Volume and Functional Changes of Remnant Pancreas After Different Types of Pancreatectomy: Exploring the Regenerative Potential

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Herein, we conducted a prospective study to investigate the correlation between changes in volume and endocrine function of the remnant pancreas. Design: Patients undergoing pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) from Jan. 2009 to Dec. 2017 were included. Computed tomography was used to determine the volume of remnant pancreas at 3 months, 1 year, and 2 years after pancreatectomy. The postoperative changes of endocrine function were also assessed. RESULTS Finally, 90 PD patients and 45 DP patients were enrolled. The remnant pancreas volume at 3 months, 1 year and 2 years compared with initial residual pancreas were 80.79%, 68.67% and 65.34% respectively (p < 0.001) in the PD patients; 106.25%, 106.62% and 110.43% (p = 0.019) in the DP patients. The DP patients have higher incidence of new-onset diabetes than PD patients (33.3% vs. 22.7%). More P-duct dilatation with severe atrophy of the remnant pancreas (p = 0.027) in the PD patients, while better volume preservation and growth (p = 0.084) in the DP patients with spleen preservation. The changes of pancreas volume didn't correlate with postoperative new-onset DM. Interestingly, PD group had greater restoration of endocrine function than DP group based on secretion of C-peptide (β ± SE: 13.26 ± 5.50, p = 0.016). CONCLUSION Remnant pancreas exhibits distinct volumetric changes with significant volume increase in DP patients but progressive volume decreases in PD patients. Despite better volume preservation in DP group, the head portion of pancreas in PD group demonstrated superior β-cell function restoration, corresponding with lower incidence of new-onset diabetes. Health sciences/Diseases Health sciences/Endocrinology Health sciences/Gastroenterology Health sciences/Medical research Pancreaticoduodenectomy Distal Pancreatectomy Pancreatogenic Diabetes C-peptide Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Summary Box What is already known about this subject? Postoperative changes in remnant pancreatic volume are not well characterized, and the effects of pancreatectomy on glucose metabolism remain inconsistently reported in previous studies. What are the new findings? This study reveals contrasting volumetric trends after different types of pancreatectomy: Distal pancreatectomy (DP) is associated with volume increase in the remnant pancreatic head, especially in cases with splenic preservation. Pancreaticoduodenectomy (PD) results in progressive atrophy of the remnant pancreatic tail, primarily linked to pancreaticojejunostomy stricture and subsequent ductal obstruction. Despite the hypertrophic changes seen in the DP group, new-onset diabetes occurred more frequently than in the PD group. This is likely due to the loss of islet-rich distal pancreatic tissue, highlighting that volume gain in the remnant head does not fully restore endocrine function. How might it impact on clinical practice in the foreseeable future Surgical techniques that optimize long-term endocrine function should be prioritized. These include: Ensuring patency of the pancreaticojejunostomy to avoid remnant atrophy in PD. Preserving the spleen and its vasculature in DP to enhance remnant pancreatic viability. Given the rising importance of long-term metabolic outcomes, preventing postoperative diabetes should be an integral part of surgical planning. Introduction Pancreatectomy is a standard treatment for several indications, such as pancreatic adenocarcinoma, pancreatic adenoma, pancreatic cysts, and chronic pancreatitis. There are two primary surgical methods of pancreatectomy, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), depending on the location and extent of the pancreatic lesion. Pancreatectomy is much safer nowadays; the mortality rate of PD has even decreased to 0% ~ 5% in high volume medical centers [ 1 ] . The improvement of survival rate after pancreatectomy had raised the consideration of long-term metabolic consequences. Pancreas is an important digestive organ comprising two major components: endocrine glands to regulate metabolism and exocrine glands to secrete digestive enzymes. [ 2 ] Islets of Langerhans is a cluster of endocrine cell, only account for 1–2% of pancreas parenchyma but play a critical role in glucose regulation. [ 3 ] Furthermore, β cells make up 50 ~ 70% of the cells in pancreatic islets that synthesize and secrete insulin to control glucose metabolism. [ 2 ] The loss of pancreatic parenchyma after pancreatectomy would lead to deterioration of glucose homeostasis due to decrease of β cells amount. Some studies have shown that glucose levels start to rise when β cells mass is reduced more than 50% compared with normal. [ 4 , 5 ] About 5–10% of diabetes mellitus cases are related to pancreatic diseases in the Western country. [ 6 ] Those new-onset diabetes mellitus after pancreatectomy is now defined as pancreatogenic diabetes mellitus (Type 3c DM). [ 6 ] Unlike the well-documented regenerative capability of the liver after major hepatectomy, the capacity for pancreatic regeneration following pancreatectomy remains controversial. This raises the question of whether changes in pancreatic volume after pancreatectomy also correlate with functional recovery of the pancreas. In mice and rats, 90% pancreatectomy can induce ductal cell proliferation and upregulate embryonic gene expression, such as Pdx1, Ngn3, and Ptf1a in mature duct cells, to promote the regenerative process. [ 7 ] However, the regenerative capability of the pancreas is decreased with age and limited in adult rats. [ 8 ] Similarly, previous observation from children suggested tissue regeneration after near-total pancreatectomy, [ 9 ] but the capacity for pancreatic regeneration is absent in adult humans. [ 10 ] You et al reported that the remnant pancreas atrophied significantly at long-term follow-up after PD. [ 11 ] However, until now, there is no study on volume change of the remnant pancreas after DP. Embryonically, the head pancreas and distal pancreas (neck, body, and tail) are derived from the different origin. [ 12 ] Hence, we conjecture the different parts of the pancreas may display different regenerative capabilities. Although the deterioration of glucose homeostasis after pancreatectomy had been demonstrated, [ 4 , 5 ] restoration of endocrine functions after different procedures remains unclear. Therefore, in this study, we tried to compare the long-term changes in pancreatic volume and endocrine function between PD and DP, and to investigate whether postoperative volume changes correlate with endocrine function recovery and explore the regenerative potential. Materials and Methods Study design and participants This is a single-institutional, non-randomized, non-experimental, prospective study. This study was approved by the Institutional Review Board of the National Cheng Kung University Hospital with approval number of B-ER-108-312 . All methods were performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki and institutional ethical guidelines for human research. We enrolled the patients from January 2009 to December 2017, who underwent pancreatectomy, including pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), for a variety of disorders at the National Cheng Kung University Hospital. The criteria for enrollment were those patients who had received pancreatectomy, PD or DP, and disease-free survival for more than 2 years if those patients with malignant pathology. Patient characteristics were analyzed, such as sex, body mass index, the pathologic diagnosis, surgical method, neoadjuvant chemotherapy, and preoperative glucose metabolic status. Perioperative comorbidities were also included in this assessment: preoperative pancreatitis, obstructive jaundice, and postoperative pancreatic duct obstruction. Additionally, part of the patients undergoing DP had spleen preservation, and we also compared the outcome between the group with or without spleen preservation. In those enrolled patients, they were received regular follow-up with examination of abdominal computed tomography, 3 months, 12 months, and 24 months after operation for benign pancreatic diseases and 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months after operation for malignant pancreatic diseases. Standard demographic and clinical data are obtained from medical records. Fasting blood sugar and HbA 1 C were also checked every 3 months. In this study, diabetes mellitus was defined as a fasting blood glucose level > 126 mg/dl, or random blood glucose level > 200 mg/dl, or HbA 1 C > 6.5%, or the use of oral antidiabetic agents or insulin injection. Pancreatic duct dilatation was defined according to the diameter of pancreatic duct > 3 mm. Outcomes For the concordance of data, we decided to collect abdominal computed tomography (CT) scan before the operation, and at 3 months, 1 year, and 2 years postoperatively to determine the volume change of the remnant pancreas after pancreatectomy. Also, laboratory data, including HbA1C, C-peptide, was analyzed at the same time points: before the operation, and at 3 months, 1 year, and 2 years postoperatively to evaluate the impact of pancreatectomy on glucose homeostasis and insulin secretion. Ultimately, we further analyzed the relationship between glucose homeostasis, insulin secretion, and the volume of remnant pancreas. Image/CT volumetry INFINITT PACS medical image processing software (INFINITT Healthcare Co., Ltd, Korea) was used to analyze the results of CT scan. The volumetry of the original pancreas and remnant pancreatic tissue was assessed by CT scan preoperatively and at 3 months, 1 year and 2 years postoperatively. Serial axial images were obtained at 3 mm intervals from the lung base to the pelvis with intravenous contrast enhancement. The total volume of the pancreas parenchyma was computed by summing the pancreas volume (mm3) of each section. Pancreas volume (mm3) of each section = Area of pancreas (mm2) × Height of each slice (3mm). The area of the pancreas parenchyma in each slice was carefully outlined, excluding the major vessels, and pancreatic tumor (Fig. 1 A-D). Of note, there is a significant difference between the actual pancreas volumes (ml) of each patient. To minimize this difference, the results of volumetry were presented in two fashions: 1. Residual volume (V%): the ratio of the remnant volume of pancreas to volume of pre-operative pancreas = the volume of the remnant pancreas (ml) ÷ the volume of the preoperative whole pancreas (ml);2. Volume change of the residual pancreas (V change %): The ratio of the remnant volume of pancreas to the volume of initial residual pancreas = the volume of the remnant pancreas (ml) ÷ the volume of presumed initial residual pancreas (ml). Statistical Analysis Continuous variables, such as age, were provided as mean value ± standard error (SE) and range; BMI were presented as mean value ± standard error (SE). Continuous variables with normal distribution in each group were compared by an independent t-test; continuous variables without normal distribution were compared by Wilcoxon rank sum test. Categorical variables were tested with χ2 test and Fisher's exact test. The Generalized Estimating Equations (GEE) was applied for the analysis of repeated measurements or other related variables. [ 13 ] A logistic regression model was applied to analyze the relationship between a binary outcome and a group of predictor variables. The correlation between two groups of continuous variables was analyzed with Spearman's rank correlation coefficient. All the statistical analysis was performed with the SAS 9.4 statistical software (SAS Institute Inc. Cary, NC, USA). All tests were two-tailed, and p < 0.05 was considered as statistically significant. Results The details of clinicopathologic characteristics and postoperative change of diabetic status of enrolled patients in this study were listed in Table 1. There were 90 and 45 patients in the PD and DP groups, respectively. Among them, 66 (73.3%) in PD, and 20 (44.4%) in DP received pancreatectomy due to malignancy. The remnant pancreas hypertrophied in the DP group, but atrophied in the PD group In DP group, mean of the pre-operative volume of pancreas was 55.51 ± 2.98ml (range: 19.26 - 121.42 ml). Initial residual volume (V%) in the DP group was 67.93% ± 1.97% (range 41.6% - 91.43%). In PD group, mean of the pre-operative volume of pancreas was 58.83 ± 2.63 ml (range 10.39 - 128.55 ml). Initial residual volume (V%) in the PD group was 51.20% ± 1.62% (range 13.31% - 85.76%). There was no significant difference in the initial residual volume (V%) between the PD and DP groups (p=0.274). The volume of remnant pancreas demonstrated hypertrophic changes in the DP group (Figure 2A) but showed progressive atrophy in the PD group during follow-up (Figure 2B). The volumetric changes of the remnant pancreas in the DP group were 106.25% ± 2.09% at 3 months, 106.62% ± 3.27% at 1 year, and 110.43% ± 4.10% at 2 years (β = 2.97, p=0.019) (Figure 2C). In contrast, the volumetric changes of the PD group at 3 months, 1 year and 2 years were 80.79% ± 2.86%, 68.67% ± 2.58%, and 65.34% ± 2.98% respectively (β = -11.85, p<0.001) (Figure 2C). The result from GEE analysis demonstrated that the DP group had significant hypertrophic changes in the remnant pancreas compared to the PD group (β =5.43, p=0.014) (Figure 2C). The incidence of hypertrophy in the PD group declined over time. Only 17.78%, 12.22%, and 10.53% PD patients exhibited hypertrophic changes in remnant pancreatic tissue at 3 months, 1 year, and 2 years of follow-up, respectively. In comparison, the DP group showed a higher incidence of hypertrophy. The proportion of patients with hypertrophic changes in the DP group increased over time, with 66.7%, 71.1%, and 73.5% of patients demonstrating tissue hypertrophy at 3 months, 1 year, and 2 years of follow-up, respectively (Figure 2D). Factors associated with volumetric changes in remnant pancreas In PD group, we analyzed the relationship among several relevant variables and the residual volume change. The results showed that pancreatic duct dilatation is the most significant factor related to the atrophic change of remnant pancreas (Supplementary Table 1). In PD group with postoperative pancreatic duct dilatation, the change of volume in the remnant pancreas compared to initial residual pancreas was 77.69%, 58.60% and 53.89% at 3-month, 1 year and 2 years follow-up respectively. In contrast, the volume change of remnant pancreas in the PD patients without postoperative pancreatic duct dilatation which compared to initial residual pancreas were 90.92%, 86.23% and 85.26% at 3-month, 1-year and 2-year follow-up respectively (Figure 3). These results demonstrated that more severe atrophy occurred in the patients with pancreatic duct dilatation at 1 year and 2 years postoperatively (β = -9.82, p = 0.027) (Figure 3). On the other hand, the factor, "spleen preservation", may positively correlate with the degree of hypertrophic changes in the DP group (Supplementary Table 2). We noticed that the volume change of remnant pancreas in the DP patients with and without spleen preservation was 124.55% and 102.74% at 1-year follow-up (p = 0.006), and 120.08% and 107.92% at 2-year follow-up (p = 0.177) respectively (Figure 4). Although the difference at 2-year follow-up is not significant due to increasing missing data, these findings indicated that DP patients with spleen preservation demonstrated more pronounced hypertrophic changes than those without spleen preservation. Higher incidence of new onset DM in the DP group than the PD group In the DP group (n=45), 21 patients were diagnosed with diabetes mellitus preoperatively and none of these patients had remission in diabetes mellitus after surgery. Among the non-diabetic patients (n=24), 8 out of 24 (33.3%) patients were diagnosed with new-onset diabetes mellitus (Table 1). In the PD group (n=90), 24 patients were diagnosed with diabetes mellitus preoperatively and 7 of 24 (29.2%) patients had remission in diabetes mellitus after surgery. Among the non-diabetic patients (n=66), 15 out of 66 (22.7%) patients were diagnosed with new-onset diabetes mellitus (Table 1). These results indicated that the DP group had a higher incidence of new-onset DM than PD group, although the difference was not statistically significant (p = 0.115). More important, we found that the remission of preoperative DM after pancreatectomy only occurred in the PD group (Table 1). Furthermore, most of new-onset DM occurred within 1 year postoperatively, especially between 3 months and 1 year (Supplementary Table 3). To further define the possible factors involved in the postoperative new-onset DM, we analyze the association between several perioperative clinical variables and the occurrence of new-onset DM. The results of univariate logistic regression demonstrated that there was no statistically significant relationship between any single variable and the occurrence of new-onset DM (Supplementary Table 4). Similarly, the results of univariate logistic regression also demonstrated that neither pancreas volume nor C-peptide level shows significant correlation with the occurrence of new-onset DM. (Supplementary Table 5). These results implied that the occurrence of pancreatogenic DM may be multifactorial. Both C-peptide level and pancreas volume cannot individually be a predictor for new-onset DM. The impact on endocrine function after pancreatectomy was more severe in the DP group In the PD group, the mean value of C-peptide level before the operation was 3.06 ng/ml and declined to 1.54 ng/ml in the 3-month follow-up (p < 0.001) (Fig.5A). Consistently, the mean value of C-peptide level before the operation in the DP group was 2.49 ng/ml and declined to 1.15 ng/ml in the 3-month follow-up (p <0.001) (Fig.5B). These results demonstrated that loss of pancreas parenchyma leads to decrease in insulin production significantly. Additionally, the mean value of C-peptide level is slightly increased during 3-months to 2-years follow-up in both PD and DP groups (Fig. 5A, B), even though the remnant pancreas in the PD group atrophied over time. The correlation between C-peptide level change and residual pancreatic tissue volume indicated that the change of C-peptide level is not positively correlated with residual pancreatic tissue volume during the whole follow-up (Supplementary Figure 1). It meant the amount of insulin production after pancreatectomy was not correlated with the pancreas volume. Interestingly, we compared the residual volume (V%) with the change of C-peptide level (C-peptide level at each time point ÷ preoperative C-peptide level, %) in both groups (Figure 5C, D). The results showed that C-peptide level declined more in the DP group than in the PD group, although the pancreas volume increased in the DP group. Postoperative change of C-peptide level was 63.6%, 66.2% and 72.5% in PD group; 52.6%, 64.4% and 71.0% in DP group at 3-month, 1-year, and 2-year follow-up respectively (Figure 5C, D). These results implied that the impact of the pancreas parenchyma loss on insulin secretion was more significant in the DP group. In consideration of the difference in the remnant pancreas volume among each case, we compared the insulin production in the DP and PD groups via calculating the ratio of the C-peptide level to the volume of remnant pancreas. The relationship between surgery types and postoperative change of C-peptide level was analyzed by GEE. As shown in Table 2, the postoperative C-peptide level in both PD and DP groups increased over time (β =16.33, p = 0.001). More importantly, the PD group had better insulin production and restoration of β-cell secretory capacity than the DP group (β =13.26, p = 0.016) (Table 2). Discussion This study is the first to systematically compare both long-term changes in pancreatic volume and endocrine function following pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Two key findings emerged from our analysis: First, despite opposite trends in remnant pancreas volume changes - atrophy in PD and hypertrophy in DP - both groups demonstrated similar patterns of partial endocrine function recovery over time, suggesting that β-cells possess compensatory capacity through enhanced secretory function rather than volume hypertrophy. Second, the anatomical location of resection proves more critical than the volume of tissue removed in determining postoperative endocrine dysfunction. DP patients experienced both greater C-peptide decline and higher incidence of new-onset diabetes mellitus than PD patients. The improvement of survival rate after pancreatectomy in recent decades promotes the consideration of long-term metabolic consequences. Several studies have also shown that glucose levels start to rise when β cells mass is reduced more than 50% of normal. [4, 5, 14] As the report by Shirakawa et al, [15] current study found that greater resection of pancreatic tissue would increase the incidence of new-onset pancreatogenic diabetes. But we also found the atrophic change of remnant pancreas developed and the volume of the remnant pancreas was not associated with pancreatogenic diabetes in PD patients as reported by You et al . [11] Most importantly, we first demonstrated hypertrophic changes in the remnant pancreas after DP, yet these patients paradoxically showed higher incidence of new-onset pancreatogenic diabetes In our study, pancreatic duct dilatation was the major factor associated with the volume atrophy of the remnant pancreas in PD patients. Pancreatic duct dilatation resulted from pancreaticojejunostomy (PJ) anastomosis stricture was a common complication in long term follow-up. Murakami et al. reported that the rate of pancreatic duct dilatation after PD was 33.3% at one year following surgery and higher atrophy rate of remnant pancreas in patients with postoperative pancreatic duct dilatation. [16] In our study, the rate of pancreatic duct dilatation in the second year was 27.6% (21 of 76 patients). Furthermore, those patients with pancreatic duct dilatation would have more severe atrophy of the remnant pancreas. PJ anastomosis stricture is the major cause of postoperative acute and chronic pancreatitis in humans and associated with morphological and functional changes later. [17] Watanabe et al. also proved that ligation of mice pancreatic duct induced degeneration and apoptosis of the pancreatic acinar cells, but he didn’t find the same phenomenon in the endocrine cells. [18] On the other hand, most of the remnant pancreas (73.5%) in the DP group had a hypertrophic change at 2-years follow-up, especially in those patients received spleen-preservation distal pancreatectomy. The splenic artery and splenic vein are preserved in the spleen preservation surgery at our hospital and the preservation of splenic vessel provides a better blood supply to the remnant head portion pancreas. Besides the blood supply issue, spleen had been proven to contain Hox11-expressing splenic stem cells, which could be applied widely as cell therapy for organ regeneration in the pancreas, heart, bone, salivary gland, and brain. [19] Hou et al reported that the spleen-derived mesenchymal stem cells would promote pancreas cell regeneration and ameliorated pancreas dysfunction in an animal model of acute pancreatitis. [20] Current development of laparoscopic technique improves the accessibility of the spleen and splenic vessels-preserving distal pancreatectomy. Hence, distal pancreatectomy with preservation of spleen and splenic vessels is a better choice based on the point of enhancing pancreas regeneration. The occurrence of new-onset DM is about 14.5% - 22.2% of the PD patients. [21] Nonetheless, the recent study reported that 30.7% - 65% of patients had remission of DM after pancreaticoduodenectomy. [22] Similarly, our results showed 29.2% of patients with preoperative DM in the PD group had remission of DM after PD within 2-year follow-up. The possible reason for the amelioration of diabetes after PD is that the pancreatic α-cells and F-cells producing glucagon and pancreatic polypeptide (PP) are predominantly distributed in the head portion. [23] Reduction of α-cells and F-cells due to PD diminished secretion of glucagon and pancreatic polypeptide (PP) and inhibit hepatic gluconeogenesis. Additionally, current evidence indicated that PDAC releasing paraneoplastic substance would cause suppression of β-cell function and peripheral insulin resistance. [24] Resection of PDAC may benefit the blood sugar control. Hirata et al. had proposed several predictors for worsening DM after PD, such as malignancy, long-standing DM, and BMI >25 in preoperative non-diabetic patients. [25] However, all of these factors did not show any significant correlation with new-onset DM in our study. Why there are contradictory reports on the new-onset or remission of DM after PD? As reported by You [11] and Watanabe [18] , severe remnant pancreas atrophy associated with exocrine degeneration by pancreaticojejunostomy stricture, we propose that the long-term intraductal pressure might further induce malfunction of endocrine cell to cause deterioration of glucose metabolism. Apart from diminishing β-cell function, duodenum also plays an important role in glucose metabolism by secreting gastric-inhibitor peptide (GIP) and glucagon-like peptide (GLP) and stimulates postprandial insulin secretion. [26] Duodenectomy may compromise enteroinsular axis and deteriorate insulin and blood glucose regulation. A recent systemic review reported that the overall incidence of new-onset DM was 39% in the patients undergoing DP for chronic pancreatitis and 14% in the patients undergoing DP for the benign or malignant lesion. [27] In our study, 8 out of 24 (33.3%) patients were diagnosed with new-onset diabetes mellitus after DP, and the incidence of new-onset DM was much higher than that in the PD group. Also, no preoperative independent predictor for new-onset DM after DP was found in our study. Shirakawa et al. claimed the resected volume > 40% was an independent predictor for new-onset DM in the DP patients. [15] Sakata et al reported the smaller residual volume of the pancreas in the patient with high incidence of new-onset DM. Nonetheless, we and several current studies suggested the same conclusion that the volume of the remnant pancreas was not associated with new-onset DM. [4, 11] The possible explanation is better digestion and nutrition status in the DP group than the PD group. [28] C-peptide is used to evaluate insulin production by the β cells in the pancreas and reflected β-cell function indirectly. In our study, we found that the concentration of C-peptide decreased with the loss of pancreas parenchyma at first. However, the C-peptide level increased at both groups during 1-year and 2-year follow-up, even though residual volume of the pancreas was decreased in the PD group. Our results also demonstrated that the postoperative change in C-peptide level (%) was not correlated with the remnant pancreas volume (%) during the follow-up. Furthermore, in the DP group, C-peptide reduction exceeded the magnitude of volume loss, while PD group showed less C-peptide decline despite greater volume decrease. This phenomenon suggests that the influence of pancreas parenchyma loss on endocrine function was more significant in the distal pancreas than in the head pancreas. The β-cells density is about two times higher in the pancreas tail than in the head region. [29] As a result, distal pancreatectomy will cause a more significant impact on insulin secretion. Besides, in rodent model, it had shown that islets originating from the dorsal bud, forming pancreas body and tail, had a greater capacity to secrete insulin than islets of ventral bud, which forms the uncinated process and lower part of the pancreas head. [30] Our data clearly showed the PD group had a better restoration of the secretory capacity of β-cells. Thus, the metabolic impact due to removal of the partial pancreas should be more significant in the DP than in the PD. This study has several limitations. First, while this is a single-institution study with relatively small sample size which may introduce bias. However, our unique long-term follow-up data tracking both volumetric and functional changes would be difficult to obtain in a multi-center setting. Second, although we used C-peptide to assess β-cell function, blood glucose levels can influence insulin secretion, potentially masking true β-cell dysfunction. The C-peptide index (CPI), which normalizes C-peptide to concurrent glucose levels, would offer a more precise evaluation of β-cell function. Nevertheless, our study is one of the few with long-term C-peptide follow-up data, providing valuable evidence for this research topic. Additionally, although data on HOMA-IR were not available to explore insulin resistance and further investigate the cause of DM, this limitation did not affect our study conclusions. Future studies should incorporate these parameters to gain a more detailed understanding of the metabolic consequences of pancreatectomy. Conclusion We demonstrated distinct volumetric changes after pancreatectomy: atrophy in PD patients but hypertrophy in DP patients. Paradoxically, DP patients had higher incidence of new-onset diabetes despite better volume preservation, suggesting that anatomical location is more critical than remnant volume for endocrine function. Our findings also highlight the importance of surgical skills to prevent postoperative stricture of pancreaticojejunostomy and to preserve splenic vessels and spleen to optimize volumetric changes of remnant pancreas. Declarations Ethics approval IRB approved by the Institutional Review Board of the National Cheng Kung University Hospital with approval number of B-ER-108-312 Consent to Participate Given the retrospective nature of this study and the use of de-identified patient data, the Institutional Review Board of the National Cheng Kung University Hospital waived the requirement for informed consent for study participation. All patient data were completely anonymized prior to analysis, and no identifying information was included in the study dataset or manuscript. The waiver of informed consent was approved as part of the ethical review process under approval number B-ER-108-312. Data availability The datasets used in the study are available from the corresponding author upon reasonable request. Author contributions WH Lu: performance the analysis and writing the manuscript, HM Tsai: instruction to perform volume calculation, TK Liao, PJ Su, CJ Wang and YJ Chao: assisting in collect cases for study, YS Shan: initiate the study idea and instruction for perform the analysis, supervise and revise in writing the manuscript, and submit the manuscript Funding The grant was supported by Taiwan Ministry of Science and Technology (MOST 108-2321-B-006-014), Ministry of Healthy and Welfare (MOHW 107-TDU-B-212-114026A), and HSU-YUAN Education Foundation (HY-2018-001) Conflicts of interest The authors declare that they have no conflicts of interest. References D J Gouma , R C van Geenen, T M van Gulik, et al., Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume. Ann Surg, 2000. 232 (6): p. 786-95. Hoang Do, O. and P. Thorn, Insulin secretion from beta cells within intact islets: location matters. Clin Exp Pharmacol Physiol, 2015. 42 (4): p. 406-14. Junghyo Jo, Manami Hara, Ulf Ahlgren, Robert Sorenson, Vipul Periwal, Mathematical models of pancreatic islet size distributions. Islets, 2012. 4 (1): p. 10-9. Kumar, A.F., R.W. Gruessner, and E.R. Seaquist, Risk of glucose intolerance and diabetes in hemipancreatectomized donors selected for normal preoperative glucose metabolism. Diabetes Care, 2008. 31 (8): p. 1639-43. B A Menge, H Schrader, T G K Breuer, et al., Metabolic consequences of a 50% partial pancreatectomy in humans. Diabetologia, 2009. 52 (2): p. 306-17. Ewald, N. and P.D. Hardt, Diagnosis and treatment of diabetes mellitus in chronic pancreatitis. World J Gastroenterol, 2013. 19 (42): p. 7276-81. Wan-Chun Li , J Michael Rukstalis, Wataru Nishimura, et al., Activation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats. J Cell Sci, 2010. 123 (Pt 16): p. 2792-802. Hitoshi Takahashi, Daiki Okamura, Marlene E Starr, Hiroshi Saito, B Mark Evers, Age-dependent reduction of the PI3K regulatory subunit p85alpha suppresses pancreatic acinar cell proliferation. Aging Cell, 2012. 11 (2): p. 305-14. Teresa Berrocal, Arturo Alvarez Luque, Inmaculada Pinilla, Luis Lassaletta, Pancreatic regeneration after near-total pancreatectomy in children with nesidioblastosis. Pediatr Radiol, 2005. 35 (11): p. 1066-70. Bjoern A Menge, Andrea Tannapfel, Orlin Belyaev, et al., Partial pancreatectomy in adult humans does not provoke beta-cell regeneration. Diabetes, 2008. 57 (1): p. 142-9. Dong-Do You, Seong-Ho Choi, Dong-Wook Choi, Jin-Seok Heo, Cheon-Yu Ho, Woo-Seok Kim, et al., Long-term effects of pancreaticoduodenectomy on glucose metabolism. ANZ J Surg, 2012. 82 (6): p. 447-51. Werlin, S.L. and P.C. Lee, Chapter 114 - Development of the Exocrine Pancreas , in Fetal and Neonatal Physiology (Third Edition) , R.A. Polin, W.W. Fox, and S.H. Abman, Editors. 2004, W.B. Saunders. p. 1142-1151. Zeger, S.L. and K.Y. Liang, Longitudinal data analysis for discrete and continuous outcomes. Biometrics, 1986. 42 (1): p. 121-30. Alexandra E Butler, Juliette Janson, Susan Bonner-Weir, Robert Ritzel, Robert A Rizza, Peter C Butler, Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes, 2003. 52 (1): p. 102-10. Sachiyo Shirakawa, Ippei Matsumoto, Hirochika Toyama, et al., Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy. J Gastrointest Surg, 2012. 16 (12): p. 2212-9. Makoto Murakami, Katayama Kanji, Shigeru Kato,et al., Clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy following pancreatoduodenectomy. Surg Today, 2017. 47 (5): p. 581-586. J R Lowes, J Rode, W R Lees, R C Russell, P B Cotton, Obstructive pancreatitis: unusual causes of chronic pancreatitis. Br J Surg, 1988. 75 (11): p. 1129-33. S Watanabe, K Abe, Y Anbo, H Katoh, Changes in the mouse exocrine pancreas after pancreatic duct ligation: a qualitative and quantitative histological study. Arch Histol Cytol, 1995. 58 (3): p. 365-74. Denise L Faustman, Claudia Giesecke, Miriam Davis, et al., Disposable No Longer: The Spleen Holds a Reservoir of Stem Cells. Journal of Stem Cell Research & Therapy, 2014. 4 (7) Ya-Chin Hou, Chen-Fang Huang, Hao-Chen Wang, Yu Wu, Yan-Shen Shan, Therapeutic Efficacy of Spleen-Derived Mesenchymal Stem Cells in Mice with Acute Pancreatitis. Journal of Stem Cell Research & Therapy, 2015. 5 (12) Hans G Beger, Bertram Poch, Benjamin Mayer, Marco Siech, New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results. Ann Surg, 2018. 267 (2): p. 259-270. Mee Joo Kang, Hye Seung Jung, Jin-Young Jang, et al., Metabolic effect of pancreatoduodenectomy: Resolution of diabetes mellitus after surgery. Pancreatology, 2016. 16 (2): p. 272-7. E H Eddes, A M Masclee, H G Gooszen, M Frölich, C B Lamers, Effect of duodenum-preserving resection of the head of the pancreas on endocrine and exocrine pancreatic function in patients with chronic pancreatitis. Am J Surg, 1997. 174 (4): p. 387-92. Raghuwansh P Sah, Sajan Jiv Singh Nagpal, Debabrata Mukhopadhyay, Suresh T Chari, New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol, 2013. 10 (7): p. 423-33. Keiichiro Hirata, Bunzo Nakata, Ryosuke Amano, Sadaaki Yamazoe, Kenjiro Kimura, Kosei Hirakawa, Predictive factors for change of diabetes mellitus status after pancreatectomy in preoperative diabetic and nondiabetic patients. J Gastrointest Surg, 2014. 18 (9): p. 1597-603. Kreymann B, Williams G, Ghatei MA, Bloom SR, Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet, 1987. 2 (8571): p. 1300-4. De Bruijn, K.M. and C.H. van Eijck, New-onset diabetes after distal pancreatectomy: a systematic review. Ann Surg, 2015. 261 (5): p. 854-61. Gilliland TM, Villafane-Ferriol N, Shah KP, et al., Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection. Nutrients, 2017. 9 (3). Xiaojun Wang, Ryosuke Misawa, Mark C Zielinski, et al., Regional differences in islet distribution in the human pancreas--preferential beta-cell loss in the head region in patients with type 2 diabetes. PLoS One, 2013. 8 (6): p. e67454. E R Trimble, P A Halban, C B Wollheim, A E Renold, Functional differences between rat islets of ventral and dorsal pancreatic origin. J Clin Invest, 1982. 69 (2): p. 405-13. Tables Table 1. Patient Characteristics Characteristic PD (n = 90 ) DP (n = 45 ) P Age (mean±SE), yrs (range) 61±1.25 (25-86) 58±2.06 (20-82) 0.126 Sex (M:F) 56:34 24:21 0.421 BMI (mean±SE) 23.8±0.37 24.8±0.45 0.154 Preoperative CRT 2 4 0.984 Preoperative jaundice 40 (44.4%) 0 <0.001 *** Preoperative pancreatitis 20 (22.2%) 7 (15.6%) 0.250 Pylorus-preserving PD 72 (80%) - Laparoscopic DP Spleen preservation* - - 22 (48.9%) 8 (17.8%) Pathology 0.002 ** Benign 24 (26.7%) 25 (55.6%) Malignancy Pancreatic ductal cancer Bile duct cancer Ampullary cancer Duodenal cancer Neuroendocrine cancer Malignant IPMN Metastatic cancer Others 66 (73.3%) 29 7 22 2 - - - 6 20 (44.4%) 11 - - - 4 1 1 3 Preoperative diabetes 24 (26.7%) 21 (46.7%) 0.033 * New onset post-OP DM 15 (22.7%) 8 (33.3%) 0.115 Resolution of pre-OP DM 7 (29.2%) 0 (0%) 0.008 ** SE, standard error; M, male; F, female; BMI, body mass index; CRT, chemoradiotherapy; PD, pancreatico-duodenectomy; DP, distal pancreatectomy; IPMN, intraductal papillary mucinous neoplasm; DM, diabetes mellitus; OP, operation *: Spleen preservation: both splenic vessels and spleen were preserved during operation. Table 2. Relationship between surgical treatment (PD or DP) and the ratio of the change of C-peptide level to the volume of remnant pancreas * Variable GEE b ±SE p-value Treatment DP Ref. PD 28.03±17.40 0.107 Time 16.33±5.03 0.001 ** Treatment*Time (interaction) DP Ref. PD 13.26±5.50 0.016 * * the ratio of the change of C-peptide level to the volume of remnant pancreas was obtained by change of C-peptide level (%) ÷ residual pancreas volume (%) Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables.docx Supplemetaryfigure1figureandlegend.docx Cite Share Download PDF Status: Published Journal Publication published 02 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 25 Nov, 2025 Reviews received at journal 24 Nov, 2025 Reviews received at journal 22 Nov, 2025 Reviewers agreed at journal 09 Nov, 2025 Reviewers agreed at journal 05 Nov, 2025 Reviews received at journal 22 Aug, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers invited by journal 14 Aug, 2025 Editor assigned by journal 14 Aug, 2025 Editor invited by journal 14 Aug, 2025 Submission checks completed at journal 10 Aug, 2025 First submitted to journal 10 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7219476","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":502088485,"identity":"5141e71d-bcda-4904-9f44-3c93ffc88893","order_by":0,"name":"Wei-Hsun Lu","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Wei-Hsun","middleName":"","lastName":"Lu","suffix":""},{"id":502088486,"identity":"cfb10570-d84c-4bac-9815-4c2c7509c165","order_by":1,"name":"Hong-Ming Tsai","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Hong-Ming","middleName":"","lastName":"Tsai","suffix":""},{"id":502088487,"identity":"107c0432-bc93-476b-bdc1-a251deb4058d","order_by":2,"name":"Ting-Kai Liao","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Ting-Kai","middleName":"","lastName":"Liao","suffix":""},{"id":502088488,"identity":"451d1136-92c3-49d6-91af-d8cd6885a912","order_by":3,"name":"Ping-Jui Su","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Ping-Jui","middleName":"","lastName":"Su","suffix":""},{"id":502088489,"identity":"1c696f0a-7f4c-443f-b9a4-dc3ea5c25adc","order_by":4,"name":"Chih-Jung Wang","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Chih-Jung","middleName":"","lastName":"Wang","suffix":""},{"id":502088490,"identity":"eb02a253-2204-4613-8af9-30de95fc0751","order_by":5,"name":"Ying-Jui Chao","email":"","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":false,"prefix":"","firstName":"Ying-Jui","middleName":"","lastName":"Chao","suffix":""},{"id":502088491,"identity":"e26ef7e2-364c-47bf-8bf3-0f7ce73fe4e2","order_by":6,"name":"Yan-Shen Shan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYHACNiC2YWBgZm4AMhJAIgbEaEkDamFE1pJAUMthICZWi8H5488e/NxxPpq/nbGBuaAmLbGBvXmbBOOPw7i13MgxN+w9czt3xmGglhnHchIbeI6VSTAk4NPCwybB23Y7twGkhbehIrFBIscMqOU2XodJ/m07lzsfrkX+DQEtBxLMpHnbDuRugGgBOkyCB78WyRs5ZtKybcm5G4FaDvMcSzNu40krtkhI+49TCx/IYW/b7HLnnT988DFPTbJsP/vhjTc+2KTh1KJwAIkDZoOiCW9MyjfgkRwFo2AUjIJRAAYAWalWsO8wR2cAAAAASUVORK5CYII=","orcid":"","institution":"National Cheng Kung University, National Cheng Kung University Hospital, National Cheng Kung University","correspondingAuthor":true,"prefix":"","firstName":"Yan-Shen","middleName":"","lastName":"Shan","suffix":""}],"badges":[],"createdAt":"2025-07-26 07:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7219476/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7219476/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-36886-4","type":"published","date":"2026-02-02T15:59:38+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89672523,"identity":"dd90bda8-8a7d-4806-a358-b1449f09a8ca","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":945380,"visible":true,"origin":"","legend":"\u003cp\u003eCalculation of pancreas volume. \u003cstrong\u003e(A) \u003c/strong\u003eCalculating the initial volume of the pancreas before PD. Outlining the pancreas parenchyma in each slice, excluding pancreatic tumor “T”, portal vein “PV”, and splenic vein “SV”. The resection line was marked as red arrow. Pancreas areas(P) in each slice was calculated by using INFINITT PACS medical image processing software. The volume of the pancreas parenchyma in each slice was computed by area of pancreas (mm2) × Height of each slice (mm).\u003cstrong\u003e (B)\u003c/strong\u003e Calculating the residual volume of the pancreas after PD. \u003cstrong\u003e(C)\u003c/strong\u003e Calculating the initial volume of the pancreas parenchyma before DP. \u003cstrong\u003e(D)\u003c/strong\u003eCalculating the residual volume of the pancreas after DP.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/6d5367649a13f2395e9b8e48.png"},{"id":89672518,"identity":"e286b17e-7b1e-4b55-a90f-d78d718052b8","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":276135,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) \u003c/strong\u003eHypertrophy in the remnant pancreas after DP, \u003cstrong\u003e(B)\u003c/strong\u003e Atrophy in the remnant pancreas after PD, \u003cstrong\u003e(C)\u003c/strong\u003eThe ratio of residual volume at postoperative 3 months, 1 year and 2 years compared to initial volume of remnant pancreas in the PD and DP groups. “a” was obtained via GEE analysis by taking “time” as variable, “initial residual volume” as reference in each group; “b” was obtained via GEE analysis by taking “group” as variable, “PD group” as reference. \u003cstrong\u003e(D)\u003c/strong\u003e Percentage of patient with hypertrophic change of remnant pancreas. Residual pancreas volume in most of DP patients had a hypertrophic change (66.7%, 71.1%, 73.5% respectively in the DP group at 3months, 1-year, 2-year); contrarily, the rate of hypertrophic change in residual pancreas in most of PD patients is rare. (17.98%, 12.22%, 10.67% respectively in the PD group) (p-value at 3months, 1-year, and 2-year were 0.002, \u0026lt;0.001, and \u0026lt;0.001)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/d932f04335d9e35f71ae62ac.png"},{"id":89673424,"identity":"a8c5583d-7585-473b-8e03-4cd0436c4a8e","added_by":"auto","created_at":"2025-08-22 13:17:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":42489,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between the residual pancreas volume and P-duct dilatation in the PD group. We compared the change of residual volume in the PD patients with pancreatic duct dilatation to the PD patients without P-duct dilatation at postoperative 3 months, 1 year and 2 years. “P-d” means pancreatic duct. “a”, p-value was obtained by two-sample t test; “b”, p-value was obtained by GEE analysis\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/54762c3240c188c711ab9682.png"},{"id":89672520,"identity":"a44d02ef-c4f4-4f3f-84bc-dd5000bfe497","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":43498,"visible":true,"origin":"","legend":"\u003cp\u003eRelationship between the residual pancreas volume and spleen preservation in the DP group. We compared the change of residual volume in the DP patients with spleen preservation to the DP patients without spleen preservation at postoperative 3 months, 1 year and 2 years. “a”, p-value was obtained by Wilcoxon rank sum test; “b”, p-value was obtained by GEE analysis\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/325ddf099e642feda335e627.png"},{"id":89672524,"identity":"07a16568-78db-4bd5-9c53-ca67312b9cb8","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":66111,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)(B)\u003c/strong\u003e C-peptide level in both groups. C-peptide level dropped significantly after partial pancreatectomy in both groups (p-value\u0026lt;0.001, compared preoperative C-peptide level with post-op 3 months C-peptide level). \u003cstrong\u003e(C)(D) \u003c/strong\u003eRelationship between C-peptide level and pancreas volume. C-peptide change (%) was obtained by C-peptide level at each time point ÷ preoperative C-peptide level. Postoperative change of C-peptide level was 63.6%, 66.2% and 72.5% in PD the group; 52.6%, 64.4% and 71.0% in the DP group at 3-month, 1-year, and 2-year follow-up respectively\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/3cd8b262c98d66c2fc0ce601.png"},{"id":102235581,"identity":"753d41f0-f0aa-4b4f-9357-74a6acd296a8","added_by":"auto","created_at":"2026-02-09 16:17:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2326993,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/ecc408e2-82f1-4c78-bd85-bf11972677e2.pdf"},{"id":89672517,"identity":"c7a60e08-fbf5-4168-8a72-2a5148129718","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":19547,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/219be016e88c3e2a66d06be5.docx"},{"id":89672526,"identity":"acd5aa1f-cbf5-43ac-8814-b20d0ca7ae0c","added_by":"auto","created_at":"2025-08-22 13:09:33","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":81365,"visible":true,"origin":"","legend":"","description":"","filename":"Supplemetaryfigure1figureandlegend.docx","url":"https://assets-eu.researchsquare.com/files/rs-7219476/v1/ea0102d16f9db2710d19671b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Volume and Functional Changes of Remnant Pancreas After Different Types of Pancreatectomy: Exploring the Regenerative Potential","fulltext":[{"header":"Summary Box ","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eWhat is already known about this subject?\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;Postoperative changes in remnant pancreatic volume are not well characterized, and the effects of pancreatectomy on glucose metabolism remain inconsistently reported in previous studies.\u003c/p\u003e\n\u003col start=\"2\" type=\"1\"\u003e\n \u003cli\u003eWhat are the new findings?\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp; This study reveals contrasting volumetric trends after different types of pancreatectomy:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eDistal pancreatectomy (DP) is associated with volume increase in the remnant pancreatic head, especially in cases with splenic preservation.\u003c/li\u003e\n \u003cli\u003ePancreaticoduodenectomy (PD) results in progressive atrophy of the remnant pancreatic tail, primarily linked to pancreaticojejunostomy stricture and subsequent ductal obstruction.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eDespite the hypertrophic changes seen in the DP group, new-onset diabetes occurred more frequently than in the PD group. This is likely due to the loss of islet-rich distal pancreatic tissue, highlighting that volume gain in the remnant head does not fully restore endocrine function.\u003c/p\u003e\n\u003col start=\"3\" type=\"1\"\u003e\n \u003cli\u003eHow might it impact on clinical practice in the foreseeable future\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp; Surgical techniques that optimize long-term endocrine function should be prioritized. These include:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eEnsuring patency of the pancreaticojejunostomy to avoid remnant atrophy in PD.\u003c/li\u003e\n \u003cli\u003ePreserving the spleen and its vasculature in DP to enhance remnant pancreatic viability.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eGiven the rising importance of long-term metabolic outcomes, preventing postoperative diabetes should be an integral part of surgical planning.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003ePancreatectomy is a standard treatment for several indications, such as pancreatic adenocarcinoma, pancreatic adenoma, pancreatic cysts, and chronic pancreatitis. There are two primary surgical methods of pancreatectomy, pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), depending on the location and extent of the pancreatic lesion. Pancreatectomy is much safer nowadays; the mortality rate of PD has even decreased to 0% ~ 5% in high volume medical centers\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. The improvement of survival rate after pancreatectomy had raised the consideration of long-term metabolic consequences.\u003c/p\u003e\u003cp\u003ePancreas is an important digestive organ comprising two major components: endocrine glands to regulate metabolism and exocrine glands to secrete digestive enzymes.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e Islets of Langerhans is a cluster of endocrine cell, only account for 1\u0026ndash;2% of pancreas parenchyma but play a critical role in glucose regulation.\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e Furthermore, β cells make up 50\u0026thinsp;~\u0026thinsp;70% of the cells in pancreatic islets that synthesize and secrete insulin to control glucose metabolism.\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e The loss of pancreatic parenchyma after pancreatectomy would lead to deterioration of glucose homeostasis due to decrease of β cells amount. Some studies have shown that glucose levels start to rise when β cells mass is reduced more than 50% compared with normal.\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e About 5\u0026ndash;10% of diabetes mellitus cases are related to pancreatic diseases in the Western country.\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e Those new-onset diabetes mellitus after pancreatectomy is now defined as pancreatogenic diabetes mellitus (Type 3c DM).\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eUnlike the well-documented regenerative capability of the liver after major hepatectomy, the capacity for pancreatic regeneration following pancreatectomy remains controversial. This raises the question of whether changes in pancreatic volume after pancreatectomy also correlate with functional recovery of the pancreas. In mice and rats, 90% pancreatectomy can induce ductal cell proliferation and upregulate embryonic gene expression, such as Pdx1, Ngn3, and Ptf1a in mature duct cells, to promote the regenerative process.\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e However, the regenerative capability of the pancreas is decreased with age and limited in adult rats.\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e Similarly, previous observation from children suggested tissue regeneration after near-total pancreatectomy,\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e but the capacity for pancreatic regeneration is absent in adult humans.\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e You et al reported that the remnant pancreas atrophied significantly at long-term follow-up after PD.\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e However, until now, there is no study on volume change of the remnant pancreas after DP. Embryonically, the head pancreas and distal pancreas (neck, body, and tail) are derived from the different origin. \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e Hence, we conjecture the different parts of the pancreas may display different regenerative capabilities. Although the deterioration of glucose homeostasis after pancreatectomy had been demonstrated, \u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e restoration of endocrine functions after different procedures remains unclear. Therefore, in this study, we tried to compare the long-term changes in pancreatic volume and endocrine function between PD and DP, and to investigate whether postoperative volume changes correlate with endocrine function recovery and explore the regenerative potential.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and participants\u003c/h2\u003e\u003cp\u003eThis is a single-institutional, non-randomized, non-experimental, prospective study. This study was approved by the Institutional Review Board of the National Cheng Kung University Hospital with approval number of \u003cb\u003eB-ER-108-312\u003c/b\u003e. All methods were performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki and institutional ethical guidelines for human research. We enrolled the patients from January 2009 to December 2017, who underwent pancreatectomy, including pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), for a variety of disorders at the National Cheng Kung University Hospital. The criteria for enrollment were those patients who had received pancreatectomy, PD or DP, and disease-free survival for more than 2 years if those patients with malignant pathology. Patient characteristics were analyzed, such as sex, body mass index, the pathologic diagnosis, surgical method, neoadjuvant chemotherapy, and preoperative glucose metabolic status. Perioperative comorbidities were also included in this assessment: preoperative pancreatitis, obstructive jaundice, and postoperative pancreatic duct obstruction. Additionally, part of the patients undergoing DP had spleen preservation, and we also compared the outcome between the group with or without spleen preservation. In those enrolled patients, they were received regular follow-up with examination of abdominal computed tomography, 3 months, 12 months, and 24 months after operation for benign pancreatic diseases and 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months after operation for malignant pancreatic diseases. Standard demographic and clinical data are obtained from medical records. Fasting blood sugar and HbA\u003csub\u003e1\u003c/sub\u003eC were also checked every 3 months. In this study, diabetes mellitus was defined as a fasting blood glucose level\u0026thinsp;\u0026gt;\u0026thinsp;126 mg/dl, or random blood glucose level\u0026thinsp;\u0026gt;\u0026thinsp;200 mg/dl, or HbA\u003csub\u003e1\u003c/sub\u003eC\u0026thinsp;\u0026gt;\u0026thinsp;6.5%, or the use of oral antidiabetic agents or insulin injection. Pancreatic duct dilatation was defined according to the diameter of pancreatic duct\u0026thinsp;\u0026gt;\u0026thinsp;3 mm.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eFor the concordance of data, we decided to collect abdominal computed tomography (CT) scan before the operation, and at 3 months, 1 year, and 2 years postoperatively to determine the volume change of the remnant pancreas after pancreatectomy. Also, laboratory data, including HbA1C, C-peptide, was analyzed at the same time points: before the operation, and at 3 months, 1 year, and 2 years postoperatively to evaluate the impact of pancreatectomy on glucose homeostasis and insulin secretion. Ultimately, we further analyzed the relationship between glucose homeostasis, insulin secretion, and the volume of remnant pancreas.\u003c/p\u003e\n\u003ch3\u003eImage/CT volumetry\u003c/h3\u003e\n\u003cp\u003eINFINITT PACS medical image processing software (INFINITT Healthcare Co., Ltd, Korea) was used to analyze the results of CT scan. The volumetry of the original pancreas and remnant pancreatic tissue was assessed by CT scan preoperatively and at 3 months, 1 year and 2 years postoperatively. Serial axial images were obtained at 3 mm intervals from the lung base to the pelvis with intravenous contrast enhancement. The total volume of the pancreas parenchyma was computed by summing the pancreas volume (mm3) of each section. Pancreas volume (mm3) of each section\u0026thinsp;=\u0026thinsp;Area of pancreas (mm2) \u0026times; Height of each slice (3mm). The area of the pancreas parenchyma in each slice was carefully outlined, excluding the major vessels, and pancreatic tumor (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA-D). Of note, there is a significant difference between the actual pancreas volumes (ml) of each patient. To minimize this difference, the results of volumetry were presented in two fashions: 1. Residual volume (V%): the ratio of the remnant volume of pancreas to volume of pre-operative pancreas\u0026thinsp;=\u0026thinsp;the volume of the remnant pancreas (ml)\u0026thinsp;\u0026divide;\u0026thinsp;the volume of the preoperative whole pancreas (ml);2. Volume change of the residual pancreas (V change %): The ratio of the remnant volume of pancreas to the volume of initial residual pancreas\u0026thinsp;=\u0026thinsp;the volume of the remnant pancreas (ml)\u0026thinsp;\u0026divide;\u0026thinsp;the volume of presumed initial residual pancreas (ml).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eContinuous variables, such as age, were provided as mean value\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error (SE) and range; BMI were presented as mean value\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error (SE). Continuous variables with normal distribution in each group were compared by an independent t-test; continuous variables without normal distribution were compared by Wilcoxon rank sum test. Categorical variables were tested with χ2 test and Fisher's exact test. The Generalized Estimating Equations (GEE) was applied for the analysis of repeated measurements or other related variables.\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e A logistic regression model was applied to analyze the relationship between a binary outcome and a group of predictor variables. The correlation between two groups of continuous variables was analyzed with Spearman's rank correlation coefficient. All the statistical analysis was performed with the SAS 9.4 statistical software (SAS Institute Inc. Cary, NC, USA). All tests were two-tailed, and p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered as statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe details of clinicopathologic characteristics and postoperative change of diabetic status of enrolled patients in this study were listed in Table 1. There were 90 and 45 patients in the PD and DP groups, respectively. Among them, 66 (73.3%) in PD, and 20 (44.4%) in DP received pancreatectomy due to malignancy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe remnant pancreas hypertrophied in the DP group, but atrophied in the PD group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn DP group, mean of the pre-operative volume of pancreas was 55.51 \u0026plusmn; 2.98ml (range: 19.26 - 121.42 ml). Initial residual volume (V%) in the DP group was 67.93% \u0026plusmn; 1.97% (range 41.6% - 91.43%). In PD group, mean of the pre-operative volume of pancreas was 58.83 \u0026plusmn; 2.63 ml (range 10.39 - 128.55 ml). Initial residual volume (V%) in the PD group was 51.20% \u0026plusmn; 1.62% (range 13.31% - 85.76%). There was no significant difference in the initial residual volume (V%) between the PD and DP groups (p=0.274).\u003c/p\u003e\n\u003cp\u003eThe volume of remnant pancreas demonstrated hypertrophic changes in the DP group (Figure 2A) but showed progressive atrophy in the PD group during follow-up (Figure 2B). The volumetric changes of the remnant pancreas in the DP group were 106.25% \u0026plusmn; 2.09% at 3 months, 106.62% \u0026plusmn; 3.27% at 1 year, and 110.43% \u0026plusmn; 4.10% at 2 years (\u0026beta; = 2.97, p=0.019) (Figure 2C). In contrast, the volumetric changes of the PD group at 3 months, 1 year and 2 years were 80.79% \u0026plusmn; 2.86%, 68.67% \u0026plusmn; 2.58%, and 65.34% \u0026plusmn; 2.98% respectively (\u0026beta; = -11.85, p\u0026lt;0.001) (Figure 2C). The result from GEE analysis demonstrated that the DP group had significant hypertrophic changes in the remnant pancreas compared to the PD group (\u0026beta; =5.43, p=0.014) (Figure 2C).\u003c/p\u003e\n\u003cp\u003eThe incidence of hypertrophy in the PD group declined over time. Only 17.78%, 12.22%, and 10.53% PD patients exhibited hypertrophic changes in remnant pancreatic tissue at 3 months, 1 year, and 2 years of follow-up, respectively. In comparison, the DP group showed a higher incidence of hypertrophy. The proportion of patients with hypertrophic changes in the DP group increased over time, with 66.7%, 71.1%, and 73.5% of patients demonstrating tissue hypertrophy at 3 months, 1 year, and 2 years of follow-up, respectively (Figure 2D).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFactors associated with volumetric changes in remnant pancreas\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn PD group, we analyzed the relationship among several relevant variables and the residual volume change. The results showed that pancreatic duct dilatation is the most significant factor related to the atrophic change of remnant pancreas (Supplementary Table 1). In PD group with postoperative pancreatic duct dilatation, the change of volume in the remnant pancreas compared to initial residual pancreas was 77.69%, 58.60% and 53.89% at 3-month, 1 year and 2 years follow-up respectively. In contrast, the volume change of remnant pancreas in the PD patients without postoperative pancreatic duct dilatation which compared to initial residual pancreas were 90.92%, 86.23% and 85.26% at 3-month, 1-year and 2-year follow-up respectively (Figure 3). These results demonstrated that more severe atrophy occurred in the patients with pancreatic duct dilatation at 1 year and 2 years postoperatively (\u0026beta; = -9.82, p = 0.027) (Figure 3).\u003c/p\u003e\n\u003cp\u003eOn the other hand, the factor, \u0026quot;spleen preservation\u0026quot;, may positively correlate with the degree of hypertrophic changes in the DP group (Supplementary Table 2). We noticed that the volume change of remnant pancreas in the DP patients with and without spleen preservation was 124.55% and 102.74% at 1-year follow-up (p = 0.006), and 120.08% and 107.92% at 2-year follow-up (p = 0.177) respectively (Figure 4). Although the difference at 2-year follow-up is not significant due to increasing missing data, these findings indicated that DP patients with spleen preservation demonstrated more pronounced hypertrophic changes than those without spleen preservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHigher incidence of new onset DM in the DP group than the PD group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the DP group (n=45), 21 patients were diagnosed with diabetes mellitus preoperatively and none of these patients had remission in diabetes mellitus after surgery. Among the non-diabetic patients (n=24), 8 out of 24 (33.3%) patients were diagnosed with new-onset diabetes mellitus (Table 1). In the PD group (n=90), 24 patients were diagnosed with diabetes mellitus preoperatively and 7 of 24 (29.2%) patients had remission in diabetes mellitus after surgery. Among the non-diabetic patients (n=66), 15 out of 66 (22.7%) patients were diagnosed with new-onset diabetes mellitus (Table 1). These results indicated that the DP group had a higher incidence of new-onset DM than PD group, although the difference was not statistically significant (p = 0.115). More important, we found that the remission of preoperative DM after pancreatectomy only occurred in the PD group (Table 1). Furthermore, most of new-onset DM occurred within 1 year postoperatively, especially between 3 months and 1 year (Supplementary Table 3).\u003c/p\u003e\n\u003cp\u003eTo further define the possible factors involved in the postoperative new-onset DM, we analyze the association between several perioperative clinical variables and the occurrence of new-onset DM. The results of univariate logistic regression demonstrated that there was no statistically significant relationship between any single variable and the occurrence of new-onset DM (Supplementary Table 4). Similarly, the results of univariate logistic regression also demonstrated that neither pancreas volume nor C-peptide level shows significant correlation with the occurrence of new-onset DM. (Supplementary Table 5). These results implied that the occurrence of pancreatogenic DM may be multifactorial. Both C-peptide level and pancreas volume cannot individually be a predictor for new-onset DM.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe impact on endocrine function after pancreatectomy was more severe in the DP group\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the PD group, the mean value of C-peptide level before the operation was 3.06 ng/ml and declined to 1.54 ng/ml in the 3-month follow-up (p \u0026lt; 0.001) (Fig.5A). Consistently, the mean value of C-peptide level before the operation in the DP group was 2.49 ng/ml and declined to 1.15 ng/ml in the 3-month follow-up (p \u0026lt;0.001) (Fig.5B). These results demonstrated that loss of pancreas parenchyma leads to decrease in insulin production significantly. Additionally, the mean value of C-peptide level is slightly increased during 3-months to 2-years follow-up in both PD and DP groups (Fig. 5A, B), even though the remnant pancreas in the PD group atrophied over time.\u003c/p\u003e\n\u003cp\u003eThe correlation between C-peptide level change and residual pancreatic tissue volume indicated that the change of C-peptide level is not positively correlated with residual pancreatic tissue volume during the whole follow-up (Supplementary Figure 1). It meant the amount of insulin production after pancreatectomy was not correlated with the pancreas volume. Interestingly, we compared the residual volume (V%) with the change of C-peptide level (C-peptide level at each time point \u0026divide; preoperative C-peptide level, %) in both groups (Figure 5C, D). The results showed that C-peptide level declined more in the DP group than in the PD group, although the pancreas volume increased in the DP group. Postoperative change of C-peptide level was 63.6%, 66.2% and 72.5% in PD group; 52.6%, 64.4% and 71.0% in DP group at 3-month, 1-year, and 2-year follow-up respectively (Figure 5C, D). These results implied that the impact of the pancreas parenchyma loss on insulin secretion was more significant in the DP group.\u003c/p\u003e\n\u003cp\u003eIn consideration of the difference in the remnant pancreas volume among each case, we compared the insulin production in the DP and PD groups via calculating the ratio of the C-peptide level to the volume of remnant pancreas. The relationship between surgery types and postoperative change of C-peptide level was analyzed by GEE. As shown in Table 2, the postoperative C-peptide level in both PD and DP groups increased over time (\u0026beta; =16.33, p = 0.001). More importantly, the PD group had better insulin production and restoration of \u0026beta;-cell secretory capacity than the DP group (\u0026beta; =13.26, p = 0.016) (Table 2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first to systematically compare both long-term changes in pancreatic volume and endocrine function following pancreaticoduodenectomy (PD) and distal pancreatectomy (DP). Two key findings emerged from our analysis: First, despite opposite trends in remnant pancreas volume changes - atrophy in PD and hypertrophy in DP - both groups demonstrated similar patterns of partial endocrine function recovery over time, suggesting that \u0026beta;-cells possess compensatory capacity through enhanced secretory function rather than volume hypertrophy. Second, the anatomical location of resection proves more critical than the volume of tissue removed in determining postoperative endocrine dysfunction. DP patients experienced both greater C-peptide decline and higher incidence of new-onset diabetes mellitus than PD patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe improvement of survival rate after pancreatectomy in recent decades promotes the consideration of long-term metabolic consequences. Several studies have also shown that glucose levels start to rise when \u0026beta; cells mass is reduced more than 50% of normal.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[4, 5, 14]\u003c/sup\u003e As the report by\u0026nbsp;Shirakawa et al,\u003csup\u003e[15]\u003c/sup\u003e current study found that greater resection of pancreatic tissue would increase the incidence of new-onset pancreatogenic diabetes. But we also found the atrophic change of remnant pancreas developed and the volume of the remnant pancreas was not associated with pancreatogenic diabetes in PD patients as reported by You \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e[11]\u003c/sup\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eMost importantly, we first demonstrated hypertrophic changes in the remnant pancreas after DP, yet these patients paradoxically showed higher incidence of new-onset pancreatogenic diabetes \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, pancreatic duct dilatation was the major factor associated with the volume atrophy of the remnant pancreas in PD patients. Pancreatic duct dilatation resulted from pancreaticojejunostomy (PJ) anastomosis stricture was a common complication in long term follow-up. Murakami \u003cem\u003eet al.\u003c/em\u003e reported that the rate of pancreatic duct dilatation after PD was 33.3% at one year following surgery and higher atrophy rate of remnant pancreas in patients with postoperative pancreatic duct dilatation.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[16]\u003c/sup\u003e In our study, the rate of pancreatic duct dilatation in the second year was 27.6% (21 of 76 patients). Furthermore, those patients with pancreatic duct dilatation would have more severe atrophy of the remnant pancreas. PJ anastomosis stricture is the major cause of postoperative acute and chronic pancreatitis in humans and associated with morphological and functional changes later.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[17]\u003c/sup\u003e Watanabe et al. also proved that ligation of mice pancreatic duct induced degeneration and apoptosis of the pancreatic acinar cells, but he didn\u0026rsquo;t find the same phenomenon in the endocrine cells.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[18]\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOn the other hand, most of the remnant pancreas (73.5%) in the DP group had a hypertrophic change at 2-years follow-up, especially in those patients received spleen-preservation distal pancreatectomy. The splenic artery and splenic vein are preserved in the spleen preservation surgery at our hospital and the preservation of splenic vessel provides a better blood supply to the remnant head portion pancreas. Besides the blood supply issue, spleen had been proven to contain Hox11-expressing splenic stem cells, which could be applied widely as cell therapy for organ regeneration in the pancreas, heart, bone, salivary gland, and brain.\u003csup\u003e[19]\u003c/sup\u003e Hou \u003cem\u003eet al\u003c/em\u003e reported that the spleen-derived mesenchymal stem cells would promote pancreas cell regeneration and ameliorated pancreas dysfunction in an animal model of acute pancreatitis.\u003csup\u003e[20]\u003c/sup\u003e\u003cstrong\u003e\u003csup\u003e\u0026nbsp;\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003eCurrent development of laparoscopic technique improves the accessibility of the spleen and splenic vessels-preserving distal pancreatectomy. Hence, distal pancreatectomy with preservation of spleen and splenic vessels is a better choice based on the point of enhancing pancreas regeneration.\u003c/p\u003e\n\u003cp\u003eThe occurrence of new-onset DM is about 14.5% - 22.2% of the PD patients.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[21]\u003c/sup\u003e Nonetheless, the recent study reported that 30.7% - 65% of patients had remission of DM after pancreaticoduodenectomy.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[22]\u003c/sup\u003e Similarly, our results showed 29.2% of patients with preoperative DM in the PD group had remission of DM after PD within 2-year follow-up.\u0026nbsp;The possible reason for the amelioration of diabetes after PD is that the pancreatic\u0026nbsp;\u0026alpha;-cells and F-cells producing glucagon and pancreatic polypeptide (PP) are predominantly distributed in the head portion.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[23]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eReduction of\u0026nbsp;\u0026alpha;-cells and F-cells due to PD diminished secretion of glucagon and pancreatic polypeptide (PP) and inhibit hepatic gluconeogenesis. Additionally, current evidence indicated that PDAC releasing paraneoplastic substance would cause suppression of \u0026beta;-cell function and peripheral insulin resistance.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[24]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eResection of PDAC may benefit the blood sugar control.\u003c/p\u003e\n\u003cp\u003eHirata \u003cem\u003eet al.\u003c/em\u003e had proposed several predictors for worsening DM after PD, such as malignancy, long-standing DM, and BMI \u0026gt;25 in preoperative non-diabetic patients.\u003csup\u003e[25]\u003c/sup\u003e However, all of these factors did not show any significant correlation with new-onset DM in our study. Why there are contradictory reports on the new-onset or remission of DM after PD? As reported by You\u003csup\u003e[11]\u003c/sup\u003e and Watanabe\u003csup\u003e[18]\u003c/sup\u003e, severe remnant pancreas atrophy associated with exocrine degeneration by pancreaticojejunostomy stricture, we propose that the long-term intraductal pressure might further induce malfunction of endocrine cell to cause deterioration of glucose metabolism.\u0026nbsp;Apart from diminishing \u0026beta;-cell function, duodenum also plays an important role in glucose metabolism by secreting gastric-inhibitor peptide (GIP) and glucagon-like peptide (GLP) and stimulates postprandial insulin secretion.\u003csup\u003e[26]\u003c/sup\u003e Duodenectomy may compromise enteroinsular axis and deteriorate insulin and blood glucose regulation.\u003c/p\u003e\n\u003cp\u003eA recent systemic review reported that the overall incidence of new-onset DM was 39% in the patients undergoing DP for chronic pancreatitis and 14% in the patients undergoing DP for the benign or malignant lesion.\u003csup\u003e[27]\u003c/sup\u003e In our study, 8 out of 24 (33.3%) patients were diagnosed with new-onset diabetes mellitus after DP, and the incidence of new-onset DM was much higher than that in the PD group. Also, no preoperative independent predictor for new-onset DM after DP was found in our study. Shirakawa \u003cem\u003eet al.\u003c/em\u003e claimed the resected volume \u0026gt; 40% was an independent predictor for new-onset DM in the DP patients.\u003csup\u003e[15]\u003c/sup\u003e Sakata \u003cem\u003eet al\u003c/em\u003e reported the smaller residual volume of the pancreas in the patient with high incidence of new-onset DM. Nonetheless, we and several current studies suggested the same conclusion that the volume of the remnant pancreas was not associated with new-onset DM.\u003csup\u003e[4, 11]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003eThe\u0026nbsp;possible explanation is better digestion and nutrition status in the DP group than the PD group.\u003csup\u003e[28]\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eC-peptide is used to evaluate insulin production by the \u0026beta; cells in the pancreas and reflected \u0026beta;-cell function indirectly. In our study, we found that the concentration of C-peptide decreased with the loss of pancreas parenchyma at first. However, the C-peptide level increased at both groups during 1-year and 2-year follow-up, even though residual volume of the pancreas was decreased in the PD group. Our results also demonstrated that the postoperative change in C-peptide level (%) was not correlated with the remnant pancreas volume (%) during the follow-up. Furthermore, in the DP group, C-peptide reduction exceeded the magnitude of volume loss, while PD group showed less C-peptide decline despite greater volume decrease. This phenomenon suggests that the influence of pancreas parenchyma loss on endocrine function was more significant in the distal pancreas than in the head pancreas. The \u0026beta;-cells density is about two times higher in the pancreas tail than in the head region.\u003csup\u003e[29]\u003c/sup\u003e As a result, distal pancreatectomy will cause a more significant impact on insulin secretion. Besides, in rodent model, it had shown that islets originating from the dorsal bud, forming pancreas body and tail, had a greater capacity to secrete insulin than islets of ventral bud, which forms the uncinated process and lower part of the pancreas head.\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003csup\u003e[30]\u003c/sup\u003e Our data clearly showed\u0026nbsp;the PD group had a better restoration of the secretory capacity of \u0026beta;-cells.\u0026nbsp;Thus, the metabolic impact due to removal of the partial pancreas should be more significant in the DP than in the PD.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, while this is a single-institution study with relatively small sample size which may introduce bias. However, our unique long-term follow-up data tracking both volumetric and functional changes would be difficult to obtain in a multi-center setting. Second, although we used C-peptide to assess \u0026beta;-cell function, blood glucose levels can influence insulin secretion, potentially masking true \u0026beta;-cell dysfunction. The C-peptide index (CPI), which normalizes C-peptide to concurrent glucose levels, would offer a more precise evaluation of \u0026beta;-cell function. Nevertheless, our study is one of the few with long-term C-peptide follow-up data, providing valuable evidence for this research topic. Additionally, although data on HOMA-IR were not available to explore insulin resistance and further investigate the cause of DM, this limitation did not affect our study conclusions. Future studies should incorporate these parameters to gain a more detailed understanding of the metabolic consequences of pancreatectomy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe demonstrated distinct volumetric changes after pancreatectomy: atrophy in PD patients but hypertrophy in DP patients. Paradoxically, DP patients had higher incidence of new-onset diabetes despite better volume preservation, suggesting that anatomical location is more critical than remnant volume for endocrine function. Our findings also highlight the importance of surgical skills to prevent postoperative stricture of pancreaticojejunostomy and to preserve splenic vessels and spleen to optimize volumetric changes of remnant pancreas.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics\u0026nbsp;approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIRB approved by the Institutional Review Board of the National Cheng Kung University Hospital with approval number of \u003cstrong\u003eB-ER-108-312\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the retrospective nature of this study and the use of de-identified patient data, the Institutional Review Board of the National Cheng Kung University Hospital waived the requirement for informed consent for study participation. All patient data were completely anonymized prior to analysis, and no identifying information was included in the study dataset or manuscript. The waiver of informed consent was approved as part of the ethical review process under approval number B-ER-108-312.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData\u0026nbsp;availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used in the study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWH Lu: performance the analysis and writing the manuscript, HM Tsai: instruction to perform volume calculation, TK Liao, PJ Su, CJ Wang and YJ Chao: assisting in collect cases for study, YS Shan: initiate the study idea and instruction for perform the analysis, supervise and revise in writing the manuscript, and submit the manuscript\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe grant was supported by Taiwan Ministry of Science and Technology (MOST 108-2321-B-006-014), Ministry of Healthy and Welfare (MOHW 107-TDU-B-212-114026A), and HSU-YUAN Education Foundation (HY-2018-001)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of\u0026nbsp;interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eD J Gouma , R C van Geenen, T M van Gulik, et al., \u003cem\u003eRates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volume.\u003c/em\u003e Ann Surg, 2000. \u003cstrong\u003e232\u003c/strong\u003e(6): p. 786-95.\u003c/li\u003e\n\u003cli\u003eHoang Do, O. and P. Thorn, \u003cem\u003eInsulin secretion from beta cells within intact islets: location matters.\u003c/em\u003e Clin Exp Pharmacol Physiol, 2015. \u003cstrong\u003e42\u003c/strong\u003e(4): p. 406-14.\u003c/li\u003e\n\u003cli\u003eJunghyo Jo, Manami Hara, Ulf Ahlgren, Robert Sorenson, Vipul Periwal, \u003cem\u003eMathematical models of pancreatic islet size distributions.\u003c/em\u003e Islets, 2012. \u003cstrong\u003e4\u003c/strong\u003e(1): p. 10-9.\u003c/li\u003e\n\u003cli\u003eKumar, A.F., R.W. Gruessner, and E.R. Seaquist, \u003cem\u003eRisk of glucose intolerance and diabetes in hemipancreatectomized donors selected for normal preoperative glucose metabolism.\u003c/em\u003e Diabetes Care, 2008. \u003cstrong\u003e31\u003c/strong\u003e(8): p. 1639-43.\u003c/li\u003e\n\u003cli\u003eB A Menge, H Schrader, T G K Breuer, et al., \u003cem\u003eMetabolic consequences of a 50% partial pancreatectomy in humans.\u003c/em\u003e Diabetologia, 2009. \u003cstrong\u003e52\u003c/strong\u003e(2): p. 306-17.\u003c/li\u003e\n\u003cli\u003eEwald, N. and P.D. Hardt, \u003cem\u003eDiagnosis and treatment of diabetes mellitus in chronic pancreatitis.\u003c/em\u003e World J Gastroenterol, 2013. \u003cstrong\u003e19\u003c/strong\u003e(42): p. 7276-81.\u003c/li\u003e\n\u003cli\u003eWan-Chun Li , J Michael Rukstalis, Wataru Nishimura, et al., \u003cem\u003eActivation of pancreatic-duct-derived progenitor cells during pancreas regeneration in adult rats.\u003c/em\u003e J Cell Sci, 2010. \u003cstrong\u003e123\u003c/strong\u003e(Pt 16): p. 2792-802.\u003c/li\u003e\n\u003cli\u003eHitoshi Takahashi, Daiki Okamura, Marlene E Starr, Hiroshi Saito, B Mark Evers, \u003cem\u003eAge-dependent reduction of the PI3K regulatory subunit p85alpha suppresses pancreatic acinar cell proliferation.\u003c/em\u003e Aging Cell, 2012. \u003cstrong\u003e11\u003c/strong\u003e(2): p. 305-14.\u003c/li\u003e\n\u003cli\u003eTeresa Berrocal, Arturo Alvarez Luque, Inmaculada Pinilla, Luis Lassaletta, \u003cem\u003ePancreatic regeneration after near-total pancreatectomy in children with nesidioblastosis.\u003c/em\u003e Pediatr Radiol, 2005. \u003cstrong\u003e35\u003c/strong\u003e(11): p. 1066-70.\u003c/li\u003e\n\u003cli\u003eBjoern A Menge, Andrea Tannapfel, Orlin Belyaev, et al., \u003cem\u003ePartial pancreatectomy in adult humans does not provoke beta-cell regeneration.\u003c/em\u003e Diabetes, 2008. \u003cstrong\u003e57\u003c/strong\u003e(1): p. 142-9.\u003c/li\u003e\n\u003cli\u003eDong-Do You, Seong-Ho Choi, Dong-Wook Choi, Jin-Seok Heo, Cheon-Yu Ho, Woo-Seok Kim, et al., \u003cem\u003eLong-term effects of pancreaticoduodenectomy on glucose metabolism.\u003c/em\u003e ANZ J Surg, 2012. \u003cstrong\u003e82\u003c/strong\u003e(6): p. 447-51.\u003c/li\u003e\n\u003cli\u003eWerlin, S.L. and P.C. Lee, \u003cem\u003eChapter 114 - Development of the Exocrine Pancreas\u003c/em\u003e, in \u003cem\u003eFetal and Neonatal Physiology (Third Edition)\u003c/em\u003e, R.A. Polin, W.W. Fox, and S.H. Abman, Editors. 2004, W.B. Saunders. p. 1142-1151.\u003c/li\u003e\n\u003cli\u003eZeger, S.L. and K.Y. Liang, \u003cem\u003eLongitudinal data analysis for discrete and continuous outcomes.\u003c/em\u003e Biometrics, 1986. \u003cstrong\u003e42\u003c/strong\u003e(1): p. 121-30.\u003c/li\u003e\n\u003cli\u003eAlexandra E Butler, Juliette Janson, Susan Bonner-Weir, Robert Ritzel, Robert A Rizza, Peter C Butler, \u003cem\u003eBeta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes.\u003c/em\u003e Diabetes, 2003. \u003cstrong\u003e52\u003c/strong\u003e(1): p. 102-10.\u003c/li\u003e\n\u003cli\u003eSachiyo Shirakawa, Ippei Matsumoto, Hirochika Toyama, et al., \u003cem\u003ePancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy.\u003c/em\u003e J Gastrointest Surg, 2012. \u003cstrong\u003e16\u003c/strong\u003e(12): p. 2212-9.\u003c/li\u003e\n\u003cli\u003eMakoto Murakami, Katayama Kanji, Shigeru Kato,et al., \u003cem\u003eClinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy following pancreatoduodenectomy.\u003c/em\u003e Surg Today, 2017. \u003cstrong\u003e47\u003c/strong\u003e(5): p. 581-586.\u003c/li\u003e\n\u003cli\u003eJ R Lowes, J Rode, W R Lees, R C Russell, P B Cotton, \u003cem\u003eObstructive pancreatitis: unusual causes of chronic pancreatitis.\u003c/em\u003e Br J Surg, 1988. \u003cstrong\u003e75\u003c/strong\u003e(11): p. 1129-33.\u003c/li\u003e\n\u003cli\u003eS Watanabe, K Abe, Y Anbo, H Katoh, \u003cem\u003eChanges in the mouse exocrine pancreas after pancreatic duct ligation: a qualitative and quantitative histological study.\u003c/em\u003e Arch Histol Cytol, 1995. \u003cstrong\u003e58\u003c/strong\u003e(3): p. 365-74.\u003c/li\u003e\n\u003cli\u003eDenise L Faustman, Claudia Giesecke, Miriam Davis, et al., \u003cem\u003eDisposable No Longer: The Spleen Holds a Reservoir of Stem Cells.\u003c/em\u003e Journal of Stem Cell Research \u0026amp; Therapy, 2014. \u003cstrong\u003e4\u003c/strong\u003e(7)\u003c/li\u003e\n\u003cli\u003eYa-Chin Hou, Chen-Fang Huang, Hao-Chen Wang, Yu Wu, Yan-Shen Shan, \u003cem\u003eTherapeutic Efficacy of Spleen-Derived Mesenchymal Stem Cells in Mice with Acute Pancreatitis.\u003c/em\u003e Journal of Stem Cell Research \u0026amp; Therapy, 2015. \u003cstrong\u003e5\u003c/strong\u003e(12)\u003c/li\u003e\n\u003cli\u003eHans G Beger, Bertram Poch, Benjamin Mayer, Marco Siech, \u003cem\u003eNew Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results.\u003c/em\u003e Ann Surg, 2018. \u003cstrong\u003e267\u003c/strong\u003e(2): p. 259-270.\u003c/li\u003e\n\u003cli\u003eMee Joo Kang, Hye Seung Jung, Jin-Young Jang, et al., \u003cem\u003eMetabolic effect of pancreatoduodenectomy: Resolution of diabetes mellitus after surgery.\u003c/em\u003e Pancreatology, 2016. \u003cstrong\u003e16\u003c/strong\u003e(2): p. 272-7.\u003c/li\u003e\n\u003cli\u003eE H Eddes, A M Masclee, H G Gooszen, M Fr\u0026ouml;lich, C B Lamers, \u003cem\u003eEffect of duodenum-preserving resection of the head of the pancreas on endocrine and exocrine pancreatic function in patients with chronic pancreatitis.\u003c/em\u003e Am J Surg, 1997. \u003cstrong\u003e174\u003c/strong\u003e(4): p. 387-92.\u003c/li\u003e\n\u003cli\u003eRaghuwansh P Sah, Sajan Jiv Singh Nagpal, Debabrata Mukhopadhyay, Suresh T Chari, \u003cem\u003eNew insights into pancreatic cancer-induced paraneoplastic diabetes.\u003c/em\u003e Nat Rev Gastroenterol Hepatol, 2013. \u003cstrong\u003e10\u003c/strong\u003e(7): p. 423-33.\u003c/li\u003e\n\u003cli\u003eKeiichiro Hirata, Bunzo Nakata, Ryosuke Amano, Sadaaki Yamazoe, Kenjiro Kimura, Kosei Hirakawa, \u003cem\u003ePredictive factors for change of diabetes mellitus status after pancreatectomy in preoperative diabetic and nondiabetic patients.\u003c/em\u003e J Gastrointest Surg, 2014. \u003cstrong\u003e18\u003c/strong\u003e(9): p. 1597-603.\u003c/li\u003e\n\u003cli\u003eKreymann B, Williams G, Ghatei MA, Bloom SR, \u003cem\u003eGlucagon-like peptide-1 7-36: a physiological incretin in man.\u003c/em\u003e Lancet, 1987. \u003cstrong\u003e2\u003c/strong\u003e(8571): p. 1300-4.\u003c/li\u003e\n\u003cli\u003eDe Bruijn, K.M. and C.H. van Eijck, \u003cem\u003eNew-onset diabetes after distal pancreatectomy: a systematic review.\u003c/em\u003e Ann Surg, 2015. \u003cstrong\u003e261\u003c/strong\u003e(5): p. 854-61.\u003c/li\u003e\n\u003cli\u003eGilliland TM, Villafane-Ferriol N, Shah KP, et al., \u003cem\u003eNutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.\u003c/em\u003e Nutrients, 2017. \u003cstrong\u003e9\u003c/strong\u003e(3).\u003c/li\u003e\n\u003cli\u003eXiaojun Wang, Ryosuke Misawa, Mark C Zielinski, et al., \u003cem\u003eRegional differences in islet distribution in the human pancreas--preferential beta-cell loss in the head region in patients with type 2 diabetes.\u003c/em\u003e PLoS One, 2013. \u003cstrong\u003e8\u003c/strong\u003e(6): p. e67454.\u003c/li\u003e\n\u003cli\u003eE R Trimble, P A Halban, C B Wollheim, A E Renold, \u003cem\u003eFunctional differences between rat islets of ventral and dorsal pancreatic origin.\u003c/em\u003e J Clin Invest, 1982. \u003cstrong\u003e69\u003c/strong\u003e(2): p. 405-13.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"621\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 621px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003ePatient Characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePD\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 90 )\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 161px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 45 )\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003eAge (mean\u0026plusmn;SE), yrs (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e61\u0026plusmn;1.25 (25-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e58\u0026plusmn;2.06 (20-82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 206px;\"\u003e\n \u003cp\u003eSex (M:F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e56:34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e24:21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eBMI (mean\u0026plusmn;SE)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e23.8\u0026plusmn;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e24.8\u0026plusmn;0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.154\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePreoperative CRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.984\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePreoperative jaundice\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e40 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePreoperative pancreatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e20 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e7 (15.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePylorus-preserving PD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e72 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eLaparoscopic DP\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSpleen preservation*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e22 (48.9%)\u003c/p\u003e\n \u003cp\u003e8 (17.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.002\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eBenign\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e24 (26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e25 (55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eMalignancy\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Pancreatic ductal cancer\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Bile duct cancer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Ampullary cancer\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Duodenal cancer\u003c/p\u003e\n \u003cp\u003eNeuroendocrine cancer\u003c/p\u003e\n \u003cp\u003eMalignant IPMN\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Metastatic cancer\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e66 (73.3%)\u003c/p\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e20 (44.4%)\u003c/p\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003ePreoperative diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e24 (26.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e21 (46.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.033\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eNew onset post-OP DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e15 (22.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e8 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 206px;\"\u003e\n \u003cp\u003eResolution of pre-OP DM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e7 (29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 161px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.008\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 621px;\"\u003e\n \u003cp\u003eSE, standard error; M,\u0026nbsp;male; F, female; BMI, body mass index; CRT, chemoradiotherapy; PD, pancreatico-duodenectomy; DP, distal pancreatectomy; IPMN, intraductal papillary mucinous neoplasm; DM, diabetes mellitus; OP, operation\u003c/p\u003e\n \u003cp\u003e*: Spleen preservation: both splenic vessels and spleen were preserved during operation.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"419\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 419px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eRelationship between surgical treatment (PD or DP) and the ratio of the change of C-peptide level to the volume of remnant pancreas *\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 193px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGEE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eb\u003c/strong\u003e\u003cstrong\u003e\u0026plusmn;SE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eDP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e28.03\u0026plusmn;17.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e16.33\u0026plusmn;5.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.001\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment*Time (interaction)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003eDP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003ePD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e13.26\u0026plusmn;5.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;0.016\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 419px;\"\u003e\n \u003cp\u003e\u003csup\u003e*\u003c/sup\u003e the ratio of the change of C-peptide level to the volume of remnant pancreas was obtained by change of C-peptide level (%) \u0026divide; residual pancreas volume (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pancreaticoduodenectomy, Distal Pancreatectomy, Pancreatogenic Diabetes, C-peptide","lastPublishedDoi":"10.21203/rs.3.rs-7219476/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7219476/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThe evidence on the regeneration and functional changes of remnant pancreas after pancreatectomy is limited. Herein, we conducted a prospective study to investigate the correlation between changes in volume and endocrine function of the remnant pancreas.\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e\u003cp\u003ePatients undergoing pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) from Jan. 2009 to Dec. 2017 were included. Computed tomography was used to determine the volume of remnant pancreas at 3 months, 1 year, and 2 years after pancreatectomy. The postoperative changes of endocrine function were also assessed.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e\u003cp\u003eFinally, 90 PD patients and 45 DP patients were enrolled. The remnant pancreas volume at 3 months, 1 year and 2 years compared with initial residual pancreas were 80.79%, 68.67% and 65.34% respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in the PD patients; 106.25%, 106.62% and 110.43% (p\u0026thinsp;=\u0026thinsp;0.019) in the DP patients. The DP patients have higher incidence of new-onset diabetes than PD patients (33.3% vs. 22.7%). More P-duct dilatation with severe atrophy of the remnant pancreas (p\u0026thinsp;=\u0026thinsp;0.027) in the PD patients, while better volume preservation and growth (p\u0026thinsp;=\u0026thinsp;0.084) in the DP patients with spleen preservation. The changes of pancreas volume didn't correlate with postoperative new-onset DM. Interestingly, PD group had greater restoration of endocrine function than DP group based on secretion of C-peptide (β\u0026thinsp;\u0026plusmn;\u0026thinsp;SE: 13.26\u0026thinsp;\u0026plusmn;\u0026thinsp;5.50, p\u0026thinsp;=\u0026thinsp;0.016).\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e\u003cp\u003eRemnant pancreas exhibits distinct volumetric changes with significant volume increase in DP patients but progressive volume decreases in PD patients. Despite better volume preservation in DP group, the head portion of pancreas in PD group demonstrated superior β-cell function restoration, corresponding with lower incidence of new-onset diabetes.\u003c/p\u003e","manuscriptTitle":"Volume and Functional Changes of Remnant Pancreas After Different Types of Pancreatectomy: Exploring the Regenerative Potential","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-22 13:09:28","doi":"10.21203/rs.3.rs-7219476/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-26T00:19:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-24T11:38:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-22T23:54:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"55030469938048237101658742013434552755","date":"2025-11-09T08:47:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143002392027232234287628890562192941129","date":"2025-11-06T00:31:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-22T16:55:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131881271959744328723027176156959242175","date":"2025-08-17T17:05:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-14T12:41:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-14T12:32:38+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-14T09:33:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-10T18:09:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-10T18:04:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"34481633-c333-4972-b123-1f462884b320","owner":[],"postedDate":"August 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":53329342,"name":"Health sciences/Diseases"},{"id":53329343,"name":"Health sciences/Endocrinology"},{"id":53329344,"name":"Health sciences/Gastroenterology"},{"id":53329345,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-02-09T16:14:20+00:00","versionOfRecord":{"articleIdentity":"rs-7219476","link":"https://doi.org/10.1038/s41598-026-36886-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-02-02 15:59:38","publishedOnDateReadable":"February 2nd, 2026"},"versionCreatedAt":"2025-08-22 13:09:28","video":"","vorDoi":"10.1038/s41598-026-36886-4","vorDoiUrl":"https://doi.org/10.1038/s41598-026-36886-4","workflowStages":[]},"version":"v1","identity":"rs-7219476","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7219476","identity":"rs-7219476","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}