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Background: Anastomotic leak is the anathema of colorectal surgery. Early diagnosis is an essential segue to early intervention. A temporary defunctioning ileostomy does not prevent an anastomotic leak and presents inherent complications of its own. Drain fluid biomarkers have been studied in colorectal surgery but not in ileal pouch surgery., Objective: This study aimed to assess drain fluid amylase as a biomarker of anastomotic leak after ileal pouch surgery and without a diverting ileostomy., Design: This was a multicenter prospective observational cohort study., Settings: The study was conducted at 4 tertiary hospitals in Queensland, Australia., Patients: This study included elective patients undergoing restorative proctectomy and ileal pouch surgery., Interventions: Measurement of rectal tube amylase and drain fluid amylase., Main Outcome Measures: The primary measure was observation of increased drain fluid amylase on the day of anastomotic leak., Results: Fifty-three patients were studied. On the day of anastomotic leak, 4 patients in the anastomotic leak group who experienced an early anastomotic leak recorded a median drain fluid amylase of 21,897 U/L compared with a median drain fluid amylase of 25 U/L for those in the no anastomotic leak group ( p < 0.0001)., Limitations: This study relies on the anastomotic leak occurring while the pelvic drain is in situ., Conclusions: The measurement of drain fluid amylase is a sensitive biomarker of early clinical anastomotic leak in patients undergoing restorative proctectomy with an ileal pouch and when a diverting ileostomy is not incorporated. This simple, inexpensive, and noninvasive test should be considered in all patients with ileal pouches as an adjunct to the clinical diagnosis and differentiation of anastomotic leak from other postoperative complications. See Video Abstract at http://links.lww.com/DCR/B958 .Estudio multicéntrico de la amilasa del líquido de drenaje como biomarcador para la detección de fugas anastomóticas después de una cirugía de reservorio ileal sin ileostomía de derivación., Antecedentes: La fuga anastomótica es el anatema de la cirugía colorrectal. El diagnóstico precoz es una transición esencial a la intervención temprana. Una ileostomía desfuncionalizante temporal no evita una fuga anastomótica y presenta sus propias complicaciones inherentes. Los biomarcadores del líquido de drenaje se han estudiado en la cirugía colorrectal, pero no en la cirugía del reservorio ileal., Objetivo: El objetivo fue evaluar la amilasa del líquido de drenaje como biomarcador de fuga anastomótica después de cirugía de reservorio ileal y sin ileostomía de derivación., Diseo: Este fue un estudio de cohorte observacional prospectivo multicéntrico., Ajustes: El estudio se realizó en 4 hospitales terciarios en Queensland, Australia., Pacientes: Se incluyeron pacientes electivos sometidos a proctectomía restauradora y cirugía de reservorio ileal., Intervenciones: Medición de la amilasa del tubo rectal y amilasa del líquido de drenaje., Principales Medidas De Resultado: La medida principal fue la observación del aumento de la amilasa en el líquido de drenaje el día de la fuga anastomótica., Resultados: Cincuenta y tres pacientes fueron estudiados. Los 4 pacientes que experimentaron una fuga anastomótica temprana registraron una mediana de amilasa en el líquido de drenaje de 21 897 U/L el día de la fuga anastomótica en comparación con una mediana de amilasa en el líquido de drenaje de 25 U/L para aquellos en el grupo sin fuga anastomótica (p < 0,0001)., Limitaciones: Este estudio se basa en que la anastomosis ocurre mientras el drenaje pélvico está in situ., Conclusiones: La medición de amilasa en el líquido de drenaje es un biomarcador sensible de fuga anastomótica clínica temprana en pacientes sometidos a proctectomía restauradora con reservorio ileal y cuando no se incorpora ileostomía derivativa. Esta prueba simple, económica y no invasiva se debe considerar en todos los pacientes con reservorio ileal como complemento del diagnóstico clínico y la diferenciación de la fuga anastomótica de otras complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B958 . (Traducción-Dr Yolanda Colorado )., (Copyright © The ASCRS 2022.)

Sulfonamides are promising classical carbonic anhydrase (CA; EC 4.2.1.1) inhibitors, being used for several medical purposes such as diuretics, anticonvulsants, topically acting antiglaucoma agents, for antiobesity and anticancer therapies. Herein, a series of chalcone-based benzenesulfonamides (3a‒m) was synthesized and assessed for its inhibitory activity against a panel of four human carbonic anhydrases (hCA isoforms I, II, IX, and XII). Most compounds displayed single- to double-digit nanomolar inhibition constants (K i s), with some derivatives being more potent and/or selective than the standard drug acetazolamide (AAZ). Among the synthesized compounds, 3g compound demonstrated the highest inhibitory activity against the hCA II isoform (K i  = 2.5 nM) with 30-, 9-, and 11-fold selectivity for hCA II over the I, IX, and XII isoforms, respectively. Structure-activity relationships for different substitution patterns were analyzed. Additionally, a molecular docking study showed that compound 3g bound to hCA II by coordinating with the zinc ion through the deprotonated benzenesulfonamide moiety, in addition to a hydrogen bond formed between an oxygen of the sulfonamide moiety and Thr199. Moreover, the chalcone core participated in van der Waals interactions with some active site residues, such as Ile91, Val121, and Leu198. Consequently, this report introduces a successful approach toward identifying compound 3g as a highly potent and selective chalcone-based benzenesulfonamide inhibitor of hCA II worthy of further investigation., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Background: Anastomotic leak (AL) is the anathema of colorectal surgery. Early diagnosis is an essential segue to early intervention. A temporary diverting ileostomy (TDI) does not prevent an AL and presents inherent complications of its own. Numerous drain fluid biomarkers (BM) have been studied in colorectal surgery and extravasated intraluminal substances (EILS) such as amylase have shown promise. The aim of this study was to assess drain fluid amylase (DFA) as a BM of AL after minimally invasive rectal resection without a TDI., Methods: A single centre prospective cohort study performed from 2018 to 2021. The primary outcome was DFA measured daily whilst the drain was in situ. Rectal tube amylase was also measured for the first two post-operative days to quantitate the intra-luminal levels of the enzyme. DFA was compared between patients who experienced AL and those who did not., Results: Of the 62 patients studied, six (9.7%) experienced AL. There was a statistically significant difference in DFA between patients who experienced AL (Median:1373.5 U/L; IQR: 306-7953) and patients who did not experience an AL (Median: 27.0 U/L; IQR: 16-38); p < 0.0001., Conclusions: The measurement of drain fluid amylase is a highly sensitive BM of early clinical anastomotic leak in patients undergoing a rectal resection with an extraperitoneal anastomosis and when a TDI is not incorporated. This simple, inexpensive and non-invasive test should be considered in all patients as an adjunct to the clinical diagnosis and differentiation of AL from other postoperative complications., (© 2022 Royal Australasian College of Surgeons.)

Purpose: To describe and update stercoral colitis clinical risk factors, relative frequency, location, and CT imaging features correlated with surgical and pathological results. Methods: CT reports over a 5-year period (05/2017–05/2022) at a single medical center were searched. Main inclusion criteria were luminal distention with formed stool, wall thickening, and surrounding inflammation. Positive cases were graded as mild (early or developing stercoral colitis) versus moderate-to-severe based on CT findings. Medical records were reviewed for risk factors and outcome data in moderate-to-severe cases. P-values were tabulated for comparison. Results: 545 total cases (71 (60, 82) years, 278 males) were identified on CT, including 452 mild (82.9%) and 93 moderate-to-severe cases (17%, 67 (55, 79) years, 48 females). Twenty cases showed evidence of perforation (3.7% total cohort, 22% moderate-to-severe cohort). Diagnosis as an incidental finding was frequent (46.0% of mild cases). Most cases involved the rectum (97.6% of mild cohort and 69% of moderate-to-severe cohort). The sigmoid was involved in 31% of moderate-to-severe cases, but 95% of the perforated subcohort (19/20, 13/20 without rectal involvement). Among the moderate-to-severe cohort, perforation was associated with slightly increased wall thickness (6.4 vs. 5.7 mm, p = 0.03), opioid use (50 vs. 23%, p = 0.04), and disease-specific mortality (11 vs. 0%, p =0.04). Perforation was less associated with major neurocognitive disorders (20 vs. 60%, p = 0.003), institutionalized status (5 vs. 38%, p = 0.005), and a prescribed bowel regimen (30 vs. 63%, p = 0.01). Conclusion: Stercoral colitis may be under-reported. Perforation tends to favor sigmoid involvement and a less traditional patient cohort. [ABSTRACT FROM AUTHOR]

Simple Summary: This review summarizes recent advances in the nuclear medicine theranostic approach. It covers the repurposing of historical radiotracers for new indications and highlights new radiotracers in solid malignancies. Additionally, the potential of combining theranostics with immunotherapy is explored, underscoring the promise of personalized and targeted therapies. The progress in theranostics signifies an exciting era in nuclear medicine with potential benefits for diverse cancer types. The theranostic approach in oncology holds significant importance in personalized medicine and stands as an exciting field of molecular medicine. Significant achievements have been made in this field in recent decades, particularly in treating neuroendocrine tumors using 177-Lu-radiolabeled somatostatin analogs and, more recently, in addressing prostate cancer through prostate-specific-membrane-antigen targeted radionuclide therapy. The promising clinical results obtained in these indications paved the way for the further development of this approach. With the continuous discovery of new molecular players in tumorigenesis, the development of novel radiopharmaceuticals, and the potential combination of theranostics agents with immunotherapy, nuclear medicine is poised for significant advancements. The strategy of theranostics in oncology can be categorized into (1) repurposing nuclear medicine agents for other indications, (2) improving existing radiopharmaceuticals, and (3) developing new theranostics agents for tumor-specific antigens. In this review, we provide an overview of theranostic development and shed light on its potential integration into combined treatment strategies. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecological malignancy and is often associated with both DNA repair deficiency and extensive metabolic reprogramming. While still emerging, the interplay between these pathways can affect ovarian cancer phenotypes, including therapeutic resistance to the DNA damaging agents that are standard-of-care for this tumor type. In this review, we will discuss what is currently known about cellular metabolic rewiring in ovarian cancer that may impact DNA damage and repair in addition to highlighting how specific DNA repair proteins also promote metabolic changes. We will also discuss relevant data from other cancers that could be used to inform ovarian cancer therapeutic strategies. Changes in the choice of DNA repair mechanism adopted by ovarian cancer are a major factor in promoting therapeutic resistance. Therefore, the impact of metabolic reprogramming on DNA repair mechanisms in ovarian cancer has major clinical implications for targeted combination therapies for the treatment of this devastating disease., (© 2024 The Author(s). BioEssays published by Wiley Periodicals LLC.)

Background: In this prospective cohort study, we evaluated features of "adult‐onset megacolon with focal hypoganglionosis." Methods: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. Key results: The median age of the patients with adult‐onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0–74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72–86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7–16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190–338) in the proximal and 95 cells/cm (IQR, 45–213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, −5.4 points (surgery) vs. ‐0.3 points (medical treatment); p < 0.001]. Conclusions and inferences: Adult‐onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients. [ABSTRACT FROM AUTHOR]

Aim: Transanal total mesorectal (taTME) excision is a method used to assist in the radical removal of the rectum. By adopting the concept of natural orifice surgery, it offers potential benefits over conventional techniques. Early enthusiasm for this strategy led to its rapid and widespread adoption. The imposing of a local moratorium was precipitated by the discovery in Norway of an uncommon multifocal pattern of locoregional recurrence. The aim of this systematic review and meta-analysis was to determine the incidence of local recurrence after taTME for rectal cancer., Method: Conforming to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines checklist, a systematic review and meta-analysis was conducted. This included case series and comparative studies between taTME and preferentially laparoscopic procedures published between 2010 and 2021., Results: There were a total of 1175 studies retrieved. After removal and screening for quality and relevance, the final analysis contained 40 studies. The local recurrence rate following taTME was 3.4% (95% CI 2.9%-3.9%, I 2  = 0%) in 4987 patients with follow-up durations ranging from 0.7 to 5.5 years. Compared with laparoscopic TME, local recurrence was not statistically different for the taTME group (p = 0.076); however, it was less probable (OR = 0.51, 95% CI 0.24-1.09, I 2  = 0%). Systemic recurrence and circumferential resection margin status were secondary outcomes; however, the differences were not statistically significant., Conclusion: Our data suggest that the local recurrence for regular laparoscopic and transanal TME surgeries may be comparable, suggesting that taTME can be performed without influencing locoregional oncological outcomes in patients treated at specialized institutions and who have been cautiously selected., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Current understanding of Multiple Sclerosis (MS) pathophysiology implicates perturbations in adaptive cellular immune responses, predominantly T cells, in Relapsing-Remitting forms (RRMS). Nevertheless, from a clinical perspective MS is a heterogeneous disease reflecting the heterogeneity of involved biological systems. This complexity requires advanced analysis tools at the single-cell level to discover biomarkers for better patient-group stratification. We designed a novel 44-parameter mass cytometry panel to interrogate predominantly the role of effector and regulatory subpopulations of peripheral blood myeloid subsets along with B and T-cells (excluding granulocytes) in MS, assessing three different patient cohorts: RRMS, PPMS (Primary Progressive) and Tumefactive MS patients (TMS) (n=10, 8, 14 respectively). We further subgrouped our cohort into inactive or active disease stages to capture the early underlying events in disease pathophysiology. Peripheral blood analysis showed that TMS cases belonged to the spectrum of RRMS, whereas PPMS cases displayed different features. In particular, TMS patients during a relapse stage were characterized by a specific subset of CD11c+CD14+ CD33+, CD192+, CD172+-myeloid cells with an alternative phenotype of monocyte-derived macrophages (high arginase-1, CD38, HLA-DR-low and endogenous TNF-a production). Moreover, TMS patients in relapse displayed a selective CD4 T-cell lymphopenia of cells with a Th2-like polarised phenotype. PPMS patients did not display substantial differences from healthy controls, apart from a trend toward higher expansion of NK cell subsets. Importantly, we found that myeloid cell populations are reshaped under effective disease-modifying therapy predominantly with glatiramer acetate and to a lesser extent with antiCD20, suggesting that the identified cell signature represents a specific therapeutic target in TMS. The expanded myeloid signature in TMS patients was also confirmed by flow cytometry. Serum neurofilament light-chain levels confirmed the correlation of this myeloid cell signature with indices of axonal injury. More indepth analysis of myeloid subsets revealed an increase of a subset of highly cytolytic and terminally differentiated NK cells in PPMS patients with leptomeningeal enhancement (active-PPMS), compared to those without (inactive-PPMS). We have identified previously uncharacterized subsets of circulating myeloid cells and shown them to correlate with distinct disease forms of MS as well as with specific disease states (relapse/remission). [ABSTRACT FROM AUTHOR]

Early adequate treatment of patients with acute pancreatitis leads to a decrease in mortality and reduces the financial burden on medical institutions and the patient, which encourages the continued search for optimal markers for assessing severity and predicting the course of the disease. The aim of this work is to study the modern aspects of the pathogenesis of acute pancreatitis and the role of various biomarkers in the diagnosis of the severity of the course of the disease and the prediction of its complications. The study of the features of the pathogenesis of acute pancreatitis continues, which naturally contributes to the emergence of new diagnostic markers of this disease. It has been proven that most of the etiological factors that cause acute pancreatitis (alcohol, hypoxia, hypercalcemia, hyperlipidemia, certain pharmacological drugs) also contribute to abnormally high oscillations of the Ca2+ level. Therefore, it can be assumed that in acute pancreatitis, Ca2+ is a common trigger for various etiological factors, which trigger the pathological process. In turn, the enzymatic cascade is the starting point for the development of local and systemic inflammatory reactions, manifested by local and systemic effects. Based on the study of the features of the course of severe forms of acute pancreatitis, we established the role of vitamin D deficiency in the development of the disease. In addition, the study of the activity of tissue plasminogen activator and/or the level of thrombin-antithrombin III complex can be interesting as markers of the development of thrombohemorrhagic complications. An increase in the number of positive results of a serological examination for Helicobacter pylori (immunoglobulin M) in patients with a severe course of acute pancreatitis after 7 days from the moment of hospitalization gives reason to consider this indicator as one of the predictors of the development of purulent complications of the disease. Preliminary studies using the proposed diagnostic markers give encouraging results regarding the prognosis for the disease and the life of this extremely complex category of patients. [ABSTRACT FROM AUTHOR]

In electrocatalysis we seldom think about the competing direct reduction reactions that may happen alongside catalytically mediated reduction‐ with direct redox chemistry often happening slower but in competition with, catalysis. One class of compounds of interest from this perspective are iron sulfides. In addition to being structurally similar to many metalloproteins, iron sulfides are also among nature's strongest chemical reductants and reported to act as catalysts for key chemical reactions including proton, nitrite, and nitrate reduction. It is important that iron sulfides can act as catalysts because they are also strong enough reductants to mediate some of the same reactions directly. This is paradoxical because in order to be a catalyst for reduction, an iron sulfide cannot also be oxidised. To investigate this phenomenon further, we assembled a test set of iron sulfides spanning both amorphous iron sulfide (FeSam) as well as the crystalline iron sulfides greigite, pyrite, and troilite. These were used to explore the relationship between direct reduction and catalysis of a reduction reaction with a secondary electron source, NO2− was chosen as a test substrate. The trends in direct reduction followed the least stable material (FeSam) to the most stable material (FeS2). Of the phases studied, troilite (FeS) showed the largest difference between direct and catalytic reduction, however amorphous iron sulfide showed the greatest selectivity for NH3/NH4+ production as both a direct reductant and a catalyst. [ABSTRACT FROM AUTHOR]

After discussion with the patient and family, the patient progressed to laparotomy with high anterior resection of the rectosigmoid colon. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed severe faecal loading throughout the entire colon with a markedly dilated rectosigmoid colon measuring 19 cm transversely without a significantly distended caecum, consistent with an acquired megacolon. A 73-year-old male was referred to a regional referral hospital by his general practitioner with abdominal pain and severe constipation on a background of lifelong chronic constipation (CC) and fragile X syndrome (FXS). [Extracted from the article]

Background: Anastomotic leak (AL) is a serious complication in digestive surgery. Early diagnosis might allow clinicians to anticipate appropriate management. The aim of this study was to assess the predictive value of amylase concentration in drain fluid for the early diagnosis of digestive tract AL. Materials and Methods: Hundred and fourteen consecutive patients "at risk" of AL, in whom a flexible drainage was placed by surgeon's choice after digestive anastomosis were included. Patients with eso-gastric, bilio-digestive, and pancreatic anastomoses were excluded. Drain amylase measurement (DAM) was routinely performed on postoperative day (POD) 1, 3, 5–7. DAM values were compared between patients with postoperative AL versus patients without AL. A receiver-operating curve (ROC) with calculation of the areas under the ROC curves area under curves was performed and a cutoff value of DAM was calculated. Results: AL occurred in 25 patients (AL group) and 89 patients did not present AL (C group). The mean DAM was significantly higher in AL group versus C Group on POD 1, 3, and 5. A cutoff value of 307 IU/L predicted the occurrence of AL with a sensitivity and specificity of 91% and 100%, respectively. Positive and negative predictive values were 100% and 97.5%, respectively. Patients with AL had an elevated DAM prior to the appearance of any clinical signs of AL. Conclusion: High level DAM could accurately predict AL for proximal and distal digestive tract anastomoses. This simple, noninvasive, and low-cost method can accurately predict early AL and help physicians to perform appropriate imaging and treatment. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic cancers. Overexpression of the urokinase-type plasminogen activator (uPA) or its cell surface receptor uPAR is a key step in the acquisition of a metastatic phenotype via multiple mechanisms, including the increased activation of cell surface localised plasminogen which generates the serine protease plasmin. This triggers multiple downstream processes that promote tumour cell migration and invasion. Increasing clinical evidence shows that the overexpression of uPA, uPAR, or of both is strongly associated with worse clinicopathological features and poor prognosis in PDAC patients. This review provides an overview of the current understanding of the uPAS in the pathogenesis and progression of pancreatic cancer, with a focus on PDAC, and summarises the substantial body of evidence that supports the role of uPAS components, including plasminogen receptors, in this disease. The review further outlines the clinical utility of uPAS components as prospective diagnostic and prognostic biomarkers for PDAC, as well as a rationale for the development of novel uPAS-targeted therapeutics. [ABSTRACT FROM AUTHOR]

COVID-19 has threatened the existence of humanity andthis infection occurs due to SARS-CoV-2 or novel coronavirus, was first reported in Wuhan, China. Therefore, there is a need to find a promising drug to cure the people suffering from the infection. The second wave of this viral infection was shaking the world in the first half of 2021. Drugs Controllers of India has allowed the emergency use of 2-deoxy-D-glucose (2DG) in 2021 for patients suffering from this viral infection. The potentiality of 2-deoxy-D-glucose to intervene in D-glucose metabolism exists and energy deprivation is an effective parameter to inhibit cancer cell development. Once 2DG arrives in the cells, it becomes phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG6P), a charged molecule expressively captured inside the cells. On the other hand, 2DG lacks the ability to convert into fructose-6-phosphate, resulting in a hampering of the activity of both glucose-6-phosphate isomerase and hexokinase, and finally causing cell death. Hence, the potential and effectiveness of 2DG with the main protease (Mpro) of novel coronavirus (nCoV) should be investigated using the molecular docking and molecular dynamics (MD) simulations. The ability of 2DG to inhibit the Mpro of nCoV is compared with 2-deoxyglucose (2DAG), an acyclic molecule, and 2-deoxy-D-ribose (2DR). The binding energy of the molecules with the Mpro of nCoV is calculated using molecular docking and superimposed analysis data is obtained. The binding energy of 2DG, 2DR and 2DAG was −2.40, −2.22 and −2.88 kcal/mol respectively. Although the molecular docking does not provide reliable information, therefore, the binding affinity can be confirmed by molecular dynamics simulations. Various trajectories such as Rg, RMSD, RMSF, and hydrogen bonds are obtained from the molecular dynamics (MD) simulations. 2DG was found to be a better inhibitor than the 2DAG and 2DR based on the results obtained from the MD simulations at 300 K. Furthermore, temperature-dependent MD simulations of the Mpro of nCoV with promising 2DG was performed at 295, 310 and 315 K, and the effective binding with the Mpro of nCoV occurred at 295 K. With the use of DFT calculations, optimized geometry and localization of electron density of the frontier molecular orbitals were calculated. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients diagnosed with pancreatic cancer have a poor prognosis at time of diagnosis, with a 5-year survival rate of merely 10%. The only treatment with curative intent is surgical resection of the tumor and adjacent tumor-containing lymph nodes. To improve surgical outcome and survival, additional (imaging) tools are needed that support complete surgical tumor resection. Firstly, more accurate monitoring of tumor response to neoadjuvant treatment and subsequent determination of resectability is needed. Secondly, an imaging tool is needed for intraoperative guidance allowing accurate identification, delineation, and complete resection of the tumor and suspected lymph nodes. Therefore, both tumor-targeted PET/CT before surgery and real time fluorescence-guidance during surgery could be helpful to improve patient outcome. This review focusses on literature considering tumor-targeted PET/CT and near-infrared fluorescence (NIRF) imaging. Several tumor-targeted agents are under clinical evaluation, and several other promising agents are currently tested preclinically, both with promising results. Their additional diagnostic value and feasibility for future implementation in standard clinical care of PDAC has yet to be established in phase III clinical trials. Background: Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient's treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC. Methods: A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers. [ABSTRACT FROM AUTHOR]