Photodynamic diagnosis of peritoneal metastasis in human pancreatic cancer using 5‑aminolevulinic acid during staging laparoscopy

Harada,Kyoichi; Murayama,Yasutoshi; Kubo,Hidemasa; Matsuo,Hisataka; Morimura,Ryo; Ikoma,Hisashi; Fujiwara,Hitoshi; Okamoto,Kazuma; Tanaka,Tohru; Otsuji,Eigo

doi:10.3892/ol.2018.8732

Photodynamic diagnosis of peritoneal metastasis in human pancreatic cancer using 5‑aminolevulinic acid during staging laparoscopy

Authors:
- Kyoichi Harada
- Yasutoshi Murayama
- Hidemasa Kubo
- Hisataka Matsuo
- Ryo Morimura
- Hisashi Ikoma
- Hitoshi Fujiwara
- Kazuma Okamoto
- Tohru Tanaka
- Eigo Otsuji
View Affiliations

Affiliations: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602‑8566, Japan, SBI Pharmaceuticals Co., Ltd., Izumi Garden Tower 20F, Tokyo 106‑6020, Japan
Published online on: May 17, 2018 https://doi.org/10.3892/ol.2018.8732
Pages: 821-828
Copyright: © Harada et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Peritoneal metastasis is an important prognostic factor for pancreatic cancer. The present study evaluated the possibility of diagnosing peritoneal metastasis by a photodynamic diagnosis using 5‑aminolevulinic acid (5‑ALA‑PDD). In vitro, protoporphyrin IX (PpIX) accumulation was examined in the AsPC‑1‑GFP cell line following 5‑ALA hydrochloride administration. In vivo, AsPC‑1‑GFP cells were injected into the peritoneal cavities of mice. Three weeks later 5‑ALA hydrochloride was intraperitoneally administered to the mice. The peritoneal nodules were observed under fluorescence excitation. A total of 34 patients were enrolled in the present study who were clinically diagnosed with pancreatic malignancy. 5‑ALA hydrochloride was orally administered to the patients prior to surgery. During the operation the abdominal cavity was observed under white light and fluorescence. In vitro and in vivo, it was confirmed that PpIX‑induced red fluorescence. In 9 patients peritoneal nodules suspected to be peritoneal metastasis were observed under white light. In 4 of the 9 patients nodules were detected on the basis of the fluorescence images. Fluorescent nodules were histopathologically diagnosed as metastatic. In the present study it was confirmed that 5‑ALA‑PDD holds promise for the rapid diagnosis of peritoneal metastasis in patients with pancreatic cancer.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Tewari M: Pancreatic cancer: A challenge to cure. Indian J Surg. 77:350–357. 2015. View Article : Google Scholar : PubMed/NCBI
3	Vincent A, Herman J, Schulick R, Hruban RH and Goggins M: Pancreatic cancer. Lancet. 378:607–620. 2011. View Article : Google Scholar : PubMed/NCBI
4	Gall TM, Tsakok M, Wasan H and Jiao LR: Pancreatic cancer: Current management and treatment strategies. Postgrad Med J. 91:601–607. 2015. View Article : Google Scholar : PubMed/NCBI
5	Michl P, Pauls S and Gress TM: Evidence-based diagnosis and staging of pancreatic cancer. Best Pract Res Clin Gastroenterol. 20:227–251. 2006. View Article : Google Scholar : PubMed/NCBI
6	Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK and Hruban RH: Recent progress in pancreatic cancer. CA Cancer J Clin. 63:318–348. 2013. View Article : Google Scholar : PubMed/NCBI
7	Pietryga JA and Morgan DE: Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol. 6:343–357. 2015.PubMed/NCBI
8	Cid-Arregui A and Juarez V: Perspectives in the treatment of pancreatic adenocarcinoma. World J Gastroenterol. 21:9297–9316. 2015. View Article : Google Scholar : PubMed/NCBI
9	Morak MJ, Hermans JJ, Smeenk HG, Renders WM, Nuyttens JJ, Kazemier G and van Eijck CH: Staging for locally advanced pancreatic cancer. Eur J Surg Oncol. 35:963–968. 2009. View Article : Google Scholar : PubMed/NCBI
10	Baekelandt BM, Hjermstad MJ, Nordby T, Fagerland MW, Kure EH, Heiberg T, Buanes T and Labori KJ: Preoperative cognitive function predicts survival in patients with resectable pancreatic ductal adenocarcinoma. HPB (Oxford). 18:247–254. 2016. View Article : Google Scholar : PubMed/NCBI
11	Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H and Kleeff J: Preoperative/neoadjuvant therapy in pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. PLoS Med. 7:e10002672010. View Article : Google Scholar : PubMed/NCBI
12	Hartwig W, Hackert T, Hinz U, Gluth A, Bergmann F, Strobel O, Büchler MW and Werner J: Pancreatic cancer surgery in the new millennium: Better prediction of outcome. Ann Surg. 254:311–319. 2011. View Article : Google Scholar : PubMed/NCBI
13	He J, Ahuja N, Makary MA, Cameron JL, Eckhauser FE, Choti MA, Hruban RH, Pawlik TM and Wolfgang CL: 2564 resected periampullary adenocarcinomas at a single institution: Trends over three decades. HPB (Oxford). 16:83–90. 2014. View Article : Google Scholar : PubMed/NCBI
14	Yamaguchi K, Okusaka T, Shimizu K, Furuse J, Ito Y, Hanada K and Shimosegawa T: Committee for revision of clinical guidelines for pancreatic cancer of Japan Pancreas Society: EBM-based Clinical Guidelines for Pancreatic Cancer (2013) issued by the Japan Pancreas Society: A synopsis. Jpn J Clin Oncol. 44:883–888. 2014. View Article : Google Scholar : PubMed/NCBI
15	Lermite E, Sommacale D, Piardi T, Arnaud JP, Sauvanet A, Dejong CH and Pessaux P: Complications after pancreatic resection: Diagnosis, prevention and management. Clin Res Hepatol Gastroenterol. 37:230–239. 2013. View Article : Google Scholar : PubMed/NCBI
16	Kimura W, Miyata H, Gotoh M, Hirai I, Kenjo A, Kitagawa Y, Shimada M, Baba H, Tomita N, Nakagoe T, et al: A pancreaticoduodenectomy risk model derived from 8575 cases from a national single-race population (Japanese) using a web-based data entry system: The 30-day and in-hospital mortality rates for pancreaticoduodenectomy. Ann Surg. 259:773–780. 2014. View Article : Google Scholar : PubMed/NCBI
17	Seppänen H, Juuti A, Mustonen H, Haapamäki C, Nordling S, Carpelan-Holmström M, Sirén J, Luettges J, Haglund C and Kiviluoto T: The results of pancreatic resections and long-term survival for pancreatic ductal adenocarcinoma: A single-institution experience. Scand J Surg. 106:54–61. 2017. View Article : Google Scholar : PubMed/NCBI
18	Schnelldorfer T, Gagnon AI, Birkett RT, Reynolds G, Murphy KM and Jenkins RL: Staging laparoscopy in pancreatic cancer: A potential role for advanced laparoscopic techniques. J Am Coll Surg. 218:1201–1206. 2014. View Article : Google Scholar : PubMed/NCBI
19	Sugiura T, Uesaka K, Mihara K, Sasaki K, Kanemoto H, Mizuno T and Okamura Y: Margin status, recurrence pattern, and prognosis after resection of pancreatic cancer. Surgery. 154:1078–1086. 2013. View Article : Google Scholar : PubMed/NCBI
20	Adham M, Jaeck D, Le Borgne J, Oussoultzouglou E, Chenard-Neu MP, Mosnier JF, Scoazec JY, Mornex F and Partensky C: Long-term survival (5–20 years) after pancreatectomy for pancreatic ductal adenocarcinoma: A series of 30 patients collected from 3 institutions. Pancreas. 37:352–357. 2008. View Article : Google Scholar : PubMed/NCBI
21	Hemming AW, Nagy AG, Scudamore CH and Edelmann K: Laparoscopic staging of intraabdominal malignancy. Surg Endosc. 9:325–328. 1995. View Article : Google Scholar : PubMed/NCBI
22	Mayo SC, Austin DF, Sheppard BC, Mori M, Shipley DK and Billingsley KG: Evolving preoperative evaluation of patients with pancreatic cancer: Does laparoscopy have a role in the current era? J Am Coll Surg. 208:87–95. 2009. View Article : Google Scholar : PubMed/NCBI
23	Gahlen J, Stern J, Laubach HH, Pietschmann M and Herfarth C: Improving diagnostic staging laparoscopy using intraperitoneal lavage of delta-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis. Surgery. 126:469–473. 1999. View Article : Google Scholar : PubMed/NCBI
24	Zöpf T, Schneider AR, Weickert U, Riemann JF and Arnold JC: Improved preoperative tumor staging by 5-aminolevulinic acid induced fluorescence laparoscopy. Gastrointest Endosc. 62:763–767. 2005. View Article : Google Scholar : PubMed/NCBI
25	Kennedy JC and Pottier RH: Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B. 14:275–292. 1992. View Article : Google Scholar : PubMed/NCBI
26	Peng Q, Warloe T, Berg K, Moan J, Kongshaug M, Giercksky KE and Nesland JM: 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer. 79:2282–2308. 1997. View Article : Google Scholar : PubMed/NCBI
27	Kriegmair M, Baumgartner R, Knüchel R, Stepp H, Hofstädter F and Hofstetter A: Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. J Urol. 155:105–110. 1996. View Article : Google Scholar : PubMed/NCBI
28	Jichlinski P, Forrer M, Mizeret J, Glanzmann T, Braichotte D, Wagnières G, Zimmer G, Guillou L, Schmidlin F, Graber P, et al: Clinical evaluation of a method for detecting superficial surgical transitional cell carcinoma of the bladder by light-induced fluorescence of protoporphyrin IX following the topical application of 5-aminolevulinic acid: Preliminary results. Lasers Surg Med. 20:402–408. 1997. View Article : Google Scholar : PubMed/NCBI
29	Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R and Reulen HJ: Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. Neurosurgery. 42:518–526. 1998. View Article : Google Scholar : PubMed/NCBI
30	Friesen SA, Hjortland GO, Madsen SJ, Hirschberg H, Engebraten O, Nesland JM and Peng Q: 5-Aminolevulinic acid-based photodynamic detection and therapy of brain tumors (review). Int J Oncol. 21:577–582. 2002.PubMed/NCBI
31	Murayama Y, Harada Y, Imaizumi K, Dai P, Nakano K, Okamoto K, Otsuji E and Takamatsu T: Precise detection of lymph node metastases in mouse rectal cancer by using 5-aminolevulinic acid. Int J Cancer. 125:2256–2263. 2009. View Article : Google Scholar : PubMed/NCBI
32	Murayama Y, Ichikawa D, Koizumi N, Komatsu S, Shiozaki A, Kuriu Y, Ikoma H, Kubota T, Nakanishi M, Harada Y, et al: Staging fluorescence laparoscopy for gastric cancer by using 5-aminolevulinic acid. Anticancer Res. 32:5421–5427. 2012.PubMed/NCBI
33	Hatakeyama T, Murayama Y, Komatsu S, Shiozaki A, Kuriu Y, Ikoma H, Nakanishi M, Ichikawa D, Fujiwara H, Okamoto K, et al: Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes in human colon cancer cells. Oncol Rep. 29:911–916. 2013. View Article : Google Scholar : PubMed/NCBI
34	Hino H, Murayama Y, Nakanishi M, Inoue K, Nakajima M and Otsuji E: 5-Aminolevulinic acid-mediated photodynamic therapy using light-emitting diodes of different wavelengths in a mouse model of peritoneally disseminated gastric cancer. J Surg Res. 185:119–126. 2013. View Article : Google Scholar : PubMed/NCBI
35	Koizumi N, Harada Y, Murayama Y, Harada K, Beika M, Yamaoka Y, Dai P, Komatsu S, Kubota T, Ichikawa D, et al: Detection of metastatic lymph nodes using 5-aminolevulinic acid in patients with gastric cancer. Ann Surg Oncol. 20:3541–3548. 2013. View Article : Google Scholar : PubMed/NCBI
36	Kondo Y, Murayama Y, Konishi H, Morimura R, Komatsu S, Shiozaki A, Kuriu Y, Ikoma H, Kubota T, Nakanishi M, et al: Fluorescent detection of peritoneal metastasis in human colorectal cancer using 5-aminolevulinic acid. Int J Oncol. 45:41–46. 2014. View Article : Google Scholar : PubMed/NCBI
37	Nishimura M, Murayama Y, Harada K, Kamada Y, Morimura R, Ikoma H, Ichikawa D, Fujiwara H, Okamoto K and Otsuji E: Photodynamic diagnosis of hepatocellular carcinoma using 5-aminolevulinic acid. Anticancer Res. 36:4569–4574. 2016. View Article : Google Scholar : PubMed/NCBI
38	Hartwig W, Werner J, Jäger D, Debus J and Büchler MW: Improvement of surgical results for pancreatic cancer. Lancet Oncol. 14:e476–e485. 2013. View Article : Google Scholar : PubMed/NCBI
39	Callery MP, Chang KJ, Fishman EK, Talamonti MS, Traverso William L and Linehan DC: Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement. Ann Surg Oncol. 16:1727–1733. 2009. View Article : Google Scholar : PubMed/NCBI
40	Pearlstone DB, Mansfield PF, Curley SA, Kumparatana M, Cook P and Feig BW: Laparoscopy in 533 patients with abdominal malignancy. Surgery. 125:67–72. 1999. View Article : Google Scholar : PubMed/NCBI
41	Shoup M, Brennan MF, Karpeh MS, Gillern SM, McMahon RL and Conlon KC: Port site metastasis after diagnostic laparoscopy for upper gastrointestinal tract malignancies: An uncommon entity. Ann Surg Oncol. 9:632–636. 2002. View Article : Google Scholar : PubMed/NCBI
42	Reymond MA, Schneider C, Kastl S, Hohenberger W and Köckerling F: The pathogenesis of port-site recurrences. J Gastrointest Surg. 2:406–414. 1998. View Article : Google Scholar : PubMed/NCBI
43	Kishi K, Fujiwara Y, Yano M, Inoue M, Miyashiro I, Motoori M, Shingai T, Gotoh K, Takahashi H, Noura S, et al: Staging laparoscopy using ALA-mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer. J Surg Oncol. 106:294–298. 2012. View Article : Google Scholar : PubMed/NCBI
44	Conio M, Demarquay JF, De Luca L, Marchi S and Dumas R: Endoscopic treatment of pancreatico-biliary malignancies. Crit Rev Oncol Hematol. 37:127–135. 2001. View Article : Google Scholar : PubMed/NCBI