Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Relationship between medical programme progress test performance and surgical clinical attachment timing and performance.

PURPOSE: Progress tests (PTs) assess applied knowledge, promote knowledge integration, and facilitate retention. Clinical attachments catalyse learning through an appropriate learning context. The relationship between PT results and clinical attachment sequence and performance are under-explored. Aims: (1) Determine the effect of Year 4 general surgical attachment (GSA) completion and sequence on overall PT performance, and for surgically coded items; (2) Determine the association between PT results in the first 2 years and GSA assessment outcomes. MATERIALS AND METHODS: All students enrolled in the medical programme, who started Year 2 between January 2013 and January 2016, were included; with follow up until December 2018. A linear mixed model was applied to study the effect of undertaking a GSA on subsequent PT results. Logistic regressions were used to explore the effect of past PT performance on the likelihood of a student receiving a distinction grade in the GSA. RESULTS: 965 students were included, representing 2191 PT items (363 surgical items). Sequenced exposure to the GSA in Year 4 was associated with increased performance on surgically coded PT items, but not overall performance on the PT, with the difference decreasing over the year. PT performance in Years 2-3 was associated with an increased likelihood of being awarded a GSA distinction grade (OR 1.62, p < 0.001), with overall PT performance a better predictor than performance on surgically coded items. CONCLUSIONS: Exposure to a surgical attachment improves PT results in surgically coded PT items, although with a diminishing effect over time, implying clinical exposure may accelerate subject specific learning. Timing of the GSA did not influence end of year performance in the PT. There is some evidence that students who perform well on PTs in preclinical years are more likely to receive a distinction grade in a surgical attachment than those with lower PT scores.

Perioperative interventions to reduce pancreatic fistula following pancreatoduodenectomy: meta-analysis.

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.

Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta-Analysis.

BACKGROUND: The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. METHOD: A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. RESULTS: Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20-1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. CONCLUSION: Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. METHODS: Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. RESULTS: Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. CONCLUSION: Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

Synchronous Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Liver and Peritoneal Metastases: A Systematic Review and Meta-analysis.

BACKGROUND: Synchronous liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have traditionally been contraindicated. More recent clinical practice has begun to promote this aggressive treatment in select patients. OBJECTIVE: This study aimed to investigate the perioperative and oncological outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, with and without liver resection, in the management of metastatic colorectal cancer. DATA SOURCES: Medline, Embase, and Cochrane Library databases were searched up to July 2020. STUDY SELECTION: Cohort studies comparing outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with and without liver resection for metastatic colorectal cancer were reviewed. No randomized controlled trials were available. INTERVENTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without synchronous liver resection were compared. MAIN OUTCOME MEASURES: The primary outcome measures were perioperative mortality and major morbidity. Secondary outcomes included 3- and 5-year overall survival and 1- and 3-year disease-free survival. RESULTS: Fourteen studies fitted the inclusion criteria, with 8 studies included in the meta-analysis. On pooled analysis, there was no significant difference in perioperative morbidity and mortality between the two groups. Patients that underwent concomitant liver resection had worse 1- and 3-year disease-free survival and 3- and 5-year overall survival. LIMITATIONS: Only a limited number of studies were available, with a moderate degree of heterogeneity. CONCLUSIONS: The addition of synchronous liver resection to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of resectable metastatic colorectal cancer was not associated with increased perioperative major morbidity and mortality in comparison with cytoreduction and hyperthermic intraperitoneal chemotherapy alone. However, the presence of liver metastases was associated with inferior disease-free and overall survival. These data support the continued practice of liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in the management of select patients with such stage IV disease.

Epidural Versus Transabdominal Wall Catheters: A Comparative Study of Outcomes After Pancreatic Resection.

BACKGROUND: This study compared epidural analgesia with local anesthetic administration via transabdominal wall catheters (TAWC), to determine the effect on perioperative outcomes in pancreatic surgery. MATERIALS AND METHODS: A retrospective review of patients undergoing open pancreatic surgery at Auckland City Hospital from 2015 to 2018 was undertaken. Data collected included patient demographics, type of perioperative analgesia, intravenous fluid and vasopressor use, length of high dependency unit stay, postoperative complications, and length of hospital stay. RESULTS: Seventy-two patients underwent pancreatic surgery, of which 47 had epidural analgesia and 25 TAWC. The median age was 64 y (range 29-85). Failure of analgesia method occurred in 45% of epidural patients and 28% of TAWC patients (P = 0.209). There was no significant difference in volume of intravenous fluid given or need for vasopressors in the first 3 postoperative days, length of high dependency unit stay (median 1 d, P = 0.2836), rates of postoperative pancreatic fistula (32% versus 40%, P = 0.6046), postoperative complications (38% versus 20%, P = 0.183), or mortality (0.04% versus 0.04%, P = 1.0). CONCLUSIONS: Epidural analgesia and TAWC may have comparable perioperative outcomes in patients undergoing pancreatic surgery. Further randomized studies with a larger cohort of patients are warranted to identify the best postoperative analgesic method in patients undergoing pancreatic resection.

A systematic scoping review of the initial experience with laparoscopic radical antegrade modular pancreatosplenectomy for pancreatic malignancy.

BACKGROUND: Laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) is a validated surgical approach for the surgical treatment of pancreatic malignancies of the body and tail of the pancreas. Open (O-) RAMPS is an established technique that offers oncological efficacy and acceptable post-operative outcomes when compared to standard distal pancreatectomy for pancreatic malignancies. This review aimed to determine the types of evidence available for L-RAMPS, and its selection criteria and reported outcomes, using systematic scoping review methodology. METHODS: A systematic review of available literature was performed in September 2020. Data extracted included patient selection criteria, technical details, total number of L-RAMPS procedures performed, lymph nodes retrieved, resection margins, survival, LOS and complications. RESULTS: Eight papers were eligible for inclusion, totalling 92 cases. There were no studies that directly compared O- to L-RAMPS. All reports were small retrospective cohorts with 3-30 patients. Selection criteria were reported in 4/8 studies and differed between studies. Technique descriptions were included in 6/8 studies. Studies reported a median of 5 (range 1-9) out of ten operative and clinical outcomes, including operative time median range 188-431 min, intraoperative blood loss median range 18-445 mL, R0 resection rate median range 91-100%, number of lymph nodes median range 11-43, and length of stay median range 12-20 days. CONCLUSIONS: L-RAMPS is infrequently reported in the literature. There are currently no data to allow for direct comparison of O- and L-RAMPS. Reports of L-RAMPS have an acceptable oncological and safety profile. A standardised description of the operative technique and outcome reporting, as well as specific training initiatives may be beneficial to broaden the application of L-RAMPS.

Systematic review and meta-analysis of risk factors of postoperative pancreatic fistula after distal pancreatectomy in the era of 2016 International Study Group pancreatic fistula definition.

BACKGROUND: Risk factors for the development of clinically relevant POPF (CR-POPF) following distal pancreatectomy (DP) need clarification particularly following the 2016 International Study Group of Pancreatic Fistula (ISGPF) definition. METHODS: A systemic search of MEDLINE, Pubmed, Scopus, and EMBASE were conducted using the PRISMA framework. Studies were evaluated for risk factors for the development CR-POPF after DP using the 2016 ISGPF definition. Further subgroup analysis was undertaken on studies ≥10 patients in exposed and non-exposed subgroups. RESULTS: Forty-three studies with 8864 patients were included in the meta-analysis. The weighted rate of CR-POPF was 20.4% (95%-CI: 17.7-23.4%). Smoking (OR 1.29, 95%-CI: 1.08-1.53, p = 0.02) and open DP (OR 1.43, 95%-CI: 1.02-2.01, p = 0.04) were found to be significant risk factors of CR-POPF. Diabetes (OR 0.81, 95%-CI: 0.68-0.95, p = 0.02) was a significant protective factor against CR-POPF. Substantial heterogeneity was observed in the comparisons of pancreatic texture and body mass index. Seventeen risk factors achieved significance in a univariate or multivariate comparison as reported by individual studies in the narrative synthesis, however, they remain difficult to interpret as statistically significant comparisons were not uniform. CONCLUSION: This meta-analysis found smoking and open DP to be risk factors and diabetes to be protective factor of CR-POPF in the era of 2016 ISGPF definition.

Systematic review of liver directed therapy for uveal melanoma hepatic metastases.

BACKGROUND: Uveal melanoma (UM) is a rare malignancy with a propensity for metastasis to the liver. Systemic chemotherapy is typically ineffective in these patients with liver metastases and overall survival is poor. There are no evidence-based guidelines for management of UM liver metastases. The aim of this study was to review the evidence for management of UM liver metastases. METHODS: A systematic review of English literature publications was conducted across Ovid Medline, Ovid MEDLINE and Cochrane CENTRAL databases until April 2019. The primary outcome was overall survival, with disease free survival as a secondary outcome. RESULTS: 55 studies were included in the study, with 2446 patients treated overall. The majority of these studies were retrospective, with 17 of 55 including comparative data. Treatment modalities included surgery, isolated hepatic perfusion (IHP), hepatic artery infusion (HAI), transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) and Immunoembolization (IE). Survival varied greatly between treatments and between studies using the same treatments. Both surgery and liver-directed treatments were shown to have benefit in selected patients. CONCLUSION: Predominantly retrospective and uncontrolled studies suggest that surgery and locoregional techniques may prolong survival. Substantial variability in patient selection and study design makes comparison of data and formulation of recommendations challenging.

Effect of vessel preservation on splenic volume and function in patients with spleen preserving distal pancreatectomies.

BACKGROUND: Spleen preservation during distal pancreatectomy (SpDP) can be accomplished by a variety of surgical approaches, but the impact on spleen function is unknown. This study aimed to compare spleen volume, function and complications between patients who underwent vessel sparing (VSDP) vs. vessel ligating (Warshaw, WDP) SpDP. METHODS: All patients who underwent SpDP at the Toronto General Hospital from 2006 to 2015 were included. Primary outcomes were pre- and post-operative spleen volumes and contrast enhancement on CT, hematologic parameters, and spleen-related complications. RESULTS: 82 patients underwent SpDP with median follow up of 20.4 months. Splenic volumes were able to be calculated on 44 patients (VSDP n = 8, WDP n = 36). There was no difference between WDP and VSDP in operative duration, blood loss, hospital length of stay, or Clavien-Dindo ≥3 complication rate. Spleen volumes did not differ from baseline in either group. On postoperative imaging more WDP patients had areas of splenic hypoperfusion (p = 0.032). These differences resolved by 3 months after surgery, there were no instances of long term infectious or bleeding complications related to poor splenic function or gastric varices. CONCLUSION: Both WDP and VSDP achieve splenic preservation. Neither technique resulted in clinically apparent spleen related complications. There is no difference in splenic volume and function in the short/long term.

Patient characteristics and clinical outcomes following initial surgical intervention for MEN1 associated pancreatic neuroendocrine tumours: A systematic review and exploratory meta-analysis of the literature.

BACKGROUND: This systematic review aimed to define the outcomes of different pancreatic resection procedures for multiple endocrine neoplasia type 1 (MEN1) associated pancreatic neuroendocrine neoplasms (pNENs). METHODS: A search of PubMed, MEDLINE and SCOPUS databases were performed in accordance with PRISMA guidelines. RESULTS: Twenty-seven studies including 533 patients undergoing initial pancreatic resection for MEN1 associated pNENs were included in this systematic review. Three hundred and sixty-six (68.7%) distal pancreatectomies (DP), 120 (22.5%) sole enucleations (SE) and 47 (8.8%) pancreaticoduodenectomies (PD) were identified. SE was associated with a higher rate of recurrence than DP (25/67, 37% vs 40/190, 21% respectively, P = 0.008) but a lower rate of endocrine insufficiency than PD (1/20, 5% vs 8/21, 38% respectively, P = 0.010). A meta-analysis of major pancreatic resections (PD or DP) vs SE in 15 studies showed that SE is associated with an increased rate of recurrence (Major resection 42/184, 23% vs SE 20/53, 38% RR 0.65 CI 0.43-0.96 P = 0.032) but reduced rate of postoperative endocrine insufficiency (Resection 37/93, 40% vs SE 0/24, 0% RR 7.37 CI 1.57-34.64 P = 0.008). Similarly, insulinomas and functional pNENs overall had lower rates of recurrence and reoperation with major resection. There was no difference in the reoperation rates or survival outcomes after SE compared with major pancreatic resections at follow-up (pooled overall mean duration: 85 months). CONCLUSION: Major pancreatic resections for MEN1 associated pNENs have a lower risk of recurrence and a higher risk of postoperative endocrine insufficiency when compared to sole enucleation, but a similar rate of reoperation and survival.

Renal outcomes following left renal vein harvest for venous reconstruction during pancreas and liver surgery.

BACKGROUND: The left renal vein (LRV) may be used for venous reconstruction during hepato-pancreato-biliary (HPB) surgery, although concerns exist about compromising renal function. This study aimed to determine renal outcomes following LRV harvest during HPB resections. METHODS: Circumferential PV/SMV resections from 2008 to 2014 were included within two groups (LRV harvest, Control). Absolute and change in Creatinine (Cr) and estimated GFR (eGFR), and rates of acute kidney injury (AKI) and chronic kidney disease (CKD), were compared. Multivariate logistic regression analyses were performed. RESULTS: 76 patients were included (LRV n = 17, Control n = 59). Median Cr and eGFR did not change within groups, although change in eGFR differed between groups at postoperative day (POD) 3 (-4.3 vs. 12.8, p = 0.0035) and 7 (-1.8 vs. 12.4, p = 0.0074). AKI occurred more frequently in the LRV group at POD1 (5/17 vs. 4/59, p = 0.023) and POD3 (5/17 vs. 3/59, p = 0012), with no difference in CKD between groups (2/11 vs. 5/33 at 3 months, p = 0.99). LRV harvest was an independent risk factor for AKI at POD1 and POD3, but not thereafter. CONCLUSIONS: Patients who undergo LRV harvest experience a higher rate of AKI in the first three post-operative days. LRV harvest during pancreas resection does not impact on long-term renal function.

Effect of portal vein embolization on treatment plan prior to major hepatectomy for hepatocellular carcinoma.

BACKGROUND: Portal vein embolization (PVE) is used before major hepatectomy for hepatocellular carcinoma (HCC) to increase future liver remnant (FLR) volume. However, this may increase tumour growth rate, leading to more extensive resections. This study aimed to determine the effect of tumour growth, following PVE, on treatment plan. METHOD: Retrospective cohort study conducted on patients treated from 2008 to 2015 with PVE before major hepatectomy for HCC. Liver and tumour volumetry was performed on pre- and post-PVE CT scans. Image-based and actioned plans were compared before and after PVE. RESULTS: Thirty-one patients received PVE. Non-tumour total liver volume decreased (median 1440 to 1394 cm3; p = 0.031), while tumour (median 161-240 cm3; p < 0.001) and FLR volumes (median 430-574 cm3; p < 0.001) increased. The treatment plan changed in 15/31 patients: more extensive resection (n = 6), less extensive resection (n = 1), no resection as scheduled (n = 8). Tumour progression accounted for a clinically relevant change in treatment plan in 8/31 patients. CONCLUSION: Following PVE in the setting of HCC, tumour progression accounts for a change in treatment plan in approximately a quarter of patients. Further research is warranted to determine whether additional liver directed therapy should routinely be used to slow the growth of HCC post-PVE.

Neoadjuvant therapy and major arterial resection for potentially reconstructable arterial involvement by stage 3 adenocarcinoma of the pancreas.

BACKGROUND: Stage 3 pancreatic ductal adenocarcinoma (PDAC) is defined by arterial involvement. This study objective was to evaluate outcomes for patients with stage 3 PDAC with potentially reconstructable arterial involvement, considered for neoadjuvant therapy (NAT) and pancreatic resection, and to compare outcomes following arterial (AR) and non-arterial resection (NAR). METHODS: This study included patients from 2009 to 2016 with biopsy-proven stage 3 PDAC who were offered NAT before surgical exploration. AR was performed if required to achieve R0 resection. Time to event outcomes were analysed from diagnosis date. RESULTS: 87/89 patients (97.8%) received NAT (chemotherapy 41.6%, chemotherapy/radiotherapy 56.2%). 46/89 (51.7%) underwent exploration; 31 underwent resection (AR n = 20, NAR n = 11). AR patients had longer operative time (681 vs. 563 min, p = 0.006) and more blood loss (1600 vs. 575 mL, p = 0.0004), with no difference for blood transfusion, pancreatic fistula, length of stay, reoperation, or mortality. R0 rate was 30/31. Post-resection 90-day mortality was 3.2%. Median overall survival was statistically comparable between the AR and NAR groups (19.7 vs. 28.4 months, p = 0.41). CONCLUSIONS: AR had comparable clinical and oncologic outcomes to NAR. Following careful selection and non-progression after NAT, major AR may cautiously be considered if required to obtain a negative resection margin.

Impact of preoperative sarcopenia on postoperative outcomes following pancreatic resection: A systematic review and meta-analysis.

BACKGROUND: Morphometric analysis of sarcopenia has garnered interest due to its putative role in predicting outcomes following surgery for a variety of pathologies, including resection for pancreatic disease. However, there are no standard recommendations on whether sarcopenia is a clinically relevant predictor of outcomes in this setting. The aim of this study was to review the prognostic impact of preoperatively diagnosed sarcopenia on postoperative outcomes following pancreatic resection. METHODS: A systematic review of published literature was performed using PRISMA guidelines, and included a search of PubMed, MEDLINE and SCOPUS databases until May 2018. RESULTS: Thirteen studies, including 3608 patients, were included. There was a significant increase in the mean duration of post-operative hospital stay (mean difference of 0.73 days, CI: 0.06-1.40, P = 0.033), there was no difference in the postoperative outcomes, including: clinically relevant postoperative pancreatic fistula, delayed gastric emptying, post-operative bile leak, surgical site infection, significant morbidity and overall morbidity. CONCLUSION: Preoperative sarcopenia is associated with prolonged hospital stay after pancreatic surgery. However, sarcopenia does not appear to be a significant negative predictive factor in postoperative morbidity although study heterogeneity and risk of bias limit the strength of these conclusions.

Neoadjuvant hyperfractionated chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma in Canada.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemoradiation and liver transplantation may be offered for unresectable perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate and survival of patients who entered a national tri-modality protocol. METHOD: Patients enrolled Jan 2009-Aug 2015 were included. Enrolment criteria: ≤65 years, brush biopsy-proven unresectable pCCA <3.5 cm diameter. Conformal radiotherapy was given concurrently with Capecitabine. Following surgical staging, patients received maintenance Cisplatin and Gemcitabine until transplant or progression. Time to event analyses were performed from start of neoadjuvant therapy. RESULTS: Of 43 patients screened, 18 started treatment; median age 53.9 (26.7-62.8) years, tumour diameter 2.7 (2.0-3.4) cm. 11/18 dropped out due to metastatic disease identified during chemoradiation (n = 2), surgical staging (n = 6), or maintenance chemotherapy (n = 3). Six patients underwent transplantation. Median follow up was 17.6 (4.9-57.7) months and overall survival 16.4 months. One and two year survival was 70.6% and 35.3%, respectively. One and 2 year post transplant survival was 83.3% and 55.6%. Median progression free survival was 11.5 months. CONCLUSION: Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although with high rates of dropout and disease progression. Further research is required to determine factors to help select patients for treatment.

Paradigms in trauma laparoscopy for anterior abdominal stab wounds: A scoping review.

INTRODUCTION: Anterior abdominal stab wounds (AASW) are a heterogeneous presentation with evolving management over time and heterogenous practice between centres. The aim of this scoping review was to identify, characterise and classify paradigms for trauma laparoscopies for AASW. METHODOLOGY: Studies were screened from Embase, Medline, Scopus, Cochrane Library and Web of Science from 1 January 1947 until 1 January 2023. Extracted data included indications for trauma laparoscopies vs laparotomies, and criteria for conversion to an open procedure. RESULTS: Of 72 included studies, 35 (48.6 %) were published in the United States, with an increasing number from South Africa since 2014. Screening tests to determine an indication for surgery included local wound exploration, computed tomography, and serial clinical examination. Two studies proposed no absolute contraindications to laparoscopy, whereas most papers supported trauma laparoscopies over laparotomies in hemodynamically stable patients with positive or equivocal screening tests. However, clinical decision trees were used inconsistently both between and within many hospital centres. Triggers for conversion to laparotomy were diverse. Older studies typically reported conversion if peritoneal breach was identified. More recent studies reported advances in technical skills and technology allowed attempt at laparoscopic repair for organ and/or vascular injury. CONCLUSION: This review emphasises that there are many different paradigms of practice for AASW laparoscopy, which are evolving over time. Significant heterogeneity of these studies highlights that meta-analysis of outcomes for trauma laparoscopy is not appropriate unless the included studies report homogenous treatment paradigms and patient cohorts. The decision to perform a trauma laparoscopy should be based on surgeon/hospital experience, patient factors, and resource availability.

Role of neoadjuvant peptide receptor radionuclide therapy in unresectable and metastatic gastro-entero-pancreatic neuroendocrine neoplasms: A scoping review.

Peptide receptor radionuclide therapy (PRRT) is an established therapy for metastatic neuroendocrine neoplasms (NEN). The role of PRRT as a neoadjuvant treatment prior to surgery or other local therapies is uncertain. This scoping review aimed to define the landscape of evidence available detailing the utility of PRRT in the neo-adjuvant setting, including the clinical contexts, efficacy, and levels of evidence. A comprehensive literature search of PUBMED, SCOPUS, and EMBASE through to December 2022 was performed to identify reports of PRRT use as neoadjuvant therapy prior to local therapies. Observational studies and clinical trials were included. A total of 369 records were identified by the initial search, and 17 were included in the final analysis, comprising 179 patients treated with neoadjuvant PRRT. Publications included case reports, retrospective cohort series and a phase 2 trial. Definitions of unresectable disease were variable. Radioisotopes used included 177Lu (n = 142) and 90Y (n = 36), used separately (n = 178) or in combination (n = 1). A combination of PRRT with chemotherapy was also explored (n = 2). Toxicity data was reported in 11/17 studies. Survival analysis was reported in 3/17 studies. Surgical resection following PRRT was reported for both the primary tumor (n = 71) and metastases (n = 12). Resection rates could not be calculated as not all publications reported whether resection was completed. Published literature exploring the use of PRRT in the neoadjuvant setting is mostly limited to case reports and retrospective cohort studies. From these limited data there is reported to be a role of PRRT in neoadjuvant setting in the literature. However, the low quality of evidence precludes any definite conclusion on the grade of disease, site of primary, isotope used or use of concomitant chemotherapy that can benefit from this application. Further prospective studies will require collaboration between multiple centers to gain sufficient high-quality evidence.

SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas.

BACKGROUND: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC. METHODS: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included. DISCUSSION: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options. TRIAL REGISTRATION: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).