Sant'Ambrogio di Torino, Italy
Sant'Ambrogio di Torino, Italy

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Vigano L.,Ospedale Mauriziano Umberto I | Capussotti L.,Ospedale Mauriziano Umberto I | De Rosa G.,Ospedale Mauriziano Umberto I | Rubbia-Brandt L.,University of Geneva
Annals of Surgery | Year: 2013

Objectives: We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. Background: CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Methods: Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. Results: A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%. The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032). After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively). Conclusions: TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment. © 2013 by Lippincott Williams & Wilkins.


Kluger M.D.,Cornell University | Vigano L.,Ospedale Mauriziano Umberto I | Barroso R.,Cornell University | Cherqui D.,Cornell University
Journal of Hepato-Biliary-Pancreatic Sciences | Year: 2013

Laparoscopic major hepatectomy remains a relatively rare operation because it is a difficult and technically demanding procedure, and a standard, safe, reproducible technique has not been widely adopted. This is compounded by "major hepatectomy" encompassing multiple different operations each with their own anatomic and procedural considerations. In 2010, we investigated our learning curve for laparoscopic liver resection. We found a significant increase in the number of major hepatectomies performed over a 12-year period, with concurrent reductions in the use of hand-assistance, pedicle clamping, median clamping time, median operative time, blood loss and morbidity. This learning curve was confirmed by a subsequent multinational study. Both hospital and surgeon volume have been shown to affect outcomes, and defining a sufficient number of repetitions before the learning curve plateaus is not easy for laparoscopic major hepatectomy. We recommend that laparoscopic competencies be developed upon a foundation of open liver surgery and that laparoscopic major hepatectomy should only be attempted after competency with less technically complex laparoscopic resections. A center advanced along its institutional learning curve provides the collective expertise necessary for safe patient selection and management. An environment with colleagues willing to share their acquired proficiency allows the surgeon to observe and critique his or her performance against colleagues. Also, the guidance of like-minded surgeons supports technical development and improved outcomes. In conclusion, steady progress can be made along the learning curve through committed practice of increasingly complex tasks and with proper coaching in a high-volume environment. © 2012 Japanese Society of Hepato-Biliary-Pancreatic Surgery and Springer.


Torzilli G.,University of Milan | Belghiti J.,University Paris Diderot | Kokudo N.,University of Tokyo | Takayama T.,Nihon University | And 8 more authors.
Annals of Surgery | Year: 2013

OBJECTIVE: The aim of this study was to investigate in a retrospective setting the patients' profile and results of those undergoing surgery for hepatocellular carcinoma (HCC) in high-volume surgical centers throughout the world. BACKGROUND: Whether surgery for HCC is a suitable approach and for which subset of patients is still controversial. The EASL/AASLD (European Association for the Study of Liver Disease/American Association for the Study of Liver Disease) guidelines, based on the Barcelona Clinic Liver Cancer (BCLC) classification, leave little room for hepatic resection; inversely, other reports promote its wider application. METHODS: On the basis of the network "Hepatocellular Carcinoma: Eastern & Western Experiences," data for 2046 consecutive patients resected for HCC in 10 centers were collected. According to the BCLC classification, 1012 (50%) were BCLC 0-A, 737 (36%) BCLC B, and 297 (14%) BCLC C. Analysis of overall survival and disease-free survival and multivariate analysis of prognostic factors were performed. FINDINGS.: The 90-day mortality rate was 2.7%. Overall morbidity was 42%. After a median follow-up of 25 months (range, 1-209 months), the 1-, 3-, and 5-year overall survival rates were 95%, 80%, and 61% for BCLC 0-A; 88%, 71%, and 57% for BCLC B; and 76%, 49%, and 38% for BCLC C (P = 0.000). The 1-, 3-, and 5-year disease-free survival rates were as follows: 77%, 41%, and 21% for BCLC 0-A; 63%, 38%, and 27% for BCLC B; and 46%, 28%, and 18% for BCLC C (P = 0.000). The multivariate analysis identified bilirubin, cirrhosis, esophageal varices, tumor size, and macrovascular invasion to be statistical and independent prognostic factors for overall survival. CONCLUSIONS: This large multicentric survey shows that surgery is in current practice widely applied among patients with multinodular, large, and macrovascular invasive HCC, providing acceptable short- and long-term results and justifying an update of the EASL/AASLD therapeutic guidelines in this sense. Copyright © 2013 by Lippincott Williams & Wilkins.


Ribero D.,Ospedale Mauriziano Umberto I | Amisano M.,Ospedale Mauriziano Umberto I | Bertuzzo F.,Ospedale Mauriziano Umberto I | Langella S.,Ospedale Mauriziano Umberto I | And 4 more authors.
Annals of Surgery | Year: 2013

Objectives: To determine which method of liver volumetry is more accurate in predicting a safe resection. Background: Before major or extended hepatectomy, assessment of the future liver remnant (FLR) is crucial to reduce the risk of postoperative hepatic insufficiency. The FLR volume is usually expressed as the ratio of FLR to nontumorous total liver volume (TLV), which can be measured directly by computed tomography (mTLV) or estimated (eTLV) on the basis of correlation existing with the body surface area. To date, these 2 methods have never been compared. Methods: All consecutive, noncirrhotic patients who underwent resection of 3 or more liver segments between April 2000 and April 2012 and for whom (i) preoperative computed tomographic scans and (ii) body surface area were available entered the study. The mTLV (calculated as TLV - tumor volume) was compared with the eTLV (calculated as -794.41 + 1267.28 × body surface area) using volumetric data (cm) and clinical outcome measures (specifically, hepatic insufficiency and 90-day mortality). Definition of hepatic insufficiency was peak postoperative serum total bilirubin level of more than 7 mg/dL or, in jaundiced patients, an increasing bilirubin level on day 5 or thereafter. Results: Two-hundred forty-three patients who had undergone major (n = 135) or extended (n = 108) hepatectomies met the inclusion criteria. Twenty-eight patients (11.5%) developed hepatic insufficiency, whereas 7 patients (2.9%) died postoperatively. Compared with the eTLV, the mTLV underestimated the liver volume in 60.1% of the patients (P < 0.01). Forty-seven and 73 patients had an inadequate FLR based on mTLV and eTLV, respectively. Portal vein occlusion (PVO) was used in 44 patients. In patients (n = 162) in whom both methods did not evidence the need for PVO, postoperative hepatic insufficiency and mortality were 4.9% and 0.6%, respectively. Conversely, in patients (n = 27) in whom the eTLV but not the mTLV evidenced the need for PVO, and thus PVO was not performed, hepatic insufficiency (22.2%; P = 0.001) and mortality (3.7%; P = ns) were higher. Conclusions: The use of eTLV identifies a subset of patients (∼11%) in whom liver volumetry with the mTLV underestimates the risk of hepatic insufficiency. © 2013 by Lippincott Williams & Wilkins.


Vigano L.,Ospedale Mauriziano Umberto I | Langella S.,Ospedale Mauriziano Umberto I | Ferrero A.,Ospedale Mauriziano Umberto I | Russolillo N.,Ospedale Mauriziano Umberto I | And 2 more authors.
Annals of Surgical Oncology | Year: 2013

Background: Management of patients with synchronous colorectal liver metastases (SCRLM) should be individually tailored. This study compares patients managed by hepatobiliary centers from diagnosis with those referred for liver resection (LR). Methods: Between 1998 and 2010, a total of 284 patients with SCRLM underwent resection; 106 resectable patients (1-3 unilobar metastases, diameter <100 mm, liver-only disease) were divided into two groups: 66 managed from diagnosis (group A) and 40 referred for LR (group B). Results: Group A contained a greater proportion of multiple metastases (55.0 vs. 34.8 %, P = 0.042). Group B always received colorectal surgery as up-front treatment (vs. 18.2 %, P < 0.0001). In group B, chemotherapy before LR was more common (72.5 vs. 33.3 %, P = 0.0001) and lasted longer (P = 0.010). More patients in group B exhibited disease progression before LR (17.5 vs. 3.0 %, P = 0.025). Group A underwent fewer surgical procedures (80.3 % simultaneous resection vs. 0 %, P < 0.00001), with similar short-term outcomes. After a median follow-up of 42.0 months, group A exhibited higher 5 year disease-free survival (DFS, 64.8 vs. 30.8 %, P = 0.005) and fewer extrahepatic recurrences (21.5 vs. 47.5 %, P = 0.005). The late-referral group (>6 months, n = 24) had shorter median overall survival (OS) and DFS than group A (49.1 and 25.3 months vs. not achieved and not achieved, P < 0.05). The early-referral group exhibited OS and DFS similar to group A. Multivariate analysis confirmed late referral as a negative predictive factor of OS and DFS. Conclusions: Monocentric management of SCRLM in hepatobiliary centers is associated with shorter preoperative chemotherapy, better disease control, fewer surgical procedures (simultaneous resection), and, compared with late-referred patients, better survival. © 2012 Society of Surgical Oncology.


Vigano L.,Ospedale Mauriziano Umberto i | Ferrero A.,Ospedale Mauriziano Umberto i | Amisano M.,Ospedale Mauriziano Umberto i | Russolillo N.,Ospedale Mauriziano Umberto i | Capussotti L.,Ospedale Mauriziano Umberto i
British Journal of Surgery | Year: 2013

Background: Laparoscopic liver surgery must reproduce open surgical steps. Intraoperative ultrasonography (IOUS) is mandatory, but reliability of laparoscopic IOUS has been poorly evaluated. The aim of this study was to compare laparoscopic versus open IOUS in staging liver tumours. Methods: All patients scheduled for liver resection between September 2009 and March 2011 were considered. Inclusion criteria were primary and metastatic tumours. Exclusion criteria were: hilar/gallbladder cholangiocarcinoma, ten or more lesions, repeat resection, laparoscopic hepatectomy, adhesions and unresectability. Following percutaneous ultrasonography and thoracoabdominal computed tomography (CT), and on indication contrast-enhanced (CE) liver magnetic resonance imaging (MRI) and/or positron emission tomography (PET)-CT, patients were scheduled for laparoscopy, laparoscopic IOUS, then laparotomy, open IOUS and Partial hepatectomy. Data were collected prospectively. Reference standards were final pathology and 6-month follow-up results. Results: Sixty-five patients were included, who had a median of 3 preoperative imaging studies (ultrasonography/CT 100 per cent, CE-MRI 67 per cent, PET-CT 54 per cent). A total of 119 lesions were diagnosed. Laparoscopic IOUS detected 22 additional lesions (+18·5 per cent) in 14 patients. Open IOUS detected two additional lesions, but did not confirm four lesions; overall 20 additional lesions (+16·8 per cent) were detected in ten patients. Pathology confirmed 14 newly detected malignant nodules (+11·8 per cent) in eight patients. After 6 months ten new nodules were identified in six patients. The sensitivity of preoperative imaging, laparoscopic IOUS and open IOUS was 83·1, 92·3 and 93·0 per cent respectively; accuracy was 79, 82 and 88 per cent. In comparison with open IOUS, the sensitivity and accuracy of laparoscopic IOUS were 98·6 and 94 per cent. Conclusion: Laparoscopic IOUS is a reliable tool for staging liver tumours with a performance similar to that of open IOUS in detecting new nodules. Copyright © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.


Muratore A.,Ospedale Mauriziano Umberto i | Ribero D.,Ospedale Mauriziano Umberto i | Zimmitti G.,Ospedale Mauriziano Umberto i | Mellano A.,Ospedale Mauriziano Umberto i | And 2 more authors.
Annals of Surgical Oncology | Year: 2010

Background: Optimal margin width is uncertain because of conflicting results from recent studies using overall survival as the end-point. After recurrence, re-resection and aggressive chemotherapy heavily affect survival time; the potential confounding effect of such factors has not been investigated. Use of recurrence-free survival (RFS) may overcome this limitation. The aim of this study is to evaluate the impact of width of resection margin on RFS and site of recurrence after hepatic resection for colorectal metastases (CRM). Methods: From a prospectively maintained institutional database (1/1999-12/2007) we identified 314 patients undergone hepatectomy for CRM (1/1999-12/2007) with detailed pathologic analysis of the surgical margin and complete follow-up imaging studies documenting disease status and site of recurrence, which was categorized as: resection margin (Marg), other intra-hepatic (otherIH), lung (L) or other extra-hepatic (otherEH). Recurrence-free estimation was the survival end-point. Results: Median follow-up was 56.5 months. Two hundred and fifteen patients (68.8%) recurred at 288 sites after a mean of 15.5 months. A positive resection margin was associated with an increased risk of Marg recurrence (P < 0.001). The presence of ≥2 metastases was the only factor increasing the risk of positive margins (P < 0.05). The width of the negative resection margin (≥1 cm versus >1 cm) was not a prognostic factor of worse RFS (30.2% versus 37.3%, P = 0.6). Node status of the primary tumour, and size and number of CRM were independent predictors of RFS. Conclusions: Tumour biology and not the width of the negative resection margin affect RFS. © 2009 Society of Surgical Oncology.


Ribero D.,Ospedale Mauriziano Umberto I | Vigano L.,Ospedale Mauriziano Umberto I | Amisano M.,Ospedale Mauriziano Umberto I | Capussotti L.,Ospedale Mauriziano Umberto I
Future Oncology | Year: 2013

Despite improved overall survival rates after potentially curative liver resection (∼50-58% at 5 years), almost half of patients experience disease recurrence highlighting the need for a precise definition of outcomes to stratify patients for clinical trials and to guide treatment decisions. In the past, several factors, such as an advanced primary T stage, the primary N+ status, a large tumor size, multiple tumors, a disease-free interval of <12 months, an elevated carcinoembryonic antigen level, the presence of an extrahepatic disease, and the margin width (<1 cm) and status (positive), have been recognized to predict poor outcomes, but most of them lack the sensitivity for accurate individual prognostication. Thus, in recent years, new factors, such as response to chemotherapy, either clinical or pathological, that more closely reflect tumor biology have been established and adopted in the clinical practice. Similarly, biomarkers of poor prognosis, especially mutations in KRAS and BRAF and the expression of thymidylate synthase, have been studied, yielding promising results. However, robust evidence of their prognostic utility awaits prospective validation. © 2013 Future Medicine Ltd.


Vigano L.,Ospedale Mauriziano Umberto i | Russolillo N.,Ospedale Mauriziano Umberto i | Ferrero A.,Ospedale Mauriziano Umberto i | Langella S.,Ospedale Mauriziano Umberto i | And 2 more authors.
Annals of Surgical Oncology | Year: 2012

Background. Liver resection (LR) is the only potentially curative treatment of colorectal liver metastases (CRLM). Its outcome over the past 2 decades was studied using actual 5-year survival rates. Methods. Data of 393 consecutive patients who underwent LR for CRLM at Mauriziano Umberto I (Turin) until June 2005 were analyzed. Excluding R2 resections (n = 4) or incomplete 5-year follow-up (n = 13), 376 patients were divided according to LR date into groups A (before 1995: 90 patients), B (1995-2000: 94 patients), C (2001-2005: 192). Results. Group C presented increased multiple and bilobar metastases compared with combined groupAandB(C vsAB: 54.7% vs 40.2%, P = 0.005; 28.1% vs 19.0%, P = 0.038, respectively), decreased metastases diameter (C vs AB: 32 vs 40 mm, P = 0.0001). The 5-year overall survival, calculated excluding 4 operative mortalities (group AB), increased over the years (A, 20.5%; B, 32.6%; C, 46.4%; P<0.0001). Early recurrences (1 year) were not decreased, extrahepatic recurrences even increased (C vs AB: 17.2%vs 8.6%, P = 0.015). Recurrence-free 5-year survival improved (C vs AB: 23.4% vs 13.9%, P = 0.019) linked to decreased liver recurrences (C vs AB: 26.8% vs 37.4%, P = 0.023). Resection rate (59% overall for liver recurrence) increased along with 5-year survival after recurrence (A, 4.0%; B, 14.2%; C, 21.4%; P<0.0001). Survival improvement was confirmed for multiple (P = 0.003) and synchronous metastases (P = 0.008), N? tumors (P = 0.005), and in patients without chemotherapy (P = 0.001). Conclusions. Long-term outcome of LR for CRLM improved over 20 years, even in patients with negative prognostic factors, linked to hepatic recurrences reduction and increased survival after recurrence. © 2012 Society of Surgical Oncology.


Ribero D.,Ospedale Mauriziano Umberto i | Amisano M.,Ospedale Mauriziano Umberto i | Lo Tesoriere R.,Ospedale Mauriziano Umberto i | Rosso S.,Center for Epidemiology and Prevention in Oncology in Piedmont | And 2 more authors.
Annals of Surgery | Year: 2011

OBJECTIVE: To assess the survival benefit of additional resection of an intraoperative positive proximal bile duct margin (BDMarg) in patients undergoing hepatectomy for hilar cholangiocarcinoma (HCCA). SUMMARY BACKGROUND DATA: Intraoperative evidence of invasive cancer at the proximal BDMarg is associated with a dismal survival irrespective of whether a final negative BDMarg is achieved with an additional resection. METHODS: Clinicopathologic, operative, and survival data of consecutive patients undergone curative intent hepatectomy with bile duct resection (n = 75) for HCC (1989-2010) were analyzed. RESULTS: Frozen-section examination of the proximal BDMarg revealed invasive cancer in 19 of the 67 patients. After additional resection, which was possible in 18 cases, a secondary R0 BDMarg resection was achieved in 15 patients (83.3%), with 2 of these having, at final pathology, positive radial and distal margins. Eventually, 8 patients were classified as R1 and 67 as R0 (54 primary R0 and 13 secondary R0). Median survival of patients who had a secondary R0 resection (30.6 months) was similar to that of primarily R0-resected patients (29.3 months) and significantly better than that of R1 patients (14.9 months) (P = 0.026). Median time to recurrence and site of recurrence were similar in R0 patients independently of the performance of an additional resection. The incidence of biliary fistula was significantly increased (44.4% vs 17.5%; P = 0.02) in patients necessitating a margin re-resection. CONCLUSIONS: Additional resection of a positive proximal BDMarg, albeit associated with an increased risk of biliary fistula, offers a significant survival benefit and should be attempted whenever possible. Copyright © 2011 by Lippincott Williams &Wilkins.

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