資料 Informed Consent in State-of-the-Art Medical Care A Narrative of a Person’s Experience of Experimental Surgery

Kaname UEMURA
（Graduate School of Core Ethics and Frontier Science, Ritsumeikan Universityy）

One of the major themes in the field of bioethics is the issue of informed consent, and informed choice (IC). There are a number of scenarios in which IC is regarded as necessary. One situation is that of clinical trials or experimental surgeries. One negative example of this was the Tuskegee Study of Untreated Syphilis in the Negro Male, which was conducted between 1932 and 1972. In the U.S, The Belmont Report was released in 1979 by a special committee to the US Congress out of regret over the Tuskegee Study. In Japan, Mitsuishi, Nudeshima and Kurihara, in 2003, made tentative plans for a law to protect the subjects in scientific research that targets the body, some portion of it, or relevant genetic information. This law stipulates, regarding risks and benefits involving research, that there are benefits that legitimate the risk to the individual subject and the people who experienced the same condition. It also stipulates that an evaluation be conducted both before and during conduct of the study, and that should there be any health hazards, the leader of the study must provide the best possible treatment. (Mitsuishi, Nudeshima, Kurihara 2003)
Also, improvements in the technology of decoding genetic information have made genetic treatment possible. As prenatal diagnoses or preimplantation diagnoses have become possible, and as situations have emerged in which genetic counseling has been requested over the treatment based on the information and responses to the information (Tamai, Nakazawa, Abe 1997). Related to this, Wexler wrote a detailed description of the emotional turmoil and domestic turbulence that one might experience upon learning through a genetic examination the possibility of developing Huntington's disease, an account based on her own experience as the daughter of Huntington's disease patient and therefore possible inheritor of the disease (Wexler 1995).
IC issue arise medical treatment scenarios, especially in the case of difficult diseases such as ALS or cancer. It is difficult for doctors to determine when a doctor should inform the patient of a disease's name and how treatment should be done. Difficult problems have also arisen in cases of Jehovah's Witnesses who refused blood transfusion for religious reasons.
IC is regarded as the provision of information on the risks and benefits, the existence or nonexistence of decision making faculties, the patients' right to make their own decisions and the problems of protecting subjects. However, there are few studies dealing with experiences of IC, particularly there was been little reasons on what sort of experiences people have with IC in clinical researches on human subjects in stateof- the-art experimental medical treatment. In this presentation, we will consider a narrative about IC in the first domestic study osteo-odontokeratoprosthesis (OOKP) conducted in 2003.

II　Subjects and methods
The subject was Ms. Tachibana (assumed name). She was born in 1952, as the last child of four siblings. She had no experience of serious illness. However, at the age of 44 (1998), she had Stevens-Johnson syndrome (SJS)（1,2） and all of a sudden became nearly blind. Then at the age of 49 (2003), her vision was restored to 0.7 through the first domestic osteo-odonto-keratoprosthesis (OOKP)（3,4）.
Methods: The author conducted series of interviews with Ms. Tachibana in 2005 and 2006（5）. The author abstracted from Ms. Tachibana's interview, her narrative about the explanation of the surgery given before the operation. This was then divided into a narrative of the doctor's explanations and Ms. Tachibana's reaction about the explanation (Table 1). Next, the author extracted her narrative about her condition after the surgery. Then the author looked at the advantages and disadvantages resulting from the surgery (Table 2)（6）. The author then reorganized Ms. Tachibana's narratives about IC and described them. In doing so, the author described her narrative using quotations from Ms. Tachibana's account to highlight her understanding and evaluation of the IC and the surgery.

III　Results
Table 1 Ms. Tachibana's understanding of the doctor's explanation of operation before surgery, and her reaction to it

Table 2　Advantages and disadvantages brought about by the restoration of vision through OOKP

[Advantages]
・ Because I never thought I would see again, I will never forget when I first saw again.
・I went out and traveled.
“The market and stuff. Well, for example vegetables, which, of course, I knew about already. I would stare at them and I didn't know why. Hmm, like this. Ohhh, that's what it is. I'll look at them again. It was as if I was filling in five year void. No matter what things I looked at, even ordinary things. Even though I was only looking at the ordinary things, I felt like they were something rare. When I looked at stars and I thought, “I can't believe it!” or something like this.
Because I know there were some times I couldn't see, I am much happier now compared with them. Losing something like that is big, isn't it?

[Disadvantages]
・Visual functions
Field of vision is narrow.
If I face a bright direction, I can see light sparking like a ring before my eyes.
There is glare in my vision, and I cannot see in the dark.
I have to use two different sets of glasses, one for looking things close up and one for looking from afar.
Even though it is said that my vision ability is stable there is a lot of mucus discharge and high pressure on my eyes high, so it is hard to say that my visual acuity are stabilized.
My eyelids cannot close.
When I blink, there is a weird feeling almost like winking. My right eye now has become droopy.
・Daily care
I can not let water in my eye , so I can not wash my face, and I also have to be careful when I take a bath.
Before I go to bed, I have to put salve into the eye and cover it, so even if I want to go to sleep, I can't do so immediately.
Also, when I get up I have to wipe the slave off.
If I do not put the salve in, the eye hurts as if the transplanted oral mucous membrane and eyelids are rubbing together. If the salve on the edge of my eye melts and reaches the lens I can't see anything.
If I sweat, the salve on the edge of my eye reaches the lens, and therefore I cannot go around so much or go out on hotter days.
I was able to move around more when I couldn't see.
I cannot have the surgery again even if I damage my eye by hitting it or something, so I must always be careful.
I always wear a sun visor in order to soften any blow that might happen to hit my eye.
・Facial features
My face now looks like an old person's.
My eyes do not have any expression, so it is beyond my control to say whether my face looks beautiful or ugly.
Since I can not wash my face, I do not put on lipstick or foundation.
Also, I may run into people and set my make up on them.
Since I am a woman, I hate not being able to make myself up, although I have got used to it recently. Also, sometimes I do not like looking at my own face.
・Dentistry
After the tooth was removed an artificial tooth was implanted. But, after the oral mucus membrane was extracted, my teeth have been perpetually numb, plaque and tartar, and sometime I do not notice drooling.
・Communication with others
Due to the various factors listed above, I feel uncomfortable when people say to me “it's so great that you can see again” or “you can see better than I.”
I worry whether or not the person I am talking to regards me as disgusting and I always look down.
I hate face-to-face situations, so I wear dark glasses so that people cannot see my eyes, but sometimes they can still see them due to the light.
・The social health system
Relief Money for Sufferers from Adverse Drug Reactions was canceled because my vision had restored.
My disability pension dropped from level 1 to level 3.
It is really frustrating that the ground of these decisions based only on my vision ability as detailed in the insurance system's diagnosis sheet.

IV Discussion
First of all, the reason Ms. Tachibana could have this operation was that Ms. Tachibana said the following words to her doctor. “Even if it takes 5 years, or even 10 years, if there is any chance for a good operation, please let me know.” At that time, Ms. Tachibana thought it was “like a kind of a joke,” and she never dreamed that having such a surgery was possible. After a while, the doctor introduced OOKP to Ms. Tachibana. Not only was the OOKP operation a first for that university hospital but also the first trial within Japan. Therefore, an Institutional Review Board was held to approve or disapprove this surgery. The Institutional Review Board continued to examine the issue for approximately a year. After the Institutional Review Board approved this surgery, however, Ms. Tachibana felt that “I was worried, indeed, to decide. At least before being examined by the Institutional Review Board, I still didn't really know whether I could have the operation.”
What we should focus on here is the explanation that Ms. Tachibana received from the doctor, in other words, the details of the IC. The advantages that could be attained are two points shown in Table 1 of “I think the doctor told me that my visual acuity would reach an average of 0.7 to 0.8″ and “the success rate of the surgery is high.” On the other hand, the risks given were that “my left eye will become pink,” “my field of vision will be narrow,” “my eyelids will not close, so I won't be able to blink,” “my iris was removed,” “we will pullout the tooth from the root bone, and then insert a lens into it,” with all of these described as “it was beyond my imagination.” Although Ms. Tachibana understood the explanations, she still said “I cannot imagine it.” Even when Ms. Tachibana was asked by the doctor if she had any questions, the problem was that “I didn't even have any idea what will happen to my body.”
I would like to further focus on the following thing. Although it was not an established treatment method, Ms. Tachibana knew that other treatment methods using regenerative medicine were being attempted at other universities at that time, and she asked whether this kind of surgery was appropriate for her. The response to this was “that was not appropriate.” This was a response as a result of the medical examination, so there were no problems. However, from this point, Ms. Tachibana thought that “if I get the surgery, this is the only technique for my case.” Furthermore, as a result of the oral surgical medical examination, Ms. Tachibana was told that “there is only one cuspid left that can be used because one cuspid is decayed and the other two are implants.” This was also the fact that became clear as a result of the medical examination. However, because Ms. Tachibana only had one cuspid tooth left that could be used for OOKP, he thought that “I had better do this while there is still one cuspid left, so there is no time but now.” Therefore, Ms. Tachibana was driven to think that in order to be able to see again, that there were no other methods available other than this surgery, and that if she is to take this surgery then there was no time to think about it. The doctor' s explanation was nothing more than an accurate report of the medical facts resulting from the medical examination, and there was no intention to induce Ms. Tachibana into accepting the surgery. However, as a result those facts effectively created this situation for Ms. Tachibana. In the first place, Ms. Tachibana wanted to be able to see, and in spite of this wish, she was “worried whether she should take the surgery or stop the surgery.”
Under this situation, Ms. Tachibana had some uncertainty. In response to the explanation from the doctor that “the success rate is high,” Ms. Tachibana thought that “even if you say the success rate is high, there is still the possibility of failure. I can't but think about the possibility of failure, so I didn't like becoming the first person for this kind of surgery.” During medical consultations, Ms. Tachibana therefore joked by saying “doctor, why don't we quit?” and “this is bad that I'm the first. I wish I could to be the second or third.” In response to this, the doctor replied “well, somebody has to be the first.” Even if these questions could be discounted to some degree, Ms. Tachibana's anxiety was not a joke. Sometimes it is easy to ask questions in a joking form, whereas it is difficult to ask questions talking in a serious way. Ms. Tachibana also felt, “for me, I thought that if I undecided about the surgery, I would have asked the doctor whether he would choose to suggest the surgery if his wife have had the same disease” and “I wanted to ask it, but in the end I couldn't ask it.” In relation to the questions that were never raised at any point, it is clear that the answers that Ms. Tachibana was seeking were not contained in the medical explanation, as shown in Table 1. Although, Ms. Tachibana needed to ask questions about various issues related to the operation and her life. Afterwards, in this kind of state-of-the-art medical treatment there was no one she could consult except for the doctor.
The reason that Ms. Tachibana decided to have the surgery was not only that she felt she was driven to do so. At that time, Ms. Tachibana's father passed away. Ms. Tachibana regretted that “I couldn't see my parent's face” at the time of his death. Therefore, considering that her mother was still in good health at the time, Ms. Tachibana thought “if her youngest child is in this kind of situation she would also be unhappy” and “I also have to stop my parent from worrying, and it is also for myself. In case the surgery is successful, then that would be great, and if it is a failure, then it just means that I can't see, and I already can't see, so I can then just feel that I am unlucky and should give up trying”. Although Ms. Tachibana felt responsible to have the surgery, because it stemmed from her own request she had made in the first place, she also hoped for herself that “I had a really strong feeling that I myself wanted to see, and that I wanted to see things again. It wasn't just the feeling of responsibility for bringing the subject up.” Her children then went to ask a fortune-teller, and were told that if the operation were to be undertaken, it would be better to have surgery after the start of the New Year. Because of all these events, Ms. Tachibana told the doctor that she would undergo the OOKP surgery.
In this way, Ms. Tachibana received the operation, which was successful. Table 2 shows the conditions of Ms. Tachibana after the surgery. When the author asked Ms. Tachibana if she would have undergone the operation if she had known before the surgery that she would end up in today's condition, she replied, “at that time, if I knew I would be able to see, I would take the operation, and, well, I did take the surgery after all.” Therefore, her attitude probably shows her evaluation of Ms. Tachibana's surgery.

V　Conclusion
Since to call for medical treatment means to go for another kind of self, this act threatens the certainty of the current self. This is the context in which IC, based on the explanation of the benefits and risks of a procedure, is conducted.
The identification of post-traumatic stress disorder (PTDS) needs the authenticity of memories of events that are thought to have possibly caused PTSD and the confirmation of which of the many events was actually the cause of PTSD. If we are unable to confirm whether events that occurred in the past actually occurred, and because of the possibility of memories changing, even if the memories are somehow able to be recalled, a political battle has arisen surrounding the confirmation of memories in the field of authentication. In contrast, the explanation of benefits and risks, on which IC is based, establish the memories and the forecasts of the future that can be estimated despite some degree of uncertainty, by setting certainties that are able to be measured. Therefore, IC, which establishes a baseline for treating uncertain events such as memories and forecasts as certainties, is a concept that is wrapped up in difficulties that are common to the political fighting that arises when setting the baseline for PTSD.
If the actual events from the introduction to OOKP by the doctor until the surgery was accepted by Ms. Tachibana are compared to the idea of IC, the gap in understanding between the two would have been revealed. When faced with a-state-of-the-art medical technology, a patient is accepting a surgery that the patient is unable to imagine, and that is conducted in the midst of the confusion of their everyday life, and that cannot be stated as the sum total of the benefits and risks.
Finally, I will introduce three anecdotes. The first is that Ms. Tachibana, whose visually acuity was restored by the surgery, asked her children before the surgery to seek spiritual advice by going to the temple and praying for their parent. The second is that Ms. Tachibana was asked prior to this report to check the information contained in Tables 1 and 2, and she saw that in Table 2 “lived comfortably” was written in the “advantage” field. Ms. Tachibana asked that the item be erased. The third point is that the author suffers from after-effects in the eyes due to Stevens-Johnson Syndrome in the same way as Ms. Tachibana, and his current condition is thought to be the same as Ms. Tachibana prior to receiving the surgery. Ms. Tachibana is aware of this fact. Therefore, each time Ms. Tachibana meets the author, she asks the author whether he has decided to take the surgery. In this way, the evaluation of accepting the surgery from the point of view of Ms. Tachibana is still undecided, and is thought to be because of the experience of accepting a surgery that could not be imagined.
<Notes>
（1） Stevens-Johnson Syndrome (SJS) is the subject of the research department fighting special disorders such as acute erythema multiforme exuditavum. The incidence is estimated at between 1 and 10 people per million of population, spread across a wide range of ages from small children to the very old. Although the causes and underlying mechanisms are not yet clear, SJS is thought to be a cutaneous response to infectious diseases and allergies. In particular, there are many cases where the cause is a pharmaceutical product. However, it is very difficult to predict whether an incident will occur prior to administering a medication. Symptoms of SJS are fever, repeated occurrence of erythema multiforme throughout the entire body, and the occurrence of inflammation of the mucocutaneous junctions of the lips, oral cavity, eyes, nose, external genitalia, etc. The prognosis is an improvement in the condition of the skin followed by after-effects remaining in the eyes, respiratory organs, etc., with the possibility of death due to multiple organ damage. The mortality rate is 6.3 % , and for the acute form, toxic epidermal necrolysis (TEN), it is 20 to 30 % (Pharmaceutical and Food Safety Bureau, Japanese Ministry of Health, Labour and Welfare, 2005; Japan Intractable Disease Information Center, 2006).
（2） The prognosis of corneal transplantation to treat corneal clouding arising as an after-effect of Stevens-Johnson Syndrome is poor, and corneal transplants have therefore become contraindicated. However, because it is very difficult to restore visual acuity by conservative treatment methods based on oral medication or ocular instillation, the development and establishment of surgical treatments have been sought, with a number of methods having been undertaken in recent years (Sotozono, 2000). There are two main methods of surgical rehabilitation of visual function for corneal disease. The first is regenerative medicine. This is a method of cultured corneal epithelium transplantation using corneal epithelial stem cells that uses amnion and oral mucosa, and this has already been applied clinically. Another method is keratoprosthesis (Nakamura and Kinoshita, 2002), which includes the OOKP surgery that was examined in this report.
（3） Keratoprosthesis is a method of replacing a cloudy cornea with a transparent prosthesis such as polymethyl methacrylate (PMMA), with the development of the ideas relating to modern keratoprosthesis having a history of over 200 years. The first time that a transplant was made into an actual human body was a quartz transplant by Nussbaum in 1855. From that time up to around 1900, various keratoprostheses were transplanted, but almost all of these were failures. Although the momentum for keratoprostheses temporarily dropped during the 1950s with the spread of corneal transplantation, the focus eventually returned with efforts made to treat cases that had been unsuccessful by corneal transplant. Although some of the pioneering efforts were also made in Japan starting from the 1970s, the long-term prognoses for all of these were poor. Within this history, in 1963 the Italian Strampelli reported osteo-odonto-keratoprosthesis, which uses the tooth root and alveolar bone from the patient to affix the optical part of the keratoprosthesis. However, in supplementary examinations of this method carried out during the same period in Britain, these were almost all failures. Therefore, in 1987 Falcinelli improved the method of Strampelli with a method to excise the iris, lens, and anterior chamber of the eye when transplanting the ocular surface, and this produced good results. This improved method of osteo-odonto-keratoprosthesis was introduced into Italy, Austria, and Germany, before being introduced to Britain by C. Liu and J. Herold in 1996. The number of medical cases using the improved method of osteo-odontokeratoprosthesis that have been reported up to now is 573, with the longest having an elapsed observation period of 27 years (Liu, Fukuda, Shimomura, Hamada, 2002; Fukuda, Liu, Shimomura, 2003; Fukuda, 2004; 2005).
（4） OOKP consists of a first period of surgery, which is preparatory surgery, and a second period of surgery that is carried out two to four months subsequently.
The first period of surgery is carried out under general anesthesia, and consists of the two surgerys of A) regenerative surgery of the ocular surface, and B) implanting an optical component into the orbicularis oculus of the fixed osteo-odonto-lamina. In surgery A, a sample of approximately 3 cm in diameter of the oral mucosa is extracted. An incision is then made into the surface of the cornea, the oral mucosa is sewn into the sclera, and a new ocular surface is formed. In B, a cuspid tooth is extracted down to the root and is shaved with a drill to create a thin wafer on which one side is the tooth root and the other side is bone (the osteo-odonto-lamina). A hole with a diameter of 3 to 4 mm is drilled through the center of the osteoodonto- lamina, and a cylindrical optical component made of PMMA is affixed to this using dental cement. The reason that a cuspid tooth is used is that the root part of a single large tooth is required to implant the optical component. This is implanted into the obicularis oculus of the lower part of the eyeball opposite to the eye being treated. After this first period of surgery, a delay of 2 to 4 months is made before the second period of surgery. This period is used to wait for granulation tissue to grow around the osteo-odonto-lamina, and for blood vessels to penetrate into the oral mucosa that was transplanted onto the ocular surface.
The second period of surgery is carried out under general anesthesia the same like in the first surgery. First, the osteo-odonto-lamina that was implanted within the obicularis oculus during the first period of surgery is extracted. The granulation tissue on the part of the tooth that will be in contact with the cornea is completely removed, while the excess granulation tissue on the bone part is cut away to leave a small amount of tissue. A U-shaped incision that is slightly larger than the diameter of the cornea is made into the oral mucosa of the ocular surface, and lifted and held down towards the bottom. The tissue of the ocular surface is cut away, the center is marked where the cornea will be exposed, and a 3 to 4 mm diameter section is cut away. In order to prevent inflammation within the eye after the surgery and to prevent a membrane from forming on the posterior surface of the optical component, the iris, lens, and anterior chamber are excised. The optical component of the posterior of the osteo-odonto-lamina is inserted into the incision in the cornea, and the lamina is sewn into the surrounding sclera and cornea. Once the sutures are finished, the raised part of the oral mucosa is cut away to match the size of the anterior of the optical component, and the optical component is protruded through the incision (Fukuda, 2004; 2005).
（5） This was an interview survey using semi-structured interviews. The interviews were held three times in the period between June 2005 and July 2006 (total 10 hours). The interviews were carried out with the permission of Ms. Tachibana and were recorded on minidisk.
（6） Ms. Tachibana was asked to verify Tables 1 and 2 shown here prior to this report, with the tables published after adding the necessary modifications.
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