[show abstract][hide abstract] ABSTRACT: Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.
[show abstract][hide abstract] ABSTRACT: Surgical treatment of perihilar cholangiocarcinoma (PCC) is the treatment of choice that can achieve long term results. Unfortunately the presence of lymph node metastases is frequent and it is one of the major negative prognostic factors in patients submitted to surgery. In literature there are few data about the prognostic significance of location, number and ratio of involved nodes. Moreover guidelines about the extent of lymph node dissection are not available. In this commentary the data of literature about prognostic significance of lymph node involvement are described and analysed.
Hepatobiliary surgery and nutrition. 10/2013; 2(5):281-3.
[show abstract][hide abstract] ABSTRACT: The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement.
A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012.
Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients (p = 0.05) and 42 and 22 months in PCC patients (p = 0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients (p = 0.05) and 18 and 43 months in PCC patients (p = 0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients (p = 0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients (p = 0.01); the 0-0.25 group did not reach the value. In PCC patients, median survival of 0, 0-0.25, and >0.25 groups of patients were 42, 23, and 11 months (p = 0.01), respectively.
LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC.
Journal of Gastrointestinal Surgery 09/2013; · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND AND AIMS: Aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma ⩽ 3 cm and compensated cirrhosis. METHODS: The study involved 544 Child-Pugh A cirrhotic patients (246 in resection group and 298 in radiofrequency group) observed in 15 Italian Centers. Overall survival and tumor recurrence rates were analyzed using Kaplan Meier method before and after propensity score matching. Cox regression models were used to identify factors associated with overall survival and tumor recurrence. RESULTS: Two cases of perioperative mortality were observed in resection group and the rate of major complications was 4.5% in resection group and 2.0% in radiofrequency group (p=0.101). Four-year overall survival rates were 74.4% in resection group and 66.2% in radiofrequency group (p=0.353). Four-year cumulative HCC recurrence rates were 56% in resection group and 57.1% in radiofrequency group (p=0.765). Local tumor progression was detected in 20.5% of ablated patients and in one resected patient (p<0.001). After propensity score matching, both survival and tumor recurrence were still not significantly different although a trend towards lower recurrence was observed in RES patients. Older age and higher alpha-fetoprotein levels were independent predictors of poor overall survival while older age and higher alanine-aminotransferase levels resulted to be independent factors associated with higher recurrence rate. CONCLUSIONS: In spite of a higher rate of local tumor progression, radiofrequency ablation can provide results comparable to liver resection in the treatment of single hepatocellular carcinoma ⩽3 cm occurring in compensated cirrhosis.
Journal of Hepatology 03/2013; · 9.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background and aims
Mucin 5AC (MUC5AC) is a glycoprotein found in different epithelial cancers, including biliary tract cancer (BTC).
The aims of this study were to investigate role of MUC5AC as serum marker for BTC and its prognostic value after surgery with curative intent.
Patients and methods
From January 2007 to July 2012 quantitative assessment of serum MUC5AC was performed with ELISA method in a total of 88 subjects. Clinical and biochemical data (including CEA and Ca 19-9) of 49 patients with BTC were compared with a control population including 23 patients with benign biliary disease (BBD) and 16 healthy control subjects (HCS).
Serum MUC5AC was higher in BTC patients (mean 17.93±10.39 ng/mL) compared to BBD (mean 5.95±5.39 ng/mL) (P < 0.01) and HCS (mean 2.74±1.35 ng/mL) (P < 0.01). Multivariate analysis showed that MUC5AC was significantly related with the presence of BTC compare with Ca 19-9 and CEA P < 0.01, P = 0.080 and P = 0.463, respectively. In BTC group serum MUC5AC ≥ 14 ng/mL was associated with lymph-node metastasis (P = 0.050) and AJCC/UICC stage IVb disease (P = 0.047). Moreover, in patients underwent surgery with curative intent, serum MUC5AC ≥ 14 ng/mL was related to worse prognosis compared with patients with lower levels, with 3-year survival rates of 21.5% and 59.3%, respectively (P = 0.039).
MUC5AC could be proposed as new serum marker for BTC. Moreover quantitative assessment of serum MUC5AC could be related to tumor stage and long-term survival in patients with BTC underwent surgery with curative intent.
[show abstract][hide abstract] ABSTRACT: Hepatocellular carcinoma is one leading cause of cancer-related death and surgical resection is still one of the major curative therapies. Recently, there has been a major effort to find mechanisms involved in carcinogenesis and early relapse. c-myc gene abnormality is found in hepatocarcinogenesis. Our aim was to analyze the role of c-myc as prognostic factor in terms of overall survival and disease-free survival and to investigate if c-myc may be an important target for therapy. We studied sixty-five hepatocellular carcinomas submitted to surgical resection with curative intent. Size, macro-microvascular invasion, necrosis, number of nodules, grading and serum alfa-fetoprotein level were registered for all cases. We evaluated the c-myc aberrations by using break-apart FISH probes. Probes specific for the centromeric part of chromosome 8 and for the locus specific c-myc gene (8q24) were used to assess disomy, gains of chromosomes (polysomy due to polyploidy) and amplification. c-myc gene amplification was scored as 8q24/CEP8 > 2. Statistical analysis for disease-free survival and overall survival were performed. At molecular level, c-myc was amplified in 19% of hepatocellular carcinoma, whereas showed gains in 55% and set wild in 26% of cases. The 1- and 3-year disease-free survival and overall survival for disomic, polysomic and amplified groups were significantly different (p=0.020 and p=.018 respectively). Multivariate analysis verified that the AFP and c-myc status (amplified vs. not amplified) were significant prognostic factors for overall patients survival. c-myc gene amplification is significantly correlated with disease-free survival and overall survival in patients with hepatocellular carcinoma after surgical resection and this model identifies patients with risk of early relapse (≤12 months). We suggest that c-myc assessment may be introduced in the clinical practice for improving prognostication (high and low risk of relapse) routinely and may have be proposed as biomarker of efficacy to anti-c-myc targeted drugs in clinical trials.
PLoS ONE 01/2013; 8(7):e68203. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: AIMS: The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques. METHODS: From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography. RESULTS: Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n = 9), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n = 4), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p = 0.047), resolution of at least one metastasis (p = 0.011), and small liver metastases (largest lesion size ≤20 mm) after chemotherapy (p = 0.007). CONCLUSION: In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate.
Journal of Gastrointestinal Surgery 10/2012; · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: INTRODUCTION:: In this review of the literature, we analyze the indications for preoperative drainage in jaundiced patients who are candidates for pancreaticoduodenectomy (PD) or major hepatectomy due to periampullary or proximal bile duct neoplasms. OBJECTIVE:: The aim of this study is to review the literature and to report on the current management of jaundiced patients with periampullary or proximal bile duct neoplasms who are candidates for PD or major liver resection. BACKGROUND:: Jaundiced patients represent a major challenge for surgeons. Alterations and functional impairment caused by jaundice increase the risk of surgery; therefore, preoperative biliary decompression has been suggested. METHODS:: A literature review was performed in the MEDLINE database to identify studies on the management of jaundice in patients undergoing PD or liver resection. Papers considering palliative drainage in jaundiced patients were excluded. RESULTS:: The first group of papers considered patients affected by middle-distal obstruction from periampullary neoplasms, in which preoperative drainage was applied selectively. The second group of papers evaluated patients with biliary obstructions from proximal biliary neoplasms. In these cases, Asian authors and a few European authors considered it mandatory to drain the future liver remnant (FLR) in all patients, while American and most European authors indicated preoperative drainage only in selected cases (in malnourished patients and in those with hypoalbuminemia, cholangitis or long-term jaundice; with an FLR < 30% or 40%) given the high risk of complications of drainage (choleperitoneum, cholangitis, bleeding, and seeding). The optimal type of biliary drainage is still a matter of debate; recent studies have indicated that endoscopy is preferable to percutaneous drainage. Although the type of endoscopic biliary drainage has not been clearly established, the choice is made between plastic stents and short, covered, metallic stents, while other authors suggest the use of nasobiliary drainage. CONCLUSIONS:: A multidisciplinary evaluation (made by a surgeon, biliary endoscopist, gastroenterologist, and radiologist) of jaundiced neoplastic patients should be performed before deciding to perform biliary drainage. Middle-distal obstruction in patients who are candidates for PD does not usually require routine biliary drainage. Proximal obstruction in patients who are candidates for major hepatic resection in the majority of cases requires a drain; however, the type, site, number, and approach must be defined and tailored according to the planned hepatic resection. Recently, the use of preoperative biliary drainage limited to the FLR has been a suggested strategy. However, multicenter, randomized, controlled trials should be conducted to clarify this issue.
[show abstract][hide abstract] ABSTRACT: The best treatment for patients with small hepatocellular carcinoma (S-HCC) is still controversial. The aim of this study was to evaluate operative and long-term results after liver resection (LR) for S-HCC, defined as tumor ≤3 cm.
Retrospective multicenter study of 588 LRs for S-HCC from 8 Italian hepatobiliary surgery units (years 1992 to 2008). Primary outcomes included operative risk. Logistic regression analysis was used to evaluate risk factors for postoperative mortality. Secondary outcomes were overall survival (OS) and disease-free survival (DFS), estimated by the Kaplan-Meier method.
Postoperative mortality was 1.9%, morbidity was 35.7% (major morbidity 7.3%), and blood transfusion rate was 13.8%. Child-Pugh class B and blood transfusions were associated with higher postoperative mortality. Rates of microvascular invasion and microsatellite nodules were 37.0% and 23.1%. After a median follow-up of 38.4 months, 5- and 10-year OS rates were 52.8% and 20.3%, with DFS of 32.4% and 21.7%. Local recurrence rate was 1.4%. Between the years 2000 and 2008, 5-year OS was significantly higher than that between the years 1992 and 1999 (61.9% vs 42.6%; p < 0.001). In multivariable analysis, Child-Pugh class B, portal hypertension, and microsatellite lesions were independently associated with poor OS. Microsatellite lesion was the only variable independently associated with poor DFS.
Liver resection for S-HCC has improved over the years, with decreased operative risk. Long-term survival after LR has increased. Despite small tumor size, rates of microsatellite nodules and microvascular invasion are not negligible. Presence of microsatellite lesions was the only variable identified as being associated with poor both OS and DFS.
Journal of the American College of Surgeons 05/2012; 215(2):244-54. · 4.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Liver resection represents the first choice of treatment for primary and secondary liver malignancies, offering the patient the best chance of long-term survival. The extensive use of major hepatectomy increases the risk of post-hepatectomy liver failure (PHLF), which is associated with a high frequency of postoperative complications, mortality and increased length of hospital stay.
The aim of this review is to investigate the different risk factors related to the occurrence of PHLF and to identify the limits for a safe liver resection in patients with normal liver and injured liver (cirrhosis, cholestasis, steatosis and post-chemotherapy liver injury).
A literature search was undertaken in PubMed and related search engines, looking for articles relating to hepatic failure following hepatectomy in normal liver or injured liver.
In spite of improvements in surgical and postoperative management, the parameters determining how much liver can be resected are still largely undefined. A number of preoperative, intraoperative and postoperative factors all contribute to the likelihood of liver failure after surgery. The safe limits for liver resection can be estimated from the data of the literature for patients with normal liver and for those with different types of liver injury.
Preoperative assessment that includes evaluation of liver volume and function of the remnant liver is a mandatory prerequisite before major hepatectomy. The critical residual liver volume for patients able to predict PHLF is mainly related to the presence of pre-existing liver disease and liver function. Among patients with normal liver, the limit for safe resection ranges from 20 to 30% future remnant liver of total liver volume. In patients with injured liver (cirrhosis, cholestasis or steatosis), preoperative assessment of the risk of PHLF should include future remnant liver volumetry and accurate liver function evaluation, including different dynamic liver function tests.
Digestive surgery 01/2012; 29(1):6-17. · 1.37 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma.
Retrospective multicenter study including 17 Italian hepatobiliary surgery units.
A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007.
Postoperative mortality, morbidity, overall survival, and disease-free survival.
Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival.
Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis.
Archives of surgery (Chicago, Ill.: 1960) 01/2012; 147(1):26-34. · 4.32 Impact Factor
[show abstract][hide abstract] ABSTRACT: To analyze the outcome of hepatocellular carcinoma (HCC) resection in cirrhosis patients, related to presence of portal hypertension (PH) and extent of hepatectomy.
A retrospective analysis of 135 patients with HCC on a background of cirrhosis was submitted to curative liver resection.
PH was present in 44 (32.5%) patients. Overall mortality and morbidity were 2.2% and 33.7%, respectively. Median survival time in patients with or without PH was 31.6 and 65.1 mo, respectively (P = 0.047); in the subgroup with Child-Pugh class A cirrhosis, median survival was 65.1 mo and 60.5 mo, respectively (P = 0.257). Survival for patients submitted to limited liver resection was not significantly different in presence or absence of PH. Conversely, median survival for patients after resection of 2 or more segments with or without PH was 64.4 mo and 163.9 mo, respectively (P = 0.035).
PH is not an absolute contraindication to liver resection in Child-Pugh class A cirrhotic patients, but resection of 2 or more segments should not be recommended in patients with PH.
World Journal of Gastroenterology 12/2011; 17(46):5083-8. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Surgery for hepatocellular carcinoma (HCC) had great improvements in the last decades with low morbidity and mortality and good long-term results. Percutaneous local ablative therapies (LAT) such as radiofrequency ablation and ethanol injection (PEI) for HCC gained consent for their efficacy and safety. In retrospective studies, patients submitted to resection (LR) or LAT frequently have important selection bias. Propensity case-matched analysis proved to reduce selection bias of retrospective studies and allow comparison between different therapies.
The aim of this study was to evaluate survival comparing LR and LAT in two groups of cirrhotic patients with HCC matched with propensity score methods.
Four hundred and seventy-eight cirrhotic patients with HCC treated with LR or LAT with curative intent between January 1995 and December 2009 were included in the study. One hundred and eighty-one patients underwent LR, and 297 patients were treated with LAT. Tumor stage and liver function were evaluated in all patients. To balance the covariates in the two groups, a one-to-one propensity case-matched analysis was used. A multivariable logistic model based on age, gender, etiology of cirrhosis, Child-Pugh class, number of nodules, maximum diameter of nodules, and serum alpha-fetoprotein level was used to estimate propensity score. One-to-one caliper matching of LR and LAT groups was performed, generating a matched sample of 176 patients with 88 patients in each group.
Median survival was 65.1 months (95% CI = 48.5-81.7) after LR and 37.3 months (95% CI = 29.3-45.3) after LAT (p = 0.008). For patients in Child-Pugh class A with single HCC and maximum diameter <5 cm, median survival was 65.0 months (95% CI = 58.4-71.6) for the LR group and 63.7 months (95% CI = 31.8-95.7) for the LAT group (p = 0.730). For patients in Child-Pugh class A with single HCC and diameter ≥5 cm, median survival was 79.9 months (95% CI = 40.1-119.8) for the LR group and 21.5 months (95% CI = 10.8-32.1) for the LAT group (p = 0.023). For patients in Child-Pugh class A with two to three nodules and maximum diameter ≤3 cm, mean survival was 69.3 months (95% CI 48.7-89.9) for the LR group and 45.7 months (95% CI = 22.8-68.7) for the LAT group (p = 0.168). For patients in Child-Pugh class A with two to three nodules and diameter >3 cm, median survival was 82.9 months (95% CI = 52.0-113.7) for the LR group and 18.9 months (95% CI = 6.3-31.4) for the LAT group (p = 0.001).
Our propensity case-matched study confirmed that survival is similar after LR and LAT for single HCC smaller than 5 cm and for oligofocal HCC (up to three nodules) smaller than 3 cm; instead, for HCC larger than 5 cm or oligofocal HCC (up to three nodules) larger than 3 cm, surgical resection improves significantly long-term survival.
Journal of Gastrointestinal Surgery 11/2011; 16(2):301-11; discussion 311. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate.
The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC.
Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded.
In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1-25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P= 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1-3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P= 0.03).
LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value.
[show abstract][hide abstract] ABSTRACT: Cholangiocarcinoma can be classified as intrahepatic (ICC) or perihilar (PCC). The objectives of this study is to evaluate the surgical outcomes of patients with PCC and ICC, identify the main prognostic factors related to survival and compare the outcome and the prognostic factors of PCC and ICC.
Ninety-five out of 152 patients observed between January 1990 and December 2007 at Surgical Division of University of Verona Medical School underwent the resection of ICC (33 patients) or PCC (62 patients).
Overall median survival was 24 months with a 3- and 5-year survival rate of 45% and 23%, respectively. Prognostic factors for survival were macroscopic types of the tumor, the resection of extrahepatic bile duct, radical resection, lymph node metastases, and macro-vascular invasion. Survival was related with the macroscopic type of the tumors with a 5-year survival rate of 26% and 13% for ICC and PCC, respectively. Univariate analysis identified that negative clinico-pathological factors where significant more frequently found in PCC compared to ICC.
We identified that ICC have longer survival rate compared to PCC. PCC showed a higher frequency of negative clinico-pathological factors such as non-radical (R+) resection, perineural infiltration and macro-vascular invasion.
Journal of Surgical Oncology 12/2009; 101(2):111-5. · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: The role of liver resection in advanced hepatocellular carcinoma (multinodular or with macroscopic vascular involvement) is still controversial. The aim of this study is to evaluate the role of surgical resection compared to other therapeutic modalities in patients with advanced hepatocellular carcinoma (HCC).
Four hundred sixty four patients with HCC observed from 1991 to 2007 were included in the study. All the patients were evaluated for the treatment of HCC in relation to the severity of liver impairment and tumor stage. All the patients included in the study had no evidence of distant metastases.
Median follow up time for surviving patients was 25 months (range 1-155). Two-hundred and eighty-three patients were in Child-Pugh class A, 161 in class B, and 20 in class C. Two-hundred and seventy-one patients had single HCC, 121 patients had two or three HCCs, and 72 more than three HCCs. One-hundred and thirty-six patients (29.3%) were submitted to liver resection (LR), 232 (50.0%) to local ablative therapies (LAT) (ethanol injection, radiofrequency ablation, chemoembolization), eight (1.7%) to liver transplantation (LT), and 88 (19%) to supportive therapy (ST). Median survival time for all patients was 36 months (95% CI 24-36). Median survival time was 57 months for LR, 30 months for LAT, and 8 months for ST, with a 5-year survival of 47%, 20%, and 2.5%, respectively (p = 0.001). Actuarial 5-year survival for patients submitted to LT was 75%. Overall survival was significantly shorter in patients with multiple HCCs compared to single HCC, with median survival times of 39, 16, and 11 months for patients with a single HCC, with two to three HCCs, and with more than three HCCs, respectively (p = 0.01). Survival for patients with single HCC was significantly longer in patients submitted to LR compared to LAT and ST with median survival times of 57, 37, and 14 months, respectively (p = 0.02). Also, in patients with multinodular HCCs (2-3 HCCs) LR showed the best results with a median survival time of 58 months compared to 22 and 8 months for LAT and ST (p = 0.01). In patients with more than three HCCs, LR did not show different results compared to LAT and ST. Seventy-three patients had evidence of macroscopic vascular involvement; median survival in this subgroup of patients was significantly shorter compared to patients without vascular involvement, 10 and 36 months, respectively. Survival for patients with macroscopic vascular involvement submitted to LR or LAT was significant longer compared to ST, with mean survivals of 27, 30, and 12 months, respectively (p = 0.01).
The present study shows that the surgery can achieve good results in patients with single HCC and good liver function. Also, patients with multinodular HCCs (two to three nodules) could benefit from LR where survival is longer than after LAT or ST. In patients with more than three HCCs, LR have similar results of LAT. Macroscopic vascular invasion is a major prognostic factor, and the LR is justified in selected patients, where it can allow good long-term results compared to ST.
Journal of Gastrointestinal Surgery 06/2009; 13(7):1313-20. · 2.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor. The resectability rate is low because at the time of diagnosis this disease is frequently beyond the limits of surgical therapy. Curative resection (R0) is the most effective treatment and the only therapy associated with prolonged disease-free survival. Based on the gross appearance of the tumor the Liver Cancer Study Group of Japan (LCSGJ) defined three types: mass-forming type (MF), periductal infiltrating type (PI), intraductal growth (IG) type. The prognostic significance of gross type has been demonstrated in Eastern countries, but this issue has not been clarified in Western countries. The aim of this study was to identify the prognostic factors for survival in a group of patients submitted to surgical resection for ICC.
Between 1990 and 2007 a total of 81 consecutive patients with ICC were submitted to surgery. Patients with peritoneal carcinomatosis, extensive vascular involvement, or multiple intrahepatic metastases were excluded from surgical resection. Tumors were classified according to TMN stage (6th edition, 2002) and LCSGJ gross type classification. Tumor gross appearance on the cut surface was categorized into the following types according to the classification proposed by the Liver Cancer Study Group of Japan: MF, PI, or IG type.
During the study period 52 patients were submitted to surgical resection with curative intent, whereas in 29 patients surgery was limited to explorative laparotomy. Curative resection (R0) was achieved in 43 patients (83%); and a major hepatic resection was performed in 63% (33/52) of the patients. Extrahepatic bile duct resection was carried out in 36% (19/52) of cases. According to the LCSGJ classification, the MF type was present in 34 patients (65%), the MF + PI type in 13 (25%), the PI type in 3 (6%), and the IG type in 2 (4%). Overall median survival time was 40 months, with a 1-, 3-, and 5-year actuarial survival rates of 83%, 50%, 20%, respectively. Survival was significantly related to the macroscopic gross type, with a median survival of 50 months for patients with the MF type, 19 months for the MF + PI type, 15 months for the PI type, and 17 months for the IG type. At univariate analysis, the macroscopic gross appearance of the tumor, the presence of lymph node metastasis, involvement of extrahepatic bile ducts, the presence of macroscopic vascular invasion, and positive resection margins were significant related to survival. At multivariate analysis, macroscopic vascular invasion and lymph nodes metastases were significant related to survival with hazard ratios of 4.11 and 2.79, respectively. Further statistical analyses were carried out to identify the relation between macroscopic gross type and prognosis. We identified that the MF + PI type tumors were significantly associated with negative prognostic factors, such as the involvement of extrahepatic bile ducts, the presence of lymph nodes metastases, the presence of macroscopic vascular invasion, the presence of perineural invasion, and higher T stage.
Curative resection of ICC is the only therapy that can achieve long-term survival. The best results were observed in patients who underwent R0 resection for MF tumors without lymph node metastases or vascular invasion. Important predictive factors related to poor survival are MF + PI macroscopic tumor type, lymph node metastases, and vascular invasion. In these patients, other therapeutic approaches (i.e., adjuvant or neoadjuvant therapy) should be evaluated to improve results.
World Journal of Surgery 04/2009; 33(6):1247-54. · 2.23 Impact Factor