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Purpose: Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) can affect systemic circulation, causing fatal complications. Standard treatment is yet to be established due to its rarity and intractability. We sought to determine the clinical efficacy of external beam radiotherapy (EBRT) in HCC treatment. Patients and methods: Our group designed this multicenter trial and recruited patients with HCC and IVC and/or RA involvement. Forty-nine patients from six institutions received EBRT with median dose of 46.7 (range: 35.4-71.5) Gy during 2009-2016. The primary outcome was overall survival (OS), and relevant predictors were evaluated. Results: Median follow-up length was 9.3 (range: 1.1-119) months. Median survival, 1-, and 2- year OS rates were 10.1 months (95% confidence interval [CI]: 7.5-12.7 months), 43.5%, and 30.1%, respectively. Significant factors affecting OS were alpha-fetoprotein level ≥300 ng/mL (risk ratio [RR]: 2.34, p  = .025), tumor multiplicity (RR: 2.56, p  = .028), and patient volume of institutions (high- vs. middle volume centers) (RR: 3.58, p  = .001). Local control rates were 88.7% and 74.5% at 1 and 2 years, respectively. The most common first failure site was the lung (21/49, 42.9%) followed by liver outside the EBRT field (17/49, 34.7%). One case of possible radiation-induced liver disease was noted, with transient alkaline phosphatase elevation. Conclusion: EBRT can yield favorable local control in HCC with IVC and/or RA involvement. Systemic treatment may be more indicated as factors reflecting tumor aggressiveness were significant, and first distant failure is common.

Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT., Methods: Tumor cell line VX2 was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used., Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 ± 0.12 kg, 57.83 ± 8.68 days, (16.73 ± 5.18 %), (29.47 ± 7.18 %), and 2.03 ± 0.13 kg, 43.67 ± 5.28 days, (63.01 ± 2.01 %), (6.02 ± 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C., Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT in rabbit model.

The liver is a large abdominal organ in the right hypondrium. Because of its anatomical situation, it is near many abdominal PTVs as well as some lower thoracic PVTs. The liver could also be at the same time the target (for irradiation of liver metastases or primary liver tumours) and organ at risk (OAR). Radiation-induced liver disease (RILD) is radiobiologically the normal tissue complication probability (NTCP), i.e., the clinical event limiting the total dose that could be delivered. This review describes radiobiological criteria justifying the NTCP data, and recommendations for conformal 3D radiotherapy and stereotactic liver irradiation., (Copyright (c) 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background/aims: The purpose of this study is to evaluate the effect of radiation therapy (RT) for tumor thrombosis (TT) in the major portal vein (PV) or inferior vena cava (IVC) from unresectable hepatocellular carcinoma., Methodology: Fifteen HCC patients with main PVTT (n = 10) and IVCTT (n 5) were treated with three-dimensional conformal RT between 2001 and 2004. The mean dose was 38.5 Gy (range 28 to 54Gy). The concurrent therapies to intrahepatic tumor included transcatheter arterial chemoembolization (TACE) in 7, TACE + hepatic arterial infusion in 2 and systemic chemotherapy in 1 patient. The therapeutic effect was assessed by tumor regression for TT., Results: An objective response was observed in 3 of 15 patients (20%). There were no patients with progressive disease. The median survival time was 10 months. In 12 cases with stable disease, time to progression (TTP) estimated above 6 months were 42% (5/12 cases). In univariate analysis, therapeutic effect and TTP were affected to survival time. All patients did not have severe deterioration of liver function., Conclusions: In the current study, we concluded that RT was superior treatment in terms of local control capability and was useful to continue further treatment because RT did not make liver function worse.

We studied morphological changes in rat abdominal aorta and vena cava inferior induced by endovascular microwave destruction. This treatment induced thrombosis and necrosis of the vascular walls, but fibrous framework was not completely destroyed. Then we observed irreversible changes in vessels: obliteration, atrophy of the aorta walls, and sclerosis of venous walls. The preserved fibrous framework of the vessel walls probably plays a role of a framework for the formation of fibrous tissue.

The aim of this study was to evaluate the efficacy of brachytherapy for preventing neointimal hyperplasia in the inferior vena cava (IVC) after stent placement. Sixteen beagles underwent Z-stent placement in the IVC and the aorta. For 8 of 16 beagles, irradiation (15 Gy) was delivered endoluminally to the stented segments of each vessel immediately after stent placement using the 192Ir. All animals were sacrificed after 6 weeks for morphometric and histopathologic examination. Morphometrically, neointimal thickness in the IVC of the radiation group was significantly decreased compared with the control group as well as that in the aorta (p < 0.05). Histopathologic findings showed the neointima in the IVC of the control group contained markedly organization of thrombus and neovascularization though that in the IVC of the radiation group consisted mainly of smooth muscle cells without organization of thrombus and neovascularization. From these data intravenous irradiation may prevent clinical restenosis after stent placement.

Background: Intratumoral ablative therapy is being used increasingly for the treatment of primary and secondary hepatic malignancies. The interstitial point-source photon radiosurgery system (PRS) is a novel ablative technique that uses radiation therapy similar in dosimetry to interstitial brachytherapy., Study Design: To determine the feasibility, toxicity, and local tissue destructive capabilities of the PRS in the liver, preliminary studies in a nontumor-bearing canine model were examined. A 6-month survival study was conducted. Each animal received three radiation treatments, in the right, central, and left hepatic regions. Three low-dose treatments were delivered to each of six animals (group A), generating a 2.0-cm-diameter radiated sphere with a dose of 20 Gy at the lesion edge. Three high-dose treatments were delivered to each of six animals (group B), generating a 3.0-cm-diameter radiated sphere with 20 Gy at the lesion edge., Results: The treatment reproducibly generated sharply demarcated hepatic ablative lesions proportional to the administered dose. Mean lesion diameter at 1 month was 1.6+/-0.2 cm in group A and 3.4+/-1.0 cm in group B. Lesion size was independent of intrahepatic location, including near vascular structures. PRS therapy, when applied to portal structures, resulted in hilar damage. Hilar damage appeared to be associated with arteriolar thrombosis and bile duct injury. Treatment of regions adjacent to large hepatic veins and the IVC was not associated with vessel thrombosis or stricture., Conclusions: PRS ablation is a generally well-tolerated method that results in consistent, well-demarcated, symmetric lesions of complete necrosis with minimal adjacent parenchymal injury. Application of such an approach for the treatment of liver tumors is promising.

Non-traumatic duodenocaval fistulae are rare, but may be the source of massive gastrointestional bleeding with associated fever and sepsis. These fistulae result from penetrating duodenal peptic ulcers or right nephrectomy and subsequent radiation to the upper abdomen. The outcome depends on early diagnosis and surgery before a potentially fatal hemorrhage occurs. The therapy of choice includes closure of the fistula and repair of the duodenum and inferior vena cava. We describe the seventh case with radiogenic duodenal ulcer. Gastrointestinal bleeding occurred 10 years after radical nephrectomy and radiation (60 Gy). The patient survived following partial pancreatoduodenectomy (Whipple).

Background: Despite verification of bidirectional conduction block after radiofrequency (RF) catheter ablation in the inferior vena cava (IVC)-tricuspid annulus (TA) isthmus, recurrence of common atrial flutter is relatively common. Although complete linear reablation is usually performed, we evaluated a simplified electrophysiological strategy selectively targeting recovered conducting isthmus tissue., Methods and Results: Twenty-one patients (18 men and 3 women, age, 54+/-10 years) with a recurrence of typical atrial flutter 6+/-7 months after an apparently successful catheter ablation in the IVC-TA isthmus prospectively underwent electrophysiologically targeted reablation during flutter. Sites with narrow electrograms or fractionated electrograms interposed between adjacent sites with double potentials considered to represent gaps were ablated without movement of the catheter. Mapping showed that 18 of 21 patients had a single gap. Successful ablation required a single application in 14 patients and, in the group as a whole, a median of one application (mean, 2+/-2; range, 1 to 11) with resultant bidirectional block in 13 of 16. A single narrow electrogram (duration, 48+/-6 ms; amplitude, 0.1+/-0.05 mV) was noted at the successful site in 11, whereas a fractionated electrogram (97+/-32 ms, 0.05+/-0.04 mV, P<.05) was noted in 9. There were four additional recurrences during a follow-up at 7+/-5 months; three were similarly ablated with a median of one pulse., Conclusions: Transmural ablation lesions in the isthmus can be recognized during flutter by double potentials separated by an isoelectric interval. Postablation recurrent flutter is usually due to a single discrete recovered gap; this is represented by a single or a fractionated potential spanning the isoelectric interval of adjacent double potentials, which can be selectively targeted to minimize repeat ablation.

Purpose: The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs., Methods and Materials: Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment., Results and Conclusion: Dogs receiving IORT to the retroperitoneum through a 4 x 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses > or = 30 Gy. Radiation changes were present in the aorta and vena cava at doses > or = 40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed a few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT.

Cancer invasion to the caudate lobe of the liver is considered an important prognostic factor in hepatic hilar bile duct cancer, and caudate lobectomy is required in cases with massive invasion. In many cases, however, the invasion is difficult to confirm even at intraoperative examination. As the caudate lobe is close to the inferior vena cava, it can be irradiated by a source in the inferior vena cava. In this paper, intracavitary irradiation of the caudate lobe via the inferior vena cava is proposed instead of resection for possible, but not confirmed, invasion. In experiments on dogs, intracavitary irradiation was performed by remote after-loading using 60Co at a dose of 20 and 300 Gy via the inferior vena cava. The radiation is so highly concentrated on the designated target that an anticancer effect can be expected. No noteworthy side effects were observed by functional and morphological studies after 20 Gy irradiation. This treatment has been applied clinically, with favorable results. This treatment modality is a non-surgical caudate lobectomy aimed at avoiding useless, and potentially hazardous, resection.