Shape-Memory Alloy Loop Snare for Endoscopic Photodynamic Therapy of Early Gastric Cancer

• Introduction
• Patients and Methods
• Patients
• PDT Procedure
• Evaluation of PDT
• Results
• Demonstration of PDT Using the SMA Loop Snare
• Results of PDT
• Discussion
• Acknowledgment
• References

Background and Study Aims: Photodynamic therapy (PDT) has proved effective in the treatment of gastric cancer, but there is room for improvement. To achieve the technical goal of carrying out endoscopic PDT, endoscopists need to determine the precise area for laser irradiation at adequate dosages. This report describes the use of a shapememory alloy (SMA) loop snare as a useful tool in endoscopic PDT.

Patients and Methods: Eleven patients with biopsyproved early gastric cancer were treated with endoscopic PDT after intravenous injection of Photofrin II (2 mg/kg b.w.). Five patients underwent PDT using the SMA loop snare, and six underwent PDT without the use of the device. Cancer lesions smaller than 2 cm in diameter were irradiated with an excimer-dye laser (4 mJ, 80 Hz, 630 nm) for 20 min.

Results: All five patients (100 %) treated with PDT using the SMA loop snare, and four of the six patients (67 %) treated with PDT without use of the SMA loop snare, showed complete remission.

Conclusions: The SMA loop snare routinely forms a circle 2 cm in diameter, covering an area of 3.14 cm², and makes it possible to mark and calculate the precise area of cancerous lesions for irradiation at appropriate dosages. The findings of this study suggest that the SMA loop snare is an effective tool for PDT in early gastric cancer.

Introduction

Photodynamic therapy (PDT), a promising new modality for the treatment of neoplasms, is based on the principle of using specific laser light irradiation to activate a photodynamic agent selectively retained by tumor tissue, so that neoplastic cells are destroyed by intracellular singlet oxygen produced by the photodynamic reaction [1] [2] [3] . PDT has been shown to be effective in the treatment of gastric cancer [4] [5] . One of the technical goals in endoscopic PDT is to determine the precise area for laser irradiation at adequate dosages. We have previously described a shape-memory alloy (SMA) loop snare and its use to measure cancerous lesions in endoscopic treatment [6]. The present report describes the use of the SMA loop snare as a tool for endoscopic PDT.

Patients and Methods

Patients

Eleven patients (nine men, two women; age 59 - 85) with biopsy-proven early gastric cancer were treated with endoscopic PDT, due to physical inability or refusal to undergo conventional therapy. Informed consent for PDT was obtained from all patients and their families. Five patients underwent PDT with the use of the SMA loop snare, and six patients underwent PDT without the device. The lesions, all less than 20 mm at the largest diameter, were measured using a wire scale or the SMA loop snare. Histological diagnoses were made according to the criteria used by the Japanese Research Society for Gastric Cancer.

PDT Procedure

The patients received polyhematoporphyrin ethers and esters (Photofrin II, 2 mg/kg, Wyeth Ledarle Japan, Tokyo) intravenously, and were screened from sunlight for 48 hours before PDT. Endoscopic examination was carried out to mark and measure the area of irradiation with the SMA loop snare (2 cm diameter). The SMA snare was powered at 50 W (coagulation mode). Via a single quartz fiber passed through a gastrointestinal fiberscope, excimer-dye laser irradiation (4 mJ, 80 Hz, 630 nm; Hamamatsu Photonics, Hamamatsu, Japan) was applied to the marked area (3.14 cm²) for 20 min. The total energy density applied to the irradiated area was calculated using the following formula [7]:

Thus, a total of 144 J/cm² was applied using the SMA loop snare. When the device was not used, the cancerous lesion and an additional 5 mm of the marginal mucosa were irradiated (4 mJ, 80 Hz, 630 nm) for 20 min. After PDT, all of the patients were advised to avoid intense sunlight for at least two weeks.

Evaluation of PDT

The patients' physical status was checked once per month. During the first year of follow-up, endoscopic examinations were carried out at one, two, and four weeks, and then three, six, nine, and twelve months after PDT, and thereafter at six-monthly intervals. Biopsies were taken at each examination. The results of PDT were evaluated as follows: complete remission (CR) when no evidence of tumor was detected either histologically or endoscopically for at least one year; partial remission (PR) when the reduction in the size of the endoscopically evaluated tumor exceeded 50 %, but persistent histologically malignant changes were found; no change (NC) when the size of the tumor decreased by less than 50 %.

Results

Demonstration of PDT Using the SMA Loop Snare

The SMA loop snare device is shown in Figure [1]. The Teflon-covered cautery is introduced through the endoscope; the loop becomes circular due to the effect of body heat and when electric current is applied. The SMA loop snare used in this study was 2 cm in diameter, and the encircled area covered 3.14 cm².

Figure [2] shows a case of early gastric cancer treated with PDT using the SMA loop snare (patient no. 4). The cancerous lesion detected in the lower corpus part of the lesser gastric curvature was of the superficial depressed type with an ulcer, representing a contraindication to endoscopic mucosal resection. PDT was therefore carried out. The lesion was encircled with the SMA loop snare, and the area of irradiation (3.14 cm²) was marked (Figure [2 A]). Excimer-dye laser irradiation (4 mJ, 80 Hz, 630 nm) was applied to the marked area for 20 min (Figure [2 B]). Initially, the irradiated gastric area became edematous (Figure [2 C]), and ulcer formation occurred. No recurrences were detected in the course of the follow-up examinations, including biopsies (Figure [2 D]).

Although PDT was successfully used for early gastric cancer, it was not successful in all cases. Successful PDT showed complete destruction of the tumor (Figure [3 A]), while unsuccessful PDT (patient no. 11) showed residual cancer cells (Figure [3 B]).

Results of PDT

The patient characteristics are summarized in Table [1]. The group treated with PDT using the SMA loop snare consisted of five men, with a mean age of 72.0 years. The mean tumor size was 13.4 mm. All five patients showed complete remission, and have survived during a follow-up period ranging from 14 to 36 months.

The group of six patients treated with PDT without the SMA loop snare consisted of four men and two women, with a mean age of 72.3 years. The mean tumor size was 12.3 mm. Four of the patients showed complete remission, and two had partial remissions. Patient no. 7 died 18 months after PDT due to hepatocellular carcinoma. Patient no. 10 died 12 months after PDT due to lung cancer. The remaining four patients have survived during a followup period ranging from 12 to 36 months.

Discussion

PDT uses light that activates photosensitizing compounds stored in tumor tissue, and selectively destroys tumors [1] [2] [3] . Photofrin II, used in this study, is known to have both a high affinity for tumor cells and a high sensitivity to light [8] [9] , suggesting that the polyhematoporphyrin ethers and esters it contains can improve the efficacy of PDT. However, further improvements are required not only in the photosensitizers, but also in the endoscopic technique used in PDT. Precisely targeted irradiation and adequate dosage of the laser beam are needed. Before the introduction of the SMA loop snare, laser beam irradiation was applied to a field that included both the lesion and an additional 5 mm parallel to the contours of the lesion. This type of irradiation may not always be precise, and two of the patients in the present study were found to have residual tumor cells after PDT. PDT is sometimes difficult to apply, depending on the location of the lesions; insufficient irradiation may also result in residual tumor cells.

Among the advantages of using the SMA loop snare before applying the laser beam are the fact that it is easier to determine the area to be irradiated by circumscribing and marking it at the same time; in addition, the lesion can be irradiated at a dosage calculated for the measured area. It is noteworthy that in this study, residual tumor cells were detected at the edges of irradiated areas when the SMA loop snare was not used. The SMA loop snare used in the study had a diameter of 2 cm (3.14 cm²), but other snare sizes are also available for cancer lesions of various sizes.

The adequate dosage of irradiation has been measured experimentally in clinical PDT of the stomach. Although the effect of irradiation for cell destruction has been studied in vitro [10] [11] , few clinical data have been reported on the relationship between irradiation dosage and tissue destruction, especially in the stomach. In previous studies [7] [12] , irradiation dosages ranging from 60 J/cm² to 150 J/cm² have been used for PDT of gastric cancer. However, whether or not such dosages are adequate needs to be confirmed again, as the area of irradiation may be miscalculated. The SMA loop snare may also be useful here for measuring more precisely the relationship between the irradiation dosage and tissue destruction.

PDT has been limited to patients who are either inoperable or who refuse surgery [13]. However, it is also a practical technique for treating gastrointestinal malignancies. The SMA loop snare described here can circumscribe a cancerous lesion within a routine circle; endoscopists would then be able to apply the laser beam to the circle at the required dosage after calculating the area. This study suggests that the SMA loop snare is an effective tool for PDT of early gastric cancer.

Acknowledgment

Research for this study was supported in part by the Grant-in-Aid for Cancer Research from the Japanese Ministry of Health and Welfare.

References

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• 13 Sibille A, Descamps C, Jonard P, et al. Endoscopic Nd:YAG treatment of superficial gastric carcinoma: experience in 18 Western inoperable patients.  Gastrointest Endosc. 1995;  42 340-345
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M.D. T. Fujimori

Dept. of Pathology Dokkyo University School of Medicine

880, Kitakobayashi, Mibu, Shimotsuga

Tochigi 321-0293

Japan

Phone: +81-282-86-1681

Email: t-fuji@dokkyomed.ac.jp

References

• 1 Gregorie HB, Horger EO, Ward JL, et al. Hematoporphyrin-derivative fluorescence in malignant neoplasms.  Ann Surg. 1968;  167 820-828
  PubMedSearch in Google Scholar
• 2 Weishaup KR, Gomer CJ, Dougherty TJ. Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor.  Cancer Res. 1976;  36 2326-2329
  PubMedSearch in Google Scholar
• 3 Gomer CJ, Dougherty TJ. Determination of [³H]- and [¹⁴C]hematoporphyrin derivative distribution in malignant and normal tissue.  Cancer Res. 1979;  39 146-151
  PubMedSearch in Google Scholar
• 4 Ell C, Grossner L, May A, et al. Photodynamic therapy of early gastric cancer with mTHPC.  Gut. 1998;  43 345-349
  PubMedSearch in Google Scholar
• 5 Grossner L, Sroka, R, Hahn EG, Ell C. Photodynamic therapy: successful destruction of gastrointestinal cancer after oral administration of aminolevulinic acid.  Gastrointest Endosc. 1995;  41 55-58
  PubMedSearch in Google Scholar
• 6 Fujimori T, Nakamura T, Yoshida S, et al. Endoscopic mucosectomy for early gastric cancer using modified strip biopsy.  Endoscopy. 1992;  24 187-189
  PubMedSearch in Google Scholar
• 7 Mimura S, Ito Y, Hayata Y, et al. Cooperative clinical trial of photodynamic therapy with Photofrin II and excimer dye laser for early gastric cancer.  Lasers Surg Med. 1996;  19 168-172
  CrossrefPubMedSearch in Google Scholar
• 8 Dellinger M, Vever-Bizet C, Brault D, et al. Uptake and photodynamic efficiency of hematoporphyrin, hydroxyethylvinyldeuteroporphyrin and hematoporphyrin derivative (Photofrin II): a study with isolated mitochondria.  Photochem Photobiol. 1990;  51 185-189
  PubMedSearch in Google Scholar
• 9 Tsuchida T, Zheng G, Pandey RK, et al. Correlation between site II-specific human serum albumin (HSA) binding affinity and murine in vivo photosensitizing efficacy of some Photofrin components.  Photochem Photobiol. 1997;  66 224-228
  PubMedSearch in Google Scholar
• 10 Schomacker KT, Walsh A, Gregory KW, Kochevar IE. Cell damage induced by Angiovist-370 and 308 nm excimer laser radiation.  Lasers Surg Med. 1997;  20 111-118
  CrossrefPubMedSearch in Google Scholar
• 11 Kochevar IE, Walsh AA, Green HA, et al. DNA damage induced by 193-nm radiation in mammalian cells.  Cancer Res. 1991;  51 288-293
  PubMedSearch in Google Scholar
• 12 Mimura S, Ichii M, Imanishi K, et al. Evaluation of photodynamic therapy for gastric cancer.  Dig Endosc. 1990;  2 265-274
  PubMedSearch in Google Scholar
• 13 Sibille A, Descamps C, Jonard P, et al. Endoscopic Nd:YAG treatment of superficial gastric carcinoma: experience in 18 Western inoperable patients.  Gastrointest Endosc. 1995;  42 340-345
  PubMedSearch in Google Scholar

M.D. T. Fujimori

Dept. of Pathology Dokkyo University School of Medicine

880, Kitakobayashi, Mibu, Shimotsuga

Tochigi 321-0293

Japan

Phone: +81-282-86-1681

Email: t-fuji@dokkyomed.ac.jp