Essential updates 2018/2019: Current topics in the surgical treatment of pancreatic ductal adenocarcinoma

Ishido, Keinosuke; Hakamada, Kenichi; Kimura, Norihisa; Miura, Takuya; Wakiya, Taiichi

doi:10.1002/ags3.12379

Cited by 24 publications

(30 citation statements)

References 209 publications

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“…To analyze the effects of PDGL-GEM@CAP/CQ on PDAC metastasis, we grew orthotopic Pan 02 tumors in mice. Such tumors metastasize primarily to the septum and mesentery, which reasonably mimics the clinical situation, in which more than 80% of cases of locally advanced pancreatic cancer metastasize to the peritoneal/omentum and liver 30 , 31 . Similar to the results in the xenograft model, PDGL-GEM@CAP/CQ showed the strongest anti-tumor effects (Figure 7 A-B) and it induced the greatest extent of necrosis as well as the greatest inhibition of fibroblast activation (Figure 7 C).…”

Section: Resultsmentioning

confidence: 81%

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Chen

Yuan

et al. 2021

Theranostics

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Background: Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. Methods: To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Gemcitabine (GEM), a first-line chemotherapeutic drug against PDAC, was loaded in 6PA-modified DGL (PDGL) nanoparticles to afford PDGL-GEM. Then PDGL-GEM was co-precipitated with the autophagy inhibitor chloroquine phosphate (CQ) and calcium phosphate to formulate PDGL-GEM@CAP/CQ. The size and morphology of the resulting “nanobomb” PDGL-GEM@CAP/CQ were characterized, and their uptake into cells, cytotoxicity and ability to inhibit autophagy were analyzed at pH 6.5 and 7.4. The anti-tumor and anti-metastasis effects of the nanobomb were explored on mice carrying Pan 02 pancreatic tumor xenografts or orthotopic tumors. Results: The pH-induced dissolution of calcium phosphate facilitated the release of CQ from the nanobomb and deep penetration of PDGL-GEM. The internalization of PDGL-GEM and subsequent intracellular release of GEM inhibited tumor growth, while CQ downregulated autophagy in tumor cells and fibroblasts. In fact, inhibition of xenograft and orthotopic tumor growth was greater with the complete PDGL-GEM@CAP/CQ than with subassemblies lacking GEM or CQ. More importantly, mechanistic studies in vitro and in vivo suggested that the nanobomb inhibits metastasis by downregulating MMP-2 and paxillin, as well as reducing fibrosis. Conclusion: The pH-sensitive PDGL-GEM@CAP/CQ shows potential for inhibiting proliferation and metastasis of pancreatic cancer through an autophagy-dependent pathway.

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Section: Resultsmentioning

confidence: 81%

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Chen

Yuan

et al. 2021

Theranostics

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“…38 Since then, many investigators have reported that the antigen was expressed not only in colorectal cancer but also in other gastrointestinal cancers such as PDAC and cholangiocarcinoma. 39,40 In PDAC, serum CA19-9 levels have been reported to reflect the prognosis of PDAC, 11,41,42 and the link between cutoff values of preoperative serum CA19-9 levels and early postoperative recurrence and poor prognosis was also investigated. 20,30,[43][44][45][46][47] On the other hand, SPan-1 is a cancer-related antigen recognized by a monoclonal antibody prepared using the human PDAC cell line SW1990 as an immune antigen, and it is a high-molecularweight mucin-like protein.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the question of how to control such a malignant behavior has become a big challenge, even for patients with resectable PDAC. 11 Previous studies investigated factors related to the uncontrollable behavior of PDAC. 12,13 In particular, serum CA19-9 level is known to correlate with postoperative prognosis, and its association with early postoperative recurrence has also attracted attention.…”

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confidence: 99%

Development of a Biomarker-Based Scoring System Predicting Early Recurrence of Resectable Pancreatic Duct Adenocarcinoma

et al. 2021

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Background Resectable pancreatic ductal adenocarcinoma (R-PDAC) often recurs early after radical resection, which is associated with poor prognosis. Predicting early recurrence preoperatively is useful for determining the optimal treatment. Patients and methods One hundred and seventy-eight patients diagnosed with R-PDAC on computed tomography (CT) imaging and undergoing radical resection at Hirosaki University Hospital from 2005 to 2019 were retrospectively analyzed. Patients with recurrence within 6 months after resection formed the early recurrence (ER) group, while other patients constituted the non-early recurrence (non-ER) group. Early recurrence prediction score (ERP score) was developed using preoperative parameters. Results ER was observed in 45 patients (25.3%). The ER group had significantly higher preoperative CA19-9 (p = 0.03), serum SPan-1 (p = 0.006), and CT tumor diameter (p = 0.01) compared with the non-ER group. The receiver operating characteristic (ROC) curve analysis identified cutoff values for CA19-9 (133 U/mL), SPan-1 (78.2 U/mL), and preoperative tumor diameter (23 mm). When the parameter exceeded the cutoff level, 1 point was given, and the total score of the three factors was defined as the ERP score. The group with an ERP score of 3 had postoperative recurrence-free survival (RFS) of 5.5 months (95% CI 3.02–7.98). Multivariate analysis for ER-related perioperative and surgical factors identified ERP score of 3 [odds ratio (OR) 4.63 (95% CI 1.82–11.78), p = 0.0013] and R1 resection [OR 3.20 (95% CI 1.01–10.17), p = 0.049] as independent predictors of ER. Conclusions For R-PDAC, ER could be predicted by the scoring system using preoperative serum CA19-9 and SPan-1 levels and CT tumor diameter, which may have great significance in identifying patients with poor prognoses and avoiding unnecessary surgery.

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“…Ductal adenocarcinoma is the most common malignancy of the pancreas. Accordingly, this tumor presents a substantial health problem worldwide 5,6 …”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, this tumor presents a substantial health problem worldwide. 5,6 Through exome sequencing of PDAC surgical specimens, in a very interesting study, Biankin et al demonstrated that the axon guidance gene family was the most frequently altered gene family. 7 Their findings suggest the potential involvement of the nervous system in PDAC carcinogenesis.In clinical pancreatic cancer management, perineural invasion (PNI) is the most significant nerve-related problem.…”

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confidence: 99%

Roles of the nervous system in pancreatic cancer

Wakiya

Ishido

Yoshizawa

et al. 2021

Annals of Gastroent Surgery

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Pancreatic ductal adenocarcinoma (PDAC), with its extremely poor prognosis, presents a substantial health problem worldwide. Outcomes have improved thanks to progress in surgical technique, chemotherapy, pre‐/postoperative management, and centralization of patient care to high‐volume centers. However, our goals are yet to be met. Recently, exome sequencing using PDAC surgical specimens has demonstrated that the most frequently altered genes were the axon guidance genes, indicating involvement of the nervous system in PDAC carcinogenesis. Moreover, perineural invasion has been widely identified as one poor prognostic factor. The combination of innovative technologies and extensive clinician experience with the nervous system come together here to create a new treatment option. However, evidence has emerged that suggests that the relationship between cancer and nerves in PDAC, the underlying mechanism, is not fully understood. In an attempt to tackle this lethal cancer, this review summarizes the anatomy and physiology of the pancreas and discusses the role of the nervous system in the pathophysiology of PDAC.

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Essential updates 2018/2019: Current topics in the surgical treatment of pancreatic ductal adenocarcinoma

Cited by 24 publications

References 209 publications

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Development of a Biomarker-Based Scoring System Predicting Early Recurrence of Resectable Pancreatic Duct Adenocarcinoma

Roles of the nervous system in pancreatic cancer

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