Pancreatic body and tail adenocarcinoma: upfront resection versus neoadjuvant therapy, a contemporary analysis.

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.

The role of repeated imaging in detecting complications in the post-operative period following pancreaticoduodenectomy: Serial CT imaging post-pancreaticoduodenectomy.

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.

Transition from open to robotic distal pancreatectomy in a low volume pancreatic surgery country: a single Australian centre experience.

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.

Clinical suspicion of pancreatic cancer despite negative endoscopic ultrasound-guided fine-needle aspiration biopsy.

BACKGROUND: The early and accurate diagnosis of pancreatic ductal adenocarcinoma is vital for improving the efficacy of therapeutic interventions and to provide patients with the best chance of survival. While endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been demonstrated to be a reliable and accurate diagnostic tool for solid pancreatic neoplasms, the ongoing management of patients with a high clinical suspicion for malignancy but with a negative EUS-FNA biopsy result can prove a challenge. METHODS: We describe five patients from a single centre who presented for further work-up of a pancreatic mass and/or imaging features concerning for a periampullary malignancy. RESULTS: All patients had at least one EUS-FNA biopsy performed which returned no malignant cells on cytology. Despite these negative cytology results, all patients underwent further invasive investigation through upfront resection (pancreaticoduodenectomy) or extra-pancreatic biopsy (laparoscopic biopsy of peritoneal nodule) due to worrisome features on imaging, biochemical factors and clinical presentation culminating in a high degree of suspicion for malignancy. The final tissue histopathological diagnosis in all patients was pancreatic ductal adenocarcinoma. CONCLUSION: This case series highlights the important clinical findings, imaging and biochemical features which need to be considered in patients who have high suspicion for malignancy despite having a negative EUS-FNA cytology result. In these patients with a high index of suspicion, surgical intervention through an upfront resection or further invasive investigation should not be delayed.

Multiple superficial femoral artery pseudoanurysms following sub intimal application of paclitaxel coated technology.

Drug coated balloons (DCB) are a commonly used endovascular option for treating patients presenting with symptomatic peripheral vascular disease. DCB have illustrated to increase primary patency and thus have been a popular choice in addressing restenosis caused by neointimal hyperplasia. Pseudoaneurysms (PSA) are a common vascular pathology, the causes of which include iatrogenic, trauma, stent fractures and angioplasty balloon overuse. Herein, we describe the case where a patient developed multiple superficial femoral artery (SFA) PSA potentially secondary to the subintimal application of paclitaxel.

Coating extracellular matrix proteins on a (3-aminopropyl)triethoxysilane-treated glass substrate for improved cell culture.

We demonstrate that a (3-aminopropyl)triethoxysilane-treated glass surface is superior to an untreated glass surface for coating with extracellular matrix (ECM) proteins when used as a cell culture substrate to observe cell physiology and behavior. We found that MDCK cells cultured on untreated glass coated with ECM removed the coated ECM protein and secreted different ECM proteins. In contrast, the cells did not remove the coated ECM protein when seeded on (3-aminopropyl)triethoxysilane-treated (i.e., silanized) glass coated with ECM. Furthermore, the morphology and motility of cells grown on silanized glass differed from those grown on non-treated glass, even when both types of glass were initially coated with laminin. We also found that cells on silanized glass coated with laminin had higher motility than those on silanized glass coated with fibronectin. Based on our results, we suggest that silanized glass is a more suitable cell culture substrate than conventional non-treated glass when coated by ECM for observations of ECM effects on cell physiology.

Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation.

Heterochromatin protein 1 (HP1) has an essential role in heterochromatin formation and mitotic progression through its interaction with various proteins. We have identified a unique HP1alpha-binding protein, POGZ (pogo transposable element-derived protein with zinc finger domain), using an advanced proteomics approach. Proteins generally interact with HP1 through a PxVxL (where x is any amino-acid residue) motif; however, POGZ was found to bind to HP1alpha through a zinc-finger-like motif. Binding by POGZ, mediated through its zinc-finger-like motif, competed with PxVxL proteins and destabilized the HP1alpha-chromatin interaction. Depletion experiments confirmed that the POGZ HP1-binding domain is essential for normal mitotic progression and dissociation of HP1alpha from mitotic chromosome arms. Furthermore, POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis.