|
1
|
Wu Q, Zhang Z, Dong H, Mei B. Combined resection for hepatocellular carcinoma with diaphragmatic invasion: a systematic review and meta-analysis. Minerva Med 2020; 111:354-361. [PMID: 33032395 DOI: 10.23736/s0026-4806.20.06407-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
INTRODUCTION According to the Staging System of Barcelona Clinic Liver Cancer (BCLC), diaphragmatic invasion (DI) is generally considered to be a manifestation of advanced hepatocellular carcinoma (HCC) with nearly no cure. However, some studies have indicated that combined liver and diaphragmatic resection may be a reasonably safe treatment option for HCC patients with diaphragmatic invasion. In this article, we conduct a systematic review to compare the short- and long-term surgical outcomes between HCC patients without diaphragmatic involvement who underwent hepatectomy alone and HCC patients with diaphragmatic involvement who underwent combined liver and diaphragmatic resection. EVIDENCE ACQUISITION PubMed, Web of Science, Embase and Cochrane library databases were searched. All related studies were checked. Hazard ratios (HR) with 95% confidence intervals were calculated for the comparison of cumulative overall survival (OS) and recurrence free survival (RFS). Odds ratios (OR) with 95% CI were calculated for the comparison of overall postoperative morbidity and mortality. EVIDENCE SYNTHESIS Seven studies met the inclusion criteria were included. There was no significant difference between the single hepatectomy group and combined liver and diaphragmatic resection group in the overall survival and recurrence free survival. Subgroup analysis showed a statistically significantly higher overall survival in HCC patients with diaphragmatic fibrous adhesion (DFA) compared with the DI group. However, there was no statistically significant difference in OS between the DI group and the single hepatectomy group. CONCLUSIONS For HCC patients with diaphragmatic involvement, combined liver and diaphragmatic resection might be considered no matter whether its diaphragmatic invasion or not.
Collapse
Affiliation(s)
- Qiqi Wu
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhiwei Zhang
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanhua Dong
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin Mei
- Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China -
| |
Collapse
|
|
2
|
Burt AD, Alves V, Bedossa P, Clouston A, Guido M, Hübscher S, Kakar S, Ng I, Park YN, Reeves H, Wyatt J, Yeh MM, Ellis DW. Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2018; 73:369-385. [DOI: 10.1111/his.13520] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alastair D Burt
- Faculty of Health and Medical Sciences; University of Adelaide; Adelaide Australia
| | - Venâncio Alves
- Department of Pathology; University of São Paulo School of Medicine; São Paulo Brazil
| | - Pierre Bedossa
- Pathology Department; AP-HP; Beaujon Hospital; Clichy France
- Centre de Recherche Bichat-Beaujon; University Paris-Diderot; Paris France
| | - Andrew Clouston
- Envoi Specialist Pathologists; Brisbane Queensland Australia
| | - Maria Guido
- Surgical Pathology and Cytopathology Unit; Department of Medicine-DIMED; University of Padova; Padova Italy
| | - Stefan Hübscher
- Department of Cellular Pathology; Institute of Immunology and Immunotherapy; University of Birmingham; Queen Elizabeth Hospital; Birmingham UK
| | | | - Irene Ng
- Department of Pathology; State Key Laboratory for Liver Research; The University of Hong Kong; Hong Kong Hong Kong
| | - Young N Park
- Department of Pathology Yonsei; Univesity College of Medicine Seodaemun-gu; Seoul Korea
| | - Helen Reeves
- Northern Institute for Cancer Research, Newcastle University; Newcastle upon Tyne UK
| | - Judith Wyatt
- Department of Histopathology; St James University Hospital; Leeds UK
| | - Matthew M Yeh
- Department of Pathology; University of Washington School of Medicine; Seattle WA USA
| | - David W Ellis
- Clinpath Laboratories; Kent Town South Australia Australia
- ICCR Steering Group Representative; Adelaide Australia
| |
Collapse
|
|
3
|
Hepatocellular carcinoma with en bloc diaphragmatic resection: A single-center experience over 14 years. Int J Surg 2018; 53:93-97. [DOI: 10.1016/j.ijsu.2018.03.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 02/12/2018] [Accepted: 03/12/2018] [Indexed: 11/17/2022]
|
|
4
|
Chok KS, Ng KK, Cheung TT, Chan AC, Chan SC, Lo CM. Resection of T4 hepatocellular carcinomas with adjacent structures, is it justified? Hepatobiliary Pancreat Dis Int 2017; 16:52-57. [PMID: 28119259 DOI: 10.1016/s1499-3872(16)60172-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND T4 hepatocellular carcinoma (HCC) with invasion to adjacent structure(s) may require resection of not only the tumor but also the invaded structure(s). This study aims to assess whether such combined resection for T4 HCC is justifiable. METHODS Adult patients with T4 HCC were divided into three groups. Group 1: tumors and invaded adjacent structures were resected together if histopathologically confirmed tumor invasion; group 2: same as group 1 but histopathologically confirmed tumor adhesion; group 3: tumor resection only. Group comparisons were made. RESULTS Totally 144 patients were included in the study. There were 71, 14 and 59 patients in groups 1, 2 and 3, respectively. The groups were comparable in demographics, complication and survival. Ten hospital deaths occurred (5, 0 and 5 in groups 1, 2 and 3, respectively; P=0.533). The 5-year overall survival (hospital mortality excluded) was 17.8% in group 1, 14.3% in group 2, and 28.9% in group 3 (P=0.191). The 5-year disease-free survival was 10.4% in group 1 and 14.5% in group 3 (no data for group 2 yet) (P=0.565). On multivariate analysis, macrovascular invasion and poor differentiation were risk factors for survival whereas combined resection did not impact patients' survival. CONCLUSIONS Combined resection achieved survival outcomes similar to tumor resection only. Patients with tumor invasion and those with tumor adhesion had comparable survival after combined resection. At centers with the required expertise, combined resection should be attempted to treat T4 HCCs with clinically suspected invasion of adjacent structures.
Collapse
Affiliation(s)
- Kenneth Sh Chok
- Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China.
| | | | | | | | | | | |
Collapse
|
|
5
|
Li A, Wu B, Cui L, Wu M. Successful en bloc resection of recurrent hepatocellular carcinoma directly invading the abdominal wall: a case report. J Med Case Rep 2015; 9:19. [PMID: 25609080 PMCID: PMC4333836 DOI: 10.1186/1752-1947-9-19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Accepted: 12/08/2014] [Indexed: 12/22/2022] Open
Abstract
Introduction Repeat hepatic resection has previously been reported as the most effective treatment for recurrence of intrahepatic carcinoma. To the best of our knowledge, en bloc resection of recurrent hepatocellular carcinoma directly invading the abdominal wall has not been previously reported. Case presentation In September 2012, a 64-year-old Chinese male patient was referred to our hospital because of primary hepatocellular carcinoma located in Couinaud’s segments III and V. Our patient first had a hepatectomy of the liver. Ten months later, he presented with an abdominal wall mass and upper abdominal pain. Computed tomography and magnetic resonance imaging scans demonstrated a 10cm tumor in his left liver with extrahepatic metastases in his abdominal wall. It was determined that he had recurrent hepatocellular carcinoma associated with direct invasion into his abdominal wall. He had an en bloc left hepatectomy with resection of the tumor in his abdominal wall. A pathological examination of the resected specimen confirmed the diagnosis of hepatocellular carcinoma involving the abdominal wall. Disease-free margins of resection were achieved. Our patient’s postoperative course was uneventful. Eight months after the last surgery, our patient died owing to recurrence and distal metastasis. Conclusion Direct invasion of hepatocellular carcinoma into the abdominal wall is rarely encountered. Complete surgical resection should be considered in patients with an appropriate hepatic functional reserve, with consideration of the technical difficulty relating to tumor involvement with surrounding tissues.
Collapse
Affiliation(s)
- Aijun Li
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
| | | | | | | |
Collapse
|
|
6
|
Tanaka S, Iimuro Y, Hirano T, Hai S, Suzumura K, Fujimoto J. Outcomes of Hepatic Resection for Large Hepatocellular Carcinoma: Special Reference to Postoperative Recurrence. Am Surg 2015. [DOI: 10.1177/000313481508100132] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Safety and efficacy of hepatic resection for large hepatocellular carcinomas (HCCs 10 cm or greater in diameter) remain controversial. Surgical results of patients with HCCs 10 cm or greater (n = 24) who underwent hepatic resection over an 11-year period were compared with those of patients with HCCs less than 10 cm (n = 291). There was no significant difference in mortality between the two groups ( P > 0.99). Overall 5-year survival rate was 44.6 per cent among patients with HCCs 10 cm or greater and 70.5 per cent among those with HCCs less than 10 cm ( P = 0.010); however, there was no significant difference in disease-free survival rate between the two groups ( P = 0.16). Incidence of synchronous intra- and extrahepatic recurrence was higher in patients with HCCs 10 cm or greater than in those with HCCs less than 10 cm ( P = 0.0012). Macrovascular invasion alone was an independent risk factor for poor prognosis (hazard ratio [HR],: 11.1) and recurrence (HR, 6.02) after hepatic resection for HCCs 10 cm or greater, which was correlated with synchronous intra- and extrahepatic recurrence. Hepatic resection for large HCCs is safe and efficacious. However, incidence of synchronous intra- and extrahepatic recurrence is high, especially in patients with macrovascular invasion.
Collapse
Affiliation(s)
- Shogo Tanaka
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yuji Iimuro
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tadamichi Hirano
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Seikan Hai
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kazuhiro Suzumura
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Jiro Fujimoto
- Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| |
Collapse
|
|
7
|
Arkadopoulos N, Kyriazi MA, Perelas A, Theodoraki K, Papantoni E, Kokoropoulos P, Danias N, Smyrniotis V. Should Diaphragmatic Involvement Preclude Resection of Large Hepatic Tumors? World J Surg 2013; 37:2197-201. [DOI: 10.1007/s00268-013-2083-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
8
|
Jeng KS, Jeng WJ, Sheen IS, Lin CC, Lin CK. Is less than 5 mm as the narrowest surgical margin width in central resections of hepatocellular carcinoma justified? Am J Surg 2013; 206:64-71. [PMID: 23388427 DOI: 10.1016/j.amjsurg.2012.06.010] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2011] [Revised: 06/05/2012] [Accepted: 06/17/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND The aim of this study was to investigate whether <5 mm as the narrowest margin width may negatively affect a patient's outcome. METHODS A prospective cohort study was designed. From January 1994 to July 2010, 196 patients with hepatocellular carcinoma undergoing central hepatectomy were divided into group A (n = 172; narrowest margin, ≥5 to <10 mm) and group B (n = 24; narrowest margin, <5 mm), and outcomes were compared. RESULTS Significant differences between groups A and B included tumor size (P = .057), infiltrative border (P = .021), satellite lesions (P = .021), and major perivascular abutment (P = .028). Marginal recurrence occurred in 50% of the patients in group B but none of those in group A (P < .001). There were no significant differences between the groups regarding recurrence, recurrence-related death, disease-free survival, and speed of recurrence, but a borderline significant difference was found regarding the cumulative probability of overall survival. After excluding early recurrence (within 1 year), group B had significantly lower cumulative probabilities of disease-free survival (P = .020) and overall survival (P < .001). CONCLUSIONS In central resections, narrowest margin width of <5 mm does not negatively affect recurrence and overall survival. However, it increases perimargin recurrence and inversely affects late outcomes.
Collapse
Affiliation(s)
- Kuo-Shyang Jeng
- Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan
| | | | | | | | | |
Collapse
|
|
9
|
Zhou YM, Sui CJ, Li B, Xu F, Kan T, Yang JM. Results of en bloc resection for hepatocellular carcinoma extending to adjacent organs. Can J Surg 2012; 55:222-6. [PMID: 22617536 DOI: 10.1503/cjs.028410] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND To curatively resect hepatocellular carcinoma (HCC) with adjacent organ extension, the combined resection of these organs is inevitable. We analyzed the safety and effectiveness of en bloc resection for HCC extending to adjacent organs. METHODS From December 2002 to May 2006, we compared the surgical outcomes of patients with HCC extending to adjacent organs with those of closely matched, randomly selected patients with HCC without adjacent organ extension. RESULTS We included 42 patients whose HCC extended to adjacent organs and 126 patients whose HCC did not extend to adjacent organs. There was no significant difference in survival, operative morbidity or mortality between the groups. In patients with HCC extending to adjacent organs, histopathological examination of the specimen revealed true tumour invasion in 13 and adhesion in 29 patients. Those with tumour invasion were more likely to have a high incidence of capsule infiltration, microvascular invasion and early intrahepatic recurrence (≤ 1 yr after hepatectomy). The 5-year overall survival of patients with tumour invasion was 11.5%, whereas that of patients with tumour adhesion was 38.1% (p = 0.033). CONCLUSION En bloc resection is a safe and effective therapy for HCC extending to adjacent organs. Tumour invasion to adjacent organs exhibits a more aggressive clinical behaviour and is associated with worse survival than tumour adhesion.
Collapse
Affiliation(s)
- Yan-Ming Zhou
- Department of Hepato-Biliary-Pancreato-Vascular Surgery, First Affiliated Hospital of Xiamen University, Xiamen, China
| | | | | | | | | | | |
Collapse
|
|
10
|
Isolated caudate lobe resection for hepatocellular carcinoma. FORMOSAN JOURNAL OF SURGERY 2012. [DOI: 10.1016/j.fjs.2012.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
|
|
11
|
Park KK, Yang SI, Yoon MH. One stage resection of spontaneous rupture of hepatocellular carcinoma in the triangular ligament with diaphragm invasion: case report and review of the literature. World J Emerg Surg 2012; 7:30. [PMID: 22995633 PMCID: PMC3544608 DOI: 10.1186/1749-7922-7-30] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2012] [Accepted: 09/12/2012] [Indexed: 12/16/2022] Open
Abstract
A spontaneous rupture of hepatocellular carcinoma (HCC) can lead to extensive hemorrhage and is a rare but life-threatening event. A 58-year-old male patient with no history of trauma presented at our institution with severe epigastric pain and abdominal distension for 6 h. His blood pressure was a 60/40 mmHg, and pulse rate was 132/min. Abdominal contrast enhanced computed tomography (CT) imaging revealed a ruptured mass under the left diaphragm and fluid collection in the upper abdomen, flanks and pelvic cavity. Exploratory laparotomy confirmed the presence of an active bleeding tumor in the triangular ligament invading into the diaphragm. The tumor was resected with an appropriate diaphragm margin. The resected tumor was 5 cm in diameter and pathologically identified as hepatocellular carcinoma with a negative surgical margin. This case report shows that ruptured hepatocellular carcinoma should be considered in the differential diagnosis of non-traumatic hemoperitoneum. And it is necessary to set a surgical plan for unpredictable HCC rupture with direct diaphragm invasion.
Collapse
Affiliation(s)
- Kwang-Kuk Park
- Department of Surgery, Kosin University College of Medicine, Busan, South Korea.
| | | | | |
Collapse
|
|
12
|
Jeng KS, Sheen IS, Jeng WJ, Lin CC, Lin CK, Su JC, Yu MC, Fang HY. High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma. Ann Surg Oncol 2012; 20:464-73. [PMID: 22911366 DOI: 10.1245/s10434-012-2593-y] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2011] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) has a high recurrence rate after resection. Abnormal activation of the sonic hedgehog (SHH) signaling pathway contributing to the carcinogenesis of some organs had been reported. We hypothesize that activation of SHH pathway contributes to the recurrence of HCC after surgical resection. METHODS In a prospective study, from January 2006 to June 2010, a total of 50 consecutive patients with HCC after curative resection were enrolled. The ratio of the expression of messenger RNA (mRNA) of SHH, patched homolog-1 (PTCH-1) and glioma-associated oncogene-1 (GLI-1) between HCC tissues and the paired noncancerous liver tissues were measured. Both the clinicopathologic characteristics and these ratios were compared between those with recurrence and those without recurrence. They were also compared between those with and without survival. RESULTS There was a statistically significant correlation among the ratios of PTCH-1 mRNA and serum AFP level (p = 0.045), tumor size (p = 0.001), vascular permeation (p = 0.043) and tumor, node, metastasis staging system (TNM) stage (p = 0.003). A borderline significant correlation was found among ratios of GLI-1 mRNA and tumor size (p = 0.062) and TNM stage (p = 0.051). There was no such significant correlation between SHH mRNA and any parameter. Both the ratios of PTCH-1 mRNA and GLI-1 mRNA significantly adversely affected recurrence (p = 0.003 and 0.005, respectively) and survival (p < 0.001 and <0.001, respectively). CONCLUSIONS Expression of PTCH-1 mRNA and GLI-1 mRNA in HCC tissues is a potential biomarker to predict postresection disease recurrence.
Collapse
Affiliation(s)
- Kuo-Shyang Jeng
- Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan
| | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Yamashita YI, Morita K, Iguchi T, Tsujita E, Soejima Y, Taketomi A, Maehara Y. Surgical impacts of an en bloc resection of the diaphragm for hepatocellular carcinoma with gross diaphragmatic involvement. Surg Today 2010; 41:101-6. [PMID: 21191699 DOI: 10.1007/s00595-010-4289-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2009] [Accepted: 02/15/2010] [Indexed: 11/30/2022]
Abstract
PURPOSE Diaphragmatic involvement is relatively uncommon in patients undergoing a hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the short- and long-term surgical impacts of HCC with gross diaphragmatic involvement in patients undergoing an en bloc resection of the diaphragm. METHODS Between 1990 and 2007, 911 patients with HCC underwent a hepatectomy at our institution. Twenty-seven patients (3.0%) had had gross involvement of the diaphragm. Thirteen patients (1.4%) had undergone an en bloc resection of the diaphragm, and 14 (1.5%) had received only a blunt dissection. The short-term surgical impacts (surgical morbidity and mortality) and long-term surgical impacts (overall and disease-free survival) were compared between the groups. RESULTS In patients with an en bloc resection of the diaphragm as compared with those who received a blunt dissection, the values of total bilirubin and the indocyanine green retention rate at 15 min were significantly better (P < 0.01 and P = 0.04, respectively), and the rate of positivity for the hepatitis B antigen was significantly higher (P = 0.02). The positive rates of microscopic fibrocapsular invasion (P = 0.03), microscopic vascular invasion (P = 0.04), and Ki-67 immunostaining (P = 0.04) were significantly higher in patients with an en bloc resection of the diaphragm. There were no significant differences in the short-term and long-term surgical impacts between the groups. CONCLUSION An en bloc resection of the diaphragm in patients with gross diaphragmatic involvement of HCC is therefore justified, since there are no significant differences in short- or long-term surgical impacts in comparison with the patients receiving blunt dissection.
Collapse
Affiliation(s)
- Yo-ichi Yamashita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Adaptation of hepatectomy for huge hepatocellular carcinoma. ACTA ACUST UNITED AC 2008; 15:410-6. [PMID: 18670843 DOI: 10.1007/s00534-007-1317-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2007] [Accepted: 09/25/2007] [Indexed: 01/27/2023]
Abstract
BACKGROUND/PURPOSE We retrospectively identified prognostic factors in patients with huge hepatocellular carcinoma (HCC) more than 10 cm in diameter and established a clinical strategy for such patients at our institution. METHODS Three-hundred and twenty patients with HCC underwent hepatectomy. Twenty-nine of them were diagnosed with HCC 10 cm or more in diameter (group L). Two hundred and ninety-one patients were diagnosed with HCC less than 10 cm (group S). The overall and disease-free survival rates in the two groups were compared, and the prognostic factors in group L were analyzed. RESULTS The overall 3-and 5-year survival rates in group L were 33.6% and 33.6%, and these rates in group S were 61.4% and 45.0%, respectively. The difference between the two groups was significant (P=0.0048). The disease-free survival rates in group L (3-year, 21.5%; 5-year, 21.5%) were also significantly worse than those in group S (3-year, 37.1%; 5-year, 25.4%; P=0.0022). Background liver (cirrhosis vs no cirrhosis) (P=0.0380) and TNM stage according to the Liver Cancer Study Group of Japan (stage II or III vs stage IV; P=0.0308) were significantly associated with prognosis by multivariate analyses. CONCLUSIONS Hepatic resection is a safe and effective treatment for huge HCC of more than 10 cm in diameter. However, we suggest that cirrhotic patients with huge HCC with the presence of both macrovascular invasion and multiple tumors may not be appropriate candidates for hepatic resection.
Collapse
|
|
15
|
Lee SG, Hwang S, Jung JP, Lee YJ, Kim KH, Ahn CS. Outcome of patients with huge hepatocellular carcinoma after primary resection and treatment of recurrent lesions. Br J Surg 2007; 94:320-6. [PMID: 17205495 DOI: 10.1002/bjs.5622] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Tumour recurrence is common after hepatic resection of hepatocellular carcinomas (HCCs) greater than 10 cm in diameter. This study evaluated the outcome of patients with huge HCC after primary resection and treatment of recurrent lesions. METHODS A retrospective review was undertaken of clinical data for 100 patients with huge HCC who underwent liver resection. RESULTS Mean(s.d.) tumour diameter was 13.3(3.0) cm; 80 per cent were single lesions. Systematic and non-systematic resections were performed in 80 and 20 per cent of patients respectively, with R0 resection achieved in 86 per cent. Overall 1-, 3- and 5-year disease-free survival rates were 43, 26 and 20 per cent respectively. Risk factors for HCC recurrence were resection margin less than 1 cm and macrovascular invasion. Extensive tumour necrosis of 90 per cent or more after preoperative transarterial chemoembolization was not a prognostic factor. Some 85 per cent of patients with recurrence received various treatments, and these patients had a longer post-recurrence survival than those who were not treated. Overall 1-, 3- and 5-year survival rates were 66, 44 and 31 per cent respectively. CONCLUSION In patients with huge HCC, hepatic resection combined with active treatment for recurrence resulted in longer-term survival. Frequent protocol-based follow-up appears to be beneficial for the early detection and timely treatment of recurrence.
Collapse
Affiliation(s)
- S G Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Centre, University of Ulsan College of Medicine, Seoul 138-736, Korea.
| | | | | | | | | | | |
Collapse
|
|
16
|
Sheen IS, Jeng KS, Shih SC, Kao CR, Chang WH, Wang HY, Wang PC, Wang TE, Shyung LR, Chen CZ. Clinical significance of the expression of isoform 165 vascular endothelial growth factor mRNA in noncancerous liver remnants of patients with hepatocellular carcinoma. World J Gastroenterol 2005; 11:187-92. [PMID: 15633213 PMCID: PMC4205399 DOI: 10.3748/wjg.v11.i2.187] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prognostic role of isoform 165 vascular endothelial growth factor messenger RNA (VEGF165 mRNA) in noncancerous liver tissues from patients with primary hepatocellular carcinoma (HCC).
METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in noncancerous liver tissues from 60 consecutive patients with HCC undergoing curative resection. We categorized the patients with VEGF165 mRNA over 0.500 in noncancerous liver tissues as group A, and those below 0.500 as group B.
RESULTS: Among the isoforms of VEGF mRNA by multivariate analysis, a higher level of VEGF165 mRNA in noncancerous liver tissue correlated significantly with a higher risk of HCC recurrence (P = 0.039) and recurrence-related mortality (P = 0.048), but VEGF121 did not. The other significant predictors of recurrence consisted of vascular permeation (P = 0.022), daughter nodules (P = 0.033), cellular dedifferentiation (P = 0.033), an absent or incomplete capsule (P = 0.037). A significant variable of recurrence-related mortality was vascular permeation (P = 0.012). As to the clinical manifestations of 16 patients who developed recurrence, the recurrent tumor number over 2, recurrent extent over two-liver segments, and the median survival after recurrence, all significantly correlated with group A patients (P = 0.043, 0.043, and 0.048, respectively). However, the presence of extrahepatic metastasis was not (P>0.05). The difference in recurrence after treatment between the two groups had no statistical significance (P>0.05).
CONCLUSION: The higher expression of isoform VEGF165 mRNA in noncancerous liver remnant of patients with HCC may be a significant biological indicator of the invasiveness of postoperative recurrence.
Collapse
Affiliation(s)
- I-Shyan Sheen
- Liver Research Unit, Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Sheen IS, Jeng KS, Shih SC, Kao CR, Wang PC, Chen CZ, Chang WH, Wang HY, Shyung LR. Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences? World J Gastroenterol 2005; 11:171-5. [PMID: 15633210 PMCID: PMC4205396 DOI: 10.3748/wjg.v11.i2.171] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.
METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study. Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx) 32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.
RESULTS: Compared with liver tissues of control patients, the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vs control 1.225, P<0.01), whereas the decreased Cx 26 mRNA (mean: 0.700 vs of control 1.205, P>0.05) and increased Cx 43 mRNA (mean: 0.241 vs control 0.100, P>0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26 mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.
CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.
Collapse
Affiliation(s)
- I-Shyan Sheen
- Division of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Sheen IS, Jeng KS, Wang PC, Shih SC, Chang WH, Wang HY, Chen CC, Shyung LR. Are gap junction gene connexins 26, 32 and 43 of prognostic values in hepatocellular carcinoma? A prospective study. World J Gastroenterol 2004; 10:2785-90. [PMID: 15334670 PMCID: PMC4572102 DOI: 10.3748/wjg.v10.i19.2785] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2004] [Revised: 02/16/2004] [Accepted: 02/23/2004] [Indexed: 12/15/2022] Open
Abstract
AIM To investigate the prognostic value of the expression of connexin (Cx) 26, 32 and 43 messenger RNA (mRNA) in hepatocellular carcinoma (HCC) tissues. METHODS Using a reverse-transcriptase polymerase chain reaction (RT-PCR), Cx 26, Cx 32 and Cx 43 mRNAs were determined in the liver tissues of 15 controls and in HCC tissues of 25 patients undergoing curative hepatic resection. The patients were followed up clinically. RESULTS Cx 26 and Cx 32 mRNAs were significantly lower in HCC tissues compared with controls (both P<0.01). By multivariate analysis, a lower level of Cx 26 and Cx 32 mRNA correlated significantly with a risk of HCC recurrence (P = 0.033) and recurrence-related mortality (P = 0.031, P = 0.031). Cx 43 mRNA was higher in HCC tissues compared with controls but did not correlate with postoperative recurrence or recurrence-related mortality. Other significant predictors of HCC recurrence included cellular dedifferentiation (P = 0.033), less encapsulation (P = 0.050), vascular permeation (P = 0.046), and daughter nodules (P = 0.046). Significant variables related to recurrence-related mortality consisted of cell dedifferentiation (P = 0.031), vascular permeation (P = 0.048), and daughter nodules (P = 0.048). The levels of Cx 26 and Cx 32 mRNAs correlated significantly with cell differentiation (P = 0.031). CONCLUSION A low expression of Cx 26 and Cx 32 mRNAs in HCC tissues is predictive of postoperative recurrence of HCCs.
Collapse
Affiliation(s)
- I-Shyan Sheen
- Department of Surgery, Mackay Memorial Hospital, No.92, Sec 2,Chung-San North Road, Taipei, Taiwan, China.
| | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Jeng KS, Sheen IS, Tsai YC. Does the presence of circulating hepatocellular carcinoma cells indicate a risk of recurrence after resection? Am J Gastroenterol 2004; 99:1503-9. [PMID: 15307868 DOI: 10.1111/j.1572-0241.2004.30227.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Alpha-fetoprotein messenger RNA (AFP mRNA) in the peripheral blood (PB) of patients with hepatocellular carcinoma (HCC) has been considered to represent isolated tumor cells. We investigated its association with the prognosis after curative resection. METHODS Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, AFP mRNA in the PB was determined prospectively in control and in 81 patients with curative resection for HCC. RESULTS Twenty-two (27.2%) and 19 (23.4%) of 81 HCC patients had AFP mRNA in their pre- and postoperative PB. Its presence preoperatively was not associated with an increased risk of HCC recurrence (54.5% vs 40.7%, p= 0.264). In contrast, the postoperative presence associated significantly with a higher incidence of recurrence (89.5% vs 30.6%, p < 0.001), irrespective of preoperative status. The odds ratio for HCC recurrence was 19.2 (95% confidence interval [CI]: 4.0- 91.7). The cmulative probability of recurrence-free survival was also much lower in patients with postoperatively positive AFP mRNA (p < 0.001). The Cox proportional hazards model also demonstrated a significant association with recurrence (p= 0.002). Preoperative serum AFP is also a significant factor and combination with postoperative AFP mRNA enhances the predictability, sensitivity (75.0%), specificity (93.3%), positive prediction (90.0%), and negative prediction (82.4%). CONCLUSIONS The postoperative detection of AFP mRNA in PB is associated with an increased risk of earlier HCC recurrence. Combination with preoperative serum AFP is useful in predictability.
Collapse
Affiliation(s)
- Kuo-Shyang Jeng
- Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China
| | | | | |
Collapse
|
|
20
|
Jeng KS, Sheen IS, Wang YC, Gu SL, Chu CM, Shih SC, Wang PC, Chang WH, Wang HY. Is the vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma of prognostic value after resection ? World J Gastroenterol 2004; 10:676-81. [PMID: 14991937 PMCID: PMC4716908 DOI: 10.3748/wjg.v10.i5.676] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To study whether vascular endothelial growth factor messenger RNA (VEGF mRNA) in the hepatocellular carcinoma (HCC) tissues obtained after curative resection has a prognostic value.
METHODS: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA was determined prospectively in liver tissues of 50 controls and in HCC tissues of 50 consecutive patients undergoing curative resection for HCC.
RESULTS: Among the isoforms of VEGF mRNA, VEGF165 and VEGF121 were expressed. By multivariate analysis, a higher level of VEGF165 in HCC tissue correlated with a significant risk of HCC recurrence (P = 0.038) and significantly with recurrence-related mortality (P = 0.045); while VEGF121 did not. Other significant predictors of HCC recurrence included cellular dedifferentiation (P = 0.033), an absent or incomplete capsule (P = 0.020), vascular permeation (P = 0.018), and daughter nodules (P = 0.006). The other significant variables of recurrence related mortality consisted of vascular permeation (P = 0.045), and cellular dedifferentiation (P = 0.053). The level of VEGF mRNA in HCC tissues, however, did not significantly correlate with tumor size, cellular differentiation, capsule, daughter nodules, vascular permeation, necrosis and hemorrhage of tumors.
CONCLUSION: The expression of VEGF mRNA, especially isoform VEGF165, in HCC tissues, may play a significant and independant role in the prediction of postoperative recurrence of HCC.
Collapse
Affiliation(s)
- Kuo-Shyang Jeng
- Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
21
|
Sheen IS, Jeng KS, Shih SC, Wang PC, Chang WH, Wang HY, Shyung LR, Lin SC, Kao CR, Tsai YC, Wu TY. Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination. World J Gastroenterol 2004; 10:31-6. [PMID: 14695764 PMCID: PMC4717073 DOI: 10.3748/wjg.v10.i1.31] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human αfetoprotein messenger RNA (hAFP mRNA). hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells.
METHODS: Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum α-fetoprotein and Child-Pugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules), hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed.
RESULTS: No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative, perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs 41%, P = 0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs 31%, P < 0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P = 0.067) and recurrence related mortality (P = 0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC recurrence (58% vs.39%, P = 0.093). The correlation between perioperative hAFP mRNA positivity and recurrence related mortality had no statistical significance (P = 0.836).
CONCLUSION: From our study, perioperative detection of hAFP mRNA in peripheral blood of patients has no clinical relevance and significant role in the prediction of HCC recurrence. Surgical resection itself may not accelerate cancer dissemination and does not increase postoperative recurrence significantly either.
Collapse
Affiliation(s)
- I-Shyan Sheen
- Divisons of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, China
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
22
|
Mok KT, Wang BW, Lo GH, Liang HL, Liu SI, Chou NH, Tsai CC, Chen IS, Yeh MH, Chen YC. Multimodality management of hepatocellular carcinoma larger than 10 cm. J Am Coll Surg 2003; 197:730-8. [PMID: 14585406 DOI: 10.1016/j.jamcollsurg.2003.07.013] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Hepatic resection for huge hepatocellular carcinoma (HCC) is challenging. The role of multimodality nonsurgical therapy for HCC larger than 10 cm is unclear. STUDY DESIGN We retrospectively investigated 131 HCC patients with main tumors larger than 10 cm in diameter seen between October 1990 and October 2001. Fifty-six patients (group A) underwent hepatectomy and 75 patients (group B) underwent nonsurgical multidisciplinary therapy including hepatic arterial infusion, transcatheter arterial embolization, and percutaneous acetic acid injection. RESULTS Patients in group B were older, had lower serum albumin levels, and there were more patients with liver cirrhosis and great vessel invasion. Median survivals of group A and B patients were 17 months and 7 months, respectively (p < 0.001). But the 1-, 3-, 5-year survival rates in group B using 38 patients undergoing 3 or more sessions of nonsurgical treatment were not significantly worse than those for group A using 53 patients with followup (57.1%, 19.0%, 16.3% versus 60.7%, 24.5%, 24.5%, respectively). Group A patients had 37.7% and 71.7% recurrence rates at 6 and 12 months, respectively, after operation, and they had a significantly higher frequency of overall extrahepatic recurrence compared with group B patients (43.4% versus 18.7%, p = 0.005). In group B, only 3 of 35 patients younger than 60 years had tumor shrinkage after nonsurgical treatment modalities in comparison to 17 of 40 patients in the elderly group (p = 0.003). Younger patients had a significantly higher prevalence of hepatitis B surface antigen positivity (85.7% versus 47.5%) and infiltrating tumor growth pattern (74.3% versus 45.0%) compared with older patients. CONCLUSIONS Our study suggests that the advantage of hepatic resection in patients with huge HCC is marginal. An effective adjuvant therapy is needed to improve outcomes after hepatic resection. The experience in using nonsurgical treatment shows that the result is poor in young patients compared with that in elderly patients.
Collapse
MESH Headings
- Acetic Acid/administration & dosage
- Age Factors
- Aged
- Antibiotics, Antineoplastic/administration & dosage
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Biopsy
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/mortality
- Carcinoma, Hepatocellular/therapy
- Chemoembolization, Therapeutic/methods
- Cisplatin/administration & dosage
- Female
- Hepatectomy/methods
- Humans
- Infusions, Intra-Arterial
- Injections, Intralesional
- Leucovorin/administration & dosage
- Liver Neoplasms/diagnosis
- Liver Neoplasms/mortality
- Liver Neoplasms/therapy
- Male
- Middle Aged
- Mitomycin/administration & dosage
- Neoplasm Recurrence, Local/epidemiology
- Neoplasm Recurrence, Local/etiology
- Neoplasm Staging
- Patient Selection
- Proportional Hazards Models
- Retrospective Studies
- Survival Analysis
- Taiwan/epidemiology
- Tomography, X-Ray Computed
- Treatment Outcome
Collapse
Affiliation(s)
- King-Tong Mok
- Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Sheen IS, Jeng KS, Wu JY. Is p53 gene mutation an indicatior of the biological behaviors of recurrence of hepatocellular carcinoma? World J Gastroenterol 2003; 9:1202-7. [PMID: 12800224 PMCID: PMC4611784 DOI: 10.3748/wjg.v9.i6.1202] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate mutant p53 gene in primary hepatocellular carcinoma and to investigate the correlation between it and the recurrence of hepatocellular carcinoma.
METHODS: Mutations of p53 gene were examined using anti-human p53 monoclonal antibody and immunohistochemical staining in 79 resected hepatocellular carcinomas. The correlations among variables of p53 positivity and invasiveness, disease free interval and survival were studied. In addition, in those who developed recurrence, the correlation among p53 positivity, clinical features and post-recurrence survival were also studied.
RESULTS: Of these 79 cases, 64 (81%) had p53 mutation. Those patients with mutant p53 positivity had significantly more tumor recurrence (76.6% vs 40.0%, P = 0.0107). However, the COX proportional hazards model showed that p53 overexpression had only weak correlations with recurrence free interval and survival time (P = 0.088 and 0.081), which was probably related to the short duration of follow-up. The invasiveness variables may be predictors of HCC recurrence. On univariate analysis, more patients with mutant p53 positivity had vascular permeation [78.1 vs 40.0%, P = 0.0088, O.R. (odds ratio) = 5.3], grade II-IV differentiation (98.4 vs 80.0%, P = 0.0203, O.R. = 15.7), no complete capsule (82.8 vs 53.3%, P = 0.0346, O.R. = 4.2) and daughter nodules (60.9 vs. 33.3%, P = 0.0527, O.R. = 3.1) than patients with negative p53 staining. On multivariate analysis, only vascular permeation and grade of differentiation remained significant (P = 0.042 and 0.012). There was no statistically significant correlation between the status of p53 in the primary lesion and the clinical features of recurrent hepatocellular carcinomas examined, including extrahepatic metastasis (P = 0.1103) and the number of recurrent tumors (P = 1.000) except for disease over more than one segment in the extent of recurrent tumors (P = 0.0043). The post-recurrence median survival was lower in patients in whom p53 mutation had been detected in the primary lesion with a weak significance (3.42 mo vs 11.0 mo, P = 0.051).
CONCLUSION: Our findings suggest that p53 mutation correlates significantly with invasiveness including vascular permeation, grade of cellular differentiation, incomplete capsule and multinodular lesions. Hepatocellular carcinomas with p53 mutations had more tumor recurrence and p53 mutation may also influence disease recurrence interval and survival time. Hepatocellular carcinomas with p53 mutations recur more extensively with a shorter survival. Therefore, p53 mutation in the primary lesion is useful as an indicator of the biological behavior of recurrent hepatocellular carcinomas.
Collapse
Affiliation(s)
- I-Shyan Sheen
- Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan
| | | | | |
Collapse
|
|
24
|
Vauthey JN, Lauwers GY, Esnaola NF, Do KA, Belghiti J, Mirza N, Curley SA, Ellis LM, Regimbeau JM, Rashid A, Cleary KR, Nagorney DM. Simplified staging for hepatocellular carcinoma. J Clin Oncol 2002; 20:1527-36. [PMID: 11896101 DOI: 10.1200/jco.2002.20.6.1527] [Citation(s) in RCA: 363] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
PURPOSE The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. PATIENTS AND METHODS The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. RESULTS Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P =.6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P =.5). Independent predictors of death were major vascular invasion (P <.001), microvascular invasion (P =.001), severe fibrosis/cirrhosis of the host liver (P =.001), multiple tumors (P =.007), and tumor size greater than 5 cm (P =.01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P <.001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P =.3). CONCLUSION The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.
Collapse
Affiliation(s)
- Jean-Nicolas Vauthey
- International Cooperative Study Group on Hepatocellular Carcinoma, Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Shuto T, Hirohashi K, Kubo S, Tanaka H, Hamba H, Kubota D, Kinoshita H. Delayed hepatic resection for ruptured hepatocellular carcinoma. Surgery 1998. [PMID: 9663249 DOI: 10.1016/s0039-6060(98)70072-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although transcatheter arterial embolization is advocated as initial therapy for ruptured hepatocellular carcinoma (HCC), hepatic resection is necessary for cure. The effectiveness of delayed hepatic resection for ruptured HCC was determined. METHODS The records of 10 patients who underwent delayed hepatic resection for ruptured HCC were reviewed. RESULTS All patients were men, and the mean age was 63 years. For hemostasis, transcatheter arterial embolization was performed in three patients, whereas in the other patients bleeding stopped without special procedures. Mean interval from rupture to hepatic resection was 74 days. Liver function test results before hepatic resection were almost normal. Trisegmentectomy in one and bisegmentectomy in four patients were performed, whereas minor hepatic resection was performed for four extrahepatic HCCs. There were no operative or hospital deaths. Four patients had cirrhosis. The mean tumor diameter was 7.5 cm. Of seven patients with recurrence, two with dissemination had tumors that ruptured on the inferior aspect of the liver. The 1- and 3-year survival rates were 77% and 48%, respectively. CONCLUSIONS Because delayed hepatic resection for ruptured HCC was safe and compared similarly with that for other patients who underwent resection for HCC, it should be used. However, when HCC ruptures in an inferior location, recurrence of tumor as dissemination is likely.
Collapse
Affiliation(s)
- T Shuto
- Second Department of Surgery, Osaka City University Medical School, Japan
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Lo CM, Lai EC, Liu CL, Fan ST, Wong J. Laparoscopy and laparoscopic ultrasonography avoid exploratory laparotomy in patients with hepatocellular carcinoma. Ann Surg 1998; 227:527-32. [PMID: 9563541 PMCID: PMC1191308 DOI: 10.1097/00000658-199804000-00013] [Citation(s) in RCA: 104] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This prospective study evaluates the value of laparoscopy and laparoscopic ultrasonography (USG) in avoiding exploratory laparotomy in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA Laparotomy and intraoperative USG is the gold standard to determine the resectability of HCC. No palliation can be offered to patients found to have unresectable disease, and the surgical exploration causes morbidity. METHODS From June 1994 to June 1996, 110 of 370 patients (30%) with HCC were considered candidates for possible hepatic resection. Preoperative liver function was assessed using Child-Pugh grading and indocyanine green retention test. The extent of disease was evaluated with radiologic studies, including percutaneous USG, computerized tomography scan, and hepatic angiogram. Nineteen patients were excluded from the study because of previous upper abdominal surgery (n = 12), ruptured tumors (n = 4), refusal by patients (n = 2), and instrument failure (n = 1). Laparoscopy and laparoscopic USG was performed on 91 patients immediately before a planned laparotomy aiming at hepatic resection. Laparotomy was aborted when definite evidence of unresectable disease was found on laparoscopic examination. RESULTS The median time required for laparoscopy and laparoscopic USG was 30 minutes (range, 10 to 120 minutes). Fifteen patients had evidence of unresectable disease on laparoscopic examination. Among the remaining 76 patients who underwent laparotomy, 9 had exploration only and 67 underwent hepatic resection. Thus, exploratory laparotomy was avoided in 63% of patients with unresectable disease. The laparoscopic examination failed to confirm unresectable disease more often when the tumor was >10 cm in diameter. The procedure accurately assessed the adequacy of the liver remnant and the presence of intrahepatic metastases, but it was less sensitive in determining the presence of tumor thrombi in major vascular structures and the extent of invasion of adjacent organs. When unresectable disease was detected without the need for a laparotomy, the postoperative recovery was faster, and the nonoperative treatment for the tumor could be initiated earlier. CONCLUSIONS Laparoscopy with laparoscopic USG avoids unnecessary laparotomy in patients with HCC and should precede a planned laparotomy aiming at hepatic resection.
Collapse
Affiliation(s)
- C M Lo
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, China
| | | | | | | | | |
Collapse
|
|
27
|
Roseman BJ, Roh MS. Prognostic factors in surgical resection for hepatocellular carcinoma. Cancer Treat Res 1997; 90:331-45. [PMID: 9367091 DOI: 10.1007/978-1-4615-6165-1_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- B J Roseman
- M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | | |
Collapse
|
|
28
|
Tung WY, Chau GY, Loong CC, Wu JC, Tsay SH, King KL, Huang SM, Chiu JH, Wu CW, Lui WY. Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s). EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 1996; 22:516-20. [PMID: 8903496 DOI: 10.1016/s0748-7983(96)93056-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Primary hepatocellular carcinoma (HCC) extending to the adjacent organ(s) is sometimes encountered in patients with large, peripherally located tumours. Over a 4-year period, a total of 151 patients received curative resection of HCC at the Surgical Department of Veterans General Hospital-Taipei, Taiwan. Of these patients, 21 underwent hepatic resection combined with en-bloc resection of the adjacent organ(s) because tumour extension was found during operation. Subsequent histological examination of the resected specimens found evidence of HCC invasion into the resected adjacent organ(s) in only nine patients (group I), and the remaining 12 patients showed no evidence of extrahepatic HCC invasion (group II). Twenty-seven HCC patients with clinico-pathologically matched tumours but without extrahepatic extension were selected as controls (group III). One patient in group I died of hepatic failure after the operation. The morbidity rate was 48% in group I and group II patients, and 30% in group III patients. The difference was not statistically significant. On evaluating the clinico-pathological factors, including DNA ploidy status of the tumours, there were no significant differences between tumours with and without extrahepatic invasion. Patients with locally invasive HCC (group I) had disease-free and overall survival rates comparable with those of the patients without local tumour invasion (group II and III). We conclude that HCC with invasion to the adjacent organ(s) does not seem to be directly related to the 'aggressiveness' of the tumour, and extrahepatic infiltration of the tumour does not preclude a chance of cure. Our results underscore the need for en-bloc resection as treatment of choice for these patients.
Collapse
Affiliation(s)
- W Y Tung
- Department of Surgery, Veterans General Hospital-Taipei and School of Medicine, National Yang-Ming University, Taiwan, Republic of China
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Pichlmayr R, Weimann A, Oldhafer KJ, Schlitt HJ, Klempnauer J, Bornscheuer A, Chavan A, Schmoll E, Lang H, Tusch G. Role of liver transplantation in the treatment of unresectable liver cancer. World J Surg 1995; 19:807-13. [PMID: 8553670 DOI: 10.1007/bf00299775] [Citation(s) in RCA: 104] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Resection remains the treatment of choice in liver cancer. In order to avoid liver transplantation in conventionally unresectable tumors ex-situ ("bench" procedure), in-situ and ante-situm resection technique should be preferred whenever feasible. Despite the deficiency of donor organs, a single center experience with 198 patients reveals that liver transplantation continues its role as a therapeutic option for selected patients. At present "favorable" indications for transplantation are International Union against Cancer (UICC) - stage II hepatocellular carcinoma as well as the subtype fibrolamellar carcinoma, uncommon tumors such as epitheloid hemangioendothelioma, hepatoblastoma, and liver metastases from neuroendocrine tumors. Due to unsatisfying results, intrahepatic bile duct-, stage III and IV hepatocellular carcinoma, hemangiosarcoma, and liver metastases from nonendocrine primaries should be excluded from liver transplantation alone. For these advanced tumors, especially in cases of extrahepatic involvement, a combination of liver transplantation and multivisceral resection has been proven feasible. However, a significant improvement in patient survival may only be expected only by currently investigated multimodality treatment protocols which will require further randomized studies.
Collapse
Affiliation(s)
- R Pichlmayr
- Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|