title: Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery and Gastroenterology, Division of General Surgery A, University of Verona Medical School, GB Rossi University Hospital, Piazzale LA Scuro 10, 37134, Verona, Italy. alfredo.guglielmi@univr.it
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guglielmi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruzzenente
authors.forename: Tommaso
authors.initials: T
authors.lastname: Campagnaro
authors.forename: Silvia
authors.initials: S
authors.lastname: Pachera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valdegamberi
authors.forename: Paola
authors.initials: P
authors.lastname: Nicoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cappellani
authors.forename: Giulio
authors.initials: G
authors.lastname: Malfermoni
authors.forename: Calogero
authors.initials: C
authors.lastname: Iacono
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000473:pathology / Q000601:surgery; D018281:Cholangiocarcinoma / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D006498:Hepatectomy / Q000379:methods* / Q000401:mortality; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome