Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study.

BACKGROUND: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS. PATIENTS AND METHODS: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance. RESULTS: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients. CONCLUSIONS: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.

A machine learning approach for predicting textbook outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: Peritoneal carcinomatosis is considered a late-stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be an effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS-HIPEC using only preoperatively known variables. METHODS: Adult patients with peritoneal carcinomatosis and who underwent CRS-HIPEC were included from a large, single-center, prospectively maintained dataset (2001-2020). TO was defined as a hospital length of stay ≤14 days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90 days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user-friendly risk calculator was then developed. RESULTS: A total of 1954 CRS-HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n = 258) achieved TO following CRS-HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery. CONCLUSION: This is a data-driven study to predict the probability of achieving TO after CRS-HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.

Marker selection strategies for circulating tumor DNA guided by phylogenetic inference.

Motivation: Blood-based profiling of tumor DNA ("liquid biopsy") has offered great prospects for non-invasive early cancer diagnosis, treatment monitoring, and clinical guidance, but require further advances in computational methods to become a robust quantitative assay of tumor clonal evolution. We propose new methods to better characterize tumor clonal dynamics from circulating tumor DNA (ctDNA), through application to two specific questions: 1) How to apply longitudinal ctDNA data to refine phylogeny models of clonal evolution, and 2) how to quantify changes in clonal frequencies that may be indicative of treatment response or tumor progression. We pose these questions through a probabilistic framework for optimally identifying maximum likelihood markers and applying them to characterizing clonal evolution. Results: We first estimate a distribution over plausible clonal lineage models, using bootstrap samples over pre-treatment tissue-based sequence data. We then refine these lineage models and the clonal frequencies they imply over successive longitudinal samples. We use the resulting framework for modeling and refining tree distributions to pose a set of optimization problems to select ctDNA markers to maximize measures of utility capturing ability to solve the two questions of reducing uncertain in phylogeny models or quantifying clonal frequencies given the models. We tested our methods on synthetic data and showed them to be effective at refining distributions of tree models and clonal frequencies so as to minimize measures of tree distance relative to the ground truth. Application of the tree refinement methods to real tumor data further demonstrated their effectiveness in refining a clonal lineage model and assessing its clonal frequencies. The work shows the power of computational methods to improve marker selection, clonal lineage reconstruction, and clonal dynamics profiling for more precise and quantitative assays of tumor progression. Availability: https://github.com/CMUSchwartzLab/Mase-phi.git. Contact: russells@andrew.cmu.edu.

Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.

Assessing the long-term priorities of pancreaticoduodenectomy survivors.

BACKGROUND: This study assessed the long-term quality of life (QOL) and priorities of pancreaticoduodenectomy (PD) survivors. METHODS: Survivors were surveyed via internet-based support groups. The relative importance of longevity, experience, costs, and QOL were assessed. RESULTS: The PD cohort (n = 247, 35%) was 60 ± 12 years, 71% female, and 93% white. With moderate agreement, patients ranked survival most important, followed by functional and emotional well-being; costs and experience were least important (W = 35.7%, p < 0.001). Well-being improved throughout survivorship (P-QOL: 39 ± 12 at ≤3 mo vs 43 ± 12 at >10 y, p = 0.170; M-QOL: 38 ± 13 at ≤3 mo vs 44 ± 16 at >10 y; p = 0.015) but remained below the general population (p < 0.001). PD patients with benign diagnoses ranked functional independence as most important (2.00 ± 1.13 vs 2.63 ± 1.19, p < 0.001, W = 41.1%); PD patients with malignant diagnoses regarded overall survival most important (2.10 ± 1.20 vs 1.82 ± 1.22, p < 0.16, W = 35.1%). The mean rank order of priorities remained concordant between short-term (<1 year) and long-term (>5 years) survivors. CONCLUSION: PD survivors experience long-term mental and physical health impairments, underscoring the importance of functional and emotional support. Survivors place paramount importance on overall survival, functional independence, and emotional well-being. Cancer survivors prioritize longevity, while survivors of chronic benign conditions prioritize functional independence.

Frequency of Locator Legacy Insert Changes With Implant Overdentures in a UK Population.

PURPOSE: To determine the frequency of insert changes for combined maxillary and mandibular implant overdentures (IOD) using the Locator Legacy system. A secondary objective was to assess the survival of dental implants with IODs. MATERIALS AND METHODS: This retrospective audit reviewed clinical records with up to 12 years follow up from 785 patients who received IODs using the Locator system at a dental hospital. From these, 151 had a combined maxillary opposed by a mandibular IOD and from this, 37 had data retrieved using a minimum data set. The frequency of insert change was recorded and descriptive analysis was provided by means and standard deviations for continuous variables. Frequencies of categorical values were reported as percentages. RESULTS: 222 implants were placed on 21 men, 16 women with a mean age 67.5 years (SD 8.8). All patients were reviewed at least once. Maxillary and mandibular IODs experienced 1.9 (SD 2.0) and 1.2 (SD 1.2) mean insert changes per patient, respectively. The mean time (SD) between initial and first insert change for maxillary and mandibular IODs was 3.4 months (SD 3.2) and 6.4 months (SD 7.2) and between the first and second insert change was 9.9 months (SD 9.0) and 10.0 months (SD 8.3), respectively. Implant failure was 21.6% and 2.7% in the maxilla and mandible respectively. CONCLUSIONS: Clinicians should anticipate the first insert change around 3 months for maxillary IOD and 6 months for mandibular IOD. Subsequently, the second insert change to be around 10 months for both maxillary and mandibular IODs.

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models.

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition.

Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones are over-represented in ctDNA, clonal diversity can appear elevated in the blood, and spatial bias in shedding can inflate subclonal variant allele frequencies (VAFs). Additionally, we find that tumors that are mostly quiescent can display similar biases but are far less detectable, and the extent of perceptible spatial bias strongly depends on sequence detection limits. Overall, we show that spatially structured shedding might cause liquid biopsies to provide highly biased profiles of tumor state. While this may enable more sensitive detection of expanding clones, it could also increase the risk of targeting a subclonal variant for treatment. Our results indicate that the effects and clinical consequences of spatially variable cell death on ctDNA composition present an important area for future work.

Risk factors for failure to rescue after hepatectomy in a high-volume UK tertiary referral center.

BACKGROUND: Mortality after severe complications after hepatectomy (failure to rescue) is strongly linked to center volume. The aim of this study was to evaluate the risk factors for failure to rescue after hepatectomy in a high-volume center. METHODS: Retrospective study of 1,826 consecutive patients who underwent hepatectomy from 2011 to 2018. The primary outcome was a 90-day failure to rescue, defined as death within 90 days posthepatectomy after a severe (Clavien-Dindo grade 3+) complication. Risk factors for 90-day failure to rescue were evaluated using a multivariable binary logistic regression model. RESULTS: The cohort had a median age of 65.3 years, and 56.6% of patients were male. The commonest indication for hepatectomy was colorectal metastasis (58.9%), and 46.9% of patients underwent major or extra-major hepatectomy. Severe complications developed in 209 patients (11.4%), for whom the 30- and 90-day failure to rescue rates were 17.0% and 35.4%, respectively. On multivariable analysis, increasing age (P = .006) and modified Frailty Index (P = .044), complication type (medical or combined medical/surgical versus surgical; P < .001), and body mass index (P = .018) were found to be significant independent predictors of 90-day failure to rescue. CONCLUSION: Older and frail patients who experience medical complications are particularly at risk of failure to rescue after hepatectomy. These results may inform preoperative counseling and may help to identify candidates for prehabilitation. Further study is needed to assess whether failure to rescue rates could be reduced by perioperative interventions.

Can preoperative Carbohydrate Antigen 19-9 predict metastatic pancreatic cancer? Results of a systematic review and meta-analysis.

BACKGROUND: To investigate the relationship between preoperative Carbohydrate Antigen19-9(CA19-9)and pancreatic cancer occult metastasis. METHODS: Systematic search of MEDLINE, CENTRAL, Web of Science and bibliographic reference lists were conducted. All comparative observational studies investigating the predictive ability of preoperative CA 19-9 in patients with pancreatic cancer were considered. Mean CA-19-9 value in the pancreatic cancer patients with and without metastasis were evaluated. Best cut-off value of CA 19-9 for metastasis was determined using ROC analysis. RESULTS: Ten comparative observational studies reporting a total of 1431 pancreatic cancer patients with (n = 496) and without (n = 935) metastasis were included. Subsequent meta-analysis demonstrated that mean preoperative CA 19-9 level was significantly higher in patients with metastases compared to those without (MD: 904.4; 95 % CI, 642.08-1166.74, P < 0.0001). The between-study heterogeneity was significant (I2: 99 %, P < 0.00001). ROC analysis yielded a cut-off CA 19-9 level of 336 with a sensitivity and specificity for predicting metastasis of 90 % and 80 %, respectively (AUC = 0.90). CONCLUSIONS: CA 19-9 level is significantly higher in patients with metastatic pancreatic cancer. A preoperative CA 19-9 value of 336 should be considered as an acceptable cut-off value to design prospective studies.

Navigating Precision Oncology: Insights from an Integrated Clinical Data and Biobank Repository Initiative across a Network Cancer Program.

Advancing cancer treatment relies on the rapid translation of new scientific discoveries to patient care. To facilitate this, an oncology biobank and data repository program, also referred to as the "Moonshot" program, was launched in 2021 within the Integrated Network Cancer Program of the Allegheny Health Network. A clinical data program (CDP) and biospecimen repository were established, and patient data and blood and tissue samples have been collected prospectively. To date, the study has accrued 2920 patients, predominantly female (61%) and Caucasian (90%), with a mean age of 64 ± 13 years. The most common cancer sites were the endometrium/uterus (12%), lung/bronchus (12%), breast (11%), and colon/rectum (11%). Of patients diagnosed with cancer, 34% were diagnosed at stage I, 25% at stage II, 26% at stage III, and 15% at stage IV. The CDP is designed to support our initiative in advancing personalized cancer research by providing a comprehensive array of patient data, encompassing demographic characteristics, diagnostic details, and treatment responses. The "Moonshot" initiative aims to predict therapy responses and clinical outcomes through cancer-related biomarkers. The CDP facilitates this initiative by fostering data sharing, enabling comparative analyses, and informing the development of novel diagnostic and therapeutic methods.

Comprehensive value implications of surgeon volume for lung cancer surgery: Use of an analytic framework within a regional health system.

Objective: We used a framework to assess the value implications of thoracic surgeon operative volume within an 8-hospital health system. Methods: Surgical cases for non-small cell lung cancer were assessed from March 2015 to March 2021. High-volume (HV) surgeons performed >25 pulmonary resections annually. Metrics include length of stay, infection rates, 30-day readmission, in-hospital mortality, median 30-day charges and direct costs, and 3-year recurrence-free and overall survival. Multivariate regression-based propensity scores matched patients between groups. Metrics were graphed on radar charts to conceptualize total value. Results: All 638 lung resections were performed by 12 surgeons across 6 hospitals. Two HV surgeons performed 51% (n = 324) of operations, and 10 low-volume surgeons performed 49% (n = 314). Median follow-up was 28.8 months (14.0-42.3 months). Lobectomy was performed in 71% (n = 450) of cases. HV surgeons performed more segmentectomies (33% [n = 107] vs 3% [n = 8]; P < .001). Patients of HV surgeons had a lower length of stay (3 [2-4] vs 5 [3-7]; P < .001) and infection rates (0.6% [n = 1] vs 4% [n = 7]; P = .03). Low-volume and HV surgeons had similar 30-day readmission rates (14% [n = 23] vs 7% [n = 12]; P = .12), in-hospital mortality (0% [n = 0] vs 0.6% [n = 1]; P = .33), and oncologic outcomes; 3-year recurrence-free survival was 95% versus 91%; P = .44, and 3-year overall survival was 94% versus 90%; P = 0. Charges were reduced by 28%, and direct costs were reduced by 23% (both P < .001) in the HV cohort. Conclusions: HV surgeons provide comprehensive value across a health system. This multidomain framework can be used to help drive oncologic care decisions within a health system.

Pilot clinical study to evaluate the efficacy of a professionally delivered high fluoride varnish on erosive tooth wear in an in-situ model.

OBJECTIVES: The aim for this pilot study was to investigate the effect of a sodium fluoride varnish on step height measured by a profilometer from human enamel worn by healthy volunteers with a novel in situ/ex vivo erosion design. METHOD: Healthy volunteers aged 18-70 years wore a palatal splint containing 8 human enamel samples and underwent two 3-day treatment periods for 6 h a day with a varnish containing sodium fluoride at 22,600 ppm and the control with the same ingredients but without fluoride. Each splint contained 4 polished and 4 unpolished samples. The interventions were applied to the surface of the enamel samples in randomised order, removed after 6 h, then immersed ex-vivo in 1 %, pH 2.7 citric acid for 2 min, repeated 4 times a day, over 2 days. Measurements of enamel were assessed blindly by microhardness on day 2 and by non-contact laser profilometry on day 3 for the two treatments. RESULTS: 24 volunteers, 2 males and 22 females aged 27-54 years, were screened and recruited. The delta microhardness, from polished samples removed at the end of day 2, for the control and fluoride treatment was 95.7 (22.9) kgf/mm2 and 123.7 (28.9) kgf/mm2, respectively (p < .005). The mean (SD) step height for the control polished enamel surfaces was 3.67 (2.07) µm and for the fluoride varnish was 1.79 (1.01) µm (p < .0005). The control unpolished enamel surfaces had a mean 2.09 (1.53) µm and the fluoride varnish was 2.11 (1.53) µm but no statistical difference was detected. CONCLUSIONS: The results from this pilot study, utilizing an in-situ model where enamel was exposed to acid over the course of 2 days, demonstrated that a high fluoride varnish containing sodium fluoride at 22,600 ppm prevented erosive wear compared to a control on the polished enamel surfaces. CLINICAL SIGNIFICANCE: Intra-oral study demonstrated that a high fluoride varnish containing sodium fluoride at 22,600 ppm reduced erosive tooth wear.

Quantifying error introduced by iterative closest point image registration.

OBJECTIVES: The aim of this paper was to quantify the analysis error introduced by iterative closest point (ICP) image registration. We also investigated whether a subsequent subtraction process can reduce process error. METHODS: We tested metrology and two 3D inspection software using calibration standards at 0.39 µm, and 2.64 µm and mathematically perfect defects (softgauges) at 2 and 20 µm, on free form surfaces of increasing complexity and area, both with and without registration. Errors were calculated in percentage relative to the size of the defect being measured. Data were analysed in GraphPad Prism 9, normal and two-way ANOVA with post-hoc Tukey's was applied. Significance was inferred at p < 0.05. RESULTS: Using ICP registration introduced errors from 0 % to 15.63 % of the defect size depending on the surface complexity and size of the defect. Significant differences were observed in analysis measurements between metrology and 3D inspection software and within different 3D inspection software, however, one did not show clear superiority over another. Even in the absence of registration, defects at 0.39 µm, and 2.64 µm produced substantial measurement error (13.39-77.50 % of defect size) when using 3D inspection software. Adding an additional data subtraction process reduced registration error to negligible levels (<1 % independent of surface complexity or area). CONCLUSIONS: Commercial 3D inspection software introduces error during direct measurements below 3 µm. When using an ICP registration, errors over 15 % of the defect size can be introduced regardless of the accuracy of adjacent registration surfaces. Analysis output between software are not consistently repeatable or comparable and do not utilise ISO standards. Subtracting the datasets and analysing the residual difference reduced error to negligible levels. CLINICAL SIGNIFICANCE: This paper quantifies the significant errors and inconsistencies introduced during the registration process even when 3D datasets are true and precise. This may impact on research diagnostics and clinical performance. An additional data processing step of scan subtraction can reduce this error but increases computational complexity.

Normal CEA Levels After Neoadjuvant Chemotherapy and Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion Predict Improved Survival from Colorectal Peritoneal Metastases.

BACKGROUND: Normal carcinoembryonic antigen (CEA) levels (≤ 2.5 ng/ml) after resection of localized colorectal cancer or liver metastases are associated with improved survival, however, these trends are understudied for colorectal peritoneal metastases (CRPM). PATIENTS AND METHODS: We conducted a retrospective single-institution study of patients with CRPM undergoing cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) with and without neoadjuvant chemotherapy (NACT). CEA was measured before and after NACT and within 3 months after CRS/HIPEC. RESULTS: A total of 253 patients (mean age 55.3 years) with CRPM undergoing CRS/HIPEC had complete CEA data and 191 also underwent NACT with complete data. The median peritoneal carcinomatosis index score (PCI) of the overall cohort was 12 and 82.7% of patients had complete cytoreduction (CC0). In total, 64 (33.5%) patients had normal CEA levels after NACT with a median overall survival (OS) of 45.2 months compared with those with an elevated CEA (26.4 months, p = 0.004). Patients with normal CEA after NACT had a lower PCI found at the time of surgery than those with elevated CEA (10 versus 14, p < 0.001), 68 (26.9%) patients with an elevated preoperative CEA level experienced normalization after CRS/HIPEC, and 118 (46.6%) patients had elevated CEA after CRS/HIPEC. Patients who experienced normalization demonstrated similar OS to patients that had normal CEA levels pre- and post-surgery and improved OS compared with those with elevated postop CEA (median 41.9 versus 47 months versus 17.1 months, respectively, p < 0.001). CONCLUSIONS: Normal CEA levels after NACT and/or CRS/HIPEC are associated with improved survival for patients with CRPM. Patients that normalize CEA levels after surgery have similar survival to those with normal preoperative levels.

Staging Computed Tomography Parameters Predict the Need for Vein Resection during Pancreaticoduodenectomy in Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Surgery-first approach is the current standard of care for resectable pancreatic ductal adenocarcinoma (PDAC), and a proportion of these cases will require venous resection. This study aimed to identify parameters on staging computed tomography (CT) that predict the need for venous resection during pancreaticoduodenectomy (PD) for resectable PDAC. METHODS: We conducted a retrospective analysis of prospectively collected data on patients who underwent PD for resectable staged PDAC (as per NCCN criteria) between 2011 and 2020. Staging CTs were independently reviewed by two specialist radiologists blinded to the clinical outcomes. Univariate and multivariate risk analyses were performed. RESULTS: In total, 296 PDs were included. Venous resection was performed in 62 (21%) cases. There was a higher rate of resection margin positivity in the vein resection group (72.6% vs. 48.7%, p = 0.001). Tumour at the neck of the pancreas, superior mesenteric vein involvement of ≥10 mm and pancreatic duct dilatation were identified as independent predictors for venous resection. DISCUSSION: Staging CT parameters can predict the need for venous resection during PD for resectable cases of PDAC. This may assist in surgical planning, patient selection and counselling. Future efforts should concentrate on validating these results or identifying additional predictors in a multicentre and prospective setting.

Investigating misdiagnosis of suspected cancer among patients undergoing pancreatoduodenectomy: three decades of experience.

BACKGROUND: Diagnostic error can result in pancreatoduodenectomy (PD) being mistakenly performed for benign disease. The aims of this study were to observe the error rate in PD over three decades and identify characteristics of benign disease that can mimic malignancy. METHODS: Patients with a benign histological diagnosis after having PD performed for suspected malignancy between 1988 and 2019 were selected for review. Preoperative clinical features, imaging and pathological samples were reviewed alongside resection specimens to identify features that may have led to misdiagnosis. RESULTS: Over the study period, 1812 patients underwent PD for suspected malignancy and 97 (5.2 %) of these had a final benign diagnosis. The rate of benign cases reduced across the study period. Some 62 patients proceeded to surgery without a preoperative tissue diagnosis; the decision to operate was made upon clinical and radiologic features alone. There were six patients who had a preoperative pathological sample suspicious for malignancy, of which two had autoimmune pancreatitis in the postoperative histology specimen. DISCUSSION: Benign conditions, notably autoimmune and chronic pancreatitis, can mimic malignancy even with the use of EUS-FNA. The results of all available diagnostic modalities should be interpreted by a multidisciplinary team and honest discussions with the patient should follow.