UNASSIGNED: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC.
UNASSIGNED: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated.
UNASSIGNED: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival.
UNASSIGNED: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

Prior observational studies suggest an association between intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC); however, the causal relationship is unclear. To elucidate causality, we conduct a prospective observational study using magnetic resonance imaging (MRI)-measured IPFD data and also perform a Mendelian randomization study using genetic instruments for IPFD. In the observational study, we use UK Biobank data (N = 29,463, median follow-up: 4.5 years) and find that high IPFD (>10%) is associated with PDAC risk (adjusted hazard ratio [HR]: 3.35, 95% confidence interval [95% CI]: 1.60-7.00). In the Mendelian randomization study, we leverage eight out of nine IPFD-associated genetic variants (p < 5 × 10-8) from a genome-wide association study in the UK Biobank (N = 25,617) and find that genetically determined IPFD is associated with PDAC (odds ratio [OR] per 1-standard deviation [SD] increase in IPFD: 2.46, 95% CI: 1.38-4.40) in the Pancreatic Cancer Cohort Consortium I, II, III (PanScan I-III)/Pancreatic Cancer Case-Control Consortium (PanC4) dataset (8,275 PDAC cases and 6,723 non-cases). This study provides evidence for a potential causal role of IPFD in the pathogenesis of PDAC. Thus, reducing IPFD may lower PDAC risk.

BACKGROUND: Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [18F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called \"desmoplastic reaction\", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with 68Ga-labeled FAP ligands suggested superior sensitivity to [18F]FDG. However, there is limited data with 18F-labeled FAP derivatives, i.e. [18F]FAPI-74, yet prospective single- and multicenter trials are already ongoing. In this proof-of-concept study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [18F]FAPI-74 PET/CT as compared to [18F]FDG PET/CT scans for staging.
METHODS: This study includes 7 patients (median age 69) who underwent both [18F]FDG PET/CT with contrast-enhancement and [18F]FAPI-74 PET with low-dose CT for primary staging (n = 3) and therapy response control after neoadjuvant (n = 1) or re-staging after palliative therapy (n = 3). The mean interval between PET scans was 11 ± 4 days (range 1-15 days). The [18F]FDG and [18F]FAPI-74 PET/CT scans were acquired at 64 ± 4.1 min (range 61-91 min) and 66.4 ± 6.3 min (range 60-76 min), respectively, after administration of 200 ± 94 MBq (range 79-318 MBq) and 235 ± 88 MBq (range 90-321 MBq), respectively. Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool.
RESULTS: Overall, 32 lesions were detected in 7 patients including primary (n = 7), lung (n = 7), bone (n = 3), lymph node (n = 13), and peritoneal metastases (n = 2). [18F]FAPI-74 detected 22% more lesions compared with [18F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [18F]FAPI-74 but was missed by [18F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [18F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast.
CONCLUSIONS: To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [18F]FAPI-74 with [18F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective study to determine the value of [18F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.

To explore patients\' experiences of pain treatment in the perioperative period after surgery for pancreatic cancer.
A qualitative descriptive design using semi-structured interviews.
This study was a qualitative study based on 12 interviews. Participants were patients that had undergone surgery for pancreatic cancer. The interviews were conducted 1 to 2 days after the epidural was turned off, in a surgical department in Sweden. The interviews were analysed with qualitative content analysis. The Standard for Reporting Qualitative Research checklist was used for reporting the qualitative research study.
The analysis of the transcribed interviews, generated one theme: Maintaining a sense of control in the perioperative phase, and two subthemes: (i) Sense of vulnerability and safety, and (ii) Sense of comfort and discomfort, were found.
The participants experienced comfort after pancreas surgery if they maintained a sense of control in the perioperative phase and when the epidural pain treatment provided pain relief without any side effects. The transition from epidural pain treatment to oral pain treatment with opioid tablets was experienced individually, from an almost unnoticed transition to the experience of severe pain, nausea, and fatigue. The sense of vulnerability and safety among the participants were affected by nursing care relationship and the environment on the ward.

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.

Partial/complete pathologic response following neoadjuvant chemotherapy (NAC) in pancreatic cancer (PDAC) patients undergoing pancreatectomy is associated with improved survival. We sought to determine whether neutrophil-to-lymphocyte ratio (NLR) dynamics predict pathologic response following chemotherapy in PDAC, and if manipulating NLR impacts chemosensitivity in preclinical models and uncovers potential mechanistic underpinnings underlying these effects.
Pathologic response in PDAC patients (n=94) undergoing NAC and pancreatectomy (7/2015-12/2019) was dichotomized as partial/complete or poor/absent. Bootstrap-validated multivariable models assessed associations between pre-chemotherapy NLR (%neutrophils÷%lymphocytes) or NLR dynamics during chemotherapy (ΔNLR = pre-surgery-pre-chemotherapy NLR) and pathologic response, disease-free survival (DFS), and overall survival (OS). To preclinically model effects of NLR attenuation on chemosensitivity, Ptf1aCre/+; KrasLSL-G12D/+;Tgfbr2flox/flox (PKT) mice and C57BL/6 mice orthotopically injected with KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx1Cre(KPC) cells were randomized to vehicle, gemcitabine/paclitaxel alone, and NLR-attenuating anti-Ly6G with/without gemcitabine/paclitaxel treatment.
In 94 PDAC patients undergoing NAC (median:4 months), pre-chemotherapy NLR (p<0.001) and ΔNLR attenuation during NAC (p=0.002) were independently associated with partial/complete pathologic response. An NLR score = pre-chemotherapy NLR+ΔNLR correlated with DFS (p=0.006) and OS (p=0.002). Upon preclinical modeling, combining NLR-attenuating anti-Ly6G treatment with gemcitabine/paclitaxel-compared with gemcitabine/paclitaxel or anti-Ly6G alone-not only significantly reduced tumor burden and metastatic outgrowth, but also augmented tumor-infiltrating CD107a+-degranulating CD8+ T-cells (p<0.01) while dampening inflammatory cancer-associated fibroblast (CAF) polarization (p=0.006) and chemoresistant IL-6/STAT-3 signaling in vivo. Neutrophil-derived IL-1β emerged as a novel mediator of stromal inflammation, inducing inflammatory CAF polarization and CAF-tumor cell IL-6/STAT-3 signaling in ex vivo co-cultures.
Therapeutic strategies to mitigate neutrophil-CAF-tumor cell IL-1β/IL-6/STAT-3 signaling during NAC may improve pathologic responses and/or survival in PDAC.
Supported by KL2 career development grant by Miami CTSI under NIH Award UL1TR002736, Stanley Glaser Foundation, American College of Surgeons Franklin Martin Career Development Award, and Association for Academic Surgery Joel J. Roslyn Faculty Award (to J. Datta); NIH R01 CA161976 (to N.B. Merchant); and NCI/NIH Award P30CA240139 (to J. Datta and N.B. Merchant).

UNASSIGNED: Malnutrition has been shown to be a risk factor for postoperative complications after pancreatoduodenectomy (PD). In addition, patients needing a PD, such as patients with pancreatic cancer or chronic pancreatitis, often are malnourished. The best route of postoperative nutrition after PD remains unknown. The aim of this randomized controlled trial is to evaluate if early postoperative enteral nutrition can decrease complications after PD compared to oral nutrition.
UNASSIGNED: This multicenter, open-label, randomized controlled trial will include 128 patients undergoing PD with a nutritional risk screening ≥3. Patients will be randomized 1:1 using variable block randomization stratified by center to receive either early enteral nutrition (intervention group) or oral nutrition (control group) after PD. Patients in the intervention group will receive enteral nutrition since the first night of the operation (250 ml/12 h), and enteral nutrition will be increased daily if tolerated until 1000 ml/12 h. The primary outcome will be the Comprehensive Complication Index (CCI) at 90 days after PD.
UNASSIGNED: This study with its multicentric and randomized design will permit to establish if early postoperative enteral nutrition after PD improves postoperative outcomes compared to oral nutrition in malnourished patients.
UNASSIGNED: https://clinicaltrials.gov/(NCT05042882) Registration date: September 2021.

Pancreatic ductal adenocarcinoma (PDAC) one of the deadliest malignant tumor. Despite considerable progress in pancreatic cancer treatment in the past 10 years, PDAC mortality has shown no appreciable change, and systemic therapies for PDAC generally lack efficacy. Thus, developing biomarkers for treatment guidance is urgently required. This review focuses on pancreatic tumor organoids (PTOs), which can mimic the characteristics of the original tumor in vitro. As a powerful tool with several applications, PTOs represent a new strategy for targeted therapy in pancreatic cancer and contribute to the advancement of the field of personalized medicine.

OBJECTIVE: The enhanced recovery after surgery (ERAS) protocol is a perioperative care bundle designed to achieve early healing after surgical procedures. This study aims to investigate the effect of the ERAS protocol on postoperative complications, length of hospital stay (LOS), and readmission rates in pancreatic surgery patients.
METHODS: The study was designed as a prospective and randomized controlled study between January 2016 and November 2018 on pancreatic surgery patients. A total of 38 patients were analyzed, 18 of whom were in the ERAS group and 20 in the control group. Patient demographics, intraoperative variables, and postoperative outcomes were recorded.
RESULTS: The groups were similar regarding age, sex, surgery type, American Society of Anesthesiologists scores, and laboratory results. There was no significant difference in the intraoperative variables. Early oral feeding was preferred, mostly in the ERAS group compared to the control group. Perioperative complication rates, including delayed gastric emptying and pancreatic fistula, LOS, and readmission rates, were similar between the two groups.
CONCLUSIONS: The ERAS protocol provided a minimal decrease in the total complication rates and had no effect on severe complications. Therefore, the ERAS protocol seems feasible and can be applied safely in pancreatic surgery patients.

Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n = 176) received GI-4000 or placebo plus gemcitabine. Subjects\' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. Results: GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13], p = 0.872), and increased frequency of immune responders (40% vs. 8%; p = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo (p = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4+/CD45RA+/Foxp3low) was observed in GI-4000-treated subjects versus placebo (p = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. Conclusion: These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.