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Indocyanine green (ICG) is one of the only clinically approved near-infrared (NIR) fluorophores used during fluorescence-guided surgery (FGS), but it lacks tumor specificity for pancreatic ductal adenocarcinoma (PDAC). Several tumor-targeted fluorescent probes have been evaluated in PDAC patients, yet no uniformity or consensus exists among the surgical community on the current and future needs of FGS during PDAC surgery. In this first-published consensus report on FGS for PDAC, expert opinions were gathered on current use and future recommendations from surgeons' perspectives. A Delphi survey was conducted among international FGS experts via Google Forms. Experts were asked to anonymously vote on 76 statements, with ≥70% agreement considered consensus and ≥80% participation/statement considered vote robustness. Consensus was reached for 61/76 statements. All statements were considered robust. All experts agreed that FGS is safe with few drawbacks during PDAC surgery, but that it should not yet be implemented routinely for tumor identification due to a lack of PDAC-specific NIR tracers and insufficient evidence proving FGS's benefit over standard methods. However, aside from tumor imaging, surgeons suggest they would benefit from visualizing vasculature and surrounding anatomy with ICG during PDAC surgery. Future research could also benefit from identifying neuroendocrine tumors. More research focusing on standardization and combining tumor identification and vital-structure imaging would greatly improve FGS's use during PDAC surgery.

Similar results have been recently reported for a considerably larger series.[1] Our surgical technique intended to minimize intra- and postoperative surgical risks.[2] Patients with significant co-morbidity were excluded, as reflected by the younger median age of patients undergoing arterial resection. A recent publication shows that, thanks to the improved effect of chemotherapy, in many patients with locally advanced pancreatic cancer, arterial resection is not necessary to achieve a radical resection.[8] Pancreatectomy with arterial resection is superior to palliation in patients with borderline resectable or locally advanced pancreatic cancer. [Extracted from the article]

As clearly shown in Table 1 of our paper,[1] the group of patients who underwent resection with radical intent had more often received neoadjuvant treatment, including FOLFIRINOX-based chemotherapy. In fact, it is already known that radiology generally overestimates the cancer stage after neoadjuvant treatment.[2] A further paper with details on our series of patients who have undergone neoadjuvant treatment, is now accepted and currently in press. Indeed, this group of patients represents 2% of the total number of patients that underwent pancreatic operations at our institution during the same time interval. [Extracted from the article]

Carcinoma-associated pancreatic fibroblasts (CAFs) are the major type of cells in the stroma of pancreatic ductal adenocarcinomas and besides their pathological release of extracellular matrix proteins, they are also perceived as key contributors to immune evasion. Despite the known relevance of tumor infiltrating lymphocytes in cancers, the interactions between T-cells and CAFs remain largely unexplored. Here, we found that CAFs isolated from tumors of pancreatic cancer patients undergoing surgical resection ( n = 15) expressed higher levels of the PD-1 ligands PD-L1 and PD-L2 compared to primary skin fibroblasts from healthy donors. CAFs strongly inhibited T-cell proliferation in a contact-independent fashion. Blocking the activity of prostaglandin E 2 (PGE 2 ) by indomethacin partially restored the proliferative capacity of both CD4 + and CD8 + T-cells. After stimulation, the proportion of proliferating T-cells expressing HLA-DR and the proportion of memory T-cells were decreased when CAFs were present compared to T-cells proliferating in the absence of CAFs. Interestingly, CAFs promoted the expression of TIM-3, PD-1, CTLA-4 and LAG-3 in proliferating T-cells. Immunohistochemistry stainings further showed that T-cells residing within the desmoplastic stromal compartment express PD-1, indicating a role for CAFs on co-inhibitory marker expression also in vivo . We further found that PGE 2 promoted the expression of PD-1 and TIM-3 on T-cells. Functional assays showed that proliferating T-cells expressing immune checkpoints produced less IFN-γ, TNF-α, and CD107a after restimulation when CAFs had been present. Thus, this indicates that CAFs induce expression of immune checkpoints on CD4 + and CD8 + T-cells, which contribute to a diminished immune function.

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4 + , CD8 + , as well as CD3 + CD4 - CD8 - T cells with a predominant central memory CD45RA - CCR7 + phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8 + TIL, with low (1.25%) frequencies in CD4 + T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.

Context: LigaSure™ is considered safe in performing pancreaticoduodenectomy (PD). However, no data are available regarding the possible damage of tissues at the resection margins and the impact thereof on histologic margin assessment., Objective: This study compares the degree of histologic damage to the resection margins when using LigaSure™ (Group 1) or traditional ligature (Group 2)., Methods: Both groups included 8 consecutive patients who underwent PD at Karolinska Institute in December 2013 (Group 1) or earlier (Group 2) by the same surgeon (M.D.C.). The quality of tissues at the circumferential margins was compared between both groups by scoring for three different kinds of damage: tissue fragmentation, hemorrhage, and cell damage., Results: The mean score for fragmentation was 1.3 (Group 1) versus 1.7 (Group 2; P=0.1). For hemorrhage the mean score was 0.8 (Group 1) versus 1.5 (Group 2; P=0.04). The mean score for cell damage was 1.4 (Group 1) compared to 1.2 (Group 2; P=0.1)., Conclusions: LigaSure™ does not cause tissue damage that could affect histologic margin assessment in PD specimens.

Aim: To evaluate the impact of body mass index (BMI) on short and long term results after pancreaticoduodenectomies (PD)., Methods: A consecutive series of PDs performed at the Karolinska University Hospital from 2004 till 2010 were retrieved from our prospective database. The patients were divided by BMI into overweight/obese (O; BMI ≥ 25 kg/m(2)) and controls (C; BMI < 25 kg/m(2)). Demographics, peri-operative data, morbidity, mortality, pancreatic fistula (PF) rate, length of stay (LOS), hospital costs, histology, and survival were analyzed. An additional sub analysis of survival was performed in patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC) and divided in underweight, normal-weight, overweight and obese., Results: A total of 367 PDs were included (O = 141/C = 226). No differences were found between O and C regarding demographics, peri-operative data, costs, morbidity or mortality. O was associated with higher intra-operative blood loss (1392 ± 115 mL vs 1121 ± 83 mL; P = 0.01), rate of PF (20% vs 9.5%; P = 0.006) and marginally longer LOS (18 ± 0.9 d vs 15 ± 1.1 d; P = 0.05). An increasing risk for PF was observed with increasing BMI. The 1, 3 and 5 years survival rate was similar in O and C in PDAC (68.7%, 26.4% and 8.8% vs 66.1%, 30.9% and 17.9% respectively; P = 0.9). When the survival was analyzed using 4 different categories of BMI (underweight, normal, overweight and obese), a trend was seen toward a difference in survival, with a worse prognosis for the underweight and obese patients compared to normal weight and overweight patients., Conclusion: Overweight increases the risk for intra-operative bleeding and PF, but do not otherwise alter short or long term outcome after PD for pancreatic cancer.