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Review
. 2017 Mar 1;9(3):23.
doi: 10.3390/cancers9030023.

Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA)

Yutaka Yonemura  1   2   3 , Yoshio Endo  4 , Emel Canbay  5 , Yang Liu  6 , Haruaki Ishibashi  7 , Akiyoshi Mizumoto  8 , Masamitu Hirano  9 , Yuuki Imazato  10 , Nobuyuki Takao  11 , Masumi Ichinose  12 , Kousuke Noguchi  13 , Yan Li  14 , Satoshi Wakama  15 , Kazuhiro Yamada  16 , Koutarou Hatano  17 , Hiroshi Shintani  18 , Hiroyuki Yoshitake  19 , Shun-Ichiro Ogura  20
Affiliations
Review

Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA)

Yutaka Yonemura et al. Cancers (Basel). .

Abstract

In the past, peritoneal metastasis (PM) was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS), therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD) was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA) could improve detection of small PM.

Keywords: ABCG2; PEPT1; aminolevulinic acid; ferrochelatase; peritoneal surface malignancies; photodynamic diagnosis (PDD).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Peritoneal metastasis from ovarian cancer emitted strong red fluorescence under irradiation of violet light after oral administration of 5-aminolevulinic acid. Peritoneal metastases were emitted as red color.
Figure 2
Figure 2
Biosynthesis pathway of PpIX and heme.
Figure 3
Figure 3
Molecular structure of 5-ALA, and 5-ALA-based PDD. Following excitation with blue light (λ = 400–410 nm), the PpIX emits a red-violet light of 635 nm. This phenomenon is potentially exploitable to detect tumor and is named 5-ALA fluorescence-guided surgery.
Figure 4
Figure 4
Immunohistologic finding of PEPT1 in peritoneal metastasis, using anti-PEPT1 rabbit polyclonal antibody H-235 (1:200 dilution; Santa Cruz Biotech, Santa Cruz, CA, USA).
Figure 5
Figure 5
Immunohistologic finding of ABCG2 in peritoneal metastasis, using anti-ABCG2 mouse monoclonal antibody BXP-21 (1:200 dilution; Convance Research 152 Products, Emeryville, CA, USA). ABCG2 expression is detected on the cell membrane.
Figure 6
Figure 6
Intraoperative finding of PDD in a patient with peritoneal metastasis from appendiceal mucinous neoplasm on right subdiaphragmatic peritoneum. Peritoneal metastasis with mucinous materials were emitted with red fluorescence by violet right.
Figure 7
Figure 7
Histologic finding of peritoneal metastasis from appendiceal mucinous neoplasm (Figure 7). Mucinous materials (*) produced from cancer cells (→) extensively occupied stromal tissue.
Figure 8
Figure 8
ALA guided cytoreductive surgery. Residual small nodules are removed under ALA PDD after macroscopic complete resection of PM under white light.
Figure 9
Figure 9
Ovarium of 35 years old woman with peritoneal metastasis from colon cancer is emitted by ALA PDD.
Figure 10
Figure 10
Histological examination revealed metastasis in ovary, which was emitted by ALA PDD.
See this image and copyright information in PMC

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