Search Results (125)

The management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remains a topic of active debate. Although neoadjuvant therapy (NAT) has shown clinical benefits in BR-PDAC, especially in increasing resectability and achieving higher rates of margin-negative (R0) resections, its role in R-PDAC is less clearly defined. Additionally, the role of immunotherapy in PDAC is still being explored, with ongoing trials investigating new combinations to overcome the tumor’s immune-resistant microenvironment. This article provides a comprehensive narrative review of the current evidence comparing NAT with upfront surgery in pancreatic cancer management, focusing on randomized controlled trials and meta-analyses that assess outcomes in R-PDAC and BR-PDAC. The review aims to determine whether NAT offers a significant survival advantage over traditional post-operative strategies and to clarify which clinical scenarios may benefit most from NAT. The literature was identified through a systematic search of PubMed, Scopus, and Google Scholar databases up to March 2025. Article selection adhered to the PRISMA guidelines. Our review of existing evidence supports NAT as the standard of care for BR-PDAC. Meanwhile, management of R-PDAC should be tailored individually, guided by risk stratification that considers both clinical parameters and molecular features. Immunotherapy and targeted therapies are still in early research phases, and their further integration as NAT remains controversial. Full article

Background/Objectives: Preoperative strategies for hepatocellular carcinoma (HCC) requiring major hepatectomy remain controversial, particularly in “borderline resectable” cases. This study aimed to evaluate the oncological benefit and perioperative safety of Yttrium-90 transarterial radioembolization (TARE) in patients undergoing right or extended right hepatectomy for HCC. Material and Methods: All consecutive patients who underwent right or extended right hepatectomy for HCC at a single tertiary center between January 2013 and December 2023 were retrospectively reviewed. Patients were grouped based on whether they received preoperative TARE or underwent upfront resection. Outcomes analyzed included perioperative morbidity and long-term oncological endpoints. Results: A total of 39 patients were included, of whom 18 received preoperative TARE and 21 underwent upfront surgery. Patients in the TARE group showed significantly greater tumor necrosis at pathology (70% vs. 10%, p = 0.002) and more frequent extended resections. Five-year cancer-specific survival (80.4% vs. 33.5%, p = 0.011), recurrence-free survival (33.8% vs. 14.0%, p = 0.047), and curative-intent disease-free survival (69.3% vs. 18.9%, p = 0.0037) were significantly higher in the TARE group. Overall survival showed a favorable trend. Intraoperative outcomes, postoperative morbidity, and 90-day mortality were comparable between groups. Conclusions: Preoperative TARE is a safe and effective neoadjuvant strategy in selected patients with HCC undergoing major hepatectomy. It may enhance long-term oncological outcomes without increasing surgical risk, supporting its potential role in the management of borderline resectable HCC. Full article

Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion’s aggressiveness, depending on its nature. According to this, CH-EUS could be applied to structure an even more dedicated approach to patient care, for example, to ascertain eligibility for surgical intervention of a pancreatic ductal adenocarcinoma (PDAC) or the response to neoadjuvant chemotherapy in cases deemed borderline resectable. In addition to PDAC, other significant issues pertain to the management of small neuroendocrine tumors (NETs) and intraductal papillary mucinous neoplasms (IPMNs). In this context, CH-EUS can be crucial. The aim of this review is to underline the most recent evidence for EUS and CH-EUS applications in pancreatic lesion aggressiveness assessment and to focus on possible future research directions to further extend the application of CH-EUS in this field. Full article

Background/Objectives: Treatment of borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer involves neoadjuvant chemotherapy followed by complex surgery, posing significant risks of toxicity, complications, and changes in quality of life (QoL). This study aims to investigate the impact of neoadjuvant chemotherapy followed by resection on overall survival (OS) and QoL. Methods: Consecutive patients with BRPC and LAPC included in a population-based study (NORPACT-2) from January 2018 to December 2020 were reviewed. Results: A total of 54 patients (BRPC; n = 43, LAPC; n = 11) underwent neoadjuvant chemotherapy followed by pancreatectomy. The majority (66.7%) received (m)FOLFIRINOX. Forty-six (85.2%) patients underwent pancreatoduodenectomy. Vascular resection was performed in 32 (59.3%) patients. Fourteen (25.9%) patients experienced major complications. The majority of the resected specimens demonstrated T2 (63%), N+ (79.6%), and R1 (85.2%) status. Median OS was 31 (CI 24.7–37.3) months. In multivariate analysis, only CAP 3 (p = 0.035) predicted worse survival. Forty (74.1%) patients experienced recurrence. Global QoL (p = 0.031), social and role functioning (p = 0.024, p = 0.031), improved three months after surgery. Pain (p = 0.042), dyspnea (p = 0.004), appetite loss (p = 0.028), and diarrhea (p = 0.007) improved post-resection. Conclusions: Patients with BRPC and LAPC undergoing neoadjuvant chemotherapy and resection have survival comparable to primary resectable pancreatic cancer. Postoperative morbidity was acceptable, and QoL recovered post-surgery. CAP grade was the only independent negative prognostic factor. Full article

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC. Full article

The incidence of pancreatic ductal adenocarcinoma (PDAC) is continuing to rise globally, while overall survival continues to be poor. Margin-negative (R0) surgical resection is essential to improve patient outcomes. With increasing understanding of the importance of anatomy and biology to establishing the resectability of PDAC, neoadjuvant therapy (NAT) has emerged as an important strategy to achieve an R0 resection, particularly for those with borderline resectable (BR-PDAC) and locally advanced disease (LA-PDAC). However, despite the multiple randomised controlled trials (RCTs) published in recent years, the optimum regime has yet to be fully established. The role of neoadjuvant chemoradiation therapy (CRT) remains controversial, possibly allowing for improved local disease control at a potential cost of interrupting systemic treatment. The emergence of stereotactic ablative radiotherapy (SABR), in place of conventional radiation therapy, improves patient tolerance of NAT and may improve local tumour control for patients with PDAC during limited fractions, minimising systemic therapy interruption. A particular niche for SABR may be as part of NAT for LA-PDAC, potentially converting a minority of patients with favourable biology to allow for resection. While pancreaticoduodenectomy can be technically challenging following NAT, there is no difference in the rate of major morbidity or mortality post operatively. Indeed, post-operative pancreatic fistula (POPF) rates may be lower following NAT. Overall, however, evidence for SABR in a neoadjuvant setting for BR- and LA-PDAC remains sparse. Full article

Background: Despite advances in chemotherapy and supportive care, pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis, with a five-year survival rate of approximately 13%. While immunotherapy has revolutionized treatment for several malignancies, its efficacy in PDAC remains limited. Recent research has shifted focus toward integrating immunotherapy with chemotherapy, radiation, and targeted therapies in an effort to overcome therapeutic resistance and improve outcomes. Ongoing clinical trials are actively investigating these multimodal strategies. Materials and Methods: A systematic search was conducted using PubMed and ScienceDirect to identify relevant studies published in the past six years. Search terms included “pancreatic adenocarcinoma immunotherapy,” “pancreatic cancer treatments,” and “combination treatments for pancreatic adenocarcinoma.” Only English-language articles were included. Results: A total of 126 articles were initially identified through the database search. After a full-text screening, 48 articles were deemed potentially relevant. Following a rigorous review, 11 studies met the inclusion criteria and were selected for analysis. These studies included randomized controlled trials, non-randomized controlled trials, and retrospective studies. Meta-analyses and case reports were excluded. Articles that failed to meet the inclusion criteria were excluded, primarily due to the absence of relevant data addressing the main objective of this review. Conclusions: Combination strategies with immunotherapy and chemotherapy offer modest survival gains in metastatic settings, yet efforts in resectable and borderline resectable disease have fallen short. These outcomes reflect the profound immunosuppressive forces of the PDAC microenvironment. A new era of treatment must move beyond broad immunotherapeutic applications toward a precision-driven model. Molecular markers, such as KRAS mutations and circulating tumor DNA (ctDNA) profiles, are beginning to illuminate paths for personalized therapy selection. Future progress will depend on biomarker-guided clinical trials, a deeper understanding of immune resistance mechanisms, and bold innovation at the intersection of immunology and tumor biology. Full article

Background/Objectives: Phyllodes tumors (PTs) are rare fibroepithelial breast neoplasms with a high propensity for local recurrence, particularly in borderline and malignant forms. Although wide local excision with negative margins is standard, the role of full-thickness chest wall resection (FTCWR) for PTs invading the chest wall remains unclear. This systematic review evaluated the outcomes of FTCWR in such cases, focusing on oncologic effectiveness and reconstruction. Methods: A comprehensive literature search of PubMed, Embase, Scopus databases, and Google Scholar (up to the end of November 2024) identified 18 case reports describing 18 patients (mean age of 42.9 years) with locally invasive PTs. Results: Most patients presented with large (>5 cm), recurrent malignant tumors fixed to the chest wall, with the largest measuring 38 cm. Median disease-free survival was 12 months (range: 1–60), with local recurrence in 5.6% and distant metastases in 22.2% of cases. Common complications included respiratory and wound-related issues. Despite the radical surgery, all patients achieved satisfactory cosmetic results. Conclusions: While FTCWR appears feasible and provides symptom relief and short-term disease control in select patients, the evidence remains limited to case reports. Its long-term oncologic benefit is still uncertain, and further research, including prospective studies and multi-center registries, is needed to elucidate its role in clinical practice. Full article

Background: We reviewed outcomes of short and long-term chemotherapy with or without breaks in pancreatic ductal adenocarcinoma (PDAC) patients. Methods: PDAC patients receiving ≥3 chemotherapy cycles between 2019 and 2024 at three institutions were included. Progression-free survival after first-line chemotherapy (PFS1), overall survival (OS) and best overall response (BOR) to chemotherapy were assessed using the Wilcoxon test, Kaplan–Meier test, and univariate and multivariate Cox regression models. Results: We screened 237 patients, and 135 patients met the study criteria. Among these patients, 25 had resectable disease, and 110 had unresectable/metastatic disease (13% borderline resectable (BRPC), 20% locally advanced (LAPC), 10% localised developing metastases, 57% de novo metastatic). Ten patients (7%) underwent genetic profiling; KRAS aberrations (N = 4), actionable PLAB2/BRCA2/FGFR2 mutations (N = 3), ATM/BRIP1 alteration (N = 1). Two patients were managed with PARP inhibitors after receiving multiple lines of chemotherapy. Median PFS1 and OS were concordant with the published literature, but select patient groups achieved prolonged survival outcomes. Among the 36 BRPC/LAPC patients, we observed >1-year PFS1 in 9 (25%) patients and >2-year OS in 3 (8%) patients. Among the 63 de novo metastatic patients, we observed >1-year PFS1 and >2-year OS in 6 (10%) patients. Among patients with localised disease, smoking history was a poor prognostic factor with respect to OS (p = 0.03). Improved PFS1 and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥3.66 months, and local treatment after first chemotherapy (p < 0.05 for all). Stereotactic body radiotherapy following first-line chemotherapy was delivered in N = 6 (27%) and N = 1 (7%) of patients with LAPC and BRPC, respectively. Chemotherapy interruption duration, but not number, was associated with PFS1 and OS only in the localised cohort (p < 0.05). In patients with de novo metastatic disease, prevalence of type 2 diabetes was adversely associated with OS (p = 0.03). Improved PFS and OS was associated with ≥6 cycles of first-line chemotherapy, its duration of ≥4.37 months, and BOR to it (only in this cohort) (p < 0.05 for all). A favourable OS was associated with >1 line of chemotherapy (p = 0.003). Conclusion: Despite challenges, extended chemotherapy and multiple treatment lines may improve survival, with localised treatments benefiting select patients. Full article

Background: Preoperative planning of patients diagnosed with pancreatic head cancer is difficult and requires specific expertise. This pilot study assesses the added value of three-dimensional (3D) patient models and computer-aided detection (CAD) algorithms in determining the resectability of pancreatic head tumors. Methods: This study included 14 hepatopancreatobiliary experts from eight hospitals. The participants assessed three radiologically resectable and three radiologically borderline resectable cases in a simulated setting via crossover design. Groups were divided in controls (using a CT scan), a 3D group (using a CT scan and 3D models), and a CAD group (using a CT scan, 3D and CAD). For the perceived fulfillment of preoperative needs, the quality and confidence of clinical decision-making were evaluated. Results: A higher perceived ability to determine degrees and the length of tumor–vessel contact was reported in the CAD group compared to controls (p = 0.022 and p = 0.003, respectively). Lower degrees of tumor–vessel contact were predicted for radiologically borderline resectable tumors in the CAD group compared to controls (p = 0.037). Higher confidence levels were observed in predicting the need for vascular resection in the 3D group compared to controls (p = 0.033) for all cases combined. Conclusions: “CAD (including 3D) improved experts’ perceived ability to accurately assess vessel involvement and supports the development of evolving techniques that may enhance the diagnosis and treatment of pancreatic cancer”. Full article

Background/Objectives: Neoadjuvant therapy (NAT) improves surgical outcomes in pancreatic cancer, but its role in elderly patients remains unclear. Due to comorbidities and lower chemotherapy tolerance, assessing NAT’s benefits and risks in this population is essential. This systematic review assesses the impact of NAT on overall survival (OS), surgical resection rates, and treatment-related toxicities(G3-4) in elderly patients with resectable, borderline, or locally advanced pancreatic cancer. Methods: A systematic search was conducted in PubMed, MEDLINE, EMBASE, Scopus, and Cochrane databases according to PRISMA guidelines. Studies reporting that NAT outcomes in elderly patients (≥70 years) were included. The Newcastle–Ottawa scale was used to assess study quality. Subgroup analyses compared NAT versus upfront surgery and outcomes in elderly versus younger patients. Results: Twelve studies (four prospective and eight retrospective) including 11,385 patients met the inclusion criteria. Among 9580 elderly patients, only 24% underwent NAT. NAT significantly improved R0 resection rates compared to upfront surgery (p < 0.001), and elderly patients receiving NAT had a median OS of 26.5 (range 15.7–39.1) months versus 20.3 months (range 11.5–23.8) of upfront surgery and versus 36.2 months (range 23.6–43.0) of NAT in young patients. Elderly patients experienced higher rates of major toxicities (17–57.5%). Personalized regimens, such as gemcitabine/nab-paclitaxel, were better tolerated than FOLFIRINOX. Conclusions: NAT is associated with improved survival and surgical outcomes in elderly pancreatic cancer patients, despite a higher risk of adverse events. Patient selection based on performance status rather than age alone is essential to optimize treatment benefits. Further prospective trials are needed to refine treatment approaches in this population. Full article

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, characterized by late diagnosis, rapid progression, and limited therapeutic options. Despite advancements, only 20% of patients are eligible for surgical resection at diagnosis, the sole curative treatment. Multidisciplinary evaluation is critical to optimize care, stratifying patients based on resectability into resectable, borderline resectable, locally advanced, and metastatic stages. Preoperative imaging, such as computed tomography (CT) and endoscopic ultrasound (EUS), remains central for staging, for vascular assessment, and tissue acquisition. Endoscopic and systemic approaches are pivotal for addressing complications like biliary obstruction and improving outcomes. Endoscopic retrograde cholangiopancreatography (ERCP) has been considered for years the gold standard for biliary drainage, although EUS-guided drainage is increasingly utilized due to its efficacy in both resectable and unresectable disease. Systemic therapies play a key role in neoadjuvant, adjuvant, and palliative settings, with ongoing trials exploring their impact on survival and resectability chance. This review highlights the evolving multidisciplinary approaches tailored to the disease stage, focusing on biliary drainage techniques, systemic therapies, and their integration into comprehensive care pathways for PDAC. The continuous refinement of these strategies offers incremental survival benefits and underscores the importance of personalized, multidisciplinary management. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult cancers to treat, with a dismal 5-year survival rate of only 8–10%. This challenging prognosis highlights the urgent need for innovative therapeutic approaches to improve outcomes for patients with PDAC. Electrochemotherapy (ECT), which enhances intracellular chemotherapeutic uptake via electric pulses, has been explored for resectable, borderline resectable (BR), locally advanced (LA), recurrent, and metastatic PDAC, either as a complement to conventional treatments or as an alternative when these are not feasible or effective, offering possible benefits in symptomatic palliation and local tumor control. Methods: A systematic review was performed in accordance with PRISMA guidelines for studies assessing the efficacy of ECT in PDAC. After searching Embase, PubMed/MEDLINE, Scopus, and Web of Science, five studies with a combined total of 43 patients in various disease stages were identified. Results: ECT showed promise in improving tumor control, alleviating cancer-related pain, and improving quality of life. One study noted a trend towards tumor size reduction of 8.3% at one-month and 16.1% at six-months follow-up (p = 0.211 and p = 0.315), although these findings were derived from studies conducted without specific comparative control groups. Severity of complication was mainly mild (Clavien–Dindo I-II), while severe complications occurred in only 2.3% of patients. Median overall survival was reported in two studies as 8 months (range 2–19) and 11.5 months (range 1–74). ECT showed efficacy for symptom management, with 60% of patients reporting reduced pain/discomfort and 40% showing enhanced quality of life in one study, while another reported pain scores as decreasing from 6 to 3 at one month and to 2 at six months. Conclusions: ECT appears to be a new promising and safe adjunct treatment modality in PDAC management across different disease stages, with potential benefits in tumor control, cancer-related pain reduction, and quality of life. Further studies are warranted to validate these findings and identify patients who could benefit most. Full article

Objective: We demonstrated for the first time the safety and feasibility of escalating up to 55 Gy/11 Gy/fr/5fr in borderline (BRPC)/unresectable locally advanced pancreatic cancer (LAPC), using the standard LINAC platform. The aim of the present study is to assess for the first time the impact of this high-dose neoadjuvant stereotactic ablative radiotherapy (SABRT) protocol on tumor resectability and pathological responses. Materials/Methods: From June 2017 to December 2022, patients with BRPC/LAPC were treated with neoadjuvant chemotherapy (ChT) and SABRT-escalated doses of SIB at 45 Gy, 50 Gy, and up to 55 Gy (BED ≥ 100). Radiological evaluation was conducted with a CT scan 6-8 weeks post-treatment to determine resectability status based on established criteria (SAR/APA2014). Surgical decisions were made by the multidisciplinary tumor board of the participating institutions. Pathological assessments post-surgery used criteria from the College of American Pathologists (CAP), categorizing resection status as R0 (negative margins), R1 (microscopic tumor margins), and R2 (macroscopic tumor margins). Tumor response was evaluated with the Tumor Response Scoring (TRS) system, as G0 (no viable cancer cells), G1 (single cells or rare small groups), G2 (residual cancer with evident regression), and G3 (extensive residual cancer). Results: Thirty-three patients (p) were included: 39.4% (13p) BRPC/60.6% (20p) LAPC. After ChT-SABRT, 45.5% (15p) were considered resectable, with 11/13 (84.6%) BRPC and 4/20 (20%) LAPC (p < 0.0001). One patient refused surgery and other patient died of COVID sepsis. Two more patients had disseminated disease at surgery. Among the 11 patients who underwent full surgery, all patients achieved either clean margins R0: 72.7% (8p) or microscopic affected margins R1: 27.3% (3p). TRS scores were G1: 27.3% (3p), G2: 54.5% (6p), and G3: 18.2% (2p). The present follow-up (FUP) was closed on 1 November 2024 (23.55 months, range: 6–71 months). The mean freedom from local progression as the first cause of disease failure was 43.30 ± 3.09 (37.23–49.38), and the median was not reached. The actuarial 1- and 2-year rates for freedom from local relapse as a first cause of disease failure were 92.3% (87.7–93.3%) and 79.7% (79.7–87.7%), respectively. Conclusions: Neoadjuvant ChT-SABRT in LAPC improves resectability rates and induces relevant tumor regression. These promising findings should be validated by larger sample sizes and extended follow-up. Full article

Background: Transanal endoscopic microsurgery (TEM) is a minimally invasive approach for excising rectal polyps, particularly those with high-grade dysplasia (HGD) or early-stage rectal cancer (T1). This study aimed to evaluate the recurrence risk and its associated factors in patients treated with TEM for HGD and T1 rectal tumors. Methods: A retrospective review was conducted on 79 patients who underwent TEM for rectal lesions at Rabin Medical Center-Hasharon Hospital from 2005 to 2019. Data collected included demographics, tumor characteristics, and follow-up outcomes, with specific focus on tumor size, resection margins, mucin production, and distance from anal verge (AV). Separate and unified analyses were performed to assess the recurrence risk factors for both HGD and T1 patients. Results: Sixty-three patients were included in the final analysis. In the unified analysis, larger tumor size was significantly associated with increased recurrence risk (OR = 2.27, p = 0.028), and mucin production was a strong predictor of recurrence in the T1 group and combined analysis (p = 0.0012 and p = 0.014, respectively). Distance from AV demonstrated a borderline association with recurrence (p = 0.053). Conclusions: Larger tumor size and mucin production are significant predictors of recurrence in TEM-treated rectal polyps. Personalized follow-up and postoperative management are essential for patients with these risk factors to reduce the recurrence risk. Full article