancement (RLE) on hepatobiliary phase images, thereby facilitating safe liver resection. Methods: Twenty patients in Child-Pugh class A underwent tumor excision surgery and indocyanine green (ICG) clearance of future remnant liver (FRL) (ICG-Krem) values were >0.05. PHLF was evaluated using the grading system of the International Study Group of Liver Surgery (ISGLS). The RLE value was defined as the signal gain percentage between the precontrast and hepatocellular images. In the whole liver and FRL, theRLE value measured the tumor-free liver parenchyma in RLE images. We examined the correlation between indocyanine green clearance (ICG-K) and MRI-based liver function in the whole liver. Preoperative PHLF evaluation was predicted using remnant hepatocellular uptake index (rHUI), remnant RLE (rRLE), coefficient variation of Rrle [Cv(rRLE)], and ICG-Krem corrected by heterogeneous liver function(HLF-ICG-Krem). Results: HLF-ICG-Krem and rRLE values correlated with INRs after postoperative day five (r = -0.55 and 0.46, p = 0.01 and 0.04, respectively). Furthermore, HLF-ICG-Krem values ≤0.05 detected two patients with higher INRs after postoperative day five. On the other hand, neither rHUI nor Cv(rRLE) was correlated with INRs after postoperative day five (r = 0.28, and -0.03, respectively; p >0.05 for both). HLF-ICG-Krem was significantly lower with PHLF than without PHLF (p = 0.005). Conclusion: HLF-ICG-Krem is useful for evaluating PHLF more correctly.

BACKGROUND/AIM Anti-EGFR antibodies or bevacizumab comprise first-line treatment for patients with RAS wild-type colorectal liver metastases (CLM). Which marker better predicts efficacy, early tumor shrinkage or morphologic response, still remains unclear. PATIENTS AND METHODS We retrospectively evaluated 155 patients with KRAS exon 2 wild-type CLM treated with bevacizumab (BEV group) or anti-EGFR antibodies (EGFR group). Three radiologists independently assessed early tumor shrinkage (ETS) and early optimal morphologic response (EOMR) from baseline and first follow-up CT scan. RESULTS Patients with ETS had longer progression-free survival (PFS) than those without ETS [hazard ratio (HR)=0.69] and ETS tended to be observed in the EGFR group, while patients with EOMR had longer PFS than those without EOMR (HR=0.64) and EOMR tended to be observed in the BEV group. CONCLUSION Among patients with KRAS exon 2 wild-type CLM, EOMR and ETS may predict better PFS, especially in patients treated with bevacizumab and anti-EGFR antibodies, respectively.

A 20-year old man was diagnosed with fibrolamellar hepatocellular carcinoma (FLHCC) with multiple lung metastases, and chemotherapy with FOLFOX was administered. Contrast enhanced CT after 3 cycles of FOLFOX showed no disease progression. We therefore performed surgical resection and radiofrequency ablation of the liver lesions and lung metastases, after obtaining the patient's informed consent. The liver lesions and lung metastases tested positive for DNAJB1-PRKACA. The treatment for FLHCC with extrahepatic metastasis has not been established; however, in a few cases, good long-term prognoses were obtained with multidisciplinary therapy. We herein report a case of FLHCC with multiple lung metastases that was treated with multidisciplinary therapies.

Purpose To evaluate the safety and efficacy of a mixture of indigo carmine and lipiodol (MIL) as a marker of pulmonary nodule before video-assisted thoracic surgery (VATS). Materials and Methods One hundred sixty-eight sessions of pulmonary marking were performed using MIL before VATS for 184 nodules (mean size, 1.2 ± 0.6 cm; range, 0.3–3.6 cm) on 157 patients (83 men and 74 women; median age, 66 years). The mean distance between the lung surface and the nodule was 0.8 ± 0.7 cm (range, 0–3.9 cm). MIL was injected near the nodule using a 23-gauge needle. Mean number of 1.2 ± 0.4 (range, 1–3) punctures were performed in a session for the target nodules, with mean number of 1.1 ± 0.3 (range, 1–3). Successful targeting, localization, and VATS were defined as achievement of lipiodol accumulation at the target site on computed tomography, detection of the nodule in the operative field by fluoroscopy or visualization of dye pigmentation, and complete resection of the target nodule with sufficient margin, respectively. Results The successful targeting rate was 100%, and the successful localization rate was 99.5%, with dye pigmentation for 160 nodules (87.0%) and intraoperative fluoroscopy for 23 nodules (12.5%). Successful VATS was achieved for 181 nodules (98.4%). Two nodules (1.1%) were not resectable, and surgical margin was positive in 1 nodule (0.5%). Complications requiring interventions occurred in 5 sessions (3.0%) and included pneumothorax with chest tube placement (n = 3) and aspiration (n = 2). No complication related to the injected MIL occurred. Conclusions MIL was safe and useful for preoperative pulmonary nodule marking.

To compare the clinical outcomes between radiofrequency ablation (RFA) and cryoablation for the treatment of clinical T1b (cT1b) renal cell carcinoma (RCC).The data of 46 patients [(39 men and 7 women, median age; 73 years, range 39-87 years)] were gathered from 3 institutions. RFA and cryoablation were performed on 23 patients each. The median number of ablation needle was 2 (range 1-4) and 4 (range 3-5, p 0.0001) in RFA and cryoablation, respectively. Technique efficacy defined as coverage of the tumor by ablative zone, adverse events, local tumor progression, and survival were compared between the RFA and cryoablation groups.The primary technique efficacy rate was significantly higher in the cryoablation group (96%, 22/23) than in the RFA group (65%, 15/23, P = 0.02). There was no significant difference in the secondary technique efficacy rate after additional RFA and cryoablation [21/23 (91%) vs. 23/23 (100%); P = 0.24]. The incidence of grade 3 or higher adverse events was similar between the 2 groups (P 0.99). There was no significant difference between local tumor progression rate after RFA and cryoablation [3/21 (14%) vs. 2/23 (9%); P = 0.66]. The 5-year overall survival rates were comparable between RFA and cryoablation (78 vs. 82%; P =0.82).Other than primary technique efficacy, the clinical outcomes between RFA and cryoablation were similar in patients with cT1b RCC.

Conservative treatments are usually attempted for the management of post-esophagectomy chylous leakage. However, surgical intervention may be needed when the chylous leakage cannot be stopped using conservative treatments. For the therapeutic management of refractory chylous leakage, it is important to identify the leakage sites when deciding if surgical intervention is required. Nine patients underwent lymphangiography for the treatment of refractory post-esophagectomy chylous leakage. Radiological findings, the daily outputs of pleural effusion after lymphangiography, and the clinical outcomes after lymphangiography were analyzed in our cases and in a retrospective collection of 24 cases from 1983 to 2015 recorded with precise detail. In the 9 cases directly studied in our center, the median postoperative day of lymphangiography was 15 days. The detection rate of leakage sites after lymphangiography was 89 %. After lymphangiography, daily outputs of pleural effusion less than 500 ml were observed in 5 patients (56 %), all of whom healed conservatively. Daily outputs of more than 500 ml were seen in 4 patients (44 %). Of these patients, 1 patient had leakage from the main trunk and underwent clipping of the thoracic duct. In the remaining 3 patients, the leakages were instead observed in branches or were not observed; the 2 patients who had no anatomical variants were healed by chemical pleurodesis, and the 1 patient who had anatomical variants required surgical intervention. In the analysis of 33 previously reported cases (which included our 9 cases), the therapeutic policy was determined after lymphangiography, and all patients were successfully healed. Early lymphangiography is recommended for patients with refractory post-esophagectomy chylous leakage. Lymphangiography may contribute valuable information in deciding whether surgical intervention is required.

In stereotactic body radiotherapy (SBRT) for centrally located non-small cell lung carcinoma (NSCLC), severe hemoptysis has been reported in several studies. We report here a rare case of hemoptysis after SBRT even though the lung tumor was peripherally located. A lung nodule of a 79-year-old man was accidentally found at the periphery of the left upper lobe. A computed tomography-guided biopsy of this nodule provided confirmation of the diagnosis of poorly differentiated adenocarcinoma. The clinical diagnosis was T1bN0M0, stage I primary lung cancer. The patient was treated with SBRT using helical tomotherapy at a dose of 60 Gy in 6 fractions (i.e., BED10 = 120). He obtained a complete response and did not experience recurrence. However, the patient suffered massive hemoptysis 4.5 years after SBRT. As hypervascularity of a left bronchial artery was observed at the left lung in accordance with SBRT field on bronchial arteriography, a bronchial artery embolization (BAE) procedure was performed. The patient has had no episodes of hemoptysis after BAE. Although SBRT for early stage NSCLC is usually safe and efficient, it is necessary to be careful for late-onset bronchial hemorrhage in SBRT, even for a peripheral tumor.

Purpose To investigate the feasibility of percutaneous drainage via the blind end of the jejunal limb (BEJL) for afferent limb syndrome and pancreatic fistula. Materials and Methods Percutaneous drainage via the BEJL was performed in eight patients (seven men and one woman; mean age, 63 y; range, 42–71 y) presenting with afferent limb syndrome (n = 6) or pancreatic fistula (n = 2) following pancreatoduodenectomy or bile duct resection with reconstruction at our institute from March 2005 to June 2013. Reconstruction was performed by using a modified Child method or the Roux-en-Y method, and the BEJL was surgically fixed to the abdominal wall. Afferent limb syndrome was caused by tumor recurrence or postoperative complications. Technical success, clinical success, and complications were evaluated retrospectively. Results Technical success of drainage via BEJL was achieved in all patients. Drainage catheters (5–10 F) were inserted into the afferent limbs of six patients, into the pancreatic duct of one patient, and into the pancreatic fistula of one patient. Metallic stents were subsequently placed to address malignant afferent limb obstruction in two patients. Clinical success was achieved in seven patients (87.5%), and no patients developed major complications. Drainage catheters were removed from four patients. The mean catheter indwelling period in all patients was 143 days (range, 21–292 d). Conclusions Percutaneous drainage via BEJL after pancreatoduodenectomy or bile duct resection may be a feasible treatment for afferent limb syndrome and pancreatic fistula.

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 20 min 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 15 min, prothrombin activity(%), platelet count, and cellular density in the liver parenchyma (p Conclusions Uptake CERH images are useful for visualizing liver uptake function.

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.

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/m(2) /cycle; level 2, 50 mg/m(2) /cycle; and level 3, 65 mg/m(2) /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/m(2) /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.

OBJECTIVE Percutaneous endoscopic gastrostomy is widely practiced, but we use interventional radiology techniques to perform percutaneous radiologic gastrostomy in cancer patients with conditions that prevent endoscope insertion due to pharyngoesophageal obstruction. This study retrospectively investigated the effectiveness of percutaneous radiologic gastrostomy at our hospital. METHODS We investigated the medical records of 105 patients who underwent percutaneous radiologic gastrostomy between 2001 and 2011. The technique used for percutaneous radiologic gastrostomy comprised insufflation to dilate the stomach via a nasogastric tube, followed by fluoroscopically guided puncture and gastrostomy tube placement. In patients for whom a nasogastric tube could not be inserted, the stomach was punctured with a fine needle under ultrasonographic guidance and insufflated via this puncture needle to achieve dilation. RESULTS Patients comprised 75 men and 30 women (mean age, 63 years). A nasogastric tube was used during percutaneous radiologic gastrostomy in 81 cases, but could not be used in 24. The percutaneous radiologic gastrostomy procedure was successful in all cases. Serious post-percutaneous radiologic gastrostomy complications comprised one case each of decreased hemoglobin requiring blood transfusion, pneumoperitonitis that was treated by a laparotomy and infected fistula requiring tube removal (3/105, 2.9%). Duration of gastrostomy tube placement was 1-731 days, and the outcome was death in 59 cases, hospital transfer in 23, tube removal in 18 and survival with gastrostomy tube in place in 5. CONCLUSIONS Serious complications requiring treatment occurred in 2.9% of cases in which percutaneous radiologic gastrostomy was performed, with mostly good effectiveness. Percutaneous radiologic gastrostomy is feasible even for patients in whom a nasogastric tube cannot be inserted.

Purpose To evaluate and compare the usefulness of equivalent cross-relaxation rate (ECR) imaging (ECRI) and diffusion-weighted imaging (DWI) in the early prediction of the response of bevacizumab-containing treatments of colorectal liver metastases. Methods and material Seven patients received bevacizumab-containing treatments for colorectal liver metastases. Serial magnetic resonance imaging was performed to evaluate responses before and 2 weeks after starting chemotherapy. In the ECRI, we adopted the off-resonance technique for preferential saturation of immobile protons to evaluate the ECR values. A single saturation transfer pulse frequency was used at a frequency of 3.5 ppm downfield from the water resonance. In the DWI, the apparent diffusion coefficient (ADC) value commonly used with two b -values was acquired by using diffusion weightings of 0 and 800 s/mm 2 . The region of interest of the metastatic lesions in the liver was separately measured by ECRI and DWI. Tumor response was assessed by response evaluation criteria in solid tumors criteria 8 weeks after starting chemotherapy. Results In this study, we had four responders and three nonresponders. There was a significant difference in the pretreatment ECR values between the responders and nonresponders ( P =.01); there was no significant difference in the ADC values between the two groups. Analysis of the percentage difference between the pretreatment and post-treatment values, termed as percentage change, showed that there were no significant differences in the percentage change of the ADC values between both groups; however, the percentage change in the ECR value was significantly greater for the responders than for the nonresponders (−41.6%±17.1% vs. –12.9%±6.9%, respectively; P =.04). Conclusion The pretreatment ECR value and percentage change of the ECR value 2 weeks after starting chemotherapy were useful parameters in the early prediction of response to bevacizumab-containing treatment in colorectal liver metastases.

Background Two standard sets of criteria are used to evaluate the tumor response of hepatocellular carcinoma (HCC): RECIST (Response Evaluation Criteria in Solid Tumors) and modified RECIST (mRECIST). The purpose was to compare two tumor response evaluation criteria, RECIST version 1.1 and mRECIST, for HCC treated using transcatheter arterial chemoembolization (TACE). Methods The radiological findings of patients who underwent TACE for HCCs in a multicenter clinical trial were examined. Sixty-five lesions in 21 patients treated with TACE without mixing iodized-oil were evaluated. The tumor size was evaluated by measuring the entire lesion, including the necrotic part, using RECIST version 1.1, whereas only the contrast-enhanced part observed during the arterial phase was measured using mRECIST. Five radiologists independently measured each lesion twice. To evaluate the inter-criteria reproducibility, the complete response (CR) rate, the response rate, the kappa statistics, and the proportion of agreement (PA) for response categories were calculated. The same analyses were conducted for inter- and intra-observer reproducibility. Results In the inter-criteria reproducibility study, the CR rate and the response rate obtained using mRECIST (56.9% and 79.7%) were higher than those obtained using RECIST version 1.1 (9.2% and 43.1%). In the inter- and intra-observer reproducibility study, mRECIST exhibited an ‘almost perfect agreement', while RECIST version 1.1 exhibited a ‘substantial agreement'. Conclusions Considerable differences in the CR rate and the response rate were observed. From the viewpoint of the high inter- and intra-observer reproducibility, mRECIST may be more suitable for tumor response criteria in clinical trials of TACE for HCC.

A phase II study of stent therapy for unresectable malignant colorectal obstruction was conducted to ascertain the clinical efficacy, safety, and procedural feasibility.Inclusion criteria comprised unresectable obstruction of the rectum or sigmoid colon; no other apparent stenosis; performance status by Eastern Cooperative Oncology Group ≤3; and maintained major organ function. The treatment protocol was to place an uncovered metal stent through the anus in an obstructive portion under x-ray fluoroscopic guidance. The patients were followed for 4 weeks after therapy, and the degree of improvement in subjective symptoms lasting ≥2 weeks was assessed as effective when the patient was decompressed with stent, or ineffective when not decompressed. Rate of clinical efficacy was defined as the proportion of effective cases.The participants of the study comprised 33 patients (13 men and 20 women; mean age, 60 y). Rate of procedure completion was 97.0% (32/33). Treatment was effective in 27 patients, ineffective in 4, and unassessable in 1, yielding a clinical efficacy rate of 81.8% (27/33). Death owing to underlying disease (n=3), stent removal owing to anal pain (n=1), and occlusion at another location (n=1) were noted. No recurrences were seen among clinically effective cases. Adverse reactions included grades 2 to 3 diarrhea (n=12), pain (n=5), bleeding (n=1), and dysuria (n=1), but no grade 4 adverse reactions or treatment-related deaths were identified.Stent therapy for unresectable malignant colorectal obstruction is effective, safe, and feasible.

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n=60) and a group given off-protocol treatment (n=27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n=23), stable disease (n=38), or progressive disease (n=26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ=0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.

The efficacy and safety of cetuximab for irinotecan-intolerant patients has not yet been evaluated in detail. We retrospectively analyzed the efficacy and safety of cetuximab monotherapy for patients with metastatic colorectal cancer (MCRC) that was intolerant to irinotecan. Among 105 patients who received cetuximab-containing chemotherapy until March 2010, 22 patients were treated with cetuximab monotherapy due to irinotecan intolerance. Cetuximab was given at the approved dosage to all patients. The performance status was 2 or 3 in 17 patients (77%). All but 1 patient had wild-type KRAS tumors. The causes of irinotecan intolerance were icterus (n = 9; 41%; median serum total bilirubin, 6.3 mg/dl), symptomatic peritoneal metastasis or obstruction (n = 8; 36%), and thrombocytopenia (n = 1; 5%). Four patients (18%) refused irinotecan due to previous irinotecan-associated toxicity. Two patients achieved a partial response with an apparent drop of serum bilirubin, for a response rate of 9.1%. The median progression-free survival and overall survival were 1.6 and 3.5 months, respectively. No grade 3 or 4 adverse events or treatment-related deaths were experienced. Cetuximab monotherapy for irinotecan-intolerant MCRC is feasible. However, the overall efficacy was modest in the present cohort, despite the fact that most of the patients had wild-type KRAS tumors; further effective therapies should be evaluated to improve the prognosis of this patient population.

No established therapy exists for unresectable intrahepatic cholangiocarcinoma (ICC). We conducted a phase I/II study to ascertain the recommended dose (RD) of hepatic arterial infusion using gemcitabine (GEM) for ICC and to assess the efficacy and safety.For patients with unresectable ICC, GEM was administered through the hepatic artery via the port system as a 30-minute infusion on days 1, 8, and 15 every 4 weeks for 5 cycles. In phase I, dosage for levels 1, 2, and 3 was set at 600, 800, and 1000 mg/m, respectively, and was increased in 3 to 6 patients at a time. Maximum tolerated dose was defined as a dosage resulting in dose-limiting toxicity in 2 of 3 patients or 3 of 6 patients, and RD was estimated during the first cycle. In the phase II, more RD patients were added to assess tumor response and toxicity.During the phase I, 16 patients were enrolled. Maximum tolerated dose was not reached. Assuming RD at 1000 mg/m, the phase II enrolled a total of 13 patients. The following Grade 3 toxicities were observed: neutropenia 20%, increased gamma-glutamyl transpeptidase 8%, increased aspartate aminotransferase 4%, increased alanine aminotransferase 4%, increased bilirubin 4%, nausea 4%, and fatigue 4%. The tumor response rate was 7.7% (complete response 0, partial response 1, stable disease 8, and progressive disease 4).Whereas the toxicity of hepatic arterial infusion with 1000 mg/m GEM for ICC was tolerable, expected efficacy could not be obtained, thus suggesting only minimal activity.

Background: The ability of molecular targeting agents to improve overall survival (OS) in metastatic colorectal cancer (MCRC) patients who underwent oxaliplatin-based chemotherapy remains controversial. Methods: We retrospectively analyzed 331 patients with MCRC who underwent first-line oxaliplatin-based chemotherapy. Treatment outcomes were compared between patients who started chemotherapy from April 2005 to March 2007 (cohort A; n = 157) and those who started it from April 2007 to March 2009 (cohort B; n = 174). To evaluate the impact of exposure to agents, we applied time-varying covariate analysis to avoid possible lead-time bias. Results: Median OS of cohorts A and B was 21.3 and 28.6 months, respectively (HR 0.66, 95% CI 0.50–0.87, p = 0.003). Exposure to bevacizumab (25 vs. 76%), anti-epidermal growth factor receptor (EGFR) (18 vs. 33%) or curative surgery after chemotherapy (4 vs. 10%) was significantly higher in cohort B. According to a multivariate Cox model with exposure to each agent or treatment as a time-varying covariate, hazard ratios of death were 0.71 (95% CI, 0.51–0.96; p = 0.03) for bevacizumab, 0.62 (95% CI, 0.40–0.89; p = 0.01) for anti-EGFR and 0.22 (95% CI, 0.06–0.57; p = 0.004) for surgery. Conclusions: Increased exposure to molecular targeting agents or surgery after chemotherapy appears to contribute to an improvement in OS in recent patients with MCRC who have undergone oxaliplatin-based chemotherapy.

Complete esophageal obstruction developed after radiation and endoscopic submucosal dissection therapy for a cervical esophageal cancer in a 77-year-old woman. After failure to recanalize the esophageal obstruction by endoscopic and catheterization techniques, the esophageal obstruction was penetrated using a trocar stylet needle via a gastrostomy route. A covered stent was placed across the esophageal obstruction, letting her take water and liquid food until she died 2 months later. There was no complication related to the procedures except transient chest discomfort and pain that subsided with symptomatic treatment.

Peritoneal venous shunts (PVSs) are widely used for palliating symptoms of refractory malignant ascites and are recognized as one of the practical methods. However, reliable clinical data are insufficient because most previous reports have been small studies from single centers. We conducted a retrospective, multicenter study to evaluate the safety and efficacy of radiologically placed PVSs in patients with malignant refractory ascites. A total of 133 patients with malignant ascites refractory to medical therapies were evaluated for patient characteristics, technical success, efficacy, survival times, adverse events, and changes in laboratory data. PVSs were successfully placed in all patients and were effective (i.e., improvement of ascites symptoms lasting 7 days or more) in 110 (82.7%). The median duration of symptom palliation was 26 days and median survival time was 41 days. The most frequent adverse event was PVS dysfunction, which occurred in 60 (45.1%) patients, among whom function was recovered with an additional minimally invasive procedure in 9. Abnormalities in coagulation (subclinical disseminated intravascular coagulation) occurred in 37 (27.8%) patients, although only 7 (5.3%) developed clinical disseminated intravascular coagulation. Other major adverse events were gastrointestinal bleeding (9.8%), sepsis (3.8%), and acute heart failure (3.0%). PVS was least effective in patients with elevated serum creatinine, bloody ascites, or gynecologic tumor. Radiological PVS is a technically feasible and effective method for palliating the symptoms from refractory malignant ascites, but preoperative evaluation and monitoring the postprocedural complications are mandatory to preclude severe adverse events after PVS.

Introduction: Cetuximab-based chemotherapy showed a statistically significantly higher response rate compared with chemotherapy such as FOLFOX. Therefore, FOLFOX plus cetuximab is suspected to be the best regimen to alleviate tumor-related symptoms with a high response rate. Case Report: Here we present the results of 8 consecutive patients with metastatic colorectal cancer with poor performance status and/or severe complications who were treated with first-line FOLFOX with cetuximab. Six of 8 patients achieved an apparent clinical benefit, including radiological response and symptoms improvement. Two patients with BRAF mutation could achieve neither clinical benefit nor radiological response. Conclusion: Although an optimal line of therapy with cetuximab is unclear yet with bevacizumab in mind, we propose that patients who need a tumor response to alleviate their symptoms due to advanced disease might be candidates for first-line cetuximab-based therapy as shown in our cases. Additionally, patients with BRAF mutant tumors might be important candidates for novel targeted therapy in the future to improve their poor prognosis.

We 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.Port-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/m(2) 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.Port-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.Initial 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.

Acute hyperammonemic encephalopathy induced by fluoropyrimidines (FPs) is a rare complication. Its pathophysiology remains unclear, especially given the currently used regimens, including intermediate-doses of 5-fluorouracil (5-FU) or oral FP agents. We aimed to characterize the clinical manifestations in cancer patients who developed hyperammonemic encephalopathy after receiving FP-based chemotherapy.We retrospectively reviewed 1786 patients with gastrointestinal or primary-unknown cancer who received FP-based regimens between 2007 and 2012. Eleven patients (0.6%) developed acute hyperammonemic encephalopathy. The incidence according to the administered anticancer drugs were as follows: 5-FU (8 of 1176, 0.7%), S-1 (1 of 679, 0.1%), capecitabine (2 of 225, 0.9%), and tegafur-uracil (UFT) (0 of 39, 0%). Ten patients (90.9%) had at least 1 aggravating factor, including infection, dehydration, constipation, renal dysfunction, and muscle loss. All the 10 patients met the definition of sarcopenia. Median time to the onset of hyperammonemic encephalopathy in the cycle was 3 days (range: 2-21). Three patients (27.3%) developed encephalopathy during the first cycle of the regimen and the remaining 8 patients during the second or more cycles. Seven patients (63.6%) had received at least 1 other FP-containing regimen before without episodes of encephalopathy.All patients recovered soon after immediate discontinuation of chemotherapy and supportive therapies, such as hydration, infusion of branched-chain amino acids, and oral lactulose intake, with a median time to recovery of 2 days (range