"Informed Consent in State-of-the-Art Medical Care; A Narrative of a Person's Experience of Experimental Surgery"

UEMURA Kaname@2008/02/29
ّwwZ^[CwZ^[񍐂PC157p.@ISSN 1882-6539@pp.155-169

last update: 20151225

Informed Consent in State-of-the-Art Medical Care
A Narrative of a Personfs Experience of Experimental Surgery

iGraduate School of Core Ethics and Frontier Science, Ritsumeikan Universityyj

One of the major themes in the field of bioethics is the issue ofinformed consent, and informed choice (IC). There are a number ofscenarios in which IC is regarded as necessary. One situation is that ofclinical trials or experimental surgeries. One negative example of this wasthe Tuskegee Study of Untreated Syphilis in the Negro Male, which wasconducted between 1932 and 1972. In the U.S, The Belmont Report wasreleased in 1979 by a special committee to the US Congress out of regretover the Tuskegee Study. In Japan, Mitsuishi, Nudeshima and Kurihara, in2003, made tentative plans for a law to protect the subjects in scientificresearch that targets the body, some portion of it, or relevant geneticinformation. This law stipulates, regarding risks and benefits involvingresearch, that there are benefits that legitimate the risk to the individualsubject and the people who experienced the same condition. It alsostipulates that an evaluation be conducted both before and during conductof the study, and that should there be any health hazards, the leader ofthe study must provide the best possible treatment. (Mitsuishi, Nudeshima,Kurihara 2003)
Also, improvements in the technology of decoding genetic informationhave made genetic treatment possible. As prenatal diagnoses or preimplantationdiagnoses have become possible, and as situations haveemerged 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 detaileddescription of the emotional turmoil and domestic turbulence that onemight experience upon learning through a genetic examination thepossibility of developing Huntingtonfs disease, an account based on herown experience as the daughter of Huntingtonfs disease patient andtherefore possible inheritor of the disease (Wexler 1995).
IC issue arise medical treatment scenarios, especially in the caseof difficult diseases such as ALS or cancer. It is difficult for doctors todetermine when a doctor should inform the patient of a diseasefs nameand how treatment should be done. Difficult problems have also arisen incases of Jehovahfs Witnesses who refused blood transfusion for religiousreasons.IC is regarded as the provision of information on the risks andbenefits, the existence or nonexistence of decision making faculties, thepatientsf right to make their own decisions and the problems of protectingsubjects. However, there are few studies dealing with experiences of IC,particularly there was been little reasons on what sort of experiencespeople have with IC in clinical researches on human subjects in stateof-
the-art experimental medical treatment. In this presentation, we willconsider 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 in1952, as the last child of four siblings. She had no experience of seriousillness. However, at the age of 44 (1998), she had Stevens-Johnsonsyndrome (SJS)i1,2j and all of a sudden became nearly blind. Then at theage of 49 (2003), her vision was restored to 0.7 through the first domestic osteo-odonto-keratoprosthesis (OOKP)i3,4j.
Methods: The author conducted series of interviews with Ms.Tachibana in 2005 and 2006i5j. The author abstracted from Ms.Tachibanafs interview, her narrative about the explanation of the surgerygiven before the operation. This was then divided into a narrative of thedoctorfs explanations and Ms. Tachibanafs reaction about the explanation(Table 1). Next, the author extracted her narrative about her conditionafter the surgery. Then the author looked at the advantages anddisadvantages resulting from the surgery (Table 2)i6j. The author thenreorganized Ms. Tachibanafs narratives about IC and described them. Indoing so, the author described her narrative using quotations from Ms.Tachibanafs account to highlight her understanding and evaluation of theIC and the surgery.

Table 1 Ms. Tachibanafs understanding of the doctorfs explanation of operation before surgery, and her reaction to it
Ms. Tachibanafs understanding of the explanationMs. Tachibanafs reaction to the explanation
My left eye will become pink. If the surgery fails, then [I] wonft beable to see and me eye will be pink. Atotal disaster. But the change of eyecolor will not matter to me.
My field of vision will be narrow. It was beyond my imagination.
My eyelids will not close, so I wonft be able to blink. It was beyond my imagination.
My iris will be removed It was beyond my imagination.
They will pullout the toothfrom the root bone, and theninsert a lens into it. It was beyond my imagination.
There is only one cuspid leftthat can be used because onecuspid is decayed and theother two are implants.I had better do this now while there isstill a tooth left, so there is no time but now.
I think the doctor told methat my visual acuity wouldreach an average of 0.7 to 0.8 @
The success rate of thesurgery is high. Even if the success rate is high, there isstill the possibility of failure. ThereforeI canft but think about the possibilityof failure, so I donft like being the firstperson for this kind of surgery.
New techniques being usedat other universities are notappropriate for me. If I get the surgery, this is the onlytechnique for my case.

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

E Because I never thought I would see again, I will never forget when I first saw again.
EI went out and traveled.
gThe market and stuff. Well, for example vegetables, which, of course,I knew about already. I would stare at them and I didnft know why.Hmm, like this. Ohhh, thatfs what it is. Ifll look at them again. It wasas 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 ordinarythings, I felt like they were something rare. When I looked at starsand I thought, gI canft believe it!h or something like this.Because I know there were some times I couldnft see, I am much happiernow compared with them. Losing something like that is big, isnft it?

EVisual functions
Field of vision is narrow.
If I face a bright direction, I can see light sparking like a ring beforemy 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.
EDaily 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, soeven if I want to go to sleep, I canft 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 canft see anything.
If I sweat, the salve on the edge of my eye reaches the lens, andtherefore I cannot go around so much or go out on hotter days.I was able to move around more when I couldnft see.
I cannot have the surgery again even if I damage my eye by hitting itor 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.
EFacial features
My face now looks like an old personfs.
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.
After the tooth was removed an artificial tooth was implanted. But,after the oral mucus membrane was extracted, my teeth have beenperpetually numb, plaque and tartar, and sometime I do not noticedrooling.
ECommunication with others
Due to the various factors listed above, I feel uncomfortable when people say to me gitfs so great that you can see againh or gyou can see better than I.h
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.
EThe 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 systemfs 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 ittakes 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 akind of a joke," and she never dreamed that having such a surgery waspossible. After a while, the doctor introduced OOKP to Ms. Tachibana.Not only was the OOKP operation a first for that university hospital butalso 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 theInstitutional Review Board approved this surgery, however, Ms. Tachibanafelt that "I was worried, indeed, to decide. At least before being examinedby the Institutional Review Board, I still didn't really know whether Icould have the operation.h
What we should focus on here is the explanation that Ms. Tachibanareceived from the doctor, in other words, the details of the IC. Theadvantages that could be attained are two points shown in Table 1 of gIthink the doctor told me that my visual acuity would reach an averageof 0.7 to 0.8h and gthe success rate of the surgery is high.h On the otherhand, the risks given were that gmy left eye will become pink,h gmy fieldof vision will be narrow,h gmy eyelids will not close, so I wonft be able toblink,h gmy iris was removed,h gwe will pullout the tooth from the rootbone, and then insert a lens into it,h with all of these described as gitwas beyond my imagination.h Although Ms. Tachibana understood theexplanations, she still said "I cannot imagine it." Even when Ms. Tachibanawas asked by the doctor if she had any questions, the problem was that "Ididn't even have any idea what will happen to my body."
I would like to further focus on the following thing. Although it wasnot an established treatment method, Ms. Tachibana knew that othertreatment methods using regenerative medicine were being attemptedat other universities at that time, and she asked whether this kind ofsurgery was appropriate for her. The response to this was gthat was notappropriate.h This was a response as a result of the medical examination,so there were no problems. However, from this point, Ms. Tachibanathought that gif I get the surgery, this is the only technique for my case.hFurthermore, as a result of the oral surgical medical examination, Ms.Tachibana was told that gthere is only one cuspid left that can be used because one cuspid is decayed and the other two are implants.h This wasalso the fact that became clear as a result of the medical examination.However, because Ms. Tachibana only had one cuspid tooth left that couldbe used for OOKP, he thought that gI had better do this while there is stillone cuspid left, so there is no time but now.h Therefore, Ms. Tachibanawas driven to think that in order to be able to see again, that there wereno other methods available other than this surgery, and that if she is totake this surgery then there was no time to think about it. The doctorfs explanation was nothing more than an accurate report of the medicalfacts resulting from the medical examination, and there was no intentionto induce Ms. Tachibana into accepting the surgery. However, as a resultthose facts effectively created this situation for Ms. Tachibana. In thefirst place, Ms. Tachibana wanted to be able to see, and in spite of thiswish, she was "worried whether she should take the surgery or stop thesurgery.h
Under this situation, Ms. Tachibana had some uncertainty. Inresponse to the explanation from the doctor that gthe success rate ishigh,h Ms. Tachibana thought that geven if you say the success rate ishigh, there is still the possibility of failure. I canft but think about thepossibility of failure, so I didnft like becoming the first person for thiskind of surgery.h During medical consultations, Ms. Tachibana thereforejoked by saying "doctor, why don't we quit?h and "this is bad that I'mthe first. I wish I could to be the second or third." In response to this, thedoctor replied "well, somebody has to be the first." Even if these questionscould be discounted to some degree, Ms. Tachibana's anxiety was not ajoke. 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 haveasked 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 anypoint, it is clear that the answers that Ms. Tachibana was seeking werenot contained in the medical explanation, as shown in Table 1. Although, Ms. Tachibana needed to ask questions about various issues related to theoperation and her life. Afterwards, in this kind of state-of-the-art medicaltreatment there was no one she could consult except for the doctor.
The reason that Ms. Tachibana decided to have the surgery was notonly that she felt she was driven to do so. At that time, Ms. Tachibana'sfather passed away. Ms. Tachibana regretted that "I couldn't see myparent's face" at the time of his death. Therefore, considering that hermother was still in good health at the time, Ms. Tachibana thought "if heryoungest 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 afailure, then it just means that I can't see, and I already can't see, so I canthen just feel that I am unlucky and should give up trying". Although Ms.Tachibana felt responsible to have the surgery, because it stemmed fromher own request she had made in the first place, she also hoped for herselfthat "I had a really strong feeling that I myself wanted to see, and that Iwanted to see things again. It wasn't just the feeling of responsibility forbringing 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 bebetter to have surgery after the start of the New Year. Because of allthese events, Ms. Tachibana told the doctor that she would undergo the OOKP surgery.
In this way, Ms. Tachibana received the operation, which wassuccessful. Table 2 shows the conditions of Ms. Tachibana after thesurgery. When the author asked Ms. Tachibana if she would have undergone the operation if she had known before the surgery that shewould end up in todayfs condition, she replied, "at that time, if I knew Iwould be able to see, I would take the operation, and, well, I did take thesurgery after all.h Therefore, her attitude probably shows her evaluationof Ms. Tachibana's surgery.

Since to call for medical treatment means to go for another kindof self, this act threatens the certainty of the current self. This is thecontext in which IC, based on the explanation of the benefits and risks of aprocedure, is conducted.
The identification of post-traumatic stress disorder (PTDS) needsthe authenticity of memories of events that are thought to have possiblycaused PTSD and the confirmation of which of the many events wasactually the cause of PTSD. If we are unable to confirm whether eventsthat occurred in the past actually occurred, and because of the possibilityof memories changing, even if the memories are somehow able to berecalled, a political battle has arisen surrounding the confirmation ofmemories in the field of authentication. In contrast, the explanation ofbenefits and risks, on which IC is based, establish the memories and theforecasts of the future that can be estimated despite some degree ofuncertainty, by setting certainties that are able to be measured. Therefore,IC, which establishes a baseline for treating uncertain events such asmemories and forecasts as certainties, is a concept that is wrapped upin difficulties that are common to the political fighting that arises whensetting the baseline for PTSD.
If the actual events from the introduction to OOKP by the doctoruntil the surgery was accepted by Ms. Tachibana are compared to theidea of IC, the gap in understanding between the two would have been revealed. When faced with a-state-of-the-art medical technology, a patientis accepting a surgery that the patient is unable to imagine, and that isconducted in the midst of the confusion of their everyday life, and thatcannot 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 herchildren before the surgery to seek spiritual advice by going to the templeand praying for their parent. The second is that Ms. Tachibana wasasked prior to this report to check the information contained in Tables1 and 2, and she saw that in Table 2 "lived comfortably" was written inthe gadvantageh field. Ms. Tachibana asked that the item be erased. Thethird point is that the author suffers from after-effects in the eyes due toStevens-Johnson Syndrome in the same way as Ms. Tachibana, and hiscurrent condition is thought to be the same as Ms. Tachibana prior toreceiving the surgery. Ms. Tachibana is aware of this fact. Therefore, eachtime Ms. Tachibana meets the author, she asks the author whether he hasdecided to take the surgery. In this way, the evaluation of accepting thesurgery from the point of view of Ms. Tachibana is still undecided, and isthought to be because of the experience of accepting a surgery that couldnot be imagined.

i1j Stevens-Johnson Syndrome (SJS) is the subject of the research department fightingspecial disorders such as acute erythema multiforme exuditavum. The incidenceis estimated at between 1 and 10 people per million of population, spread across awide range of ages from small children to the very old. Although the causes andunderlying mechanisms are not yet clear, SJS is thought to be a cutaneous responseto infectious diseases and allergies. In particular, there are many cases where thecause is a pharmaceutical product. However, it is very difficult to predict whether anincident will occur prior to administering a medication. Symptoms of SJS are fever, repeated occurrence of erythema multiforme throughout the entire body, and theoccurrence of inflammation of the mucocutaneous junctions of the lips, oral cavity,eyes, nose, external genitalia, etc. The prognosis is an improvement in the conditionof 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 rateis 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 andWelfare, 2005; Japan Intractable Disease Information Center, 2006).
i2j The prognosis of corneal transplantation to treat corneal clouding arising as anafter-effect of Stevens-Johnson Syndrome is poor, and corneal transplants havetherefore become contraindicated. However, because it is very difficult to restorevisual acuity by conservative treatment methods based on oral medication orocular instillation, the development and establishment of surgical treatments havebeen sought, with a number of methods having been undertaken in recent years(Sotozono, 2000). There are two main methods of surgical rehabilitation of visualfunction for corneal disease. The first is regenerative medicine. This is a method ofcultured corneal epithelium transplantation using corneal epithelial stem cells thatuses amnion and oral mucosa, and this has already been applied clinically. Anothermethod is keratoprosthesis (Nakamura and Kinoshita, 2002), which includes theOOKP surgery that was examined in this report.
i3j Keratoprosthesis is a method of replacing a cloudy cornea with a transparentprosthesis such as polymethyl methacrylate (PMMA), with the development of theideas relating to modern keratoprosthesis having a history of over 200 years. Thefirst time that a transplant was made into an actual human body was a quartztransplant by Nussbaum in 1855. From that time up to around 1900, variouskeratoprostheses were transplanted, but almost all of these were failures. Althoughthe momentum for keratoprostheses temporarily dropped during the 1950s with thespread of corneal transplantation, the focus eventually returned with efforts made totreat cases that had been unsuccessful by corneal transplant. Although some of thepioneering efforts were also made in Japan starting from the 1970s, the long-termprognoses for all of these were poor. Within this history, in 1963 the Italian Strampellireported osteo-odonto-keratoprosthesis, which uses the tooth root and alveolarbone from the patient to affix the optical part of the keratoprosthesis. However, insupplementary examinations of this method carried out during the same period inBritain, these were almost all failures. Therefore, in 1987 Falcinelli improved themethod of Strampelli with a method to excise the iris, lens, and anterior chamberof 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-odontokeratoprosthesisthat have been reported up to now is 573, with the longest havingan elapsed observation period of 27 years (Liu, Fukuda, Shimomura, Hamada, 2002;Fukuda, Liu, Shimomura, 2003; Fukuda, 2004; 2005).
i4j OOKP consists of a first period of surgery, which is preparatory surgery, and asecond 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 ofthe two surgerys of A) regenerative surgery of the ocular surface, and B) implantingan 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 isextracted. An incision is then made into the surface of the cornea, the oral mucosais sewn into the sclera, and a new ocular surface is formed. In B, a cuspid toothis extracted down to the root and is shaved with a drill to create a thin wafer onwhich 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 thisusing dental cement. The reason that a cuspid tooth is used is that the root part ofa single large tooth is required to implant the optical component. This is implantedinto the obicularis oculus of the lower part of the eyeball opposite to the eye beingtreated. After this first period of surgery, a delay of 2 to 4 months is made beforethe second period of surgery. This period is used to wait for granulation tissue togrow around the osteo-odonto-lamina, and for blood vessels to penetrate into theoral mucosa that was transplanted onto the ocular surface.The second period of surgery is carried out under general anesthesia the samelike in the first surgery. First, the osteo-odonto-lamina that was implanted withinthe obicularis oculus during the first period of surgery is extracted. The granulationtissue on the part of the tooth that will be in contact with the cornea is completelyremoved, while the excess granulation tissue on the bone part is cut away to leave asmall amount of tissue. A U-shaped incision that is slightly larger than the diameterof the cornea is made into the oral mucosa of the ocular surface, and lifted and helddown towards the bottom. The tissue of the ocular surface is cut away, the centeris marked where the cornea will be exposed, and a 3 to 4 mm diameter sectionis cut away. In order to prevent inflammation within the eye after the surgeryand to prevent a membrane from forming on the posterior surface of the opticalcomponent, the iris, lens, and anterior chamber are excised. The optical componentof 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 suturesare finished, the raised part of the oral mucosa is cut away to match the size of theanterior of the optical component, and the optical component is protruded through the incision (Fukuda, 2004; 2005).
i5j This was an interview survey using semi-structured interviews. The interviewswere 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 wererecorded on minidisk.
i6j 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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Masahiko Fukuda, 2005, "Clinical studies of keratoprostheses", Journal of ClinicalOphthalmology, 59(11), pp. 300-305.
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Christopher Liu, Masahiko Fukuda, Yuji Shimomura, Suguru Hamada, 2002,"Introduction to improved osteo-odonto-keratoprosthesis", Folia OphthalmologicJaponica, 53-6, pp. 472-475.
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* I'd like you to acknowledge having deleted, in this text page, some figures which were published in original text. These figures was quotated from Liu Christopher, Masahiko FUKUDA, KaichiSHIMOMURA, Takeshi HAMADA.iFile preparer: OKADA Kiyotakaj

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