BACKGROUND: The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor\'s relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors.
METHODS: Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis.
RESULTS: Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD.
CONCLUSIONS: While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.

OBJECTIVE: Some researchers are concerned that the performance of pancreatic resection in cases of low malignancy with distal localization will increase, resulting in the occurrence or worsening of post-operative glucose intolerance. Herein, we retrospectively investigated the relationship between the pancreatic resection ratio and post-operative glucose intolerance in distal pancreatectomy (DP).
METHODS: Total 135 patients who underwent DP at our hospital and were followed up for > 12 months between January 2013 and December 2022 were included. Of these, 52 patients were included, excluding those with pre-operative diabetes and those who underwent pancreatectomy using other than a stapling device. The pancreatic resection ratio (%) was measured using pancreatic volumetry by manually tracing the pancreatic area on computed tomography images obtained before and after surgery and the relationship with post-operative glucose intolerance was investigated.
RESULTS: Among the 52 patients, 13 (25.0%) showed post-operative worsening of glucose tolerance (impaired glucose tolerance [IGT] group). The pancreatic resection ratios were 51.1% and 34.8% in the IGT (13 patients) and non-IGT groups (39 patients), respectively (p = 0.0027). The cut-off value for the IGT group was 46.5%. The resection site was divided into two groups as follows. One group was resected near the portal vein (portal group) and the other group was resected more caudally (caudal group). Mean pancreatic resection ratios were 46.5% and 28.5% in cases of resection of the portal group (30 patients) and caudal group (22 patients), respectively (p < 0.0001). The thickness of the pancreas at the resection site was 13.1 mm in the portal group and 17.7 mm in the caudal group (p < 0.0001) and the incidence of pancreatic fistula was 6.7% and 9.1%, respectively (p = 0.7472). The incidence of post-operative glucose intolerance was 40.0% (12/30) in the portal group and 4.5% (1/22) in the caudal group (p = 0.0016).
CONCLUSIONS: In cases of low-grade tumors and benign disease, pancreatic resection with preservation of the remaining pancreatic volume should be considered whenever possible.

UNASSIGNED: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC.
UNASSIGNED: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated.
UNASSIGNED: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival.
UNASSIGNED: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

BACKGROUND: The value of splenectomy for body localization (≥ 5 cm from spleen hilum) of pancreatic ductal adenocarcinoma (B-PDAC) is uncertain. This study assessed spleen-preserving distal pancreatectomy (SPDP) results for B-PDAC.
METHODS: This single-center study included patients who underwent SPDP (Warshaw\'s technique) or distal splenopancreactomy (DSP) for B-PDAC from 2008 to 2019. Propensity score matching was performed to balance SPDP and DSP patients regarding sex, age, American Society of Anesthesiologists (ASA), body mass index (BMI), laparoscopy, pathological features [American Joint Committee on Cancer (AJCC)/tumor node metastasis classification (TNM)], margins, and neoadjuvant/adjuvant therapies.
RESULTS: A total of 129 patients (64 male, median age 68 years, median BMI 24 kg/m2) were enrolled with a median follow-up of 63 months (95% CI 52-96 months), including 59 (46%) SPDP and 70 (54%) DSP patients. A total of 39 SPDP patients were matched to 39 DSP patients. SPDP patients had fewer harvested nodes (19 vs 22; p = 0.038) with a similar number of positive nodes (0 vs 0; p = 0.237). R0 margins were achieved similarly in SPDP and DSP patients (75% vs 71%; p = 0.840). SPDP patients were associated with decreased comprehensive complication index (CCI, 8.7 vs 16.6; p = 0.004), rates of grade B/C postoperative pancreatic fistula (POPF, 14% vs 29%; p = 0.047), and hospital stay (11 vs 16 days; p < 0.001). SPDP patients experienced similar disease-free survival (DFS, 5 years: 38% vs 32%; p = 0.180) and overall survival (OS, 5 years 54% vs 44%; p = 0.710). After matching, SPDP patients remained associated with lower CCI (p = 0.034) and hospital stay (p = 0.028) while not associated with risks of local recurrence (HR 0.85; 95% CI 0.28-2.62; p = 0.781), recurrence (HR 1.04; 95% CI 0.61-1.78; p = 0.888), or death (HR 1.20; 95% CI 0.68-2.11; p = 0.556).
CONCLUSIONS: SPDP for B-PDAC is associated with less postoperative morbidity than DSP, without impairing oncological outcomes.

This study aimed to compare outcomes of hand-sewn and stapler closure techniques of pancreatic stump in patients undergoing distal pancreatectomy (DP). Impact of stapler closure reinforcement using mesh on outcomes was also evaluated. Literature search was carried out using multiple data sources to identify studies that compared hand-sewn and stapler closure techniques in management of pancreatic stump following DP. Odds ratio (OR) was determined for clinically relevant postoperative pancreatic fistula (POPF) via random-effects modelling. Subsequently, trial sequential analysis was performed. Thirty-two studies with a total of 4,022 patients undergoing DP with hand-sewn (n = 1,184) or stapler (n = 2,838) closure technique of pancreatic stump were analyzed. Hand-sewn closure significantly increased the risk of clinically relevant POPF compared to stapler closure (OR: 1.56, p = 0.02). When stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.54, p = 0.002). When only randomized controlled trials were considered, there was no significant difference in clinically relevant POPF between hand-sewn and stapler closure techniques (OR: 1.20, p = 0.64) or between reinforced and standard stapler closure techniques (OR: 0.50, p = 0.08). When observational studies were considered, hand-sewn closure was associated with a significantly higher rate of clinically relevant POPF compared to stapler closure (OR: 1.59, p = 0.03). Moreover, when stapler closure was considered, staple line reinforcement significantly reduced formation of such POPF (OR: 0.55, p = 0.02). Trial sequential analysis detected risk of type 2 error. In conclusion, reinforced stapler closure in DP may reduce risk of clinically relevant POPF compared to hand-sewn closure or stapler closure without reinforcement. Future randomized research is needed to provide stronger evidence.

BACKGROUND: The spleen plays a significant role in the clearance of circulating microorganisms. Sequelae of splenectomy, especially immunodeficiency, can have a deleterious effect on a patient\'s health and even lead to death. Hence, splenectomy should be avoided and spleen preservation during elective surgery has become a treatment goal. However, this cannot be achieved in every patient due to intraoperative technical difficulties or oncological reasons. Autogenic splenic implantation (ASI) is currently the only possible way to preserve splenic function when a splenectomy is necessary. Experience largely stems from trauma patients with a splenic rupture. Splenic immune function can be measured by the body\'s clearing capacity of encapsulated bacteria. The aim of this study is to assess the splenic immune function after ASI was performed during minimally invasive (laparoscopic or robotic) distal pancreatectomy with splenectomy.
METHODS: This is the protocol for a multicentre, randomized, open-labelled trial. Thirty participants with benign or low-grade malignant lesions of the distal pancreas requiring minimally invasive distal pancreatectomy and splenectomy will be allocated to either additional intraoperative ASI (intervention) or no further intervention (control). An additional 15 patients who will undergo spleen-preserving distal pancreatectomy serve as the control group with normal splenic function. Six months postoperatively, after assumed restoration of splenic function, patients will be given a Salmonella typhi (Typhim Vi™) vaccine. The Salmonella typhi vaccine is a polysaccharide vaccine. The specific antibody titres immediately before and 4 to 6 weeks after vaccination will be measured. The ratio between pre- and post-vaccination antibody count is the primary outcome measure and secondary outcome measures include intraoperative details, length of hospital stay, 30-day mortality and morbidity.
CONCLUSIONS: This study will investigate the splenic immune function of patients who undergo ASI during minimally invasive distal pancreatectomy with splenectomy. The splenic immune function will be measured using the surrogate outcome of specific antibody titre after vaccination with a Salmonella typhi vaccine. The results will reveal details about splenic function after ASI and guide further treatment options for patients when a splenectomy cannot be avoided. It might eventually lead to a new standard of care making sometimes more demanding and time-consuming spleen-preserving procedures redundant.
BACKGROUND: International Standard Randomized Controlled Trials Number (ISRCTN) ISRCTN10171587. Prospectively registered on 18 February 2019.

BACKGROUND: Glucose tolerance worsens after distal pancreatectomy (DP); however, the long-term incidence and factors affecting interindividual variation in this worsening are unclear.
OBJECTIVE: To investigate the changes in diabetes-related traits before and after DP and to clarify the incidence of diabetes and its predictors.
METHODS: Among 493 registered patients, 117 underwent DP. Among these, 56 patients without diabetes before surgery were included in the study. Glucose and endocrine function were prospectively assessed using a 75-g oral glucose tolerance test preoperatively, 1 month after DP, and every 6 months thereafter for up to 36 months. Pancreatic volumetry was performed using multidetector row computed tomography before and after surgery.
RESULTS: Insulin secretion decreased and blood glucose levels worsened after DP. Residual pancreatic volume was significantly associated with the reserve capacity of insulin secretion but not with blood glucose levels or the development of diabetes. Among 56 patients, 33 developed diabetes mellitus. The cumulative incidence of diabetes at 36 months after DP was 74.1%. Multivariate Cox regression analysis showed that impaired glucose tolerance as a preoperative factor as well as a decreased insulinogenic index and impaired glucose tolerance at 1 month postoperatively were identified as risk factors for diabetes following DP.
CONCLUSIONS: Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP; the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.

Introduction Postoperative pancreatic fistula (POPF) is a critical complication occurring with a high incidence after distal pancreatectomy. To minimize the risk of POPF, we developed an innovative pancreas ligation device capable of closing the pancreatic stump without causing traumatic injury to the pancreatic duct and artery. We conducted an ex vivo follow-up study to compare the pressure resistance of the pancreas ligation device with that of a regular linear stapler. Materials and methods The pancreases were excised from 20 pigs and divided into two groups: ligation group (n = 10) and stapler group (n = 10). Distal pancreatectomy was performed, and the pancreatic stump was closed using either a pancreas ligation device or a regular linear stapler. The main pancreatic duct was cannulated with a 4-French catheter connected to a cannula and syringe filled with contrast medium. Using fluoroscopy detection, pressure resistance was defined as the maximum pressure without leakage from the pancreatic stump. Results No significant differences were found between the two groups regarding sex, age, body weight, or pancreatic thickness. In the ligation group, no leakage was observed at the stump in any pancreas. However, in the stapler group, six of 10 pancreases showed leakage at the staple line or into the parenchyma. Pressure resistance was significantly higher in the ligation group than in the stapler group (median: 42.8 vs. 34.3 mmHg, P = 0.023). Conclusions These findings suggest the effectiveness of a pancreas ligation device in reducing the incidence of POPF after distal pancreatectomy. Our ligation device is expected to be a useful alternative to a linear stapler for pancreatic stump closure.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy. Radical surgical resection offers the only potential cure. There is increasing agreement that radical antegrade modular pancreatosplenectomy (RAMPS) may benefit patients with tumors in the body and tail of the pancreas. To address this, the Chinese Study Group for Pancreatic Cancer (CSPAC)-3 trial is proposed to compare the effect of RAMPS and standard retrograde pancreatosplenectomy (SRPS) on patient survival and preoperative safety METHODS: The randomized controlled trial will be multicenter and two-armed with blinded outcomes and intention-to-treat analysis. Three hundred patients with resectable body and tail pancreatic adenocarcinoma will be enrolled and randomly assigned to RAMPS or SRPS. Adjuvant chemotherapy based on an initial regimen will be recommended 4-6 weeks after surgery if no serious complication occurs. The hypothesis that RAMPS improves survival outcomes compared with SRPS will be tested using a superiority trial. The primary outcome will be overall survival (OS). Secondary outcomes will include recurrence-free survival (RFS), R0 resection rate, the number of harvested lymph nodes, postoperative complications, and quality of life scores.
CONCLUSIONS: The use of RAMPS has increased over the past decade. It is reported that RAMPS is superior to SRPS in improving both the rate of R0 resection and lymph node yield. Despite these advantages, however, there is little high-level documentation of the superiority of RAMPS in terms of survival and this needs to be investigated. To address this issue, CSPAC has instigated the first prospective, randomized phase III control trials, aiming to explore the optimal surgical strategy for improving the prognosis and OS of patients with left-sided pancreatic cancer Trial registration Chinese Clinical Trial Registry ChiCTR2100053844; pre-results. Registered on December 1, 2021.

UNASSIGNED: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking.
UNASSIGNED: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265).
UNASSIGNED: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group.
UNASSIGNED: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer.
UNASSIGNED: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.