Search Results (24)

Nectins constitute a family of Ca(2+)-independent immunoglobulin-like adhesion molecules. They are involved in cell proliferation, morphogenesis, growth, development, and immune modulation. Due to their broad involvement in physiological processes, extensive research is being conducted on the expression of individual nectins in a variety of cancers and their potential in diagnosis, prognosis, and treatment. The overexpression of nectin-1 may be a poor prognostic factor in gastrointestinal cancers (intestine and pancreas). Similarly, the overexpression of nectin-2 is a worse prognostic factor (greater tumor advancement and shorter patient survival) in cancers such as gallbladder, esophagus, and breast cancer. Changes in nectin-3 expression also affect the advancement of, e.g., colorectal cancer. Additionally, a significant factor here seems to be the change in the localization of nectin-3 expression within cellular structures. The most extensively studied nectin-4 also shows prognostic potential in many cancers. Most often, its high expression correlates with poor prognosis (e.g., gastric cancer), but it may also be a positive prognostic factor, e.g., in salivary gland cancer. Therapy based on nectin-4 is already known and used in the case of urothelial cancers. The expression of nectin-like protein 5 (necl-5) also shows prognostic and therapeutic potential in pancreatic and lung cancers, as well as in multiple myeloma. Full article

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) has been used for selected patients with pancreatic cancer infiltrating the celiac axis. We compared the short- and long-term outcomes between DP-CAR and distal pancreatectomy alone (DP) in patients receiving neoadjuvant therapy. Methods: Patients undergoing DP-CAR from 2013 to 2022 were retrospectively reviewed. Clinicopathologic features, post-operative morbidity, and survival outcomes were compared with patients undergoing DP after neoadjuvant chemotherapy. Results: Twenty-two DP-CAR and thirty-four DP patients who underwent neoadjuvant chemotherapy were identified. There were no differences in comorbidities or CA19-9 levels. OR time was longer for DP-CAR (304 vs. 240 min, p = 0.007), but there was no difference in the transfusion rate (22.7% vs. 14.7%). Vascular reconstruction was more common in DP-CAR (18.2% vs. 0% arterial, p = 0.05; 40.9% vs. 12.5% venous, p = 0.04). There was no difference in morbidity or mortality between the two groups. Although there was a trend towards larger tumors in DP-CAR (5.1 cm vs. 3.8 cm, p = 0.057), the overall survival from the initiation of treatment (32 vs. 28 months, p = 0.43) and surgery (30 vs. 24 months, p = 0.43) were similar. Discussion: DP-CAR is associated with similar survival and morbidity compared to DP patients requiring neoadjuvant chemotherapy and should be pursued in appropriately selected patients. Full article

Background: Propensity score matching (PSM) was used to investigate the prognostic value of a novel GLUCAR index [Glucose × (C-reactive protein ÷ albumin)] in unresectable locally advanced pancreatic cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT). Methods: The PSM analysis comprised 142 LA-PAC patients subjected to definitive CCRT. Receiver operating characteristic (ROC) curve analysis was utilized to identify relevant pre-CCRT cutoffs that could effectively stratify survival results. The primary and secondary objectives were the correlations between the pre-CCRT GLUCAR measures and overall survival (OS) and progression-free survival (PFS). Results: The ROC analysis revealed significance at 43.3 for PFS [area under the curve (AUC): 85.1%; sensitivity: 76.8%; specificity: 74.2%; J-index: 0.510)] and 42.8 for OS (AUC: 81.8%; sensitivity: 74.2%; specificity: 71.7%; J-index: 0.459). Given that these cutoff points were close, the standard cutoff point, 42.8, was selected for further analysis. Comparative survival analyses showed that pre-CCRT GLUCAR ≥ 42.8 (n = 71) measures were associated with significantly shorter median PFS (4.7 vs. 15.8 months; p < 0.001) and OS (10.1 vs. 25.4 months; p < 0.001) durations compared to GLUCAR < 42.8 measures (n = 71). The multivariate analysis results confirmed the independent significance of the GLUCAR index on PFS (p < 0.001) and OS (p < 0.001) outcomes. Conclusions: Elevated pre-CCRT GLUCAR levels are robustly and independently linked to significantly poorer PFS and OS outcomes in unresectable LA-PAC patients treated with definitive CCRT. Full article

Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5–7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer. Full article

Patients with locally advanced gastric cancer (LAGC) often require multivisceral resection (MVR) of the involved organs to achieve R0 resection and local disease control. The aim of the present study was to systematically review all available literature on the postoperative and long-term outcomes of MVR for gastric cancer. The PubMed database was systematically searched by two independent investigators for studies concerning MVR for LAGC. In total, 30 original studies with 3362 patients met our inclusion criteria. R0 resection was achieved in 67.77% (95% CI, 65.75–69.73%) of patients. The spleen, colon and pancreas comprised the most frequently resected organs in the context of MVR. Pancreatic fistulae (10.08%, 95% CI, 7.99–12.63%), intraabdominal abscesses (9.92%, 95% CI, 7.85–12.46%) and anastomotic leaks (8.09%, 95% CI, 6.23–10.45%) constituted the most common postoperative complications. Using the available data, we estimated the mean 1-year survival at 62.2%, 3-year survival at 33.05%, and 5-year survival at 30.21% for the entire cohort. The survival rates were mainly correlated with lymphatic invasion, tumor size and patient age. Therefore, gastrectomy, together with MVR, is feasible and may offer a survival advantage compared to gastrectomy alone or no other surgical treatment in a selected group of patients. Consequently, both patient and tumor characteristics should be carefully assessed to optimize candidate selection. Full article

Pancreatic cancer (PDAC) is one of the most aggressive solid tumors and is showing increasing incidence. The aim of our review is to provide practical help for all clinical oncologists and to summarize the current management of PDAC using a simple “ABC method” (A—anatomical resectability, B—biological resectability and C—clinical conditions). For anatomically resectable PDAC without any high-risk factors (biological or conditional), the actual standard of care is represented by surgery followed by adjuvant chemotherapy. The remaining PDAC patients should all be treated with initial systemic therapy, though the intent for each is different: for borderline resectable patients, the intent is neoadjuvant; for locally advanced patients, the intent is conversion; and for metastatic PDAC patients, the intent remains just palliative. The actual standard of care in first-line therapy is represented by two regimens: FOLFIRINOX and gemcitabine/nab-paclitaxel. Recently, NALIRIFOX showed positive results over gemcitabine/nab-paclitaxel. There are limited data for maintenance therapy after first-line treatment, though 5-FU or FOLFIRI after initial FOLFIRINOX, and gemcitabine, after initial gemcitabine/nab-paclitaxel, might be considered. We also dedicate space to special rare conditions, such as PDAC with germline BRCA mutations, pancreatic acinar cell carcinoma and adenosquamous carcinoma of the pancreas, with few clinically relevant remarks. Full article

Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% (n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% (n = 5) of patients. Furthermore, 8.7% (n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl’s Prussian blue to detect iron deposits on available tumor samples (n = 56). ZIP14 expression was significantly higher in less advanced tumors (p = 0.01) and correlated with mitochondrial mass (p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl’s Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation. Full article

Purpose: To systematically review all studies comparing multi-agent to single-agent chemotherapy in the first and second-line setting for unresectable pancreatic adenocarcinoma, so as to compare the outcomes of young and elderly patients. Methods: This review searched three databases for relevant studies. The inclusion criteria were diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, comparison of an elderly versus young population, comparison of single-agent versus multi-agent chemotherapy, data on survival outcomes, and randomised controlled trials. The exclusion criteria were phase I trials, incomplete studies, retrospective analyses, systematic reviews, and case reports. A meta-analysis was performed on second-line chemotherapy in elderly patients. Results: Six articles were included in this systematic review. Three of these studies explored first-line treatment and three explored second-line treatment. In the subgroup analysis, the meta-analysis showed statistically improved overall survival for elderly patients receiving single-agent second-line treatment. Conclusions: This systematic review confirmed that combination chemotherapy improved survival in the first-line treatment of advanced pancreatic adenocarcinoma, regardless of age. The benefit of combination chemotherapy in second-line studies for elderly patients with advanced pancreas cancer was less clear. Full article

Introduction: Stereotactic MR-guided Adaptive RadioTherapy (SMART) is a novel process to treat pancreatic tumors. We present an update of the data from our prospective registry of SMART for pancreatic tumors. Materials and methods: After the establishment of the SMART indication in a multidisciplinary board, we included all patients treated for pancreatic tumors. Primary endpoints were acute and late toxicities. Secondary endpoints were survival outcomes (local control, overall survival, distant metastasis free survival) and dosimetric advantages of adaptive process on targets volumes and OAR. Results: We included seventy consecutive patients in our cohort between October 2019 and April 2022. The prescribed dose was 50 Gy in 5 consecutive fractions. No severe acute SMART related toxicity was noted. Acute and late Grade ≤ 2 gastro intestinal were low. Daily adaptation significantly improved PTV and GTV coverage as well as OAR sparing. With a median follow-up of 10.8 months since SMART completion, the median OS, 6-months OS, and 1-year OS were 20.9 months, 86.7% (95% CI: (75–93%), and 68.6% (95% CI: (53–80%), respectively, from SMART completion. Local control at 6 months, 1 year, and 2 years were, respectively, 96.8 % (95% CI: 88–99%), 86.5 (95% CI: 68–95%), and 80.7% (95% CI: 59–92%). There was no grade > 2 late toxicities. Locally Advanced Pancreatic Cancers (LAPC) and Borderline Resectable Pancreatic Cancers (BRPC) patients (52 patients) had a median OS, 6-months OS, and 1-year OS from SMART completion of 15.2 months, 84.4% (95% CI: (70–92%)), and 60.5% (95% CI: (42–75%)), respectively. The median OS, 1-year OS, and 2-year OS from initiation of induction chemotherapy were 22.3 months, 91% (95% CI: (78–97%)), and 45.8% (95% CI: (27–63%)), respectively. Twenty patients underwent surgical resection (38.7 % of patients with initially LAPC) with negative margins (R0). Conclusion: To our knowledge, this is the largest series of SMART for pancreatic tumors. The treatment was well tolerated with only low-grade toxicities. Long-term OS and LC rates were achieved. SMART achieved high secondary resection rates in LAPC patients. Full article

Background and Aims: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). Methods: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. Results: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm² × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). Conclusions: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application. Full article

Pancreas cancer has a poor prognosis despite aggressive treatment and is the fourth leading cause of cancer death in the United States. At diagnosis, most patients have either metastatic or locally advanced disease. In this article, we review the evolution of treatments in locally advanced pancreas cancer (LAPC) and discuss the various radiation therapy fractionation schemes. Furthermore, we examine the data supporting dose escalation and the delivery of ablative biologically effective doses in the setting of LAPC. Finally, we review the role of MRI-guided radiation therapy in escalating dose while sparing organs at risk in the era of stereotactic magnetic resonance-guided adaptive radiation therapy. Full article

Pancreatic cancer (PC) remains the seventh leading cause of cancer-related deaths worldwide and the third in the United States, making it one of the most lethal solid malignancies. Unfortunately, the symptoms of this disease are not very apparent despite an increasing incidence rate. Therefore, at the time of diagnosis, 45% of patients have already developed metastatic tumours. Due to the aggressive nature of the pancreatic tumours, local interventions are required in addition to first-line treatments. Locoregional interventions affect a specific area of the pancreas to minimize local tumour recurrence and reduce the side effects on surrounding healthy tissues. However, compared to the number of new studies on systemic therapy, very little research has been conducted on localised interventions for PC. To address this unbalanced focus and to shed light on the tremendous potentials of locoregional therapies, this work will provide a detailed discussion of various localised treatment strategies. Most importantly, to the best of our knowledge, the aspect of localised drug delivery systems used in PC was unprecedentedly discussed in this work. This review is meant for researchers and clinicians considering utilizing local therapy for the effective treatment of PC, providing a thorough guide on recent advancements in research and clinical trials toward locoregional interventions, together with the authors’ insight into their potential improvements. Full article

Neuroendocrine tumors (NETs) represent a heterogeneous malignancy group of neoplasms, with a limited amount of data from Latin America. Thus, this observational study aimed to provide data about the prevalence, incidence, and survival rates for NET in Ecuadorian hospitals. The study was conducted using data from the Society for the Fight Against Cancer (SOLCA). We evaluated patients with NETs (2000–2020) using the HJ-Biplot method and Cox proportional hazards. Annual age-adjusted incidence and limited-duration prevalence in multivariable analyses as well as hazard ratios (HRs) for mortality and survival were obtained. In the years 2000–2020, the age-adjusted incidence rate increased by 9-fold in the stomach and by 7-fold in the breast. The incidence rates were 1.38 per 100,000 persons in the lung and at 1.79 per 100,000 persons in gastroenteropancreatic sites (rectum, stomach, and pancreas). The prevalence increased from 0.0027% in 2000 to 0.0736% in 2019 and 0.0245% in 2020. Overall survival was worse for metastatic NETs (HR, 4.061; 95% CI, 1.932–8.540; p < 0.001) and advanced local NETs (HR, 2.348; 95% CI, 1.007–5.475 p < 0.048) than for localized NETs. In conclusion, the NET incidence increased in the last 20 years and survival decreased over time, especially for metastatic tumors in the pancreas and the nostril. Full article

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, is an aggressive and lethal form of cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages and a lack of specific diagnostic markers result in an end-stage diagnosis when the tumour has locally advanced or metastasised. PDAC is resistant to most of the available chemotherapy and radiation therapy treatments, making surgery the most potent curative treatment. The desmoplastic tumour microenvironment contributes to determining PDAC pathophysiology, immune response and therapeutic efficacy. The existing therapeutic approaches such as FDA-approved chemotherapeutics, gemcitabine, abraxane and folfirinox, prolong survival marginally and are accompanied by adverse effects. Several studies suggest the role of cannabinoids as anti-cancer agents. Cannabinoid receptors are known to be expressed in pancreatic cells, with a higher expression reported in pancreatic cancer patients. Therefore, pharmacological targeting of the endocannabinoid system might offer therapeutic benefits in pancreatic cancer. In addition, emerging data suggest that cannabinoids in combination with chemotherapy can increase survival in transgenic pancreatic cancer murine models. This review provides an overview of the regulation of the expanded endocannabinoid system, or endocannabinoidome, in PDAC and will explore the potential of targeting this system for novel anticancer approaches. Full article