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Sellner F. Isolated Pancreatic Metastases of Renal Cell Carcinoma-A Paradigm of a Seed and Soil Mechanism: A Literature Analysis of 1,034 Observations. Front Oncol 2020; 10:709. [PMID: 32547940 PMCID: PMC7273884 DOI: 10.3389/fonc.2020.00709] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/15/2020] [Indexed: 12/15/2022] Open
Abstract
Previously documented arguments, in favor of the suspected impact of a seed and soil mechanism, in the development and progression of isolated pancreatic metastasis of renal cell carcinomas (isPM) are: (1) uniform and independent from the side of the primary tumor distribution of isPM within the pancreas and, (2) the similar survival rates for singular and multiple isPM. In addition, the present study adds new arguments that further confirm the importance of an seed and soil mechanism in isPM: (1) Within the singular isPM, the size of the metastasis does not affect the overall survival; (2) Within the group of multiple isPMs, the overall survival does not depend on the number of metastases; (3) For synchronous and metachronous isPM, survival rates are also not different, and (4) Within the group of metachronous isPM there is also no correlation between the overall survival and interval until metastases occurs. This unusual ineffectiveness of otherwise known risk factors of solid cancers can be explained plausibly by the hypothesis of a very selective seed and soil mechanism in isPM. It only allows embolized renal carcinoma cells in the pancreas to complete all steps required to grow into clinically manifest metastases. In all other organs, on the other hand, the body is able to eliminate the embolized tumor cells or at least put them into a dormant state for many years. This minimizes the risk of occult micrometastases in distant organs, which could later—after isPM treatment—grow into clinically manifest metastases, so that the prognosis of the isPM is only determined by an adequate therapy of the pancreatic foci, and prognostic factors, such as total tumor burden or interval until the occurrence of the isPM remain ineffective.
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Affiliation(s)
- Franz Sellner
- Surgical Department, Kaiser Franz Josef Hospital, Vienna, Austria
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CT Appearance of Hepatocellular Carcinoma after Locoregional Treatments: A Comprehensive Review. Gastroenterol Res Pract 2015; 2015:670965. [PMID: 26798332 PMCID: PMC4700180 DOI: 10.1155/2015/670965] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 09/09/2015] [Accepted: 09/14/2015] [Indexed: 02/08/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a major health problem worldwide, affecting more than 600,000 new patients per year. Curative treatments are available in a small percentage of patients, while most of them present in stages requiring locoregional treatments such as thermoablation, transarterial chemoembolization, and/or radioembolization. These therapies
result in specific imaging features that the general radiologist has to be aware of in order to assess the response to treatment and to correctly manage the follow-up of treated patients. Multiphasic helical computed tomography has become a popular imaging modality for detecting hypervascular tumors and characterizing liver lesions. On this basis, many staging and diagnostic systems have been proposed for evaluating response to all different existing strategies. Radiofrequencies and microwaves generate thermoablation of tumors, and transarterial chemoembolization exploits the double effect of the locoregional administration of drugs and embolizing particles. Eventually radioembolization uses a beta-emitting isotope to induce necrosis. Therefore, the aim of this comprehensive review is to analyze and compare CT imaging appearance of HCC after various locoregional treatments, with regard to specific indications for all possible procedures.
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Mainenti PP, Romano F, Pizzuti L, Segreto S, Storto G, Mannelli L, Imbriaco M, Camera L, Maurea S. Non-invasive diagnostic imaging of colorectal liver metastases. World J Radiol 2015; 7:157-169. [PMID: 26217455 PMCID: PMC4506934 DOI: 10.4329/wjr.v7.i7.157] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Revised: 05/10/2015] [Accepted: 06/01/2015] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer is one of the few malignant tumors in which synchronous or metachronous liver metastases [colorectal liver metastases (CRLMs)] may be treated with surgery. It has been demonstrated that resection of CRLMs improves the long-term prognosis. On the other hand, patients with un-resectable CRLMs may benefit from chemotherapy alone or in addition to liver-directed therapies. The choice of the most appropriate therapeutic management of CRLMs depends mostly on the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are available and those have a pivotal role in the workup of patients with CRLMs. Although extensive research has been performed with regards to the diagnostic performance of ultrasonography, computed tomography, positron emission tomography and magnetic resonance for the detection of CRLMs, the optimal imaging strategies for staging and follow up are still to be established. This largely due to the progressive technological and pharmacological advances which are constantly improving the accuracy of each imaging modality. This review describes the non-invasive imaging approaches of CRLMs reporting the technical features, the clinical indications, the advantages and the potential limitations of each modality, as well as including some information on the development of new imaging modalities, the role of new contrast media and the feasibility of using parametric image analysis as diagnostic marker of presence of CRLMs.
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Peixoto RD, Lim HJ, Kim H, Abdullah A, Cheung WY. Patterns of surveillance following curative intent therapy for gastroesophageal cancer. J Gastrointest Cancer 2015; 45:325-33. [PMID: 24756830 DOI: 10.1007/s12029-014-9601-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE Our aims were to examine surveillance strategies after curative treatment of early gastroesophageal (GE) cancer and to evaluate the impact of different approaches on outcomes. METHODS A total of 292 patients with non-metastatic GE cancer who were referred to the BC Cancer Agency from 2001 to 2010 for curative intent treatment were analyzed. Surveillance practices were classified into the following: cohort 1 (discharge to general practitioner), cohort 2 (follow-up by oncologist with clinical assessments), cohort 3 (specialist follow-up with laboratory investigations), and cohort 4 (specialist follow-up with imaging or endoscopy). Outcomes were compared across cohorts using Kaplan-Meier methods and Cox regression. RESULTS In total, median age was 63 years and 76 % were men. Eighty-nine (30%), 18 (6%), 32 (11%), and 152 (53%) patients were classified into cohorts 1 to 4, respectively. Patients with primary lesions involving the distal esophagus were more likely to undergo intensive surveillance which involved imaging studies and endoscopic procedures (p = 0.001). Individuals affected by specific histological subtypes, such as squamous cell carcinoma and the signet cell variant, and those whose disease were managed with definitive chemoradiotherapy without surgery were also more inclined to receive intensive follow-up (p = 0.008 and p = 0.001, respectively) There were no significant differences in overall (p = 0.34) or relapse-free survival (p = 0.59) among the different surveillance strategies, even after adjusting for measured prognostic factors. CONCLUSION In this population-based analysis, outcomes of GE cancer were comparable irrespective of surveillance strategy. Intensive follow-up with routine imaging and endoscopy may not be justified given the financial implications of these costly investigations.
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Affiliation(s)
- Renata D Peixoto
- Division of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, 600 West 10th Avenue, Vancouver, BC, V5Z 4E6, Canada
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Microwave ablation of liver metastases to overcome the limitations of radiofrequency ablation. Radiol Med 2013; 118:949-61. [PMID: 23892957 DOI: 10.1007/s11547-013-0968-1] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 02/08/2012] [Indexed: 12/15/2022]
Abstract
PURPOSE The purpose of our study was to evaluate technical success, effectiveness and safety of microwave ablation (MWA) in patients with unresectable liver metastases, where radiofrequency ablation (RFA) presents some limits. MATERIALS AND METHODS Twenty-five patients (17 men, 8 women) with 31 liver metastases >3 cm or located near vessels (>3 mm) were treated in a total of 29 sessions. Tumours were subdivided as follows: colorectal metastases (n=21) and no colorectal metastases (n=10). All procedures were performed percutaneously under ultrasound (US) guidance. Follow-up was performed with computed tomography (CT) scan at 1, 3, 6 and 12 months after treatment; mean follow-up period was 12.04 (range, 3-36) months. Technical success, mean disease-free survival, effectiveness and safety were evaluated. RESULTS Technical success was obtained in all cases. Mean disease-free survival was of 20.5 months. Local recurrence was recorded in 12.9% of metastases treated (4/31). No major complications were recorded. The rate of minor complications was 44.8% (13/29 sessions). Mortality at 30 days was 0%. CONCLUSIONS Percutaneous MWA of liver metastases >3 cm or located near vessels (>3 mm) can be considered a valid and safe option, probably preferable to RFA. Further studies are required to confirm these encouraging initial results.
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Baek HU, Kim SB, Cho EH, Jin SH, Yu HJ, Lee JI, Bang HY, Lim CS. Hepatic resection for hepatic metastases from gastric adenocarcinoma. J Gastric Cancer 2013; 13:86-92. [PMID: 23844322 PMCID: PMC3705137 DOI: 10.5230/jgc.2013.13.2.86] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2013] [Revised: 04/21/2013] [Accepted: 04/22/2013] [Indexed: 11/20/2022] Open
Abstract
PURPOSE The effects of hepatic resection on patients with metastatic tumors from gastric adenocarcinomas are unclear. Therefore, we analyzed early clinical outcomes in patients who underwent surgical resection for hepatic metastases from gastric adenocarcinomas. MATERIALS AND METHODS From January 2003 to December 2010, 1,508 patients with primary gastric cancers underwent curative gastric resections at the Korea Cancer Center Hospital. Of these patients, 12 with liver-only metastases underwent curative hepatic resection. Their clinical data were analyzed retrospectively. RESULTS The median follow-up period was 12.5 months (range, 1~85 months); no operative mortalities or major complications were observed. Three patients underwent synchronous resections, and 9 underwent metachronous resections. In the latter group, the median interval between gastrectomy and hepatectomy for hepatic metastasis was 10.5 months (range, 5~47 months). The overall 1- and 5-year survival rates of these 12 patients were 65% and 39%, respectively, with a median overall survival of 31.0 months; 2 patients survived for >5 years. CONCLUSIONS Hepatic resection can be a feasible procedure for treating hepatic metastases from gastric adenocarcinomas. Although this study was small and involved only selected cases, the outcomes of the hepatic resections were comparable and long-term (>5 years) survivors were identified. Surgical resection of the liver can be considered a feasible option in managing hepatic metastases from gastric adenocarcinomas.
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Affiliation(s)
- Hyoung-Un Baek
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Sang Bum Kim
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Eung-Ho Cho
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Sung-Ho Jin
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Hang Jong Yu
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Jong-Inn Lee
- Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Ho-Yoon Bang
- Department of Surgery, Konkuk University Hospital, Seoul, Korea
| | - Chang-Sup Lim
- Department of Surgery, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea
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Mainenti PP, Mancini M, Mainolfi C, Camera L, Maurea S, Manchia A, Tanga M, Persico F, Addeo P, D'Antonio D, Speranza A, Bucci L, Persico G, Pace L, Salvatore M. Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents. ABDOMINAL IMAGING 2010; 35:511-521. [PMID: 19562412 DOI: 10.1007/s00261-009-9555-2] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2009] [Accepted: 06/11/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND To compare contrast-enhanced US (CE-US), multidetector-CT (MDCT), 1.5 Tesla MR with extra-cellular (Gd-enhanced) and intracellular (SPIO-enhanced) contrast agents and PET/CT, in the detection of hepatic metastases from colorectal cancer. MATERIALS AND METHODS A total of 34 patients with colo-rectal adenocarcinoma underwent preoperatively CE-US, MDCT, Gd- and SPIO-enhanced MR imaging (MRI), and PET/CT. Each set of images was reviewed independently by two blinded observers. The ROC method was used to analyze the results, which were correlated with surgical findings, intraoperative US, histopathology, and MDCT follow-up. RESULTS A total of 57 hepatic lesions were identified: 11 hemangiomas, 29 cysts, 1 focal fatty liver, 16 metastases (dimensional distribution: 5/16 < 5 mm; 3/16 between 5 mm and <10 mm; 8/16 ≥ 10 mm). Six of 34 patients were classified as positive for the presence of at least one metastasis. Considering all the metastases and those ≥ 10 mm, ROC areas showed no significant differences between Gd- and SPIO-enhanced MRI, which performed significantly better than the other modalities (P < 0.05). Considering the lesions <10 mm, ROC areas showed no significant differences between all modalities; however MRI presented a trend to perform better than the other techniques. Considering the patients, ROC areas showed no significant differences between all the modalities; however PET/CT seemed to perform better than the others. CONCLUSIONS Gd- and SPIO-enhanced MRI seem to be the most accurate modality in the identification of liver metastases from colo-rectal carcinoma. PET/CT shows a trend to perform better than the other modalities in the identification of patients with liver metastases.
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Lee JW, Kim SK, Lee SM, Moon SH, Kim TS. Detection of Hepatic Metastases Using Dual-Time-Point FDG PET/CT Scans in Patients with Colorectal Cancer. Mol Imaging Biol 2010; 13:565-572. [DOI: 10.1007/s11307-010-0394-x] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Omed A, Lawrance JAL, Murphy G, Laasch HU, Wilson G, Illidge T, Tipping J, Zivanovic M, Jeans S. A retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies. Clin Radiol 2010; 65:720-8. [PMID: 20696299 DOI: 10.1016/j.crad.2010.05.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2009] [Revised: 03/14/2010] [Accepted: 05/07/2010] [Indexed: 01/25/2023]
Abstract
AIM To evaluate the efficacy and safety of selective internal radiation therapy (SIRT). MATERIALS AND METHODS A retrospective analysis was undertaken of all patients who underwent SIRT at a single institution. Diagnostic and therapeutic angiograms, computed tomography (CT) images, positron-emission tomography (PET) images, and planar isotope images were analysed. The response to SIRT was analysed using radiological data and tumour markers. Overall survival, complications, and side effects of SIRT were also analysed. RESULTS The initial 12 patients were included on an intention-to-treat basis, between 21/09/2005 and 07/05/2008. All patients had advanced disease and multiple prior courses of chemotherapy. One patient did not receive yttrium-90 due to complex vascular anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following work-up angiography. A response was seen using PET in 80% of patients. Using CT, the response of the tumour to therapy in the treated hepatic segments demonstrated a 20% partial response, stable disease in 50%, and progressive disease in 30%. Estimated median survival was 229 days, with 64% of patients still alive at the time of writing. No major complications were observed, although 82% of patients experienced side-effects following SIRT, mainly nausea, vomiting, and abdominal pain. CONCLUSIONS There have been no complications in the 12 SIRT patients. Tumour response was seen in four out of five patients who underwent PET. Objective CT response rates were mixed and are perhaps partially explained by advanced disease and limitations of using measurements to assess response. This complex and potentially hazardous service has been successfully and safely established.
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Affiliation(s)
- A Omed
- Manchester Medical School, University of Manchester, Stopford Building, Manchester, UK.
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Tsujimoto H, Ichikura T, Ono S, Sugasawa H, Hiraki S, Sakamoto N, Yaguchi Y, Hatsuse K, Yamamoto J, Hase K. Outcomes for patients following hepatic resection of metastatic tumors from gastric cancer. Hepatol Int 2010; 4:406-13. [PMID: 20305759 DOI: 10.1007/s12072-009-9161-y] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2009] [Revised: 09/20/2009] [Accepted: 12/11/2009] [Indexed: 12/12/2022]
Abstract
PURPOSE Although several studies have reported the efficacy of hepatic resection for the long-term survival of patients with gastric cancer metastases, the optimal treatment remains to be determined. METHODS Seventeen patients underwent a hepatic resection for gastric cancer metastases at the National Defense Medical College Hospital. We retrospectively analyzed the clinical outcomes of surgical resection and identified factors associated with prognosis for patients who underwent hepatectomy for gastric cancer metastases. RESULTS In 17 patients, the accumulated 5-year survival rate after hepatic resection was 31.5% and the median survival time was 34 months. Univariate and multivariate analyses showed that gastric tumors less than 6.0 cm and D2 lymphadenectomy were the most important predictors of survival. The five patients who survived more than 5 years after hepatic resection had a D2 lymphadenectomy, modest lymphatic invasion, primary gastric tumors less than 6.0 cm, and a solitary liver metastasis. CONCLUSION Although recent progress in adjuvant therapy should be the key to a good prognosis, we believe that surgical resection may bring some hope of long-term survival for judiciously selected patients with hepatic metastases from gastric cancer.
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Affiliation(s)
- Hironori Tsujimoto
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513 Japan.
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Konopke R, Kersting S, Distler M, Dietrich J, Gastmeier J, Heller A, Kulisch E, Saeger HD. Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases. Liver Int 2009; 29:89-102. [PMID: 18673436 DOI: 10.1111/j.1478-3231.2008.01845.x] [Citation(s) in RCA: 113] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND Patient outcome after resection of colorectal liver metastases can be predicted by various prognostic factors. AIMS Development of a model for risk stratification based on analysis of prognostic factors. METHODS Data of 201 patients were collected prospectively and included in a single-centre trial. A total of 20 factors were analysed as to their influence on recurrence-free and overall survival. Independent prognostic factors were entered into a model of a clinical risk score. RESULTS Median recurrence-free survival reached 24 months for all patients; median overall survival was 50 months. Only a synchronous manifestation of primary colorectal carcinoma and liver metastases, the presence of four or more metastases and a carcino-embryonic antigen level of 200 ng/ml or more significantly influenced recurrence-free and overall survival in the multivariate analysis. The derived risk stratification grouped the patients according to the following criteria: low risk, zero prognostic factors (n=112); intermediate risk, one factor (n=74); high risk, two or more factors (n=15). The median recurrence-free survival for low, intermediate and high risk were 30.0, 23.0 and 11.0 months, respectively; the median overall survival was 94.0, 40.0 and 33.0 months. Compared with the low-risk group, patients with intermediate risk demonstrated an increased hazard ratio (HR) of 1.57-fold for recurrence (P=0.018) and 1.91-fold for mortality (P=0.007). For the high-risk group, the HR rose significantly to 3.26 for recurrence (P<0.0005) and to 3.10 for mortality (P=0.001). CONCLUSIONS The presented clinical score may allow for patients with colorectal liver metastases to be stratified appropriately and for optimization of their subsequent therapeutic management.
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Affiliation(s)
- Ralf Konopke
- Department of General, Thoracic and Vascular Surgery, University of Technology, Dresden, Germany.
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Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the Ca(2+)-binding proteins S100A6 and S100A11. PLoS One 2008; 3:e3767. [PMID: 19048101 PMCID: PMC2585013 DOI: 10.1371/journal.pone.0003767] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2008] [Accepted: 10/30/2008] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND It is unknown, on the proteomic level, whether the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known. METHODOLOGY/PRINCIPAL FINDINGS In this study, tissue from colon-derived liver metastases (n = 17) were classified, laser-microdissected, and analysed by ProteinChip arrays (SELDI). The resulting spectra were compared with data for primary colorectal (CRC) and hepatocellular carcinomas (HCC) from our former studies. Of 49 signals differentially expressed in primary HCC, primary CRC, and liver metastases, two were identified by immunodepletion as S100A6 and S100A11. Both proteins were precisely localized immunohistochemically in cells. S100A6 and S100A11 can discriminate significantly between the two primary tumor entities, CRC and HCC, whereas S100A6 allows the discrimination of metastases and HCC. CONCLUSIONS Both identified proteins can be used to discriminate different tumor entities. Specific markers or proteomic patterns for the metastases of different primary cancers will allow us to determine the biological characteristics of metastasis in general. It is unknown how the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known.
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Role of IV iodinated contrast material in 18F-FDG PET/CT of liver metastases. AJR Am J Roentgenol 2008; 191:1436-9. [PMID: 18941082 DOI: 10.2214/ajr.07.3750] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The purpose of our study was to investigate the role of IV iodinated contrast material in the evaluation of hepatic metastases at (18)F-FDG PET/CT. MATERIALS AND METHODS We retrospectively identified 39 patients (25 men and 14 women) with suspected isolated hepatic metastases from colorectal cancer who underwent FDG PET/CT. The CT protocol included acquisition of unenhanced and multiphase contrast-enhanced CT images through the liver. At two separate sittings, four readers (two radiologists and two nuclear medicine physicians) noted and characterized all hepatic lesions in consensus, first based on PET and unenhanced CT images and later based on PET and contrast-enhanced CT images. The nature of detected lesions was established by histopathologic or clinicoradiologic correlation. RESULTS A total of 178 hepatic lesions were identified, consisting of 137 metastases and 41 benign lesions. Using lesion-based analyses with Obuchowski's method for paired observations, 172 of 178 lesions (97%) were detected at PET/contrast-enhanced CT compared with only 135 of 178 (76%) at PET/unenhanced CT (p = 0.0004). Specifically, 114 of 137 (83%) hepatic metastases were detected on PET/contrast-enhanced CT compared with 92 of 137 (67%) on PET/unenhanced CT (p = 0.012). One hundred thirty-one of 178 lesions (73%) were accurately characterized at PET/contrast-enhanced CT compared with 101 of 178 (57%) at PET/unenhanced CT (p = 0.004). CONCLUSION IV iodinated contrast material administration improves the detection of hepatic metastases and the characterization of focal hepatic lesions at PET/CT.
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Detection of liver metastases: Gadoxetic acid-enhanced three-dimensional MR imaging versus ferucarbotran-enhanced MR imaging. Eur J Radiol 2008; 73:131-6. [PMID: 18996659 DOI: 10.1016/j.ejrad.2008.09.027] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2008] [Revised: 09/18/2008] [Accepted: 09/23/2008] [Indexed: 12/13/2022]
Abstract
PURPOSE To compare the diagnostic performance of gadoxetic acid-enhanced MRI with ferucarbotran-enhanced MRI for the detection of liver metastases. MATERIALS AND METHODS Thirty-six patients with 80 liver metastases who underwent gadoxetic acid-enhanced MRI using a three-dimensional volumetric interpolated technique and ferucarbotran-enhanced MRI with a mean interval of 7 days (range, 5-10 days) were included in this study. Two observers independently interpreted the two sets of images - the gadoxetic acid set (unenhanced, early dynamic and 20min delayed phase images) and the ferucarbotran set (unenhanced and ferucarbotran-enhanced T2*-weighted-gradient echo and T2-weighted turbo spin echo images). Diagnostic accuracy was evaluated using the alternative-free response receiver operator characteristic (ROC) method. Sensitivity and positive predictive value were also evaluated. RESULTS There was a trend toward increased areas under the ROC curve (Az values) for the gadoxetic acid set (0.950, 0.948) as compared with the ferucarbotran set (0.941 and 0.939) of images, but no significant difference was found for both observers (p<0.05). Sensitivities of the gadoxetic acid set (93.8% and 92.5%) were also slightly better than those of the ferucarbotran set (88.8% and 87.5%) with no significant difference (p=0.13). The two image sets showed similar positive predictive values (98.7% and 98.6%, respectively). CONCLUSIONS Gadoxetic acid-enhanced MRI showed comparable diagnostic performance to ferucarbotran-enhanced MRI for the detection of liver metastases.
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Dual-Time-Point FDG-PET/CT for the Detection of Hepatic Metastases. Mol Imaging Biol 2008; 10:335-40. [DOI: 10.1007/s11307-008-0159-y] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2008] [Revised: 04/19/2008] [Accepted: 05/06/2008] [Indexed: 12/23/2022]
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Malcontenti-Wilson C, Chan L, Nikfarjam M, Muralidharan V, Christophi C. Vascular targeting agent Oxi4503 inhibits tumor growth in a colorectal liver metastases model. J Gastroenterol Hepatol 2008; 23:e96-e104. [PMID: 17559382 DOI: 10.1111/j.1440-1746.2007.04899.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Oxi4503 is a potent vascular targeting agent belonging to the family of combretastatins. These agents produce an acute reduction in tumor blood flow leading to tumor necrosis. Despite evidence of its efficacy in certain malignancies, the effect on colorectal liver metastases remains largely unknown. This study investigates the effect of Oxi4503 on colorectal liver metastases in a murine model. METHODS The effect of a single dose of Oxi4503 on established tumors in a murine model of colorectal liver metastases was assessed following administration of 1-50 mg/kg Oxi4503. In addition, the effects of continuous, daily and intermittent dosing (1-5 mg/kg) on tumor necrosis and growth were studied by quantitative histological and stereological analysis. The effect of multiple dosing on long-term survival was also assessed using the Kaplan-Meier analysis. The microvascular effects of therapy were studied by scanning electron microscopy of microvascular resin casts. RESULTS A single dose of 5 or 50 mg/kg of Oxi4503 produced significant tumor necrosis compared to the controls. Subcutaneous continuous dosing infusion with Oxi4503 at 1 mg/kg/day reduced tumor growth compared to the controls, but was associated with marked systemic toxicity. Daily administration over 21 days was associated with significant mortality. Intermittent dosing of Oxi4503 (two doses, 3 days apart) produced the greatest reduction in tumor growth with minimal toxicity and conferred a significant survival advantage. Microvascular casts demonstrated significant disruption of tumor vessels. CONCLUSIONS A single dose of Oxi4503 produced significant necrosis and microvascular injury in colorectal liver metastases. Intermittent dosing with Oxi4503 produced the maximum reduction in tumor growth, minimal toxicity, and a significant improvement in survival. Oxi4503 is a potential anticancer agent. Further research into its mechanism of action and its synergistic use with other therapies is warranted.
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McGahan JP, Khatri VP. Imaging findings after liver resection by using radiofrequency parenchymal coagulation devices: initial experiences. Radiology 2008; 247:896-902. [PMID: 18487541 DOI: 10.1148/radiol.2473070949] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
PURPOSE To retrospectively evaluate the imaging features and potential pitfalls in interpreting the findings at the site of surgery in patients undergoing hepatic resection by using the InLine and TissueLink radiofrequency devices for parenchymal coagulation prior to transection. MATERIALS AND METHODS This HIPAA-compliant study was approved by the Institutional Review Board with waiver of informed consent. Twenty-six patients (14 men, 12 women; mean age, 56 years), in whom intraoperative Inline and TissueLink devices were used for resection of hepatocellular carcinoma or metastatic liver disease or other liver tumors, were identified. Information such as tumor characteristics, diagnostic studies, surgical therapy, and surveillance methods were reviewed. All computed tomographic (CT) and positron emission tomographic (PET) scans and the single magnetic resonance and ultrasonographic images of the abdomen were retrospectively reviewed by a radiologist and compared with the initial interpreting physician's report. RESULTS Of 35 CT scans, 33 revealed a hypodense line of demarcation (mean thickness, 13.2 mm) between the surgical resection clips and the normal liver parenchyma. This demarcation was interpreted as "could not exclude site recurrence" in three cases and "recurrence or probable recurrence" in five cases. In two CT scans, the hypodense demarcation was not present. In all seven PET scans, the uniform hypermetabolic activity associated with the demarcation was labeled as a recurrence. At follow-up CT (median, 12.5 months), marginal recurrence was not detected in 25 patients, though in one case there was a recurrence in close proximity to the surgical site. CONCLUSION The use of InLine and TissueLink devices during hepatectomy is associated with a linear hypodense demarcation at the surgical margin that also demonstrates a symmetrical rimlike hypermetabolic activity seen on PET scans.
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Affiliation(s)
- John P McGahan
- Departments of Radiology and Surgery, University of California Davis Medical Center, 4501 X St, Suite 3010, Sacramento, CA 95817, USA
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18
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Liver resection for breast cancer metastasis: does it improve survival? Surg Today 2008; 38:293-9. [PMID: 18368316 DOI: 10.1007/s00595-007-3617-2] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2006] [Accepted: 05/02/2007] [Indexed: 10/22/2022]
Abstract
PURPOSE To assess the outcome and prognostic factors of liver surgery for breast cancer metastasis. METHODS We retrospectively examined 16 patients who underwent partial liver resection for breast cancer liver metastasis (BCLM). All patients had been treated with chemotherapy or hormonotherapy, or both, before referral for surgery. We confirmed by preoperative radiological examinations that metastasis was confined to the liver. The survival curve was estimated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted to evaluate the role of the known factors of breast cancer survival. RESULTS The median age of the patients was 54 years (range 38-68) and the median disease-free interval between the diagnoses of breast cancer and liver metastasis was 54 months (range 7-120). Nine major and 7 minor hepatectomies were performed. There was no postoperative death. The overall 1-, 3-, and 5-year survival rates were 94%, 61%, and 33%, respectively. The median survival rate was 42 months. Univariate analysis revealed that hormone receptor status, number of metastases, a major hepatectomy, and a younger age were associated with a poorer prognosis. The survival rate was not influenced by the disease-free interval, grade or stage of breast cancer, or intraoperative blood transfusions. The number of liver metastases was identified as a significant independent factor of survival according to the Cox proportional hazard model (P = 0.04). CONCLUSIONS Liver resection, when done in combination with adjuvant therapy, can improve the prognosis of selected patients with BCLM.
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Prognostic Importance of Superior Diaphragmatic Adenopathy at Computed Tomography in Patients With Resectable Hepatic Metastases From Colorectal Carcinoma. J Comput Assist Tomogr 2008; 32:173-7. [DOI: 10.1097/rct.0b013e3181570370] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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20
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Konopke R, Bunk A, Kersting S. The role of contrast-enhanced ultrasound for focal liver lesion detection: an overview. ULTRASOUND IN MEDICINE & BIOLOGY 2007; 33:1515-26. [PMID: 17618038 DOI: 10.1016/j.ultrasmedbio.2007.04.009] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2006] [Revised: 02/21/2007] [Accepted: 04/18/2007] [Indexed: 05/16/2023]
Abstract
The development of new ultrasound (US) contrast agents and sonographic techniques has considerably improved the possibilities of ultrasound in the assessment of liver tumors. An overview is given on diagnostic potential of contrast-enhanced US (CEUS) and real-time low mechanical index technique in the detection of various focal liver lesions compared with computed tomography, magnetic resonance imaging or intraoperative US. In two of our own studies that included 100 patients each we showed an increase of correct findings in CEUS compared with B-mode US from 64% to 87% and from 67% to 84% as confirmed by intraoperative evaluation of the liver. Especially after chemotherapy and in the case of small metastases, significantly more metastases were correctly detected by CEUS compared with B-mode US. These results and clinical study results in the literature show that CEUS allows tumor detection and direct visualization of the tumor vascularity and put contrast-enhanced sonography among recommended noninvasive imaging methods for focal liver lesions with improvements in diagnostic strategy.
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Affiliation(s)
- R Konopke
- Department of Visceral, Thoracic, and Vascular Surgery, Carl Gustav Carus University Hospital, Dresden University of Technology, Dresden, Germany
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21
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Konopke R, Kersting S, Bergert H, Bloomenthal A, Gastmeier J, Saeger HD, Bunk A. Contrast-enhanced ultrasonography to detect liver metastases : a prospective trial to compare transcutaneous unenhanced and contrast-enhanced ultrasonography in patients undergoing laparotomy. Int J Colorectal Dis 2007; 22:201-7. [PMID: 16733650 DOI: 10.1007/s00384-006-0134-5] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/05/2006] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The advent of contrast-enhanced ultrasound (CEUS) has called into question the efficacy of standard ultrasonographic techniques. In this study, we evaluated B-mode and color-duplex imaging and CEUS in the detection of liver metastases, using intraoperative and histological findings as a reference. MATERIALS AND METHODS Before laparotomy, 108 patients suspected of having liver metastases were prospectively examined with B-mode and color-duplex imaging, followed by contrast-enhanced ultrasound (2.4 ml SonoVue). Patients with unresectable tumors (n=8) were excluded from the analysis. The sonographic diagnosis in the remaining 100 patients was compared to the intraoperative and histological findings. RESULTS/FINDINGS CEUS improved the sensitivity for detecting liver lesions from 56.3% (B-mode) to 83.8% (CEUS) (p=0.004). In particular, the contrast agent led to an improvement in ultrasonographic detection in the following cases: nodular metastases smaller than one centimeter; after adjuvant chemotherapy; for tumors near the surface of the liver; and for lesions situated around the ligamentum teres. INTERPRETATION/CONCLUSIONS CEUS provides significant improvement in the detection of liver metastases, and should therefore, be performed routinely in the surveillance of cancer patients.
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Affiliation(s)
- R Konopke
- Department of Visceral, Thoracic and Vascular Surgery, Carl Gustav Carus University Hospital, University of Technology, Fetscherstr. 74, 01307 Dresden, Germany.
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22
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Harun N, Nikfarjam M, Muralidharan V, Christophi C. Liver regeneration stimulates tumor metastases. J Surg Res 2007; 138:284-90. [PMID: 17254608 DOI: 10.1016/j.jss.2006.06.024] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2006] [Revised: 06/09/2006] [Accepted: 06/22/2006] [Indexed: 12/11/2022]
Abstract
BACKGROUND Partial hepatectomy for patients with colorectal liver metastases is associated with a tumor recurrence rate approaching 80% post-resection. Different factors and phases associated with regeneration of the liver are implicated in tumor recurrence. This study investigates the effects of the early and late phases of liver regeneration and the impact of the degree of liver resection on stimulating tumor growth and metastasis. MATERIALS AND METHODS Groups of mice underwent partial hepatectomy (37% or 70%) and were then challenged with colorectal liver carcinoma (CRC) tumors immediately after liver resection (early and late phase effect) or 6 days post liver resection (late phase effect). Tumor growth, degree of proliferation, tumor morphology, and the presence of extrahepatic metastases were investigated 21 days post-tumor induction. RESULTS The late phase of liver regeneration plays a significant role in tumor stimulation and metastasis. The degree of hepatectomy also appears to be an important factor. The degree of hepatic resection significantly influences tumor growth and the extent of extrahepatic metastases, particularly in the lungs. CONCLUSIONS Elucidation of the processes involved in the late phase of liver regeneration may assist in the development and timing of adjuvant agents to minimize tumor recurrence during this phase.
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Affiliation(s)
- Nadia Harun
- Department of Surgery, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
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Takahashi S, Konishi M, Nakagohri T, Gotohda N, Hanaoka T, Saito N, Kinoshita T. Importance of intra-individual variation in tumour volume of hepatic colorectal metastases. Eur J Surg Oncol 2006; 32:1195-200. [PMID: 16968660 DOI: 10.1016/j.ejso.2006.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2006] [Accepted: 08/07/2006] [Indexed: 11/24/2022] Open
Abstract
AIMS The efficacy of surgical resection for multiple colorectal hepatic metastases (MCHM) has been controversial. We examined the survival of patients who received surgery for MCHM and examined the factors associated with survival. METHODS A retrospective analysis was performed of 50 consecutive patients who received hepatic resections for MCHM, defined as four or more metastatic lesions of colorectal cancer. RESULTS Overall survival after hepatic resection for MCHM was 48% at 3years and 43% at 5years (median survival, 22.3months). Multivariate analyses revealed that a coefficient of variation (CV) in volume of hepatic metastases in each individual patient above 1.8 (P=0.01, HR=4.08, 95% CI=1.33-12.5) was the only poor prognostic factor after resection of MCHM. CONCLUSIONS A CV in volume of hepatic metastases in each individual patient above 1.8 predicts poor survival after hepatectomy of MCHM. Thus, the CV in volume of hepatic metastases in each individual patient might be useful in planning the therapeutic strategy for patients with MCHM.
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Affiliation(s)
- S Takahashi
- Department of Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Chiba, Japan.
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Veenendaal LM, van Hillegersberg R, Smakman N, van der Bilt JDW, van Diest PJ, Kranenburg O, Borel Rinkes IHM. Synergistic effect of interstitial laser coagulation and doxorubicin in a murine tumor recurrence model of solitary colorectal liver metastasis. Ann Surg Oncol 2006; 13:168-75. [PMID: 16424982 DOI: 10.1245/aso.2006.03.076] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2005] [Accepted: 08/30/2005] [Indexed: 11/18/2022]
Abstract
BACKGROUND Interstitial laser coagulation (ILC) is gaining acceptance for treatment of unresectable colorectal liver metastases. However, local recurrence rates are still high. To overcome this problem, we investigated the potential of additional systemic therapy after ILC in a murine model. METHODS Single C26 colon carcinoma nodules (approximately 1 mm3) expressing firefly luciferase were implanted in the left liver lobe of 32 BALB/c mice. Seven days after implantation, tumors were treated with either ILC alone (neodymium-yttrium aluminum garnet; 6 W/cm; 800 J/cm) or ILC followed by 1 mg/kg of doxorubicin intravenously. Controls received either doxorubicin alone or sham treatment. Tumor load was measured by in vivo bioluminescent imaging. RESULTS Solitary colorectal liver metastases developed over 7 days after tumor implantation in the liver. Extrahepatic disease was not observed. The ILC dose was set to ablate the liver metastases with recurrent tumor growth in 9 of 16 mice after 7 days. After ILC plus doxorubicin, complete tumor destruction occurred without recurrence (0 of 14). Sham treatment or treatment with doxorubicin alone showed an exponential increase in tumor load. CONCLUSIONS A murine tumor recurrence model after local ablative treatment of solitary liver metastasis was developed. The combination of ILC and doxorubicin had a strong synergistic effect that led to complete tumor remission in all animals treated.
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Affiliation(s)
- Liesbeth M Veenendaal
- Department of Surgery, University Medical Center Utrecht, P. O. Box 85500, 3508 GA Utrecht, The Netherlands
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von Breitenbuch P, Köhl G, Guba M, Geissler E, Jauch KW, Steinbauer M. Thermoablation of colorectal liver metastases promotes proliferation of residual intrahepatic neoplastic cells. Surgery 2006; 138:882-7. [PMID: 16291389 DOI: 10.1016/j.surg.2005.05.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2004] [Revised: 04/11/2005] [Accepted: 05/09/2005] [Indexed: 01/02/2023]
Abstract
BACKGROUND Resection of liver neoplasms is believed to promote growth of residual intrahepatic neoplastic cells. As the effects of radiofrequency thermoablation (RFA) are still unknown, we aimed to compare the influence of RFA versus liver resection on residual intrahepatic neoplastic cells. METHODS A primary metastasis was established by injection of syngenic CT-26 coloncarcinoma cells into the right liver lobe of Balb/C mice. Five days later, 3 x 10(5) GFP-transfected CT-26 tumor cells were injected intraportally, and the primary metastasis was treated by resection (group I, n = 7) or RFA (group II, n = 7). The effect of resection/RFA on the growth of single intrahepatic GFP neoplastic cells was evaluated by intravital microscopy 7 days later. RESULTS Resection of a primary metastasis enhanced the proliferation of residual intrahepatic neoplastic cells, compared with the control group. RFA led to an increased survival of residual neoplastic cells (5% +/- 2% vs 1% +/- 1% single cells) and significantly promoted the proliferation of neoplastic cells, compared with resection (13% +/- 4% vs 2% +/- 2% micrometastases). CONCLUSIONS RFA strongly promotes intrahepatic growth of residual neoplastic cells. On the basis of our findings, RFA should not be recommended as an alternative curative treatment to resection. Furthermore, if RFA is performed as palliative therapy, postinterventional chemotherapy may be advisable to overcome the stimulation of residual neoplastic cells by RFA.
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Affiliation(s)
- P von Breitenbuch
- Universität Regensburg, Klinik und Poliklinik für Chirurgie, Regensburg, Germany.
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Veenendaal LM, Borel Rinkes IHM, van Hillegersberg R. Multipolar radiofrequency ablation of large hepatic metastases of endocrine tumours. Eur J Gastroenterol Hepatol 2006; 18:89-92. [PMID: 16357626 DOI: 10.1097/00042737-200601000-00016] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Radiofrequency ablation (RFA) is a reliable method of creating thermally induced coagulation necrosis. Local recurrence after RFA of hepatic metastases is directly dependent on tumour size related to the free margin of ablation. To produce larger coagulation volumes a bipolar radiofrequency device was developed that allows the simultaneous activation of three active needles. This technique was used at laparotomy in a patient with liver metastases of an endocrine tumour. Coagulation size up to 12 cm in diameter could be created. The postoperative recovery of the patient was uncomplicated. No local recurrence was seen after 13 months of follow-up with computed tomography scan. The use of simultaneously operated multiple radiofrequency electrodes in a multipolar mode expands the treatment options for patients with large and unresectable intrahepatic metastases.
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Affiliation(s)
- Liesbeth M Veenendaal
- Department of Surgery, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
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27
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Holmer C, Lehmann KS, Risk J, Roggan A, Germer CT, Reissfelder C, Isbert C, Buhr HJ, Ritz JP. Colorectal tumors and hepatic metastases differ in their optical properties—relevance for dosimetry in laser-induced interstitial thermotherapy. Lasers Surg Med 2006; 38:296-304. [PMID: 16526042 DOI: 10.1002/lsm.20300] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES The therapeutic application of laser light is a promising alternative to surgical resection of colorectal liver metastases. The extent of tumor destruction achieved by this strategy depends primarily on light distribution in the target tissue. Knowledge about optical properties is necessary to predict light distribution in the tissue for careful irradiation planning. The aim of this study was to compare the optical behavior of healthy colon tissue with that of colorectal carcinomas and their hepatic metastases in the native and coagulated state in order to test the effect of malignant degeneration, metastasis, and thermal coagulation on optical parameters. MATERIALS AND METHODS Ninety tissue samples were taken from patients with a colorectal carcinoma and concomitant liver metastases: healthy colon tissue (n = 30); colon carcinoma (n = 30); liver metastases (n = 30). Optical properties were measured according to the single integrating sphere principle in the native state and after thermal coagulation in the wavelength range of 800-1,100 nm and analyzed by inverse Monte Carlo simulation. RESULTS The highest optical penetration depth for all tissue types was obtained at the end of the spectral range investigated. The highest penetration depths of 4.13 mm (healthy colon), 7.47 mm (colon carcinoma tissue), and 4.08 (liver metastases) were at 1,060 nm, although the values decreased significantly after thermal coagulation. Comparing healthy colon-to-colon carcinoma always revealed a significantly lower absorption and scattering coefficient in the tumor tissue. This resulted in a higher optical penetration depth of the laser light in the colon carcinoma tissue (P < 0.05). A direct comparison disclosed no agreement between the optical properties of the primary tumor and the liver metastases. In the native state, colon carcinoma tissue had a lower scattering coefficient (P < 0.05), higher anisotropy factor, and optical penetration depth than liver metastases (P < 0.05). The absorption coefficient did not differ significantly. The differences in the native state were equalized by tissue coagulation. CONCLUSIONS Colon carcinoma tissue has a higher optical penetration depth than healthy colon tissue, which speaks in favor of tumor selectivity for interstitial laser application, since large treatment volumes can be obtained in the tumor. The lack of agreement between primary tumors and their concomitant liver metastases indicates a modification of optical behavior through metastasis. Thermal coagulation of tissue leads to changes in the optical properties, which are clearly less pronounced in carcinoma tissue. The data obtained in this study clearly show that an individual irradiation schedule is necessary for effective and safe dosimetry in laser-induced thermotherapy (LITT).
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Affiliation(s)
- Christoph Holmer
- Department of General, Vascular and Thoracic Surgery, Charité-Campus Benjamin Franklin, Berlin, Germany
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Abdelmoumene A, Chevallier P, Chalaron M, Schneider F, Verdun FR, Frascarolo P, Meuli R, Schnyder P, Denys A. Detection of liver metastases under 2 cm: comparison of different acquisition protocols in four row multidetector-CT (MDCT). Eur Radiol 2005; 15:1881-7. [PMID: 15868125 DOI: 10.1007/s00330-005-2741-x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2004] [Revised: 02/21/2005] [Accepted: 03/02/2005] [Indexed: 12/27/2022]
Abstract
This study compared different acquisition protocols performance to detect small liver metastases (<2 cm). Thirty consecutive patients with histologically proven hepatic metastases were explored by MDCT at the liver equilibrium phase by four successive acquisitions. We compared the following protocols (1-4): 5/30/1.5 (section thickness/table speed/pitch); 5/15/0.75; 5/11.25/0.75; and 2.5/15/1.5 with the same X-ray dose. The gold standard was based on patient radiological follow-up. Evolutive lesions were considered as true positive (TP). The described lesions, not found on the follow-up exams despite tumoral progression, were considered as false positive (FP). Stable lesions could not be considered as metastasis and were eliminated. One hundred and seventy-six lesions were detected: 61 TP and 91 FP. Twenty-four lesions were eliminated. The mean kappa values for protocols 1, 2, 3 and 4 were, respectively, 0.43, 0.68, 0.73 and 0.51 (0.61-0.80: substantial agreement) and the mean areas under the ROC curve were, respectively, 0.76, 0.87, 0.86 and 0.80. The results of protocols 2 and 3 were significantly superior to those of protocols 1 and 4. MDCT protocols using thin sections or an increased table speed are less efficient in detecting small metastases.
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Affiliation(s)
- Amina Abdelmoumene
- Department of Diagnostic and Interventional Radiology, University Hospital Centre (CHUV), 1011 Lausanne, Switzerland.
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Gananadha S, Morris DL. Novel in-line multielectrode radiofrequency ablation considerably reduces blood loss during liver resection in an animal model. ANZ J Surg 2005; 74:482-5. [PMID: 15191488 DOI: 10.1111/j.1445-1433.2004.03035.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Liver resection is widely used in the treatment of primary and secondary liver tumours. One of several important factors associated with mortality both in cirrhotic and non-cirrhotic patients after liver resection is operative blood loss. We evaluated the use of a prototype radiofrequency ablation probe to treat the transection plane prior to liver resection in the sheep model. METHODS In-line radiofrequency ablation (RFA) was performed on the liver using a prototype device consisting of 11 electrodes mounted on a 8-cm base. The RITA 1500 generator was used for power delivery. Ultrasonic aspirator (UA) and clamp resection were performed on the liver of sheep with and without in-line RFA. The blood loss was measured by weighing swabs. RESULTS A total of 26 liver resections were performed. The mean (SD) blood loss with UA resection was 0.032 g (0.011) versus 0.005 (0.005) g without and with prior in-line RFA, respectively (P = 0.001). The mean (SD) blood loss with clamp resection was 0.087 (0.10) g versus 0.01 (0.008) without and with in-line RFA, respectively (P = 0.155). CONCLUSION In-line RFA makes liver resection easier with minimal blood loss and may make cirrhotic liver resection easier with minimal blood loss. This is likely to improve the operative safety of liver resection.
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Affiliation(s)
- Sivakumar Gananadha
- University of New South Wales Department of Surgery, St George Hospital, Sydney, Australia
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Lodge JPA, Menon KV, Fenwick SW, Prasad KR, Toogood GJ. In-contiguity and non-anatomical extension of right hepatic trisectionectomy for liver metastases. Br J Surg 2005; 92:340-7. [PMID: 15672439 DOI: 10.1002/bjs.4830] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Abstract
Background
In some patients undergoing right hepatic trisectionectomy for metastases, extension of the resection beyond the falciform ligament is necessary to achieve tumour clearance. The aim of the present study was to assess the early and long-term outcomes and hepatic function in patients who underwent extensive liver resection beyond right trisectionectomy.
Methods
Thirty-eight patients who had extension of a right trisectionectomy, either in contiguity (IC) or in a non-anatomical (NA) fashion, for liver metastases were included in the study. In-hospital mortality, hepatic function and other morbidity were recorded. Survival outcomes were analysed for the subgroup of patients with colorectal liver metastases. The clinical risk score described by the Memorial Sloan–Kettering Cancer Center was applied to all patients with colorectal liver metastases.
Results
Sixteen patients had IC resection, 15 NA resection, and seven had both IC and NA procedures. There was one in-hospital death. Hepatic dysfunction was seen in 25 patients and two developed liver failure. Disease-free actuarial 3-year survival was 42 per cent for patients with colorectal liver metastases. Survival was significantly better in patients with a clinical risk score of 3 or less.
Conclusion
Extension of right trisectionectomy for liver metastases was associated with a low risk of death and hepatic failure.
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Affiliation(s)
- J P A Lodge
- Hepatobiliary and Transplant Unit, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
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Gazelle GS, McMahon PM, Beinfeld MT, Halpern EF, Weinstein MC. Metastatic Colorectal Carcinoma: Cost-effectiveness of Percutaneous Radiofrequency Ablation versus That of Hepatic Resection. Radiology 2004; 233:729-39. [PMID: 15564408 DOI: 10.1148/radiol.2333032052] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To evaluate the relative cost-effectiveness of radiofrequency (RF) ablation and hepatic resection in patients with metachronous liver metastases from colorectal carcinoma (CRC) and compare the outcomes, cost, and cost-effectiveness of a variety of treatment and follow-up strategies. MATERIALS AND METHODS A state-transition decision model for evaluating the (societal) cost-effectiveness of RF ablation and hepatic resection in patients with CRC liver metastases was developed. The model tracks the presence, number, size, location, growth, detection, and removal of up to 15 individual metastases in each patient. Survival, quality of life, and cost are predicted on the basis of disease extent. Imaging, ablation, and resection affect outcomes through detection and elimination of individual metastases. Several patient care strategies were developed and compared on the basis of cost, effectiveness, and incremental cost-effectiveness (expressed as dollars per quality-adjusted life-year [QALY]). Extensive sensitivity analysis was performed to evaluate the impact of alternative scenarios and assumptions on results. RESULTS A strategy permitting ablation of up to five metastases with computed tomographic (CT) follow-up every 4 months resulted in a gain of 0.65 QALYs relative to a no-treat strategy, at an incremental cost of $2400 per QALY. Compared with this ablation strategy, a strategy permitting resection of up to four metastases, one repeat resection, and CT follow-up every 6 months resulted in an additional gain of 0.76 QALYs at an incremental cost of $24 300 per QALY. Across a range of model assumptions, more aggressive treatment strategies (ie, ablation or resection of more metastases, treatment of recurrent metastases, more frequent follow-up imaging) were superior to less aggressive strategies and had incremental cost-effectiveness ratios of less than $35 000 per QALY. Findings were insensitive to changes in most model parameters; however, results were somewhat sensitive to changes in size thresholds for RF ablation, the number of metastases present, and surgery and treatment costs. CONCLUSION RF ablation is a cost-effective treatment option for patients with CRC liver metastases. However, in most scenarios, hepatic resection is more effective (in terms of QALYs gained) than RF ablation and has an incremental cost-effectiveness ratio of less than $35 000 per QALY.
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Affiliation(s)
- G Scott Gazelle
- Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Zero Emerson Place, Suite 2H, Boston, MA 02114, USA
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Dabbs DJ, Geisinger KR, Ruggiero F, Raab SS, Nalesnik M, Silverman JF. Recommendations for the reporting of tissues removed as part of the surgical treatment of malignant liver tumors. Hum Pathol 2004; 35:1315-23. [PMID: 15668887 DOI: 10.1016/j.humpath.2004.06.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The Association of Directors of Anatomic and Surgical Pathology (ADASP) has developed recommendations for the surgical pathology report for primary and metastatic epithelial tumors in the liver. These recommendations are reported herein.
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Affiliation(s)
- David J Dabbs
- Department of Pathology, University of Pittsburgh School of Medicine, PA 15213, USA
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Yu B, Li SY, An P, Zhang YN, Liang ZJ, Yuan SJ, Cai HY. Comparative study of proteome between primary cancer and hepatic metastatic tumor in colorectal cancer. World J Gastroenterol 2004; 10:2652-6. [PMID: 15309713 PMCID: PMC4572187 DOI: 10.3748/wjg.v10.i18.2652] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis.
METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With two-dimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis.
RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21 ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-α. Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database.
CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-α is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.
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Affiliation(s)
- Bo Yu
- Department of General Surgery, General Hospital of Beijing Military Command, Beijing 100700, China.
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Nozawa H, Watanabe T, Ohnishi T, Tada T, Tsurita G, Sasaki S, Kitayama J, Nagawa H. Detection of cancer cells in mesenteric vein and peripheral vessels by measuring telomerase activity in patients with colorectal cancer. Surgery 2004; 134:791-8. [PMID: 14639358 DOI: 10.1016/s0039-6060(03)00382-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND Liver metastasis is an important factor determining prognosis in colorectal cancer. The objective of this study was to assess whether colorectal cancer cells in the drainage veins can be detected by measuring telomerase activity and its detection is correlated with liver metastasis. METHODS Telomeric repeat amplification protocol assay in combination with an immunomagnetic sorting was used for measuring telomerase activity of epithelial cells in blood samples collected from mesenteric (tumor-drainage) vein and peripheral vessels of 41 colorectal cancer patients. Telomerase activity was calculated as relative telomerase activity (RTA) against a control template and analyzed in terms of liver metastasis. RESULTS RTA of mesenteric blood samples was significantly higher in patients with liver metastasis (60.8%; n=7) than in those without metastasis (19.7%; n=34; P=.019). The RTA of peripheral blood sample was also higher in patients with liver metastasis (26.8%) than in those without metastasis (11.1%; p=.17). Moreover, 57% of cases with liver metastasis exhibited a positive telomerase activity in mesenteric blood sample, whereas it was 18% in cases without metastasis. CONCLUSIONS Our assay was proven to be a feasible method for detecting cancer cells in tumor-drainage veins. High telomerase activity of mesenteric blood samples reflected the existence of liver metastasis of colorectal cancer.
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Affiliation(s)
- Hiroaki Nozawa
- Department of Surgical Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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Martinho JMDSG, Moraes HPD, Oliveira MED, Moreira LFP, Silva ACD, Pereira LDS, Maia F. Modelo de indução de necrose focal hepática: estudo experimental em ratos. Acta Cir Bras 2004. [DOI: 10.1590/s0102-86502004000100008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVO: Investigar a área de necrose focal induzida pela injeção intra-hepática de quatro diferentes substâncias no fígado de ratos. MÉTODOS: Foram utilizados 25 ratos Wistar, com peso variando entre 200 a 250 g, distribuidos em 5 grupos, que receberam 0,1cc das seguintes substâncias: Grupo I (Gr. I) - soro fisiológico a 0,9% (controle). Grupo II (Gr. II) - glicose hipertônica a 50%. Grupo III (Gr. III) - NaCl a 20%. Grupo IV (Gr. IV) - formol a 10%. Grupo V (Gr. V) - etanol. Os animais foram submetidos a laparotomia para que a punção fosse realizada no lobo hepático médio sob visão direta. Todos os animais foram sacrificados após 24 horas da injeção.. Os fígados foram avaliados histologicamente, com o intuito de mensurar a área do tecido necrótico. RESULTADOS: Nos cinco grupos estudados observou-se: Gr. I - 2829mm² (controle); Gr. II - 3805mm² (glicose hipertônica); Gr. III - 3930mm² (NaCl); Gr. IV - 4532mm² (formol) e Gr. V - 6432mm² (etanol). A análise estatística destes valores foi feita pelo método das comparações múltiplas. CONCLUSÃO: 1. O soro fisiológico foi à substância que causou a menor área de necrose (P< 0,05). 2. O NaCl a 20% e a glicose hipertônica a 50% produzem efeitos semelhantes (P > 0,05). 3. O formol a 10% produziu necrose mais extensa que a glicose hipertônica a 50% (P < 0,05) e que o NaCl a 20%, porém não apresentou diferença estatisticamente significativa com esta última (P > 0,05). 4. O etanol foi à substância que, comparada com as outras, mais necrose produziu (P < 0,05).
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Passos de Jesus Mazza R, Bertevello PL, Matos de Miranda Torrinhas R, Nonogaki S, Avancini Ferreira Alves V, Gama Rodrigues J, Waitzberg DL. Effect of glutamine dipeptide on hepatic regeneration in partially hepatectomized malnourished rats. Nutrition 2003; 19:930-5. [PMID: 14624941 DOI: 10.1016/s0899-9007(03)00177-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Glutamine promotes hepatic regeneration in nourished (N) rats. The aim of the present study was to evaluate the effects of glutamine-enriched total parenteral nutrition (TPN) on liver regeneration in malnourished (MN) rats.Seventy-two male Wistar rats ( congruent with 270 g) were assigned to one of two groups: N and MN. Each group was then subdivided into three groups: the first underwent partial hepatectomy (PH) and received standard TPN enriched with L-alanyl-L-glutamine (Ala-Gln); the second also underwent PH and received standard TPN, but enriched with a solution containing proline and alanine (Ala-Pro); and the third underwent no surgical procedure (control group). All experimental groups received isocaloric (188 kcal. kg(-1). d(-1)) and isonitrogenous (1.12 g of nitrogen. kg(-1). d(-1)) TPN for 96 h. All animals were injected with bromodeoxyuridine 2 h before death. The hepatic regeneration index (HRI), hepatic growth percentage (HG) and hepatic morphology were analyzed. In MN rats, HRI and HG were higher with glutamine enrichment (HRI = 81 and HG = 190) than with proline-containing TPN (HRI = 66 and HG = 154; P < 0.05) and HRI was 100 times higher in animals that underwent PH than in control animals. Morphologic analysis of hepatic tissue showed no difference among the six groups.Glutamine-enriched TPN promoted growth of the remnant liver in MN rats after PH, maintained cellular proliferation in the various experimental groups after surgery, and maintained hepatic morphology of MN rats after surgery.
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Affiliation(s)
- Rosângela Passos de Jesus Mazza
- Laboratory of Surgical Metabiology and Nutrition, Department of Gastroenterology, University of São Paulo Medical School, and the Department of Pathology, Federal University of São Paulo, São Paulo, Brazil
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Gazelle GS, Hunink MGM, Kuntz KM, McMahon PM, Halpern EF, Beinfeld M, Lester JS, Tanabe KK, Weinstein MC. Cost-effectiveness of hepatic metastasectomy in patients with metastatic colorectal carcinoma: a state-transition Monte Carlo decision analysis. Ann Surg 2003; 237:544-55. [PMID: 12677152 PMCID: PMC1514476 DOI: 10.1097/01.sla.0000059989.55280.33] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE To evaluate the cost-effectiveness of hepatic resection ("metastasectomy") in patients with metachronous liver metastases from colorectal carcinoma (CRC), and to investigate the impact of operative and follow-up strategies on outcomes, cost, and cost-effectiveness. SUMMARY BACKGROUND DATA There is substantial evidence that resection of CRC liver metastases can result in long-term survival in some patients. However, several unresolved issues are difficult to address using currently available clinical data. These include the appropriate threshold for resection, whether to perform repeat resection, and the relative cost-effectiveness of the procedure(s). METHODS The authors developed a state-transition Monte Carlo decision model to evaluate the (societal) cost-effectiveness of hepatic metastasectomy in patients with metachronous CRC liver metastases. The model tracks the presence, number, size, location, growth, detection, and removal of up to 15 individual metastases in each patient. Survival, quality of life, and cost are predicted on the basis of disease extent. Imaging and surgery affect outcomes via detection and removal of individual metastases. Several patient management strategies were developed and compared with respect to cost, effectiveness, and incremental cost-effectiveness ($/quality-adjusted life year [QALY]). A reference strategy in which metastasectomy is not offered and imaging is not performed for the purpose of assessing resectability or operative planning ("no-surgery" strategy) was included for comparison. Extensive sensitivity analysis was performed to evaluate the impact of alternative model assumptions on results. RESULTS A strategy permitting resection of up to six metastases and one repeat resection, with CT follow-up every 6 months, resulted in a gain of 2.63 QALYs relative to the no-test/no-treat strategy, at an incremental cost of 18,100 US dollars/QALY. When additional surgical strategies were considered, the incremental cost-effectiveness ratio (ICER; relative to the next least effective strategy) of the six metastases, one repeat, 6-month strategy was 31,700 US dollars/QALY. Across a range of model assumptions, more aggressive treatment strategies (i.e., resection of more metastases, resection of recurrent metastases) were superior to less aggressive strategies and had ICERs below 35,000 US dollars/QALY. Findings were insensitive to changes in most model parameters but somewhat sensitive to changes in surgery and treatment costs. CONCLUSIONS Hepatic metastasectomy is a cost-effective option for selected patients with metachronous CRC metastases limited to the liver. When considering metastasectomy, more aggressive approaches are generally preferred to less aggressive approaches. Overall, surgeons should be encouraged to consider resection for all patients whose metastases can technically be removed.
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Affiliation(s)
- G Scott Gazelle
- Institute for Technology Assessment, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Zero Emerson Place, Suite 2H, Boston, MA 02114, USA.
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Muralidharan V, Nikfarjam M, Malcontenti-Wilson C, Christophi C. Interstitial laser hyperthermia and the biological characteristics of tumor: study in a murine model of colorectal liver metastases. JOURNAL OF CLINICAL LASER MEDICINE & SURGERY 2003; 21:75-83. [PMID: 12737647 DOI: 10.1089/104454703765035493] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND DATA Percutaneously applied interstitial laser hyperthermia (ILH) is a minimally invasive therapy that is currently used in the treatment of liver metastases. Despite its documented efficacy, theoretical considerations and evidence based on animal studies suggest the potential for stimulating tumor growth, especially following surgery. This study investigates the influence of ILH on tumor behaviour in an animal model of colorectal liver metastases. MATERIALS AND METHODS A model of colorectal cancer liver metastases in male inbred CBA mice was used. Laser hyperthermia was applied to tumor tissue using a bare optical quartz from a Medilas fibertom 4100 Nd:YAG surgical laser generator. Liver injury by ILH was initially produced in three experimental groups of animals at different time points in the development of metastases. ILH was applied (i) to normal liver 10 days prior to tumor induction, (ii) immediately prior to tumor induction, and (iii) 15 days after tumor induction to achieve approximately 8% liver destruction. Animals were killed 21 days after tumor induction, and the effects of ILH on overall tumor development were compared with controls using stereological assessment of tumor volume and by histology. In a separate experimental group, the effects of ILH on fully established tumors were examined. Suitable tumors were selected 21 days after induction and partially destroyed by ILH at a standard energy setting. Animals were then killed 15 days later, and the growth rate of the residual viable tumors was compared to control tumors having undergone sham procedures. RESULTS No significant stimulation of tumor growth was evident in any of the experimental groups following ILH, irrespective of the time of application. Incomplete tumor destruction also had no influence on subsequent tumor growth. CONCLUSION ILH does not influence the biological characteristics of tumors during any stage of the metastatic process.
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Affiliation(s)
- V Muralidharan
- Department of Surgery, Melbourne University, Austin Hospital, Melbourne, Victoria, Australia
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Okano K, Maeba T, Moroguchi A, Ishimura K, Karasawa Y, Izuishi K, Goda F, Usuki H, Wakabayashi H, Maeta H. Lymphocytic infiltration surrounding liver metastases from colorectal cancer. J Surg Oncol 2003; 82:28-33. [PMID: 12501166 DOI: 10.1002/jso.10188] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND OBJECTIVES Tumor infiltrating lymphocytes (TILs) have been recognized as a tumor-host reaction in various primary neoplasms. Although several studies reported TILs surrounding metastatic liver tumors, to the authors' knowledge few evaluations of the clinical significance of such features in patients with colorectal liver metastases have been carried out. METHODS Forty-one patients who underwent initial hepatic resection for liver metastases from colorectal cancer were studied. Lymphocytic infiltration surrounding metastatic liver tumor was graded as weak or dense according to the mean number of TILs from 10 high-power microscopic fields (< or =50 or >50/HPF). RESULTS Dense lymphocytic infiltration between the metastatic tumor and hepatic parenchyma was seen in 18 of 41 patients (44%). Histologically, tumor invasion of the portal vein was rare in patients with dense TILs (12%) compared with patients with weak TILs (36%). Patients with dense TILs survived longer than patients with weak TILs after hepatic resection (P = 0.013). Multivariate analysis using the Cox proportional hazard model identified this pathological variable as a significant independent prognostic factor after hepatic resection. CONCLUSIONS The extent of lymphocytic infiltration between the metastatic nodule and hepatic parenchyma may reflect host defensive activity in the liver and is closely related to prognosis in patients who underwent hepatic resection for liver metastases from colorectal cancer.
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Affiliation(s)
- Keiichi Okano
- First Department of Surgery, Kagawa Medical University, Kagawa, Japan.
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Kinkel K, Lu Y, Both M, Warren RS, Thoeni RF. Detection of hepatic metastases from cancers of the gastrointestinal tract by using noninvasive imaging methods (US, CT, MR imaging, PET): a meta-analysis. Radiology 2002; 224:748-56. [PMID: 12202709 DOI: 10.1148/radiol.2243011362] [Citation(s) in RCA: 360] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To perform a meta-analysis to compare current noninvasive imaging methods (ultrasonography [US], computed tomography [CT], magnetic resonance [MR] imaging, and (18)F fluorodeoxyglucose [FDG] positron emission tomography [PET]) in the detection of hepatic metastases from colorectal, gastric, and esophageal cancers. MATERIALS AND METHODS A MEDLINE literature search and review of article bibliographies and our institutional charts of patients with colorectal cancer identified data with histopathologic correlation or at least 6 months of patient follow-up. Two authors independently abstracted data sets and excluded data without contingency tables or data published more than once. Summary-weighted estimates of sensitivity were obtained and stratified according to specificity of less than 85% or 85% and higher. A covariate analysis was used to evaluate the influence of patient- or study-related factors on sensitivity. RESULTS Among 111 data sets, nine US (509 patients), 25 CT (1,747 patients), 11 MR imaging (401 patients), and nine PET (423 patients) data sets met the inclusion criteria. In studies with a specificity higher than 85%, the mean weighted sensitivity was 55% (95% CI: 41, 68) for US, 72% (95% CI: 63, 80) for CT, 76% (95% CI: 57, 91) for MR imaging, and 90% (95% CI: 80, 97) for FDG PET. Results of pairwise comparison between imaging modalities demonstrated a greater sensitivity of FDG PET than US (P =.001), CT (P =.017), and MR imaging (P =.055). CONCLUSION At equivalent specificity, FDG PET is the most sensitive noninvasive imaging modality for the diagnosis of hepatic metastases from colorectal, gastric, and esophageal cancers.
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Affiliation(s)
- Karen Kinkel
- Department of Radiology, Geneva University Hospital, Rue Micheli-du-Crest 24, Switzerland.
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Abstract
Long-term results after liver resection for colorectal liver metastases show 5-year survival rates between 35 and 40%. However, only a limited number of patients appear to be candidates for resection, far more patients prove to have unresectable disease. Present challenges in liver surgery for colorectal metastases are to improve patient selection, to increase the resectability rate and to improve survival by multimodality treatment approaches. The variables most consistently associated with a poor prognosis and tumour recurrence are tumour-positive resection margins and the presence of extra-hepatic disease. Hence, patient selection and preoperative staging should concentrate on accurate imaging of the liver lesions and the detection of extrahepatic disease. For liver imaging, spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), supplemented by intra-operative ultrasound, are currently regarded as the best methods for evaluating the anatomy and resectability of colorectal liver metastases. Extrahepatic disease should be investigated by spiral CT of the chest and abdomen and when possible by 2-fluouro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). Resection remains the gold standard for the surgical treatment of colorectal liver metastases. In experienced centres, resection is a safe procedure and mortality rates are below 5%. The aim of resection should be to obtain tumour-negative resection margins. Edge cryosurgery should be considered in cases where very close resection margins are anticipated. The role of adjuvant chemotherapy after resection is still controversial, although two recent studies show a clear benefit. For the moment, local tumour ablative therapies such as cryotherapy and radiofrequency therapy should be considered as an adjunct to hepatic resection in those cases in which resection can not deal with all of the tumour lesions. In these cases, there seems a beneficial effect of a combined treatment consisting of resection and local tumour ablation. At this stage, there are no randomised data that local tumour ablation is as effective as resection. For a selected group of patients with unresectable liver metastases, there may be a chance to turn unresectable disease to resectable disease by aggressive neo-adjuvant chemotherapy or portal vein embolisation. For patients with unresectable disease, many different chemotherapy schedules may be used based on systemic drug administration. Regional chemotherapy and isolated liver perfusion should only be used within a study design.
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Affiliation(s)
- T Ruers
- Department of Surgery, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
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Muralidharan V, Malcontenti-Wilson C, Christophi C. Effect of blood flow occlusion on laser hyperthermia for liver metastases. J Surg Res 2002; 103:165-74. [PMID: 11922731 DOI: 10.1006/jsre.2002.6365] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND Interstitial laser hyperthermia (ILH) is an in situ ablative technique for the treatment of colorectal liver metastases. A significant factor limiting tumor destruction is hepatic blood flow. Modulation of hepatic blood flow may increase the size of tumor necrosis achieved. Our aim was to investigate the effect of blood flow occlusion on ILH-induced necrosis in both tumor and normal liver tissue. MATERIALS AND METHODS A model of colorectal liver metastases in male inbred CBA mice was used. ILH was applied to normal liver and tumor tissue using a bare optical quartz fiber from an SYL500 Nd:YAG surgical laser generator, with and without hepatic blood flow occlusion, and the extent of necrosis was studied. Tumor blood flow was assessed by laser Doppler flowmetry and scanning electron microscopy. RESULTS Hepatic blood flow occlusion resulted in a significant reduction in blood flow in normal liver tissue (37.9% +/- 5.8, P < 0.001) and in the periphery of the tumor (17.5% +/- 7.8, P < 0.001). It did not affect the blood flow in the center of the tumor (13.4% +/- 4.3, P = 0.07). ILH of normal liver tissue, at low power (2 W), with hepatic blood flow occlusion, resulted in a significant increase in the diameter of necrosis. This effect was not seen when higher power (5 W) was used in normal liver. No significant effect was noted within tumor tissue at either power setting. CONCLUSION The overall effect of hepatic blood flow occlusion in ILH-induced tissue necrosis appears to be negligible in tumor tissue. Its main applicability appears to be at the tumor-host interface, where a decrease in blood flow may lead to higher temperatures and therefore to a greater degree of tumor cell destruction.
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Affiliation(s)
- V Muralidharan
- Department of Surgery, Alfred Hospital, Monash University, Commercial Road, Prahran, 3181, Australia
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Abstract
BACKGROUND Despite the widespread use of surgical resection as a treatment for hepatic colorectal metastases, the value of resecting more than three metastases remains controversial. It was the objective of this study to determine if resection of larger numbers of metastases affects patient survival. METHOD The survival of 123 consecutive patients who underwent curative hepatic resection for colorectal metastases between 1989 and 1999 by a single surgeon was analysed retrospectively. Kaplan-Meier survival statistics and Cox regression were used to determine the factors that affected survival, and logistic regression was used to determine the factors that affected the risk of recurrence of hepatic disease. RESULTS The median survival rate for the whole group of patients was 38 months, with 1, 3 and 5 year survival rates of 88%, 53% and 31% respectively. The survival rate of patients undergoing resection of four to seven metastases (n=22; 5 year survival=39%) was not significantly different to that of patients undergoing resection of one to three metastases (n=91; 5 year survival=30%), P=0.9. Age, sex, primary cancer site, hepatic disease distribution, resection margins and adjuvant hepatic arterial chemotherapy (HAC) did not affect survival. Local invasion of the hepatic metastases (relative risk (RR)=2.9; P=0.001) and hepatic disease recurrence (RR=2.1; P =0.007) were the only factors that independently affected survival. Local invasion of the hepatic metastasis was the only factor associated with an increased risk of hepatic recurrence (RR=2.8; P=0.03). Adjuvant HAC did not affect the risk of hepatic recurrence (RR=1.5, P=0.4). CONCLUSION Although there are no randomized trials that quantify any survival benefit from resection of liver metastases, the comparison of our results with well documented historical evidence indicates that surgical resection of up to seven colorectal liver metastases can result in a significant survival benefit.
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Affiliation(s)
- Paul Moroz
- University of Western Australia, Department of General Surgery, Royal Perth Hospital and Cancer Research Institute, Perth, Western Australia, Australia
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Okano K, Maeba T, Ishimura K, Karasawa Y, Goda F, Wakabayashi H, Usuki H, Maeta H. Hepatic resection for metastatic tumors from gastric cancer. Ann Surg 2002; 235:86-91. [PMID: 11753046 PMCID: PMC1422399 DOI: 10.1097/00000658-200201000-00011] [Citation(s) in RCA: 171] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To assess the surgical results and clinicopathologic features of hepatic metastases from gastric adenocarcinoma to identify patients with a better probability of survival. SUMMARY BACKGROUND DATA Many studies have reported the benefit of hepatic resection for metastatic tumors from colorectal cancer. However, indications for a surgical approach for gastric adenocarcinoma involving the liver have not been clearly defined. METHODS Ninety (11%) of 807 patients with primary gastric cancer were diagnosed with synchronous (n = 78) or metachronous (n = 12) hepatic metastases. Of these, 19 underwent 20 resections intended to cure the metastatic lesion in the liver. The clinicopathologic features of the hepatic metastases in, and the surgical results for, the 19 patients were analyzed. RESULTS The actuarial 1-year, 3-year, and 5-year survival rates after hepatic resection were, respectively, 77%, 34%, and 34%, and three patients survived for more than 5 years after surgery. Solitary and metachronous metastases were significant determinants for a favorable prognosis after hepatic resection. Pathologically, a fibrous pseudocapsule between the tumor and surrounding hepatic parenchyma was found in 13 of the 19 patients (68%). The presence of a peritumoral fibrous pseudocapsule and a well-differentiated histologic type of metastatic nodule were significant prognostic factors. Factors associated with the primary lesion were not significant prognostic determinants in patients who underwent curative resection of the primary cancer. CONCLUSIONS Solitary and metachronous metastases from gastric cancer should be treated by a surgical approach and confer a better prognosis. A new prognostic factor, the presence of a pseudocapsule, may be helpful in defining indications for postoperative adjuvant treatment.
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Affiliation(s)
- Keiichi Okano
- First Department of Surgery, Kagawa Medical University, Kagawa, Japan.
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Moroz P, Jones SK, Winter J, Gray BN. Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model. J Surg Oncol 2001; 78:22-9; discussion 30-1. [PMID: 11519064 DOI: 10.1002/jso.1118] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND OBJECTIVES Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.
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Affiliation(s)
- P Moroz
- Centre for Applied Cancer Studies, The University of Western Australia, Nedlands, Perth, Western Australia, Australia.
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Wickremesekera JK, Chen W, Cannan RJ, Stubbs RS. Serum proinflammatory cytokine response in patients with advanced liver tumors following selective internal radiation therapy (SIRT) with (90)Yttrium microspheres. Int J Radiat Oncol Biol Phys 2001; 49:1015-21. [PMID: 11240242 DOI: 10.1016/s0360-3016(00)01420-6] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
PURPOSE To determine the changes in serum levels of proinflammatory cytokines within 48 h after selective internal radiation treatment (SIRT) in patients with advanced liver cancers. METHODS AND MATERIALS Twenty-eight patients with advanced liver cancers who underwent SIRT were recruited into the study. Serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha, and interferon-gamma were determined prior to and 3, 6, 12, 24, and 48 h after SIRT. Their changes were correlated to adverse reactions following treatment as assessed by constitutional symptom scores, and routine blood and liver function tests at 24 and 48 h post-SIRT and falls in serum carcinoembryonic antigen (CEA) level 1 month post-SIRT. RESULTS Serum IL-6 levels were significantly increased at 24 (p < or = 0.05) and 48 h (p < or = 0.01) post-SIRT. In contrast, there was no significant change in the serum levels of other cytokines studied. The increase in serum IL-6 at 24 h post-SIRT was significantly correlated with the changes in serum alanine transferase (p < or = 0.05) and C-reactive protein (p < or = 0.001) levels and total leukocyte counts (p < or = 0.001) at both 24 and 48 h post-SIRT. Changes in serum IL-6 level were also significantly correlated to the rise of serum aspartate transaminase levels at 48 h post-SIRT (p < or = 0.001), but not with the scores of constitutional symptoms or the changes of serum CEA at 1 month post-SIRT. CONCLUSION Absence of significant changes in most of proinflammatory cytokines studied confirmed that SIRT is a reasonably safe and well-tolerated treatment with minimal side-effect from the point of view of cytokine-related inflammation. The correlation of serum IL-6 changes with several liver enzymes and C-reactive protein but not with clinical symptom scores or serum CEA levels suggests that the rise in IL-6 levels in the first 48 h following SIRT most likely reflect normal liver cell damage rather than tumor cell damage.
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Affiliation(s)
- J K Wickremesekera
- Wakefield Gastroenterology Centre and Research Institute, Wakefield Hospital, Wellington, Newtown, New Zealand
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48
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Abstract
Metastatic liver disease is the commonest cause of death in patients with colorectal cancer. A small proportion of these patients (10%) may be treated by surgical resection with five year survival approaching 35-40%. Alternative treatment modalities for localised hepatic disease include in situ ablative techniques that have the advantages of percutaneous application and minimal morbidity. These include Interstitial Laser Thermotherapy (ILT), Radio Frequency Ablation, Percutaneous Microwave therapy, and Focussed Ultrasound Therapy. This article focuses specifically on the development and utilisation of ILT in the treatment of colorectal liver metastases. It provides a review of the pathophysiological factors involved, present status of clinical studies, and future directions. ILT is a safe technique for the treatment of colorectal liver metastases. It may be delivered by minimally invasive techniques to lesions considered unresectable by present criteria. Limitations include the extent and completeness of tumour necrosis achieved as well as imaging techniques. Clinical problems include a lack of controlled studies. Assessment of long-term survival in prospective randomised trials is needed to assess the efficacy of this procedure.
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Affiliation(s)
- V Muralidharan
- Hepato-Biliary Section, Monash University, Department of Surgery, Alfred Hospital, Prahran, Australia.
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49
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Tanaka T, Konno H, Baba S, Kanai T, Matsumoto K, Matsuda I, Ohba K, Ohta M, Kamiya K, Nakamura S. Prevention of hepatic and peritoneal metastases by the angiogenesis inhibitor fr-118487 after removal of growing tumor in mice. Jpn J Cancer Res 2001; 92:88-94. [PMID: 11173549 PMCID: PMC5926577 DOI: 10.1111/j.1349-7006.2001.tb01052.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
We established a mouse rising dbl quote, left (low)primary tumor resection model" in which a transplanted tumor was resected after an orthotopic transplantation of colorectal cancer tissue to estimate the therapeutic effect of an angiogenesis inhibitor on metastasis. The angiogenesis inhibitor FR-118487 is a member of the fumagillin family. Here, 1 mg / kg / day of FR-118487 was subcutaneously administered to nude mice for 1 week, 2 weeks, or 4 weeks through an osmotic pump. Liver metastasis developed in 7 of 9 control mice, 2 of 6 mice that underwent the tumor resection 2 weeks after transplantation (early resection), and in all 7 of the mice that underwent the tumor resection 4 weeks after transplantation (late resection). In the short treatment trial, the FR-118487 administration immediately after the early resection completely inhibited both hepatic and peritoneal metastases, whereas its administration after the late resection had no effect on liver metastasis. In the prolonged treatment trial, inhibitory effects of prolonged treatment with FR-118487 on both hepatic and peritoneal metastases after the late resection were clearly demonstrated. The mice of the resection-alone group all died within 106 days after tumor inoculation, due to metastases of colon carcinoma. In contrast, half of the mice that underwent resection and then received antiangiogenic therapy were alive at the end of the observation period (160 days after transplantation). In conclusion, the combination of surgery and subsequent antiangiogenic therapy may be useful to prevent the distant metastasis of colorectal cancer and to improve the prognosis of patients with colorectal cancer.
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Affiliation(s)
- T Tanaka
- Department of Surgery II, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu, 431-3192, Japan.
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50
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Abstract
Tumor ablation by using radio-frequency energy has begun to receive increased attention as an effective minimally invasive approach for the treatment of patients with a variety of primary and secondary malignant neoplasms. To date, these techniques have been used to treat tumors located in the brain, musculoskeletal system, thyroid and parathyroid glands, pancreas, kidney, lung, and breast; however, liver tumor ablation has received the greatest attention and has been the subject of a large number of published reports. In this article, the authors review the technical developments and early laboratory results obtained with radio-frequency ablation techniques, describe some of the early clinical applications of these techniques, and conclude with a discussion of challenges and opportunities for the future.
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Affiliation(s)
- G S Gazelle
- Decision Analysis and Technology Assessment Group, Department of Radiology, Massachusetts General Hospital, Zero Emerson Pl, Ste 2H, Boston, MA 02114, USA.
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