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Purpose: This study was designed to investigate the clinical outcome of patients with irresectable, intrahepatic cholangiocarcinoma (IHC) treated with computed tomography (CT)-guided HDR-brachytherapy (CT-HDRBT) for local tumor ablation., Method: Fifteen consecutive patients with histologically proven cholangiocarcinoma were selected for this retrospective study. Patients were treated by high-dose-rate internal brachytherapy (HDRBT) using an Iridium-192 source in afterloading technique through CT-guided percutaneous placed catheters. A total of 27 brachytherapy treatments were performed in these patients between 2006 and 2009. Median tumor enclosing target dose was 20 Gy, and mean target volume of the radiated tumors was 131 (±90) ml (range, 10-257 ml). Follow-up consisted of clinical visits and magnetic resonance imaging of the liver every third month. Statistical evaluation included survival analysis using the Kaplan-Meier method., Results: After a median follow-up of 18 (range, 1-27) months after local ablation, 6 of the 15 patients are still alive; 4 of them did not get further chemotherapy and are regarded as disease-free. The reached median local tumor control was 10 months; median local tumor control, including repetitive local ablation, was 11 months. Median survival after local ablation was 14 months and after primary diagnosis 21 months., Conclusion: In view of current clinical data on the clinical outcome of cholangiocarcinoma, locally ablative treatment with CT-HDRBT represents a promising and safe technique for patients who are not eligible for tumor resection.

Purpose: To determine the safety and efficacy of computed tomography (CT)-guided brachytherapy in hepatocellular carcinoma (HCC)., Methods and Materials: A total of 83 patients were recruited, presenting with 140 HCC- lesions. Treatment was performed by CT-guided high-dose-rate (HDR) brachytherapy with an iridium-192 source. The primary endpoint was time to progression; secondary endpoints included local tumor control and overall survival (OS). A matched-pair analysis with patients not receiving brachytherapy was performed. Match criteria included the Cancer of the Liver Italian Program (CLIP) score, alpha-fetoprotein, presence, and extent of multifocal disease. For statistical analysis, Kaplan-Meier and Cox regression were performed., Results: Mean and median cumulative TTP for all patients (n = 75) were 17.7 and 10.4 months. Five local recurrences were observed. The OS after inclusion reached median times of 19.4 months (all patients), 46.3 months (CLIP score, 0), 20.6 months (CLIP score, 1) 12.7 months, (CLIP score, 2), and 8.3 months (CLIP score, >or=3). The 1- and 3-year OS were 94% and 65% (CLIP score, 0), 69% and 12% (CLIP score, 1), and 48% and 19% (CLIP score, 2), respectively. Nine complications requiring intervention were encountered in 124 interventions. Matched-pair analysis revealed a significantly longer OS for patients undergoing CT-guided brachytherapy., Conclusion: Based on our results the study treatment could be safely performed. The study treatment had a beneficial effect on OS in patients with advanced HCC, with respect to (and depending on) the CLIP score and compared with OS in a historical control group. A high rate of local control was also observed, regardless of applied dose in a range of 15 to 25 Gy., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

For evaluation of triple-phase multislice computed tomography (CT) for assessment of hepatocellular carcinoma (HCC) before liver transplantation. All HCC patients who underwent liver transplantation at our institution between 2001 and 2006 and had contrast-enhanced abdominal 4-/16-slice CT [unenhanced, arterial (20 s delay), portal venous (40 s), and venous (80 s) scan] within 100 days before transplantation were enrolled retrospectively. CT data were reviewed by two observers. Results were correlated to histopathologic findings by means of a lesion-by-lesion evaluation. Thirty-two patients with 76 HCC-lesions were included. The lesion-based sensitivity of observer 1 and 2 was 78% (59/76) and 83% (63/76) (false positives, n = 6 and n = 10). The sensitivity of observer 1/2 was 89%/95% for lesions >20 mm (n = 37), 94% for lesions 11-20 mm (n = 18), and 43%/53% for lesions <10 mm (n = 21). The mean detection rates of unenhanced, arterial, portal venous, and venous phase scans were 30%, 74%, 59%, and 40%. All detected lesions were visible on arterial and/or portal venous scans (arterial only, 24%; portal venous only, 9%). Arterial and portal venous phase scans are the strongest contributors to the high detection rate of triple-phase multislice-CT in HCC. However, the detection of small HCC measuring <10 mm and false positive findings remains a challenge.

Aims: Liver resection represents a curative treatment approach in patients suffering from liver metastases from gastric cancer. However, its value in the treatment of these patients remains controversial. This study was conducted to evaluate the safety and effectiveness of liver resection in these conditions and to identify criteria for the selection of suitable patients., Methods: From January 1988 to December 2002, 24 patients underwent liver resection for metastatic gastric cancer. The outcome of these 24 patients was retrospectively reviewed using a prospective database. Patient, tumour and operative parameters were analyzed for their influence on long-term survival., Results: One patient died and four patients (17%) developed complications during the postoperative course. The overall one-, three- and five-year survival was 38%, 16% and 10%, respectively. After curative resection (n=17), the one-, three- and five-year survival rate was 53%, 22% and 15%, respectively, and patients with metachronous metastases restricted to the liver (n=5) had a one-, three- and five-year survival of 80%, 40% and 40%, respectively. In the univariate analysis, extrahepatic manifestation showed in tendency (p=0.069) and resection margins statistically significant (p=0.005) influence on survival. The multivariate analysis revealed only resection margins as an independent prognostic factor for survival., Conclusions: Long-term survival can be achieved by liver resection in well selected patients and may be considered in the multidisciplinary treatment approach of metastatic gastric cancer. Patients with metastatic disease restricted to the liver in whom a curative resection can be achieved seem to be most suitable for liver resection.

The purpose of the study was to establish a diagnostic approach to the preparation of patients with colorectal liver metastases considered for transarterial radioembolization (RE). Twenty-two patients sequentially underwent computed tomography (CT; thorax/abdomen), magnetic resonance imaging (MRI; liver; hepatocyte-specific contrast), positron emission tomography (PET/PET-CT; F18-fluoro-desoxy-glucose), and angiography with perfusion scintigraphy [planar imaging; tomography with integrated CT (SPECT-CT)]. The algorithm was continued when no contraindication or alternative treatment option was found. The impact of each test on the therapy decision and RE management was recorded. Patient evaluation using CT revealed contraindications for RE in 4/22 patients (18%). Of the remaining 18 patients, 2 were excluded and 3 were assigned to locally ablative treatment based on MRI and PET results (28%). The remaining 13 patients entered the planning algorithm: SPECT-CT revealed gastrointestinal tracer accumulations in 4 (31%) patients [SPECT, 2 (15%)], making a modified application necessary. In five patients (38%), planar scintigraphy revealed relevant hepatopulmonary shunting. Therapy was finally administered to all 13 patients without therapy-related pulmonary or gastrointestinal morbidity. Each part of the diagnostic algorithm showed a relevant impact on patient management. The sequential approach appears to be suitable and keeps the number of unnecessary treatments and therapy risks to a minimum.

Brachytherapy for the treatment of liver metastases is a novel approach. In this procedure, techniques of locally ablative treatment in interventional radiology and radiation therapy are combined. After computed tomography (CT)-guided percutaneous implantation of catheters into the hepatic tumor, the irradiation is performed in an afterloading technique. This minimally invasive procedure offers circumscriptive high-dose rate irradiation of the lesion to treat in a single session, irrespective of breathing motion or potential cooling effects of neighboring vessels. Good local control rates have been achieved in several tumor entities, including both secondary and primary malignancies of the liver. This article gives an overview of the application technique, possible adverse events, and outcome with special attention to the pancreatic cancer scenario.

Background and Objectives: The value of liver resection for metastases from breast cancer is still controversial. This study was conducted to clarify safety and effectiveness of hepatectomy in this conditions and to identify selection criteria for patients suitable for liver resection., Methods: From January 1988 to December 2006, 39 patients underwent liver resection for metastases from breast cancer. The outcome of these 39 patients was retrospectively reviewed using a prospective database. Prognostic factors for patient survival were determined by univariate and multivariate analysis., Results: None of the patients died perioperatively and the morbidity rate was 13% (n = 5). The overall 1-, 3-, and 5-year survival rates were 77%, 50%, and 42%, respectively. In the univariate analysis, metastatic manifestation prior to hepatectomy, vascular invasion and resection margin revealed statistically significant influence on survival. The multivariate analysis identified only resection margin as an independent prognostic factor for survival., Conclusions: Liver resection should be considered in the multimodal treatment approach of patients with metastatic breast cancer. Hepatic resection can be performed with low risk and offers a chance of long-term survival. Achievement of a curative resection and less important absence of previous metastatic manifestation represent suitable criteria to select patients for liver resection., ((c) 2007 Wiley-Liss, Inc.)

Background and Aims: The surgical strategy for treatment of synchronous liver metastases from colorectal cancer remains controversial. This retrospective analysis was conducted to compare the postoperative outcome and survival of patients receiving simultaneous resection of liver metastases and primary colorectal cancer to those receiving staged resection., Materials and Methods: Between January 1988 and September 2005, 219 patients underwent liver resection for synchronous colorectal liver metastases, of whom, 40 patients received simultaneous resection of liver metastases and primary colorectal cancer, and 179 patients staged resections. Patients were identified from a prospective database, and records were retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on postoperative morbidity and mortality as well as on long-term survival., Results: Simultaneous liver resections tend to be performed for colon primaries rather than for rectal cancer (p = 0.004) and used less extensive liver resections (p < 0.001). The postoperative morbidity was comparable between both groups, whereas the mortality was significantly higher in patients with simultaneous liver resection (p = 0.012). The mortality after simultaneous liver resection (n = 4) occurred after major hepatectomies, and three of these four patients were 70 years of age or older. There was no significant difference in long-term survival after formally curative simultaneous and staged liver resection., Conclusion: Simultaneous liver and colorectal resection is as efficient as staged resections in the treatment of patients with colorectal cancer and synchronous liver metastases. To perform simultaneous resections safely a careful patient selection is necessary. The most important criteria to select patients for simultaneous liver resection are age of the patient and extent of liver resection.

Background: This study was conducted to evaluate the safety and efficacy of liver resection in patients with hepatic metastases from renal cell carcinoma and to identify selection criteria for patients suitable for resection., Methods: Between January 1988 and March 2006, 31 patients underwent liver resection for metastases from renal cell carcinoma. Patients were identified from a prospective database and retrospectively reviewed. Patient, tumor, and operative parameters were analyzed for their influence on long-term survival., Results: The overall 1-, 3- and 5-year survival rates were 82.2%, 54.3%, and 38.9%, respectively. One patient was deceased and 4 developed complications during the postoperative course. In the univariate analysis, site of the primary tumor (P = 0.013), disease-free interval (P = 0.012), and resection margins (P = 0.008) showed significant influence on long-term survival. In the multivariate analysis, only the resection margins were identified as an independent prognostic factor after liver resection., Conclusions: Liver resection is effective and safe in the treatment of patients with hepatic metastases from renal cell carcinoma and offers the chance of long-term survival and cure. Achieving a margin-negative resection is the most important criterion in the selection of suitable patients for liver resection. However, the number of patients in the present study was small, and investigations of larger series may provide further prognostic parameters in these patients.

Aims: Numerous patients suffer from recurrence after resection of liver metastases from colorectal cancer. Recurrence is frequently restricted to the liver and repeat liver resection may offer a curative option in these patients. This study was conducted to clarify safety and effectiveness of this treatment and to identify prognostic factors of a favourable outcome after repeat hepatectomy., Methods: Between January 1988 and March 2006 in our institution 811 patients underwent 841 liver resections for metastases from colorectal cancer. Among these, 94 patients underwent a repeat hepatectomy. Patients were identified from a prospective database and retrospectively reviewed. Results of different time periods were assessed and prognostic factors for a favourable outcome were determined., Results: The perioperative morbidity and mortality was 24% (23 of 94) and 3% (3 of 94), respectively. The one-, three-, five- and ten-year survival for all patients in this series was 89%, 55%, 38% and 23%, respectively. In the univariate analysis, pT-stage of the primary, diameter of the largest metastases, surgical radicality, period of resection and distribution of metastases showed statistically significant influence on survival. The multivariate analysis revealed only pT-stage of the primary tumour, surgical radicality and period of resection as independent prognostic factors., Conclusions: Repeat hepatectomy is a safe and effective treatment for recurrent liver metastases from colorectal cancer. Perioperative risk and long-term survival were similar when compared to the results obtained during the initial resection. Achieving a curative resection is the most relevant prognostic factor for a favourable prognosis after repeat liver resection.

Background: Ultrasound is known to be useful in imaging radiofrequency ablation (RFA) lesions intra- and postoperatively. The presented study intends to prove the value of ultrasound examination as a means of screening RFA-treated patients for local tumor recurrence., Patients and Methods: During a period of 47 months, 91 RFA treatments were performed in 61 patients in a single institution. Indications for RFA were hepatocellular carcinoma (74%), colorectal metastases (18%), recurrent cholangiocellular carcinoma (5%) and one neuroendocrine tumor metastasis as well as one metastasis of pancreatic cancer (1.5% each). RFA was only considered in non-resectable liver cancer. All applications were conducted under sonographic guidance following preoperative evaluation. Postoperative screening included sonographic examinations at intervals of 3, 6 and 12 months postoperatively, and further annual follow-up examinations. Mean follow-up period was 11.8 months., Results: Within the first 12 months after treatment, the lesions become more and more inhomogenous with mixed echogeneity. Occasionally, this evolves as a misleading finding, mimicking early tumor recurrence. To clarify suspicious cases (31%), magnetic resonance imaging (20%) or computed tomography (10%) was engaged. Ultrasound led to the detection of local tumor recurrence in 78% of recurrent HCC (13 patients), but only in 67% of metastatic diseases (3 patients). Overall local recurrence rate was 18%., Conclusion: Ultrasound screening as a follow-up of primary hepatic malignancies is, due to its sensitivity, capable of detecting early local recurrence despite its low specifity. Appropriate application of particular criteria of local recurrence allows B-mode ultrasound to play a major role in screening RFA-treated patients.

Background: Malignant epithelioid hemangioendothelioma is a rare vascular tumor described mostly in soft tissue, lungs, or liver. The outcome after a wide variety of therapeutic measures, ranging from extended surgical therapy to no therapy, is reported to be variable. Therefore, we reviewed our experience with resective therapy for this rare liver tumor, including orthotopic liver transplantation., Material and Methods: During a period of 5 years, seven patients with the histological diagnosis of hepatic epithelia hemangioendothelioma were seen. In five of them, the liver pathology was detected at random, and all patients were prospectively followed. The therapeutic measures and course of disease are given as case reports., Results: Three patients received formal liver resection and two received liver grafts, one partial and one whole. One further patient is scheduled for transplantation and one is undergoing alternative therapy, with the tumor remaining stable. All resected patients recovered quickly and are alive and well 2 months to 4 years later without signs of tumor recidivism., Conclusion: Anatomic liver resection, or in the case of diffuse tumor spread, orthotopic liver transplantation, show favorable long-term results for the treatment of hepatic epithelioid hemangioendothelioma. Therefore, surgical therapy is proposed as the treatment of choice for this entity.

Purpose: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation., Methods and Materials: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D(90), i.e., the dose achieved in at least 90% of the pseudolesion volume., Results: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D(90) for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1)., Conclusions: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays.

Purpose: To assess the outcome of interventional hepatic arterial port placement in a prospective phase II trial., Materials and Methods: One-hundred five consecutive patients were included in this study. Primary endpoint was port patency; secondary endpoints were complications, toxicity, response, and progression free and overall survival. Seventy-eight patients presented with liver metastasis only, 6 patients had additional minor extrahepatic disease, and 21 patients had no evidence of disease after liver resection, laser-induced thermotherapy, or computed tomography (CT)-guided interstitial brachytherapy of liver metastasis. Exclusive access route was the femoral artery. Subgroup analysis compared either 4-F catheters (n = 58) to 2.2-F (n = 33) and 2.7-F (n = 20) microcatheters or different strategies in anatomic variants of the celiac branch: neglect (n = 10) or embolization of minor hepatic feeders (n = 11), splenic arterial port (n = 8), double port (n = 7)., Results: Technical success was 99%. Assisted port patency after 6 months was 93%. Complications demanding port revisions were significantly lower in patients receiving 4-F versus 2.2-F and 2.7-F systems (P <.001), with disconnection as the major problem with use of microcatheters. Hepatic artery thrombosis occurred in 10 patients (9%), with successful lysis in two patients. With use of 4-F and 2.2-F catheters, there was no difference with respect to catheter occlusion or hepatic thrombosis. No differences were noted in complications or outcome applying four different strategies in celiac branch variants. In a subgroup of patients receiving folinic acid/5-fluorouracil (170 mg/600 mg; 10% dose escalation per cycle) for 5 days every 4 weeks only 15% experienced Grade 3 toxicity. Patients with liver metastasis and salvage therapy demonstrated progression-free survival of 63% after 6 months and a median survival of 16 months., Conclusion: Interventional placement of hepatic arterial port systems may overcome frequent hepatic arterial chemotherapy failures as encountered in all published major trials on hepatic arterial infusion.

Purpose: To assess safety and efficacy of CT-guided brachytherapy of liver malignancies., Patients and Methods: 21 patients with 21 liver malignancies (19 metastases, two primary liver tumors) were treated with interstitial CT-guided brachytherapy applying a (192)Ir source. In all patients, the use of image-guided thermal tumor ablation such as by radiofrequency or laser-induced thermotherapy (LITT) was impeded either by tumor size > or = 5 cm in seven, adjacent portal or hepatic vein in ten, or adjacent bile duct bifurcation in four patients. Dosimetry was performed using three-dimensional CT data sets acquired after CT-guided positioning of the brachytherapy catheters., Results: The mean tumor diameter was 4.6 cm (2.5-11 cm). The mean minimal tumor dose inside the tumor margin amounted to 17 Gy (12-20 Gy). The proportion of the liver parenchyma exposed to > 5 Gy was 18% (5-39%) of total liver parenchyma minus tumor volume. Nausea and vomiting were observed in six patients after brachytherapy (28%). One patient demonstrated obstructive jaundice due to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. We commonly encountered asymptomatic increases of liver enzymes. Local control rates after 6 and 12 months were 87% and 70%, respectively., Conclusion: CT-guided brachytherapy is safe and effective. This technique displays broader indications compared to image-guided thermal ablation by radiofrequency or LITT with respect to tumor size or localization.

Rationale and Objectives: The authors correlate computed tomography (CT) findings in biphasic spiral technique with histopathology in patients with hepatocellular carcinoma (HCC) who had undergone liver resection (LR) or orthotopic liver transplantation (OLT)., Methods: Preoperative biphasic spiral CT findings in 33 consecutive patients (23 men, 10 women, aged 43-74 years; LR group: n = 17; OLT group; n = 16) with liver cirrhosis and HCC were reviewed retrospectively by consensus of two radiologists and correlated with pathology from liver specimens., Results: Of the 16 patients in the OLT group with 1 to 5 confirmed HCC lesions (total lesions: 29; mean lesion diameter: 2 cm; range: 0.6-5.0 cm), CT before OLT depicted 22 lesions in 15 patients (sensitivity for lesions with a diameter of 0.5-1.0 cm, 20%; for lesions 1.1-2.0 cm, 82%; and for lesions 2.1-3.0 cm and > 3.0 cm, 86% and 100%, respectively). Among the 17 patients in the LR group (total lesions: 21; mean lesion diameter: 5.4 cm; range: 1.0-11.0 cm), CT detected 18 lesions. Lesion-by-lesion sensitivity, as correlated with pathology, was calculated at 76% and 86% in the OLT and LR groups, respectively (overall sensitivity, 80%). The diameter of CT detected lesions, compared with liver specimens, corresponded in 90% of lesions (maximum deviation, 15%). Characteristic CT findings of HCC included unenhanced hypoattenuating focal liver lesions (32 lesions), with hyperattenuation (38 lesions) in the arterial phase of contrast material administration., Conclusions: Biphasic spiral CT for preoperative HCC detection correlated with pathology in 80%, thus proving this technique to represent a sensitive imaging modality for pretherapeutic evaluation of HCC.