Resectable Pancreatic Cancer Research Articles

Clinicopathological predictive factors in long-term survivors who underwent surgery for pancreatic ductal adenocarcinoma: A single-center propensity score matched analysis.

Long-term survivors (LTSs) after pancreatic resection of pancreatic ductal adenocarcinoma (PDAC) represent a particular subgroup of patients that remains poorly understood. The primary endpoint was to identify clinicopathological factors associated with LTSs after pancreatic resection for PDAC. This was a retrospective study of patients who had undergone pancreatic resection for PDAC. Long survival was defined as a patient who survived at least 60months. Patients were divided in two groups: LTS and short-term survivor (STS). The two groups were compared regarding epidemiological, clinical, and pathological data. Propensity score matching (PSM) was used to reduce selection bias with a 1:2 ratio. Multivariable analysis of significative predictive factors before and after PSM was done. Three hundred and thirty-three patients were enrolled: 46 (13.8%) in the LTS group and 287 (86.2%) in the STS group. Using PSM, 138 patients were analyzed: 46 in the LTS group and 92 in the STS group. At the multivariate analysis of significative predictive factor after PSM, adjuvant chemotherapy, well-differentiated tumors (G1), and R0 status were related to long-term survival (p=0.052, 0.010 and p=0.019, respectively). Kaplan-Meier survival curves confirmed these data. Additionally, Kaplan-Meier survival curves showed that pathological stage I was a favorable factor with respect to stage II, III, and IV. Long-term survival is possible after pancreatic cancer resection, even if in a small percentage. Significant predictors of long-term survival are administration of adjuvant chemotherapy, American Join Committee on Cancer stage I, well-differentiated tumor (G1), and R0 resection.

Clinicopathological relevance of SMAD4 and RUNX3 in patients with resected pancreatic cancer

Abstract Objectives Treating pancreatic ductal adenocarcinoma (PDAC) is a major clinical challenge, owing to its poor prognosis. Understanding the underlying molecular interactions may be crucial in determining PDAC intractability. We elucidated the combinatory role of SMAD family member 4 (SMAD4) and Runt-related transcription factor 3 (RUNX3) in PDAC. Methods Formalin-fixed and paraffin-embedded tissues were obtained from 101 patients who underwent surgical resection of PDAC. SMAD4 and RUNX3 expression in the tissues was evaluated using immunohistochemistry. SMAD4 and KRAS mutations were evaluated using Sanger sequencing. SMAD4 copy number variations were evaluated using quantitative real-time PCR. These molecular characteristics were compared with clinicopathological features of patients. Results Retained SMAD4 expression in PDAC tissues was associated with higher tumor, node, metastasis (TNM) stage, and metastatic recurrence. Defective RUNX3 expression was associated with higher TNM stages. Further analysis to determine significance of retained SMAD4 indicated that all these cases had defective RUNX3 expression; therefore, the combined expression status of retained SMAD4 and defective RUNX3 expression in tissues was determined to be associated with higher TNM stage and metastatic recurrence than defective SMAD4 expression with defective or retained RUNX3 expression. Survival analysis showed that patients with tumors with retained SMAD4 and defective RUNX3 expression had relatively worse overall survival (OS) rates. KRAS mutations were not associated with SMAD4/RUNX3 expression or OS. Conclusions Despite inherent limitations of this retrospective study and small sample size, our findings highlight the potential combined role of SMAD4 and RUNX3 in node metastasis and metastatic recurrence in patients with resected pancreatic cancer.

A05 - HPB Interrogating the spatial biology of pancreatic cancer-associated fibroblasts

Abstract Background Cancer-associated fibroblasts (CAFs) are key players in the fibrotic tumour microenvironment (TME) of pancreatic cancer. Recent evidence has demonstrated the existence of multiple CAF subtypes, however there is relatively little evidence validating and corroborating these CAF subtypes in resected human pancreatic cancer. Furthermore, the spatial interactions between CAF subtypes and the epithelial and immune compartments of the pancreatic cancer TME is not well understood. Method We designed and optimised a bespoke 8-plex immunofluorescence panel for the purposes of CAF subtype profiling and elucidation of CAF spatial biology: panCK, FAP, SMA, CTGF, S100A4, IL6, LIF, PDGFR. This was applied to a cohort of n=215 resected pancreatic cancer, well characterised with highly granular clinico-pathological and transcriptomic data through the Australian Pancreatic Cancer Genome Initiative. Spatial analysis was performed with novel computational biology techniques. Results We demonstrate seven CAF subtypes which cluster to form distinct, highly prognostic “enrichment profiles” (EPs). The cold EP represents quiescent CAFs in close proximity to immune cells (multivariate HR 0.45, 95% CI 0.30-0.68, p<0.001), and the fibrotic EP represents activated CAFs in close proximity to epithelial cells (multivariate HR 2.22, 95% CI 1.48-3.35, p<0.001). We also demonstrate the prognostic power of high spatial entropy (loss of tissue architecture, correlating with the fibrotic EP) vs low spatial entropy (preservation of tissue architecture, correlating with the cold EP) (HR 2.22, 95% CI 1.47-3.35, p<0.001). Conclusion We begin to unravel the elusive spatial biology of pancreatic CAFs in a large resected human cohort. We see changes in immune cell infiltrate, modulation of cellular relationships, and greater tissue disorganisation as a result of CAF activation. These features are highly prognostic and we hypothesise they are driven by changes in crosstalk between TME compartments. Current work focuses on application of these techniques to a large resected neoadjuvantly-treated cohort, allowing further interrogation of the notorious fibrotic post-neoadjuvant pancreatic cancer TME. If accepted for presentation we look forward to presenting both cohorts simultaneously.

HPB SO38 - Assessing current pancreatic cancer reporting practice against the PACT-UK Synoptic Reporting Template: An initial clinical audit

Abstract Background In the last decade, the incidence of pancreatic cancer has increased by 9% in the UK. The gold standard for initial assessment of pancreatic cancer (or even peri-ampullary cancer) resectability is pancreatic-protocol CT scan. The PACT-UK project introduced a synoptic template for pancreatic cancer to standardise CT reporting practice across UK and enable consistent reporting of pertinent aspects of resectability status such as vascular involvement of the tumour. The aim of this audit is to assess the quality of current CT reports received by a tertiary hepato-pancreato-biliary (HPB) unit against the standards set out by PACT-UK. Method A retrospective analysis of 66 patients who underwent pancreatic resection between September 2023 and May 2024 at a tertiary HPB centre was undertaken. Patients were excluded from the analysis if they underwent resection for benign pancreatic pathology, were diagnosed with pathology other than peri-ampullary cancer or did not have a formal report of their CT scan. Initial CT scans performed at presentation and if available, subsequent up-to-date staging scan prior to surgery were assessed against the PACT-UK reporting template, in accordance with their guidance. The audit was registered with our clinical audit team (no. 11643). Results In total, 42 patients with peri-ampullary cancers were included in this audit. All patients had a reported CT scan on presentation. Additionally, 24 patients had a reported staging CT scan. The compliance (i.e. more than 90% information available) with PACT-UK reporting standards was 0% for initial presentation scans and 4.2% (n=1) for staging scans. The only staging scan with >90% compliance was reported using the PACT-UK template. Majority (more than 80%) of CT scan reports lacked information on aspects such as pancreatic duct size, predicted tumour type and radiological stage, variant vascular anomalies, and arterial/venous involvement. Conclusion This audit highlights the substandard quality of current CT reporting for peri-ampullary cancer. There is an urgent need to adopt a structured and dedicated reporting template to address the issue. Utilising a template such as the one developed by PACT-UK will help ensure that relevant information is formally reported to facilitate optimal decision-making at MDT meetings, and assist surgeons in operative planning and oncologists in assessing treatment response.

HPB SO47 - Adjuvant chemotherapy for early pancreatic cancer: Meta-analysis of survival benefit and the need for a national study of UK practice

Abstract Background Stage I pancreatic cancer is defined as disease localised to the pancreas (T1-T2, N0, M0). Whilst landmark trials have demonstrated adjuvant chemotherapy (AC) improves survival in resectable disease, early stages comprise only 3-8% of cases. The benefit of AC in stage 1 pancreatic cancer is yet to be defined and there currently exists no data outlining the use of AC for early disease in the United Kingdom (UK). We aimed to perform a meta-analysis evaluating comparative outcomes of pancreatic cancer resection with or without AC in patients with stage I pancreatic cancer and outline plans for a national collaborative study. Method A systematic search of MEDLINE, CENTRAL and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without AC were included and their risk of bias were assessed using ROBINS-I tool. Survival outcomes were analysed using hazard ratio (HR) and odds ratio (OR) for the time-to-event and dichotomous outcomes, respectively. Results We included six studies reporting 6,874 patients with resected stage 1 pancreatic cancer of whom 3,951 patients had no AC and the remaining 2,923 patients received AC. The use of AC was associated with significantly higher overall survival (HR 0.71, P<0.00001) and 2-year survival (65.1% versus 57.4%, OR 1.99, P=0.04) compared to no use of AC. There was no statistically significant difference in 1-year (86.8% versus 78.4%, OR 1.60, P =0.25), 3-year (46.0% versus 44.0%, OR 1.07; P =0.43), or 5-year survival (24.8% versus 23.3%, OR 1.03; P =0.81) between the two groups. Conclusion Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that AC may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. National evaluation of the use of AC within the UK is currently lacking but is necessary. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.

Preoperative assessment of pancreatic cancer with [68Ga]Ga-DOTA-FAPI-04 PET/MR versus [18F]-FDG PET/CT plus contrast-enhanced CT: a prospective preliminary study.

To assess the diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging in the preoperative evaluation of pancreatic cancer and compare it with that of [18F]-FDG PET/CT plus contrast-enhanced CT (CECT). Thirty-one patients with pancreatic cancer underwent preoperative [68Ga]Ga-DOTA-FAPI-04 PET/MR, [18F]-FDG PET/CT, and CECT imaging. Two nuclear medicine physicians independently reviewed two sets of images (set 1, [68Ga]Ga-DOTA-FAPI-04 PET/MR; set 2, [18F]-FDG PET/CT plus CECT) and reached a consensus on tumour resectability, N staging (N0 or N positive) and M staging (M0 or M1). Based on the above indices, the resectability of the tumour was determined according to a five-point scale. Clinical, operative, and pathological findings were used as a reference standard to compare the diagnostic performance of the two imaging sets via the McNemar test. The diagnostic performance of [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging was not significantly different from that of [18F]-FDG PET/CT plus CECT imaging in the assessment of tumour resectability (area under the receiver operating characteristic curve: 0.854 vs. 0.775, p = 0.192), N staging [accuracy: 82.4% (14 of 17 patients) vs. 58.8% (10 of 17 patients), p = 0.125] and M staging [accuracy: 100% (31 of 31 patients) vs. 90.3% (28 of 31 patients), p = 0.250]. However, compared with [18F]-FDG PET/CT plus CECT imaging, [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging changed the M stage in three patients by upstaging from M0 to M1 in 2 patients and downstaging from M1 to M0 in 2 patients. In 13 patients with liver metastases, the number of liver metastases detected via [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging was greater than that detected via [18F]-FDG PET/CT plus CECT imaging (324 vs. 240). In 3 patients with peritoneal metastases, [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging detected more peritoneal metastases than did [18F]-FDG PET/CT plus CECT imaging. [68Ga]Ga-DOTA-FAPI-04 PET/MR imaging has diagnostic accuracy comparable to [18F]-FDG PET/CT plus CECT in terms of preoperative staging and assessment of resectability in pancreatic cancer; additionally, it exhibits superior capability in detecting liver and peritoneal metastases. Consequently, [68Ga]Ga-DOTA-FAPI-04 PET/MR has the potential to become a one-stop imaging tool for the preoperative evaluation of pancreatic cancer.

Enhancing Perioperative Outcomes of Pancreatic Surgery with Wearable Augmented Reality Assistance System: A Matched-Pair Analysis

Objective: The present study aimed to evaluate the safety of the first wearable augmented reality assistance system (ARAS) specifically designed for pancreatic surgery and its impact on perioperative outcomes. Background: Pancreatic surgery remains highly complex and is associated with a high rate of perioperative complications. ARAS, as an intraoperative assistance system, has the potential to reduce these complications. Methods: This prospective, single-center study included 20 patients who underwent pancreatic surgery using ARAS. These patients were matched in a 1:3 ratio with 60 patients from our retrospective data who underwent standard pancreatic resection. Matching variables were selected based on factors associated with poor intraoperative outcomes. Results: A higher proportion of patients in the ARAS group were diagnosed with borderline resectable pancreatic cancer and received neoadjuvant chemotherapy (20.0% vs 6.7%, P = 0.085). Additionally, more patients in the ARAS group required arterial resection compared with the control group (15.0% vs 0.0%, P = 0.002). Nevertheless, the ARAS group had a significantly shorter operative time (246 vs 299 minutes, P = 0.004) and required significantly fewer intraoperative blood transfusions (0.0 ± 0.0 vs 0.5 ± 1.4 units, P = 0.014). None of the patients in the ARAS group had positive resection margins (0.0% vs 20.0%, P = 0.045). Furthermore, patients in the ARAS group experienced a significantly shorter hospital stay (13.8 ± 6.6 vs 17.9 ± 8.2 days, P = 0.046). Conclusions: ARAS is a safe and effective assistance system for pancreatic surgery, offering superior perioperative outcomes compared with standard procedures.

Prognostic significance of creatine kinase in resected pancreatic cancer.

Creatine kinase (CK) levels decrease with cancer progression and muscle wasting, but its association with pancreatic ductal adenocarcinoma (PDAC) remains unclear. The aim of this study was to investigate CK as a prognostic biomarker and surrogate marker for muscle mass in patients with PDAC. A retrospective analysis of 476 patients with PDAC was conducted. CK levels were categorized into low and high groups using receiver-operating characteristic (ROC) curve analysis. Among the 476 patients, 200 (42.0%) and 276 (58.0%) were classified into the low and high CK groups, respectively. The low CK group had significantly poorer overall survival (p < .001) and recurrence-free survival (p < .001) compared to the high CK group. Multivariate analysis identified low CK as an independent poor prognostic factor (p < .001). The low CK group had significantly lower skeletal muscle index (p = .048) than the high CK group; however, the difference was slight and not significantly associated with sarcopenia. Additionally, combined risk assessment incorporating CK and resectability facilitated a more nuanced prognostic stratification. CK served as a reliable prognostic marker independent from resectability but was less effective as a marker for sarcopenia in PDAC.

Variation in Lymph Node Assessment After Pancreatic Cancer Resection: Patient, Surgeon, Pathologist, or Hospital?

BackgroundWe sought to define individual contributions at the patient, surgeon, pathologist, and hospital levels on lymph node assessment after pancreatic cancer resection. MethodsSEER-Medicare beneficiaries who underwent pancreatic cancer resection were identified. Multi-level multivariable regression was performed to assess the proportion of variance explained by patient, surgeon, pathologist, and hospitals on lymph node assessment (≥12 versus <12). Results2,872 patients underwent pancreaticoduodenectomy by 646 distinct surgeons and 1,063 distinct pathologists across 308 hospitals. Patient-related characteristics contributed the most to the variance in adequate lymph node assessment (71.0%). After accounting for all explanatory variables in the full model, 5.5% of the residual provider-level variation was attributed to the pathologist, 35.2% to the surgeon, and 59.3% to the hospital. ConclusionsPatient-to-patient variation was the greatest underlying contributor to variations in adequate lymph node assessment related to pancreatic cancer surgery. Variation among hospitals was greater than among surgeons or pathologists.

Transfusion of Irradiated Autologous Blood for Hepatobiliary and Pancreatic Cancer Resections: A Feasibility Study

Transfusion of Irradiated Autologous Blood for Hepatobiliary and Pancreatic Cancer Resections: A Feasibility Study

Genome-wide microRNA Analysis Identified miR-210-3p Over-expression in Pancreatic Cancer Tissues as a Predictor of their Local Invasiveness.

The severe malignancy of pancreatic ductal adenocarcinoma (PDAC) is mainly due to frequent local invasiveness and distant metastasis. As for local invasiveness, we previously reported that cancer-specific molecular alterations detected on resected PDAC specimen surfaces, so-called molecular surgical margin (MSM) positiveness, were significantly associated with postoperative locoregional recurrence and distant metastasis. However, due to anatomical limitations, achieving adequate surgical margins during pancreatic cancer resection is often challenging. Therefore, predicting local invasiveness based on the primary tumor's gene profile is crucial to avoid positive MSM. Genome-wide miRNA expression profiles were examined and compared between MSM-positive and negative cases. Candidate miRNAs were evaluated in another validation cohort, and their clinicopathological characteristics were examined. Mimic or inhibitor constructs of the candidate miRNA were transfected to PDAC cell lines to evaluate the miRNA function in the pancreatic cancer cell lines and detect the downstream targets. Among some candidates with highly expressed miRNAs in MSM-positive cases by miRNA expression array, recurrence-free survival (RFS) was significantly shorter in the miR-210-3p high expression group (p=0.015). High miR-210-3p was significantly associated with large tumor diameter (p=0.001), anterior invasion positive (p=0.010), and positive lymph node metastasis (p<0.001). miR-210-3p inhibition in PDAC cell lines resulted in decreased proliferation and invasiveness. The iron-sulfur cluster assembly enzyme (ISCU) gene was identified as a target of miR-210-3p. ISCU reduction was significantly observed in PDAC primary tumors with high levels of miR-210-3p, leading to mitochondrial dysfunction in miR-210-3p-overexpressing PDAC cell lines, as demonstrated by glycolysis stress tests. Highly expressed hypoxia-inducible miR-210-3p in primary PDAC tissues induces locally invasive characteristics through mitochondrial dysfunction by suppressing ISCU expression, which may result in poor postoperative RFS outcomes.

The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.

Clinical impact of the prognostic nutritional index and skeletal muscle index for the incompletion of adjuvant chemotherapy for pancreatic cancer

Adjuvant chemotherapy is a standard therapeutic option for resected pancreatic cancer. However, the risk factors for incompletion of adjuvant chemotherapy remain unclear. We retrospectively reviewed the medical records of 72 patients who underwent radical pancreatectomy and received S-1 adjuvant chemotherapy for pancreatic cancer. The patients were assigned to two groups according to their completion or incompletion of adjuvant chemotherapy. We compared the perioperative skeletal muscle mass index (SMI) and nutritional status using prognostic nutritional index (PNI) between the two groups. The completion and incompletion groups included 46 (64%) and 26 (36%) patients, respectively. Overall survival was shorter in the incompletion group than in the completion group (median survival time, 20.2 months vs. 42.0 months; log-rank, p=0.018). Decreasing rate of PNI (12.7% vs. 0.2%, p=0.010) and decreasing rate of SMI (26.9% vs. 12.5%, p=0.001) were significantly larger in the incompletion group than in the completion group. Multivariate analysis showed that decreasing rate of PNI (p=0.016), decreasing rate of SMI (p=0.013), and old age (p=0.049) were independent risk factors for incompletion of S-1 adjuvant chemotherapy. Regarding the time-series variations, PNI improved from 1 to 3 months after pancreatectomy in the completion group (p=0.006). Furthermore, the decreasing slope of SMI was stronger in the incompletion group. Postoperative decrease of PNI and SMI is associated with the incompletion of S-1 adjuvant chemotherapy.

Intraoperative Guidance of Pancreatic Cancer Resection Using a Toll-like Receptor 2-Targeted Fluorescence Molecular Imaging Agent.

Human TLR2 is broadly expressed among pancreatic adenocarcinomas, and the highly specific TLR2L-800 fluorescence molecular imaging agent has potential for use in fluorescence-guided surgery to increase R0 margins and improve patient survival.

Trajectory Analysis of Healthcare Use Before and After Gastrointestinal Cancer Surgery.

Frailty correlates with worse post-operative outcomes and higher surgical costs, but the long-term impact on healthcare utilization remains ill-defined. We sought to evaluate patterns of healthcare utilization pre- and post-surgery among patients with gastrointestinal cancer and characterize the association with frailty. Data on patients who underwent surgical resection for liver, biliary, pancreatic, colon and rectal cancer were obtained from the 2005-2020 SEER-Medicare database. Frailty was assessed using the claims-based frailty index. Group-based trajectory modelling identified clusters of patients with discrete patterns of healthcare utilization. Multivariable regression was performed to predict cluster membership based on preoperative factors, including frailty. Among 66,684 beneficiaries, four distinct utilization trajectories based on data from 12 months before and after surgery were identified. Following a surge in utilization during the month of surgery, most patients reverted to pre-surgery baseline utilization (low: n=6588, 9.9%; moderate: n=17,627, 26.4%; high: n=29,850, 44.8%). However, a notable trajectory involving 12,619 (18.9%) patients was identified, wherein surgery precipitated a transition from a "low" pre-surgery utilization state to a "high" utilization state post-surgery. Frail patients were more likely to be among those individuals who transitioned to high utilizers (low: 4.2% vs. vs. transition: 12.6% vs. high: 7.5%; p<0.001). On multivariable analysis incorporating preoperative variables, frailty was associated with high group trajectory membership (ref: least and moderate; highest: OR 4.90, 95%CI 4.49-5.35; p<0.001). Patients with gastrointestinal cancer demonstrated distinct clusters of healthcare utilization after surgical resection. Preoperative predictive models may help differentiate different health care utilization trajectories to help tailor care for patients in the postoperative period.

Clinical usefulness of C-reactive protein-albumin-lymphocyte (CALLY) index as a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer.

The C-reactive protein-albumin-lymphocyte (CALLY) index, which simultaneously evaluates the nutritional, immunological, and inflammatory statuses, is a new prognostic biomarker in patients with various cancers; however, no study has reported the clinical significance of the CALLY index in patients with pancreatic cancer. This study aimed to investigate whether the preoperative CALLY index is a prognostic biomarker in patients undergoing surgical resection of pancreatic cancer. We retrospectively enrolled 461 patients with pancreatic cancer who underwent surgical resection between January 2013 and December 2022. The overall survival (OS) and relapse-free survival (RFS) rates were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. The optimal cut-off value for the preoperative CALLY index was 1.9. In the low CALLY group, patients were older (p = 0.012), more patients underwent pancreaticoduodenectomy (p = 0.002), the median tumor size was larger (p < 0.001), more patients had pathologically confirmed metastatic lymph nodes (p = 0.015) and worse pathological stage (p = 0.015), and fewer patients received adjuvant chemotherapy (p = 0.003). A low CALLY index was associated with decreased OS (22.1 vs. 37.9months) and RFS (12.4 vs. 16.4months). Univariate and multivariate analyses showed that the preoperative CALLY index was an independent prognostic factor for OS (p < 0.001) and RFS (p = 0.045). The preoperative CALLY index is a prognostic biomarker for both OS and RFS in patients undergoing surgery for pancreatic cancer.

Increased Proportion of the Squamous Cell Carcinoma Components Is Associated with Aggressive Behavior and a Worse Prognosis in Resected Pancreatic Adenosquamous Carcinoma.

Pancreatic adenosquamous carcinoma (PASC) is a subtype of pancreatic cancer with a poorer prognosis than pancreatic ductal carcinoma (PDAC). The pathogenesis of this histological subtype has not been fully explained due to its rarity. Of the 245 patients who underwent pancreatic resection for pancreatic cancer, six (2.3%) were diagnosed with PASC. They were retrospectively allocated to Group A (≥ 50% adenocarcinoma components) or Group S (≥ 50% squamous cell carcinoma components). The six patients with PASC were all males between the ages of 63 and 77years, with tumors of 12 to 52mm in diameter. Tumors were located in the pancreatic head (n = 2) and the pancreatic tail (n = 4). Relative to Group A, all three patients in Group S had larger tumors diameters, ≥ 40mm with invasion to other organs. Cancer-specific survival of Group S was worse than that of the PDAC group (median survival, 1.5years vs. 4.1years). All patients in Group A were alive at the end of follow-up. Recurrence-free survival of Group S was inferior to that of the PDAC group (median survival, 0.2years vs. 1.8years; Group A, not defined). Immunohistochemistry revealed the MIB-1 positivity rate in squamous cell carcinoma regions was 1.8 times higher than that in adenocarcinoma regions in the same specimens. In PASC patients, an increased proportion of squamous cell carcinoma components was associated with aggressive behavior and a worse prognosis. This was due to the high MIB-1 positivity rate of squamous cell carcinoma components.

Targeting Human Pancreatic Cancer with a Fluorophore-Conjugated Mucin 4 (MUC4) Antibody: Initial Characterization in Orthotopic Cell Line Mouse Models.

Background/Objectives: Pancreatic cancer is the third leading cause of death related to cancer. The only possible cure presently is complete surgical resection; however, this is limited by difficulty in clearly defining tumor margins. Enhancement of the visualization of pancreatic ductal adenocarcinoma (PDAC) tumor margins using near-infrared dye-conjugated tumor-specific antibodies was pioneered by using anti-CEA, anti-CA19.9, and anti-MUC5AC in orthotopic mouse models of pancreatic cancer. Recently, an antibody to Mucin 4 (MUC4) conjugated to a fluorescent probe has shown promise in targeting colon tumors in orthotopic mouse models. Methods: In the present study, we targeted pancreatic cancer using an anti-MUC4 antibody conjugated to IRDye800 (anti-MUC4-IR800) in orthotopic mouse models. Two pancreatic cancer human cell lines were used, SW1990 and CD18/HPAF. Results: Anti-MUC4-IR800 targeted the two pancreatic cancer cell line tumors in orthotopic mouse models with high tumor-to-pancreas ratios and high tumor-to-liver ratios, with greater targeting seen in SW1990. Conclusions: The present results suggest anti-MUC4-IR800's potential to be used in fluorescence-guided surgical resection of pancreatic cancer.

Assessing Influence of Mismatch Repair Mutations on Survival in Patients After Resection of Pancreatic Ductal and Periampullary Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma. Methods: This is a single-institution, retrospective study based on a prospectively maintained database. Pancreatic ductal adenocarcinoma (N = 342) and periampullary adenocarcinoma patients (N = 76) who underwent pancreatic resection surgery between 2016 and 2021 were included. Immunohistochemistry staining results of MMR proteins and next-generation sequencing data were recorded. Cancer-type dependent Cox regression analyses were performed to assess overall and disease-free survival, which was complemented with a 1:2 propensity-score matching for each of the cancer types in order to compare oncologic outcomes. Results: A total of 418 pancreatic cancer patients were included in the analysis. Fifteen patients (3.5%) were diagnosed as dMMR (PDAC N = 7 and periampullary adenocarcinoma N = 8). Cox regression modeling of dMMR status interaction with TNM staging and cancer type revealed that dMMR status strongly improves overall survival (p < 0.05). After propensity-score matching, Cox regression identified dMMR status as a significant marker of improved overall survival (HR = 0.27, 95%CI 0.09-0.88, p = 0.029). Conclusions: Overall, our findings suggest that dMMR status is associated with markedly improved survival outcomes in patients after resection of pancreatic and periampullary cancer. Future large-scale studies are needed to further validate this finding.

Oncological Outcomes of Open Versus Minimally Invasive Surgery for Ductal Adenocarcinomas of Pancreatic Head: A Propensity Score Matching Analysis.

Minimally invasive pancreatic resections (MIPRs) have been shown to be safe and feasible, but there is still a lack of high-level evidence on oncological outcomes for cephalic pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to compare the oncological outcomes of patients undergoing MIPR and open pancreatic resection (OPR) for pancreatic head cancer in a single high-volume center. Data from a prospectively collected database of patients who underwent radical-intent surgery for resectable and borderline resectable PDAC of the head at our institution between January 2013 and May 2023 were retrieved and analyzed, comparing the surgical and oncological outcomes of MIPR and OPR, using a propensity score matching analysis. In the study period, 220 patients were selected. After matching, a total of 81 MIPRs and 81 OPRs were compared. No difference was found regarding R0 rate (OPR 83.9% vs. MIPR 74.1%, p = 0.122). Median overall survival (24 and 31 months for the OPR and MIPR groups, respectively; log rank p = 0.665) and disease-free survival (12 and 21 months for the OPR and MIPR groups, respectively; log rank p = 0.118) did not differ between the groups. The MIPR group was associated with a greater number of harvested lymph nodes (22 vs. 16, p = 0.0008), longer operative time (565 vs. 420 min, p < 0.0001), and shorter length of stay (12 vs. 18 days; p = 0.0001). No differences between the groups were found regarding all other postoperative and pathological outcomes. Regarding oncological outcomes, MIPR appeared to be comparable to OPR for treating patients with PDAC of the head. Despite an increased operative time, MIPR was associated with a greater number of LNs harvested and a shorter length of stay.