The Impact of Liver Resection Volume on Pancreatic Function: Novel Insights into Acute Liver-Pancreas Crosstalk After Hepatectomy

doi:10.21203/rs.3.rs-3612408/v1

Download PDF

Article

The Impact of Liver Resection Volume on Pancreatic Function: Novel Insights into Acute Liver-Pancreas Crosstalk After Hepatectomy

https://doi.org/10.21203/rs.3.rs-3612408/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 21 Mar, 2024

Read the published version in Scientific Reports →

You are reading this latest preprint version

The liver and pancreas work together to recover homeostasis after hepatectomy. This study aimed to investigate the effect of liver resection volume on the pancreas. We collected clinical data from 338 living liver donors. They were categorized into left lateral sectionectomy (LLS), left lobectomy, and right lobectomy (RL) groups. Serum pancreatic enzymes were compared among the groups. Serum amylase values peaked on postoperative day (POD) 1. Though they quickly returned to preoperative levels on POD 3, 45% of cases showed abnormal values on POD 7 in the RL group. Serum lipase levels were highest at POD 7. Lipase values increased 4.2-fold on POD 7 in the RL group and 80% of cases showed abnormal values. The RL group’s lipase was twice that of the LLS group. A negative correlation existed between the remnant liver volume and amylase (r = -0.291)/lipase (r = -0.380) on POD 7. Furthermore, a significant correlation was observed between POD 7 serum bilirubin and amylase (r = 0.245)/lipase (r = 0.330) levels, indicating cooccurrence with liver and pancreatic dysfunction. Pancreatic dysfunction due to hepatectomy occurs in a resection/remnant liver volume-dependent manner. It would be beneficial to closely monitor pancreatic function in patients undergoing a major hepatectomy.

Health sciences/Gastroenterology/Gastrointestinal system

Health sciences/Gastroenterology/Hepatology

Health sciences/Risk factors

Maintenance of systemic homeostasis requires the coordination of multiple organs and tissues. To respond to multiple stress, higher organisms have developed a system of inter-organ communication, called inter-organ crosstalk^1–3. Although the benefits outweigh the risks, surgery does put a strain on the body. The organs must work together to overcome the stress caused by surgery. Dysregulation of inter-organ coordination leads to new problems after surgery. In short, elucidation of inter-organ crosstalk is essential for comprehending the effects of surgery. However, these mechanisms are not fully understood.

The liver and pancreas are digestive organs that work cooperatively to maintain proper metabolic status. Thus, the dysfunction of one organ can affect the function of the other. Furthermore, they are anatomically connected by the portal system. Therefore, an organic change from surgery on one organ can have unfavorable effects on the other organ. For example, it has long been known that insulin hypersecretion from pancreatic islets occurs after a partial hepatectomy^4,5. Furthermore, previous studies have shown hyperamylasaemia and pancreatitis after hepatectomy and liver transplantation (LT)^6–9. Although most often hyperamylasaemia and pancreatitis can be subclinical, it can manifest as severe pancreatitis resulting in multiple organ failure, increasing morbidity and mortality following liver surgery^10,11. Several lines of evidence from clinical studies have demonstrated that portal vein pressure increased after major hepatectomy in patients without cirrhosis^12–14. Portal congestion following hepatectomy has been proposed as one of the pathophysiologic mechanisms responsible for pancreatic impairments^15,16. However, the detailed mechanism of liver-pancreas crosstalk and associated risk factors remains unclear.

Given the potential role of portal congestion in pancreatic stress, it is imperative to understand how the resection volume of liver impacts on pancreas. Despite its importance, no analysis has been conducted on human populations. This represents a significant gap in our understanding and underscores the urgent need for further investigation. Therefore, this study aimed to investigate the effect of liver resection volume on the pancreas. Here, by analyzing living liver donors, a cohort with relatively uniform liver and pancreatic function, we have demonstrated a significant relationship between liver resected volume and pancreatic burden.

Comparison of the clinical characteristics and operation-related factors across the groups

First, we investigated the clinical characteristics and operative outcomes according to each of the procedures. Of the 338 donors, 208 (61.5%) were included in the LLS group, 89 (26.3%) in the LL group, and 41 (12.1%) in the RL group. A comparison of the clinical characteristics and operation-related factors between groups is shown in Table 1. There were significant differences in age and body mass index between groups. There were no significant differences in body surface area and calculated standard liver volume across the groups.

Table 1

Comparison of the clinical characteristics and operation-related factors in the entire cohort.
	All (n = 338)	RL (n = 41)	LL (n = 89)	LLS (n = 208)	P value	RL vs. LL P value	RL vs. LLS P value	LL vs. LLS P value
Gender, male, n	166 (49.1)	17 (41.5)	46 (51.7)	103 (49.5)	0.552
Age, year	35 (20–67)	44 (24–63)	42 (20–56)	33 (23–67)	< 0.001	0.205	< 0.001	< 0.001
Body height, m	1.65 (1.46–1.93)	1.62 (1.52–1.86)	1.66 (1.48–1.93)	1.65 (1.46–1.84)	0.257
Body weight, kg	60.0 (39.0-94.7)	60.4 (46.9–82.0)	62.6 (43.0-90.6)	58.8 (39.0-94.7)	0.086
Body mass index, kg/m²	21.9 (17.3–31.4)	22.5 (18.5–28.3)	22.3 (17.3–30.8)	21.5 (17.5–31.4)	0.016	> 0.999	0.161	0.035
Body surface area, m²	1.65 (1.28–2.15)	1.63 (1.40–2.06)	1.69 (1.38–2.12)	1.64 (1.28–2.15)	0.153
Standard liver volume, mL	1169 (908–1520)	1151 (994–1459)	1198 (980–1502)	1157 (908–1520)	0.154
Preoperative AST, U/L	16 (10–51)	16 (12–33)	16 (11–51)	16 (10–46)	0.649
Preoperative ALT, U/L	15 (5–65)	15 (8–41)	15 (5–65)	16 (6–62)	0.678
Preoperative amylase, U/L	84 (22–300)	70 (43–169)	88 (43–239)	87 (22–300)	0.026	0.109	0.021	> 0.999
Preoperative lipase, U/L	31 (12–64)	30 (18–61)	33 (19–64)	31 (12–62)	0.918
Operative outcomes
Operation time, min	327 (167–728)	398 (253–690)	367 (214–641)	293 (167–728)	< 0.001	0.027	< 0.001	< 0.001
Intraoperative blood loss, mL	530 (0-3050)	410 (70-1940)	800 (122–3050)	510 (0-2720)	< 0.001	< 0.001	0.413	< 0.001
Graft volume, g	260 (93–872)	625 (390–872)	363 (212–686)	224 (93–382)	< 0.001	< 0.001	< 0.001	< 0.001
Postoperative outcomes
POD1 AST, U/L	341 (89-2010)	384 (146–1248)	361 (147–1397)	309 (89-2010)	0.233
POD1 ALT, U/L	404 (82-1864)	399 (227–1238)	415 (189–1277)	385 (82-1864)	0.644
POD1 total bilirubin, mg/dL	1.52 (0.58–7.07)	2.58 (1.17–5.33)	1.58 (0.58–7.07)	1.42 (0.59–6.13)	< 0.001	< 0.001	< 0.001	0.605
Postoperative hospital stay, day	10 (7–57)	11 (8–52)	10 (7–57)	10 (7–44)	0.099
AST, aspartate transaminase; ALT, alanine transaminase; LL, left lobectomy group; LLS, left lateral sectionectomy group; POD, postoperative day; RL, right lobectomy group.

In the RL group, operation time was significantly longer compared to other groups. The LL group was significantly associated with a greater amount of intraoperative blood loss. Conversely, there were no significant differences in intraoperative bleeding between the RL group and the LLS group (P = 0.413). Consistently, actual graft volumes were significantly different between the groups (P < 0.001).

Assessment of preoperative serum amylase and lipase values

A comparison of the preoperative serum amylase and lipase during the perioperative period across the groups is shown in Fig. 1. There was a significant difference in the preoperative serum amylase levels between the LLS group and the RL group (Fig. 1a). There were no significant differences in comparisons among the other groups. Because the LLS group was significantly younger than the RL group (Table 1), we analyzed the correlation between age and preoperative amylase levels. We found a slight negative correlation there (r = -0.097, P = 0.074) (Fig. 1b). In contrast, there were no significant differences in the preoperative serum lipase levels across the groups (Fig. 1c). Moreover, there was no correlation between age and preoperative lipase levels (Fig. 1d).

The RL group shows a more significant increase in amylase and lipase after surgery

Next, we clarified the chronological changes in amylase and lipase after hepatectomy (Fig. 2) and compared them across the groups (Supplemental Fig. 1). The amylase values peaked on the day after surgery. They quickly returned to preoperative levels on POD 3 (Fig. 2a). Postoperative amylase levels in the RL group were higher than those in other groups. The pattern of chronological change was similar for all three groups (Fig. 2b).

In contrast, the lipase increase on the day after hepatectomy was mild. Notably, the highest postoperative lipase levels were often found at POD 7. In the RL group, especially, there was an initial small increase, a decrease, and then a significant increase again (Fig. 2c). These results indicated the presence of a bimodal peak in the postoperative lipase dynamics of the RL group (Fig. 2d).

Based on the differences in the preoperative amylase values, we further examined the relative values to the preoperative values. In the RL group, the amylase value increased 1.5-fold on POD 1 compared to those of before surgery (Supplemental Fig. 1). On POD 1, there was a significant difference between the RL group and the LLS group (P = 0.024). In the comparison of relative values, the higher values in the RL group were more remarkable than in the other groups. Likewise, in comparing relative values of lipase, the higher values in the RL group were more noticeable than in the other groups. Surprisingly, the lipase values increased 4.2-fold on POD 7 in the RL group. The RL groups showed a significant 2-fold increase compared to the LLS group (P < 0.001) (Supplemental Fig. 1).

Effect of liver resection on postoperative lipase homeostasis may persist for several weeks

Next, we assessed the clinical significance of amylase and lipase values on POD 7. Figure 3 shows the percentage of cases with abnormal values in the measurements on POD 7. In the measurement of amylase, abnormal values are found in approximately 25% of the cases (34/134). In the RL group, 45% of cases showed abnormal values. Regarding lipase, approximately 75% of the cases (80/106) exhibited abnormal values on POD 7. Abnormal values were observed in more than 80% of cases after right or left lobectomy. These observations suggested that the effect of liver resection on postoperative lipase homeostasis may persist for several weeks. Therefore, although we were not able to evaluate all the cases, we assessed lipase levels at approximately four weeks after surgery. Consequently, many of the cases showed a trend toward improvement at one month after surgery (Fig. 3c).

Negative correlation between the remnant liver volume and pancreatic impairment

The above data suggest a greater effect on pancreatic homeostasis in the RL group with larger resected liver volume. To clarify the relationship between the remnant liver volume and pancreatic impairment, we performed a correlation test. The ratio of remnant to total liver volume was calculated using the following formula: (standard liver volume - resected volume) /standard liver volume. As a result, we found a significant moderate negative correlation among them (Fig. 4).

Risk factor for abnormal amylase and lipase values on POD 7

To seek the risk factor for the abnormal values on POD 7, we performed a binary logistic regression analysis. Significant variables linked with the abnormal lipase levels, which were found through a univariate analysis (P < 0.05), as listed in Supplemental Table 1, were entered into a binary regression analysis. Binary logistic regression indicated that the preoperative lipase value was a significant predictor of the abnormal lipase value on POD 7 (Wald = 8.610, P = 0.003). The odds ratio (OR) was 1.128 (95% confidence interval [CI]: 1.041–1.223). Regarding the abnormal amylase values on POD 7, the graft volume was significant at the 5% level (Wald = 9.306, P = 0.002). The OR was 1.006 (95% CI: 1.002–1.009) (Supplemental Table 2). Collectively, these results suggest that the greater the amount of liver resected, the greater the impact on the pancreas.

No synergistic effect of aging on the amylase and lipase values on POD 7

We examined whether the effect of resection volume on pancreatic enzyme levels varied with age. A bubble plot consisting of remnant liver volume, age, pancreatic enzyme levels on POD 7, and graft type is shown in Fig. 5. In addition, we analyzed the correlation between age and pancreatic function tests on POD 7 in the RL group (Supplemental Fig. 2). In the present cohort, the synergistic effect of aging was not obvious.

Implications from the correlation between postoperative liver and pancreatic dysfunction

To draw a definitive conclusion, direct evidence of the relationship between pancreatic impairment and portal vein pressure after hepatectomy would be ideal. However, continuous measurement of portal vein pressure during the perioperative period was not ethically feasible in living donors. Portal venous pressure increase after hepatectomy has recently been documented to correlate with liver dysfunction.¹³ Thus, we assessed the association between liver and pancreas dysfunction following hepatectomy. We examined the correlation between serum bilirubin levels, a representative marker of postoperative liver dysfunction, on POD 7 and amylase levels on POD 7. A significant positive correlation was observed (r = 0.245, P = 0.005) (Fig. 6a). Similarly, there was a significant positive correlation between serum bilirubin levels on POD 7 and lipase levels on POD 7 (r = 0.330, P < 0.001) (Fig. 6b). In summary, our findings underscore the link between postoperative liver and pancreatic dysfunction. These results indicate that clinicians need to be aware of the potential for pancreatic dysfunction in patients showing signs of postoperative liver dysfunction.

We have investigated liver-pancreas crosstalk after hepatectomy. Our study demonstrated that the impact on the pancreas was resection/remnant liver volume-dependent. Interestingly, we also found different kinetics in serum amylase and lipase after living donor hepatectomy.

Previous studies have shown various pancreatic reactions associated with liver surgery. ^4–11 Most of the studies reported subclinical hyperamylasaemia, but there were some reports of clinically relevant pancreatitis. The detailed mechanism still remains unclear. One possible explanation for these reactions could be an ischemic reperfusion injury (IRI). In general, IRI occurs in LT or hepatectomy under a temporary vascular clamp for hemorrhage control. The spillage of cytokines and reactive oxygen species from the liver has been implicated in the pathogenesis of pancreatic injury.^17–20 Another possible explanation could be portal congestion.^15,16 Theoretically, portal vein congestion related to liver surgery is divided into two types: intraoperative congestion, associated with surgical manipulation such as a vascular clamp, and postoperative transitional congestion. Miyagawa et al. reported that the use of the Pringle maneuver increased the incidence of postoperative hyperamylasemia. They also found that the degree of hyperamylasemia was increased by portal congestion with prolonged vascular occlusion time.¹⁵ Following hepatectomy, diverting the whole portal flow to the remnant liver causes an increase in portal venous pressure.^21,22 This transitional portal venous overpressure can lead to postoperative liver failure as well as pancreatic vein congestion. Moreover, pancreatic congestion can be linked to impaired pancreatic function.^23,24 In the present study, as institutional policy, we routinely performed hepatectomy without a vascular clamp. Therefore, it is unlikely that IRI and intraoperative portal vein congestion were the direct main cause of stress to the pancreas in this cohort. Taken together, these data suggest that the impact of transitional portal venous overpressure was significant. The key result of our study, in which pancreatic enzymes became elevated in a resection/remnant liver volume-dependent manner, supports this interpretation.

How does pancreatic damage due to hepatectomy affect the remnant liver? Several in vitro and in vivo studies demonstrated insulin hypersecretion after hepatectomy.^4,5 The liver plays a central role in the control of glucose homeostasis collaborating with insulin and other hormones.^25–27 Thus, insulin hypersecretion after hepatectomy is thought to be a reasonable adaptation physiologically. Paradoxically, pancreatic impairment interferes with insulin hypersecretion leading to disruption of blood glucose homeostasis, resulting in unfavorable postoperative outcomes including liver dysfunction.^28–30 More importantly, insulin, a representative anabolic hormone, is essential for liver regeneration.^31–33 Collectively, we need to recognize that serious damage to the pancreas may have a negative impact on liver regeneration after hepatectomy.

We explored a correlation between postoperative liver and pancreatic dysfunction. Severe liver dysfunction after hepatectomy is recognized as posthepatectomy liver failure (PHLF). The incidence of PHLF fluctuates based on the diagnostic criteria employed and is presently estimated to be 3–28%.^34–37 PHLF continues to be the leading cause of postoperative mortality and poses a substantial clinical challenge for the hepatobiliary surgeon. Once PHLF develops, options are often limited to best supportive care. Needless to say, the optimal strategy is to reduce the risk of PHLF occurrence. Our findings emphasize the necessity of recognizing the potential for concomitant pancreatic dysfunction in patients with PHLF. Additionally, they indicate the importance of offering optimal supportive care not only for the liver but also for the pancreas in patients with PHLF. Determining effective pancreatic intervention for PHLF is a topic that warrants further exploration.

Our study demonstrated novel insight into the underlying relationship between a resection/remnant liver volume and postoperative amylase/lipase dynamics; however, there are several limitations. First, this is a retrospective single-institution cohort study. Additionally, though we found hyperamylasemia and hyperlipasemia after hepatectomy for living liver donors, we have not yet clarified the involvement of pancreatic hormones such as glucagon and insulin. Needless to say, pancreatic hormones and cytokines need to be evaluated to elucidate liver-pancreas crosstalk following hepatectomy. Finally, we evaluated the total amylase activity, including salivary and pancreatic amylases. Any type of surgery under general anesthesia often increase salivary amylase, which is probably caused by tracheal intubation. Ideally, we should have measured pancreatic amylase, but it was not feasible. Thus, serum lipase was measured for a more pancreas-specific evaluation. Interestingly, our results demonstrated different kinetics in serum amylase and lipase after living donor hepatectomy. The different course, which is difficult to explain by differences in half-life alone,³⁸ may indicate different adaptations to glucose and lipid metabolism after hepatectomy. This result evokes the notion of a heterogeneity of stress and its adaptation in different pancreatic cells and tissues. Until this point is clarified, extensive postoperative evaluation, including monitoring various pancreatic functions, would be better, at least in high-risk cases.

In conclusion, we specifically examined the association between liver resection volume and pancreatic function. Our study indicated pancreatic impairment due to hepatectomy occurs in a resection/remnant liver volume-dependent manner. Our findings emphasize the need to recognize the potential for concomitant pancreatic dysfunction in patients with PHLF. It would be advisable to closely monitor the pancreatic function of patients who have undergone a major hepatectomy, particularly in the initial postoperative month. Understanding liver-pancreas crosstalk following liver resection is essential for the success of hepatectomy in all cases. We expect that future studies will expand our understanding of the heterogeneity and whether different pancreatic cells/tissues have different adaptations to hepatectomy.

Patients and study design

This single-center, retrospective, observational study was approved by the Ethics Committees of Jichi Medical University (Ethics Committee Approval Case Number 20 − 001). Our study did not include minors. This study was designed and carried out in accordance with the Declaration of Helsinki and Istanbul. The need for written informed consent for the present study was waived by the Institutional Review Board of Jichi Medical University in view of its retrospective design, in accordance with national and local guidelines, such as the fact that all clinical/ laboratory measurements and procedures were part of routine care.

A total of 339 living liver donors undergoing hepatectomy at our facility between 2003 and 2023 were included in this study. One case using grafts from donors with familial amyloid polyneuropathy was excluded. Finally, 338 consecutive cases were analyzed. Baseline clinical data were obtained from the medical records. In this study, plasma enzymatic activities of total amylase were analyzed.

Surgical procedures and operative management

The type of donor hepatectomy was selected based on the recipient’s standard liver volume, weight, and graft volume determined by preoperative computed tomographic volumetry. We performed a left lateral sectionectomy (LLS) for LLS grafts and an in vivo segment 3 (S3) resection during LLS for S2 monosegment grafts as previously reported.³⁹ The donor’s biliary anatomy was evaluated using intraoperative real-time cholangiography performed three times to determine the biliary anatomy, decide on the biliary transection line, and confirm absence of biliary leakage. Donor graft hepatectomy was routinely performed with intraoperative ultrasonographic guidance. Mostly, we transected the liver parenchyma without blood inflow clamping.

Classification and comparison of patients

The 338 living donors were divided into three groups, based on the type of hepatectomy as follows: the left lateral sectionectomy (LLS) group, the left lobectomy (LL) group, and the right lobectomy (RL) group. The donors for monosegmentectomy graft (n = 17) and reduced LLS graft (n = 15) were included in the LLS group. The donors who underwent posterior sectionectomy (n = 2) were included in the RL group. In comparing perioperative factors, the medical records for each case were reviewed and compared among the groups.

Statistical analyses

Continuous variables were expressed as the medians (ranges) and analyzed using nonparametric methods for non-normally distributed data (Mann–Whitney U-test). Categorical variables were reported as numbers (percentages) and analyzed using the chi-squared test or Fisher’s exact test, as appropriate. In multiple comparisons, results were assessed using the Kruskal-Wallis test with a Dunn-Bonferroni adjustment. The correlation between two parameters was analyzed by the Spearman rank-order method. Variables with a significant relationship to abonormal amylase/lipase values on postoperative day (POD) 7, in univariate analysis were used in a binary logistic regression model. A difference was considered to be significant for values of P < 0.05. Statistical analyses were performed using GraphPad Prism (v9.5.1; GraphPad Software, San Diego, CA, USA, https://www.graphpad.com) and JASP (v0.17.2; JASP team, Amsterdam, The Netherlands).

Data Availability Statement

The data generated or analyzed during this study are included in this published article and its supplementary information files.

Author contributions statement

TW contributed to the study conception and design. TW, YS, YO, YS, NO, YH, TH, TO, and KT performed surgical resection and collected the clinical data. TW wrote the first draft of the manuscript paper. YS, YO, YS and NS contributed to the review, and/or critical revision of the manuscript. All authors have approved the final article.

Additional Information

Competing interests

The authors declare no competing interests.

The corresponding author is responsible for submitting a competing interests statement on behalf of all authors of the paper.

Funding

There was no funding for this study.

Ethics approval and consent to participate

This study was approved by the Ethics Committees of Jichi Medical University (Ethics Committee Approval Case Number 20-001). Informed consent was obtained in the form of opt-out on our website (https://www.jichi.ac.jp/transplant/contents/disclosure.html), with the approval of the Ethics Committees of Jichi Medical University. The need for written informed consent for the present study was waived by the Institutional Review Board of Jichi Medical University in view of its retrospective design, in accordance with national and local guidelines, such as the fact that all clinical/ laboratory measurements and procedures were part of routine care. Our study did not include minors. This study was designed and carried out in accordance with the Declaration of Helsinki and Istanbul.

Consent for publication

Consent for publication was obtained in the form of opt-out on our website (https://www.jichi.ac.jp/transplant/contents/disclosure.html), with the approval of the Ethics Committees of Jichi Medical University.

Priest, C. & Tontonoz, P. Inter-organ cross-talk in metabolic syndrome. Nature metabolism 1, 1177–1188, doi:10.1038/s42255-019-0145-5 (2019).
Castillo-Armengol, J., Fajas, L. & Lopez-Mejia, I. C. Inter-organ communication: a gatekeeper for metabolic health. EMBO reports 20, e47903, doi:10.15252/embr.201947903 (2019).
Evans, R. M. & Wei, Z. Interorgan crosstalk in pancreatic islet function and pathology. FEBS letters 596, 607–619, doi:10.1002/1873-3468.14282 (2022).
Hirano, T., Manabe, T., Ando, K., Yamaki, K. & Tobe, T. Effect of partial hepatectomy on glucose-stimulated insulin release from perfused rat pancreas. International journal of pancreatology: official journal of the International Association of Pancreatology 8, 51–57, doi:10.1007/bf02930223 (1991).
Moreau, F. et al. Early effects of liver regeneration on endocrine pancreas: in vivo change in islet morphology and in vitro assessment of systemic effects on β-cell function and viability in the rat model of two-thirds hepatectomy. Horm Metab Res 46, 921–926, doi:10.1055/s-0034-1389995 (2014).
Miyagawa, S., Makuuchi, M., Kawasaki, S. & Kakazu, T. Changes in serum amylase level following hepatic resection in chronic liver disease. Arch Surg 129, 634–638 (1994).
Tsuzuki, T., Shimizu, S., Takahashi, S. & Iio, H. Hyperamylasemia after hepatic resection. Am J Gastroenterol 88, 734–736 (1993).
Krokos, N. V. et al. Acute pancreatitis after liver transplantation: incidence and contributing factors. Transpl Int 8, 1–7 (1995).
Tissieres, P. et al. Acute pancreatitis after orthotopic liver transplantation in children: incidence, contributing factors, and outcome. J Pediatr Gastroenterol Nutr 26, 315–320 (1998).
Sathasivam, S., Ritchie, A., Brooks, A. J. & Morris, D. L. Acute pancreatitis following liver resection: report of three fatal cases and a review of the literature. ANZ J Surg 74, 643–645, doi:10.1111/j.1445-1433.2004.03113.x (2004).
Camargo, C. A., Jr., Greig, P. D., Levy, G. A. & Clavien, P. A. Acute pancreatitis following liver transplantation. J Am Coll Surg 181, 249–256 (1995).
Allard, M. A. et al. Posthepatectomy portal vein pressure predicts liver failure and mortality after major liver resection on noncirrhotic liver. Ann Surg 258, 822–829; discussion 829–830, doi:10.1097/SLA.0b013e3182a64b38 (2013).
Bogner, A. et al. Intraoperative Increase of Portal Venous Pressure is an Immediate Predictor of Posthepatectomy Liver Failure After Major Hepatectomy: A Prospective Study. Annals of Surgery 274 (2021).
Gavriilidis, P., Hammond, J. S. & Hidalgo, E. A systematic review of the impact of portal vein pressure changes on clinical outcomes following hepatic resection. HPB 22, 1521–1529, doi:https://doi.org/10.1016/j.hpb.2020.07.006 (2020).
Miyagawa, S. et al. Serum Amylase elevation following hepatic resection in patients with chronic liver disease. Am J Surg 171, 235–238, doi:10.1016/s0002-9610(97)89556-6 (1996).
Sjovall, S., Holmin, T., Evander, A. & Stenram, U. Splenic and gastro-duodenal vein occlusion–influence on the pancreatic gland and on the outcome of experimental pancreatitis. International journal of pancreatology: official journal of the International Association of Pancreatology 3, 143–149, doi:10.1007/bf02798925 (1988).
Arkadopoulos, N. et al. Pancreatic injury after major hepatectomy: a study in a porcine model. Surg Today 42, 368–375, doi:10.1007/s00595-011-0039-y (2012).
Varsos, P. et al. Desferrioxamine Attenuates Pancreatic Injury after Major Hepatectomy under Vascular Control of the Liver: Experimental Study in Pigs. HPB Surg 2012, 714672, doi:10.1155/2012/714672 (2012).
Li, Y. et al. Protective effects of deferoxamine mesylate preconditioning on pancreatic tissue in orthotopic liver autotransplantation in rats. Transplant Proc 43, 1450–1455, doi:10.1016/j.transproceed.2010.09.176 (2011).
Unalp, O. V. et al. The effects of the Pringle maneuver on the pancreas: can octreotide be protective? Jop 10, 284–291 (2009).
Bell, R., Begum, S., Prasad, R., Taura, K. & Dasari, B. V. M. Volume and flow modulation strategies to mitigate post-hepatectomy liver failure. Frontiers in oncology 12, 1021018, doi:10.3389/fonc.2022.1021018 (2022).
Oliver, R. H. & Sutton, P. M. The effects of partial hepatectomy on portal pressure in rats. Br J Surg 53, 138–141, doi:10.1002/bjs.1800530213 (1966).
Webb, L., Smith-Laing, G., Lake-Bakaar, G., McKavanagh, S. & Sherlock, S. Pancreatic hypofunction in extrahepatic portal venous obstruction. Gut 21, 227–231, doi:10.1136/gut.21.3.227 (1980).
Kuroda, T. et al. Pancreatic congestion in liver cirrhosis correlates with impaired insulin secretion. J Gastroenterol 50, 683–693, doi:10.1007/s00535-014-1001-8 (2015).
Petersen, M. C., Vatner, D. F. & Shulman, G. I. Regulation of hepatic glucose metabolism in health and disease. Nature Reviews Endocrinology 13, 572–587, doi:10.1038/nrendo.2017.80 (2017).
Han, H.-S., Kang, G., Kim, J. S., Choi, B. H. & Koo, S.-H. Regulation of glucose metabolism from a liver-centric perspective. Experimental & Molecular Medicine 48, e218-e218, doi:10.1038/emm.2015.122 (2016).
Röder, P. V., Wu, B., Liu, Y. & Han, W. Pancreatic regulation of glucose homeostasis. Experimental & Molecular Medicine 48, e219-e219, doi:10.1038/emm.2016.6 (2016).
Han, S. et al. Intraoperative hyperglycemia during liver resection: predictors and association with the extent of hepatocytes injury. PLoS One 9, e109120, doi:10.1371/journal.pone.0109120 (2014).
Okabayashi, T. et al. Effect of perioperative intensive insulin therapy for liver dysfunction after hepatic resection. World J Surg 35, 2773–2778, doi:10.1007/s00268-011-1299-9 (2011).
Hassanain, M. et al. Randomized clinical trial of the impact of insulin therapy on liver function in patients undergoing major liver resection. British Journal of Surgery 100, 610–618, doi:10.1002/bjs.9034 (2013).
Abu Rmilah, A. A., Zhou, W. & Nyberg, S. L. Hormonal Contribution to Liver Regeneration. Mayo Clinic proceedings. Innovations, quality & outcomes 4, 315–338, doi:10.1016/j.mayocpiqo.2020.02.001 (2020).
Michalopoulos, G. K. Hepatostat: Liver regeneration and normal liver tissue maintenance. Hepatology 65, 1384–1392, doi:10.1002/hep.28988 (2017).
Abu Rmilah, A. et al. Understanding the marvels behind liver regeneration. Wiley interdisciplinary reviews. Developmental biology 8, e340, doi:10.1002/wdev.340 (2019).
Niederwieser, T. et al. Early postoperative arterial lactate concentrations to stratify risk of post-hepatectomy liver failure. Br J Surg 108, 1360–1370, doi:10.1093/bjs/znab338 (2021).
Sultana, A. et al. Prospective evaluation of the International Study Group for Liver Surgery definition of post hepatectomy liver failure after liver resection: an international multicentre study. HPB (Oxford) 20, 462–469, doi:10.1016/j.hpb.2017.11.007 (2018).
Yamamoto, G. et al. ALPlat criterion for the resection of hepatocellular carcinoma based on a predictive model of posthepatectomy liver failure. Surgery 167, 410–416, doi:10.1016/j.surg.2019.09.021 (2020).
Wang, Y. Y. et al. Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma. Ann Surg 274, e1209-e1217, doi:10.1097/sla.0000000000003803 (2021).
Ismail, O. Z. & Bhayana, V. Lipase or amylase for the diagnosis of acute pancreatitis? Clin Biochem 50, 1275–1280, doi:10.1016/j.clinbiochem.2017.07.003 (2017).
Mizuta, K. et al. Living donor liver transplantation for neonates using segment 2 monosubsegment graft. Am J Transplant 10, 2547–2552, doi:10.1111/j.1600-6143.2010.03274.x (2010).

No competing interests reported.

SupplementalFigure1.pptx
Supplemental Content 1: Supplemental Figure 1, Assessment of serum amylase and lipase values after hepatectomy.
SupplementalFigure2.pptx
Supplemental Content 2: Supplemental Figure 2, Correlation between age and the pancreatic function test on postoperative day 7.
SupplementalTablev4.docx
Supplemental Content 3: Supplemental Table 1, Comparison between groups with normal and abnormal lipase levels in POD 7. Supplemental Content 4: Supplemental Table 2, Comparison between groups with normal and abnormal amylase levels in POD 7.

Download PDF

Journal Publication

published 21 Mar, 2024

Read the published version in Scientific Reports →

Editorial decision: Revision requested
07 Jan, 2024
Reviews received at journal
06 Jan, 2024
Reviews received at journal
29 Dec, 2023
Reviewers agreed at journal
28 Dec, 2023
Reviewers invited by journal
18 Dec, 2023
Editor assigned by journal
18 Dec, 2023
Editor invited by journal
16 Nov, 2023
Submission checks completed at journal
16 Nov, 2023
First submitted to journal
14 Nov, 2023

You are reading this latest preprint version

The Impact of Liver Resection Volume on Pancreatic Function: Novel Insights into Acute Liver-Pancreas Crosstalk After Hepatectomy

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Results

Comparison of the clinical characteristics and operation-related factors across the groups

Assessment of preoperative serum amylase and lipase values

The RL group shows a more significant increase in amylase and lipase after surgery

Effect of liver resection on postoperative lipase homeostasis may persist for several weeks

Negative correlation between the remnant liver volume and pancreatic impairment

Risk factor for abnormal amylase and lipase values on POD 7

No synergistic effect of aging on the amylase and lipase values on POD 7

Implications from the correlation between postoperative liver and pancreatic dysfunction

Discussion

Methods

Patients and study design

Surgical procedures and operative management

Classification and comparison of patients

Statistical analyses

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1