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Pancreatic cancer

Open AccessPublished:January 02, 2023DOI:https://doi.org/10.1016/j.ejso.2023.01.001

      Abstract

      The need for a common education and training track in surgical oncology across Europe has been emphasized. ESSO provides several hands-on courses for skills training and face-to-face discussions. The core curriculum provides a framework for the overall theoretical requirements in surgical oncology. The UEMS/EBSQ fellowship exam is designed to test core competencies in the candidate's core knowledge in their prespecified area of expertise. A core set of points for each cancer type is lacking. Hence, a condensed outline of themed expected to be covered in the curriculum and relevant to an optimal practice in surgical oncology is provided. This article outlines pancreatic cancer.

      1. Introduction

      There is a need to unify knowledge and skills in surgical oncology across Europe. To this end, a core curriculum in surgical oncology has been updated [
      • van der Hage J.
      • et al.
      The ESSO core curriculum committee update on surgical oncology.
      ], providing a dense, point-by-point outline of central aspects of cancer care that the cancer surgeon should have expressed knowledge about. Notably, this dense lexicon may serve as a broad guide for studies in cancer surgery. However, there is a need to have further vetted input about the specific cancers, such as ‘pancreatic cancer’. In this article, referral to a ‘student’ is regarding both trainees and specialist surgeons, as the training background varies considerably and the curriculum is hence directed towards both junior trainees and specialist surgeons who pursue a career in cancer surgery. All surgeons are life-long students - in theory and in practice.
      The education and training in pancreatic surgery is not uniform across Europe nor the World [
      • Parks R.W.
      • Guest R.V.
      Education and training in pancreatic surgery.
      ]. The diagnosis and management of any specific cancer type is known to experience trends in knowledge, emerging challenges, ongoing debates and, a change in the knowledgebase from which both decisions and discussions are generated. Some of these are expressed in the form of consensus documents [
      • Prades J.
      • et al.
      Bratislava Statement: consensus recommendations for improving pancreatic cancer care.
      ], other topics or debates may seem more nebulous as themes emerge in meetings or conferences. For the junior student, it may be a difficult task to grasp the overview of core themes in any given cancer subdiscipline.
      Hence, based on the European fellowship exam candidates request, we have prepared an essential set of themes to present a set of core knowledge needed for a specific disease beyond the core curriculum in surgical oncology. This will not be a textbook, nor a comprehensive review. Rather, it should provide an overview of themes and associated references for further study, but with more detail than the core curriculum overview [
      • van der Hage J.
      • et al.
      The ESSO core curriculum committee update on surgical oncology.
      ]. Here, we present the knowledge and emerging evidence in the field of pancreatic cancer.

      2. Epidemiology, risk factors and early diagnosis

      Pancreatic cancer is increasing in most parts of the Western world. In general, pancreatic cancer is less common than many other large cancer groups, but due to an increasing incidence in an aging population, and the high lethality rate, it is rapidly becoming one of the most frequent causes of cancer deaths [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ,
      • Park W.
      • et al.
      Pancreatic cancer: a review.
      ].
      Known risk factors are related to lifestyle characteristics such as smoking, alcohol consumption and overweight [
      • Park W.
      • et al.
      Pancreatic cancer: a review.
      ]. The overall strongest risk factor is increasing age. Chronic and hereditary pancreatitis are known risk factors to pancreatic cancer. Hereditary pancreatitis is related to genetic risk, and both familial pancreatic cancer and genetic syndromes are associated with a higher incidence of pancreatic cancer [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ,
      • Shah I.
      • et al.
      Association between family history and risk of pancreatic cancer in patients with BRCA1 and BRCA2 pathogenic variants.
      ,
      • Sawhney M.S.
      • et al.
      ASGE guideline on screening for pancreatic cancer in individuals with genetic susceptibility: summary and recommendations.
      ,
      • Laks S.
      • et al.
      Management recommendations for pancreatic manifestations of von Hippel-Lindau disease.
      ]. New-onset diabetes is increasingly appreciated as an early warning sign [
      • Shen B.
      • et al.
      Association between age at diabetes onset or diabetes duration and subsequent risk of pancreatic cancer: results from a longitudinal cohort and mendelian randomization study.
      ], although screening recommendations are not yet clear. Cystic lesions are a risk factor for pancreatic cancer [
      • Søreide K.
      • Marchegiani G.
      Clinical management of pancreatic premalignant lesions.
      ], and largely refers to mucinous cysts (mucinous cystic neoplasia (MCN) or intraductal papillary mucinous neoplasia (IPMN).
      Identification of families of genetic risk are increasingly important from a screening and early detection perspective [
      • Olakowski M.
      • Bułdak Ł.
      Current status of inherited pancreatic cancer.
      ,
      • Li S.
      • et al.
      Cancer risks associated with BRCA1 and BRCA2 pathogenic variants.
      ,
      • Clark N.M.
      • et al.
      Genetic testing among patients with high-risk breast, ovarian, pancreatic, and prostate cancers.
      ] and, also, as targeted drugs may be directed to those with a BRCA1/2 mutational profile. Pancreatic cancer developed on a background of hereditary non-polyposis colon cancer (HNPCC/Lynch syndrome) may be important as cancers with microsatellite instability may be rare responders to immunotherapy. Olaparib is currently approved in the metastatic setting for BRCA1/2 mutants, and ongoing trials are underway on use of this in the adjuvant setting. The treatment landscape for pancreatic cancer is evolving with new treatment approaches [
      • Leidner R.
      • et al.
      Neoantigen T-cell receptor gene therapy in pancreatic cancer.
      ]. Guidelines [
      • Sohal D.P.S.
      • et al.
      Metastatic pancreatic cancer: ASCO guideline update.
      ,
      • Tempero M.A.
      • et al.
      Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology.
      ] should be consulted in addition to updates from trials.

      3. Precursor lesions and premalignant cysts

      Precursors to pancreatic cancer occur, in practical terms, in the form of pancreatic cysts [
      • Aunan J.R.
      • et al.
      Pancreatic cystic lesions and risk of cancer.
      ]. Cysts have become an increasing workload for surgeons involved in pancreatic diseases. A refined approach in choice of diagnostics and choice of surveillance over surgery is important [
      • Søreide K.
      • Marchegiani G.
      Clinical management of pancreatic premalignant lesions.
      ], with changing perceptions with emerging data, and new knowledge accumulating in new guidelines. Specific guidelines have been proposed, yet varies considerably in recommendations [
      • Aziz H.
      • et al.
      Comparison of society guidelines for the management and surveillance of pancreatic cysts: a review.
      ]. The fellowship exam candidate should be able to know and discuss the core principles of cyst detection, management, surveillance and indications for surgery [
      • Søreide K.
      • Marchegiani G.
      Clinical management of pancreatic premalignant lesions.
      ].
      The candidate should also be aware of the role of Pancreatic Intraepithelial Neoplasia (PanINs) as the morphological component in the progression model of pancreatic cancer [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ]. The distinction of PanIN to cystic precursor lesions, such as IPMN, should be clear.

      4. Understanding the pathobiology of pancreatic cancer

      Both the adjustable and genetic risk factors insufficiently explain the aetiology of pancreatic cancer [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ]. However, increased risk ratios have been reported in patients with germ line mutations and hereditary disorders with exposure to environmental carcinogens. Therefore, a better understanding of the pathobiology is essential for its prevention and choice of treatment. Basic knowledge of pancreatic carcinogenesis includes the important RAS-pathway, including mutations in KRAS (found in >95% of all pancreatic cancers), CDKN2A, TP53, and SMAD4 [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ,
      • Park W.
      • et al.
      Pancreatic cancer: a review.
      ]. The carcinogenesis evolves morphologically in the pancreatic duct through the pancreatic intraepithelial neoplasia (PanIN) precursors and subsequent malignancy with tumor spread into the local and distant microenvironment. Knowledge on the unique features of stromal proliferation and metabolic adaptation to obtain nutrients in a hypoxic environment and inherent chemoresistance is important in this regard [
      • Wood L.D.
      • et al.
      Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment.
      ,
      • Hingorani S.R.
      Epithelial and stromal co-evolution and complicity in pancreatic cancer.
      ]. Moreover, these driving mutations play an increasing role in diagnosis with the use of high-throughput DNA analyses.

      5. Staging and the evolution of borderline and locally advanced disease

      Appropriate staging is an important part of classifying disease and choosing appropriate treatment. Staging as based on clinical, radiological, laboratory/biomarker and pathological examinations should be incorporated into a comprehensive understanding of strengths and pitfalls [
      • Roalsø M.
      • et al.
      Refined TNM-staging for pancreatic adenocarcinoma - real progress or much ado about nothing?.
      ]. Borderline resectable and locally advanced pancreatic cancer is defined by several different systems [
      • Khachfe H.H.
      • et al.
      Borderline resectable and locally advanced pancreatic cancers: a review of definitions, diagnostics, strategies for treatment, and future directions.
      ,
      • Christians K.K.
      • Evans D.B.
      Pancreaticoduodenectomy and vascular reconstruction: indications and techniques.
      ,
      • Bratlie S.O.
      • et al.
      Resectable, borderline, and locally advanced pancreatic cancer-"the good, the bad, and the ugly" candidates for surgery?.
      ], while the NCCN definition is the most frequently used [
      • Tempero M.A.
      • et al.
      Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology.
      ]. Definition used for borderline resectable and locally advanced cancers is important for operation planning and for reconstruction alternatives [
      • Bockhorn M.
      • et al.
      Borderline resectable pancreatic cancer: a consensus statement by the international study group of pancreatic surgery (ISGPS).
      ] of vessels (Fig. 1) when needed [
      • Christians K.K.
      • Evans D.B.
      Pancreaticoduodenectomy and vascular reconstruction: indications and techniques.
      ,
      • Kleive D.
      • et al.
      Pancreatoduodenectomy with portal vein resection.
      ]. The definitions used is also important for comparison of trials results [
      • Søreide K.
      Neoadjuvant and adjuvant therapy in operable pancreatic cancer: both honey and milk (but No bread?).
      ], as slight deviation in inclusion and exclusion criteria hampers the head-to-head comparison between studies.
      Fig. 1
      Fig. 1Borderline resectability as defined by venous tumor contact
      Legend: Venous tumor contact in pancreatic cancer invasion of SMV/PV. (a) Less than or equal to 180° tumor contact without deformity. (b) More than 180° tumor contact without deformity.
      (c) Less than or equal to 180° tumor contact with deformity (arrows). (d) Tear drop deformity (arrows). SMV superiomesenteric vein, PV portal vein, T tumor, V vein. Dashed line 180° of lumen circumference. Reproduced with permission from Kleive et al. [
      • Kleive D.
      • et al.
      Pancreatoduodenectomy with portal vein resection.
      ], ©Springer.
      In pancreatic cancer, the technical definition of resectability staging prevails over the formal TNM classification in clinical practice [
      • Bratlie S.O.
      • et al.
      Resectable, borderline, and locally advanced pancreatic cancer-"the good, the bad, and the ugly" candidates for surgery?.
      ,
      • Oba A.
      • et al.
      New criteria of resectability for pancreatic cancer: a position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS).
      ]. Together with imaging features, tumour biomarkers and clinical fitness, the decision to pursue systemic therapy first, upfront surgery or simple palliative care is made. Decisions should be made in a multidisciplinary team setting [
      • Kirkegård J.
      • Mortensen F.V.
      The multidisciplinary team conference.
      ].

      6. Neoadjuvant and adjuvant treatment and trials

      Optimal survival in pancreatic cancer is achieved through multimodal therapy (Fig. 2) for both resectable, borderline and locally advanced pancreatic cancer [
      • Khorana A.A.
      • et al.
      Potentially curable pancreatic cancer: American society of clinical oncology clinical practice guideline update.
      ]. The treatment sequencing and best multimodal combination remains uncertain, as several trials are ongoing and robust data still awaited [
      • Seo Y.D.
      • Katz M.H.G.
      Preoperative therapy for pancreatic adenocarcinoma-precision beyond anatomy.
      ]. While neoadjuvant treatment is becoming the standard in the treatment algorithm of borderline and locally advanced pancreatic cancer [
      • Khachfe H.H.
      • et al.
      Borderline resectable and locally advanced pancreatic cancers: a review of definitions, diagnostics, strategies for treatment, and future directions.
      ], the role in primary or ‘upfront’ resectable pancreatic cancer is still debated [
      • Versteijne E.
      • et al.
      Neoadjuvant chemoradiotherapy versus upfront surgery for resectable and borderline resectable pancreatic cancer: long-term results of the Dutch randomized PREOPANC trial.
      ,
      • van Dam J.L.
      • et al.
      Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: a meta-analysis of randomised controlled trials.
      ,
      • Katz M.H.G.
      • et al.
      Efficacy of preoperative mFOLFIRINOX vs mFOLFIRINOX plus hypofractionated radiotherapy for borderline resectable adenocarcinoma of the pancreas: the A021501 phase 2 randomized clinical trial.
      ,
      • Chawla A.
      Contemporary trials evaluating neoadjuvant therapy for resectable pancreatic cancer.
      ,
      • Sternby H.
      • Andersson B.
      Nationwide trends and outcomes of neoadjuvant chemotherapy in pancreatic cancer - an analysis of the Swedish national pancreatic cancer registry.
      ]. Ongoing trials are exploring the option of so-called total neoadjuvant treatment (TNT) whereby the full length of treatment is given prior to surgery [
      • Labori K.J.
      Short-course or total neoadjuvant chemotherapy in resectable and borderline resectable pancreatic cancer - current status and future perspectives.
      ,
      • De Simoni O.
      • et al.
      Could total neoadjuvant therapy followed by surgical resection Be the new standard of care in pancreatic cancer? A systematic review and meta-analysis.
      ,
      • Barrak D.
      • et al.
      Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response.
      ], rather than split into pre- and post-surgical treatment courses. Resection of ‘oligometastatic disease’ (e.g. a single liver metastasis) in pancreatic cancer (Fig. 2) is controversial [
      • Frountzas M.
      • et al.
      Oligometastatic pancreatic cancer" definition: the first step.
      ]. In a few, select patients with good and durable response from pre-operative (induction or conversion) therapy, resection can be offered with reasonable outcomes [
      • Hamad A.
      • et al.
      Surgical treatment of hepatic oligometastatic pancreatic ductal adenocarcinoma: an analysis of the National Cancer Database.
      ].
      Fig. 2
      Fig. 2Overview of contemporary concepts of multimodal therapy in pancreatic cancer
      Legend: Different settings for resectable, borderline, locally advanced and metastatic pancreatic cancer. Adjuvant therapy after surgery is the standard in upfront resectable disease, but trials are exploring the role of ‘neoadjuvant’ therapy. Total neoadjuvant therapy (TNT) is an emerging concept, used for all categories. A subgroup of borderline and locally advanced proceed to surgery. Estimated survival time (far right) are accumulated outcomes, but large variation and heterogeneity across studies exist.
      Basic knowledge about chemotherapy should include arguments in favour of neoadjuvant chemotherapy and upfront surgery, respectively, taking into account local staging by imaging, biological status (i.e. high CA19-9), need for biliary stenting, and patient performance status (Fig. 2). For preoperative chemotherapy, a tissue-diagnosis is required and hence either ERCP or EUS (or both) are required for tissue samples and for placing a stent to relieve of jaundice prior to oncological treatment [
      • Du J.
      • et al.
      Stent selection in preoperative biliary drainage for patients with operable pancreatic cancer receiving neoadjuvant therapy: a meta-analysis and systematic review.
      ]. Procedure related complications may occur (e.g. ERCP-induced acute pancreatitis) and should be acknowledged in the risk/benefit consideration. Pre-operative stenting of the jaundiced patient should not be done as a routine in otherwise resectable tumours [
      • Lee P.J.
      • et al.
      Preoperative biliary drainage in resectable pancreatic cancer: a systematic review and network meta-analysis.
      ], unless infectious complications occur or neoadjuvant chemotherapy is planned. All pre-operative imaging should be done before any stenting of the biliary tract, if possible, to obtain high-quality staging.
      The literature on the effect of adjuvant chemotherapy is well-documented, among others through the ESPAC1-4 and PRODIGE trials [
      • Klaiber U.
      • et al.
      Adjuvant treatment for pancreatic cancer.
      ,
      • Jones R.P.
      • et al.
      Patterns of recurrence after resection of pancreatic ductal adenocarcinoma: a secondary analysis of the ESPAC-4 randomized adjuvant chemotherapy trial.
      ,
      • Conroy T.
      • et al.
      Five-year outcomes of FOLFIRINOX vs gemcitabine as adjuvant therapy for pancreatic cancer: a randomized clinical trial.
      ,
      • Neoptolemos J.P.
      • et al.
      Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.
      ], that supports the routine use of adjuvant chemotherapy after surgery, with the most recent trial on modified FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) compared to Gemcitabine monotherapy presenting a median overall survival of almost 55 months for mFOLFIRINOX (compared to 36 months for Gemcitabine-based treatment) [
      • Conroy T.
      • et al.
      Five-year outcomes of FOLFIRINOX vs gemcitabine as adjuvant therapy for pancreatic cancer: a randomized clinical trial.
      ].
      Intraoperative radiotherapy is controversial and only used at few centres in the setting of potentially curable or operable pancreatic cancer [
      • Calvo F.A.
      • et al.
      ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy in borderline-resected pancreatic cancer.
      ,
      • Ahn D.H.
      • Bekaii-Saab T.
      The continued struggle for defining a role for radiotherapy in pancreas cancer.
      ]. Trials on targeted therapy are ongoing and there is some evidence that certain pancreatic cancer subtypes may respond better to such treatment [
      • Seo Y.D.
      • Katz M.H.G.
      Preoperative therapy for pancreatic adenocarcinoma-precision beyond anatomy.
      ,
      • Casolino R.
      • et al.
      Reshaping preoperative treatment of pancreatic cancer in the era of precision medicine.
      ].
      The majority of patients starting on ‘induction or conversion’ chemotherapy for locally advanced (or, oligometastatic) pancreatic cancer will progress and hence go on to palliative chemotherapy. However, a select number of patients have stable disease or response and can be surgically explored for potential resection.

      7. Enhanced recovery and perioperative care

      Knowledge on perioperative care is essential as these may impact the outcome of pancreatic surgery. Enhanced recovery after surgery (ERAS) principles should be known and guided towards those intended for pancreatic surgery [
      • Melloul E.
      • et al.
      Guidelines for perioperative care for pancreatoduodenectomy: enhanced recovery after surgery (ERAS) recommendations 2019.
      ,
      • Kuemmerli C.
      • et al.
      Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.
      ].
      Prehabilitation for high-risk patients before surgery has experienced an increased interest [
      • Bongers B.C.
      • et al.
      Enhanced recovery after surgery programmes in older patients undergoing hepatopancreatobiliary surgery: what benefits might prehabilitation have?.
      ,
      • Bundred J.R.
      • et al.
      Prehabilitation prior to surgery for pancreatic cancer: a systematic review.
      ], particularly as more elderly, frail and comorbid patients present with technically resectable pancreatic cancer but borderline clinical reserves. Assessment of nutritial needs [
      • Gianotti L.
      • et al.
      Nutritional support and therapy in pancreatic surgery: a position paper of the International Study Group on Pancreatic Surgery (ISGPS).
      ], including exocrine supplement, is important for optimal outcomes [
      • Phillips M.E.
      • et al.
      Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines.
      ]. Home-based exercise programs and frailty assessment is clinically relevant for patients with pancreatic cancer [
      • Russell T.B.
      • et al.
      Results from a UK-wide survey: the nutritional assessment and management of pancreatic resection patients is highly variable.
      ,
      • Rostoft S.
      • van Leeuwen B.
      Frailty assessment tools and geriatric assessment in older patients with hepatobiliary and pancreatic malignancies.
      ,
      • Gupta P.
      • et al.
      Effect of exercise on pancreatic cancer patients during treatment: a scoping review of the literature.
      ].

      8. Surgery and related complications

      Pancreatic surgery is complex and knowledge about the various indications, the variation in techniques and the relevant associated complications is essential. Pancreatoduodenectomy [
      • Grochola L.F.
      • et al.
      Standard pancreatoduodenectomy for resectable pancreatic cancer.
      ], open and laparoscopic distal pancreatectomy [
      • Stättner S.
      • et al.
      Open distal pancreatectomy for pancreatic cancer.
      ,
      • Søreide K.
      • et al.
      Laparoscopic distal pancreatectomy.
      ] and total pancreatectomy [
      • Bayram O.
      • et al.
      Total pancreatectomy.
      ] each have their own specific indications, contraindications, and short-term and long-term considerations to be aware of. The evolution of surgery for pancreatic cancer including some of the newer concepts of vessel resections and radical surgery is required knowledge [
      • Christians K.K.
      • Evans D.B.
      Pancreaticoduodenectomy and vascular reconstruction: indications and techniques.
      ,
      • Kleive D.
      • et al.
      Pancreatoduodenectomy with portal vein resection.
      ,
      • Schneider M.
      • et al.
      Technical advances in surgery for pancreatic cancer.
      ,
      • Hackert T.
      • et al.
      Fifty years of surgery for pancreatic cancer.
      ], even if some of these procedures are only performed in select patients at very high-volume centres.
      An overview of the indications, contraindications, potential benefits and limitations to minimal-invasive surgery is required [
      • Søreide K.
      • et al.
      Laparoscopic distal pancreatectomy.
      ,
      • Jiao L.R.
      • et al.
      Robotic surgery for pancreatic cancer.
      ,
      • Ban D.
      • et al.
      International expert consensus on precision anatomy for minimally invasive distal pancreatectomy: PAM-HBP surgery project.
      ,
      • Asbun H.J.
      • et al.
      The Miami international evidence-based guidelines on minimally invasive pancreas resection.
      ]. Appreciation of the benefits and risks of enucleation procedures should be required. The variants of pancreatic head resection and the outcomes of trials exploring extended lymphadenectomy, pylorus-resecting or -sparing and advanced vascular techniques, including vein resection and the rare indications for arterial resection and reconstruction. As most centres will not perform such advanced procedures, there is still a need to have an overview of which patient may be eligible for such approaches.
      Several modes of resection and repair exist [
      • Daamen L.A.
      • et al.
      A web-based overview, systematic review and meta-analysis of pancreatic anastomosis techniques following pancreatoduodenectomy.
      ,
      • Miao Y.
      • et al.
      Management of the pancreatic transection plane after left (distal) pancreatectomy: expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS).
      ,
      • Shrikhande S.V.
      • et al.
      Pancreatic anastomosis after pancreatoduodenectomy: a position statement by the international study group of pancreatic surgery (ISGPS).
      ], and knowledge including a broad overview of the most common techniques is expected [
      • Daamen L.A.
      • et al.
      A web-based overview, systematic review and meta-analysis of pancreatic anastomosis techniques following pancreatoduodenectomy.
      ,
      • Shrikhande S.V.
      • et al.
      Pancreatic anastomosis after pancreatoduodenectomy: a position statement by the international study group of pancreatic surgery (ISGPS).
      ,
      • Sachs T.E.
      • Tseng J.F.
      Landmark series in pancreatic tumors: anastomotic techniques and route of reconstruction.
      ]. The candidate should have sound knowledge on possible prevention, early recognition, and treatment of complications after pancreatic surgery, for both surgical and non-surgical issues [
      • Smits F.J.
      • et al.
      Algorithm-based care versus usual care for the early recognition and management of complications after pancreatic resection in The Netherlands: an open-label, nationwide, stepped-wedge cluster-randomised trial.
      ]. Knowledge of the most recent consensus definitions exist for typical complications related to pancreatic surgery, including post-operative pancreatic fistula [
      • Bassi C.
      • et al.
      The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years after.
      ], post-pancreatectomy haemorrhage [
      • Wente M.N.
      • et al.
      Postpancreatectomy hemorrhage (PPH): an international study group of pancreatic surgery (ISGPS) definition.
      ], delayed gastric emptying [
      • Wente M.N.
      • et al.
      Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS).
      ] chyle leak [
      • Besselink M.G.
      • et al.
      Definition and classification of chyle leak after pancreatic operation: a consensus statement by the International Study Group on Pancreatic Surgery.
      ] and, more recently, post-pancreatectomy acute pancreatitis [
      • Marchegiani G.
      • et al.
      Postpancreatectomy acute pancreatitis (PPAP): definition and grading from the international study group for pancreatic surgery (ISGPS).
      ].

      9. Long-term outcomes

      Furthermore, diagnosis and treatment of long-term consequences of pancreatic surgery is necessary to enhance quality of life and decrease morbidity. There are a wide range of instruments available to measure quality of life (QoL) outcomes in pancreatic cancer surgical patients, although only few are disease-specific [
      • Toms C.
      • et al.
      Quality of life instruments and trajectories after pancreatic cancer resection: a systematic review.
      ,
      • James N.E.
      • et al.
      Quality of life after pancreatic surgery - a systematic review.
      ]. Most of the included studies reported no significant changes in QoL outcomes at short- or long-term follow-up [
      • Toms C.
      • et al.
      Quality of life instruments and trajectories after pancreatic cancer resection: a systematic review.
      ,
      • James N.E.
      • et al.
      Quality of life after pancreatic surgery - a systematic review.
      ]. Dietary or nutritional issues, diabetes or other complications may occur in long-term survivors.

      10. Experimental or adjunct treatments

      Some techniques are being explored for added value in treatment of pancreatic cancer, with lack of robust data to firmly guide clinical decisions. Ablation techniques including irreversible electroporation (IRE) [
      • Ratnayake B.
      • et al.
      Margin accentuation irreversible electroporation in stage III pancreatic cancer: a systematic review.
      ,
      • White R.R.
      • et al.
      The landmark series: locally advanced pancreatic cancer and ablative therapy options.
      ] remains experimental but may have an interest in combination with immune therapy in future trials [
      • Granata V.
      • et al.
      Local ablation of pancreatic tumors: state of the art and future perspectives.
      ].

      11. Key sources for further studies

      It is imperative to seek new and updated knowledge as well as establish a study base of existing data for in-depth studies. The continued consensus work of the International Study Group of Pancreatic Surgery (ISGPS) should be recognized [
      • Bockhorn M.
      • et al.
      Borderline resectable pancreatic cancer: a consensus statement by the international study group of pancreatic surgery (ISGPS).
      ,
      • Gianotti L.
      • et al.
      Nutritional support and therapy in pancreatic surgery: a position paper of the International Study Group on Pancreatic Surgery (ISGPS).
      ,
      • Miao Y.
      • et al.
      Management of the pancreatic transection plane after left (distal) pancreatectomy: expert consensus guidelines by the International Study Group of Pancreatic Surgery (ISGPS).
      ,
      • Shrikhande S.V.
      • et al.
      Pancreatic anastomosis after pancreatoduodenectomy: a position statement by the international study group of pancreatic surgery (ISGPS).
      ,
      • Bassi C.
      • et al.
      The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years after.
      ,
      • Wente M.N.
      • et al.
      Postpancreatectomy hemorrhage (PPH): an international study group of pancreatic surgery (ISGPS) definition.
      ,
      • Wente M.N.
      • et al.
      Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS).
      ,
      • Besselink M.G.
      • et al.
      Definition and classification of chyle leak after pancreatic operation: a consensus statement by the International Study Group on Pancreatic Surgery.
      ,
      • Probst P.
      • et al.
      Evidence map of pancreatic surgery-A living systematic review with meta-analyses by the international study group of pancreatic surgery (ISGPS).
      ]. Available guidelines and consensus reports should be consulted [
      • Prades J.
      • et al.
      Bratislava Statement: consensus recommendations for improving pancreatic cancer care.
      ,
      • Tempero M.A.
      • et al.
      Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology.
      ,
      • Aziz H.
      • et al.
      Comparison of society guidelines for the management and surveillance of pancreatic cysts: a review.
      ,
      • Melloul E.
      • et al.
      Guidelines for perioperative care for pancreatoduodenectomy: enhanced recovery after surgery (ERAS) recommendations 2019.
      ,
      • Phillips M.E.
      • et al.
      Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines.
      ,
      • Li M.
      Clinical practice guidelines for the interventional treatment of advanced pancreatic cancer (5(th) edition).
      ,
      • Martin-Perez E.
      • et al.
      Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer.
      ]. There are several sources of updated information on pancreatic cancer, such as the “Map of Pancreatic Surgery” (freely accessible via www.evidencemap.surgery) [
      • Probst P.
      • et al.
      Evidence map of pancreatic surgery-A living systematic review with meta-analyses by the international study group of pancreatic surgery (ISGPS).
      ]. For pancreatic cancer, an ESSO-endorsed “Textbook of Pancreatic Cancer” in 2 vol is available from Springer, some of which are cited here [
      • Parks R.W.
      • Guest R.V.
      Education and training in pancreatic surgery.
      ,
      • Kleive D.
      • et al.
      Pancreatoduodenectomy with portal vein resection.
      ,
      • Kirkegård J.
      • Mortensen F.V.
      The multidisciplinary team conference.
      ,
      • Søreide K.
      Early diagnosis of sporadic pancreatic cancer.
      ]. Continuous updates will also be possible through ESSO pre-conference HPB courses and HPB masterclass courses (www.essoweb.org). Similarly, courses may be offered through the European-African Hepatobiliary-Pancreatic Association (E-AHPBA).

      Declaration of competing interest

      None reported.

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