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Purpose: Shared decision‐making (SDM) is crucial in pancreatic cancer treatment due to its choice‐sensitive nature and limited prognosis. Treatment of pancreatic cancer is organized in a network approach. Several obstacles exist on different levels—patient, healthcare professional, organizational, societal—that impede integration of SDM. This study aims to identify barriers and facilitators to SDM implementation within a comprehensive cancer network. Methods: A qualitative research design was applied, involving interviews and focus groups on barriers and facilitators with healthcare professionals involved in the implementation of SDM. In one comprehensive cancer network in the Netherlands, including seven hospitals, a project was initiated with the goal of empowering patients and healthcare professionals in SDM throughout primary, secondary and tertiary healthcare settings. A total of 17 participants were assessed. Directed qualitative content analysis was performed by two researchers. Results: Main findings revealed barriers such as time constraints, lack of priority of physicians, little involvement of general practitioners, and insufficient social context of patients in referrals, alongside facilitators including learning communities with practical SDM examples, metro mapping, involvement of case manager in implementation and patient empowerment strategies. Conclusion: Addressing cultural, systemic barriers and developing innovative strategies are of importance to enhance SDM in pancreatic cancer treatment in a network approach. This study provides understanding of SDM implementation in complex healthcare settings and offers valuable guidance for future interventions seeking to improve decision‐making processes in pancreatic cancer treatment and beyond. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC), also known as pancreatic ductal adenocarcinoma, is the most prevalent type of pancreatic tumor, predominantly impacting the exocrine portion of the pancreas. Individuals diagnosed with PDAC face a grim prognosis due to its highly malignant nature. By the year 2030, it is projected to emerge as the second leading cause of cancer-related fatalities. PDAC is known for its high degree of genomic instability. This review offers a summary of the frequently mutated genes in PDAC, as well as the morphological features, molecular profiles, available treatment options, and ongoing research in the field of PDAC. [ABSTRACT FROM AUTHOR]

Abstract Purpose Shared decision‐making (SDM) is crucial in pancreatic cancer treatment due to its choice‐sensitive nature and limited prognosis. Treatment of pancreatic cancer is organized in a network approach. Several obstacles exist on different levels—patient, healthcare professional, organizational, societal—that impede integration of SDM. This study aims to identify barriers and facilitators to SDM implementation within a comprehensive cancer network. Methods A qualitative research design was applied, involving interviews and focus groups on barriers and facilitators with healthcare professionals involved in the implementation of SDM. In one comprehensive cancer network in the Netherlands, including seven hospitals, a project was initiated with the goal of empowering patients and healthcare professionals in SDM throughout primary, secondary and tertiary healthcare settings. A total of 17 participants were assessed. Directed qualitative content analysis was performed by two researchers. Results Main findings revealed barriers such as time constraints, lack of priority of physicians, little involvement of general practitioners, and insufficient social context of patients in referrals, alongside facilitators including learning communities with practical SDM examples, metro mapping, involvement of case manager in implementation and patient empowerment strategies. Conclusion Addressing cultural, systemic barriers and developing innovative strategies are of importance to enhance SDM in pancreatic cancer treatment in a network approach. This study provides understanding of SDM implementation in complex healthcare settings and offers valuable guidance for future interventions seeking to improve decision‐making processes in pancreatic cancer treatment and beyond.

Background: The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Objectives: We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival. Design: In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed. Methods: The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC). Results: A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation. Conclusion: KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC. Plain language summary: Diagnostic and theranostic interest of searching for a KRAS mutation in echoendoscopic ultrasound biopsies of pancreatic adenocarcinomas The echoendoscopic ultrasound diagnostic of pancreatic adenocarcinomas sometimes remains difficult due to the nature of these tumors with a particular microenvironment. For more than 30 years, several authors have underlined the importance of searching for a KRAS mutation on samples taken by echoendoscopic ultrasound to improve diagnostic performance. However, this research is not common practice. Our retrospective study made it possible to review the files of 85 patients with pancreatic adenocarcinoma in whom an echoendoscopic ultrasound biopsy was performed with a search for the KRAS mutation (with second-generation fine needle biopsy). Forty-four percent could have been considered positive for the diagnosis of PDAC thanks to the search for the KRAS mutation without repeating new samples. Furthermore, knowledge of the KRAS mutation type from diagnosis would make it possible to isolate mutations justifying possible targeted treatments. [ABSTRACT FROM AUTHOR]

Objective Pancreatic cancer is a leading cause of cancer-related deaths in developed countries, with a 5-year average survival rate of less than 5%, making it a malignant disease. Gemcitabine (GEM), an FDA-approved pyrimidine antimetabolite, is widely used in pancreatic cancer treatment. However, due to its targeting of all dividing cells, severe side effects are frequently observed in patients undergoing GEM treatment for pancreatic cancer. Consequently, meta-analyses have shown that the combination of GEM with other active compounds significantly improves the 1-year survival rate of pancreatic cancer patients. Epigallocatechin3-gallate (EGCG), an active compound found in green tea (Camellia sinensis), has proven anticancer activity in pancreatic cancer. Subsequent studies have demonstrated that EGCG enhances the sensitivity of pancreatic cancer cells to GEM. However, among the studies conducted to date, the impact of the combination of EGCG and GEM on the expression of critical microRNAs, which act as key epigenetic regulators in pancreatic cancer pathology, has not been investigated. This study aims to determine the cytotoxic and apoptotic effects of the combination of GEM and EGCG on PANC1 cells and to examine its effectiveness on the expression levels of microRNAs involved in cancer progression. Material and Method Cytotoxicity of GEM and EGCG in PANC1 cells was assessed using the WST-1 assay, and combination effects were analyzed using isobologram analysis. Apoptosis analysis was performed using the Annexin V method. miRNA isolation was conducted with the miRNeasy Kit, followed by cDNA synthesis using the miScript II Reverse Transcription Kit. Changes in the expression of miRNAs involved in cancer cell proliferation, apoptosis, and metastasis were examined using real-time qRT-PCR analysis. Results The IC50 values for GEM at 24, 48, and 72 hours were determined as 72.85 μM, 26.55 μM, and 9.38 μM, respectively. EGCG's IC50 values at 24, 48, and 72 hours were determined as 64.36 μM, 48.34 μM, and 19.73 μM, respectively. When combined at a 2:3 ratio (GEM: EGCG) at 24 and 72 hours, a synergistic effect was observed, while at 48 hours, a strong synergistic drug interaction was observed. At a concentration of only 26.55 μM, the group treated with GEM showed a 4.2-fold increase in apoptosis compared to the control group receiving fresh medium. In contrast, the combination treatment (EGCG: 4.71 μM, GEM: 3.14 μM) resulted in a remarkable 12.04-fold increase in apoptosis. After combination treatment, the expression of tumor suppressor miRNAs, miR-137, and miR-130a-3p, increased, while the expression of oncogenic miRNAs, including miR-27a-3p, miR-425- 5p, miR-183-5p, miR-187-3p, miR-21-5p, miR-324-5p, and miR-486-5p, decreased. Conclusion EGCG can sensitize pancreatic cancer to GEM through epigenetic mechanisms, shedding light on novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Summary: In this short review, we aim to summarize the essential news and highlights in pancreatic cancer that were presented at ASCO 2023. We focus in particular on primary resectable as well as advanced or metastatic disease. Therefore, the first results of the NORPACT-1 trial and the updated data from the NAPOLI-3 study are summarized. We discuss these studies and their potential influence on daily clinical practice with regard to current standard of care. [ABSTRACT FROM AUTHOR]

Pancreaticoduodenectomy is one of the major gastrointestinal surgeries and still has significant complication rates. Although most complications appear postoperatively, severe intraoperative difficulties and complications can occur in certain circumstances. Here, we presented the management of two cases who underwent two-stage pancreaticoduodenectomy due to intraoperative problems. Two patients have become hemodynamically unstable during an elective pancreatic resection combined with both arterial and venous reconstructions. All the gastrointestinal reconstructions were postponed to second sessions for damage control surgery. A two-stage pancreaticoduodenectomy is an option to be considered in a hemodynamically unstable patient during elective pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

Background Pancreatic cancer is a highly aggressive and fatal disease with limited treatment options and poor prognosis for patients. This study aimed to investigate the impact of XYA-2 {N-(3,7-dimethyl-2,6-octadienyl)-2-aza-2-deoxychaetoviridin A}, a nitrogenated azaphilon previously reported from a deep-sea-derived fungus on the progression of pancreatic cancer cells. Methods The inhibitory effects of XYA-2 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion were assessed using various assays. The CCK-8 assay, clone formation assay, flow cytometry assay, wound healing assay, and transwell assay were employed to evaluate cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion, respectively. Moreover, we employed RNA-seq and bioinformatics analyses to uncover the underlying mechanism by which XYA-2 influences pancreatic cancer cells. The revealed mechanism was subsequently validated through qRT-PCR. Results Our results demonstrated that XYA-2 dose-dependently inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest and apoptosis. Additionally, XYA-2 exerted a significant inhibitory effect on the invasion and migration of cancer cells. Moreover, XYA-2 was found to regulate the expression of genes involved in multiple cancer-related pathways based on our RNA-seq and bioinformatics analysis. Conclusion These findings highlight the potential of XYA-2 as a promising therapeutic option for the treatment of pancreatic cancer.

This research article presents the synthesis of a novel series of hybrid analogues of Coumarin-Triazole-Chalcone, which are potential bioactives with a novel mode of action for anticancer therapy. The compounds have been synthesized via aldol condensation and 1,3-dipolar cycloaddition, resulting in the generation of hybrid heterocyclic systems that combine two or more pharmacophores. The synthesized compounds have then been screened for anticancer activity against various human cancer cell lines, including A549 (lung cancer), HeLa (Cervix carcinoma), PANC1 (pancreatic cancer), HT1080 (Fibrosarcoma) and HEK293 (Human embryonic kidney cells), in vitro. One of the compounds, para-nitrile chalcone 9a, demonstrates significant IC50 values in the range of 3.1 to 7.02 µg/mL when compared to the others. All the compounds 9a-d have shown higher IC50 values towards HEK-293 cells indicating their non-toxic nature towards normal cells. Furthermore, in silico approaches have been employed to assess the efficacy of compounds that are active in the MTT assay against molecular targets. The authors conducted docking studies of the proteins PI3K and AKT, which are common target biomarkers in Pancreatic cancer, Lung cancer, Cervical cancer, and Fibrosarcoma, with compound 9a and some known inhibitors. The results show that compound 9a has a good binding affinity with AKT (-10.6) and PI3K (-10.3). However, it is found to be more specific for AKT as its binding site amino acid interactions are similar to those of known AKT inhibitors. These findings provide evidence that hybrid heterocyclic systems may be useful for developing potential bioactives with a novel mode of action for anticancer therapy. [ABSTRACT FROM AUTHOR]

Introduction. Despite advances in the last few decades, pancreatic cancer is still characterized by systematically increasing morbidity and high mortality with a low survival rate. The introduction of nab-paclitaxel (nab-P) to the first-line treatment of patients with metastatic pancreatic adenocarcinoma in combination with gemcitabine resulted in improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Material and methods. This study analyzes OS and PFS in pancreatic cancer patients treated with nab-P in the real world setting in Poland, based on data from the National Health Fund (NFZ) database. Results. Data from 873 patients were found (2014–2019). PFS in the entire population was 169 days (95% CI 147–189) without difference between men and women, but significantly better in younger patients (29–50 years). OS in the entire population was 379 days (95% CI 337–non-assessable), with no difference between men and women. A statistically significant longer PFS and OS was demonstrated in the group of patients diagnosed in 2014–2016. Conclusion. Nab-paclitaxel, when used in clinical practice, provides treatment results similar to those in clinical trials. Collecting and periodically analyzing demographic and clinical data could help to assess the place of nab-P in the treatment of patients with pancreatic cancer more accurately. [ABSTRACT FROM AUTHOR]

Background/Aim: Staging laparoscopy (SL) for pancreatic cancer (PC) is considered useful to improve accuracy of staging and resectability. However, given the current accuracy of preoperative imaging, the routine application of SL remains unclear. Therefore, we aimed to investigate the importance of SL in patients with PC without radiological distant metastasis. Patients and Methods: This was a prospective, cohort, observational study. SL was performed in all patients with PC without radiological distant metastasis before pancreatectomy or chemotherapy at the Yamaguchi University Hospital. Results: Between July 2020 and March 2023, 55 patients underwent SL with peritoneal cytology. The median age was 71, with 53% male patients. SL revealed occult metastasis in six (11%) patients including positive peritoneal cytology (n=6), and peritoneal dissemination (n=1). The resectability of unresectable locally advanced (UR-LA) was associated with a significantly increased risk of occult metastasis (p=0.0211). The median operative time was 40 min, and the median volume of blood loss was 3 ml. There were no severe complications (Clavien-Dindo III or higher). Conclusion: SL with peritoneal cytology regardless of previous abdominal surgery is safe and effective to determine accurate staging. Therefore, SL with peritoneal cytology should be considered for patients with PC without radiological distant metastasis, especially in those with UR-LA. [ABSTRACT FROM AUTHOR]

Context • Pancreatic cancer (PC) is one of the most malignant digestive cancers, characterized by a poor prognosis. PC patients receiving chemotherapy can endure immense physical and psychological pain, negatively impacting spiritual well-being and QoL. Objective • The study intended to investigate PC patients’ statuses regarding spiritual well-being and QoL, to identify and analyze the influencing factors, and to develop feasible spiritual-care plans, which could provide a reference for clinicians in promoting the spiritual well-being and QoL of PC chemotherapy patients. Design • The research team performed a prospective survey. Setting • The study took place at the Second Affiliated Hospital of the Army Medical University in Chongqing, China. Participants • Participants were 120 patients who underwent chemotherapy for pancreatic cancer (PC) at the hospital between November 2020 and April 2022. The research team selected participants using convenience sampling. Outcome Measures • The outcome measures included: (1) a self-designed questionnaire to identify participants’ demographic and clinical characteristics and (2) the Functional Assessment of Chronic Illness TherapySpiritual Well-being Scales (FACIT-Sp). The research team used the FACIT-Sp’s two subscales, FACT-G and the FACIT-Sp-12, to evaluate participants’ quality of life (QoL) and spiritual well-being, respectively. Results • The total scores for participants’ spiritual wellbeing and QoL were 26.2 ± 5.39 and 65.44 ± 17.1, respectively. Spiritual well-being was positively correlated with the QoL (P < .001). According to the multiple linear regression analysis, the main factors influencing spiritual well-being were age (P < .01), education level (P < .001), average monthly income per capita of the family (P<.001), recurrence (P<.001), and pain (P<.05). The main factors influencing QoL were age (P = .008), education level (P<.001), average monthly income per capita of the family (P<.001), recurrence (P<.001), and pain (P<.01). Conclusions • Patients who undergo chemotherapy for PC experience a low-to-medium level of spiritual wellbeing and a medium level of QoL. The detrimental factors include: (1) being middle-aged, (2) having a low education level, (3) having a low family income, (4) suffering a recurrence of the disease, and (5) experiencing moderateto-severe pain. Medical practitioners should provide extra care and support to protect the spiritual well-being of these patients and ultimately improve their QoL. [ABSTRACT FROM AUTHOR]

Many complex systems such as the Internet, the World Wide Web, the brain, and the causes of diseases can be described by networks with nodes representing agents and links representing relationships or interactions between nodes. Despite these systems seeming utterly different at first glance, they are all made up of interacting parts. Individual objects in this type of system are not isolated but connected through links or relationships. Long non-coding RNAs (LncRNAs), one of the factors related to many diseases, are specific genes in the human genome that control many different biological processes. lncRNAs have been shown to regulate cancer development and occurrence. We used link prediction bioinformatics tools to identify lncRNAs affecting various types of cancers. To achieve this goal, two-part networks were used using CN (Common Neighbors), AA (Adamic/Adar), PA (Preferential Attachment), and JC (Jaccard's Coefficient) algorithms. The results indicated that all the obtained lncRNAs with a high score had been reviewed in other research articles, which was a sign of the correctness of our algorithms. 4.5% of the obtained results lacked scientific and research studies, all with a high score for future studies and included lncRNA H19 and SPRY4-IT1. In addition, in one case with a high score and first position in the Excel file obtained using the Jaccard coefficient algorithm, lncRNA with the symbol AC09510.3 was associated with adenocarcinoma. Still, this possible link has not been investigated in any article yet. Conclusion: The current study may identify novel lncRNAs implicated in Adenocarcinoma, vulva squamous cell carcinoma, basal cell carcinoma, gestational choriocarcinoma, chromophobe renal cell carcinoma, brain cancer, pancreatic cancer, hepatocellular carcinoma, prostate cancer, embryonal cancer, germ cell cancer, and choriocarcinoma; however, further research is required to determine the potential functions of this lncRNAs in cancers mentioned above. [ABSTRACT FROM AUTHOR]

Hepatoid carcinoma is a rare primary malignancy in the pancreas. We report a case with a long indolent course of primary pancreatic hepatoid carcinoma (PHC) before curative surgery, with an estimated doubling time of 429 days. After surgery, the patient took adjuvant TS-1 (tegafur, gimeracil, and oteracil). They did not have recurrence or metastases 9 months after surgery. We reported their pathological features. We review PHC's clinical features, pathological diagnosis, and reported treatment experiences. [ABSTRACT FROM AUTHOR]

Pancreatic cancer, despite significant medical advances, is still a significant clinical problem. This article focuses on discussing risk factors, diagnostic methods, and treatment options. These elements are crucial in making a prompt diagnosis and initiating treatment. On average, a physician in primary care sees a patient with undiagnosed pancreatic cancer once every few years. Knowing the underlying symptoms and referring the patient to an appropriate center can significantly increase survival. Diagnostic methods include physical examination, numerous imaging techniques, and determination of tumor markers in serum. Surgical treatment combined with adjuvant chemotherapy is the only chance of cure for pancreatic cancer patients qualified for surgery. However, most patients experience tumor recurrence. When a tumor recurs, treatment for these patients and patients with unresectable disease is palliative chemotherapy. Numerous studies are currently underway to improve diagnostic and treatment methods. [ABSTRACT FROM AUTHOR]

Aim: Coeliac trunk and hepatic artery variations are not uncommon and may complicate surgery in patients with periampullary cancer. We aimed to assess the prevalence and types of variations of the coeliac trunk and hepatic arteries and their relationship with surgical complications in patients undergoing pancreatoduodenectomy. Materials and Methods: In this single-center study, we retrospectively reviewed the preoperative contrast-enhanced abdominal computed tomography scans of patients with periampullary cancer. Coeliac trunk branching with a particular focus on hepatic artery origin was assessed on arterial phase images. Results: The study included a total of 66 patients [39 (59.1%) men] with a mean age of 63.92±12.98 years. The most frequent tumor origin was the pancreatic head, seen in 41 (62.1%) cases, followed by the ampulla in 15 (22.7%), distal common bile duct in seven (12.1%), and colon tumors invading the duodenum in two (3%). Arterial variations were observed in 15 (22.7%) cases. Total perioperative complications occurred in 14 cases (13 fistulas and one hematoma). There was a higher rate of complications in the group with variations (n=5, 33.3%) compared to the group without variations (n=9, 17.6%), but it was not statistically significant (p=0.496). Conclusion: Coeliac trunk and hepatic arterial variations are very common but do not seem to significantly increase complications in patients undergoing pancreatoduodenectomy. [ABSTRACT FROM AUTHOR]

Invasive pancreatic ductal carcinoma is a representative refractory malignant tumor, and even with the development of early diagnosis and treatment techniques, the treatment outcome has been remarkably poor. Surgical resection is the curative treatment for resectable pancreatic cancer and borderline resectable pancreatic cancer. However, the survival rate in patients with pancreatic cancer treated by resection alone is low because of the high postoperative recurrence rate. In this review article, we report recent studies on perioperative treatment for pancreatic cancer. Perioperative therapy is the addition of chemotherapy or radiation therapy before or after surgery to improve resectability and curative effects. Because it is difficult to cure redsecttable pancreatic cancer by surgery alone, multidisciplinary treatment combined with perioperative adjuvant chemotherapy is the current standard of care. Although perioperative chemotherapy and chemoradiotherapy have been investigated for borderline resectable pancreatic cancer, the effectiveness of preoperative treatment has not been sufficiently proven. Potentially curative pancreatic cancer is treated by surgery plus perioperative therapy; treatment cannot be either alone. We regard the successful completion of surgery and perioperative care as the key to improving treatment outcomes. Therefore, ongoing randomized controlled trials for the treatment of BR-pancreatic cancer are expected to induce further improvements survival outcomes of patients with BRpancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: The usefulness of various prognostic factors for pancreatic cancer has been reported, but limited studies have focused on these changes during chemotherapy. The purpose of the present study was to investigate the prognostic factors and to evaluate the significance of these changes during chemotherapy in patients with advanced pancreatic cancer (APC). Materials and Methods: We retrospectively analyzed 213 patients with APC who underwent chemotherapy between January 2006 and December 2018 at Kofu Municipal Hospital and University of Yamanashi Hospital. Univariate and multivariate cox regression models were applied to investigate independent prognostic factors. Results: Multivariate analysis revealed that Eastern Cooperative Oncology Group Performance Status 2 (hazard ratio [HR] 4.07, P < 0.01), neutrophil-to-lymphocyte ratio (NLR) ≥3.9 (HR 1.97, P < 0.001), modified Glasgow prognostic score 1--2 (HR 2.77, P < 0.001), carcinoembryonic antigen ≥5.0 (HR 1.44, P = 0.026), carbohydrate antigen 19-9 ≥37 (HR 1.83, P = 0.004), ΔNLR >0 (HR 2.01, P < 0.001), ΔCEA (subtracting the baseline from the start of second cycles of chemotherapy) >0 (HR 1.64, P = 0.002), and ΔCA19-9>0 (HR 1.77, P = 0.002) were independent negative prognostic factors. Conclusion: Baseline and change in tumor markers and NLR are useful in predicting overall survival in APC patients undergoing chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer has a poor 5-year survival and carries significant morbidity. Pain is a commonly studied symptom in pancreatic cancer; however, few studies examine the frequency of multiple patient-reported symptoms. Our aim is to ascertain patient-reported symptom burden at initial consultation with a palliative care provider and compare patient prognostic awareness to provider estimation of prognosis. Methods: Data were extracted from the standardized Quality Data Collection Tool (QDACT). Adults with pancreatic cancer seen by a palliative care provider were included. Descriptive statistics were used to describe demographic features, symptom prevalence and burden, as well as assess patient prognosis awareness defined by congruence or incongruence with provider estimated prognosis. Results: 285 patients were included in our analysis. The average age was 68 years (SD: 12.4), 87.2% were white, 50% male. The mean number of moderate/severe symptoms was 2.6 (SD: 2) out of 9 symptoms. Tiredness (66.7%), appetite (64.5%) and pain (46.2%) had the highest rates of moderate/severe symptom burden. Patients with a prognosis of 1-6 months had the lowest proportion of congruence with provider estimation (56.5%). Conclusion: Our study suggests targets to improve patient-centered care of pancreatic cancer. Patients commonly have multiple symptoms that are moderate/severe at time of palliative care referral. While pain has been well-reported, tiredness and decreased appetite are more prevalent at initial visit. This emphasizes the importance of assessing multiple symptoms and working closely with palliative care for early referral. Overall, one third of patient prognosis estimates differed from the provider assessment of prognosis. Our data support the importance of early referral to palliative care to manage symptoms and better prepare patients for end-of-life care. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5‐year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery. However, certain aspects of NAT against PDAC, including the optimal regimen, the use of radiotherapy, and the selection of patients that would benefit from NAT, have yet to be fully elucidated. This review describes the major signaling pathways and molecular mechanisms involved in PDAC initiation and progression in addition to the immunosuppressive tumor microenvironment of PDAC. We then review current guidelines, ongoing research, and future research directions on the use of NAT based on randomized clinical trials and other studies. Finally, the current use of and research regarding targeted therapy for PDAC are examined. This review bridges the molecular understanding of PDAC with its clinical significance, development of novel therapies, and shifting directions in treatment paradigm. [ABSTRACT FROM AUTHOR]

Objectives: Pancreatic cancer (PC) is one of the cancers with the worst prognosis in the world. Despite protooncogenes such as BRCA and PALB2, effective, inexpensive, and simple methods for predicting the prognosis of patients with metastatic PC are still lacking. We aim to investigate whether mean platelet volume/platelet (MPV/PLT) and platelet indices such as MPV and plateletcrit (PCT) have a prognostic significance in patients with metastatic PC. Methods: Patients diagnosed with metastatic PC in 3 centers in Turkey between 2016 and 2022 were analyzed retrospectively. We recorded patient's demographic data such as age, gender, performance status and platelet, MPV and PCT. Overall survival (OS) and progression-free survival (PFS) were also recorded. There were 80 patients in our study. Results: Median PFS was found 6.2 months for MPV/PLT ratio <0.045 group and 6.3 months for MPV/PLT ratio >0.045 group retrospectively. The median PFS of the MPV/PLT ratio =0.045 groupwas shorter than MPV/PLT ratio >0.045 group, but there wasn't statistically meaningful difference between the groups (p:0,957). Median OS for the MPV/PLT ratio =0.045 groupwas 10.1 months and the MPV/PLT ratio for the >0.045 group was 9 months, but there wasn't statistically significant difference between the groups (p:0.506). There was nosurvival difference between the groups when comparing both MPV and PCT status. Conclusion: MPV/PLT ratio is a cheap, simple and useful marker and can be used in our daily practice to predict the prognosis of patients with advanced PC, if confirmed by prospective studies and larger patient numbers. [ABSTRACT FROM AUTHOR]

Abstract Background The gap in treatment and health outcomes after diagnosis of pancreatic cancer is a major public health concern. We aimed to investigate the differences in the health outcomes and treatment of pancreatic cancer patients in healthcare vulnerable and non-vulnerable areas. Methods This retrospective cohort study evaluated data from the Korea National Health Insurance Corporation-National Sample Cohort from 2002 to 2019. The position value for relative comparison index was used to define healthcare vulnerable areas. Cox proportional hazard regression was used to estimate the risk of mortality in pancreatic cancer patients according to healthcare vulnerable areas, and multiple logistic regression was used to estimate the difference in treatment. Results Among 1,975 patients, 279 (14.1%) and 1,696 (85.9%) lived in the healthcare vulnerable and non-vulnerable areas, respectively. Compared with the non-vulnerable area, pancreatic cancer patients in the vulnerable area had a higher risk of death at 3 months (hazard ratio [HR]: 1.33, 95% confidence interval [CI] = 1.06–1.67) and 6 months (HR: 1.23, 95% CI = 1.03–1.48). In addition, patients with pancreatic cancer in the vulnerable area were less likely to receive treatment than patients in the non-vulnerable area (odds ratio [OR]: 0.70, 95% CI = 0.52–0.94). This trend was further emphasized for chemotherapy (OR: 0.68, 95% CI = 0.48–0.95). Conclusion Patients with pancreatic cancer belonging to medically disadvantaged areas receive less treatment and have a higher risk of death. This may be a result of the late diagnosis of pancreatic cancer among these patients.

Columbianetin acetate (CE) is one of the effective components of Angelica pubescens. So far, the specific role and molecular mechanism of CE in pancreatic cancer are not clear. Thus, this study aimed to explore the specific mechanism of CE on pancreatic cancer. The target genes combined with CE were predicted through the PharmMapper database and the 3D molecular structure of CE. Then, the Cancer Genome Atlas (TCGA) and Cistrome data browser (DB) databases were used to screen Meiotic nuclear divisions 1 (MND1)-related genes, transcription factors, and transcription factor data sets, and the intersection of the above data sets. The "limma" package in the R and gene expression profiling interactive analysis (GEPIA) databases were used to analyze the correlation and survival difference between the target genes and MND1 to predict the degree of association between CE and MND1. Western blotting and RT-PCR experiments revealed the regulatory relationship among CE, E2F1, and MND1 at the cellular level. The specific effects of CE on pancreatic cancer cells were explored through CCK8, wound healing, migration, and flow cycle experiments. E2F1, also the predictive transcription factor of MND1, was also the predictive target protein of CE. At the same time, E2F1 and MND1 were closely related in pancreatic tissue. In the cell function experiment, CE and interference with E2F1 expression could reduce the gene and protein expression of MND1, which was closely associated with cell proliferation, migration, and cycle development. Similarly, interfering with the expression of mnd1 can also inhibit the further development of tumor cells. CE may inhibit the development of pancreatic cancer cells by reducing the expression of MND1. This implies that CE may be a potential novel agent for the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Introduction: Systemic treatment of pancreatic adenocarcinoma in the population of people over 65 years old is a challenge resulting from both the extremely unfavourable prognosis of this cancer and the particularly high sensitivity to the toxicity of chemotherapy in the elderly. This article presents the effectiveness and side effects of first-line chemotherapy according to the FOLFIRINOX regimen in patients over 65 years of age diagnosed with advanced pancreatic adenocarcinoma. Material and methods: The analysis was conducted in a group of 43 patients diagnosed with locally advanced inoperable pancreatic cancer or metastatic pancreatic cancer. Patients were treated between 2017 and 2021 in the Clinical Oncology Department, University Clinical Centre, Katowice, Poland. Results: In the study group, the median overall survival was 9.8 months; the median progression-free survival was 8.8 months. Treatment toxicity occurred in all patients. Adverse events of G3 and G4 severity (common terminology criteria for adverse events 5.0) occurred in 8% of patients. In 2 patients (5%), chemotherapy toxicity was the reason for discontinuation of systemic treatment. Conclusions: Triple-drug chemotherapy in a group of patients aged over 65 years with a diagnosis of advanced pancreatic cancer shows similar effectiveness to the general treated population, and with proper medical supervision the severity of side effects is at an acceptable level. [ABSTRACT FROM AUTHOR]

Purpose: A novel cystine-knot peptide–based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin αvβ6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer. Methods: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. Results: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7–14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean < 1.0). The effective dose was calculated to be 2.538 × 10−2 mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n = 5), liver (n = 4), and peritoneum (n = 2), confirmed by biopsy and/or contrast-enhanced CT. Conclusion: 18F-FP-R01-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18F-FP-R01-MG-F2 PET is feasible, but larger studies are required to define the role of this approach. Trial registration: NCT02683824. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment. [ABSTRACT FROM AUTHOR]

Case Presentation: Early diagnosis and rapid treatment of cancer is essential for good clinical outcomes for patients. In this case, an 85-year-old man presented with failure to thrive and was noted to have rapid-onset, multiple seborrheic keratoses (Leser-Trélat sign) on his chest and back. He was ultimately diagnosed with pancreatic cancer using computed tomography. Discussion: Leser-Trélat sign is a rare cutaneous marker for underlying malignancy. Identification of this sign can help guide diagnostic imaging and lab work to identify an occult internal malignancy, resulting in more rapid diagnosis, earlier treatment, and potentially better clinical outcomes. [ABSTRACT FROM AUTHOR]

A 67-year-old man had suffered from persistent abdominal cramping pain for six months, with radiation to the back. Adenocarcinoma of pancreatic body with celiac encasement was diagnosed. Neoadjuvant chemotherapy was given and regressive tumor size was noted. Further operation of distal pancreatectomy with celiac axis resection (DP-CAR), including transection of the left gastric artery (LGA), was performed. The middle colic artery (MCA) was utilized for reconstruction of LGA, with LGA-MCA anastomosis. Intraoperative indocyanine green (ICG) fluorescence was used to confirm the blood supply. DP-CAR is a complicated procedure for tumor involving celiac axis but would bring benefit if en bloc resection was achieved. Reconstruction of the transected vessels was important to reduce further complications. Intraoperative indocyanine green (ICG) fluorescence imaging is a feasible method of evaluating the blood supply to the stomach and liver after the DP-CAR procedure. [ABSTRACT FROM AUTHOR]

Objectives: Prognostic importance of metastatic lymph nodes in pancreatic cancer is always garnered attention due to dismal prognosis, with some quantitative factors drawing attention for significantly predicting outcomes. Size is one of the easy approach morphological characteristics of the lymph node, and data for effect of largest metastatic lymph node (LMLN) size on survival outcomes are lacking in pancreatic cancer. We aim to evaluate the effect of LMLN size on the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Methods: This retrospective study evaluates the effect of LMLN size on survival outcomes by grouping the patients who were surgically treated for PDAC, according to their lymph node stage and calculated cutoff value for LMLN size, between February 2015 and May 2020. Results: In the study cohort of 131 patients, the mean age was 63.9±10.8 years and 77 patients were female. Ninety-nine of the patients had pN1, 32 had pN2 stage disease. The optimal cutoff point of LMLN size for predicting the prognosis was calculated as 7.5 mm (sensitivity = 81% and specificity = 81%). 34 (34.3%) of pN1 and 7 (21.9%) of pN2-staged patients had lymph node smaller than 7.5 mm. Three-year survival was significantly longer for patients whose LMLN size was <7.5 mm (56.2-18.2%, p<0.001). Whereas, the patients with LMLN size <7.5 mm had statistically significant longer median survival rate in the subgroup of patients with pN1 lymph node stage, no significant difference in median survival rates was observed between subgroups of pN2 patients (p=0.237). Conclusion: The present study demonstrated that the LMLN size was one of the potential predictors of survival in patients with PDAC. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of common malignant neoplasms. It is characterized by poor prognosis and high mortality, which is mainly due to detection in an advanced stage. This review presents epidemiological and clinical characteristics of pancreatic cancer, as well as current strategies of systemic treatment of advanced disease, including first- and second-line chemotherapy, as well as molecularly targeted therapies and immunotherapy. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PaCa) suffers from poor treatment options for locally advanced cases. Chemophototherapy (CPT) is an emerging anti-tumor modality, and porphyrin–phospholipid liposomes have been shown to be versatile drug carriers for CPT in preclinical rodent models. Here we show that in the syngeneic subcutaneous KPC PaCa tumor model, exhausted CD8+ T cells are localized in the tumor, and that CPT is enhanced in combination with immune checkpoint blockade (ICB). Addition of ICB using anti-programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies resulted in ablation of medium-sized, established KPC tumors (∼200 mm3) without recurrence for over 100 days. Mice rejected subsequent tumor re-challenge. Flow cytometry and tumor slice analysis following injection of a fluorescently labeled anti-PD-1 antibody showed that CPT improved antibody delivery to the tumor microenvironment. Treatment of large established tumors (∼400 mm3) using with CPT and ICB induced appreciable tumor regression and delay in regrowth. Taken together, these data demonstrate the utility of combining CPT with immunotherapies. [ABSTRACT FROM AUTHOR]

Background: The gap in treatment and health outcomes after diagnosis of pancreatic cancer is a major public health concern. We aimed to investigate the differences in the health outcomes and treatment of pancreatic cancer patients in healthcare vulnerable and non-vulnerable areas.Methods: This retrospective cohort study evaluated data from the Korea National Health Insurance Corporation-National Sample Cohort from 2002 to 2019. The position value for relative comparison index was used to define healthcare vulnerable areas. Cox proportional hazard regression was used to estimate the risk of mortality in pancreatic cancer patients according to healthcare vulnerable areas, and multiple logistic regression was used to estimate the difference in treatment.Results: Among 1,975 patients, 279 (14.1%) and 1,696 (85.9%) lived in the healthcare vulnerable and non-vulnerable areas, respectively. Compared with the non-vulnerable area, pancreatic cancer patients in the vulnerable area had a higher risk of death at 3 months (hazard ratio [HR]: 1.33, 95% confidence interval [CI] = 1.06-1.67) and 6 months (HR: 1.23, 95% CI = 1.03-1.48). In addition, patients with pancreatic cancer in the vulnerable area were less likely to receive treatment than patients in the non-vulnerable area (odds ratio [OR]: 0.70, 95% CI = 0.52-0.94). This trend was further emphasized for chemotherapy (OR: 0.68, 95% CI = 0.48-0.95).Conclusion: Patients with pancreatic cancer belonging to medically disadvantaged areas receive less treatment and have a higher risk of death. This may be a result of the late diagnosis of pancreatic cancer among these patients. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive, deadly, and is rarely diagnosed early. Regulatory T cells (Treg) are a multifunctional class of immunosuppressive T cells that help maintain immunologic homeostasis and participate in autoimmune diseases, transplants, and tumors. This cell type mediates immune homeostasis, tolerance, and surveillance and is associated with poor outcomes in PDAC. Tregs remodel the tumor immune microenvironment, mediate tumor immune escape, and promote tumor invasion and metastasis. A promising area of research involves regulating Tregs to reduce their infiltration into tumor tissues. However, the complexity of the immune microenvironment has limited the efficacy of immunotherapy in PDAC. Treg modulation combined with other treatments is emerging. This review summarizes the mechanisms of Tregs activity in tumor immune microenvironments in PDAC and the latest developments in immunotherapy and clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: Eighty percent of patients with pancreatic cancer present with unresectable/metastatic disease. Although clinical trials evaluating the efficacy of systemic treatments have been conducted in selected patient groups, reported survivals are short. In our study, we aimed to evaluate real-life data and factors affecting survival in patients with unresectable/metastatic pancreatic cancer. Methods: The files of the patients who were followed up in our outpatient clinic with the diagnosis of pancreatic adenocarcinoma were evaluated retrospectively. A total of 151 patients had de-novo or recurrent, unresectable/metastatic disease. Variables that may affect the survival of these patients were recorded. Results: The median overall survival (OS) of patients receiving no systemic therapy for unresectable/metastatic disease and patients receiving chemotherapy was 2.4 months(m) and 9.3m, respectively (p <0.001). Patients with unresectable/metastatic disease had a median OS of 11.6 m and 8.9 m (p=0.02) for recurrent disease and de-novo disease, respectively. The median OS of patients with isolated lung metastases and other patients were 15.4m and 7.8m (p=0.02), respectively. Conclusion: In unresectable/metastatic pancreatic cancer, recurrent disease and isolated lung metastasis are good prognostic factors. These parameters can be used as stratification factors in prospective studies. Real-life survival data are in compliance with the literature. There is a need for new treatments to improve survival in pancreatic cancer, and studies to identify new markers that determine the course of the disease and can create targets in treatment. [ABSTRACT FROM AUTHOR]

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Background/Aim: Locally advanced pancreatic cancer has been considered for a long period of time as an unresectable lesion and therefore, all patients have been traditionally addressed to the oncological services for palliative purposes. However, due to the wide usage of newer oncological agents in association with improved surgical techniques, radical surgical procedures became feasible. The aim of this study was to present the different surgical procedures that were performed in locally advanced pancreatic cancer patients in order to achieve radical resections. Patients and Methods: Between 2019 and 2020, six cases were submitted to pancreatic and vascular resections in Fundeni Clinical Hospital. Results: In all cases, surgery with curative intent was attempted; portal vein resection was performed in five cases, whereas arterial resection was performed in three cases. Reconstruction was performed by direct re-anastomosis, by placing cadaveric or synthetic grafts. The postoperative outcomes were favourable in all cases. Conclusion: Vascular resections can be safely associated with pancreatic resections in cases presenting locally advanced pancreatic lesions, with acceptable morbidity rates. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background/Aim: Adenocarcinoma of the pancreas is one of the most aggressive malignant diseases in humans. Characteristics of this tumour type are poor response to radiotherapy and chemotherapeutic agents as well as metastasis in the absence of an organ capsule. The best therapeutic option is surgical removal of the tumour followed by chemotherapy or radiotherapy. Yet, even after surgical R0- resection, the 5-year survival probability is only about 20% because of the high recurrence rate of this tumour and complications due to metastases. Furthermore, recent studies have shown that the perioperative period is a particularly vulnerable phase, during which tumour progression and metastasis may be facilitated. The effects of analgesics administered during the perioperative period are still unknown. The present work investigated the effects of analgesics on pancreatic cancer cell migration in vitro. Materials and Methods: The migratory potential of pancreatic cancer cells was analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semi-permeable membrane under different stimuli. Cell concentration was measured by reading fluorescence (Ex/Em=530/590 nm) in a plate reader. Results: Migration in PANC-1 pancreatic cancer cells was significantly decreased after 24 h stimulation with 100 μM of ropivacaine, 100 nM of sufentanil, 1,000 μM of ropivacaine and 1,000 nM of sufentanil. In the PaTu 8988t cell line, incubation with 10 μM of ropivacaine caused a slight but statistically significant increase in migration, whereas lidocaine, metamizole and paracetamol did not significantly affect migration. Conclusion: The risk of tumour progression and metastasis seems to be increased during major oncological surgical interventions. The recent advances in the molecular and biological understanding of pathogenesis of pancreatic cancer have not yet significantly improved patient outcome. Therefore, further studies are needed to identify the underlying mechanisms of this aggressive tumour and establish new therapeutic options for the future. [ABSTRACT FROM AUTHOR]

Background & Aims: Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapeutics owing to dense fibrotic stroma orchestrated by cancer-associated pancreatic stellate cells (CAPaSC). CAPaSC also support cancer cell growth, metastasis, and resistance to apoptosis. Currently, there is no effective therapy for PDAC that specifically targets CAPaSC. We previously reported a rationally designed protein, ProAgio, that targets integrin αvβ3 at a novel site and induces apoptosis in integrin αvβ3-expressing cells. Because both CAPaSC and angiogenic endothelial cells express high levels of integrin αvβ3, we aimed to analyze the effects of ProAgio in PDAC tumor. Methods: Expression of integrin αvβ3 was examined in both patient tissue and cultured cells. The effects of ProAgio on CAPaSC were analyzed using an apoptosis assay kit. The effects of ProAgio in PDAC tumor were studied in 3 murine tumor models: subcutaneous xenograft, genetic engineered (KrasG12D; p53R172H; Pdx1-Cre, GEM-KPC) mice, and an orthotopic KrasG12D; p53R172H; Pdx1-Cre (KPC) model. Results: ProAgio induces apoptosis in CAPaSC. ProAgio treatment significantly prolonged survival of a genetically engineered mouse–KPC and orthotopic KPC mice alone or in combination with gemcitabine (Gem). ProAgio specifically induced apoptosis in CAPaSC, resorbed collagen, and opened collapsed tumor vessels without an increase in angiogenesis in PDAC tumor, enabling drug delivery into the tumor. ProAgio decreased intratumoral insulin-like growth factor 1 levels as a result of depletion of CAPaSC and consequently decreased cytidine deaminase, a Gem metabolism enzyme in cancer cells, and thereby reduced resistance to Gem-induced apoptosis. Conclusions: Our study suggests that ProAgio is an effective PDAC treatment agent because it specifically depletes CAPaSC and eliminates tumor angiogenesis, thereby enhancing drug delivery and Gem efficacy in PDAC tumors.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of pancreatic tumors. Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In the adjuvant setting, the standard treatment is six months of chemotherapy with 5-fluorouracile, irinotecan and oxaliplatin. Chemoradiation may improve the survival of patients with incompletely resected tumours (R1). This remains to be confirmed by a prospective trial. Neoadjuvant chemoradiation is a promising treatment especially for patients with borderline resectable tumours. For patients with locally advanced tumours, there is no standard. An induction chemotherapy followed by chemoradiation for non progressive patients reduces the rate of local relapse. Whereas in the first trials of chemoradiation large fields were used, the treated volumes have been reduced to improve tolerance. Tumour movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique has poor evidence-based recommendation. Stereotactic body radiation therapy is also being studied, as a neoadjuvant or exclusive treatment. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) has received increased attention over the past decades with the potential to noninvasively treat cancer via light exposure. Due to the limited light penetration depth within the tissue (typically less than 1 cm), the PDT optical fiber typically needs to be placed close to the cancerous region to ensure the treatment outcome. In this article, we present a novel soft robot laparoscope design that enables accurate and safe deployment of the PDT optical fiber for pancreatic tumor treatment. To achieve this, the proposed soft robot is able to produce three degrees of freedom motions: linear translation, in-plane bending, and axial rotation. A micro camera is integrated with the soft robot to provide intraoperative image guidance during the procedure. The robot forward kinematics model was obtained via a generalized calibration method, and the differential kinematics was derived analytically. Benchtop characterization results indicated that the soft robot was able to achieve 1.4 ± 0.4 mm position and 1.5° ± 1.1° orientation accuracy, respectively. The robot was experimentally validated in two in vivo mice models, and the results indicated that the proposed system successfully reduced the tumor size from 15.3 and 11.8 mm3 to 12.1 and 4.4 mm3, respectively. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy enhances survival rates for pancreatic cancer (PC) patients postsurgery, yet less than 60% complete adjuvant therapy, with a smaller fraction undergoing neoadjuvant treatment. Our study aimed to predict which patients would complete pre- or postoperative chemotherapy through machine learning (ML)., Methods: Patients with resectable PC identified in our institutional pancreas database were grouped into two categories: those who completed all intended treatments (i.e., surgery plus either neoadjuvant or adjuvant chemotherapy), and those who did not. We applied logistic regression with lasso penalization and an extreme gradient boosting model for prediction, and further examined it through bootstrapping for sensitivity., Results: Among 208 patients, the median age was 69, with 49.5% female and 62% white participants. Most had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. The PC predominantly affected the pancreatic head. Neoadjuvant and adjuvant chemotherapies were received by 26% and 47.1%, respectively, but only 49% completed all treatments. Incomplete therapy was correlated with older age and lower ECOG status. Negative prognostic factors included worsening diabetes, age, congestive heart failure, high body mass index, family history of PC, initial bilirubin levels, and tumor location in the pancreatic head. The models also flagged other factors, such as jaundice and specific cancer markers, impacting treatment completion. The predictive accuracy (area under the receiver operating characteristic curve) was 0.67 for both models, with performance expected to improve with larger datasets., Conclusions: Our findings underscore the potential of ML to forecast PC treatment completion, highlighting the importance of specific preoperative factors. Increasing data volumes may enhance predictive accuracy, offering valuable insights for personalized patient strategies., (© 2024 Wiley Periodicals LLC.)

Glycolysis-dominant metabolic pathway in cancer cells can promote their therapeutic resistance against radiotherapy (RT). Carbon monoxide (CO) as a glycolysis inhibitor can enhance the efficiency of RT. Herein, an X-ray responsive CO-releasing nanocomposite (HA@AuNC@CO) based on strong host-guest interactions between the radiosensitizer and CO donor for enhanced RT is developed. The encapsulated gold nanoclusters (CD-AuNCs) can effectively generate cytotoxic reactive oxygen species (ROS) under X-ray radiation, which not only directly inactivate cancer cells but also induce in situ CO gas generation from adamantane modified metal carbonyl (Ada-CO) for glycolysis inhibition. Both in vitro and in vivo results demonstrate that HA@AuNC@CO exhibits active targeting toward CD44 overexpressed cancer cells, along with excellent inhibition of glycolysis and efficient RT against cancer. This study offers a new strategy for the combination of gas therapy and RT in tumor treatment., (© 2024 Wiley‐VCH GmbH.)

Objectives: To demonstrate how medical purchasing power parities (mPPP) may harmonize economic evaluations from different jurisdictions and enable comparisons across jurisdictions.Methods: We describe the use of mPPPs and illustrate this with an example of economic evaluations of nab-paclitaxel with gemcitabine (Nab-P + Gem) versus gemcitabine monotherapy in the setting of metastatic pancreatic cancer. Following a literature search, we extracted data from cost-effectiveness studies on these treatments performed in various countries. mPPPs from the Organization for Economic Co-operation and Development were used to convert reported costs in the jurisdiction of origins to US dollars for the most current year using two possible pathways: (1) reported costs first adjusted by mPPP then adjusted by exchange index; and (2) reported costs first adjusted by exchange index then adjusted by mPPP.Results: Despite many of the pharmaco-economic evaluations sharing similar assumptions and inputs, even after mPPP conversion, residual heterogeneity was attributable to perspectives, discount rate, outcomes, and costs, among others; including in studies conducted in the same jurisdiction.Conclusion: Despite the methodological challenges and heterogeneity within and across jurisdictions, we demonstrated that mPPP offers a way to compare economic evaluations across jurisdictions. [ABSTRACT FROM AUTHOR]

This is the first case report of a 60-yr-old female who underwent therapy for metastatic pancreatic cancer with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). Upon the progression of her disease, she was switched to gemcitabine and nab-paclitaxel. Per genomic sequencing, her tumor was found to be a KRAS wildtype and BRAF V600E mutation, which then warranted treatment with the MEK1 and MEK2 inhibitor, cobimetinib. The patient has achieved a complete response (CR) to a combination of gemcitabine, nab-paclitaxel, and cobimetinib. It has been 16 mo since the start of the treatment, and the patient continues to demonstrate a complete durable response both serologically and radiologically. [ABSTRACT FROM AUTHOR]

Background: Little research is available regarding the treatments combining surgical resection with systemic chemotherapy for advanced pancreatic neuroendocrine neoplasm patients. We retrospectively elucidated whether sunitinib administration before surgery in advanced pancreatic neuroendocrine neoplasm (Pan‐NEN) patients increases survival. Methods: This study included 106 of 326 Pan‐NEN patients with distant metastases and/or unresectable locally advanced tumors who visited our department to receive sunitinib for more than 1 mo during April 2002 to December 2019. Risk factors for overall survival (OS) and disease‐free survival (DFS) were analyzed. Results: The median duration of preoperative sunitinib administration and observation time after sunitinib were 6 and 26.5 mo, respectively. Of 106 patients, 31 (29.2%) underwent surgery following sunitinib administration. Hepatectomy, synchronous hepatopancreatectomy, pancreatectomy, and lymphadenectomy were performed for 13, 12, 5, and 1 patient, respectively. The 5‐y OS rates in the resected and nonresected groups were 88.9% and 14.1%, respectively (P <.001). In the multivariate analysis, the absence of surgical resection following sunitinib (hazard ratio [HR], 13.1; P =.001), poor differentiation (HR, 5.5; P =.007), and bilateral liver metastases (HR, 3.7; P =.048) were independent risk factors for OS, although large liver tumor volumes were more evident in the nonresected group, as patient characteristics. The median DFS was 16.1 mo in 22 patients who underwent R0/1 resections, and risk factors for postoperative recurrence were Ki‐67 index >7.8% (HR, 7.4; P =.02) and R1 resection (HR, 4.4; P =.04). Conclusion: Surgical resection after sunitinib administration improved OS in advanced Pan‐NENs. [ABSTRACT FROM AUTHOR]