|
1
|
Kierans AS, Cunha GM, King MJ, Marks RM, Miller FH, Lee JM, Qayyum A. Standardized reporting of intrahepatic cholangiocarcinoma. Abdom Radiol (NY) 2025; 50:1584-1594. [PMID: 39373770 DOI: 10.1007/s00261-024-04582-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/08/2024] [Accepted: 09/09/2024] [Indexed: 10/08/2024]
Affiliation(s)
| | | | | | - Robert M Marks
- University of California San Diego Medical Center, San Diego, USA
| | | | - Jeong Min Lee
- Seoul National University Hospital, Seoul, Republic of Korea
| | | |
Collapse
|
|
2
|
Kendall T, Overi D, Guido M, Braconi C, Banales J, Cardinale V, Gaudio E, Groot Koerkamp B, Carpino G. Recommendations on maximising the clinical value of tissue in the management of patients with intrahepatic cholangiocarcinoma. JHEP Rep 2024; 6:101067. [PMID: 38699072 PMCID: PMC11060959 DOI: 10.1016/j.jhepr.2024.101067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/04/2024] [Accepted: 03/08/2024] [Indexed: 05/05/2024] Open
Abstract
Background & Aims Patients with intrahepatic cholangiocarcinoma can now be managed with targeted therapies directed against specific molecular alterations. Consequently, tissue samples submitted to the pathology department must produce molecular information in addition to a diagnosis or, for resection specimens, staging information. The pathologist's role when evaluating these specimens has therefore changed to accommodate such personalised approaches. Methods We developed recommendations and guidance for pathologists by conducting a systematic review of existing guidance to generate candidate statements followed by an international Delphi process. Fifty-nine pathologists from 28 countries in six continents rated statements mapped to all elements of the specimen pathway from receipt in the pathology department to authorisation of the final written report. A separate survey of 'end-users' of the report including surgeons, oncologists, and gastroenterologists was undertaken to evaluate what information should be included in the written report to enable appropriate patient management. Results Forty-eight statements reached consensus for inclusion in the guidance including 10 statements about the content of the written report that also reached consensus by end-user participants. A reporting proforma to allow easy inclusion of the recommended data points was developed. Conclusions These guiding principles and recommendations provide a framework to allow pathologists reporting on patients with intrahepatic cholangiocarcinoma to maximise the informational yield of specimens required for personalised patient management. Impact and Implications Biopsy or resection lesional tissue from intrahepatic cholangiocarcinoma must yield information about the molecular abnormalities within the tumour that define suitability for personalised therapies in addition to a diagnosis and staging information. Here, we have developed international consensus guidance for pathologists that report such cases using a Delphi process that sought the views of both pathologists and 'end-users of pathology reports. The guide highlights the need to report cases in a way that preserves tissue for molecular testing and emphasises that reporting requires interpretation of histological characteristics within the broader clinical and radiological context. The guide will allow pathologists to report cases of intrahepatic cholangiocarcinoma in a uniform manner that maximises the value of the tissue received to facilitate optimal multidisciplinary patient management.
Collapse
Affiliation(s)
- Timothy Kendall
- University of Edinburgh Centre for Inflammation Research and Edinburgh Pathology, University of Edinburgh, Edinburgh, UK
| | - Diletta Overi
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Maria Guido
- Department of Medicine, DIMED, University of Padua, Padua, Italy
| | - Chiara Braconi
- School of Cancer Sciences, University of Glasgow, CRUK Scotland Cancer Centre, Beatson West of Scotland Cancer Centre, Glasgow, UK
| | - Jesus Banales
- Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, CIBERehd and University of the Basque Country (UPV/EHU), San Sebastian, Spain
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain
| | - Vincenzo Cardinale
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Guido Carpino
- Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
3
|
Alvaro D, Gores GJ, Walicki J, Hassan C, Sapisochin G, Komuta M, Forner A, Valle JW, Laghi A, Ilyas SI, Park JW, Kelley RK, Reig M, Sangro B. EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma. J Hepatol 2023; 79:181-208. [PMID: 37084797 DOI: 10.1016/j.jhep.2023.03.010] [Citation(s) in RCA: 114] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 04/23/2023]
Abstract
Intrahepatic cholangiocarcinoma (iCCA) develops inside the liver, between bile ductules and the second-order bile ducts. It is the second most frequent primary liver cancer after hepatocellular carcinoma, and its global incidence is increasing. It is associated with an alarming mortality rate owing to its silent presentation (often leading to late diagnosis), highly aggressive nature and resistance to treatment. Early diagnosis, molecular characterisation, accurate staging and personalised multidisciplinary treatments represent current challenges for researchers and physicians. Unfortunately, these challenges are beset by the high heterogeneity of iCCA at the clinical, genomic, epigenetic and molecular levels, very often precluding successful management. Nonetheless, in the last few years, progress has been made in molecular characterisation, surgical management, and targeted therapy. Recent advances together with the awareness that iCCA represents a distinct entity amongst the CCA family, led the ILCA and EASL governing boards to commission international experts to draft dedicated evidence-based guidelines for physicians involved in the diagnostic, prognostic, and therapeutic management of iCCA.
Collapse
|
|
4
|
Abstract
PURPOSE OF REVIEW Hepatolithiasis is a disease characterized by intrahepatic stone formation. In this article, we review the features of this disease and explore the established and emerging treatment modalities. RECENT FINDINGS Recent reports show an increasing prevalence of hepatolithiasis, likely owed to increased immigration and shifts in the Western diet. New pharmacotherapy options are limited and are often only supportive. Endoscopic intervention still cruxes on removal of impacted stones, though new techniques such as bile duct exploratory lithotomy and lithotripsy continue to advance management. Although hepatectomy of the effected portion of the liver offers definitive therapy, alternative less invasive modalities such as combined endoscopic/interventional radiology modalities have been utilized in select patients. Additionally, liver transplant serves as an option for otherwise incurable hepatolithiasis with coexisting liver dysfunction. Multiple emerging pharmacologic and procedural interventions may provide novel treatment for hepatolithiasis. While definitive therapy remains resection of affected liver segments, these modalities offer hope for less invasive approaches in the future.
Collapse
|
|
5
|
Watanabe Y, Matsuyama Y, Izumi N, Kubo S, Kokudo N, Sakamoto M, Shiina S, Takayama T, Nakashima O, Kudo M. Effect of surgical margin width after R0 resection for intrahepatic cholangiocarcinoma: A nationwide survey of the Liver Cancer Study Group of Japan. Surgery 2020; 167:793-802. [PMID: 32044110 DOI: 10.1016/j.surg.2019.12.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 12/13/2019] [Accepted: 12/18/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Data are inconsistent regarding the effects of a wide surgical margin for intrahepatic cholangiocarcinoma on recurrence-free survival and overall survival. This study was performed to investigate the effect of surgical margin width in patients undergoing R0 resection for intrahepatic cholangiocarcinoma, using a nationwide database in Japan. METHODS In total, 635 patients with intrahepatic cholangiocarcinoma who were treated by an R0 resection from 2000 to 2007 were identified from the database of a Japanese nationwide survey. Patients were divided into quartiles of the surgical margin width as follows: marginal (<1 mm), narrow (1-4 mm), intermediate (5-9 mm), and wide groups (≥10 mm). Multivariable Cox regression models for recurrence-free survival and overall survival were constructed with adjustment for preoperative and postoperative clinicopathologic factors. RESULTS Compared with the marginal group, the risk-adjusted hazard ratios (95% confidence intervals) in the narrow, intermediate, and wide groups for recurrence-free survival were 0.92 (0.62-1.37), 0.91 (0.61-1.37), and 0.81 (0.56-1.17), and those for overall survival were 0.79 (0.51-1.24), 0.93 (0.59-1.47), and 0.70 (0.46-1.08), respectively. In 398 patients without lymph node metastasis, the hazard ratios for overall survival were 0.62 (0.34-1.11), 0.63 (0.34-1.17), and 0.51 (0.29-0.90), and those of mass-forming type intrahepatic cholangiocarcinoma were 0.48 (0.21-1.08), 0.43 (0.19-0.96), and 0.40 (0.19-0.82), respectively. CONCLUSION Surgical margin width appears to have a limited effect on the prognosis of intrahepatic cholangiocarcinoma except in patients without lymph node metastasis, where a wide surgical margin is associated with favorable outcomes. This survival benefit of a wide surgical margin is especially apparent for the mass-forming type intrahepatic cholangiocarcinoma.
Collapse
Affiliation(s)
- Yukihiro Watanabe
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan; Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Norihiro Kokudo
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan
| |
Collapse
|
|
6
|
Shimizu S, Okumura T, Oshiro Y, Fukumitsu N, Fukuda K, Ishige K, Hasegawa N, Numajiri H, Murofushi K, Ohnishi K, Mizumoto M, Nonaka T, Ishikawa H, Sakurai H. Clinical outcomes of previously untreated patients with unresectable intrahepatic cholangiocarcinoma following proton beam therapy. Radiat Oncol 2019; 14:241. [PMID: 31881895 PMCID: PMC6935160 DOI: 10.1186/s13014-019-1451-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 12/19/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The effectiveness of proton beam therapy (PBT) as initial treatment for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is unclear, particularly as related to ICC histological subtypes. We performed this study to address this gap in knowledge. METHODS Thirty-seven patients with unresectable ICC who underwent PBT as their initial treatment were evaluated. Twenty-seven patients had Child-Pugh class A liver function, 11 exhibited jaundice, and 10 had multiple tumors. Nineteen, 7, and 11 tumors were classified as mass forming (MF), periductal infiltrating (PI), and intraductal growth (IG) types, respectively, based on gross appearance in imaging studies. Patients were classified into the curative group (n = 25) and palliative group (n = 12) depending on whether the planning target volume covered all the macroscopic tumors. RESULTS The 1- and 2-year overall survival rates were 60.3, and 41.4%, respectively; the median survival time (MST) was 15 months for all patients. The MSTs for curative and palliative groups were 25 and 7 months, respectively. Curative treatment and adjuvant chemotherapy significantly improved overall survival, while the presence of periductal infiltrating type tumors was a negative prognostic factor. In the curative group, the 1- and 2-year local control rates were 100 and 71.5%, respectively, while the 1-, and 2-year progression-free survival rates were 58.5, and 37.6%, respectively. No severe acute toxicities were observed. Three patients experienced grade 3 biliary tract infection, although it was unclear whether this was radiotherapy-related. CONCLUSION PBT may yield to improve survival and local tumor control among patients with unresectable ICC.
Collapse
Affiliation(s)
- Shosei Shimizu
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
| | - Toshiyuki Okumura
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Yoshiko Oshiro
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Nobuyoshi Fukumitsu
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kuniaki Fukuda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Kazunori Ishige
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Naoyuki Hasegawa
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Haruko Numajiri
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Keiko Murofushi
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Kayoko Ohnishi
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Masashi Mizumoto
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Tetsuo Nonaka
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hitoshi Ishikawa
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| | - Hideyuki Sakurai
- Department of Radiation Oncology and Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8575, Japan
| |
Collapse
|
|
7
|
Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. Surgery 2018; 163:1114-1120. [DOI: 10.1016/j.surg.2018.01.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Revised: 12/19/2017] [Accepted: 01/03/2018] [Indexed: 12/15/2022]
|
|
8
|
Shiraki T, Kuroda H, Takada A, Nakazato Y, Kubota K, Imai Y. Intraoperative frozen section diagnosis of bile duct margin for extrahepatic cholangiocarcinoma. World J Gastroenterol 2018; 24:1332-1342. [PMID: 29599608 PMCID: PMC5871828 DOI: 10.3748/wjg.v24.i12.1332] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 03/05/2018] [Accepted: 03/06/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma (CCA).
METHODS We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis (PSD) postoperatively. Then, association between FSD and local recurrence was analyzed with special reference to borderline.
RESULTS Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent (20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival (RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively.
CONCLUSION During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD.
Collapse
Affiliation(s)
- Takayuki Shiraki
- Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Hajime Kuroda
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Atsuko Takada
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Yoshimasa Nakazato
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Keiichi Kubota
- Department of Gastroenterological Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Yasuo Imai
- Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi 321-0293, Japan
| |
Collapse
|
|
9
|
Gross pathological classification of peripheral cholangiocarcinoma determines the efficacy of hepatectomy. J Gastroenterol 2013; 48:647-59. [PMID: 23001251 DOI: 10.1007/s00535-012-0666-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 08/14/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Peripheral cholangiocarcinoma (PCC) can be grossly classified as mass-forming (MF), periductal-infiltrating (PI), and intraductal papillary (IP) types. IP-PCC should be distinguished from other types of PCC because patients with IP-PCC have a more favorable prognosis. We hypothesized that gross pathological classification of non-IP-PCC could determine the efficacy of hepatectomy. METHODS We retrospectively reviewed 224 histologically proven PCCs (including 172 PCCs from patients having non-IP type tumors) from patients who underwent hepatectomy between 1977 and 2007. Non-IP-PCCs were further classified as MF, MF mixed with PI (MF-PI), and PI for comparison. RESULTS Of the 224 patients with PCC, 52 had IP-PCC (23.2 %), and 172 had non-IP-PCC (76.8 %). One hundred one of the 172 non-IP-PCC patients had a curative resection (curative resection rate 58.7 %). The follow-up duration ranged from 1.1 to 193.1 months (median 13.4 months). Overall survival (OS) rates for the non-IP-PCC patients at 1 and 5 years were 58.4 and 15.1 %, respectively. Absence of symptoms, lower alkaline phosphatase levels, normal carcinoembryonic antigen (CEA), and presence of MF-type PCC independently and favorably affected OS for the non-IP-PCC patients following hepatectomy. Independent factors favorably predicting OS for the MF-PCC patients were the absence of symptoms, hepatolithiasis, normal CEA levels, successful curative hepatectomy, and negative lymph node metastasis, while for the MF-PI-PCC patients following hepatectomy, one independent factor, successful curative hepatectomy, favorably predicted OS. For the PI-PCC patients, the independent factors favorably predicting OS were normal albumin levels and negative lymph node metastasis. CONCLUSIONS It is important to correctly differentiate between the gross pathological classifications of non-IP-PCC because of their distinct characteristics and outcomes following hepatectomy. Correct gross pathological classification is essential for further translational investigations.
Collapse
|
|
10
|
Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg 2012; 254:824-29; discussion 830. [PMID: 22042474 DOI: 10.1097/sla.0b013e318236c21d] [Citation(s) in RCA: 183] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE Define the optimal surgical margin in patients undergoing surgery for intrahepatic cholangiocarcinoma (IHCC). BACKGROUND DATA Surgery is the most effective treatment for IHCC. However, the influence of R1 resection on outcome is controversial and that of margin width has not been evaluated. METHODS We studied 212 patients undergoing curative resection of mass-forming-type IHCC. The respective influences on survival of resection status (R0 vs R1), surgical margin width, pTNM stage, and the latter's components were evaluated. RESULTS Incidence of R1 resection was 24%. Overall, R1 resection was not an independent predictor of survival [odds ratio (OR) 1.2 (0.7-2.1)] in contrast to the pTNM stage [OR 2.10 (1.2-3.5)]. In the 78 pN+ patients, survival was similar after R0 and R1 resections (median: 18 vs 13 months, respectively, P = 0.1). In the 134 pN0 patients, R1 resection was an independent predictor of poor survival [OR 9.6 (4.5-20.4)], as was the presence of satellite nodules [OR 1.9 (1.1-3.2)]. In the 116 pN0 patients with R0 resections, median survival was correlated with margin width (≤1 mm: 15 months; 2-4 mm: 36 months; 5-9 mm: 57 month; ≥10 mm: 64 month, P < 0.001) and a margin >5 mm was an independent predictor of survival [OR 2.22 (1.59-3.09)]. CONCLUSION Patients undergoing surgery for IHCC are at high risk of R1 resections. In pN0 patients, R1 resection is the strongest independent predictor of poor outcome and a margin of at least 5 mm should be created. The survival benefits of resection in pN+ patients and R1 resection in general are very low.
Collapse
|
|
11
|
|
|
12
|
Saxena A, Bester L, Chua TC, Chu FC, Morris DL. Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option. Ann Surg Oncol 2009; 17:484-91. [PMID: 19876691 DOI: 10.1245/s10434-009-0777-x] [Citation(s) in RCA: 142] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2009] [Indexed: 12/15/2022]
Abstract
BACKGROUND There are no treatment options for unresectable intrahepatic cholangiocarcinoma (ICC) with proven efficacy. The objective of this study was to present data on the safety and efficacy of a novel treatment option, yttrium-90 ((90)Y) radioembolization for unresectable ICC. METHODS Twenty-five patients underwent resin-based (90)Y radioembolization for unresectable ICC between January 2004 and May 2009. Patients were assessed at 1 month and then at 3-month intervals after treatment. Radiologic response was evaluated with the Response Criteria in Solid Tumors (RECIST) criteria. Clinical and biochemical toxicities were prospectively recorded. Survival was calculated by the Kaplan-Meier method and potential prognostic variables were identified. RESULTS No patient was lost to follow-up. The median follow-up was 8.1 (range, 0.4-56) months and the median survival after (90)Y radioembolization was 9.3 months. Two patients died within 1 month of treatment; the median follow-up for the remaining 23 was 8.9 (range, 1.5-56) months. Two factors were associated with an improved survival: peripheral tumor type (vs. infiltrative, P = .004) and Eastern Cooperative Oncology Group performance status of 0 (vs. 1 and 2, P < .001). On imaging follow-up of 23 patients, a partial response to treatment was observed in 6 patients (24%), stable disease in 11 patients (48%), and progressive disease in 5 patients (20%). The most common clinical toxicities were fatigue (64%) and self-limiting abdominal pain (40%). Two patients (8%) each developed grade III bilirubin and albumin toxicity. One patient (4%) developed grade III alkaline phosphatase toxicity. CONCLUSIONS (90)Y radioembolization may be a relatively safe and efficacious treatment for unresectable ICC. In the absence of other effective therapeutic options, this treatment warrants further investigation.
Collapse
Affiliation(s)
- Akshat Saxena
- Department of Surgery, St. George Hospital, University of New South Wales, Sydney, NSW, Australia.
| | | | | | | | | |
Collapse
|
|
13
|
Ebata T, Kamiya J, Nishio H, Nagasaka T, Nimura Y, Nagino M. The concept of perihilar cholangiocarcinoma is valid. Br J Surg 2009; 96:926-34. [PMID: 19591162 DOI: 10.1002/bjs.6655] [Citation(s) in RCA: 82] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND The term perihilar cholangiocarcinoma has been used for all tumours involving or requiring resection of the hepatic confluence. However, it does not distinguish between intrahepatic and extrahepatic hilar tumours, and has no clinicopathological basis. This retrospective study examined whether the concept of perihilar cholangiocarcinoma is valid clinically. METHODS Some 250 patients with perihilar cholangiocarcinoma were divided into extrahepatic (EHC, 167 patients) and intrahepatic (IHC, 83) groups based on tumour location. Clinicopathological data were compared between these groups. RESULTS Liver, portal vein, venous and lymphatic invasion, and nodal metastasis were more common in IHCs than EHCs, whereas histological grade and incidence of perineural invasion were similar. IHCs were more advanced at the time of surgery; stage III or IV disease was found in 37.7 per cent of EHCs and 59 per cent of IHCs. Survival was marginally better for patients with EHCs than for those with IHCs (29.3 versus 20 per cent at 5 years; P = 0.057), but survival rates were similar for each tumour stage in the American Joint Committee on Cancer classification. CONCLUSION Combining EHC and IHC under the term perihilar cholangiocarcinoma is valid, as these tumours have comparable biological behaviour, with similar clinical management depending on stage and invasion.
Collapse
Affiliation(s)
- T Ebata
- Department of Surgery, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | | | | | | | | | |
Collapse
|
|
14
|
Guglielmi A, Ruzzenente A, Campagnaro T, Pachera S, Valdegamberi A, Nicoli P, Cappellani A, Malfermoni G, Iacono C. Intrahepatic cholangiocarcinoma: prognostic factors after surgical resection. World J Surg 2009; 33:1247-1254. [PMID: 19294467 DOI: 10.1007/s00268-009-9970-0] [Citation(s) in RCA: 235] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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.
Collapse
Affiliation(s)
- Alfredo Guglielmi
- 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.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Abstract
Primary malignancies of the liver include tumors arising from the hepatocytes (hepatocellular carcinoma and the fibrolamellar variant) and the intrahepatic bile ducts (intrahepatic cholangiocarcinoma). Hepatocellular carcinoma is the most common primary cancer of the liver and is a leading cause of death from cancer worldwide. Although it is uncommon in the United States, the incidence of hepatocellular carcinoma is rising. Hepatitis, ethanol use, and cirrhosis often dominate the clinical picture and may dictate prognosis. New clinical and pathological staging systems have allowed for the more accurate stratification of patients to more appropriately identify patients for resection, transplantation, and percutaneous ablation therapies. A correlation between liver volume and surgical outcome has recently been demonstrated, with small liver remnant size being associated with increased morbidity. Portal vein embolization has therefore been proposed as one way to induce hypertrophy of the anticipated liver remnant before resection. Initial reports have shown that portal vein embolization decreases the incidence of postoperative complications. More recently, systemic chemotherapy and chemoembolization have been investigated as both primary and neoadjuvant therapy. Chemoimmunotherapy with 5-fluorouracil and interferon may be associated with a superior response rate in the fibrolamellar variant of hepatocellular carcinoma. Two recent randomized studies have also indicated improved survival after hepatic artery embolization in selected patients.
Collapse
Affiliation(s)
- Timothy M Pawlik
- The University of Texas M.D. Anderson Cancer Center, Department of Surgical Oncology, Houston, Texas 77030, USA
| | | | | | | |
Collapse
|