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Christopher B Nahm,1–3 Saxon J Connor,4 Jaswinder S Samra,1,2,5 Anubhav Mittal1,2,5 1Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, Sydney, Australia; 2Northern Clinical School, Sydney Medical School, The University of Sydney, Sydney, Australia; 3Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, Australia; 4Department of Surgery, Christchurch Hospital, Christchurch, New Zealand; 5Australian Pancreatic Centre, Sydney, Australia Abstract: Postoperative pancreatic fistula (POPF) remains the major cause of morbidity after pancreatic resection, affecting up to 41% of cases. With the recent development of a consensus definition of POPF, there has been a large number of reports examining various risk factors, prediction models, and mitigation strategies for this costly complication. Despite these strategies, the rates of POPF have not significantly diminished. Here, we review the literature and evidence regarding both traditional and emerging concepts in POPF prediction, prevention, and management. In particular, we review the evidence for the association between postoperative pancreatitis and POPF, and present a novel proposed mechanism for the development of POPF. Keywords: postoperative pancreatic fistula, postoperative pancreatitis, distal pancreatectomy, pancreaticoduodenectomy

Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients., Methods: This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival., Results: Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months)., Conclusion: A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Minimally invasive surgical necrosectomy plays an important role in the management of infected pancreatic necrosis, with a goal of removing debris and debriding necrotic tissue. Pulse lavage is designed to simultaneously hydrostatically debride and remove the infected necrotic tissue with suction. It is also able to remove significant amounts of debris without traumatic manipulation of the necrotic tissue which may be adherent to surrounding tissue and can result in injury., Methods and Results: The surgical technique of utilising a waterjet pulse lavage device during the minimally invasive necrosectomy is detailed. Sixteen patients being managed via a step-up approach underwent endoscopic necrosectomy via a radiologically placed drain tract. All sixteen patients were successfully managed endoscopically without conversion to open necrosectomy, and survived their admission. There were no complications associated with the use of the waterjet pulse lavage., Conclusion: Waterjet pulse lavage is a useful adjunct in minimally invasive necrosectomy, which reduces the length of the necrosectomy procedure, and facilitates removal of necrotic tissue while minimising the risk of traumatising healthy tissue., (© 2024. The Author(s).)

Importance: Ampullary adenocarcinoma (AA) is characterized by clinical and genomic heterogeneity. A previously developed genomic classifier defined biologically distinct phenotypes with greater accuracy than standard histologic classification. External validation is needed before routine clinical use., Objective: To test external validity of the prognostic value of the hidden genome classifier of AA., Design, Setting, and Participants: This retrospective cohort study took place at 6 international academic institutions. Consecutive patients (n = 192) who underwent curative-intent resection of histologically confirmed AA were included. The data were analyzed from January 2005 through July 2020., Exposures: The multilevel meta-feature regression model previously trained on a prospectively sequenced cohort of 3411 patients (1001 pancreatic adenocarcinoma, 165 distal bile duct adenocarcinoma, and 2245 colorectal adenocarcinoma) was applied to AA sequencing data to quantify the relative proportions of parental cell of origin., Main Outcome and Measures: Genomic classification was correlated with immunohistologic subtype (intestinal [INT] or pancreatobiliary [PB]) and with overall survival (OS), using the log-rank test and Cox proportional hazard models., Results: Among 192 patients with AA (median age, 69.0 [IQR, 60.0-74.0] years and 134 were male [64%]), concordance between immunohistologic and genomic subtypes was 55%. Most INT subtype tumors were categorized into the colorectal genomic subtype (43 of 57 [72.9%]). Of the 114 PB subtype tumors, 29 had a pancreatic genomic profile (25.4%) and 24 had a distal bile duct genomic profile (21.1%). Whereas the standard immunohistologic subtypes were not associated with survival (log rank P = .26), predicted genomic probabilities were correlated with survival probability. Genomic scores with higher colorectal probability were associated with higher survival probability; higher pancreatic and distal bile duct probabilities were associated with lower survival probability., Conclusions and Relevance: The AA genomic classifier is reproducible with available molecular testing in a diverse international cohort of patients and improves stratification of the divergent clinical outcomes beyond standard immunohistologic classification. These data provide a molecular classification that may be incorporated into clinical trials for prospective validation.

Aims/hypothesis: Almost all beta cells contact one capillary and insulin granule fusion is targeted to this region. However, there are reports of beta cells contacting more than one capillary. We therefore set out to determine the proportion of beta cells with multiple contacts and the impact of this on cell structure and function., Methods: We used pancreatic slices in mice and humans to better maintain cell and islet structure than in isolated islets. Cell structure was assayed using immunofluorescence and 3D confocal microscopy. Live-cell two-photon microscopy was used to map granule fusion events in response to glucose stimulation., Results: We found that 36% and 22% of beta cells in islets from mice and humans, respectively, have separate contact with two capillaries. These contacts establish a distinct form of cell polarity with multiple basal regions. Both capillary contact points are enriched in presynaptic scaffold proteins, and both are a target for insulin granule fusion. Cells with two capillary contact points have a greater capillary contact area and secrete more, with analysis showing that, independent of the number of contact points, increased contact area is correlated with increased granule fusion. Using db/db mice as a model for type 2 diabetes, we observed changes in islet capillary organisation that significantly reduced total islet capillary surface area, and reduced area of capillary contact in single beta cells., Conclusions/interpretation: Beta cells that contact two capillaries are a significant subpopulation of beta cells within the islet. They have a distinct form of cell polarity and both contact points are specialised for secretion. The larger capillary contact area of cells with two contact points is correlated with increased secretion. In the db/db mouse, changes in capillary structure impact beta cell capillary contact, implying that this is a new factor contributing to disease progression., (© 2024. The Author(s).)

Objective: Postoperative pancreatic fistula (POPF) represents a leading cause of morbidity and mortality following major pancreatic resections. This study aimed to evaluate the use of postoperative drain fluid lipase-to-amylase ratio (LAR) for the prediction of clinically relevant fistulae (CR-POPF)., Methods: Consecutive patients undergoing pancreaticoduodenectomy between 2017 and 2021 at a tertiary centre were retrospectively reviewed. Univariable and multivariable analyses were performed to identify predictors for CR-POPF (ISGPS grade B/C). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the performance of LAR and determine optimum prediction thresholds., Results: Among 130 patients, 28 (21.5%) developed CR-POPF. Variables positively associated with CR-POPF included soft gland texture, acinar cell density, diagnosis other than PDAC or chronic pancreatitis, resection without neoadjuvant therapy, and postoperative drain fluid lipase, amylase, and LAR (all P <0.05). Multivariable regression analysis identified LAR as an independent predictor of CR-POPF ( P <0.05). ROC curve analysis showed that LAR had moderate ability to predict CR-POPF on POD1 (AUC,0.64; 95%CI,0.54-0.74) and excellent ability on POD3 (AUC,0.85; 95%CI,0.78-0.92) and POD 5 (AUC,0.86; 95%CI,0.79-0.92). Optimum thresholds were consistent over PODs 1 to 5 (ratio>2.6) and associated with 92% sensitivity and 46% to 71% specificity., Conclusions: Postoperative drain fluid LAR represents a reliable predictor for the development of CR-POPF. With early prognostication, the postoperative care of patients at risk of developing high-grade fistulas may be optimized., Competing Interests: The authors have not received any grant support and declare no conflicts of interest. The first author is not a surgeon in training. Research protocol was approved by the Northern Sydney Local Health District ethics committee as a negligible/low risk project. Data were deidentified and retrospectively collected, and therefore, informed consent was not required from each patient. This study was not a trial or animal study. All authors agree with the content of the article. The article has not been published previously nor is it under consideration elsewhere., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Late presentation of disease at the time of diagnosis is one of the major reasons for dismal prognostic outcomes for PDAC patients. Currently, there is a lack of clinical biomarkers, which can be used to diagnose PDAC patients at an early resectable stage. This study performed proteomic mass spectrometry to identify novel blood-based biomarkers for early diagnosis of PDAC. Serum specimens from 88 PDAC patients and 88 healthy controls (60 discovery cohort and 28 validation cohort) were analyzed using data independent acquisition high resolution mass spectrometry to identify candidate biomarker proteins. A total of 249 proteins were identified and quantified by the mass spectrometric analysis. Six proteins were markedly (>1.5 fold) and significantly (p < .05; q < 0.1) increased in PDAC patients compared to healthy controls in discovery cohort. Notably, four of these six proteins were significantly upregulated in an independent validation cohort. The top three upregulated proteins (i.e., Polymeric Immunoglobulin Receptor [PIGR], von Willebrand Factor [vWF], and Fibrinogen) were validated using enzyme linked immunosorbent assay, which led to selection of PIGR and vWF as a diagnostic biomarker panel for PDAC. The panel showed high ability to diagnose early stage (stage I and II) PDAC patients (area under the curve [AUC]: 0.8926), which was further improved after the addition of clinically used prognostic biomarker (Ca 19-9) to the panel (AUC: 0.9798). In conclusion, a novel serum protein biomarker panel for early diagnosis of PDAC was identified., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objectives: There is a paucity of data regarding the use of neoadjuvant therapy in pancreatic body or tail ductal adenocarcinomas. Given the differing tumour biology and aggressive nature of pancreatic body or tail adenocarcinomas, patients presenting with these tumours may benefit from upfront resection., Methods: A retrospective cohort study was performed analysing patients who underwent distal pancreatectomy for pancreatic ductal adenocarcinoma between January 2013 and June 2022. Patients who underwent upfront resection were compared to those who underwent neoadjuvant therapy., Results: Forty-one patients underwent upfront distal pancreatectomy, while 40 patients underwent neoadjuvant therapy before curative intent resection. Neoadjuvant therapy did not improve overall survival (37 vs. 34 months, p = 0.962) or disease-free survival (13 vs. 15 months, p = 0.414), as compared with upfront resection. There was no significant difference in the rate or R0 resection or post-operative outcomes., Conclusion: No significant improvement in survival was demonstrated for patients undergoing neoadjuvant therapy for pancreatic ductal adenocarcinoma of the pancreatic body or tail when compared to upfront resection. Considering the potential for disease progression given the more aggressive tumour biology of pancreatic body and tail adenocarcinomas, appropriate surgical candidates should be offered upfront resection to provide the best chance of survival and cure., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Clinically relevant postoperative pancreatic fistula (CR-POPF) is the leading cause of morbidity and mortality after pancreatic surgery. Post-pancreatectomy acute pancreatitis (PPAP) has been increasingly understood as a precursor and exacerbator of CR-POPF. No longer believed to be the consequence of surgical technique, the solution to preventing CR-POPF may lie instead in non-surgical, mainly pharmacological interventions. Five databases were searched, identifying eight pharmacological preventative strategies, including neoadjuvant therapy, somatostatin and its analogues, antibiotics, analgesia, corticosteroids, protease inhibitors, miscellaneous interventions with few reports, and combination strategies. Two further non-surgical interventions studied were nutrition and fluids. New potential interventions were also identified from related surgical and experimental contexts. Given the varied efficacy reported for these interventions, numerous opportunities for clarifying this heterogeneity remain. By reducing CR-POPF, patients may avoid morbid sequelae, experience shorter hospital stays, and ensure timely delivery of adjuvant therapy, overall aiding survival where prognosis, particularly in pancreatic cancer patients, is poor.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second-highest cause of cancer-related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer-associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis., Methods: This review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single-cell RNA-sequencing (scRNA-seq) and other single-cell analysis technologies. It will further explore the emerging role of single-cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer-associated fibroblasts, and immune cells in PDAC progression., Results and Conclusion: The application of scRNA-seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA-seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in-depth understanding of intratumoral heterogeneity in the PDAC microenvironment., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Postoperative pancreatic fistula (POPF) represents one of the most severe complications following pancreatic surgery. Despite being a leading cause of morbidity and mortality, its pathophysiology is poorly understood. In recent years, there has been growing evidence to support the role of postoperative or post-pancreatectomy acute pancreatitis (PPAP) in the development of POPF. This article reviews the contemporary literature on POPF pathophysiology, risk factors, and prevention strategies., Methods: A literature search was conducted using electronic databases, including Ovid Medline, EMBASE, and Cochrane Library, to retrieve relevant literature published between 2005 and 2023. A narrative review was planned from the outset., Results: A total of 104 studies fulfilled criteria for inclusion. Forty-three studies reported on technical factors predisposing to POPF, including resection and reconstruction technique and adjuncts for anastomotic reinforcement. Thirty-four studies reported on POPF pathophysiology. There is compelling evidence to suggest that PPAP plays a critical role in the development of POPF. The acinar component of the remnant pancreas should be regarded as an intrinsic risk factor; meanwhile, operative stress, remnant hypoperfusion, and inflammation represent common mechanisms for acinar cell injury., Conclusions: The evidence base for PPAP and POPF is evolving. Future POPF prevention strategies should look beyond anastomotic reinforcement and target underlying mechanisms of PPAP development., Competing Interests: Conflict of interest The authors have not received any grant support and declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Post-operative pancreatic fistula (POPF) is perhaps one of most dreaded pancreatoduodenectomy-related complications. Various approaches to mitigate this risk have been explored, with conflicting results and no clear consensus on the comparative superiority of any one technique. We postulate that regardless of technique, the key to reducing POPF is a robust pancreatic anastomosis with careful apposition of tissues, in particular the duct-to-mucosa anastomosis., Method: We describe the fashioning of a pancreatojejunostomy with an external pancreatic stent in the setting of a high-risk anastomosis with help of a 10 × magnification surgical microscope. A technical description with a short, edited video is presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimize outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimized. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis., Methods: Five databases were searched for relevant and original papers published from January 2000 to December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies., Results: Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30 758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs were determined. Potential triage tests (negative predictive value >90%) were identified for the ruling out of CR-POPF and included postoperative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/l) and in mixed surgical cohorts (2500 U/l), POD3 drain amylase in PD patients (1000-1010 U/l) and drain lipase in mixed surgery groups (180 U/l). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1., Conclusions: The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multivariable risk-stratification models and the improvement of pancreatectomy outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Nil to declare.

Background: The diagnosis of postoperative or post-pancreatectomy acute pancreatitis (PPAP) is controversial. In 2021, the International Study Group of Pancreatic Surgery (ISGPS) published the first unifying definition and grading system for PPAP. This study sought to validate recent consensus criteria, using a cohort of patients undergoing pancreaticoduodenectomy (PD) in a high-volume pancreaticobiliary specialty unit., Methods: All consecutive patients undergoing PD at a tertiary referral centre between January 2016 and December 2021 were retrospectively reviewed. Patients with serum amylase recorded within 48h from surgery were included for analysis. Postoperative data were extracted and evaluated against the ISGPS criteria, including the presence of postoperative hyperamylasaemia, radiologic features consistent with acute pancreatitis, and clinical deterioration., Results: A total of 82 patients were evaluated. The overall incidence of PPAP was 32% (26/82) in this cohort, of which 3/26 demonstrated postoperative hyperamylasaemia and 23/26 had clinically relevant PPAP (Grade B or C) when correlated radiologic and clinical criteria., Conclusions: This study is among the first to apply the recently published consensus criteria for PPAP diagnosis and grading to clinical data. While the results support their utility in establishing PPAP as a distinct post-pancreatectomy complication, there remains a need for future large-scale validation studies., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The management of high-grade pancreatic trauma is controversial., Aim: To review our single-institution experience on the surgical management of blunt and penetrating pancreatic injuries., Methods: A retrospective review of records was performed on all patients undergoing surgical intervention for high-grade pancreatic injuries [American Association for the Surgery of Trauma (AAST) Grade III or greater] at the Royal North Shore Hospital in Sydney between January 2001 and December 2022. Morbidity and mortality outcomes were reviewed, and major diagnostic and operative challenges were identified., Results: Over a twenty-year period, 14 patients underwent pancreatic resection for high-grade injuries. Seven patients sustained AAST Grade III injuries and 7 were classified as Grades IV or V. Nine underwent distal pancreatectomy and 5 underwent pancreaticoduodenectomy (PD). Overall, there was a predominance of blunt aetiologies (11/14). Concomitant intra-abdominal injuries were observed in 11 patients and traumatic haemorrhage in 6 patients. Three patients developed clinically relevant pancreatic fistulas and there was one in-hospital mortality secondary to multi-organ failure. Among stable presentations, pancreatic ductal injuries were missed in two-thirds of cases (7/12) on initial computed tomography imaging and subsequently diagnosed on repeat imaging or endoscopic retrograde cholangiopancreatography. All patients who sustained complex pancreaticoduodenal trauma underwent PD without mortality. The management of pancreatic trauma is evolving. Our experience provides valuable and locally relevant insights into future management strategies., Conclusion: We advocate that high-grade pancreatic trauma should be managed in high-volume hepato-pancreato-biliary specialty surgical units. Pancreatic resections including PD may be indicated and safely performed with appropriate specialist surgical, gastroenterology, and interventional radiology support in tertiary centres., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Meckels diverticulum (MD) causes a number of acute surgical pathologies and can contain ectopic tissue with the surgical aim to resect all ectopic mucosa. This has traditionally implied a small bowel resection (BR); though contemporary literature has demonstrated Meckel's diverticulectomy to be safe. The aim of this study was to determine optimal resection strategy, and assess MD histopathological features and their relationship to outcomes., Methods: A 19-year retrospective review of patient medical records across seven hospitals was conducted with demographic, clinical and pathological data collected. Analysis was conducted using a student's t-test for continuous variables and chi-squared test for categorical variables. Univariate regression was performed to identify risk factors. P < 0.05 was considered statistically significant., Results: One hundred and sixty patients underwent resection of MD, 70 (44%) had Meckel's diverticulectomy and 90 (56%) had BR. No significant difference in length (P = 0.486), width (P = 0.238), or ratio (P = 0.188) of diverticulectomy compared to BR, with fewer complications in diverticulectomy. In all, 24 (15.3%) MD were perforated, of whom 5 had gastric mucosa, 2 had mixed ectopic mucosa and 1 carcinoid tissue. There were no cases of ectopic mucosa in the resection margin requiring re-operation, or causing base perforation. MD specimen with greater length: width ratio was a risk factor for perforation OR 1.437 P = 0.042 but not for malignancy P = 0.813 or ectopic tissue P = 0.185., Conclusion: Meckel's diverticulectomy is safe via laparoscopic or open approach compared with BR. Despite higher perforation rates in MD with greater length: width ratio, no malignancy or ectopic risk was identified, supporting diverticulectomy as a safe operative approach., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: Post-pancreaticoduodenectomy haemorrhage is a potentially life-threatening complication. Delay in the detection and subsequent management of complications contribute significantly to post-operative mortality and morbidity associated with pancreaticoduodenectomy., Methods: All patients undergoing pancreaticoduodenectomy at an Australian-based tertiary referral center between 2017 and 2022 were reviewed retrospectively. We identified those patients who suffered a post-pancreaticoduodenectomy haemorrhage and further analysed those patients who had their post-pancreaticoduodenectomy haemorrhage identified on repeated CT imaging performed within 24 h of their previous CT scan., Results: A total of 232 pancreaticoduodenectomies were identified for analysis during the study period, of which 23 patients (9.9%) suffered a post-pancreaticoduodenectomy haemorrhage. We present four patients who had their post-pancreaticoduodenectomy haemorrhage identified on repeat CT scan in the setting of a recent (within 24 h) CT scan which showed no evidence of active haemorrhage or pseudoaneurysm formation. All patients received prompt and definitive endovascular management through stent insertion or coil embolization resulting in successful cessation of bleeding. Three patients made an uncomplicated recovery thereafter. Unfortunately, one patient died as a complication of the bleed despite early and definitive endovascular intervention., Conclusion: Our study highlights the importance of having a low threshold for repeated CT imaging in the post-pancreaticoduodenectomy setting, particularly when there remains a high index of suspicion clinically for a post-operative complication, even in the context of previous benign imaging. Given the complexity of pancreaticoduodenectomy, we believe early detection with liberal imaging allows the best chance at successfully managing the morbidity and mortality associated in the post-pancreaticoduodenectomy setting., (© 2023 Royal Australasian College of Surgeons.)

Background: The long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains suboptimal largely due to the absence of consideration of aggressive tumor biology., Objective: The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes., Methods: Clinicopathological data were obtained for 5 independent cohorts of consecutive unselected patients, totaling n = 1298, including n = 442 that underwent molecular subtyping. The main outcome measure was disease-specific survival following surgical resection for PDAC stratified according to the American Joint Commission for Cancer (TNM) staging criteria, margin status, and molecular subtype., Results: TNM staging criteria and margin status confers prognostic value only in tumors with classical pancreatic subtype. Patients with tumors that are of squamous subtype, have a poor outcome irrespective of favorable traditional pathological staging [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04-2.28, P = 0.032]. Margin status has no impact on survival in the squamous subtype (16.0 vs 12.1 months, P = 0.374). There were no differences in molecular subtype or gene expression of tumors with positive resection margin status., Conclusions: Aggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Granular cell tumours (GCTs) of the pancreas are mostly benign and exceptionally rare, with no unique identifying radiological features. Following a case discussion of a patient with GCT, a comprehensive review of available literature was conducted to identify the common diagnostic features associated with GCT., Methods: Following a case report identified in our institution, a systematic review was conducted by two authors in accordance with Preferred Reporting Items for Systematic review and Meta-Analysis protocols (PRISMA) guidelines. Databases MEDLINE, EMBASE, Scopus, World of Science, and grey literature were searched on August 2021. Inclusion criteria were histopathology diagnosed granular cell tumour of the pancreas., Results: A 37-year-old male presented with 1 month of abdominal pain and an MRI demonstrating a dilated main pancreatic duct, distal parenchymal atrophy, but no focal lesion. Repeat MRI at 6 months re-demonstrated similar findings and subsequent endoscopic ultrasound was suspicious for main duct IPMN. Following multidisciplinary team discussion, a spleen-preserving distal pancreatectomy was performed. Histopathology demonstrated granular cell tumour with cells diffusely positive for S100 and no malignant transformation. 11 case reports were identified in the literature with diagnosis confirmed on tissue histopathology based on positive immunohistochemical staining for S-100 protein. Eight patients presented with gastrointestinal symptoms with abdominal pain the main presenting complaint (50%). 10 patients underwent CT with portal venous contrast and all underwent endoscopic examination. Imaging findings were similar in five studies for EUS which demonstrated a hypoechoic lesion with homogenous appearance. On non-contrast CT GCT was iso-enhancing, and with portal venous contrast demonstrated hypo-enhancement that gradually enhanced on late phases. Pre-operative diagnosis of pancreatic carcinoma was described in six cases based on imaging and biopsy, resulting in progression to surgical resection. Nine patients were managed surgically and no complications identified on follow-up (6-52 months)., Conclusion: The currently proposed management pathway includes EUS with biopsy and CT, and surgical resection recommended due to malignancy risk. Improved sample collection with EUS-FNA and microscopic assessment utilising S-100 immunohistochemistry may improve pre-operative diagnosis. Limitations include rare numbers in reported literature and short follow-up not allowing an assessment of GCT's natural history and malignancy risk. Additional cases would expand the current dataset of GCTs of the pancreas, so that surgical resection may be avoided in the future., (© 2023. The Author(s).)

Background: Advances in technology and techniques have allowed for robotic distal pancreatectomies to be readily performed in patients at high volume centres. This study describes the experience of a single surgeon during the learning curve and transition from open to robotic distal pancreatectomy in Australia, a traditionally low volume pancreatic surgery country., Methods: All patients undergoing distal pancreatectomy at an Australian-based tertiary referral centre between 2010 and 2021 were reviewed retrospectively. Demographic, clinicopathologic and survival data were analysed to compare perioperative and oncological outcomes between patients who underwent open, laparoscopic and robotic distal pancreatectomies., Results: A total of 178 distal pancreatectomies were identified for analysis during the study period. Ninety-one open distal pancreatectomies (ODP), 48 laparoscopic distal pancreatectomies (LDP), and 39 robotic distal pancreatectomies (RDP) were performed. Robotic distal pancreatectomy was non-inferior with respect to perioperative outcomes and yielded statistically non-significant advantages over LDP and ODP., Conclusion: RDP is feasible and can be performed safely in well-selected patients during the learning phase at large pancreatic centres in a traditionally low-volume country like Australia. Referral to large pancreatic centres where access to the robotic platform and surgeon experience is not a barrier, and where a robust multidisciplinary team meeting can take place, remains pivotal in the introduction and transition toward the robotic approach for management of patients with pancreatic body or tail lesions., (© 2022 Royal Australasian College of Surgeons.)