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1.
J Clin Exp Hepatol ; 11(3): 321-326, 2021.
Article in English | MEDLINE | ID: mdl-33994715

ABSTRACT

BACKGROUND: Resection is rarely indicated in giant hepatic hemangiomas (HHs) that are symptomatic. Enucleation (EN), compared with anatomical resection (AR), is considered the better technique to resect them as EN has been reported to have lower morbidity while conserving the normal liver tissue. But no study has yet clearly established the superiority of EN over AR. In addition, the independent predictors of postoperative morbidity have not been established. METHODS: All consecutive patients operated for HH at two specialized hepatobiliary centers were reviewed. Patient demographics, operative variables, and postoperative outcomes were analyzed and compared between two techniques. Postoperative complications were graded as per Clavien-Dindo classification of surgical complications. The aims of this study were to compare two techniques of HH resection with respect to postoperative outcomes and to identify the risk factors for 90-day major postoperative morbidity and mortality. RESULTS: A total of 64 patients, including 41 who underwent AR, 22 who underwent EN, and 1 who underwent liver transplantation, were operated for hemangiomas during the study period. Ten patients (9 who were operated for hemangiomas of size ≤4 cm and 1 who underwent transplantation) were excluded. Fifty-four patients, the majority being women (85%), with a median age of 48 years, were operated for giant HH. These patients were classified into two groups based on the technique of resection, namely, EN (22 patients) and AR (32 patients). Both groups were comparable in all aspects except that the number of liver segments resected was significantly more with AR. Postoperative outcomes were similar in both groups. Independent predictors of 90-day major complications including mortality were the use of total vascular exclusion (relative risk [RR]: 2.3, p = 0.028) and duration of surgery >4.5 h (RR: 2.3, p = 0.025). CONCLUSION: Both techniques yield similar results with respect to 90-day postoperative morbidity and mortality. The choice of technique should be based on the location of tumor and simplicity of liver resection.

2.
Hepatology ; 72(3): 965-981, 2020 09.
Article in English | MEDLINE | ID: mdl-31875970

ABSTRACT

BACKGROUND AND AIMS: Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME-based classification of ICC tumors that detects potentially targetable ICC subtypes. APPROACH AND RESULTS: We established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population-counter package and compared with immunohistochemistry. We performed an unsupervised TME-based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME-based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor-infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival. CONCLUSION: We showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Immunophenotyping/methods , Signal Transduction/immunology , Tumor Microenvironment/immunology , Bile Duct Neoplasms/classification , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/immunology , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/classification , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/immunology , Cholangiocarcinoma/pathology , Drug Discovery , Female , Humans , Immune Checkpoint Inhibitors/pharmacology , Immunity/immunology , Immunohistochemistry , Inflammation/immunology , Inflammation/pathology , Male , Middle Aged , Prognosis , Transcriptome
3.
HPB (Oxford) ; 19(7): 638-648, 2017 07.
Article in English | MEDLINE | ID: mdl-28495439

ABSTRACT

BACKGROUND: There are two philosophical approaches to planning liver resection for malignancy: one strives towards zero postoperative mortality by stringent selection of candidates, thus inherently limiting patients selected; the other, accepts a low yet definite postoperative mortality rate, and offers surgery to all those with potential gain in survival. The aim of this study was to retrospectively analyse an alternative and evolving strategy, and its impact on short-term outcomes. METHOD: 3118 consecutive hepatectomies performed in 2627 patients over 3 decades (1980-2011) were analysed. Patient demographics, tumour characteristics, operative details, and postoperative outcomes were analysed. RESULTS: 1528 patients (58%) were male. Colorectal liver metastases (1221 patients, 47%) and hepatocellular carcinoma (584 patients, 22%) were the most common diagnoses. Anatomical resections were performed in 2045 (66%), some form of vascular clamping was used in 2385 (72%), and blood transfusion was required in 1130 (36%) patients. Use of preoperative techniques to increase feasibility and safety of complex liver resections allowed expansion of indications to include sicker patients with larger tumours in the later period of the study. Overall morbidity and mortality rates were 31% and 3% respectively. During the first vs. second half of the study period the postoperative morbidity and mortality were 19% vs. 36% (p < 0.001) and 2% vs. 4% (p = 0.006) respectively. CONCLUSION: With increasing experience, more patients were accepted for complex hepatectomies. However, there was a definite yet contained increase in postoperative morbidity and mortality.


Subject(s)
Carcinoma, Hepatocellular/surgery , Clinical Decision-Making , Hepatectomy , Liver Neoplasms/surgery , Patient Selection , Aged , Blood Transfusion , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Clinical Competence , Colorectal Neoplasms/pathology , Databases, Factual , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
4.
World J Surg ; 40(11): 2745-2757, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27272270

ABSTRACT

BACKGROUND: The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 ± 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). METHODS: All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. RESULTS: The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90-day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CONCLUSIONS: CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH.


Subject(s)
Hepatectomy/adverse effects , Hepatectomy/methods , Liver Neoplasms/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Blood Transfusion , Female , Humans , Male , Middle Aged , Postoperative Complications , Propensity Score , Retrospective Studies , Young Adult
5.
Hepatobiliary Surg Nutr ; 5(6): 470-477, 2016 Dec.
Article in English | MEDLINE | ID: mdl-28124001

ABSTRACT

BACKGROUND: The management of pancreatic trauma is complex. The aim of this study was to report our experience in the management of pancreatic trauma. METHODS: All patients hospitalized between 2005 and 2013 for pancreatic trauma were included. Traumatic injuries of the pancreas were classified according to the American Association for Surgery of Trauma (AAST) in five grades. Mortality and morbidity were analyzed. RESULTS: A total of 30 patients were analyzed (mean age: 38±17 years). Nineteen (63%) patients had a blunt trauma and 12 (40%) had pancreatic injury ≥ grade 3. Fifteen patients underwent exploratory laparotomy and the other 15 patients had nonoperative management (NOM). Four (13%) patients had a partial pancreatectomy [distal pancreatectomy (n=3) and pancreaticoduodenectomy (n=1)]. Overall, in hospital mortality was 20% (n=6). Postoperative mortality was 27% (n=4/15). Mortality of NOM group was 13% (n=2/15) in both cases death was due to severe head injury. Among the patients who underwent NOM, three patients had injury ≥ grade 3, one patient had a stent placement in the pancreatic duct and two patients underwent endoscopic drainage of a pancreatic pseudocyst. CONCLUSIONS: Operative management of pancreatic trauma leads to a higher mortality. This must not be necessarily related to the pancreas injury alone but also to the associated injuries including liver, spleen and vascular trauma which may cause impaired outcome more than pancreas injury.

6.
HPB (Oxford) ; 17(7): 611-23, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25980326

ABSTRACT

OBJECTIVES: Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. METHODS: The outcomes of 149 patients with huge HCCs who underwent resection during 1995-2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. RESULTS: Independent predictors of 3-month mortality (18.1%) were: total bilirubin level >34 µmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease. CONCLUSIONS: According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.


Subject(s)
Carcinoma, Hepatocellular/surgery , Decision Support Techniques , Hepatectomy , Liver Neoplasms/surgery , Medical Futility , Patient Selection , Adolescent , Adult , Aged , Aged, 80 and over , Bilirubin/blood , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/economics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cost-Benefit Analysis , Disease Progression , Disease-Free Survival , Female , France , Health Care Costs , Hepatectomy/adverse effects , Hepatectomy/economics , Hepatectomy/mortality , Humans , Kaplan-Meier Estimate , Liver Neoplasms/blood , Liver Neoplasms/economics , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Odds Ratio , Platelet Count , Predictive Value of Tests , Risk Assessment , Risk Factors , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor Burden , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/mortality , Young Adult
7.
Ann Surg ; 262(1): 93-104, 2015 Jul.
Article in English | MEDLINE | ID: mdl-24950284

ABSTRACT

OBJECTIVE: To identify independent predictors of 90-day mortality after liver resection for patients undergoing standard total vascular exclusion (TVE) with hypothermic portal perfusion and venovenous bypass. The secondary endpoint was to evaluate the long-term outcomes. BACKGROUND: Tumors invading the vena cava and/or the hepatocaval confluence are indications for standard TVE. The inclusion of liver hypothermic perfusion permits safe TVE. There are a limited number of reports focusing on this complex technique and no relevant analysis of short-term and long-term results. METHODS: Seventy-seven consecutive liver resections performed using standard TVE with hypothermic portal perfusion and venovenous bypass between 1998 and 2010 were analyzed. The independent predictors and rates of 90-day mortality, morbidity, and long-term survival were evaluated. RESULTS: The 90-day mortality rate was 19.5% (15 cases). Three independent predictors of mortality were identified: age-adjusted Charlson Comorbidity Index 3 or more (P = 0.0231; odds ratio = 47.565; 95% confidence interval = 1.701-1330.414), tumor size 10 cm or more (P = 0.0442; odds ratio = 6.374; 95% confidence interval = 1.049-38.734), and the presence of 50/50 criteria (P = 0.0407; odds ratio = 6.217; 95% confidence interval = 1.080-35.782). The overall 5-year survival rate was 30.4%. CONCLUSIONS: Liver resection using standard TVE with hypothermic portal perfusion and venovenous bypass is associated with a high mortality rate. The identification of preoperative predictors of mortality should improve the selection of patients for this aggressive surgery. Compared with nonsurgical management, the long-term results are acceptable and justify this aggressive surgery in selected patients.


Subject(s)
Hepatectomy/methods , Liver Neoplasms/surgery , Vascular Neoplasms/surgery , Adult , Aged , Common Bile Duct/surgery , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Hepatic Artery/surgery , Hepatic Veins/pathology , Hepatic Veins/surgery , Humans , Hypothermia, Induced , Liver/blood supply , Liver/pathology , Liver/surgery , Liver Diseases/etiology , Liver Neoplasms/pathology , Male , Medical Audit , Middle Aged , Neoplasm Invasiveness , Patient Selection , Portal Vein/surgery , Reperfusion Injury/etiology , Retrospective Studies , Survival Analysis , Treatment Outcome , Vascular Neoplasms/secondary , Vena Cava, Inferior/pathology , Vena Cava, Inferior/surgery
8.
HPB (Oxford) ; 17(1): 79-86, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24992279

ABSTRACT

INTRODUCTION: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection. METHODS: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection. RESULTS: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis. CONCLUSION: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.


Subject(s)
Bile Duct Neoplasms/surgery , Bile Ducts, Intrahepatic/surgery , Cholangiocarcinoma/surgery , Hepatectomy/adverse effects , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Bile Ducts, Intrahepatic/pathology , Chi-Square Distribution , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Female , France , Hepatectomy/mortality , Humans , Kaplan-Meier Estimate , Logistic Models , Lymph Node Excision , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Registries , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Tumor Burden , Young Adult
9.
Liver Transpl ; 20(12): 1475-85, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25267365

ABSTRACT

Primary hyperoxaluria type 1 (PH1) is a hepatic metabolic defect leading to end-stage renal failure. The posttransplant recurrence of kidney disease can suggest a need for combined liver-kidney transplantation (LKT). However, the risk of LKT is theoretically far higher than the risk of kidney-alone transplantation (KAT). An unselected consecutive series of 54 patients with PH1 was analyzed according to the type of transplantation initially performed between May 1979 and June 2010 at 10 French centers. The duration of dialysis, extrarenal lesions, age, and follow-up were similar between the groups. Postoperative morbidity and mortality did not differ between the groups, and 10-year patient survival rates were similar for the LKT (n = 33) and KAT groups (n = 21; 78% versus 70%). Kidney graft survival at 10 years was better after LKT (87% versus 13%, P < .001) . Four patients (12.1%) lost their first kidney graft in the LKT group, whereas 19 (90%) did in the KAT group (P < .001). The recurrence of oxalosis occurred in 11 renal grafts (52%) in the KAT group but in none in the LKT group (P < .001). End-stage renal failure resulting from rejection was also higher in the KAT group (19% versus 9%, P < 0.0001). A second kidney transplant was performed for 15 patients (71%) in the KAT group versus 4 patients (12%) in the LKT group (P < 0.001). In conclusion, LKT for PH1 provides better kidney graft survival, less rejection, and similar long-term patient survival and is not associated with an increased short-term mortality risk. LKT must be the first-line treatment for PH1 patients with end-stage renal disease.


Subject(s)
Hyperoxaluria, Primary/surgery , Kidney Transplantation , Liver Transplantation , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , France , Graft Survival , Humans , Hyperoxaluria/complications , Hyperoxaluria/surgery , Hyperoxaluria, Primary/mortality , Immunosuppressive Agents/therapeutic use , Infant , Kidney Failure, Chronic/surgery , Male , Middle Aged , Reoperation , Treatment Outcome , Young Adult
10.
Food Chem Toxicol ; 50(3-4): 1134-48, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22155268

ABSTRACT

The aim of this systematic review was to collect data concerning the effects of diets containing GM maize, potato, soybean, rice, or triticale on animal health. We examined 12 long-term studies (of more than 90 days, up to 2 years in duration) and 12 multigenerational studies (from 2 to 5 generations). We referenced the 90-day studies on GM feed for which long-term or multigenerational study data were available. Many parameters have been examined using biochemical analyses, histological examination of specific organs, hematology and the detection of transgenic DNA. The statistical findings and methods have been considered from each study. Results from all the 24 studies do not suggest any health hazards and, in general, there were no statistically significant differences within parameters observed. However, some small differences were observed, though these fell within the normal variation range of the considered parameter and thus had no biological or toxicological significance. If required, a 90-day feeding study performed in rodents, according to the OECD Test Guideline, is generally considered sufficient in order to evaluate the health effects of GM feed. The studies reviewed present evidence to show that GM plants are nutritionally equivalent to their non-GM counterparts and can be safely used in food and feed.


Subject(s)
Animal Feed , Plants, Genetically Modified , Animals , Animals, Genetically Modified , DNA/analysis , DNA/genetics , Herbicides
11.
HPB (Oxford) ; 13(8): 536-43, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21762296

ABSTRACT

BACKGROUND: An extended left hepatectomy is a complex hepatic resection often performed for large tumours in close relationship to major hilar structures. Operative outcomes of this resection for colorectal liver metastases (CLM) remain unclear. The aim of the present study was to assess short- and long-term outcome for patients with CLM after an extended left hepatectomy. METHODS: A retrospective analysis of consecutive patients undergoing an extended left hepatectomy for CLM in a large, single-centre cohort between January 1990 and January 2006 was performed. RESULTS: Thirty-one patients (3.9%) from a consecutive series of 802 patients who had undergone hepatic resection were identified as having met the definition of an extended left hepatectomy and were included for further analysis. Maximum tumour size was more than 60 mm in 15 patients, with a median size of 67.5 mm for the total group (range: 20 to 160 mm). Twenty-six patients presented with initially unresectable metastases, related to large tumour size in 11 patients and to a close relation with major vascular structures in six patients. Preoperative chemotherapy was administered to 29 patients. Combined vascular resection was performed in five patients. The mortality rate at 90 days was zero and post-operative morbidity occurred in 17 patients. R0 and R1 resections were performed in 17 and 11 patients, respectively. Three- and 5-year overall survival was 38% and 27%, respectively. Disease-free survival was 9% and 4% at 3 and 5 years. Morbidity did not differ between patients with and without a caudate lobectomy (9 of 17 patients vs. 8 of 14 patients, respectively) (P= 0.815). CONCLUSIONS: An extended left hepatectomy for CLM can provide significant long-term survival. However, morbidity is increased in this complex procedure. A caudate lobectomy does not impact surgical outcome.


Subject(s)
Colorectal Neoplasms/pathology , Hepatectomy , Liver Neoplasms/surgery , Adult , Aged , Chemotherapy, Adjuvant , Chi-Square Distribution , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Hepatectomy/adverse effects , Hepatectomy/mortality , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Neoadjuvant Therapy , Netherlands , Retrospective Studies , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment Outcome , Tumor Burden
12.
Ann Surg ; 253(6): 1069-79, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21451388

ABSTRACT

BACKGROUND: An expansion of resectability criteria of colorectal liver metastases (CLM) is justified provided "acceptable" short-term and long-term outcomes. The aim of the present study was to ascertain this paradigm in an era of modern liver surgery. METHODS: All consecutive patients who underwent hepatic resection for CLM at our institute between 1990 and 2010 were included in the study. Ninety-day mortality and morbidity rates were determined in the total study population and in 2 separate time periods (group I: 1990-2000; group II: 2000-2010). Similarly, overall and progression-free survival rates were determined. Independent predictors of postoperative morbidity were identified at multivariate analysis. RESULTS: Between 1990 and 2010, 1394 hepatectomies were performed in 1028 patients. Overall perioperative mortality and postoperative morbidity rates were 1.3% and 33%, respectively. Although patients in group II were older, had more often comorbid illnesses, and presented with more extensive liver disease, similar perioperative mortality rates were observed (1.1% in group I and 1.4% in group II; P = 0.53). A trend toward a higher morbidity rate was observed in group II (34% vs 31% in group I; P = 0.16). Independent predictors of postoperative morbidity were: treatment between 2000 and 2010, total hepatic ischemia time of 60 minutes or more, maximum size of CLM of 30 mm or more at histopathology, and presence of abnormalities in the nontumoral liver parenchyma. Although a trend toward lower overall survival was observed in patients with significant postoperative complications, no significant differences were observed in long-term outcomes between both treatment periods. CONCLUSION: After an aggressive multidisciplinary treatment of CLM, acceptable overall mortality and morbidity rates were observed. Perioperative mortality rates did not differ according to treatment period; however, more recently operated patients experienced more postoperative complications. These favorable short-term outcomes, without worsening of long-term outcomes, justify an expansion of the criteria for resectability in this patient category.


Subject(s)
Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/surgery , Aged , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Hepatectomy/mortality , Humans , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Patient Selection , Survival Analysis , Time Factors , Treatment Outcome
13.
Bull Acad Natl Med ; 195(8): 1827-9, 2011 Nov.
Article in French | MEDLINE | ID: mdl-22844744
14.
Eur J Nutr ; 48 Suppl 1: S33-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19937442

ABSTRACT

It is amazing to see how much the approach of the food risk analysis evolved in the recent years. For half a century and the birth of the risk assessment methodology in the food domain, only no appreciable health risk was considered acceptable by the manager. This is the vocabulary used in the case of a voluntary, deliberated human action, as the use of food additives (definition of ADI). In the case of risks not resulting from such an action, as that of the presence of contaminants, the risk assessor allocates provisional tolerable daily, weekly or monthly intake that are the basis for regulation. This vocabulary is in agreement with the objective which consists in approaching closer possible of the zero risk which is the wish of a majority of the consumers. Some years ago, the risk managers insisted to obtain from the assessors as often as possible a quantitative risk evaluation. More recently even, the managers would like to decide on the basis of a balance of risk and benefit acceptable for management purposes. Finally, they hope that general principles and tools will be available for conducting a quantitative risk-benefit analysis for foods and food ingredients. What is possible in the case of functional foods (FF)? Based on the definition of FF proposed in the programme FUFOSE, one has to distinguish between different situations in order to assess the risk: that of a micro-, that of a macro-component or that of a whole food. These situations have been clearly described in the document resulting from FOSIE. The standardized methodology relevant to assess micro-components is not well adapted to the assessment of whole food. Concepts of substantial equivalence and of history of safe use could be useful tools in this case. However, quantitative risk assessment remains a very difficult exercise. If a process for the assessment of health benefit of FF has been proposed as an outcome of the PASSCLAIM action, the quantification of this benefit needs adequate tools. An EFSA scientific colloquium on "Risk-Benefit Analysis of Foods" organized in July 2006 concluded that the risk-benefit analysis should mirror the current risk analysis paradigm and that its assessment should be performed with common scales. Disability adjusted life years (DALYs) or quality adjusted life years (QUALYs) have been proposed as some of these common scales. However, the meeting "concluded that the data available to undertake a quantitative risk-benefit assessment may be too scarce". Because it was considered that it was premature to formulate guidelines on good risk-benefit analysis practice and it is now time to "learning by doing", a reference to the upcoming ILSI Europe project BRAFO was done. All these aspects are discussed, in particular in relation to the specific case of FF.


Subject(s)
Consumer Product Safety , Functional Food/adverse effects , Functional Food/standards , Risk Assessment , Humans , Nutritive Value , Product Surveillance, Postmarketing , Quality-Adjusted Life Years
15.
Ann Surg ; 246(1): 97-104, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17592297

ABSTRACT

SUMMARY BACKGROUND DATA: Chronic portal obstruction can lead to formation of portal cavernoma (PC). Half of all patients with PC will develop cholestasis, termed portal biliopathy, and some will progress to symptomatic biliary obstruction. Because of the high hemorrhage risk associated with biliary surgery in patients with PC, the optimal therapeutic strategy is controversial. METHODS: Retrospective review of a single hepatobiliary center experience, including 64 patients with PC identified 19 patients with concurrent symptomatic biliary obstruction. Ten patients underwent initial treatment with a retroperitoneal splenorenal anastomosis. For the remaining 9 patients, portal biliopathy was managed without portosystemic shunting (PSS). Outcomes, including symptom relief, the number of biliary interventions, and survivals, were studied in these 2 groups. RESULTS: Within 3 months of PSS, 7 of 10 patients (70%) experienced a reduction in biliary obstructive symptoms. Five of these 10 patients subsequently underwent uncomplicated biliary bypass, and none has recurred with biliary symptoms or required biliary intervention with a mean follow-up of 8.2 years. For patients without PSS, repeated percutaneous and endobiliary procedures were required to relieve biliary symptoms. Four of the 9 patients with persistent PC required surgical intrahepatic biliary bypass, which was technically more challenging. With a mean follow-up of 8 years, 1 of these 9 patients died of severe cholangitis, 1 remained jaundiced, and 7 were asymptomatic. CONCLUSIONS: This study, which represents the largest published experience with the surgical treatment of patients with symptomatic portal biliopathy, indicates that retroperitoneal splenorenal anastomosis improves outcomes and should be the initial treatment of choice.


Subject(s)
Cholestasis/therapy , Drainage/methods , Portal Vein , Portasystemic Shunt, Surgical/methods , Practice Guidelines as Topic , Vascular Diseases/complications , Adolescent , Adult , Aged , Aged, 80 and over , Angiography , Child , Cholangiography , Cholestasis/diagnosis , Cholestasis/etiology , Constriction, Pathologic , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Ultrasonography, Doppler , Vascular Diseases/diagnosis
16.
Ann Surg ; 240(6): 1052-61; discussion 1061-4, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15570210

ABSTRACT

OBJECTIVE: To evaluate the influence of the response to preoperative chemotherapy, especially tumor progression, on the outcome following resection of multiple colorectal liver metastases (CRM). SUMMARY BACKGROUND DATA: Hepatic resection is the only treatment that currently offers a chance of long-term survival, although it is associated with a poor outcome in patients with multinodular CRM. Because of its better efficacy, chemotherapy is increasingly proposed as neoadjuvant treatment in such patients to allow or to facilitate the radicality of resection. However, little is known of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of hepatic resection. METHODS: We retrospectively analyzed the course of 131 consecutive patients who underwent liver resection for multiple (> or =4) CRM after systemic chemotherapy between 1993 and 2000, representing 30% of all liver resections performed for CRM in our institution during that period. Chemotherapy included mainly 5-fluorouracil, leucovorin, and either oxaliplatin or irinotecan for a mean of 9.8 courses (median, 9 courses). Patients were divided into 3 groups according to the type of response obtained to preoperative chemotherapy. All liver resections were performed with curative intent. We analyzed patient outcome in relation to response to preoperative chemotherapy. RESULTS: There were 58 patients (44%) who underwent hepatectomy after an objective tumor response (group 1), 39 (30%) after tumor stabilization (group 2), and 34 (26%) after tumor progression (group 3). At the time of diagnosis, mean tumor size and number of metastases were similar in the 3 groups. No differences were observed regarding patient demographics, characteristics of the primary tumor, type of liver resection, and postoperative course. First line treatments were different between groups with a higher proportion of oxaliplatin- and/or irinotecan-based treatments in group 1 (P < 0.01). A higher number of lines of chemotherapy were used in group 2 (P = 0.002). Overall survival was 86%, 41%, and 28% at 1, 3, and 5 years, respectively. Five-year survival was much lower in group 3 compared with groups 1 and 2 (8% vs. 37% and 30%, respectively at 5 years, P < 0.0001). Disease-free survival was 3% compared with 21% and 20%, respectively (P = 0.02). In a multivariate analysis, tumor progression on chemotherapy (P < 0.0001), elevated preoperative serum CA 19-9 (P < 0.0001), number of resected metastases (P < 0.001), and the number of lines of chemotherapy (P < 0.04), but not the type of first line treatment, were independently associated with decreased survival. CONCLUSIONS: Liver resection is able to offer long-term survival to patients with multiple colorectal metastases provided that the metastatic disease is controlled by chemotherapy prior to surgery. Tumor progression before surgery is associated with a poor outcome, even after potentially curative hepatectomy. Tumor control before surgery is crucial to offer a chance of prolonged remission in patients with multiple metastases.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Hepatectomy , Liver Neoplasms/secondary , Camptothecin/administration & dosage , Colorectal Neoplasms/pathology , Contraindications , Enzyme Inhibitors/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Retrospective Studies , Topoisomerase I Inhibitors
17.
Ann Surg ; 240(4): 644-57; discussion 657-8, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15383792

ABSTRACT

OBJECTIVE: To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. SUMMARY BACKGROUND DATA: Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. METHODS: From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. RESULTS: Seventy-five percent of procedures were major hepatectomies (> or =3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, > or =3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. CONCLUSIONS: Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Hepatectomy , Liver Neoplasms/secondary , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Forecasting , Humans , Leucovorin/administration & dosage , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Longitudinal Studies , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Prospective Studies , Risk Factors , Survival Rate , Treatment Outcome
18.
Ann Surg ; 238(6): 871-83; discussion 883-4, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14631224

ABSTRACT

OBJECTIVE: To determine the risk, the benefit, and the main factors of prognosis of third liver resections for recurrent colorectal metastases. SUMMARY BACKGROUND DATA: Recurrence following liver resection is frequent after a first as after a second hepatectomy. Second liver resections yield a similar survival to that obtained with first liver resection, but little is known about third hepatectomy. METHODS: This study reports a retrospective analysis of 60 patients who underwent a third liver resection for colorectal metastases in a 16-year experience (1984-2000). Patients were identified from a prospective database that collected 615 consecutive patients who cumulated 883 hepatectomies (615 first, 199 second, 60 thirds, and 9 fourths). Third hepatic resections were compared with first and second procedures, in terms of risk and benefit for the patient. Prognostic factors of survival after third hepatic resection were determined by univariate and multivariate analysis. RESULTS: A third hepatic resection was attempted in 68 of 115 of liver recurrences following a second hepatectomy (59%) and achieved in 88% of the cases (60 of 68). There was no intraoperative mortality or postoperative deaths within the 2 months. Fifteen patients developed postoperative complications (25%), a rate similar to that of first and second hepatectomies. Overall 5-year survival was 32% and disease-free survival was 17% after the third resection. Survival compared favorably to that of patients with recurrence following a second hepatectomy who could not be operated (5% at 3 years) or who failed to be resected (15% at 2 years, P = 0.0001). It also compared favorably to that of patients who underwent only two hepatectomies (5-year survival, 27%). When estimated from the time of first hepatectomy, survival was 65% at 5 years for the 60 patients who underwent three hepatic resections. Concomitant extrahepatic tumor was treated in 16 patients (27%) by 11 abdominal procedures and 5 pulmonary resections. By multivariate analysis, tumor size > 30 mm for first liver metastases, presence of extrahepatic tumor at second hepatectomy, and noncurative pattern of third liver resection were independent prognostic factors of reduced survival. CONCLUSIONS: Third hepatectomy is safe and provides an additional benefit of survival similar to that of first and second liver resections. It is worthwhile when curative and integrated into an intended multimodal strategy of tumoral eradication.


Subject(s)
Colorectal Neoplasms/pathology , Hepatectomy/statistics & numerical data , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Hepatectomy/adverse effects , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
19.
Ann Surg ; 238(4): 508-18; discussion 518-9, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14530722

ABSTRACT

OBJECTIVE: To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA: LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. METHODS: Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. RESULTS: Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively. Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT. On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. CONCLUSIONS: LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Liver Transplantation , Analysis of Variance , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/virology , Chi-Square Distribution , Feasibility Studies , Female , Humans , Liver Cirrhosis/complications , Liver Neoplasms/mortality , Liver Neoplasms/virology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local/surgery , Prognosis , Survival Analysis , Treatment Outcome
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