A total of 137 patients was included in the study. Among them, 14 patients (10.22%) were underweight, 65 patients (47.45%) were normal weight and 58 patients (42.34%) were overweight. The basic demographics and tumor characteristics between three groups are summarized in Table 1. The mean body mass index of patients in Group 1, Group 2, and Group 3 were 17.43±1.08, 21.29±1.22, and 25.38±2.68, respectively. Other variables, including age, gender, Child-Pugh score, ASA score, liver cirrhosis, tumor size, tumor number, and the tumor stage have no significant difference between the three groups.
Short-term Outcomes and Complications
Table 2 displays the perioperative and postoperative outcomes of the three groups. The conversion rate in the three groups were 16.67%, 27.45%, and 26.09% (P = 0.8284), respectively. The mean postoperative hospital length of stay for the three groups was 10.85±4.04 days, 11.57±5.56 days, and 10.88±5.7 days (P = 0.7615), respectively. Notably, the overall complication rate in the underweight group was much higher than that in the normal weight and overweight groups (42.85% vs 23.08% vs 17.2%, P = 0.048, respectively). And for the postoperative complications, underweight patients developed grade III or higher of the Clavien-Dindo classification more easily than the other two groups (P = 0.042). In cohort group, bile leak was the most frequent postoperative complication, followed by intraabdominal sepsis, ascites, as well as pneumonia.
Long-term Outcomes
The median follow-up durations in the three groups were 26 months, 30 months and 28 months, respectively. The DFS and OS of the cohort are shown in Table 3. The overall 90-day mortality was 1.46%, and there was no difference between the three groups. The median disease free survival duration of Group 1, 2, and 3 were 28.71 months, 28.08 months, and 33.83 months, respectively. There was no significant difference of 1-year DFS between the three groups (p = 0.24). But as for the 3- and 5- year DFS, overweight patients had a longer 3- and 5-years DFS (41.4%, 36.2%) than underweight (21.4%, 14.3%) and normal weight (28.1%, 21.9%) patients (P<0.05). Likewise, the median OS of the three groups were 32.14, 32.43, and 37.09, respectively. And there was no significant difference of 1-, 3-, and 5-year OS between the three groups. As to the 5- year OS, overweight patients had a trended of longer 5-year OS (40.8%) than underweight (28.6%) and normal weight (28.1%) patients, but it did not reach statistics significance (P>0.05).
Discussion
Laparoscopic hepatectomy has become a feasible option for patients with liver malignancy. As a new technique, researchers have given more attention to short-term and long-term outcomes. Although being overweight and obese does not preclude one to laparoscopy (16), still little is known about the influence of recipient BMI on the long-term outcomes especially the recurrence rate and the overall survival rate after LH for HCC. In the present study, we observed the patients with elevated BMI accounted for 42.33%. General surgeon will encounter more and more overweight and obese patients with liver cancer in the future. Therefore, it is important to fully understand the effect of elevated BMI on these patients. We carried out this retrospective analysis using our institutional database and we have shown that: (i) being overweight did not increase the conversion rate; (ii) being underweight is associated with an increased number and more severe complications; (iii) being overweight is associated with lower 3- and 5-years tumor recurrence, and being underweight is associated with higher 3- and 5-years tumor recurrence. (iv) being either underweight, normal weight, or overweight had a comparable 1-year and 3-year overall survival rate. But as to 5-years OS, being overweight had a higher chance of survival. It was interesting to detect that being overweight did not have any negative impact on prognosis after LH for liver carcinoma. Actually, a significant protective effect of overweight was observed for perioperative complications and tumor recurrence. Meanwhile, being underweight increased risk of perioperative complications and tumor recurrence.
Many studies have demonstrated that the increased BMI would increase the risk of laparoscopic conversion rate and prolong operative time (18,19) and thus the surgeons tended to be reluctant to perform laparoscopic surgery for overweight patients. However, there were no difference of conversion rate and operative time across the three groups in our study, which was consistent with Troisi et al. analysis (20). This may be because that all laparoscopic procedures were performed by same experienced surgeon team who have finished the learned curve and were capable enough to perform liver tumor using laparoscopic skill, and also there were no patients’ BMI more than 40. Meanwhile, not in line with previous studies, which found that overweight patients had a worse outcome than their leaner counterparts (21), our results showed that overweight patients had a lower complication rate (17.2 %) compared to the underweight (42.85%) and normal weight patients (23.08%), the decreased BMI values was a risk factor for higher incidence of postoperative complications. We also found severe complications for grade III to IV according to the Clavien classification were much higher in underweight group than that in normal weight and overweight group. One cause may be overweight patients are protected by adequate fat storage, better nutrition, and systemic insulin resistance that underweight people do not have (22), Meanwhile the patients with a preoperative lower BMI is more likely to indicate the excessive nutritional consumption and malnutrition resulting from more aggressive tumor (23).
To our knowledge, little research has investigated the association between BMI and prognosis in patients undergoing LH with liver cancer. Yeuh-Shih Chang al reported overweight status had better oncologic outcomes following hepatectomy in HCC patients (24), but the end point of Chang’s study was 6-month of survival. The follow-up duration was relatively short, and more data were needed on the overall survival rate as an important therapeutic measure of liver cancer if treatment intensity and life expectancy were judged (25). Our study aimed to verify long-term outcome of liver carcinoma patients who underwent LH, and our data revealed underweight patients had much higher 3- and 5- years cumulative tumor recurrence rate than that in the other two groups. As we know that liver tumors are a consumptive disease, a higher proportion of later stage (stage III) in underweight group in our study was the main cause of a worse outcome. Underweight patients may be malnutrition, possible immune deficiency and then cannot withstand the hepatic resection coupled with other therapies. Also, weight loss or low serum albumin levels of liver disease would be contributed to the high postoperative complications and high 3-and 5-years DFS. Our result showed overweight had a better 3- and 5-years DFS and had a tendency of longer 5-years overall survival rate. BMI ≥ 23kg/m2 is a direct indicator for Asian patients with liver cancer who may benefit from more aggressive anticancer treatment to reduce the tumor recurrence. But as to the overall survival rate, it was comparable between the three groups. Chronic disorders such as cardiovascular disease, hypertension and diabetes, which are closely related to obesity will increase the risk of physical disability and mortality rates in the long run (26). It is reported that nearly 70% of deaths related to high BMI are due to cardiovascular disease and over 60% of those deaths occurs among the obese patients (27). In our study, the high BMI related morality also increased the OS, thus lose the advantage of low tumor recurrence of the overweight group.
Even more, it has been previously reported that postoperative complications had a negative impact on the tumor recurrence and long-term survival rate, especially for severe postoperative complications (28). In our study, we again verified that postoperative complication may have an effect on the prognosis of liver cancer patients. We found underweight patients suffered more complications and had a worse DFS. One reason is that the surgical trauma and tissue damage of the complications could result in the immune suppression, and in turn increase the possibility of immune escape and tumor progression (29, 30). Secondly, large number of cytotoxic mediators from inflammatory response caused by the infected complications could provide a microenvironment for the growth and invasion of tumor cells, and further promote the development of tumor recurrence (31). At the same time, minimally invasive laparoscopic surgery could avoid the complications such as poor wound healing and pulmonary infection caused by long incision, which brought more advantages for overweight patients.
This study has some limitations. First, this was a retrospective, non-randomized survey that may have suffered from selection bias. Second, this was a single-center study and there is still no standard treatment for liver cancer. Our results might have been influenced by our surgical strategy. Thirdly, we only used BMI to estimate obesity, which was not enough to assess the abdominal adiposity of Asian people.
Despite these limitations, our study helps to clarify that LH for treatment of overweight patients with hepatocellular carcinoma is feasible and safe and has a proactive effect for perioperative complications and tumor occurrence. These results need to be validated by larger randomized and prospective studies.