Journal of Military Pharmaco-Medicine N0 1-2021 SURGICAL OUTCOME AFTER HEPATIC RESECTION FOR HEPATOCELLULAR CARCINOMA IN ELDERLY PATIENTS Le Thanh Son1, Ngo Viet Thi2 SUMMARY Objectives: To evaluate the surgical outcome and prognostic factors after hepatic resection using Takasaki method in elderly people Subjects and methods: Sixty patients over 60 years old underwent hepatectomy using Takasaki method at Binh Dan Hospital from January 2015 to January 2019 Results: Takasaki technique for liver resection was applied successfully in all patients Major hepatectomy (more than liver segments) was performed in 40% of cases The mean blood loss was 427.25 ± 158.4 mL The R0 margin after resection was obtained in 93.4% of cases with low major complications rate (liver failure: 1.7%, post-operative bile leak: 3.3%, ascites: 5%, abdominal infection: 5%, pneumonia: 3.3%, pleural effusion: 3.3%, wound infection: 1.7% The mean overall survival time was 24.4 ± 1.25 months, overall survival rate at 1, and years after hepatectomy were 88.3%, 66.1% and 50.9% respectively Recurrence rate at 1, and years were 18%, 52% and 60% respectively Conclusion: Hepatectomy using Takasaki method is an effective and safe procedure in elderly patients with hepatocellular carcinoma * Keywords: Takasaki technique; Hepatocellular carcinoma; Elderly patients; Anatomic hepatectomy INTRODUCTION Elderly people often have many chronic diseases with impaired organs function The number of ageing people in the world has increased rapidly in the last three decades It is estimated that by 2050 there will be around billion elderly persons [3] Vietnam is no exception The rate of Vietnamese elderly people rocketed recently with the rate of population ageing in 1989, 1999 and 2009 was 7.2%, 8.3% and 9.5% respectively [1, 2] Hepatocellular carcinoma (HCC) ranks fifth among the most prevalent cancers worldwide, and is the fourth most common cause of cancer-related death Therefore, it is a major global health problem Most cases of HCC are attributable to chronic liver disease resulting from chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection Most cases of HCC are estimated to occur in low resource or middle-resource countries, particularly in Eastern Asia and sub-Saharan Africa The disease incidence is lower in developed countries (Western countries or North America) This is a very common disease with poor outcome, especially in male patients Hospital 103, Vietnam Military Medical University Binh Dan Hospital, Ho Chi Minh City Corresponding author: Ngo Viet Thi (ngovietthi@yahoo.com) Date received: 20/11/2020 Date accepted: 22/01/2021 142 Journal of Military Pharmaco-Medicine N0 1-2021 Recently, hepatic resection procedures were performed based on knowledge of modern surgical anatomy of the liver and the surgeon can plan to resect the liver segments precisely At present, hepatectomy is a standard treatment of HCC especially hepatectomy using Takasaki method Although several studies have reported on clinical outcomes of hepatic resection of HCC in elderly patients, feasibility of Methods * Treatment procedure: Pre-operation assessment: Patients’ clinical characteristics were noted (medical history and treatment, chronic conditions, serum AFP, viral hepatitis markers, liver functions, diagnosed platelet by counts imaging HCC was studies with computerized tomography (CT) and/or the operation, peri-operative risks and the magnetic resonance imaging (MRI) and long-term outcomes remain controversial liver biopsy if needed based on AASLD Moreover, suitable criteria for the selection guidelines The patients were classified of hepatectomy procedures in elderly by AJCC classification and liver resection patients have still been under investigation was indicated based on APASL guidelines since HCC being-diagnosed in advanced stage in this specific group Therefore, in this study, we aimed to evaluate the efficacy of hepatectomy for elderly HCC patients using Takasaki method based on: - Survival outcome and recurrence rate after hepatectomy using Takasaki method in elderly HCC patients - The complications rate after hepatectomy using Takasaki method in elderly HCC * Surgical treatment: Liver resection using Takasaki method * Surgical outcome: Intra and postoperative, long-term outcome * Data analysis: Using SPSS 16.0 This study was conducted in accordance with the declaration of Helsinki and the guidelines of the Ethics Committee of Vietnam Military Medical University patients SUBJECTS AND METHODS Subjects The study included 60 patients older than 60 years who underwent initial hepatic resection using Takasaki method for HCC at Binh Dan Hospital from January 2015 to January 2019 RESULTS General characteristics Patients’ median age was 65.8 ± 4.7 years old More than 75% of patients were under 70 years old Male/female ratio was 7/3 with the majority of the patients being males (70%) 143 Journal of Military Pharmaco-Medicine N0 1-2021 * Concomitant disease: Table 1: Concomitant disease Concomitant disease Cardiovascular Respiratory Metabolism n % Hypertension 32 52.4 Myocardial infarction/angina 13.1 Heart failure 5.0 Asthma 5.0 Chronic obstruction pulmonary disease 14.7 Diabetes mellitus 13.1 Osteoporosis 10 16.3 Overall, pre-operative liver function was compensated with Child-Pugh class A (95%), class B (5%) and no patients with Child-Pugh class C were found Mean serum bilirubin was 16.5 µmol/L (maximum 41.1 µmol/L, minimum 5.1 µmol/L) Etiological factors for HCC in our group were: HBV (58.6%), HCV (26.7%), alcohol (7.8%), other factors (6.9%) All platelet count was over 100.000/mm3 Mean serum AFP pre-operation was 237.5 ng/mL (maximum 2000 ng/mL, minimum 1.83 ng/mL) 81.7% of patients had AFP < 200 ng/mL, 18.3% of patients had AFP > 200 ng/mL According to ASA classification, ASA II accounted for 70%, ASA I was present in 30% Table 2: Tumor location Tumor location Number of tumors Percentage (%) Segment I 1.6 Segment II 3.2 Segment IV 11.1 Segment V 7.9 Segment VI 7.9 Segment VII 9.5 Segment VIII 12.7 Left lateral segment (II - III) 12 19.0 Posterior segment 6.4 Right lobe 4.8 Left lobe 10 15.9 Regarding tumor size, tumor less than cm was found in 58.3%, > cm in 41.7% Tumors differentiation were graded as well, moderate and poor with corresponding rate of 43.4%, 41.7% and 15% 144 Journal of Military Pharmaco-Medicine N0 1-2021 Table 3: Tumor staging by AJCC AJCC Stage Number of patients Percentage (%) Stage I 46 76.7 Stage II 5.0 Stage III 11 18.3 Table 4: Intra-operative factors Level of hepatectomy Minor hepatectomy Type of hepatectomy n % Anterior sectionectomy 17 28.3 Posterior sectionectomy 8.3 Left lateral sectionectomy 14 23.3 Segments Right hepatectomy 16 26.7 Segments Left hepatectomy 13.3 Segments Major hepatectomy Mean operative time was 128.6 minutes (range: 60 - 300 minutes, SD: 47.3 minutes) Mean blood loss: 427.25 ± 158.4 mL (minimum 100 mL, maximum 1,500 mL) Blood transfusion: cases (11.7%) Resection margin: R0 was obtained in 93.4% of cases 6.6% of the cases had positive margin Table 5: Post-operative complications Complications Related to surgery Related to concomitant disease Number of patients Percentage (%) Liver failure 1.7 Bile leakage 3.3 Ascites 5.0 Abdominal infection 5.0 Pleural effusion 3.3 Wound infection 1.7 Nosocomial pneumonia 3.3 * Survival outcome: The mean observation time was 22.3 ± 8.4 months, maximum 36 months Overall survival time estimated by Kaplan-Meier was 24.4 ± 1.25 months (95%CI: 21.9 to 26.9 months) The overall survival rates at 1, and years were 88.3%, 66.1% and 50.9% respectively 145 Journal of Military Pharmaco-Medicine N0 1-2021 * Recurrence rate after hepatectomy: Recurrence rate at 1, and years were 18%, 52% and 60% respectively; mean recurrence time was 22.1 months (range: - 36 months) DICUSSION General characteristics The mean age of our study group was 65.8 years Many researches show that HCC is generally diagnosed in middleaged and elderly population with the peak age of from 50 to 60 years old in many Western and Asia nations [8] The chronological age of 60 is currently accepted as a threshold to define an “elderly” person socially according to definition of WHO Most studies showed that HCC is diagnosed more commonly in men than in women The male/female ratio in our study was 7/3 Study by RT Poon had the same results with 78% of male patients, equivalent to Anne Adert’s finding (63.6% male vs 36.4% female) [8] However, in comparison to younger patients, older population with HCC is characterized by a higher prevalence of females The reasons for the higher proportion of females in elderly HCC patients are that the average life expectancy at birth for females is longer than that of males, and thus the proportion of females is higher than that of males in the elderly population [9] The concomitant diseases (pulmonary, cardiovascular, musculoskeletal disorders…) are the crucial comorbidities in elderly, especially in post-operative period In our 146 study, the prevalence of cardiovascular diseases, COPD and diabetes mellitus were 70.5%, 14.7% and 13.1% respectively in which more than half of the patients suffered from hypertension Our result is similar to A Andert’s findings where the prevalence of coronary heart disease, COPD and diabetes mellitus were 75%, 15% and 21% respectively Type of hepatectomy In this study, we performed major hepatectomy for 24 in a total of 60 cases (40%) Regarding major hepatectomy, it seems that the degree of liver regeneration at one month after hepatectomy in elderly patients is not significantly different from that in younger patients [10] Operative time The mean operative time in our study was 128.6 ± 47.3 minutes In one study to compare outcome of hepatectomy in super-elderly patients (older than 80 years old) with younger patients, the result showed no difference in operating time between the two groups Other researches gave the same conclusion, even in term of major hepatectomy [11, 12] Intra-operative blood loss and blood transfusion Many studies showed that intraoperative blood loss and blood transfusion also impacted strongly treatment outcome following liver resection However, the intra-operative blood loss due to hepatectomy of HCC elderly patients is similar to that of younger ones [9] Journal of Military Pharmaco-Medicine N0 1-2021 Mean intraoperative blood loss in our study was 427.25 ± 158.4 mL which is similar to the study by Yoon (2017), Polignano (2008), but less than in study by Nishikawa (2013), Figueras (2003) and Kaibori (2009) [9] The difference in intraoperative blood loss can be explained by the imperfect technique of liver resection (the Takasaki method was published in 2007) and many researchers believe that it will be standardized through time when the surgeon is more experienced Complications and mortality The complications rate in our study was 16.7%, mostly minor complication (1 case with transient post-operative hepatic failure, case of bile leak, cases of nosocomial pneumonia, cases of ascites with small pleural effusion) and all were treated conservatively We had cases of abdominal infection requiring aspiration via ultrasound, one of which had bile leakage after hepatectomy There were no deaths related to treatment or major complications which need to be re-operated during follow-ups Other studies had the same results with overall complication rates being approximately 24% Common complications are mostly wound infection and respiratory failure/ post-operative pneumonia [7] Survival outcome Mean observation time was 19.2 months in 60 cases of our study The overall survival time was 43.5 ± 2.27 months Overall survival rate at 1, and years were 85.1%, 71% and 64.9%, respectively Other studies also conclude that the long-term outcome, especially in survival time, after hepatectomy for HCC is almost the same as those of younger patients [9] Figure 1: The survival rate 147 Journal of Military Pharmaco-Medicine N0 1-2021 Recurrence outcome Recurrence rate at 1, and years after liver resection in our group were 18%, 52% and 60% respectively Mean recurrence time estimated by Kaplan-Meier was 22.1 months (6 - 36 months) Other studies showed that the recurrence rate at 1, and years after hepatectomy for HCC in elderly people vary from 21.9 - 30%, 30 - 50% and 60 - 73.7%, which is similar to our result Figure 2: Recurrent time CONCLUSION Hepatectomy using Takasaki method to treat HCC elderly patients is a feasible, safe and effective procedure with good outcome and low levels of mortality and morbidity REFERENCES Bộ Kế Hoạch Đầu tư - Tổng cục thống kê Tổng điều tra dân số nhà Việt Nam năm 2009: Cấu trúc tuổi - giới tính tình trạng nhân dân số Việt Nam Bộ Kế Hoạch Đầu tư - Tổng cục thống kê 2011 148 Trần Văn Long Tình hình sức khỏe người cao tuổi thử nghiệm can thiệp nâng cao kiến thức - thực hành phòng chống bệnh tăng huyết áp xã huyện Vụ Bản, tỉnh Nam Định giai đoạn 2011 - 2012 Luận án Tiến sĩ Y tế Công cộng 2015:78-95 United Nations - Department of Economic and Social Affairs Office of the High Commissioner for Human rights Current status of the social situation, well-being, participation in development and rights of older persons worldwide 2010 T Akinyemiju, S Abera, M Ahmed, N Alam, MA Alemayohu, et al The burden of primary liver cancer and underlying etiologies Journal of Military Pharmaco-Medicine N0 1-2021 from 1990 to 2015 at the global, regional, and national level: Results from the global burden of disease study JAMA Oncol 2015; 3(12):1683-1691 Bosch X Muñoz N Epidemiology of hepatocellular carcinoma in: Okuda K, Ishak KG (eds) neoplasms of the liver, Springer 1987 A Jemal, F Bray, MM Center, J Ferlay, E Ward, D Forman Global cancer statistics CA Cancer J Clin 2011; 61(2):69-90 RT Poon, ST Fan, CM Lo, CL Liu, H Ngan, IO Ng, J Wong Hepatocellular carcinoma in the elderly: Results of surgical and nonsurgical management Am J Gastroenterol 1999; 94(9):2460-2466 A Andert, T Lodewick, TF Ulmer, M Schmeding, W Schoning, U Neumann, K Dejong, C Heidenhain Liver resection in the elderly: A retrospective cohort study of 460 patients - 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