Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

BACKGROUND: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan. METHOD: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC). RESULTS: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively. CONCLUSION: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.

Hepatic arterial infusion chemotherapy vs transcatheter arterial embolization for patients with huge unresectable hepatocellular carcinoma.

For the treatment of huge unresectable hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) or transcatheter arterial embolization (TAE) generally had poor effects and high complication rates. Our previous study found that Hepatic arterial infusion chemotherapy (HAIC) is a safe procedure and provides better survival than symptomatic treatment for the patients with huge unresectable HCC. The aim of the study is to compare the effect of HAIC vs TAE in patients with huge unresectable HCC.Since 2000 to 2005, patients with huge (size > 8 cm) unresectable HCC were enrolled. Twenty-six patients received HAIC and 25 patients received TAE. Each patient in the HAIC group received 2.5 + 1.4 (range: 1-6) courses of HAIC and in the TAE group received 1.8 + 1.2 (range: 1-5) courses of TAE. Baseline characteristics and survival were compared between the HAIC and TAE group.The HAIC group and the TAE group were similar in baseline characteristics and tumor stages. The overall survival rates at 1 and 2 years were 42% and 31% in the HAIC group and 28% and 24% in the TAE group. The patients in the HAIC group had higher overall survival than the TAE group (P = .077). Cox-regression multivariate analysis revealed that HAIC is the significant factor associated with overall survival (relative risk: 0.461, 95% confidence interval: 0.218-0.852, P = .027). No patients died of the complications of HAIC but three patients (12%) died of the complications of TAE.In conclusion, HAIC is a safe procedure and provides better survival than TAE for patients with huge unresectable HCCs.

Evaluating primary intra-arterial chemotherapy versus intravenous plus intra-arterial chemotherapy for advanced intraocular retinoblastoma.

PURPOSE: Although intra-arterial chemotherapy (IAC) is commonly used for treating intraocular retinoblastoma, it is not a systemic therapy. We aimed to investigate whether the addition of intravenous chemotherapy (IVC) before IAC administration had any effects (whether beneficial or adverse) on patient outcomes. METHODS: This multicenter retrospective cohort study included 213 patients with advanced intraocular retinoblastoma who received IVC plus IAC (n = 103) or IAC alone (n = 110) between April 2009 and January 2017. Eyes were grouped according to the International Intraocular Retinoblastoma Classification. Kaplan-Meier and Cox regression analyses were performed to compare survival outcomes between the two groups. Moreover, details regarding enucleation were recorded. RESULTS: The 3-year ocular survival rates were 62% in the IVC plus IAC group and 68% in the IAC group (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.55-1.43, P = 0.61). Moreover, the corresponding 3-year overall survival rates were 97% and 93%, respectively (HR 1.56, 95% CI 0.41-5.90, P = 0.51), while the 3-year event-free survival rates were 76% and 72%, respectively (HR 0.96, 95% CI 0.56-1.65, P = 0.89). CONCLUSIONS: Within a 3-year follow-up period, IVC plus IAC produced no additional benefit over primary IAC for treating advanced intraocular retinoblastoma in terms of local tumor control and extending survival. Longer follow-up periods are required to assess long-term efficacy.

Intra-arterial infusion chemotherapy versus isolated upper abdominal perfusion for advanced pancreatic cancer: a retrospective cohort study on 454 patients.

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.

Role and limitation of neoadjuvant hepatic arterial infusion chemotherapy in advanced hepatocelluar carcinoma patients with Child-Pugh class A.

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) have a poor oncologic outcome. In this study, we evaluated the role and limitation of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients with Child-Pugh class A and the efficacy of liver resection subsequent to downstaging after neoadjuvant HAIC. METHODS: In the present retrospective study, 103 patients with advanced HCC, who underwent neoadjuvant HAIC from April 2003 to March 2015 were analyzed. Response to HAIC was evaluated by dividing time period into after 3 cycles and after 6 cycles, each defined as early and late period. Liver resection after neoadjuvant HAIC was offered in patients who were considered as possible candidates for curative resection with tumor-free margin as well as sufficient future liver remnant volume. RESULTS: The median survival time (MST) in all patients was 14 ± 1.7 months. Response rate and disease control rate were 36.3% (37) and 81.4% (83) in early period, respectively, and 26.4% (14) and 47.2% (25), in late period, respectively (P = 0.028). Twelve patients (11.7%) underwent liver resection after neoadjuvant HAIC and the MST was 37 ± 6.6 months. One-, 3-, and 5-year recurrence-free survival after liver resection were 58.3%, 36.5%, and 24.3% respectively. Liver resection was identified as the only independent prognostic factor that associated with overall survival in multivariate analysis (P = 0.002) CONCLUSION: HAIC could be further alternative for the treatment of advanced HCC in patients with good liver function. If liver resection is possible after neoadjuvant HAIC, liver resection would provide better outcomes than HAIC alone.

Net health benefit of hepatic resection versus intraarterial therapies for neuroendocrine liver metastases: A Markov decision model.

BACKGROUND: Management of patients with neuroendocrine liver metastasis (NELM) remains controversial. We sought to compare the net health benefit (NHB) of hepatic resection (HR) versus intraarterial therapy (IAT) among patients with NELM. METHODS: A decision analytic Markov model was created to estimate and compare the cost effectiveness associated with different management strategies (HR vs IAT) for a simulated cohort of patients with NELM. The primary (base case) analysis was calculated based on a 57-year-old male patient with metachronous, symptomatic NELM that involved <25% of the liver in the absence of extrahepatic disease. The endpoints were quality-adjusted life-months (QALMs), quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and NHB. RESULTS: In the base case analysis, HR was strongly favored over IAT providing NHB of 20.0 QALMs and an ICER of $8,427 per QALY. In the Monte Carlo simulation, the greatest NHB for HR was among patients with functioning/symptomatic NELM, regardless of liver tumor burden. In the symptomatic group, IAT was favored only in a minority of old patients (>60 years) with extrahepatic disease and synchronous NELM. In contrast, in patients with nonfunctioning/asymptomatic NELM, hepatic tumor burden was the most important variable and HR was always cost ineffective in large tumors, independent of patient age and extrahepatic disease characteristics. CONCLUSION: A Markov decision model demonstrated that HR was the preferred strategy among patients with symptomatic NELM, regardless of hepatic disease burden. In contrast, IAT should be preferred for patients with large volume nonfunctioning/asymptomatic NELM.

[Hepatic arterial infusion chemotherapy for colorectal liver metastases].

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.

[Analysis of methods of administration on local arterial infusion chemotherapy for severe advanced hepatocellular carcinoma].

Between 1986 and 1994, hepatic local arterial infusion chemotherapy with implanted reservoir was performed for 51 patients with hepatocellular carcinoma (HCC) who were not indicated for surgery, PEIT and/or TAE because of the advanced stage of tumors and impaired liver function. We compared direct effects, survival rates, and rates of outpatients by dividing these 51 patients into 3 groups according to the methods of administration--repeated one-shot arterial infusion group, continuous arterial infusion group and intermittent high-dose arterial infusion group. There were no significant differences among these three groups in terms of background factors. The continuous infusion group had significantly better survival rates than the repeated one-shot infusion group, and the survival rate of the intermittent high-dose infusion group was similar to that of the continuous infusion group, although there were no significant differences in effectiveness among the three groups. Patients in the continuous infusion group and intermittent high-dose infusion group could receive almost all of their treatment as outpatients. Furthermore, more patients in the intermittent high-dose infusion group could receive whole treatment without hospitalization than patients in the continuous infusion group. Because intermittent high-dose arterial infusion of 5-FU showed about the same survival rate as continuous arterial infusion and because it can maintain high quality of life, it is suggested to be a standard method for local arterial infusion of 5-FU for severe advanced HCC.

[Long-term survival in patients with breast cancer after intra-arterial infusion chemotherapy].

Twenty two patients with locally advanced breast cancer survived for more than 5 years after intra-arterial infusion chemotherapy (IA). In this study, we compared these long-term-survivors with thirteen cases who died within 2 years. The results were as follows. (1) ER positive rate of the long-term-survivors (90%) was significantly higher than in short-term-survivors (25.0%). (2) There was no difference between the response rates of each group; 63.2% in long-term-survivors vs. 53.8% in short-term-survivors. (3) Adjuvant endocrine therapies were carried out in the former group, and their D.F.I. were considerably longer than in the latter group. (4) Common sites of recurrence in long-term-survivors were soft tissues and bones, compared with visceral in short-term-survivors. Post-recurrence survivals of the former were, also, longer than in the latter. From these results, we confirmed that preoperative IA and following adjuvant endocrine therapies induces favorable results in the treatment of hormone sensitive breast cancer.

[Long-term follow-up study of transcatheter arterial chemotherapy in patients with advanced breast cancer].

Intra-arterial infusion chemotherapy (I.A) was applied to 32 cases with advanced breast cancer. The subclavian artery was intubated and one shot of 30 mg of adriamycin was given every 3 days, with a total dose of over 150 mg. Then mastectomy was performed after this chemotherapy. Long-term follow-up study revealed that the response rates of the primary tumor to I.A chemotherapy provided the prospects for their prognosis. The 3-and 5-year survival of good responders (% tumor regression greater than or equal to 70%) was significantly better than those of poor responders (% tumor regression less than 70%). Then, four patients with advanced breast cancer were treated with combination of I.A infusion chemotherapy of Adriamycin and photoradiation by argon laser. The mean interval time for 50% tumor regression was shorter than in the cases treated with Adriamycin alone. In vitro, the effects of the photoradiation for MCF-7 breast cancer cell line were observed only at a high concentration of Adriamycin.

A simplified surgical technical procedure for intra-arterial chemotherapy in secondary liver cancer. Experience in 50 patients.

The purpose of this study was to prove that only one intra-arterial catheter for hepatic chemotherapy can perfuse the whole liver in all anatomic cases, including cases with aberrant or accessory hepatic arteries. The ligations of various hepatic arteries induce the immediate aperture of intra hepatic arterial shunts and a total revascularization of the whole liver by the only remaining hepatic artery. Based on the experience from 50 consecutive cases of surgical implantation of intra-arterial catheters for local chemotherapy, the simplified technique is analysed principally as a function of anatomical variations of the hepatic artery. The usual procedure (catheter implanted into the gastro-duodenal artery) was performed in 58% of the cases, while in 28% of the cases this was possible only after section of a right and/or a left aberrant or accessory hepatic artery. Unusual implantations were necessary in 14% of the cases to ensure complete perfusion of liver. The evaluation was based on three criteria: intra-operative perfusion of fluorescein, post-operative scan with 99mTc macro-aggregated albumin and objective clinical responses after intra-arterial chemotherapy. The perfusion of the whole liver was good in all cases except one. Unusual procedures gave the same clinical objective responses after intra-arterial chemotherapy (61%) as usual procedures (48%) (chi-square: P = 0.40).