In this study, we confirmed pancreatic volumetric atrophy after gastric cancer surgery, assessed the factors influencing pancreatic volumetric atrophy, and evaluated the impact of atrophy on BMI reduction and quality of life. Previous studies have shown that pancreatic exocrine insufficiency occurs in patients with diabetes mellitus or chronic pancreatitis and was accompanied by a decrease in pancreatic volume [17–18], residual pancreatic volume also decreases in patients undergoing pancreaticoduodenectomy [8–9]. Although it has been reported in the literature [10–11] that pancreatic volume continues to decrease after gastric cancer surgery, and pancreatic exocrine and endocrine function decreases with pancreatic atrophy, this study further explored the factors influencing pancreatic volume atrophy after gastric cancer surgery and the effect of atrophy on BMI reduction and quality of life on this basis. It has been reported [10] that pancreatic volume decreased continuously 5 years after gastric cancer surgery, the degree of PV decrease after TG was greater than the degree of PV decrease after DG at 5 years after surgery, and the degree of PV decrease in Roux-en-Y reconstruction was greater than the degree of PV decrease in Billroth I reconstruction after DG. Our study showed that 142 patients with gastric cancer had a significant decrease in pancreatic volume one year after surgery (P < 0.001), with a preoperative pancreatic volume of 67.74 ± 16.27 cm3, and a 1-year postoperative pancreatic volume of 51.25 ± 14.41 cm3. Among them, the pancreatic volume of total gastrectomy, distal gastrectomy, and proximal gastrectomy also tended to be significantly reduced by each surgical procedure (P < 0.05). In addition, the relative percentage of postoperative/preoperative pancreatic volume between several surgical procedures ranged from 74.17 to 81.36%, which is consistent with the PV% reported by Satoi et al. [11]. However, probably due to the fact that we only analysed pancreatic atrophy at 1 year postoperatively, which is a short period of time, we failed to find differences in pancreatic atrophy between several surgical procedures.

The structural and functional integrity of the digestive system is essential for the normal digestion of food, and pancreatic secretion is a complex process subject to both neural and endocrine regulation. Usually, after feeding, the dilatation of the stomach by the chyme and the diastole of the gastric fundus stimulate the vagus nerve and cause the secretion of pancreatic juice [5]. The absence of the gastric sinusogastric fundus reflex after gastrectomy leads to a reduction in nerve-stimulated pancreatic secretion [19]; the entry of chyme into the duodenum also stimulates pancreatic secretion, and reconstructive surgeries bypassing the duodenum, such as the Billroth-II and Roux-en-Y reconstructions, where chyme is unable to pass through the duodenum, lead to a reduction in the release of cholecystokinin and a reduction in the stimulation of pancreatic secretion [20]. After gastrointestinal reconstruction, accelerated gastric emptying shortens the intestinal transit time, which can be accompanied by a feedback imbalance in pancreatic enzyme secretion [5]. In addition, gastric lymph node dissection and vagotomy lead to a loss of pancreatic nerve supply [21], which further aggravates pancreatic exocrine insufficiency. Based on these results, we hypothesised that these fewer stimuli resulted in pancreatic atrophy, possibly related to decreased exocrine pancreatic function. Therefore, it seems reasonable that pancreatic volume decreases after gastrectomy. In conclusion, the mechanism of pancreatic volume atrophy after gastrectomy is complex and requires further studies.

Although postoperative pancreatic volume atrophy after gastric cancer is now gaining attention, the influencing factors of pancreatic atrophy and the effects of atrophy have not been reported. Preoperative diabetes mellitus, malignancy, surgical approach, pancreatico-enteric anastomosis approach, pancreatic duct dilatation, and adjuvant radiotherapy have been suggested as possible risk factors for residual pancreatic atrophy after pancreaticoduodenal surgery [9]. In our study, after excluding patients with diabetes mellitus and pancreatic-like diseases, possible relevant factors affecting pancreatic volume atrophy were investigated. Our findings showed that T3 and T4 stages, preoperative low levels of HDL-C and smoking history are influential factors in pancreatic atrophy. Currently,sime studeies confirmed that the later tumour stages were associated with the lower the nutritional status of the patient [22, 23, 24]. Our results concluded that T3 and T4 stages are influencing factors of pancreatic atrophy. The reason for this may be that patients with T3 and T4 stages have deeper tumour infiltration and larger tumour sizes, increased tumour consumption, and high physical exertion of the patient, leading to low nutritional status. The nutritional stability of the organism can maintain the normal metabolism of each tissue cell, when the nutritional deficiency of the organism reduces the nutrient substrate that maintains the normal proliferation of each tissue cell, it will result in the slowing down of cell proliferation, and even lead to the increase of apoptosis [25–26], which will may cause the pancreatic atrophy. In addition, we consider that it may also be due to the fact that the larger tumours in the T3 and T4 stages compress the pancreatic tissues, triggering local blood circulation disorders and promoting pancreatic cell necrosis and apoptosis, which in turn aggravates pancreatic atrophy. However, due to our small sample size, there may be bias in the data, and larger sample sizes and more in-depth studies are needed in the future to confirm and explain that late T stage can affect pancreatic atrophy. HDL is a nanoparticle with anti-atherosclerotic, anti-inflammatory and antioxidant properties associated with cardiovascular and metabolic health. Low levels of HDL-C are an important risk factor for atherosclerotic cardiovascular disease [27]. Atherosclerosis is a chronic inflammatory condition that occurs in arterial vessels throughout the body and is the pathological basis of cardiovascular diseases such as stroke and coronary heart disease, leading to narrowing of the vascular lumen, increased vascular permeability, and decreased blood flow, which triggers ischemia or hypoxia of tissues and organs in the body [28] and may cause pancreatic atrophy. This could explain our results in which low preoperative levels of HDL-C exacerbated postoperative pancreatic volume atrophy. The possible reason for exacerbation of pancreatic atrophy by smoking is that nicotine is an important component of cigarettes and may mediate the development of pancreatic disease. animal studies have demonstrated that nicotine in tobacco induces vacuolisation or swelling of pancreatic alveolar cells, leading to morphological changes in pancreatic exocrine secretion [29–30]. In addition aryl hydrocarbon receptor ligand agonists in cigarette smoke induce CD4 cells to produce IL-22, which promotes the progression of pancreatic fibrosis through the activation of pancreatic stellate cells [31]. Clinical studies have also found that cigarette smoking can increase the risk of complications associated with chronic pancreatitis, such as pancreatic calcification, pancreatic pseudocysts, and pancreatic exocrine insufficiency [32–33]. Pancreatic enzyme replacement therapy (PERT) is the cornerstone of pancreatic exocrine insufficiency treatment, aiming to improve gastrointestinal symptoms and nutritional status, to improve the quality of life of patients, and to prevent and eliminate secondary events that may result from pancreatic enzyme deficiency [34–35]. Pancreatic enzyme interventions are not routinely performed in our hospital after gastric cancer surgery, therefore only a few patients have used pancreatic enzymes. Only 15 patients in our study took pancreatic enzymes for more than 1 month within 1 year after surgery, however, probably because of the small number of people have taken pancreatic enzymes and the different specifications and quantities of pancreatin, no effect of pancreatic enzymes on pancreatic volume atrophy was found.

The final aim of this study was to assess the impact of pancreatic atrophy and we used prospectively collected patient weight and quality of life questionnaires to analyse the correlation of pancreatic atrophy with reduced BMI and quality of life. We used the GIQLI [13]scale to assess the quality of life of our patients. GIQLI is a widely accepted scale for assessing quality of life after gastrointestinal surgery, and many studies have used the GIQLI scale to assess the quality of life of patients after gastric cancer surgery [6]. The results of our study showed that BMI reduction was correlated with pancreatic atrophy severity, and low gastrointestinal symptom scores on the GIQLI scale were correlated with pancreatic atrophy severity. Low epigastric fullness scores, abdominal distension scores, and frequency of anal farting scores were associated with pancreatic atrophy severity in the gastrointestinal symptom score subgroup. It can be seen that pancreatic atrophy is associated with dyspeptic symptoms such as fullness, bloating and excessive farting. Overall, the results of our study showed that patients with severe pancreatic atrophy have a greater reduction in body mass index and a more severe deterioration in quality of life, particularly in terms of gastrointestinal symptoms such as epigastric fullness, abdominal flatulence, and more frequent anal farting.

Our study has some limitations. Firstly, it was a single-institution retrospective study. Secondly, the sample sizes of several procedures, (distal gastric Roux-en-Y, PG-Esophagogastrostomy and PG-Double-tract) were small. In addition, we only analysed pancreatic volume atrophy at 1 year postoperatively and failed to find differences in pancreatic atrophy between several surgical procedures. In the future, data on postoperative pancreatic volume at longer follow-up periods are needed to further analyse the differences in pancreatic atrophy between different surgical approaches and to further explore the factors affecting pancreatic atrophy and the impact of pancreatic atrophy.

In conclusion, this study found that pancreatic atrophy was significant in patients with gastric cancer 1 year after surgery, regardless of the surgical procedure. Clinicians need to monitor pancreatic function, BMI, and life quality more carefully in patients with T3 and T4 stages, preoperative low levels of HDL-C and smoking history, and patients found to have reduced pancreatic volume during follow-up should accept the necessary endocrine and exocrine replacement therapy.