Intraoperative photodynamic diagnosis of lymph node metastasis in esophageal cancer patients using 5‑aminolevulinic acid

Motoori,Masaaki; Yano,Masahiko; Tanaka,Koji; Kishi,Kentaro; Takahashi,Hidenori; Inoue,Masahiro; Saito,Takuro; Sugimura,Keijiro; Fujiwara,Yoshiyuki; Ishikawa,Osamu; Sakon,Masato

doi:10.3892/ol.2015.3685

Intraoperative photodynamic diagnosis of lymph node metastasis in esophageal cancer patients using 5‑aminolevulinic acid

Authors:
- Masaaki Motoori
- Masahiko Yano
- Koji Tanaka
- Kentaro Kishi
- Hidenori Takahashi
- Masahiro Inoue
- Takuro Saito
- Keijiro Sugimura
- Yoshiyuki Fujiwara
- Osamu Ishikawa
- Masato Sakon
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Affiliations: Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537‑8511, Japan, Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537‑8511, Japan
Published online on: September 8, 2015 https://doi.org/10.3892/ol.2015.3685
Pages: 3035-3039

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Abstract

Lymph node metastasis is the strongest prognostic factor in esophageal cancer patients who have undergone esophagectomy. The accurate diagnosis of lymph node metastasis is important, but the pre‑operative diagnostic accuracy is poor. The intraoperative diagnosis based on histopathological examination of frozen tissue specimens is complicated and time‑consuming. Therefore, the establishment of a simple and rapid intraoperative diagnostic method is essential. Exogenous application of 5‑aminolevulinic acid (ALA) causes a selective accumulation of protoporphyrin IX, which is a fluorescent substrate, in cancer cells. The present study evaluated the feasibility of photodynamic diagnosis using ALA (ALA‑PDD) for lymph node metastasis in esophageal cancer. A total of 292 lymph nodes were analyzed from 8 esophageal squamous cell cancer patients treated with esophagectomy. The patients were administered ALA orally prior to surgery. Excised lymph nodes were cut in half and examined by spectrometer. The diagnostic results of ALA‑PDD were compared to those of the histopathological examination. Among the 292 lymph nodes, 19 nodes (6.5%) were histologically metastatic and 21 nodes (7.2%) were PDD‑positive. The sensitivity and specificity of ALA‑PDD were 84.2% (16/19) and 98.2% (268/273), respectively. The area of cancer nests of the PDD‑negative lymph nodes was <2 mm2. Metastatic lymph nodes, including cancer nests >4 mm2, were correctly diagnosed by ALA‑PDD. In conclusion, this study demonstrated that ALA‑PDD of lymph node metastasis in patients with esophageal cancer is feasible. Further investigation would make this method a simple and rapid intraoperative diagnostic tool.

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1	Akiyama H, Tsurumaru M, Udagawa H and Kajiyama Y: Radical lymph node dissection for cancer of the thoracic esophagus. Ann Surg. 220:364–372. 1994. View Article : Google Scholar : PubMed/NCBI
2	Wu LF, Wang BZ, Feng JL, Cheng WR, Liu GR, Xu XH and Zheng ZC: Preoperative TN staging of esophageal cancer: Comparison of miniprobe ultrasonography, spiral CT and MRI. World J Gastroenterol. 9:219–224. 2003.PubMed/NCBI
3	Nishimaki T, Tanaka O, Ando N, Ide H, Watanabe H, Shinoda M, Takiyama W, Yamana H, Ishida K, Isono K, et al: Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer. Ann Thorac Surg. 68:2059–2064. 1999. View Article : Google Scholar : PubMed/NCBI
4	Yoshioka S, Fujiwara Y, Sugita Y, Okada Y, Yano M, Tamura S, Yasuda T, Takiguchi S, Shiozaki H and Monden M: Real-time rapid reverse transcriptase-polymerase chain reaction for intraoperative diagnosis of lymph node micrometastasis: Clinical application for cervical lymph node dissection in esophageal cancers. Surgery. 132:34–40. 2002. View Article : Google Scholar : PubMed/NCBI
5	Miyata H, Yano M, Doki Y, Yasuda T, Yoshioka S, Sugita Y, Takiguchi S, Fujiwara Y and Monden M: A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis in recurrent laryngeal nerve chain nodes. J Surg Oncol. 93:477–484. 2006. View Article : Google Scholar : PubMed/NCBI
6	Hinnen P, de Rooij FW, van Velthuysen ML, Edixhoven A, van Hillegersberg R, Tilanus HW, Wilson JH and Siersema PD: Biochemical basis of 5-aminolaevulinic acid-induced protoporphyrin IX accumulation: A study in patients with (pre)malignant lesions of the oesophagus. Br J Cancer. 78:679–682. 1998. View Article : Google Scholar : PubMed/NCBI
7	Daniltchenko DI, Riedl CR, Sachs MD, Koenig F, Daha KL, Pflueger H, Loening SA and Schnorr D: Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study. J Urol. 174:2129–2133. 2005. View Article : Google Scholar : PubMed/NCBI
8	Denzinger S, Burger M, Walter B, Knuechel R, Roessler W, Wieland WF and Filbeck T: Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study. Urology. 69:675–679. 2007. View Article : Google Scholar : PubMed/NCBI
9	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
10	Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F and Reulen HJ: ALA-Glioma Study Group: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol. 7:392–401. 2006. View Article : Google Scholar : PubMed/NCBI
11	Sobin LH, Gospodarowicz MK and Wittekind CH: TNM classification of malignant tumors (7th). Wiley-Blackwell. Oxford, UK: 2009.
12	Webber J, Herman N, Kessel D and Fromm D: Current concepts in gastrointestinal photodynamic therapy. Ann Surg. 230:12–23. 1999. View Article : Google Scholar : PubMed/NCBI
13	Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, Roelandts R, Wennberg AM and Morton CA: International Society for Photodynamic Therapy in Dermatology: Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International society for photodynamic therapy in dermatology, 2005. J Am Acad Dermatol. 56:125–143. 2007.
14	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
15	Gaullier JM, Berg K, Peng Q, Anholt H, Selbo PK, Ma LW and Moan J: Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res. 57:1481–1486. 1997.PubMed/NCBI
16	Messmann H, Knuchel R, Bäumler W, Holstege A and Schölmerich J: Endoscopic fluorescence detection of dysplasia in patients with Barrett's esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization. Gastrointest Endosc. 49:97–101. 1999. View Article : Google Scholar : PubMed/NCBI
17	Rhodes LE, de Rie M, Enström Y, Groves R, Morken T, Goulden V, Wong GA, Grob JJ, Varma S and Wolf P: Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol. 140:17–23. 2004. View Article : Google Scholar : PubMed/NCBI
18	Pech O, Gossner L, May A, Rabenstein T, Vieth M, Stolte M, Berres M and Ell C: Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia. Gastrointest Endosc. 62:24–30. 2005. View Article : Google Scholar : PubMed/NCBI