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Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients

  • Original article
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Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Purpose

To determine the feasibility, safety and histological change of preoperative endoscopic ultrasound-guided fine-needle injection (PEU-FNI) of immature DCs (iDCs) with OK-432 in pancreatic cancer patients.

Methods

Nine patients enrolled in the trial (DC group) and were compared with 15 patients operated on without iDC injection (non-DC group). Adverse events of PEU-FNI and postoperative complications were evaluated according to CTC-AE ver.3.0 and the Clavien–Dindo classification/ISGPF definition, respectively. Histological changes within the tumor and lymph nodes were evaluated by immunohistochemical examination of infiltrating inflammatory cells (CD4+, CD8+, Foxp3+ and CD83+).

Results

There were no severe toxicities following PEU-FNI, except for one transient grade 3 fever, and there were no significant differences in the incidence of postoperative complications between the two groups. Colliquative necrosis and diffusely scattered TUNEL-positive cells were observed at the injection sites. CD83+ cells significantly accumulated in the regional lymph nodes of the DC group as well as Foxp3+ cells in the regional and distant lymph nodes. The two DC group patients, one of which was stage IV with distant lymph node metastasis, survived more than 5 years without requiring adjuvant theraphy.

Conclusion

PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.

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Acknowledgments

This research was supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Health, Labour and Welfare (MO20591636). We thank Dr. Atsushi Irisawa and Dr. Hiromasa Ohohira for endoscopic intratumoral dendritic cell injections, and Dr. Hitoshi Ohto for dendritic cell production.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Regenerative Surgery, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan

    Hisahito Endo, Akira Kenjo, Mika Hoshino, Tetsu Sato, Takayuki Anazawa, Takashi Kimura, Takao Tsuchiya & Mitsukazu Gotoh

  2. Department of Surgery, Fukushima Prefectural Aizu General Hospital, 10-75 Shiromae, Aizuwakamatsu, Fukushima, 965-8555, Japan

    Takuro Saito

  3. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Masanori Terashima

  4. Department of Internal Medicine, Fukushima Prefectural Aizu General Hospital, 10-75 Shiromae, Aizuwakamatsu, Fukushima, 965-8555, Japan

    Atsushi Irisawa

  5. Department of Gastroenterology and Rheumatology, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan

    Hiromasa Ohira, Takuto Hikichi & Tadayuki Takagi

Authors
  1. Hisahito Endo
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  2. Takuro Saito
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  10. Atsushi Irisawa
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  14. Mitsukazu Gotoh
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Corresponding author

Correspondence to Mitsukazu Gotoh.

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Endo, H., Saito, T., Kenjo, A. et al. Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK-432 for resectable pancreatic cancer patients. J Hepatobiliary Pancreat Sci 19, 465–475 (2012). https://doi.org/10.1007/s00534-011-0457-7

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  • DOI: https://doi.org/10.1007/s00534-011-0457-7

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