[Show abstract][Hide abstract] ABSTRACT: Background The aim of this case–control study was to identify clinicopathological factors and test three relevant biomarkers for their ability to predict early intrahepatic recurrence after curative liver resection for colorectal liver metastases (CLM). Methods Of the 184 patients with CLM undergoing hepatectomy between January 2007 and December 2009, thirty patients had intrahepatic disease recurrence within 6 months. The control group was randomly selected from a cohort of patients between April 1997 and December 2005 who have survived without disease recurrence after CLM resection for over 5 years. Both groups were matched for size of metastasis greater than 5.0 cm, the presence of multiple metastases, and synchronous versus metachronous CLM. The final study population consisted of 60 patients with CLM undergoing R0 hepatectomy, 30 of whom had early intrahepatic-only recurrences (study group) and 30 patients without recurrence for more than 5 years (control group). Both groups were analyzed and compared for the presence of clinical factors and expression levels of CD133, survivin, and Bcl-2 within tumor tissue. Results Characteristics of patients were similar between the two groups except primary tumor location and administration of postoperative chemotherapy. Expression level of CD133 and survivin were significantly increased in tumors of patients with recurrence compared to patients without recurrence. On multivariate analysis high tumor expression levels of CD133 (odds ratio [OR] 14.7, confidence interval [CI] 1.8–121.3, p = 0.012) and survivin (OR 9.5, CI 2.1–44.3, p = 0.004) and postoperative chemotherapy (OR 4.8, CI 1.01–22.9, p = 0.049) were independent factors associated with early intrahepatic recurrence. Conclusions Tumor expression levels of CD133 and survivin may be a useful predictor of early intrahepatic recurrence after hepatectomy for CLM. Administration of postoperative chemotherapy may prevent early intrahepatic recurrence.
World Journal of Surgery 01/2015; · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffuse adult high grade gliomas (HGG) with necrosis encompass anaplastic oligodendrogliomas (AO) with necrosis (grade III), glioblastomas (GBM, grade IV) and glioblastomas with an oligodendroglial component (GBMO, grade IV). Here, we aimed to search for prognostic relevance of histological classification and molecular alterations of these tumors.
210 patients were included (63 AO, 56 GBM and 91 GBMO). GBMO group was split into "anaplastic oligoastrocytoma (AOA) with necrosis grade IV/GBMO", restricted to tumors showing intermingled astrocytic and oligodendroglial component, and "GBM/GBMO" based on tumors presenting oligodendroglial foci and features of GBM. Genomic arrays, IDH1 R132H expression analyses and IDH direct sequencing were done.
1p/19q codeletion characterized AO whereas no IDH1 R132H expression and intact 1p/19q characterized both GBM and GBM/GBMO. AOA with necrosis/GBMO mainly demonstrated IDH1 R132H expression and intact 1p/19q. Other IDH1 or IDH2 mutations were extremely rare. Both histological and molecular classifications were predictive of PFS and OS (p<10(-4) ).
Diffuse adult HGG with necrosis can be split into three histomolecular groups of prognostic relevance: 1p/19q codeleted AO, IDH1 R132H- GBM, and 1p19q intact IDH1 R132H+ gliomas that might be classified as IDH1 R132H+ GBM. Because of histomolecular heterogeneity, we suggest to remove the name GBMO.
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[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs).
The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing.
1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023).
The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.
[Show abstract][Hide abstract] ABSTRACT: Portal triad clamping (PTC) has been widely adopted in an attempt to decrease bleeding during liver parenchymal transection. As a larger proportion of patients are treated with chemotherapy prior to liver resection, the safety of PTC in patients with chemotherapy-associated liver injury remains poorly investigated. This study aims to evaluate the influence of PTC on early postoperative outcomes in patients with chemotherapy-associated liver injury undergoing major hepatectomy for colorectal liver metastases (CLM).
From January 2000 to October 2010, 53 patients with histologically proven chemotherapy-associated liver injuries [sinusoidal obstruction syndrome (SOS; n = 41), steatohepatitis (n = 5), and both SOS and steatohepatitis (n = 7)] who underwent major hepatectomy for CLM were divided into two groups; patients undergoing intermittent TPC (n = 20) and those who did not undergo TPC (n = 33). Perioperative clinicobiological factors, morbidity including septic complications, and mortality were analyzed and compared between the two groups.
Intraoperative blood transfusions and postoperative liver function were comparable between the two groups. Sepsis and biloma occurred more often in patients undergoing PTC longer than 30 min than in those undergoing PTC ≤ 30 min (66.7 % versus 17.1 %, p = 0.002, and 33.3 versus 0 %, p = 0.002, respectively). A multiple logistic regression analysis showed that prolonged PTC (>30 min) and the ratio of future liver remnant volume to total liver volume ≤ 43 % were independent factors for predicting postoperative sepsis [odds ratio (OR): 32.68; 95 % confidence interval (95 % CI): 2.86-372.82; p = 0.005--and odds ratio: 9.70; 95 % CI: 1.04-90.86; p = 0.047, respectively].
Portal triad clamping can be safely used in patients with chemotherapy-associated liver injury who require major liver resection. Prolonged PTC can increase the occurrence of postoperative biliary and septic complications.
World Journal of Surgery 03/2012; 36(8):1848-57. · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aluminium hydroxide is used as an effective adjuvant in a wide range of vaccines for enhancing immune response to the antigen. The pathogenic role of aluminium hydroxide is now recognized by the presence of chronic fatigue syndrome, macrophagic myofasciitis and subcutaneous pseudolymphoma, linked to intramuscular injection of aluminium hydroxide-containing vaccines. The aim of this study is to verify if the subcutaneous pseudolymphoma observed in this patient in the site of vaccine injection is linked to an aluminium overload. Many years after vaccination, a subcutaneous nodule was discovered in a 45-year-old woman with subcutaneous pseudolymphoma. In skin biopsy at the injection site for vaccines, aluminium (Al) deposits are assessed by Morin stain and quantification of Al is performed by Zeeman Electrothermal Atomic Absorption Spectrophotometry. Morin stain shows Al deposits in the macrophages, and Al assays (in μg/g, dry weight) were 768.10±18 for the patient compared with the two control patients, 5.61±0.59 and 9.13±0.057. Given the pathology of this patient and the high Al concentration in skin biopsy, the authors wish to draw attention when using the Al salts known to be particularly effective as adjuvants in single or repeated vaccinations. The possible release of Al may induce other pathologies ascribed to the well-known toxicity of this metal.
Journal of Trace Elements in Medicine and Biology 03/2012; · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Indocyanine green (ICG) retention is a validated test of hepatic function in patients with chronic liver disease. The underlying mechanism for the impairment of ICG retention in patients undergoing chemotherapy for colorectal liver metastases (CLM) remains unclear. We sought to elucidate the mechanism for impairment of ICG retention in patients with CLM.
Clinicopathologic data of 98 patients with CLM undergoing hepatectomy were analyzed. The archived nontumoral liver parenchyma bearing no CLM were immunostained with CD34 antibody to determine the sinusoidal capillarization.
Of 98 patients, 80 received preoperative chemotherapy. Sinusoidal obstruction syndrome (SOS) occurred in 39 patients (39.8%). The development of SOS in patients receiving oxaliplatin-based chemotherapy was significantly higher compared to those receiving non-oxaliplatin-based chemotherapy (P=0.003). SOS was independently associated with abnormal ICG retention rate at 15 minutes (ICG-R15) (odds ratio 3.45, 95% confidence interval 1.31-9.04, P=0.012) and CD 34 overexpression (odds ratio 18.76, 95% confidence interval 4.58-76.81, P<0.001). ICG-R15 correlated with CD34 expression within the nontumoral liver parenchyma (r=0.707, P<0.001) and severity of SOS (r=0.423, P<0.001). CD34 positive areas were likely situated at the peripheral area of SOS, and both SOS score and number of cycles of oxaliplatin-based chemotherapy significantly correlated with CD34 expression (r=0.629, P<0.001 and r=0.522, P<0.001, respectively).
These results suggest that the deterioration of hepatic functional reserve due to SOS is associated with sinusoidal capillarization, indicated by CD34 overexpression within nontumoral liver parenchyma adjacent to SOS.
Annals of Surgical Oncology 03/2012; 19(7):2230-7. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A multidisciplinary approach involving preoperative chemotherapy has become common practice in patients with colorectal liver metastases (CLM). The definition of a safe future liver remnant (FLR) volume based on preoperative clinical data in these patients is lacking. Our aim was to identify predictors of postoperative morbidities in patients undergoing major hepatectomy after intensive preoperative chemotherapy for CLM.
Between January 2000 and August 2010, a total of 101 consecutive patients with CLM underwent major hepatectomy after preoperative chemotherapy (≥6 cycles of oxaliplatin or irinotecan regimen with or without targeted therapies). The FLR ratio was calculated by two formulas: actual FLR (aFLR) ratio, and standardized FLR (sFLR) ratio. Predictors of postoperative overall morbidity, sepsis, and liver failure were identified by univariate and multivariate analyses.
Fifty-eight patients (57.4%) had 95 postoperative complications. Sepsis and postoperative liver failure occurred in 23 (22.8%) and 16 patients (15.8%), respectively. On univariate analysis, small aFLR ratio was significantly associated with all complications, and sFLR ratio was associated with sepsis and liver failure. In receiver-operating characteristic analysis, the cutoff of aFLR ratio in predicting overall morbidity, sepsis, and liver failure was 44.8, 43.1, and 37.7%, respectively, and that of sFLR ratio in predicting sepsis and liver failure was 43.6 and 48.5%, respectively. On multivariate analysis, these aFLR and sFLR ratio cutoffs were independent predictors of all complications and of sepsis and liver failure, respectively.
This study provides a cutoff FLR ratio for safe postoperative outcome after major hepatectomy in CLM patients receiving six or more cycles of preoperative chemotherapy.
Annals of Surgical Oncology 03/2012; 19(8):2526-38. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the TNF and interleukin-1/Toll-like receptor superfamilies. However, TRAF4 does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that TRAF4-deficient mice (TRAF4-KO) exhibit altered locomotion coordination typical of ataxia. TRAF4-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. TRAF4 was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that TRAF4 is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in TRAF4-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and PARP1 cleavage (western blotting). Consistent with this phenotype, MAG and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of TRAF4 (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of TRAF4 to myelination and to cerebellar homeostasis, and link the loss of TRAF4 function to demyelinating or neurodegenerative diseases.
PLoS ONE 02/2012; 7(2):e30917. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preoperative breast cancer diagnosis on core biopsies has become a standard of care in many countries. Controversies exist concerning the accuracy of HER2 testing on biopsies as compared with surgical specimens, and few data exist concerning the use of emerging technologies such as bright-field in-situ hybridization in such a setting. A French multicenter, cross-sectional, histopathological study assessed the concordance of HER2 status determined by immunohistochemistry and silver (SISH) or chromogenic in-situ hybridization (CISH) on core-needle biopsies with HER2 status determined by fluorescence in-situ hybridization (FISH) on surgical specimens. The concordance between biopsy and operative results was also assessed for each method. We studied 260 breast tumors from 24 centers between April 2003 and August 2009. Excellent concordance (κ: 0.92-0.97) was shown between immunohistochemistry and FISH with low discordance rates (2-4%), high specificity (97-98%) and sensitivity values (95-99%), with no significant difference according to the immunohistochemistry interpretation guidelines used. The correlation between SISH and CISH on biopsies and FISH on surgical samples was strong (κ: 0.96 and 0.94, respectively), with no significant difference between false negative rates or sensitivity and specificity values (2 and 5%, 99 and 96%, 98 and 98%, respectively). Whatever the evaluation technique, excellent concordance between biopsies and surgical specimens was observed (κ ≥ 0.97; discordance rates between 1 and 2%), with high sensitivity (98-99%) and specificity (98-100%). Based on these results, when FISH cannot be used, SISH and/or CISH could be proposed as an alternative method to determine HER2 status and to confirm any ambiguous immunohistochemistry results, either for preoperative percutaneous biopsies or for surgical specimens. They could also be used for quality controls and immunohistochemistry calibration.
Modern Pathology 01/2012; 25(5):675-82. · 6.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The adverse oncological effect of portal vein embolization (PVE) in patients with colorectal liver metastases (CLM) remains controversial. This study was designed to evaluate the effect of PVE on change of tumor characteristics using tumor specimens obtained from sequential hepatectomy before and after PVE.
Between December 1996 and April 2009, among 55 patients who achieved two-stage hepatectomy (TSH) combined with PVE, 39 had available cancer tissue blocks from both the first- and second-stage hepatectomy and constituted the study population. The immunohistochemistry of Ki67 and Bcl-2 before and after PVE was performed. Biomarker expressions and clinicopathological variables were assessed and their impact on recurrence was analyzed.
Whereas tumor volume and carcinoembryonic serum level significantly increased after PVE, the expression of Ki67 and Bcl-2 remained similar before and after PVE. The Bcl-2 ratio (expressed as Bcl-2 after PVE over Bcl-2 before PVE) was an independent prognostic factor for recurrence-free survival (P=0.030). Patients with Bcl-2 ratio ≤ 1 had a significantly longer median recurrence-free survival compared with those with Bcl-2 ratio >1 receiving or not receiving adjuvant chemotherapy (24.8 months versus 8.9 or 5.8 months, respectively).
Bcl-2 ratio may predict early recurrence and identify patients who do not require postoperative chemotherapy in patients undergoing TSH with PVE for CLM.
Journal of Gastrointestinal Surgery 11/2011; 16(3):554-61. · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients' characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05-1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6-13/20 vs. 10-18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use.
Breast Cancer Research and Treatment 11/2011; 132(3):895-915. · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While the participation of adipocytes is well known in tissue architecture, energy supply and endocrine processes, their implication during natural cancer history is just beginning to unfold. An extensive review of the literature concerning the impact of resident adipocytes on breast cancer development/progression was performed. This review provides in vitro and in vivo evidence that adipocytes located close to invasive cancer cells, referred to as cancer-associated adipocytes (CAAs), are essential for breast tumor development/progression. Their deleterious function is dependent, at least partly, on their crosstalk with invasive cancer cells. Indeed, this event leads to dramatic phenotypic and/or functional modifications of both cell types. Adipocytes exhibit delipidation and acquire a fibroblast-like shape. In parallel, cancer cell aggressiveness is exacerbated through increased migratory and invasive properties. Moreover, obesity is currently a sign of poor prognosis in human carcinomas. In this context, a high number of "obese" resident adipocytes might be predicted to be detrimental. Accordingly, there are some similarities between the molecular alterations observed in hypertrophied adipocytes and in CAAs. How adipocytes function to favor tumorigenesis at the molecular level remains largely unknown. Nevertheless, progress has been made recently and molecular clues are starting to emerge. Deciphering the cellular and molecular mechanisms behind the adipocyte-cancer cell heterotypic crosstalk is of great interest since it might provide new targets for improving diagnosis/prognosis and for the design of innovative therapeutic strategies. They might also improve our understanding of the relationship between obesity/metabolic disorders and cancer risk and/or poor patient outcome.
The International journal of developmental biology 09/2011; 55(7-9):851-9. · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin has been approved by the European Medicines Agency (EMEA) for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry [IHC] 3+ or IHC 2+/ fluorescence in situ hybridization [FISH]-positive or IHC 2+/ silver in situ hybridization [SISH]-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal (GE) junction. HER2 testing in gastric cancer (GC) differs from testing in breast cancer (BC) due to major differences in the tumor biology; as the disease is progressing rapidely, we recommend to test every GC at diagnosis and to offer a rapid testing (less than five days) in the metastatic setting. IHC should be the initial testing methodology and FISH or SISH should be used to retest IHC 2+ samples. As GC more frequently shows incomplete membrane staining and focal staining for HER2, HER2 testing guidelines have been adapted from BC protocols. The scoring system is slightly different in respect to the characteristics of GC. For in situ hybridization, SISH should be used in order to identify heterogeneous staining with a higher accuracy than FISH. Enrollment in training and quality assurance programs is highly recommended. In case of negativity on biopsy, it is recommended to retest for HER2, when possible, on surgical specimens and/or metastasis. This will ensure accurate and consistent HER2 testing results, which will allow the appropriate selection of patients eligible for treatment with trastuzumab.
Annales de Pathologie 04/2011; 31(2):78-87. · 0.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammatory bowel disease (IBD) exposes patients to an increased risk of colorectal cancer (i-CRC) and differences between i-CRC and sporadic colorectal cancer (s-CRC) pathogenesis were reported. In s-CRC, studies indicate abnormalities in the tumor-suppressor gene Cdx2. This study compared CDX2, β-catenin, and TP53 expression in i-CRC, s-CRC, noncancer IBD, and normal control colonic mucosa.
Expression was investigated by immunohistochemistry in 10 normal, 20 s-CRC, 11 noncancer colonic IBD and 30 i-CRC samples, and in four samples of Crohn's disease (CD)-associated small bowel adenocarcinoma (i-SBA).
In normal and noncancer IBD samples, CDX2 was confined to the colonocytes nuclei. CDX2 expression was normal in 90% of i-CRC, regardless of tumor differentiation or inflammation intensity. By contrast, CDX2 expression was altered in 45% s-CRC, particularly at the front of invasion in undifferentiated tumors. β-Catenin was restricted to cell membrane in all controls, in 91% noncancer IBD, and in 84% i-CRC samples, whereas 35% s-CRC showed cytoplasmic redistribution and exclusive nuclear staining at the front of invasion. TP53 was strongly and homogeneously expressed in i-CRC nuclei compared to normal control or s-CRC, and increases with inflammation intensity. Nested or diffuse TP53 was found in 81.8% of noncancer IBD samples with a higher proportion of TP53-expressing cells in the most inflamed samples. CDX2, β-catenin, and TP53 expression in CD-associated SBA appears similar to that of i-CRC. Neither Cdx2 nor β-catenin alterations are prominent features of i-CRC.
In i-CRC and CD-associated SBA, carcinogenesis is associated early with p53 mutations and to inflammation intensity.
[Show abstract][Hide abstract] ABSTRACT: Several factors have been reported to affect liver regeneration after portal vein embolization (PVE); however, the effect of sinusoidal obstruction syndrome (SOS) has not been evaluated. Therefore, we assessed the effect of SOS on liver regeneration after PVE in patients with multiple bilobar colorectal liver metastases scheduled to undergo two-stage hepatectomy (TSH) combined with PVE.
The subjects of this study were 78 patients prospectively scheduled to undergo TSH between December 1996 and August 2009. Archived formalin-fixed, paraffin-embedded nontumoral tissue samples were collected from the 1st- and 2nd-stage hepatectomies in 42 and 45 patients, respectively, and SOS and steatohepatitis were diagnosed pathologically. We analyzed the clinicopathological variables affecting liver regeneration after PVE.
Sinusoidal obstruction syndrome was diagnosed in 11 (26.2%) and 20 patients (44.4%) at the time of the 1st- and 2nd-stage hepatectomy, respectively. Patients with SOS at the 1st-stage hepatectomy had a significantly lower hypertrophy ratio of the future remnant liver (FRL) after PVE than patients without SOS (16.8 ± 24.0 vs 55.6 ± 32.5; P < 0.001). Multivariate logistic regression analysis revealed that SOS was an independent factor predicting lower FRL hypertrophy after PVE (Δ% FRL <20: hazard ratio 31.7, 95% confidence interval 2.84-355.12; P = 0.005). The incidence of postoperative transient liver failure after the 2nd-stage hepatectomy in patients presenting with SOS was higher than that in those without SOS, but the difference did not reach significance (25.0% vs 4.0%; P = 0.052). Steatohepatitis was confirmed at the 1st- and 2nd-stage hepatectomy in 6 (14.3%) and 3 (6.7%) patients, respectively.
Sinusoidal obstruction syndrome inhibits FRL hypertrophy after PVE and induces postoperative liver failure. Therefore, an alternative strategy is needed to perform TSH safely in the presence of SOS.
Surgery Today 01/2011; 41(1):7-17. · 1.21 Impact Factor