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ABSTRACT: BACKGROUND:: Liver-first reversed management (RM) for the treatment of patients with simultaneous colorectal liver metastases (CRLM) includes liver-directed chemotherapy, the resection of the CRLM, and the subsequent resection of the primary cancer. Retrospective data have shown that up to 80% of patients can successfully undergo a complete RM, whereas less than 30% of those undergoing classical management (CM) do so. This registry-based study compared the 2 approaches. METHODS:: The study was based on the LiverMetSurvey (January 1, 2000 to December 31, 2010) and included patients with 2 or more metastases. All patients had irinotecan and/or oxaliplatin-based chemotherapy before liver surgery. Patients undergoing simultaneous liver and colorectal surgery were excluded. RESULTS:: A total of 787 patients were included: 729 in the CM group and 58 in the RM group. Patients in the 2 groups had similar numbers of metastases (4.20 vs 4.80 for RM and CM, P = 0.231) and Fong scores of 3 or more (79% vs 87%, P = 0.164). Rectal cancer, neoadjuvant rectal radiotherapy, and the use of combined irinotecan/oxaliplatin chemotherapy were more frequent in the RM group (P < 0.001), whereas colorectal lymph node involvement was more frequent in the CM group (P < 0.001). Overall survival and disease-free survival were similar in the RM and CM groups (48% vs 46% at 5 years, P = 0.965 and 30% vs 26%, P = 0.992). CONCLUSIONS:: Classical and reversed managements of metastatic liver disease in colorectal cancer are associated with similar survival when successfully completed.
Annals of surgery 11/2012; 256(5):772-779. · 7.90 Impact Factor
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ABSTRACT: Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.
Molecular Cancer Therapeutics 02/2011; 10(4):687-96. · 5.23 Impact Factor
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ABSTRACT: An increasing number of surgical and radiological observations call Couinaud's concept of eight liver segments into question and such inconsistencies are commonly explained with anatomical variations. This paper was intended to demonstrate that, beyond variability, another anatomical principle may allow to understand supposedly differing concepts on liver segmentation.
The study was performed on 25 portal vein casts scanned by helical CT. The branches of the right and left portal vein and their corresponding territories were determined both anatomically and mathematically (MEVIS LiverAnalyzer, MEVISLab).
The number of branches coming-off the right and left portal vein was never 8, but many more (mean number 20, range 9-44). Different combinations of these branches and their respective territories, carried out in this study, yielded larger entities and supposedly contradictory subdivisions (including Couinaud's eight segments), without calling upon anatomical variability.
We suggest the human liver to be considered as corresponding to 1 portal venous territory at the level of the portal vein, to 2 territories at the level of the right and left branch of the portal vein, and to 20 at the level of the rami of the right and left branch. This "1-2-20-concept" is a rationale for reconciling apparent discrepancies with the eight-segment concept. On a pragmatic level, in cases in which imaging or surgical observations do not fit with Couinaud's scheme, we propose clinicians not to autonomically conclude to the presence of an anatomical variation, but to become aware of the presence of an average of 20 (and not 8) second-order portal venous territories within the human liver.
Anatomia Clinica 10/2010; 32(8):761-5. · 0.93 Impact Factor
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Hepatology 04/2010; 51(4):1116-8. · 11.66 Impact Factor
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Laura Rubbia-Brandt,
Gregory Y Lauwers,
Huamin Wang, Pietro E Majno,
Kenneth Tanabe,
Andrew X Zhu,
Catherine Brezault,
Olivier Soubrane,
Eddie K Abdalla,
Jean-Nicolas Vauthey,
Gilles Mentha,
Benoit Terris
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ABSTRACT: Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage.
The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001).
Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
Histopathology 03/2010; 56(4):430-9. · 3.08 Impact Factor
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ABSTRACT: In patients with synchronous colorectal liver metastases, an approach reversing the traditional therapeutic order - i.e. starting with chemotherapy first, doing the liver surgery second, and performing the colorectal surgery last - is theoretically appealing as it avoids the risk of metastatic progression during treatment of the primary tumor. The present series updates on a previously reported pilot experience.
35 patients with advanced synchronous colorectal metastases and nonobstructive colorectal tumors were treated with the reversed approach. Data were collected in a prospective database.
The median number of metastases was 6, the median size of the largest metastasis was 6 cm. Five patients could not complete the program (one death from sepsis during chemotherapy, 3 cases of progressive disease under treatment, and one case of vanishing liver metastases). The remaining 30 patients responded and underwent R0 liver resections with no major complications. One patient needed a Hartmann's procedure for obstruction after a first-step hepatectomy, and 1 patient had a rectal anastomotic leak. Median survival was 44 months. Overall survival rates of the 30 patients who completed the program at 1, 2, 3, 4 and 5 years were 100, 89, 60, 44 and 31%.
The reverse approach appeared feasible and safe, with operability and survival rates better than expected for patients with similar severity. Potential problems, in particular regrowth of vanishing metastases and primary tumors, chemotherapy-associated liver damage, and large bowel obstruction, can be minimized by careful multidisciplinary selection, planning and execution.
Digestive surgery 02/2008; 25(6):430-5. · 1.37 Impact Factor
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ABSTRACT: The outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years.
Patients' characteristics, operative data, chemotherapies and follow-up were recorded. CRLM severity was quantified according to Fong's clinical risk score (CRS), modified to take into account the presence of bilateral liver metastases. Three periods were analyzed, in which different indications, surgical strategies and uses of chemotherapy were applied: 1984-1992, 1993-1998, and 1999-2005.
Between January 1984 and December 2005, 210 liver resections were performed in 180 patients (1984-1992, 43 patients; 1993-1998, 42 patients; 1999-2005, 95 patients). CRLM severity increased throughout the time periods, as did the use of neoadjuvant chemotherapies, repeat resections, and multistep procedures. While the disease-free survival did not improve over time, the 1-, 3- and 5-year overall survival rate increased from 85%, 30%, and 23% in the first period, to 88%, 60%, and 34% in the second period, and to 94%, 69%, and 46% in the third period.
Analysis according to the CRS showed that despite the fact that patients had more severe disease, the overall survival improved over the years, mainly thanks to more aggressive treatment of recurrent disease. Management of advanced CRLM should, from the start, take into account the likelihood of secondary procedures.
Annals of Surgical Oncology 02/2008; 15(1):134-43. · 4.17 Impact Factor
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ABSTRACT: The term "fascia" is a very frequently used notion, particularly in an anatomical, surgical, and radiological context. A closer look at the underlying concepts, however, reveals that the denomination is all but a consistent one. It is this use of one and the same term for very different entities that is one of the sources for controversial opinions on fascial structures and their applications in surgical practice. This article summarizes and illustrates examples of structures called fasciae. Considering the impossibility to give a simple, universal definition, we conclude that a precise description and iconographic documentation of the structure under consideration remain mandatory. They should replace the presumably unequivocal, but in fact often nebulous, notion "fascia" in surgical, radiological, and anatomical articles.
The American surgeon 06/2007; 73(5):451-3. · 1.28 Impact Factor
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Gilles Mentha,
Emiliano Giostra, Pietro E Majno,
Wolf O Bechstein,
Peter Neuhaus,
John O'Grady,
Raaj K Praseedom,
Andrew K Burroughs,
Yves P Le Treut,
Preben Kirkegaard,
Xavier Rogiers,
Bo-Goran Ericzon,
Krister Hockerstedt,
René Adam,
Juergen Klempnauer
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ABSTRACT: The results of liver transplantation for Budd-Chiari syndrome (BCS) are poorly known and the role and timing of the procedure are still controversial. The aim of this study was to investigate the results of transplantation for BCS, focusing on overall outcome, on prognostic factors and on the impact of the underlying disease.
An enquiry on 248 patients representing 84% of the patients transplanted for BCS in the European Liver Transplantation Registry between 1988 and 1999.
Of the 248 patients, 70.4% were female and 29.6% male. The mean age was 35.7 years. The overall actuarial survival was 76% at 1 year, 71% at 5 years and 68% at 10 years. 77% of deaths occurred in the first 3 months: 47% were due to infection and multiple organ failure, and 18% to graft failure or hepatic artery thrombosis. Late mortality (>1 year) occurred in nine patients, due to BCS recurrence in four of them. The only pre-transplant predictors of mortality on multivariate analysis (Cox) were impaired renal function and a history of a shunt.
Liver transplantation for BCS is an effective treatment, irrespective of the underlying cause, and should be considered before renal failure occurs.
Journal of Hepatology 04/2006; 44(3):520-8. · 9.26 Impact Factor
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Axel Andres,
Christian Toso,
Philippe Morel,
Sandrine Demuylder-Mischler,
Domenico Bosco,
Reto Baertschiger,
Nadine Pernin,
Pascal Bucher, Pietro E Majno,
Leo H Bühler,
Thierry Berney
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ABSTRACT: The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome.
Transplant International 12/2005; 18(11):1226-30. · 2.92 Impact Factor
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Transplantation 07/2005; 79(12):1771-2; author reply 1773. · 4.00 Impact Factor
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Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 04/2005; 24(3):383-6. · 1.25 Impact Factor
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ABSTRACT: Altered portal hemodynamics and inflammation may occur following transcatheter arterial chemoembolization (TACE), but early biological and portal perfusion changes are not well characterized when this procedure is performed selectively.
We studied variations in portal flow velocity (PFV) using Doppler ultrasonography, as well as serum TNFa, vCAM-1, and E-Selectin at 2 and 24 hours after supraselective TACE in 15 consecutive patients with cirrhosis and hepatocellular carcinoma.
Variations in PFV occurred both in the embolized and non-embolized liver lobe. PFV increased significantly at 2 hours in the right and left portal vein. At 24 hours, right PFV remained elevated. Serum TNFa increased significantly at 2 hours, but VCAM-1 and E-Selectin levels remained unchanged. Changes in right and left PFV showed a positive correlation (r=0.9, p<0.001). No correlation could be observed between biological and Doppler changes in portal veins.
In patients with cirrhosis and hepatocellular carcinoma, PFV increased in both liver lobes 2 hours after supraselective TACE, in association with high serum TNFa. Diffuse changes in PFV after TACE suggests that mechanisms involved in the regulation of portal and hepatic arterial hemodynamics are present in patients with cirrhosis. A major role for TNFa in acute portal flow velocity variations is unlikely in this situation.
Medical science monitor: international medical journal of experimental and clinical research 10/2003; 9(9):CR383-8. · 1.70 Impact Factor
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Journal of the American College of Surgeons 12/2002; 195(5):737-9. · 4.55 Impact Factor
