BACKGROUND:To report management and survival outcomes of gallbladder cancer (GBC) in the United Kingdom and to identify prognostic factors associated with disease-free survival (DFS) and overall survival (OS). METHODS:Patients undergoing surgery for GBC between January 2014 and December 2022 across 24 UK centres were included. Demographic, treatment, histopathological, and survival data were analysed. RESULTS:516 patients underwent surgery for GBC, with a median follow-up of 25 months. Patients with T3-T4 tumours more frequently presented with jaundice, had non-incidental disease, and underwent major hepatectomy compared with those with T1-T2 tumours. Advanced stage, nodal metastasis, vascular invasion, and perineural invasion were more common in patients undergoing major hepatectomy, which was also associated with higher major morbidity and 30-day mortality. Propensity score-matched analysis demonstrated no significant benefit in DFS or OS among patients who received adjuvant therapy compared with those who did not. On multivariable analysis, T3-T4 stage, nodal disease, and perineural invasion predicted poorer DFS, while T3-T4 stage and nodal disease predicted worse OS. DISCUSSION:This nationwide study demonstrates the evolution of management practices for GBC in the UK. Adverse tumour biology remains the principal determinant of survival following surgery for GBC.

Pancreatic cancer remains a significant challenge to diagnose and treat, with considerable regional variation in management and outcomes. This study aimed to evaluate real-world outcomes of patients receiving adjuvant treatment for pancreatic cancer at a single centre in Northwest England over an 11-year period. Data were collected retrospectively on all patients who underwent surgery for pancreatic ductal adenocarcinoma between 2009 and 2020. Collected data included patient demographics, surgical details and adjuvant treatment received, including number of chemotherapy cycles and dose reductions. 30-day/inpatient mortality was low (2.4%). Adjuvant chemotherapy delivery rates were high (82%) with 67.4% of patients completing the intended number of cycles. There was no additional survival benefit for patients who started chemotherapy within 8 weeks post-surgery compared to those who began later. Dose reductions did not impact survival, provided patients completed the full course of treatment (mOS 27.5 months vs. 28.5 months; HR 1.14, 95% CI 0.76–1.70 p = 0.513). Following centralisation of care, a greater proportion of patients commenced adjuvant treatment (86% vs 69% p < 0.05). A high proportion of patients received adjuvant treatment, with a centralised clinic model leading to increased rates of adjuvant chemotherapy delivery. Completion of the full chemotherapy course was more critical than dose intensity. Larger prospective studies are needed to investigate the factors contributing to regional variations.

Preclinical models vary in complexity and cost. Traditional 2D cell cultures that are high throughput and cost effective, but lack the complexity of multicellular interactions. Animal models and more complex, but are costly, raise ethical concerns and are not a human model to better understand human disease or response to novel treatments. Human precision cut tissue slice (hPCTS) models bridge this gap, maintaining the architecture and microenvironment of original tissues. This study examines the viability and functionality of hPCTS using different tissue culture formats. Previous studies have cultured hPCTS with gentle agitation, either on an insert or floating in tissue culture medium. More recently the use of a proprietary flow system for hPCTS culture has been explored, aiming to provide a more physiologically relevant environment. CELLBLOKS® provide a commercially available flow system platform designed for cell culture that we adapted to accommodate hPCTS. hPCTS were cultured for 15 days using an organotypic polytetrafluoroethylene Millicell insert, a CELLBLOKS® hydrophilic polyethylene terephthalate flow system plate or without an insert. Viability was assessed through MTS assays, while functionality was determined by measuring urea and albumin secretion across the 15 days in culture. The Millicell inserts maintained higher and more consistent viability and functionality over 15 days. Slices cultured with no inserts showed decreased viability and functionality after 7 days in culture. In contrast, CELLBLOKS® cultured hPCTS showed significantly decreased viability and function after 3 days in culture. This study suggests that while the CELLBLOKS® system shows promise for 2D cell line cultures, Millicell Biopore™ inserts offer a more reliable method for maintaining complex hPCTS cultures, preserving both viability and function. As a viable, human-specific alternative to animal models, hPCTS support the 3Rs and have the potential to reduced and potentially replace the use of animals in preclinical research, improving human disease modelling.

Preclinical models vary in complexity and cost. Traditional 2D cell cultures that are high throughput and cost effective, but lack the complexity of multicellular interactions. Animal models and more complex, but are costly, raise ethical concerns and are not a human model to better understand human disease or response to novel treatments. Human precision cut tissue slice (hPCTS) models bridge this gap, maintaining the architecture and microenvironment of original tissues. This study examines the viability and functionality of hPCTS using different tissue culture formats. Previous studies have cultured hPCTS with gentle agitation, either on an insert or floating in tissue culture medium. More recently the use of a proprietary flow system for hPCTS culture has been explored, aiming to provide a more physiologically relevant environment. CELLBLOKS® provide a commercially available flow system platform designed for cell culture that we adapted to accommodate hPCTS. hPCTS were cultured for 15 days using an organotypic polytetrafluoroethylene Millicell insert, a CELLBLOKS® hydrophilic polyethylene terephthalate flow system plate or without an insert. Viability was assessed through MTS assays, while functionality was determined by measuring urea and albumin secretion across the 15 days in culture. The Millicell inserts maintained higher and more consistent viability and functionality over 15 days. Slices cultured with no inserts showed decreased viability and functionality after 7 days in culture. In contrast, CELLBLOKS® cultured hPCTS showed significantly decreased viability and function after 3 days in culture. This study suggests that while the CELLBLOKS® system shows promise for 2D cell line cultures, Millicell Biopore™ inserts offer a more reliable method for maintaining complex hPCTS cultures, preserving both viability and function. As a viable, human-specific alternative to animal models, hPCTS support the 3Rs and have the potential to reduced and potentially replace the use of animals in preclinical research, improving human disease modelling.

Minimally invasive liver resections are widely used in hepatobiliary centres. This study compares oncological and survival outcomes between laparoscopic (LLR) and open liver resections (OLR) for colorectal liver metastases (CRLM) using propensity score matching (PSM). A retrospective single-centre study of patients undergoing liver resection for CRLM from January 2016 to December 2019 was conducted. Key co-variates were matched using PSM, and surgical and survival outcomes were compared before and after matching. Of 303 patients, 214 underwent OLR and 91 LLR. LLR was associated with shorter intensive treatment unit and inpatient stays, but with longer Pringle and operative times. In the unmatched cohort, LLR showed significantly better overall and disease-free survival. However, after PSM, while LLR showed reduced blood loss and shorter hospital stays, differences in survival outcomes were no longer significant, possibly due to the absence of bi-lobar disease in the laparoscopic group. In selected patients with CRLM, LLR demonstrates comparable long-term oncological and survival outcomes to OLR, as evidenced by our propensity score-matched analysis. This equivalence, combined with demonstrated advantages in short-term postoperative recovery, including reduced blood loss and shorter hospital stays, further supports a paradigm shift towards LLR as a standard approach for resectable CRLM. These findings emphasize the importance of patient selection and procedural expertise in achieving optimal outcomes.

Cholangiocarcinoma is a malignancy of significant unmet clinical need with limited therapeutic options. Most patients are diagnosed at advanced or metastatic stages, where surgical resection with curative intent is no longer an option. Gemcitabine-cisplatin chemotherapy has been the standard of care for these patients, remaining unchanged for over a decade. Recently, the addition of the programmed death ligand 1 inhibitor, durvalumab, to this regimen demonstrated an objective response rate of 26.7% in a phase III trial, becoming the new standard of care for advanced cholangiocarcinoma. Although considered a success in cholangiocarcinoma treatment, the results indicate that only a small proportion of patients respond to treatment with immune checkpoint inhibitors. Emerging evidence suggests that many cholangiocarcinoma tumors exhibit an immunologically 'cold' tumor microenvironment, characterised by predominance of immunosuppressive immune populations and limited infiltration of cytotoxic T cells, which contributes to their resistance to immune checkpoint inhibitors. This review provides a comprehensive overview of the research studies that have employed immunomodulatory strategies in cholangiocarcinoma aimed at priming the tumor microenvironment for a more effective response to immune checkpoint inhibitors. This update will also evaluate the strengths and limitations of current pre-clinical models of cholangiocarcinoma, with emphasis on more advanced translational models. These complex models remain underutilised, hindering the development of novel therapeutic approaches. We suggest that these complex preclinical models may help translation of therapies into clinical practice.

BACKGROUND:The role of liver transplantation as a treatment option for de novo resectable peri-hilar cholangiocarcinoma (pCCA) is controversial. This study investigated the outcomes following resection of early-stage pCCA in the UK. METHODS:Patients undergoing resection for pCCA between 2014 and 2022 across 22 UK centres were included. Early-stage pCCA was defined as tumour size<3cm with no nodal disease (N0) on histopathology analysis. Clinical and survival data were collated. RESULTS:Of the 450 patients included, 138 patients underwent resection for early-stage pCCA. In the early-stage pCCA group, CD ≥ IIIa morbidity was 39.1 % (n = 54) and 90-day mortality was 10.1 % (n = 14). Sixty-four (46.4 %) patients received adjuvant chemotherapy, but this was reduced in those with CD ≥ IIIa morbidity (n = 17, 31.5 %). Early-stage tumours had a significantly lower vascular invasion (n = 57, 41.3 %) and R1 margin (n = 46, 33.3 %) compared to later-stage pCCA [62.2 % (n = 194) and 54.2 % (n = 169) respectively, p < 0.001). The median disease-free and overall survival was significantly better in patients with early-stage pCCA compared to more advanced tumours (p < 0.001). Male gender (p = 0.039) and Post-Hepatectomy Liver Failure (PHLF, p = 0.010) were associated with significantly worse disease-free survival, while biliary drainage (p = 0.013), PHLF (p < 0.001) and vascular invasion (p = 0.030) were associated with significantly poorer overall survival. CONCLUSION:Resection of early-stage pCCA tumours is associated with good clinical and survival outcomes in centralised HPB centres.

Background and Aims: Adequate preoperative biliary drainage (PBD) is recommended in most patients with resectable perihilar cholangiocarcinoma (pCCA). Most expert centers use endoscopic plastic stents rather than self-expandable metal stents (SEMSs). In the palliative setting, however, use of SEMSs has shown longer patency and superior survival. The aim of this retrospective study was to compare stent dysfunction of SEMSs versus plastic stents for PBD in resectable pCCA patients. Methods: In this multicenter international retrospective cohort study, patients with potentially resectable pCCAs who underwent initial endoscopic PBD from 2010 to 2020 were included. Stent failure was a composite end point of cholangitis or reintervention due to adverse events or insufficient PBD. Other adverse events, surgical outcomes, and survival were recorded. Propensity score matching (PSM) was performed on several baseline characteristics. Results: A total of 474 patients had successful stent placement, of whom 61 received SEMSs and 413 plastic stents. PSM (1:1) resulted in 2 groups of 59 patients each. Stent failure occurred signi fi cantly less in the SEMSs group (31% vs 64%; P < . 001). Besides less cholangitis after SEMSs placement (15% vs 31%; P = .012), other PBD-related adverse events did not differ. The number of patients undergoing surgical resection was not significantly different (46% vs 49%; P = .71). Complete intraoperative SEMSs removal was successful and without adverse events in all patients. Conclusions: Stent failure was lower in patients with SEMSs as PBD compared with plastic stents in patients with resectable pCCA. Removal during surgery was quite feasible. Surgical outcomes were similar.

Cholangiocarcinoma (CCA) is an adenocarcinoma of the hepatobiliary system with a grim prognosis. Incidence is rising globally and surgery is currently the only curative treatment, but is only available for patients who are fit and diagnosed in an early-stage of disease progression. Great importance has been placed on developing preclinical models to help further our understanding of CCA and potential treatments to improve therapeutic outcomes. Preclinical models of varying complexity and cost have been established, ranging from more simplistic in vitro 2D CCA cell lines in culture, to more complex in vivo genetically engineered mouse models. Currently there is no single model that faithfully recaptures the complexities of human CCA and the in vivo tumour microenvironment. Instead a multi-model approach should be used when designing preclinical trials to study CCA and potential therapies.

Abstract Background Perihilar cholangiocarcinoma (pCCA) is the most common cancer of biliary epithelia. While potentially curative, surgical resection is associated with high morbidity and mortality. Surgical site infections (SSIs) are common and pernicious. Preoperative biliary instrumentation is universal: to confirm histological diagnosis and deploy stents to relieve jaundice. Patients receive multiple antibiotic courses as periprocedural prophylaxis and to treat cholangitis. They are at high risk of harbouring bacteria not quelled by perioperative prophylactic antibiotics given for other general surgical procedures. Studying the biliary microbiome, this quality improvement project sought to reduce SSIs through informed changes to local guidelines on perioperative antibiotic prophylaxis. Method Health records of all patients undergoing resection for pCCA in a UK hepatopancreatobiliary centre from February 2009 to January 2024 were analysed retrospectively (n=118). For all patients, we routinely sent intraoperative bile swabs for culture and sensitivity. Informed by these microbiology results, multidisciplinary discussion led to changes to local guidelines in March 2019. Formerly, cefuroxime and metronidazole were given on anaesthetic induction, with subsequent antibiotic choice and duration according to surgeon preference. New guidance stipulated teicoplanin and piperacillin/tazobactam be given on induction and for 72 hours postoperatively. We studied the impact of these changes on SSIs within 30 days. Results 75 patients received cefuroxime and metronidazole; 43 patients were given teicoplanin and piperacillin/tazobactam after the policy change. Proportions of patients who developed any SSI substantially fell following the guideline change (55% v 28%; p=0.0049), primarily owing to reductions in intraperitoneal collections (39% v 21%; p=0.047). Rates of deep (8% v 2%; p=0.21) and superficial incisional infections (8% v 5%; p=0.49) were not significantly affected. Associated secondary outcomes were drops in post-hepatectomy liver failure (17% v 5%; p=0.047), and 90-day mortality (16% v 5%; p=0.067), albeit the latter was not statistically significant. Conclusion Invasive investigative work-up, disease complications and exposure to multiple courses of antibiotics prior to resection of pCCA subject patients’ biliary systems to colonisation with antimicrobial-resistant bacteria. We urge centres that undertake these operations to introduce intraoperative bile cultures as a part of routine practice to inform local guidance on perioperative antimicrobial prophylaxis. We demonstrated effective antibiotics in the perioperative period can have enormous benefits to patient outcomes.

Abstract Background Radical resection of perihilar cholangiocarcinoma (pCCA) is only an option for the minority presenting at an early stage. Sensitivity of radiological imaging to detect liver and peritoneal metastases is insufficient. Our published 2017 cohort study demonstrated over a quarter of patients with no radiologically detectable metastatic disease were subsequently found to have unresectable disease by staging laparoscopy. However, less than 3% of these patients had preoperative PET-CT, which is now strongly recommended in new national guidance.Advances in CT and MRI sensitivity and increased PET-CT use demanded a reassessment of the need for staging laparoscopy in diagnostic assessment of resectability. Method All patients referred to a tertiary UK hepatobiliary centre with a new diagnosis of radiologically suspected or biopsy-proven pCCA from January 2020 to January 2024 were included (n=305). Patients were identified through a prospectively maintained cancer database. Electronic health records were interrogated for demographic data, preoperative radiological imaging, and details related to operative procedures. Those referred with, or subsequently found to have, any of the following conditions were excluded: recurrent pCCA, intrahepatic or distal cholangiocarcinoma, gallbladder cancer or benign hepatobiliary disease. Results All patients underwent CT chest, abdomen and pelvis. 194 (64%) received contrast MRI liver or MRCP. Based on these, 242 (79%) had locally advanced or metastatic cancer, comorbidities precluding resection or otherwise declined surgery. PET-CT was employed to investigate all remaining 63 patients, which discovered metastatic disease in 16 patients (25%). 47 patients proceeded to staging laparoscopy. This yielded metastatic or locally advanced disease in five patients (11%); a near-statistically significant drop compared to our previously published yield of 27.2% (p=0.060). Two (5%) had open-and-close laparotomies for irresectable disease, compared to 16 of 114 (14%) in our 2017 publication (p=0.14). Conclusion Technological advances of CT and MRI and use of PET-CT have vastly improved detection of irresectable pCCA. This study reinforces the merits of PET-CT in identifying occult disease, and we would encourage units that undertake these resections to utilise this imaging modality prior to undertaking staging laparoscopy. Nevertheless, peritoneal spread remains challenging to exclude radiologically, and diagnostic laparoscopy endures as a vital tool in the prevention of open-and-close laparotomies.

Background: Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites. Methods: We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments. Results: Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p =0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6–0.4 paracenteses/month, p =0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant. Conclusions: Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention.

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%. High frequency somatic mutations in genes not typically associated with cholangiocarcinoma included mTOR, ABL1 and NOTCH1. We identified non-synonymous mutation (p.Glu38del) in MAP3K9 in ten tumors, associated with increased peri-vascular invasion (Fisher's exact, p < 0.018). Mutation-enriched pathways were primarily immunological, including innate Dectin-2 (FDR 0.001) and adaptive T-cell receptor pathways including PD-1 (FDR 0.007), CD4 phosphorylation (FDR 0.009) and ZAP70 translocation (FDR 0.009), with overlapping HLA genes. We observed cancer-associated mutations in over half of our patients. Many of these mutations are not typically associated with cholangiocarcinoma yet may increase eligibility for contemporary targeted trials. We also identified a targetable MAP3K9 mutation, in addition to oncogenic and immunological pathways hitherto not described in any cholangiocarcinoma subtype.

Abstract Background Preoperative biliary drainage is required in the majority of patients with resectable perihilar cholangiocarcinoma (pCCA). Most centres use plastic stents rather than uncovered self-expanding metal stents (uSEMS) because of the potential difficulties associated in removing uSEMS. In the palliative setting, however, uSEMS are associated with superior patency and even improved survival. The aim of this study is to compare the utility of uSEMS versus plastic stents in the pre-operative drainage of patients with resectable pCCA. Methods In this retrospective, multicentre, international cohort study, all consecutive patients with a high suspicion of resectable pCCA who underwent an initial endoscopic biliary drainage with uSEMS or plastic stent between 2010–2020 were included. Analyses were stratified by groups according to initial stent type. The primary outcome was stent failure, which was a composite endpoint of cholangitis and/or re-intervention due to biliary complications or inadequate biliary drainage. Propensity score matching (1:1) was performed to adjust for age, gender, primary sclerosing cholangitis, Bismuth classification, WHO performance status and ASA classification. Results A total of 474 patients with successful initial stent placement were included. Of these patients 61 received uSEMS and 413 plastic stents. Matching resulted in two groups of 59 patients. Stent failure occurred significantly less in the uncovered uSEMS group (31% vs 64%, P<0.001) and resulted in a significant reduction in the number of repeat ERCP procedures (14% vs 54%, P<0.001). Despite this the number of patients eventually required percutaneous transhepatic biliary drainage was similar (9% vs 7%, P=1). uSEMS placement was also associated with a reduction in episodes of cholangitis (15% vs 31%, P=0.012), although other ERCP and stent related complications did not differ. The number of patients ultimately undergoing surgical resection was not significantly different (81% vs 90%, P=0.19) between groups with uSEMS removal during surgery successful in all patients. The median overall survival after initial stent placement was 482 days [95% CI, 338–787] in the uSEMS group and 429 [95% CI, 263–881] in the plastic stent group (log-rank P=0.81). Survival after surgical resection was similar and post-operative outcomes also comparable: R1 resections (58% vs 59%, P=0.569), complications according to Clavien-Dindo (P=0.227), and hepatico-jejunostomy associated complications (leak: 4% vs 14%, P=0.393, stricture: 15% vs 21%, P=0.822). Conclusions Stent failure occurred significantly less often in uSEMS group resulting in fewer drainage procedures and reduced episodes of cholangitis. Removal of uSEMS during surgery was feasible and surgical outcomes were comparable. Although preoperative biliary drainage by uSEMS shows promising results further study is warranted and multicentre randomized controlled trials with a clear treatment strategy should be performed.

Abstract Background Cholangiocarcinoma (CCA) is an aggressive malignancy with increasing incidence and persistently poor prognosis. None surgical treatment options for these patients are limited and a preponderance to chemoresistance means the benefits from chemotherapy are modest. The development of new targeted therapeutic strategies that prolong survival and reduce the risk of recurrence post-surgery are required. Accurate models that recapitulate tumour biology are essential to test and identify these novel therapies. Precision-cut tissue slices (PCTS) are patient-derived whole tissue explants that can be cultured ex-vivo. By retaining all aspects of the tumour micro-environment they recapitulate critical aspects of cancer biology, a significant advantage over 3D organoid culture. Our aim is to establish the use of the PCTS technique in CCA as the first step towards creating a patient-derived model of cholangiocarcinoma for use as a drug discovery platform. Methods CCA tissue samples and matched healthy liver tissue were collected from the operating theatre during surgical resection from fully consented patients. Multiple tissue slices (250μm, 5mm diameter) were prepared using a Krumdiek tissue slicer. Tissue slices were randomly incubated in triplicate and cultured for 0–15 days in 24 well plates. Tissue perfusion and air-liquid interface was maintained using Millipore well inserts. Tissue viability was determined at timepoints utilising MTS and ATP viability assays along with histological markers of proliferation (Ki-67) and apoptosis (cleaved-caspase 3). Maintenance of tissue morphology and phenotype during culture was confirmed on histological H&E staining and by staining of tumour specific markers (e.g CK19) on IHC and Western Blot. Results Thus far n=4 patients have had PCTS generated (3=pCCA 1=iCCA) from their tumour along with matched healthy liver. Following optimisation of the experimental protocol viability of the matched normal and tumour tissue slices can be maintained for upto 10 days, as assessed via in-situ MTS assay. Histological assessment of tissue slices harvested at day 0, 1,3,7 of culture shows the morphological and phenotypic structures of the source tumour to be maintained during ex-vivo culture. Viability of the tumour cells was additionally confirmed through the absence of cleave-caspase 3 markers of apoptosis on IHC staining. Conclusions This initial work has shown it is feasible to generate PCTS of CCA from resected surgical specimens with good viability. Further work is still required to ensure that our model retains a robust recapitulation of the in-vivo tumour including examination of the gene-expression profile. However, these initial results provide encouragement for the use of PCTS as a patient-derived model for drug discovery in CCA.

A 44-year-old woman was transferred to the ED from an outside hospital because of hemoptysis and concern for left-sided pulmonary infiltrate with associated pleural effusion. The patient presented to this outside hospital multiple times over the past 3 months because of left-sided shoulder pain, diffuse myalgias, and supraventricular tachycardia. On her third visit, she was found to have a left-sided pleural effusion and underwent diagnostic and therapeutic thoracentesis; 1.5 L of fluid was removed. Fluid studies reportedly demonstrated an exudative pleural effusion with negative bacterial cultures and no evidence of neoplastic process. The patient was referred to the Rheumatology Department by the outside hospital for suspected underlying autoimmune process. In the months leading up to her current presentation, the patient had been prescribed one prednisone burst and two prednisone tapers. She was then placed on a regimen of 10 mg prednisone daily and 200 mg hydroxychloroquine bid by her primary care doctor. This was tapered by the Rheumatology Department such that the patient was on 7.5 mg of prednisone daily on arrival to this ED. Rheumatologic workup until this point revealed only low titer (1:80) positive antinuclear antibody. Prior to these ED visits, the patient had been otherwise healthy with only a history of a Roux-en-Y gastric bypass 17 years earlier. Aside from recent daily low-dose prednisone use, the patient did not have other preexisting immune compromise or risk factors for aspiration such as seizure disorder, chronic alcohol use, or cognitive impairment. Before her transfer, the patient experienced foul-smelling, maroon-colored hemoptysis as well as anemia that required a higher level of care. On arrival to the ED, she was in acute hypoxic respiratory failure. The patient was intubated emergently and was admitted to the medical critical care unit for further treatment.

Background: Surgery for perihilar cholangiocarcinoma (pCCA) offers the only possibility of long-term survival, but remains a formidable undertaking. Traditionally, 90-day post-operative complications and death are used to define operative risk. However, there is concern that this metric may not accurately capture long-term morbidity after such complex surgery. Methods: A retrospective review of a prospective database of patients undergoing surgery for pCCA at a Western centre between January 2009-2020. Results: Eighty-five patients underwent surgical resection for pCCA with a median overall survival of 36.3 months. Post-op (<90day) morbidity rates were high with 46% of patients developing a major complication (Clavien-Dindo grade 3-4). Post-op mortality rate was 13%. In total 38% (28/74) of patients experienced at least 1 episode of delayed morbidity (>90-days of surgery) resulting in 53 separate admissions with a median LOS of 7 days (IQR 2-15). These episodes were predominately secondary to biliary obstruction with the majority requiring radiological intervention (Clavien-Dindo grade 3). The development of long-term morbidity was associated with increased recurrence rates and correlated with poorer OS (27.6 months vs. 65.7 months HR 2.2 CI 1.63-2.77). Conclusions: Routinely cited 90-day morbidity and mortality does not accurately capture the patient morbidity experienced following surgery for pCCA. Surgery clearly offers a survival benefit and should be pursued in selected patients, but they must be fully counselled on the potential for long-term morbidity before embarking on this strategy.