This study retrospectively analyzed patients with benign or low-grade malignant pancreatic tumors treated at Qilu Hospital from January 2015 to May 2022. The included patients must meet the following criteria: (a) diagnosed as benign or low-grade malignant tumors by pathology; (b) no major blood vessels, vital organs and common bile duct invasion (c) laparoscopic operation; (d) complete medical and follow-up data. Some patients were excluded if they were forced to undergo LPD and LDP due to vital organ invasion such as the splenic vessels and duodenum or a suspicion of high-grade malignancies based on intraoperative frozen pathology. The maximum tumor diameter was evaluated by preoperative imaging. Patients undergoing LapEN procedure were divided into large tumor group (≥4 cm) and small tumor group (<4 cm) according to tumor diameter. The screening process is shown in Figure 1. After screening, this retrospective study enrolled 194 patients, including 29 large tumor LapEN patients, 106 small tumor LapEN patients, 11 large tumor LPD patients and 48 large tumor LDP patients.

All data were from the medical records of Qilu Hospital of Shandong University. The serological parameters were collected within 3 days before the procedure. The imaging parameters were obtained based on a contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) examination within 7 days prior to surgery. We evaluated the feasibility and safety of the LapEN procedure by intraoperative and postoperative parameters and complications. Intraoperative variables included American Society for of Anaesthesiologists (ASA) physical status classification, operative time, blood loss and pancreatic wound suture, obtained from the operative notes written by the surgeon. The Postoperative hospital stays, duration of fasting, visual analogue scale (VAS), red blood cell transfusion rate, occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF), post-pancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) were assessed to verify the safety of the operation. In addition, data on new-onset diabetes, exocrine insufficiency, and tumor recurrence were obtained through follow-up. Postoperative follow-up data were conducted by telephone. All patients were followed up for a minimum of 6 months.

This study was conducted according to the principles of the Declaration of Helsinki. All patients signed written informed consent. The analysis of patient data was approved by the Ethics Committee of Qilu Hospital of Shandong University.

LapEN was performed as we have previously reported (15, 16). The surgical procedure for LapEN of large tumors was shown in Figure 2. The patient was placed in the supine position on the operating table with the legs spread apart. The main surgeon was on the right side of the patient and the assistant was on the left side of the patient. The laparoscopic assistant stood between the patient’s legs and was responsible for adjustment of the laparoscope. A total of 5 trocars were used during the procedure. A 10-mm trocar was inserted lower edge of the umbilical region and used for observing. A 12-mm trocar located in the right mid-clavicular line, and a 5-mm trocar located at the right anterior axillary line. Symmetrically, another two 5-mm trocars located in the left mid-clavicular line and left anterior axillary line. The whole abdominal cavity was explored first. Next, the gastrocolic ligament was opened to reveal the anterior aspect of the pancreas. The lesion was enucleated from the pancreatic parenchyma (Figure 2C). Surgeons should pay attention to protect the main pancreatic duct (MPD) and major blood vessels during the operation. If an injury of the MPD happened during the resection, we used PDS II (polydioxanone) synthetic absorbable suture for repair, and insert a stent if necessary (Figure 2D). For tumors whose margins could not be determined, we usually used intraoperative ultrasound for evaluation. Finally, the pancreatic wound was carefully examined and one or two drainage tubes were placed there. Tumor specimens were sent to the pathology department for examination.

LPD and LDP were performed under the standardized surgical procedure. If the spleen would be preserved in LDP, we would perform the Warshaw (17) or Kimura (18) procedure.

POPF was defined based on the 2016 International Study Group of Pancreatic Fistula (ISGPF) definition and classification (19). POPF was defined as an amylase level in any measurable excreted fluid that was 3 times higher than the upper limit of the institution’s normal serum amylase level. The upper limit of serum amylase in our hospital is 105 U/L. The original “grade A” POPF, the biochemical fistula, was no longer considered an actual postoperative complication. Grade B and C POPF are classified as CR-POPF.

According to the ISGPF, DGE was defined as reinsertion of a nasogastric tube 3 days after surgery or failure to start to oral diet 7 days after surgery (20). The definition of PPH was based on ISGPF, Included grade B (intervention is required) and C (patient in critical condition) (21). The diagnosis of new-onset diabetes after surgery was based on the 2021 American Diabetes Association (ADA) Standards of Medical Care in Diabetes (22). Exocrine insufficiency was defined as pancreatic enzyme insufficiency requiring pancreatic enzyme supplementation therapy.

Statistical analyses were performed by SPSS 26 (SPSS, Inc., Chicago, IL). For measurement data, the Kolmogorov–Smirnov and Shapiro–Wilk normality tests were used to evaluate its normality. Normally distributed values were described by the mean ± standard deviation, and nonnormally distributed values were described by the median and the range. Student’s t-test and Mann–Whitney U-test was performed to compare measurement data. Categorical data were recorded as percentages, and were compared by Pearson Chi square or Fisher’s exact tests. All p values were two-sided, and p < 0.05 was considered statistically significant.

A total of 194 patients was enrolled in this study. The baseline characteristics of all enrolled patients are listed in Table 1. Among them, 135 patients underwent LapEN, 11 patients underwent LPD and 48 patients underwent LDP. In the overall, the median age of patients was 44 (11–79) years, and 147 (75.8%) patients were females. The median tumor size was 3.0 cm (range, 0.6–12.0 cm), and 87 (44.8%) patients had tumors located in the head of the pancreas. All tumors were surgically removed completely, and a postoperative pathological examination was performed to diagnose. The pathological diagnosis of all tumors was shown in Table 2. SCN (25%), SPT (30.7%), and MCN (20.5%) account for the majority of patients with large pancreatic tumors. Unlike the former, the proportion of PNET (43.4%) was highest in the small tumor group. At the end of follow-up, all patients were alive.

A total of 135 patients underwent LapEN procedure, 29 (21.5%) were classified in the large tumor group (≥4 cm) and 106 (78.5%) to the small tumor group (<4 cm) based on tumor diameter. The clinicopathologic characteristics of patients undergoing LapEN procedure were listed in Table 3. The mean tumor diameter was 5.7 ± 1.7 cm in the large tumor group, and was 2.0 ± 0.7 cm in the small tumor group. One case of MCN had the largest tumor with a diameter of 10 cm. Patients in the large tumor group had a significantly greater proportion of cystic lesions than in the small tumor group (79.3% vs. 48.1%, p = 0.003). Postoperative pathology showed that the proportion of PNET was significantly lower in patients with large tumors than in those with small tumors (3.4% vs. 43.4%, p < 0.001). The mean operating time for LapEN procedure was 144.9 ± 59.9 min. Because of the difficulty in intraoperative search for tumors, 3 (2.2%) patients were converted to open surgery. There was no difference between both groups in terms of operative time (150.5 ± 46.7 vs. 143.3 ± 63.2 min, p = 0.569), intraoperative blood loss [50 mL (5–400 mL) vs. 50 mL (2–300 mL), p = 0.545], and conversion rate (0% vs. 2.8%, p = 1.000). In the perioperative setting, large tumor only seemed to lengthen hospital stay after the operation [8 days (3–21 days) vs. 6 days (2–30 days), p = 0.009]. The incidence of long-term and short-term complications for patients in two subgroups was not significantly different. CR-POPF was the most common postoperative complication. The CR-POPF rate in LapEN cohort was 21.5%, including 28 cases were grade B and one case was grade C. Only one patient was found to have a tumor recurrence at 6 months postoperatively and was prepared to undergo surgery at a later date.

The standard procedure for pancreatic head tumors is the pancreaticoduodenectomy, and distal pancreatectomy is the standard procedure for pancreatic body and tail tumors. For those patients with large tumors (≥4 cm) who did not undergo LapEN surgery, other appropriate procedures were selected according to the location of the tumor, including 11 cases of LPD and 48 cases of LDP. To compare the safety and feasibility of different procedures for patients with large pancreatic tumors, we classified patients according to tumor location and then analyzed separately. The clinicopathologic characteristics of these patients were shown in Tables 4, 5.

In large pancreatic head tumors cohort, 19 patients underwent LapEN and 11 patients underwent LPD. There were no significant differences in the demographic parameters between the both subgroups (Table 4). Compared to the LapEN group, the operative time was significantly longer (396.8 ± 92.4 vs. 160.0 ± 41.4 min, p < 0.001) and intraoperative blood loss increased significantly [300 mL (range, 50–1,000 mL) vs. 50 mL (range, 10–400 mL), p < 0.001] in LPD group. In addition, the conversion to open surgery rate of LPD was significantly higher than that of LapEN (45.5% vs. 0%, p = 0.012). In terms of postoperative parameters, postoperative hospital stays [9 days (range, 3–21 days) vs. 14 days (range, 10–26 days), p = 0.006] and duration of fasting [3 days (range, 1–11 days) vs. 6 days (range, 4–13 days), p < 0.001] for patients undergoing LapEN were significantly shorter than for patients undergoing LPD procedure. The red blood cell transfusion rate (0% vs. 54.5%, p = 0.001) and postoperative pain scores [3 (range, 2–4) vs. 4 (range, 3–6), p = 0.001] were significantly lower in LapEN than in LPD. There were no significant differences in the incidence of CR-POPF and other short-term complications between both subgroups. In terms of long-term complications, the incidence of exocrine insufficiency was significantly higher in patients undergoing LPD (36.4% vs. 0%, p = 0.012).

In large pancreatic body and tail tumors cohort, 10 patients underwent LapEN and 48 patients underwent LDP. The subgroups did not significantly differ on the demographic parameters (Table 5). Of the patients who underwent LDP, 12 cases underwent intraoperative splenectomy, 20 cases underwent Kimura procedure and 16 cases underwent Warshaw procedure. During the LDP, the operative time was significantly prolonged (223.1 ± 67.7 vs. 132.5 ± 53.0 min, p < 0.001) and intraoperative blood loss increased significantly [150 mL (range, 20–1,000 mL) vs. 40 mL (range, 5–300 mL), p = 0.001] than LapEN. In terms of short-term and long-term complications, there were no significant differences between both subgroups.