Pancreatic neuroendocrine tumors in French VHL mutation carriers: a multicentric retrospective study.

BACKGROUND: Von Hippel-Lindau disease (VHL) is a rare autosomal dominant hereditary cancer-predisposition syndrome caused by germline pathogenic variants (PV) in VHL gene. It is associated with a high penetrance of benign and malignant vascular tumors in multiples organs, including pancreatic neuroendocrine tumors (PanNETs), whose long-term natural history is ill-known. METHODS: Patients with both documented germline PV in VHL gene and PanNETs included in the French PREDIR database between 1995 and 2022 were included. Primary endpoint was the proportion of patients with PanNET-related metastases and secondary endpoint was overall survival (OS). Genotype/phenotype correlations were studied. RESULTS: We included 121 patients with 259 PanNETs. Median age at diagnosis was 38 years. Median follow-up was 89.5 months. PanNET surgical resection was performed in 51 patients. Overall, 29 patients (24%) had metastases (5 synchronous, 10 metachronous), with a higher risk in case of larger PanNET size (p=0.0089; best threshold 28 mm) and grade 2 PanNET (p=0.048), and a pejorative prognostic impact (p=0.043). Patients with PV in VHL exon 1 had larger PanNETs (p=0.018), more often metastatic disease (48% vs 11.5%; p < 0.001) and a trend toward shorter OS (p=0.16). CONCLUSION: The risk of metastases associated to VHL-related PanNETs remains low (24%) but increases with tumor size >28 mm, higher grade and in case of PV located VHL exon 1. These data might help improving the management of these patients, who should be referred to an expert center.

Distal Pancreatectomy for Body Pancreatic Ductal Adenocarcinoma: Is Splenectomy Necessary? A Propensity Score Matched Study.

BACKGROUND: The value of splenectomy for body localization (≥ 5 cm from spleen hilum) of pancreatic ductal adenocarcinoma (B-PDAC) is uncertain. This study assessed spleen-preserving distal pancreatectomy (SPDP) results for B-PDAC. PATIENTS AND METHODS: This single-center study included patients who underwent SPDP (Warshaw's technique) or distal splenopancreactomy (DSP) for B-PDAC from 2008 to 2019. Propensity score matching was performed to balance SPDP and DSP patients regarding sex, age, American Society of Anesthesiologists (ASA), body mass index (BMI), laparoscopy, pathological features [American Joint Committee on Cancer (AJCC)/tumor node metastasis classification (TNM)], margins, and neoadjuvant/adjuvant therapies. RESULTS: A total of 129 patients (64 male, median age 68 years, median BMI 24 kg/m2) were enrolled with a median follow-up of 63 months (95% CI 52-96 months), including 59 (46%) SPDP and 70 (54%) DSP patients. A total of 39 SPDP patients were matched to 39 DSP patients. SPDP patients had fewer harvested nodes (19 vs 22; p = 0.038) with a similar number of positive nodes (0 vs 0; p = 0.237). R0 margins were achieved similarly in SPDP and DSP patients (75% vs 71%; p = 0.840). SPDP patients were associated with decreased comprehensive complication index (CCI, 8.7 vs 16.6; p = 0.004), rates of grade B/C postoperative pancreatic fistula (POPF, 14% vs 29%; p = 0.047), and hospital stay (11 vs 16 days; p < 0.001). SPDP patients experienced similar disease-free survival (DFS, 5 years: 38% vs 32%; p = 0.180) and overall survival (OS, 5 years 54% vs 44%; p = 0.710). After matching, SPDP patients remained associated with lower CCI (p = 0.034) and hospital stay (p = 0.028) while not associated with risks of local recurrence (HR 0.85; 95% CI 0.28-2.62; p = 0.781), recurrence (HR 1.04; 95% CI 0.61-1.78; p = 0.888), or death (HR 1.20; 95% CI 0.68-2.11; p = 0.556). CONCLUSION: SPDP for B-PDAC is associated with less postoperative morbidity than DSP, without impairing oncological outcomes.

Role of the fatty pancreatic infiltration in pancreatic oncogenesis.

Although pancreatic precancerous lesions are known to be related to obesity and fatty pancreatic infiltration, the mechanisms remain unclear. We assessed the role of fatty infiltration in the process of pancreatic oncogenesis and obesity. A combined transcriptomic, lipidomic and pathological approach was used to explore neoplastic transformations. Intralobular (ILF) and extralobular (ELF) lipidomic profiles were analyzed to search for lipids associated with pancreatic intraepithelial neoplasia (PanINs) and obesity; the effect of ILF and ELF on acinar tissue and the histopathological aspects of pancreatic parenchyma changes in obese (OB) and non-obese patients. This study showed that the lipid composition of ILF was different from that of ELF. ILF was related to obesity and ELF-specific lipids were correlated to PanINs. Acinar cells were shown to have different phenotypes depending on the presence and proximity to ILF in OB patients. Several lipid metabolic pathways, oxidative stress and inflammatory pathways were upregulated in acinar tissue during ILF infiltration in OB patients. Early acinar transformations, called acinar nodules (AN) were linked to obesity but not ELF or ILF suggesting that they are the first reversible precancerous pancreatic lesions to occur in OB patients. On the other hand, the number of PanINs was higher in OB patients and was positively correlated to ILF and ELF scores as well as to fibrosis. Our study suggests that two types of fat infiltration must be distinguished, ELF and ILF. ILF plays a major role in acinar modifications and the development of precancerous lesions associated with obesity, while ELF may play a role in the progression of PDAC.

Outcome and survival were similar with laparoscopic and open pancreatectomy in 102 solid pseudopapillary neoplasms.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPNP) are rare tumors predominantly in young women. We report the largest single-center cohort study comparing resection of SPNP by laparoscopic approach (LA) and the open approach (OA). METHOD: Between 2001 and 2021, 102 patients (84% women, median age: 30) underwent pancreatectomy for SPNP and were retrospectively studied. Demographic, perioperative, pathological, early and the long-term results were evaluated between patients operated by LA and those by OA. RESULTS: Population included 40 LA and 62 OA. There were no significant differences in demographics data between the groups. A preoperative biopsy by endoscopic ultrasound was performed in 45 patients (44%) with no difference between the groups. Pancreatoduodenectomy (PD) was less frequently performed by LA (25 vs 53%, p = 0.004) and distal pancreatectomy (DP) was more frequently performed by LA (40 vs 16%, p = 0.003). In the subgroup analysis by surgical procedure, LA-PD was associated with one mortality, less median blood loss (180 vs 200 ml, p = 0.034) and fewer harvested lymph nodes (11 vs 15, p = 0.02). LA-DP was associated with smaller median tumor size on imaging (40 vs 80mm, p = 0.048), shorter surgery (135 vs 190 min, p = 0.028), and fewer complications according to the median comprehensive complication index score (0 vs 8.7, p = 0.048). LA-Central pancreatectomy was associated with shorter surgery (160 vs 240, p = 0.037), less median blood loss (60 vs 200, p = 0.043), and less harvested lymph nodes (5 vs 2, p = 0.025). After a median follow-up of 60 months, two recurrences (2%) were observed and were unrelated to the approach. CONCLUSIONS: The LA for SPNP appears to be safe, should be applied cautiously in case of PD for large lesion, and was not associated with recurrence.

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial.

PURPOSE: GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS: Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS: Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION: This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.

Characteristics and treatment options of glucagonomas: a national study from the French Group of Endocrine Tumors and ENDOCAN-RENATEN network.

OBJECTIVE: Glucagonoma is a very rare functional pancreatic neuroendocrine tumor (PanNET). We aimed to provide data on the diagnosis, prognosis, and management of patients with glucagonoma. DESIGN AND METHODS: In this retrospective national cohort, we included all patients with glucagonoma, defined by at least 1 major criterion (necrolytic migratory erythema [NME] and/or recent-onset diabetes, and/or weight loss ≥ 5 kg) associated with either glucagonemia > 2 × upper limit of normal or positive glucagon immunostaining. Antisecretory efficacy was defined as partial/complete resolution of glucagonoma symptoms. Antitumor efficacy was assessed according to the time to next treatment (TTNT). RESULTS: Thirty-eight patients were included with median age 58.7 yo, primary PanNET located in the tail (68.4%), synchronous metastases (63.2%). Median Ki-67 index was 3%. Most frequent glucagonoma symptoms at diagnosis were NME (86.8%), weight loss (68.4%), and diabetes (50%). Surgery of the primary PanNET was performed in 76.3% of cases, mainly with curative intent (61.5%). After surgery, complete resolution of NME was seen in 93.8% (n = 15/16). The secretory response rates were 85.7%, 85.7%, 75%, and 60% with surgery of metastases (n = 6/7), chemotherapy (n = 6/7), liver-directed therapy (n = 6/8), and somatostatin analogs (n = 6/10), respectively. All lines combined, longer TTNT was reported with chemotherapy (20.2 months). Median overall survival (OS) was 17.3 years. The Ki-67 index > 3% was associated with shorter OS (hazard ratio 5.27, 95% CI [1.11-24.96], P = .036). CONCLUSION: Patients with glucagonoma had prolonged survival, even in the presence of metastases at diagnosis. Curative-intent surgery should always be considered. Chemotherapy, peptide receptor radionuclide therapy, or liver-directed therapy seems to provide both substantial antitumor and antisecretory efficacies.

The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy.

Pancreatic ductal adenocarcinoma is associated with a poor prognosis and there are few treatment options. The development of immunotherapy in pancreatic ductal adenocarcinoma has been difficult, and immune checkpoint inhibitors are only effective in a very small subset of patients. Most obstacles for treatment have been related to intertumoural and intratumoural heterogeneity, the composition of tumour stroma, and crosstalk with cancer cells. Improved molecular characterisation of pancreatic ductal adenocarcinoma and a better understanding of its microenvironment have paved the way for novel immunotherapy strategies, including the identification of predictive biomarkers, the development of rational combinations to optimise effectiveness, and the targeting of new mechanisms. Future immunotherapy strategies should consider individual characteristics to move beyond the traditional immune targets and circumvent the resistance to therapies that have been developed so far.

Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6).

In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of the tumor mass and is remarkably devoid of functional blood vessels. This raises an unresolved question of how PDAC cells obtain essential metabolites and water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in obtaining and transferring lipids from blood-borne particles to PDAC cells via trogocytosis of CAF plasma membranes. We have also determined that CAF-expressed phospholipid scramblase anoctamin 6 (ANO6) is an essential CAF trogocytosis regulator required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membranes contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membrane initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells. Importantly, ANO6-dependent trogocytosis also supports the immunosuppressive function of pancreatic CAFs towards cytotoxic T cells by promoting transfer of excessive amounts of cholesterol. Further, blockade of ANO6 antagonizes tumor growth via disruption of delivery of exogenous cholesterol to cancer cells and reverses immune suppression suggesting a potential new strategy for PDAC therapy.

High Tumor Uptake on 18F-FDOPA PET/CT Indicates Poor Prognosis in Patients with Metastatic Midgut Neuroendocrine Tumors: A Study from the Groupe d'étude des Tumeurs Endocrines and ENDOCAN-RENATEN Network.

PET/CT with 6-18F-fluoro-l-dopa (18F-FDOPA) has high diagnostic performance for midgut neuroendocrine tumors (NETs). We explored the prognostic role of 18F-FDOPA PET/CT uptake in metastatic midgut NETs. Methods: We included, in a test cohort (n = 166) and a full external validation cohort (n = 86), all consecutive patients with metastatic midgut NETs who underwent 18F-FDOPA PET/CT in 5 expert centers from 2010 to 2021. We measured the maximal uptake (SUVmax and SUVpeak) of the tumor and nontumor liver on each 18F-FDOPA PET/CT scan. We measured overall survival (OS) from the time of PET/CT and assessed prognostic factors using Kaplan-Meier and multivariable Cox proportional-hazards analyses in the test cohort, with replication in the validation cohort. Results: Patients had similar characteristics in both cohorts. In the test cohort, median follow-up was 60.3 mo. Patients with an SUVpeak tumor-to-liver (T/L) ratio of more than 4.2 had significantly shorter survival than those with a ratio of 4.2 or less (P = 0.01), with a 5-y OS rate of 74.1% ± 4.5% versus 95% ± 3.4%, respectively. On multivariable analysis, an SUVpeak T/L ratio of more than 4.2 remained associated with shorter OS (hazard ratio, 2.30; 95% CI, 1.02-5.22; P = 0.046) after adjustment for age, grade, number of previous lines, number of metastatic sites, and presence of carcinoid syndrome. In the validation cohort, the 5-y OS rate was 100% versus 57.8% ± 12.5% in patients with an SUVpeak T/L ratio ≤ 4.2 or > 4.2, respectively (P = 0.075). An increasing SUVpeak T/L ratio over time tended to have a pejorative prognostic impact. Conclusion: Tumor uptake on 18F-FDOPA PET/CT is an independent prognostic factor in patients with metastatic midgut NETs.

Updates in histopathological classification and tissue biomarkers of digestive neuroendocrine neoplasms: What the clinician should know.

Histopathological classifications of neuroendocrine neoplasms (NEN) change regularly and the latest WHO classification published in 2022, which concerns all NEN in the body, attempts to standardize classifications in the different locations. Differentiation and proliferation mainly assessed by Ki-67 index are still the cornerstone of those classifications. However, many markers are now used for diagnostic (to check neuroendocrine differentiation, to identify the site of origin of a metastasis, to help separating high-grade neuroendocrine tumors/NET and neuroendocrine carcinoma/NEC), prognostic or theranostic purposes. NENs are often heterogeneous and this can lead to difficulties in classifications, biomarker and prognostic assessment. These different points are discussed successively in this review, insisting especially on the frequent digestive, gastro-entero-pancreatic (GEP) localizations.

Guidelines on human factors in critical situations 2023.

OBJECTIVE: To provide guidelines to define the place of human factors in the management of critical situations in anaesthesia and critical care. DESIGN: A committee of nineteen experts from the SFAR and GFHS learned societies was set up. A policy of declaration of links of interest was applied and respected throughout the guideline-producing process. Likewise, the committee did not benefit from any funding from a company marketing a health product (drug or medical device). The committee followed the GRADE® method (Grading of Recommendations Assessment, Development and Evaluation) to assess the quality of the evidence on which the recommendations were based. METHODS: We aimed to formulate recommendations according to the GRADE® methodology for four different fields: 1/ communication, 2/ organisation, 3/ working environment and 4/ training. Each question was formulated according to the PICO format (Patients, Intervention, Comparison, Outcome). The literature review and recommendations were formulated according to the GRADE® methodology. RESULTS: The experts' synthesis work and application of the GRADE® method resulted in 21 recommendations. Since the GRADE® method could not be applied in its entirety to all the questions, the guidelines used the SFAR "Recommendations for Professional Practice" A means of secured communication (RPP) format and the recommendations were formulated as expert opinions. CONCLUSION: Based on strong agreement between experts, we were able to produce 21 recommendations to guide human factors in critical situations.

Detection of Nine Oncogenes Amplification in Lung and Colorectal Cancer Formalin-Fixed Paraffin-Embedded Tissue Samples using Combined Next-Generation Sequencing-Based Script and Digital Droplet Polymerase Chain Reaction.

INTRODUCTION: Gene copy number variations have theranostic impact and require reliable methods for their identification. We aimed to evaluate the reliability of combined next-generation sequencing (NGS) and digital droplet PCR (ddPCR) method for gene amplification evaluation. METHODS: We conducted a retrospective multicentric observational study. MET/ERBB2 amplifications were assessed in patients with lung or colorectal carcinoma (cohort A), from 2016 to 2020, by fluorescence in situ hybridization (FISH)/immunohistochemistry (IHC), NGS and ddPCR. NGS-based script and ddPCR were then used to detect amplifications of 7 additional oncogenes (EGFR, KRAS, BRAF, FGFR1, FGFR2, FGFR3, PIK3CA) in a cohort of patients (cohort B). RESULTS: 55 patients (9 control, 25 ERBB2-amplified and 21 MET-amplified) out of 3779 patients tested were included in cohort A. Correlation coefficient between NGS-based script and FISH/IHC results were .88 for MET (P < .001) and .89 (P < .001) for ERBB2. Using a threshold ratio of 1.56 with the NGS-based script, the sensitivity was 100% for both genes and the specificity 69% for MET and 90% for ERBB2, respectively. With an alternative 1.76 threshold, sensitivity was 94% for MET and 96% for ERBB2, while specificity was 85% for MET and 90% for ERBB2. Correlation coefficient between FISH and ddPCR ratio was .90 for MET and .88 for ERBB2. In both cohorts, NGS-based script and ddPCR results were significantly correlated regarding all genes (P < .001). CONCLUSION: Combined NGS-based script and ddPCR method is reliable and easily feasible for the detection of gene amplifications, providing useful data for guided therapy in cancer.

Spatial and temporal heterogeneity of digestive neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are initially monoclonal neoplasms that progressively become polyclonal, with very different genotypic and phenotypic characteristics leading to biological differences, including the Ki-67 proliferation index, morphology, or sensitivity to treatments. Whereas inter-patient heterogeneity has been well described, intra-tumor heterogeneity has been little studied. However, NENs present a high degree of heterogeneity, both spatially within the same location or between different lesions, and through time. This can be explained by the emergence of tumor subclones with different behaviors. These subpopulations can be distinguished by the Ki-67 index, but also by the expression of hormonal markers or by differences in the intensity of uptake on metabolic imaging, such as 68Ga-somatostatin receptor and Fluorine-18 fluorodeoxyglucose positron emission tomography. As these features are directly related to prognosis, it seems mandatory to move toward a standardized, improved selection of the tumor areas to be studied to be as predictive as possible. The temporal evolution of NENs frequently leads to changes in tumor grade over time, with impact on prognosis and therapeutic decision-making. However, there is no recommendation regarding systematic biopsy of NEN recurrence or progression, and which lesion to sample. This review aims to summarize the current state of knowledge, the main hypotheses, and the main implications regarding intra-tumor spatial and temporal heterogeneity in digestive NENs.

Pacpaint: a histology-based deep learning model uncovers the extensive intratumor molecular heterogeneity of pancreatic adenocarcinoma.

Two tumor (Classical/Basal) and stroma (Inactive/active) subtypes of Pancreatic adenocarcinoma (PDAC) with prognostic and theragnostic implications have been described. These molecular subtypes were defined by RNAseq, a costly technique sensitive to sample quality and cellularity, not used in routine practice. To allow rapid PDAC molecular subtyping and study PDAC heterogeneity, we develop PACpAInt, a multi-step deep learning model. PACpAInt is trained on a multicentric cohort (n = 202) and validated on 4 independent cohorts including biopsies (surgical cohorts n = 148; 97; 126 / biopsy cohort n = 25), all with transcriptomic data (n = 598) to predict tumor tissue, tumor cells from stroma, and their transcriptomic molecular subtypes, either at the whole slide or tile level (112 µm squares). PACpAInt correctly predicts tumor subtypes at the whole slide level on surgical and biopsies specimens and independently predicts survival. PACpAInt highlights the presence of a minor aggressive Basal contingent that negatively impacts survival in 39% of RNA-defined classical cases. Tile-level analysis ( > 6 millions) redefines PDAC microheterogeneity showing codependencies in the distribution of tumor and stroma subtypes, and demonstrates that, in addition to the Classical and Basal tumors, there are Hybrid tumors that combine the latter subtypes, and Intermediate tumors that may represent a transition state during PDAC evolution.

Performance of a blood-based RNA signature for gemcitabine-based treatment in metastatic pancreatic adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, and chemotherapy is a key treatment for advanced PDAC. Gemcitabine chemotherapy is still an important component of treatment; however, there is no routine biomarker to predict its efficacy. Predictive tests may help clinicians to decide on the best first-line chemotherapy. Methods: This study is a confirmatory study of a blood-based RNA signature, called the GemciTest. This test measures the expression levels of nine genes using real-time polymerase chain reaction (PCR) processes. Clinical validation was carried out, through a discovery and a validation phases, on 336 patients (mean 68.7 years; range, 37-88 years) for whom blood was collected from two prospective cohorts and two tumor biobanks. These cohorts included previously untreated advanced PDAC patients who received either a gemcitabine- or fluoropyrimidine-based regimen. Results: Gemcitabine-based treated patients with a positive GemciTest (22.9%) had a significantly longer progression-free survival (PFS) {5.3 vs. 2.8 months; hazard ratio (HR) =0.53 [95% confidence interval (CI): 0.31-0.92]; P=0.023} and overall survival (OS) [10.4 vs. 4.8 months; HR =0.49 (95% CI: 0.29-0.85); P=0.0091]. On the contrary, fluoropyrimidine-based treated patients showed no significant difference in PFS and OS using this blood signature. Conclusions: The GemciTest demonstrated that a blood-based RNA signature has the potential to aid in personalized therapy for PDAC, leading to better survival rates for patients receiving a gemcitabine-based first-line treatment.

Quantitative imaging predicts pancreatic fatty infiltration on routine CT examination.

PURPOSE: The purpose of this study was to assess the performance of quantitative computed tomography (CT) imaging for detecting pancreatic fatty infiltration, using the results of histopathological analysis as reference. MATERIALS AND METHODS: Sixty patients who underwent pancreatic surgery for a pancreatic tumor between 2016 and 2019 were retrospectively included. There were 33 women and 27 men with a mean age of 56 ± 12 (SD) years (age range: 18-79 years). Patients with dilatation of the main pancreatic duct, chronic pancreatitis, or preoperative treatment were excluded to prevent any bias in the radiological-pathological correlation. Pancreatic fatty infiltration was recorded at pathology. Pancreatic surface lobularity, pancreatic attenuation, visceral fat area, and subcutaneous fat area were derived from preoperative CT images. The performance for the prediction of fatty infiltration was assessed using area under receiver operating characteristic curve (AUC) and backward binary logistic regression analysis. Results were validated in a separate cohort of 34 patients (17 women; mean age, 50 ± 14 [SD] years; age range: 18-73). RESULTS: A total of 28/60 (47%) and 17/34 (50%) patients had pancreatic fatty infiltration in the derivation and validation cohorts, respectively. In the derivation cohort, patients with pancreatic fatty infiltration had a significantly higher PSL (P < 0.001) and a lower pancreatic attenuation on both precontrast and portal venous phase images (P = 0.011 and 0.003, respectively), and higher subcutaneous fat area and visceral fat area (P = 0.010 and 0.007, respectively). Multivariable analysis identified pancreatic surface lobularity > 7.6 and pancreatic attenuation on portal venous phase images < 83.5 Hounsfield units as independently associated with fatty infiltration. The combination of these variables resulted in an AUC of 0.85 (95% CI: 0.74-0.95) and 0.83 (95% CI: 0.67-0.99) in the derivation and validation cohorts, respectively. CONCLUSION: CT-based quantitative imaging accurately predicts pancreatic fatty infiltration.

68 Ga-DOTATOC PET/CT Imaging of a Muscular Solitary Fibrous Tumor.

ABSTRACT: A 73-year-old woman was referred for 68 Ga-DOTATOC PET/CT staging of a grade 2 pancreatic neuroendocrine tumor, which showed the primary pancreatic tumor, liver metastases, one left pleural metastasis, and high uptake in a mass of the right triceps brachii muscle. Two years before, she underwent 18 F-FDG PET/CT and 111 In-pentetreotide scan, respectively, with low and high uptake of each radiotracer in the triceps mass. Histopathological analysis revealed a solitary fibrous tumor. Immunohistochemistry showed no staining for SSTR-2 and SSTR-5, suggesting tumor overexpression of another somatostatin receptor. This case highlighted a potential pitfall on 68 Ga-DOTATOC PET/CT.

Laparoscopic intraoperative pancreatoscopy for main duct intraductal papillary mucinous neoplasms assessment.

Video 1Intraoperative pancreatoscopy during laparoscopic pancreatic resection for main pancreatic duct intraductal papillary mucinous neoplasms.