Rutin is a valuable traditional Chinese medicine known for its anti-inflammatory and anticancer effects. It has been shown to be effective in treating various inflammation-associated diseases. Here, we investigated the influence of rutin on acute pancreatitis and tumorigenesis. Using C57BL/6J mice and Kras mutant transgenic mice, we induced pancreatitis and acinar regeneration models. Pancreatic malondialdehyde (MDA), superoxide dismutase (SOD) activity and reduced glutathione (GSH) contents were measured for oxidative stress. Histological staining and a pancreatic acinar 3D culture model were used to clarify the influence of rutin on ADM in vivo and in vitro. Western blotting was adopted to detect ADM markers amylase and CK19. We found that rutin ameliorated inflammatory injury to the pancreas in both caerulein- and arginine-induced AP. Then, we revealed that the anti-damage effect of rutin may be due to its inhibition of oxidative stress. In addition, an acinar 3D culture model showed that rutin inhibited the formation of ADM by activating AMPK in acinar cells. Finally, the activation of AMPK is believed to be a potential mechanism by which rutin exerts inhibitory effects on Kras-driven tumorigenesis. Rutin inhibited AP-induced pancreatic injury and oncogenic Kras-driven tumorigenesis by inhibiting ADM.

Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.

Pancreatic exocrine insufficiency (PEI) is defined as a reduction in pancreatic exocrine secretion below the level that allows the normal digestion of nutrients. Pancreatic disease and surgery are the main causes of PEI. However, other conditions and upper gastrointestinal surgery can also affect the digestive function of the pancreas. PEI can cause symptoms of nutritional malabsorption and deficiencies, which affect the quality of life and increase morbidity and mortality. These guidelines were developed following the United European Gastroenterology framework for the development of high-quality clinical guidelines. After a systematic literature review, the evidence was evaluated according to the Oxford Center for Evidence-Based Medicine and the Grading of Recommendations Assessment, Development, and Evaluation methodology, as appropriate. Statements and comments were developed by the working groups and voted on using the Delphi method. The diagnosis of PEI should be based on a global assessment of symptoms, nutritional status, and a pancreatic secretion test. Pancreatic enzyme replacement therapy (PERT), together with dietary advice and support, are the cornerstones of PEI therapy. PERT is indicated in patients with PEI that is secondary to pancreatic disease, pancreatic surgery, or other metabolic or gastroenterological conditions. Specific recommendations concerning the management of PEI under various clinical conditions are provided based on evidence and expert opinions. This evidence-based guideline summarizes the prevalence, clinical impact, and general diagnostic and therapeutic approaches for PEI, as well as the specifics of PEI in different clinical conditions. Finally, the unmet needs for future research are discussed.

Metastatic tumours to the pancreas are rare but most commonly arise from primary renal cell carcinoma (RCC). Contrary to other metastatic malignancies, metastatic RCC demonstrates indolent behaviour; with a long latency between primary tumour presentation and the development of metastasis, as well as a predilection to isolated pancreas-only disease. As such, pancreatic metastasectomy has evolved as a treatment option for patients with metastatic RCC; reported to associate with improved outcomes in selected patients. The aim of this study was to describe the clinicopathological characteristics and patient outcomes in a series of patients undergoing pancreatic resection for metastatic RCC in a high volume, regional hepatopancreatobiliary (HPB) centre.

Retrospective review of all patients who underwent pancreatic metastasectomy for pathologically-confirmed metastatic RCC over an eighteen-year period. Clinicopathological characteristics and outcomes were collected and analysed.

Fifteen patients underwent pancreatic resection for metastatic RCC between October 2004 and October 2022. Two patients underwent synchronous nephrectomy and pancreatectomy. In thirteen patients, the pancreas was the only site of metastatic disease. For those with metachronous metastases, the median disease-free interval (DFI) was 126 months from initial nephrectomy.Five-year disease-free and overall survival were 32.7 % and 63.3 %, respectively. No clinicopathological factor was found to associate with overall survival (OS); however, patients with synchronous metastatic disease had a significantly shorter disease-free survival (p = 0.029). Similarly, patients with a longer DFI (≥ ten years) between RCC primary and the development of pancreatic metastases had a trend towards improved OS (p = 0.074).Post-operative morbidity and mortality rates were comparable to that of pancreatic surgery for primary pancreatic pathology.

This case series supports the role of pancreatic resection in patients with metastatic RCC, with acceptable rates of morbidity and mortality and favourable patient outcomes. The long DFI between nephrectomy and pancreatic metastases highlights the importance of long-term follow-up for patients diagnosed with RCC.

Pancreatic adenocarcinoma located in the pancreatic body might require a portomesenteric venous resection (PVR), but data regarding surgical risks after distal pancreatectomy (DP) with PVR are sparse. Insight into additional surgical risks of DP-PVR could support preoperative counseling and intraoperative decision making. This study aimed to provide insight into the surgical outcome of DP-PVR, including its potential risk elevation over standard DP.

We conducted a retrospective, multicenter study including all patients with pancreatic adenocarcinoma who underwent DP ± PVR (2018-2020), registered in four audits for pancreatic surgery from North America, Germany, Sweden, and The Netherlands. Patients who underwent concomitant arterial and/or multivisceral resection(s) were excluded. Predictors for in-hospital/30-day major morbidity and mortality were investigated by logistic regression, correcting for each audit.

Overall, 2924 patients after DP were included, of whom 241 patients (8.2%) underwent DP-PVR. Rates of major morbidity (24% vs. 18%; p = 0.024) and post-pancreatectomy hemorrhage grade B/C (10% vs. 3%; p = 0.041) were higher after DP-PVR compared with standard DP. Mortality after DP-PVR and standard DP did not differ significantly (2% vs. 1%; p = 0.542). Predictors for major morbidity were PVR (odds ratio [OR] 1.500, 95% confidence interval [CI] 1.086-2.071) and conversion from minimally invasive to open surgery (OR 1.420, 95% CI 1.032-1.970). Predictors for mortality were higher age (OR 1.087, 95% CI 1.045-1.132), chronic obstructive pulmonary disease (OR 4.167, 95% CI 1.852-9.374), and conversion from minimally invasive to open surgery (OR 2.919, 95% CI 1.197-7.118), whereas concomitant PVR was not associated with mortality.

PVR during DP for pancreatic adenocarcinoma in the pancreatic body is associated with increased morbidity, but can be performed safely in terms of mortality.

Postoperative pancreatic fistula (POPF) remains a common and dreaded complication after pancreatic resections and is associated with increased morbidity and mortality. Over the years, several different strategies have been investigated to prevent and mitigate POPF. However, when a POPF occurs, a consensus on the optimal management strategy of grade B and grade C POPF is still lacking, and the current management strategy is often based on local expertise and driven by patient's condition. Nevertheless, whereas the incidence of POPF after pancreatic surgery has remained stable, the overall mortality related to this complication has decreased over the years. This reflects an improvement in the management of this complication, which has become increasingly conservative. The aim of this review is to provide an updated evidence-based overview on the management strategies of POPF for surgeons and physicians in the clinical practice.

With improvements in surgical technique and advances in pancreatic endocrine and exocrine replacement therapy, the indications for, and threshold to perform, total or completion pancreatectomy in the modern surgical era are ever evolving. The following review will evaluate such indications for pancreatic cancer including pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms. The authors also review the literature on oncologic outcomes of total and completion pancreatectomy for pancreatic cancer. Finally, they discuss the quality of life and postoperative management of the a-pancreatic state.

Recently, more and more total pancreatectomy (TP) has been performed for central-located pancreatic ductal cell adenocarcinoma (PDCA), which abuts or involves both gastroduodenal and splenic arteries and demands transaction of both of them for complete resection. Spiked by Warshaw's procedure (spleen-preserving distal pancreatectomy with excision of splenic vessels), the authors developed a new procedure "Whipple over the splenic artery (WOTSA)" to replace TP by leftward extension of pancreatic parenchyma transaction line and preservation of pancreatic tail and spleen after excision of the splenic artery. This uncontrolled before and after study assesses the safety and efficacy of a new technique "Whipple over the splenic artery (WOTSA)" as a treatment for pancreatectomy for ductal adenocarcinoma (PDAC), which traditionally requires TP for a complete excision.

The study group comprised 40 consecutive patients who underwent WOTSA for PDAC between August 2019 and September 2022. Their clinicopathological characteristics and survival were compared with those of a historical control group comprising 30 consecutive patients who underwent TP between January 2016 and July 2019.

None of the 40 patients in the WOTSA group required reoperation due to infarction of the pancreas and/or spleen remnant. Diabetes mellitus (DM) medication after WOTSA were none in 19, oral hypoglycemic agents in 19, and insulin preparations in 2 patients. Compared with TP, patients who underwent WOTSA exhibited similar rates of major operative complications, clear pancreatic parenchyma transaction margin, and a number of harvested positive lymph nodes, but a higher rate of adjuvant chemotherapy completion and a trend toward better median disease-free survival (14 vs. 7.5 months, P =0.023).

Compared to TP, WOTSA can be safely performed and have much better postoperative glycemic status without cost of higher operative risk or impaired surgical radicality. These findings indicate that most TPs for PDAC potentially can be replaced by WOTSAs.

Individuals with hereditary pancreatic cancer risk include high risk individuals (HRIs) with germline genetic susceptibility to pancreatic cancer (PC) and/or a strong family history of PC. Previously, studies have shown that PC surveillance in HRIs can downstage PC diagnosis and extend survival leading to pancreatic surveillance being recommended for certain HRIs. However, the optimal surveillance strategy remains uncertain, including which modalities should be used for surveillance, how frequently should surveillance be performed, and which sub-groups of HRIs should undergo surveillance. Additionally, in the ideal world PC surveillance should also be cost-effective. Cost-effectiveness analysis is a valuable tool that can consider the costs, potential health benefits, and risks among various PC surveillance strategies. In this review, we summarize the cost-effectiveness of various PC surveillance strategies for HRIs for hereditary pancreatic cancer and provide potential avenues for future work in this field. Additionally, we include cost-effectiveness studies among individuals with new-onset diabetes (NoD), a high-risk group for sporadic PC, as a comparison.

The goal of surveillance programs for individuals at risk (IAR) from familial pancreatic cancer (FPC) families or families with other inherited tumor syndromes predisposing to the development of pancreatic adenocarcinoma (PDAC), such as hereditary pancreatitis or Peutz-Jeghers syndrome, is the dectection and consecutive curative resection of early PDAC or even better its high-grade precursor lesions. Although the indication for surgery is quite established, the extent of surgery is not well defined due to the lack of evidence-based data. In addition, multiple factors have to be taken into account to determine an optimal personalized surgical strategy. This holds especially true since pancreatic surgery is associated with a relatively high morbidity and might impair the quality of life significantly. In this article the surgical aspects in the setting of hereditary PDAC are discussed.

Pancreatic diabetes is associated with glycemic variability, poor metabolic control, and reduced quality of life. Though hybrid closed-loop (HCL) insulin delivery systems were not originally developed for these types of diabetes, they could address the therapeutic challenge. We aimed to evaluate long-term metabolic control in ten adult patients (mean ± SD age: 59 ± 12) treated with HCL insulin delivery systems for pancreatitis or pancreatectomy-induced diabetes. After a median of 346 days (range 64 - 631) with HCL insulin delivery, continuous glucose monitoring showed 59±19 % time-in-range [70-180 mg/dl] (versus 49±24 % before HCL insulin delivery, P = 0. 049) and 0.8 ± 1.0 % time-below-range [< 70 mg/dl] (versus 2.2 ± 2.6 %, P = 0.142), with the coefficient of glucose variability at 35.4 ± 7.6 (versus 37.8 ± 7.1, P = 0.047). HbA1c decreased from 8.5 ± 1.7 % to 7.7 ± 1.3 % [69±18 to 60±14 mmol/mol] (P = 0.076). No patient experienced an acute adverse metabolic event.

Background: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is associated with major postoperative morbidity and mortality. Several scoring systems have been described to stratify patients into risk groups according to the risk of POPF. The aim of this study was to compare scoring systems in patients who underwent a PD. Methods: A total of 196 patients undergoing PD from July 2019 to June 2022 were identified from a prospectively maintained database of the University Hospital Ghent. After performing a literature search, four validated, solely preoperative risk scores and the intraoperative Fistula Risk Score (FRS) were included in our analysis. Furthermore, we eliminated the variable blood loss (BL) from the FRS and created an additional score. Univariate and multivariate analyses were performed for all risk factors, followed by a ROC analysis for the six scoring systems. Results: All scores showed strong prognostic stratification for developing POPF (p < 0.001). FRS showed the best predictive accuracy in general (AUC 0.862). FRS without BL presented the best prognostic value of the scores that included solely preoperative variables (AUC 0.783). Soft pancreatic texture, male gender, and diameter of the Wirsung duct were independent prognostic factors on multivariate analysis. Conclusions: Although all predictive scoring systems stratify patients accurately by risk of POPF, preoperative risk stratification could improve clinical decision-making and implement preventive strategies for high-risk patients. Therefore, the preoperative use of the FRS without BL is a potential alternative.

Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.

Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed.

SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6).

Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Pancreatoduodenectomies are complex surgical procedures with considerable postoperative morbidity and mortality. Here, we describe complications and outcomes in patients requiring surgical revisions following pancreatoduodenectomy.

A total of 1048 patients undergoing a pancreatoduodenectomy at our institution between 2002 and 2019 were analyzed retrospectively. All patients with surgical revisions were included. Revisions were divided into early and late using a cut-off of 5 days after the first surgery. Statistical significance was examined by using chi-square tests and Fisher's exact tests. Survival analysis was performed using Kaplan-Meier curves and log-rank tests.

A total of 150 patients with at least 1 surgical revision after pancreatoduodenectomy were included. Notably, 64 patients had a revision during the first 5 days and were classified as early revision. Compared with the 86 patients with late revisions, we found no differences concerning wound infections, delayed gastric emptying, or acute kidney failure. After late revisions, we found significantly more cases of sepsis (31.4% late versus 15.6% early, p = 0.020) and reintubation due to respiratory failure (33.7% versus 18.8%, p = 0.031). Postoperative mortality was significantly higher within the late revision group (23.2% versus 9.4%, p = 0.030).

Arising complications after pancreatoduodenectomy should be addressed as early as possible as patients requiring late surgical revisions frequently developed septic complications and multiorgan failure.

Post-operative diarrhoea is a common adverse event after pancreatic surgery. While the risk factors for this condition have been identified, the increasing trend of administering chemotherapy before surgery might change these factors. This study aimed to identify the risk factors of post-operative diarrhoea in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy.

A retrospective cohort study.

Patients who underwent neoadjuvant chemotherapy and pancreatectomy because of PDAC between 2021 and 2023 were included. The preoperative characteristics of, operative details of and post-operative outcomes in patients with and without post-operative diarrhoea were collected and compared. The independent risk factors of post-operative diarrhoea were identified using logistic regression analysis. STROBE checklist was used.

Post-operative diarrhoea occurred in 65 out of 145 (44.8%) patients during hospitalization. Elevated white blood cell count, advanced tumour stage, and late abdominal drain removal were independent risk factors for post-operative diarrhoea (p < .001, p = .006 and p = .009, respectively).

Some perioperative factors influence post-operative diarrhoea in patients who undergo neoadjuvant chemotherapy. More attention should be paid to patients at a higher risk of post-operative diarrhoea, with an emphasis on high-quality management for these patients.

Pancreatic neuroendocrine tumors (PNETs) represent 1-2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched.

This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test.

Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence.

This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.

Total pancreatectomy results in complete loss of insulin and glucagon. Sensor-augmented pumps (SAPs) allow fine-tuning of the basal insulin rate, which helps avoid both hypo- and hyperglycemic events. We herein report a case of total pancreatectomy treated with a SAP with no evidence of ketoacidosis without any insulin administration during a certain period of time. Furthermore, we observed a sudden drop in blood glucose levels without insulin, which may have been due to glucose effectiveness. Our case is valuable in arguing the concept of glucose effectiveness in the absence of insulin and glucagon.

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in the early stages and lacks reliable biomarkers. The scope of this project was to establish quantitative nuclear magnetic resonance (NMR) spectroscopy to comprehensively study blood serum alterations in PDAC patients. Serum samples from 34 PDAC patients obtained before and after pancreatectomy as well as 83 age- and sex-matched control samples from healthy donors were analyzed with in vitro diagnostics research (IVDr) proton NMR spectroscopy at 600 MHz. Uni- and multivariate statistics were applied to identify significant biofluid alterations. We identified 29 significantly changed metabolites and 98 lipoproteins when comparing serum from healthy controls with those of PDAC patients. The most prominent features were assigned to (i) markers of pancreatic function (e.g., glucose and blood triglycerides), (ii) markers related to surgery (e.g., ketone bodies and blood cholesterols), (iii) PDAC-associated markers (e.g., amino acids and creatine), and (iv) markers for systemic disturbances in PDAC (e.g., gut metabolites DMG, TMAO, DMSO2, and liver lipoproteins). Quantitative serum NMR spectroscopy is suited as a diagnostic tool to investigate PDAC. Remarkably, 2-hydroxybutyrate (2-HB) as a previously suggested marker for insulin resistance was found in extraordinarily high levels only after pancreatectomy, suggesting this metabolite is the strongest marker for pancreatic loss of function.

Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery.

To summarize and analyze current research results on QOL after pancreatic surgery.

A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively.

A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear.

The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.

Introduction  Central pancreatectomy (CP) represents an organ-preserving type of pancreatic resection. The procedure has been associated with improved long-term functional results, but increased postoperative morbidity rates, compared with the more radical resection types. The purpose of the present study was to present the outcomes of three consecutive CPs performed in our department. Materials and Methods  Between January 2021 and January 2022, three patients (A, B, and C) were submitted to a CP in our department. Relevant patient data including data of the detailed preoperative assessment, operations notes, and recovery charts were prospectively collected and reviewed for all subjects. A scheduled follow-up, at the outpatient clinic, was conducted to assess the long-term functional results. Results  The postoperative course of patient A, a 56-year-old male, was complicated by a grade C postoperative pancreatic fistula that required a reoperation. Patient B, a 66-year-old female, developed a biochemical leak that resolved spontaneously while patient C, a 64-year-old male, had a completely uneventful recovery. The length of hospital stay for the three patients was 24, 12, and 8 days, respectively. Regarding the long-term results, patient B was lost to follow-up while both patient A and C were followed up, as outpatients, 21 and 10 months after the operation. During follow-up, in patient A, we did not record the presence of symptoms consistent with pancreatic exocrine insufficiency, the hemoglobin A1C (HbA1C) levels were 7.1% while no additional medications were needed to be prescribed to maintain the glycemic control following surgery. In patient C, a significant weight loss was recorded (body mass index reduction of 11 kg/m 2 ) without however the presence of malabsorption-specific symptoms. The HbA1C levels were 7.7% and optimal glycemic control was achieved with oral antiglycemic agents alone. Conclusion  CP should be regarded as a type of pancreatic resection with certain and very limited oncological indications. An approach of balancing the advantages out of the superior postoperative functional results with the drawbacks of the increased procedure-associated morbidity could highlight the patient group that could potentially experience benefits out of this limited type of resection.

Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT).

A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured.

101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT.

For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.

To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance.

Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified.

A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408).

Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I2 : 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I2 : 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P <0.01).

The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.

To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.

Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.

Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.

Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).

This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients.

Being an underdiagnosed and under or insufficiently treated condition, surgical pancreatic exocrine insufficiency (PSP) is the condition in which pancreatic enzymes are insufficient for digestion because of gastrointestinal (GI) surgery involving the upper GI tract, biliary ducts, or the pancreas, and and leading to potential malnutrition and deterioration in quality of life. Age, obesity, history of tobacco use, family history of diabetes, surgery due to a malignant tumor, presence of steatorrhea, jaundice, weight loss, and intraoperative findings of hard pancreatic texture have been associated with a higher risk of PSP. Pancreatoduodectomy (PD) has demonstrated an increased risk of developing PSP, with a prevalence between 19-100%. Distal pancreatectomy (DP) and central pancreatectomy (CenP) are associated with less risk of PSP, with a prevalence of 0-82% and 3.66-8.7%, respectively. In patients with chronic pancreatitis (CP), PSP was associated with 80% in Partington-Rochelle procedure, 86% in Frey procedure, 80% in duodenum preserving pancreatic head procedure, >60% in PD and 27.5-63% in DP. Fecal elastase-1 (FE-1) is a generally accepted tool for diagnosis. Treatment is recommended to start as soon as a diagnosis is achieved, or clinical suspicion is high. Pancreatic enzyme replacement therapy improves symptoms of malabsorption, facilitates weight gain, and ultimately improves patients' quality of life. Starting dosage is between 10,000-50,000 units in snacks and 50,000-75,000 units in main meals, administered throughout food intake, though further data specifically on PSP are needed. Follow-up in PSP is recommended on an on-demand basis, where malnutrition should be assessed.

Gastric venous congestion (GVC) after total pancreatectomy (TP) is rarely studied despite its high 5% to 28% incidence and possible association with mortality. This study aimed to provide insight about incidence, risk factors, management, and outcome of GVC after TP.

This retrospective observational single-center study included all patients undergoing elective TP from 2008 to 2021. The exclusion criteria ruled out a history of gastric resection, concomitant (sub)total gastrectomy for oncologic indication(s) or celiac axis resection, and postoperative (sub)total gastrectomy for indication(s) other than GVC.

The study enrolled 268 patients. The in-hospital major morbidity (Clavien-Dindo grade ≥IIIa) rate was 28%, and the 90-day mortality rate was 3%. GVC was identified in 21% of patients, particularly occurring during index surgery (93%). Intraoperative GVC was managed with (sub)total gastrectomy for 55% of the patients. The major morbidity rate was higher for the patients with GVC (44% vs 24%; p = 0.003), whereas the 90-day mortality did not differ significantly (5% vs 3%; p = 0.406). The predictors for major morbidity were intraoperative GVC (odds ratio [OR], 2.207; 95% confidence interval [CI], 1.142-4.268) and high TP volume (> 20 TPs/year: OR, 0.360; 95% CI, 0.175-0.738). The predictors for GVC were portomesenteric venous resection (PVR) (OR, 2.103; 95% CI, 1.034-4.278) and left coronary vein ligation (OR, 11.858; 95% CI, 5.772-24.362).

After TP, GVC is rather common (in 1 of 5 patients). GVC during index surgery is predictive for major morbidity, although not translating into higher mortality. Left coronary vein ligation and PVR are predictive for GVC, requiring vigilance during and after surgery, although gastric resection is not always necessary. More evidence on prevention, identification, classification, and management of GVC is needed.

Total pancreatectomy with islet autotransplantation is a therapeutic option to effectively achieve pain relief and improvements in quality of life for selected patients with debilitating pain from chronic pancreatitis. The understanding of the best application and clinical execution of this procedure is in evolution, with outcomes studies and clinical trials in progress.

Malnutrition in visceral surgery is frequent; it calls for screening prior to an operation, and its postoperative occurrence should be sought out and prevented, if possible. Organization of an individualized nutritional support strategy is based on systematic nutritional assessment and adapted to the type of surgery, the objectives being to forestall malnutrition and to reduce induced morbidity (immunosuppression, delayed wound healing, anastomotic fistulas…). Nutritional support is part and parcel of enhanced recovery after surgery (ERAS), and has shown effectiveness in the field of visceral surgery. Oral feeding should always be privileged to the greatest possible extent, complemented if necessary by nutritional supplements. If nutritional support is required, enteral nutrition should be favored over parenteral nutrition. As for the role of pharmaco-nutrition or immuno-nutrition, it remains ill-defined. Lastly, each type of visceral surgery entails specific modifications of the anatomy of the digestive system and is liable to have specific functional consequences, which should be known and taken into account in view of effectively tailoring nutritional support.

Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF).

TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking.

Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life.

After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857).

This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring.

Total pancreatectomy with islet autotransplantation (TPIAT) is the treatment of choice to preserve pancreatic endocrine function, alleviate pain, and improve quality of life (QoL) when other strategies are ineffective for chronic pancreatitis (CP) patients. This study utilized pancreatic disease-specific surveys developed by the European Organisation for Research and Treatment of Cancer (EORTC) to conduct a comprehensive, single-center examination of a large cohort of patients to gain understanding of QoL post-TPIAT. Two validated QoL surveys of the EORTC-QLQ-C30 and QLQ-PAN26-were administered in a prospective cohort of CP patients during pre-and post-operative scheduled visits. A total of 116 patients responded to the preoperative survey and were included in this study. The global health scale of QLQ-C30 was significantly improved after TPIAT when compared to baseline with delta scores of 24.26, 20.54, and 26.7 at 1, 2, and 3 years post-TPIAT (p < 0.001). The EORTC-PAN26 revealed significant improvements in symptom scales for pancreatic pain, bloating, digestive symptoms, taste, indigestion, weight loss, body image, and future worries. The comprehensive surveys in such a large cohort expands the QoL criterion in CP patients and indicates significant improvement in QoL post-TPIAT, further validating TPIAT as a treatment option for refractory CP.

Pancreatic adenocarcinoma represents a therapeutic challenge due to the high toxicity of antineoplastic treatments and secondary effects of pancreatectomy. T-514, a toxin isolated from Karwinskia humboldtiana (Kh) has shown antineoplastic activity on cell lines. In acute intoxication with Kh, we reported apoptosis on the exocrine portion of pancreas. One of the mechanisms of antineoplastic agents is the induction of apoptosis, therefore our main objective was to evidence structural and functional integrity of the islets of Langerhans after the administration of Kh fruit in Wistar rats.

TUNEL assay and immunolabelling against activated caspase-3 were used to detect apoptosis. Also, immunohistochemical tests were performed to search for glucagon and insulin. Serum amylase enzyme activity was also quantified as a molecular marker of pancreatic damage.

Evidence of toxicity on the exocrine portion, by positivity in the TUNEL assay and activated caspase-3, was found. On the contrary, the endocrine portion remained structurally and functionally intact, without apoptosis, and presenting positivity in the identification of glucagon and insulin.

These results demonstrated that Kh fruit induces selective toxicity on the exocrine portion and establish a precedent to evaluate T-514 as a potential treatment against pancreatic adenocarcinoma without affecting the islets of Langerhans.

Although intraoperative peritoneal lavage often is performed routinely with the aim of reducing peritoneal contamination, evidence of lavage benefit in elective pancreatic surgery is limited.

We retrospectively classified patients who had undergone pancreatic surgery to groups given or not given peritoneal lavage, then comparing clinical results. This saline lavage was performed at the end of the operation. The primary endpoint was rate of surgical site infection. Frequency of peritoneal recurrence also was evaluated.

Among all 104 patients in the study, incidence of infectious complications in the lavage group (n = 65) was significantly higher than in the non-lavage group (n = 39; 35% vs. 15%, P = 0.041), while incidences of postoperative complications overall and surgical site infection did not differ between lavage (80% and 26%) and non-lavage groups (67% and 10%, P = 0.162 and 0.076, respectively). Among 63 patients undergoing pancratoduodenectomy, frequencies of positive bacterial cultures of drainage fluids on postoperative days 1 and 3 were greater in the non-lavage group (P < 0.001 and P = 0.012), but surgical site infection was significantly more frequent in the lavage group (P = 0.043). Among patients with pancreatic and biliary cancers, lavage did not affect frequency of peritoneal recurrence.

Intraoperative lavage did not prevent surgical site infection or peritoneal recurrence of pancreatobiliary cancer.

The safety and feasibility of completion total pancreatectomy (TP) for remnant pancreatic neoplasms remain controversial and are rarely compared with that of initial TP. Thus, we aimed to compare the safety of these two procedures inducing a pancreatic state.

Patients who underwent TP for pancreatic neoplasms between 2006 and 2018 at our institution were included in this study. Tumor pathologies were classified into three subgroups according to survival curves. We used 1:1 propensity score matching (PSM) to analyze age, sex, Charlson Comorbidity Index, and tumor stage. Finally, we analyzed the primary outcome Clavien-Dindo classification (CDC) grade, risks of other safety-related outcomes, and the survival rate of patients with invasive cancer.

Of 54 patients, 16 underwent completion TP (29.6%) and 38 (70.4%) underwent initial TP. Before PSM analysis, age and Charlson Comorbidity Index were significantly higher, and T category and stage were significantly lower for the completion TP group. Upon PSM analysis, these two groups were equivalent in CDC grade [initial TP vs. completion TP: 71.4% (10/14) vs. 78.6% (11/14); p = 0.678] and other safety-related outcomes. Additionally, while the overall survival and recurrence-free survival of patients with invasive cancer were not significantly different between these two groups, the T category and stage tended to be remarkably severe in the initial TP group.

PSM analysis for prognostic factors showed that completion TP and initial TP have similar safety-related outcomes that can be used as a decision-making reference in the surgery of pancreatic tumors.

Minimally invasive total pancreatectomy (MITP) is considered safe and feasible with limited evidence on this procedure. The aim of this study was to systematically analyze the current literature on MITP compared to open TP (OTP).

Randomized controlled trials and prospective non-randomized comparative studies were sought systematically in MEDLINE, Web of Science and CENTRAL from their inception until December 2021. Outcome measures included operative time, length of hospital stay (LOH), spleen-preservation rate, estimated blood loss (EBL), need for transfusion, venous resection rate, delayed gastric emptying (DGE), biliary leakage, postpancreatectomy hemorrhage (PPH), reoperation rate, overall 30-day morbidity (Clavien-Dindo > IIIa), 90-day mortality, 90-day readmission, examined lymph nodes (ELN). Pooled results are presented as odds ratios (OR) or mean difference (MD) with 95% confidence interval (CI).

7 observational studies with a total of 4212 patients were included. MITP had a decreased EBL and transfusion rate, lower 30-day morbidity and 90-day mortality with a longer LOH compared to OTP. There were no significant differences regarding operative time, spleen preservation rate, DGE, biliary leakage, venous resection rate, PPH, reoperation, 90-day readmission and ELN.

Based on the available studies, MITP is safe and feasible compared to OTP in highly experienced hands from high-volume centers. Further high-quality studies are needed to verify the conclusion.