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348
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R. Oyama and T. Ikebe
1.7.5 Oral Lesions DuetoPregnancy
Pregnancy Gingivitis
Pregnant women are more susceptible to gingivitis because estrogen, a female hormone, affects
the growth of periodontal disease bacteria as well
as periodontal tissues, which is thought to be
associated with progesterone-induced prostaglandin production. The concentration of female
hormones are known to be 10 to 30 times higher
at the end of pregnancy than during menstruation, and pregnancy gingivitis is more likely to
occur during the second and third pregnancy trimesters. Clinically, it is characterized by a
rounded swelling of the interdental papillae on
the anterior teeth. Pregnant women with periodontal disease are known to be at risk for low
birth weight infant and premature birth.
Pregnancy Epulis
It is found in about 1% of pregnant women and
develops around the third month of pregnancy.
After delivery, the lesions spontaneously shrink
and fade away. Histopathologically, it often consists of granulomatous or angiomatous tissues.
As in usual epulis, it is most frequently seen on
the interdental papillae of anterior teeth. The
lesions also bleed easily. Since pregnant women
are susceptible for periodontitis and dental plaque
aggravates the symptoms, plaque control such as
brushing instruction is very important for pregnant women. Surgical excision should be waited
until after childbirth.
Herpes Gestationis (Pemphigoid
Gestationis)
Edematous erythema with severe pruritus appears
on the abdomen, buttocks, and extremities, and
small bullae appear on the erythema, which often
occurs in the second and third trimester, or immediately after delivery. Oral mucosal lesions are
rare and it is transient and disappears spontaneously. Anti-BP180 autoantibodies cause this
lesion.
1.7.6 Supine Hypotensive Syndrome
During dental treatment of pregnant women in
the third pregnancy trimester, cerebral anemia
may occur due to hypotension. When a pregnant
woman in this period is placed in the supine position, the uterus presses on the inferior vena cava
and the venous return is obstructed, resulting in a
decrease in cardiac output and hypotension. It is
important to avoid the horizontal position for
dental treatment of pregnant women in the third
pregnancy trimester. Dental treatment should be
performed in the left side down position or in a
reclined position.
References
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(Sanfujinka Shinryo Guideline Sankahen). Tokyo:
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Board of Perinatal Medicine; 2016. p. 208–10; (in
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6. Christina J.Infections at the maternal–fetal interface:
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7. Kobayashi Y, Yamamoto T. 077 Gestational hypertension (Ninshin Kouketsuatsu Shoukougun).
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1594, 2005.
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clinical presentations JACC state-of-the-art review. J
Am Coll Cardiol. 2020;76(14):2020.
10. The Japanese Society of Diabetes and Pregnancy, editor. Manual of diagnosis and management of abnormalities of glucose metabolism in pregnant women
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metabolic and reproductive disorder. Biomed
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with pregestational diabetes mellitus. J Pernat Med.
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14. Cox J, etal. Detection of postnatal depression: development of the 10-item edinburgh postnatal depression
scale. Br J Psychiatry. 1987;150:782–6.
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Cold Spring Harb Perspect Biol. 2010;2(12):a003178.
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HIV.HIDS info. https://aidsinfo.nih.gov. Accessed 17
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feeding on transmission of HIV-1. A randomized clinical trial. JAMA. 2000;283:1167–74.
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Training note no. 81 management of breast disease. Tokyo: Japan Association of Obstetricians and
Gynecologists; 2009. p.1–106; (III) (in Japanese).
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Organ Transplantation (Bone
https://t.me/medicina_free
Marrow Transplantation, Liver
Transplantation)
AkiraSasaki, TakeshiTakahara, TadahideNoguchi,
andYoshiyukiMori
20
1 Organ Transplantation
AkiraSasaki, TakeshiTakahara
1.1 Introduction
Organ transplantation is a medical procedure in
which organs are transferred from a donor to a
recipient to restore function to a patient whose
organ function has been severely impaired by serious illness or accident. Donors are classied into
two groups: cadavers and living organisms, and
cadavers can be brain dead or in cardiac arrest.
Most recipients are experiencing organ failure,
and their life expectancies are short or their daily
quality of life is signicantly impaired. The development and advancement of immunosuppressive
drugs have improved the outcome of organ trans-
A. Sasaki
Department of Surgery, Iwate Medical University
School of Medicine, Yahaba, Iwate, Japan
T. Takahara (*)
Department of Surgery, Fujita Health University,
Toyoake, Aichi, Japan
T. Noguchi
Department of Dentistry, Oral and Maxillofacial
Surgery, School of Medicine, Jichi Medical
University, Shimotsuke, Tochigi, Japan
Y. Mori
Department of Dentistry, Oral and Maxillofacial
Surgery, Saitama Medical Center, Jichi Medical
University, Saitama, Japan
plantation. After transplantation, if patients take
immunosuppressive drugs and are careful about
rejection and infections, most of them can lead
almost the same daily lives as healthy people.
1.2 The History ofTransplantation
Medicine
Liver transplantation and lung transplantation
were rst performed in the United States in 1963,
and heart transplantation was rst performed in
South Africa in 1967. In Japan, Niigata University
performed a temporary kidney transplantation for
a patient with acute renal failure in 1956, the
University of Tokyo performed a living kidney
transplantation for a patient with chronic renal
failure in 1964, and Chiba University performed
its rst liver transplantation in the same year.
Organ transplantation in Japan began at about the
same time as the rest of the world. In Japan, various problems related to Wada heart transplantation at Sapporo Medical University in 1968
created a sense of distrust toward brain death and
organ transplantation, which may have contributed to the slow progress of transplantation in
Japan compared to Europe and the United States.
Since the Law Concerning Organ Transplantation
was enacted in 1997, and the Law Concerning
Organ Transplantation was revised in 2009, the
number of brain death organ donations has been
gradually increasing (Fig.20.1) [1].
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
T. Chiba, H. Yamada (eds.), Internal Medicine for Dental Treatments,
https://doi.org/10.1007/978-981-99-3296-2_20
351
352
10
20
30
40
50
60
70
80
Before the revision After the revision
https://t.me/medicina_free
Enforcement of the
Organ Transplant Law.
10
8
0
0
0
1997
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
5
4
6
3
9
5
Fig. 20.1 Number of organ donations (created based on [1])
A. Sasaki et al.
Enforcement of the
revised law
76
64
58
50
47
45
44
29
13
13
7
3
2016 2017
1.3 Organ Donation
removal from the donor is 4h for the heart, 8h
for the lungs, 12h for the liver and small intes-
Organ donation is possible after brain death or
tine, and 24h for the pancreas and kidneys.
cardiac arrest. In 1997, the Law on Organ
Transplantation was enacted to recognize brain
death as human death and to allow organ trans-
1.4 Rejection
plantation after brain death as long as the patient
expressed in writing the intention to donate
organs according to the determination of brain
death. The family must also agree to the
determination of brain death and organ donation.
The International Society for Transplantation
(IST) approved Japan’s revised Organ Transplant
Law in 2008 and the revised Organ Transplant
Law in 2010, which allows organ donation with
the consent of the family even if the patient’s will
to donate is unknown. The revised law also
includes a lowering of the age limit for organ
donation and a ban on organ donation from children suspected of having been abused. The age
limit for organ donation is 50years or younger
for the heart, 70years or younger for the lungs,
70years or younger for the kidneys, 60years or
younger for the pancreas, and 60years or younger
for the small intestine; there is no age limit for the
liver at this time. The following organs can be
donated after brain death: heart, lung, liver, kidney, pancreas, small intestine, and eyeball. The
organs that can be donated after cardiac arrest are
the kidney, pancreas, and eyeball. In the case of
organ donation after brain death, the time allowed
for the resumption of blood ow after organ’s
A transplanted organ is non-self to the recipient
and is recognized as an antigen by the major his-
tocompatibility complex (MHC). The recipient’s
immune cells attack the transplanted organ,
which results in rejection. Rejection can be
divided into three categories: hyperacute rejec-
tion, acute rejection, and chronic rejection.
Hyperacute rejection is thought to be caused by
humoral immunity, and thrombus formation
occurs within 24h after transplantation, result-
ing in organ ischemia. It is thought to be related
to the recipient’s existing anti-human-leukocyte-
antigen (HLA) antibodies. Acute rejection often
occurs between 1week and 3months after trans-
plantation, and is mainly related to cellular
immunity. Cellular immunity is induced by anti-
gen presentation by MHC class II antigens of
donor-derived organs. Chronic rejection often
occurs after 3 months of transplantation is
thought to be mainly due to the effect of humoral
immunity, which has been recently reported to
be related to antibody-mediated rejection. It is
difcult to control with general immunosuppres-
sive drugs, and retransplantation may be
considered.
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1.5 GVHD
Graft-versus-host disease (GVHD) is a condition
in which donor-derived immune competent cells
regard the host as an antigen, often due to rejection of hematopoietic stem cells. It can be divided
into acute GVHD and chronic GVHD.In acute
GVHD, skin symptoms are often the rst symptoms, and the main organs affected are the skin,
gastrointestinal tract, and liver. Steroids are
administered as a treatment. Chronic GVHD
refers to GVHD that develops after 100days of
transplantation, and it is believed that more
organs are affected by chronic than acute GVHD.
1.6 Bone Marrow Transplantation
andPeripheral Blood Stem
Cell Transplantation
1.6.1 Bone Marrow Transplantation
Bone marrow transplantation is the transplantation of normal bone marrow cells from a donor
into a patient with leukemia or aplastic anemia by
intravenous infusion. When bone marrow transplantation is performed, the donor and recipient
must match in terms of HLA, and if incompatible
bone marrow cells are transplanted, rejection and
GVHD may occur.
1.6.2 Peripheral Blood Stem Cell
Transplantation
Daily injections of granulocyte colonystimulating factor (G-CSF), which increases the
number of hematopoietic stem cells in the blood,
can be administered to donors to obtain enough
hematopoietic stem cells from the peripheral
blood for transplantation. Depending on the body
weight of the recipient, bone marrow transplants
require 600 to 1000cc of infused bone marrow
uid, whereas peripheral blood stem cell transplants often require less than 200cc. Peripheral
blood stem cell transplantation is associated with
a higher incidence of GVHD than bone marrow
transplantation because of the large number of
donor-derived lymphocytes in addition to hematopoietic stem cells. On the other hand, the effect
of graft versus leukemia (GVL) is also high, and
it is expected to reduce the recurrence rate.
1.7 Liver Transplantation
Liver transplantation is a newer medical treat-
ment developed by Starzl et al. in the United
States. After overcoming the hardships of its
early days, the results of liver transplantation
have dramatically progressed through improve-
ments in surgical techniques, organ preservation
methods, immunosuppressive drugs, and periop-
erative management. In the United States,
approximately 6000 deceased donor liver trans-
plantation are performed annually. In Japan, the
Deceased Donor Liver Transplantation Bill was
enacted in October 1997, making deceased donor
liver transplantation legally feasible, and the rst
deceased donor liver transplantation in Japan was
performed at Shinshu University in February
1999.
On the other hand, in Japan, living donor liver
transplantation, in which a partial liver from a
healthy person is transplanted, was rst performed at Shimane University in November
1989, followed by Kyoto University and Shinshu
University. The cases of living donor liver transplantation have been accumulated solemnly, and
the results are better than those of deceased donor
liver transplantation. The current indications for
liver transplantation are as follows.
1.7.1 Indications forLiver
Transplantation
1. Children
(a) Post necrotic liver cirrhosis: congenital
liver brosis and neonatal hepatitis.
(b) Cholestatic liver cirrhosis: biliary atresia,
Alagille syndrome, primary biliary cholangitis, secondary biliary cirrhosis, progressive
familial bile stasis.
(c) Fulminant hepatitis: viral hepatitis, drug-
induced liver injury.
(d) Metabolic diseases: Wilson’s disease,
alpha1-antitrypsin deciency, hemochromatosis, hyperoxaluria, glycogenosis (types I
and V), Crigler-Najjar syndrome, NiemannPick disease, protoporphyrinemia,
hypertyrosinemia.
(e) Malignant tumor: hepatoblastoma, hepato-
cellular carcinoma.
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A. Sasaki et al.
(f) Benign tumor: hepatic lymphangioma.
(g) Others: hemophilia.
2. Adults
(a) Post necrotic liver cirrhosis: hepatitis B
cirrhosis, hepatitis C cirrhosis, alcoholic cirrhosis, autoimmune cirrhosis, cirrhosis of
unknown origin.
(b) Biliary cholangitis: primary biliary cholan-
gitis, primary sclerosing cholangitis (PSC).
(c) Fulminant hepatitis: viral hepatitis, drug-
induced liver injury.
(d) Metabolic diseases: Wilson’s disease,
alpha1-antitrypsin deciency, hemochromatosis, familial amyloid polyneuropathy,
citrullinemia.
(e) Malignant tumor: hepatocellular
carcinoma.
(f) Benign tumor: diffuse cavernous hemangi-
oma, multiple hepatic cysts, cavernous sinusoidal hemangioendothelioma.
(g) Other: Budd-Chiari syndrome.
1.7.2 Deceased Donor Liver
Transplantation
1. Donor surgery: In brain death donor surgery,
multiple organ harvesting teams proceed in
parallel. A midline incision from the upper
clavicle to the pubic symphysis is used to
remove the abdominal and the thoracic organs
(heart, lungs, etc.). A liver biopsy is performed
as necessary to conrm that there is no trauma
to the liver cirrhosis, or severe fatty liver. The
graft is removed by irrigating the abdominal
aorta and portal vein with ice-cold preservation uid (UW solution is commonly used).
The graft is then immersed in UW solution
and transported ice-cold. The graft can usually be stored for 12h.
2. Recipient surgery: Different transplantation
methods, such as whole liver, partial liver,
split liver transplantation, and auxiliary partial orthotopic liver transplantation depend on
how the grafted liver is transplanted.
Depending on the recipient’s body size, either
whole or partial liver transplantation is
1.7.3 Living Partial Liver
1. Donor surgery: The most important factor in
selected. To compensate for the recent shortage of donors, a split liver transplantation can
save the lives of two recipients by dividing the
graft into two parts and using both parts as
grafts. In fulminant hepatitis, when the autologous liver is considered regenerable, half of
the autologous liver is left, and a partial liver
graft is transplanted only during the period
when the patient is out of acute liver failure.
Total hepatectomy of the recipient is performed by the following procedures: hepatotransplantation, hepatic portal dissection
(dissection of the hepatic artery, portal vein,
and common bile duct), and treatment of the
inferior vena cava (taping above and below the
liver). The transplantation is completed by
removing the recipient’s diseased liver and
reconstructing the hepatic artery and portal
vein as the inow tracts of the grafted liver and
the inferior vena cava and the bile duct as the
outow tracts. If the recipient’s inferior vena
cava is preserved, the inferior vena cava, portal
vein, hepatic artery, and bile duct of the graft
should be anastomosed in this order. When the
recipient’s inferior vena cava is resected, the
graft liver is anastomosed in the following
order: superior inferior vena cava, portal vein,
hepatic artery, inferior vena cava, and bile duct.
Transplantation
donor surgery is safety. The donor is a perfectly healthy person who donates their organs
altruistically, and is not a patient. Therefore,
postoperative complications that interfere
with social life must be prevented.
In living donor partial liver transplantation,
the volume of the liver required by the recipient determines where the graft should be taken
from the donor. Based on the recipient’s body
surface area, a standard liver volume is calculated, and a graft with a volume of at least 40%
of the standard liver volume is used. Generally,
a lateral zone graft is used in children, and a
left or right lobe graft is used in adults.
accessory hepatic vein
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It is important to note that donor hepatectomy, standard normal hepatectomy, avoids
warm ischemia to the graft as much as possible to maintain sufcient graft viability; the
hepatic artery and portal vein are separated
after the liver dissection. Intraoperative cholangiography is performed to conrm the location of the bile ducts, and the position of the
bile ducts is determined. After removal of the
graft, the graft is irrigated from the portal vein
on a back table with a perfusion uid, such as
UW solution, at a temperature of 4 °C or
lower. If necessary, hepatic venoplasty of the
graft is performed.
hepatic vein
2. Recipient surgery: The process of recipient
surgery up to total hepatectomy includes hepatotransplantation, hilarization, and dissection of the short hepatic vein. In patients with
biliary atresia who have undergone Kasai’s
operation in the past, there is a high degree of
adhesion in the gastrointestinal tract, which
must be carefully dissected. After the graft is
removed, the hepatic vein and portal vein are
anastomosed to restore hepatic blood ow,
followed by the hepatic artery and bile duct.
The two types of biliary reconstruction are
bile duct–jejunal anastomosis and bile ductbile duct anastomosis (Fig.20.2).
V
8
V
5
choledochocholedochostomy
Fig. 20.2 Right lobe graft (bile duct-bile duct anastomosis)
hepatic artery
portal vein
decompression stent tubes
common bile duct
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A. Sasaki et al.
1.8 Notes fromDentistry
Perspective
TadahideNoguchi,YoshiyukiMori
1.8.1 Pre- andPosttransplant Oral
Status andResponse
Hematopoietic stem cell transplantation is now
used in the treatment of leukemia and malignant
lymphoma, but its anticancer drug therapy and
systemic radiation therapy can damage the oral
mucosa and pose a risk of systemic complications.
Therefore, dental treatment and oral care before
transplantation should be actively performed.
Before Transplantation
Intraoral examination and dental treatment
before transplantation: Before treatment, check
for caries, periodontal disease, and other lesions
that may cause problems during treatment. It is
desirable to complete dental treatment at least 2
weeks before the pre-transplant procedure, but
rst-aid should be performed so that the patient
can progress without problems until the transplant treatment is completed.
If possible, extract the source of infection (e.g.,
severely periodontally diseased teeth with deep
pockets and pus discharge, periapical pathosis or
impacted wisdom teeth with a history of inammation,) because they may cause dental infection.
After extraction, the extraction sockets should be
covered with mucosa to prevent exposure of the
bone. Prophylactic antibiotics should be administered before proceeding with tooth extraction.
In addition, thorough plaque control should be
performed to prevent stomatitis (aiming for a
plaque control record [PCR] of 20% or less), and
patients should learn self-care to maintain oral
cleanliness and prevent xerostomia (moisturizing
gel, mouth rinse, aznolene ointment, etc.) during
transplant treatment.
used, and if the pain is severe, a rinsing solution
containing xylocaine should be used.
Oral Care After Transplantation
Treatment of graft-versus-host disease
(GVHD): There are two types of GVHD: acute
GVHD that occurs within 100days of transplantation and chronic GVHD that occurs later. Acute
GVHD presents with redness, erosion, and bleeding of the oral mucosa and resembles radiation
stomatitis. In chronic GVHD, oral symptoms are
often present at the rst sign of disease, and 80%
of patients have oral symptoms. Symptoms
include lichen planus-like oral mucosal lesions
and xerostomia due to salivary gland disorders
similar to Sjögren’s syndrome (Fig.20.3). The
guidelines of the Japanese Society for
Hematopoietic Cell Transplantation state that
chronic GVHD should be diagnosed using the
Treatment ofStomatitis After
Pretreatment (Chemotherapy, Total-Body
Irradiation) andDuring Transplantation
Therapy
Thorough oral hygiene and symptomatic treatment are essential. Azulene rinses should be
Fig. 20.3 Chronic GVHD. Upper: a keratotic lesion
resembling oral lichen planus is seen on the mucous membrane of the right cheek. Lower: White keratotic lesion on
tongue is observed
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Table 20.1
Clinical signs of chronic GVHD
Organ Diagnostic signs Characteristic signs
Oral Lichen planus-like
Created based on [2]
Clinical signs of chronic GVHD
changes
Xerostomia, mucosal atrophy, mucosal cysts,
pseudomembranes, ulceration
diagnostic criteria proposed by the NIH consensus development project [2] (Table20.1).
Treatment includes topical steroids or local
injections of steroids, and intraoral PUVA (ultraviolet) therapy. At the same time, treatment for
xerostomia should be continued.
We have occasionally encountered cases of
oral candidiasis caused by the use of steroids or
immunosuppressive drugs, and the symptoms
have worsened. There are two diagnostic methods for oral candidiasis: (1) isolation and identication of Candida by culture; and (2) observation
of mycelium by microscopy. Because Candida is
an indigenous bacteria, it is not possible to diagnose oral candidiasis even if it is detected only by
culture tests, and it is necessary to detect Candida
mycelium in lesions for denitive diagnosis
(Fig.20.4).
If steroid ointment is being applied, it should
be temporarily discontinued, and topical application of antifungal agent (miconazole:
FLORIDGEL® for oral use) or itraconazole
(Itrizole® Oral Solution 1%) should be swallowed after the medication has been distributed
throughout the mouth. Alternatively, rinse the
mouth with a polyene antifungal agent (amphotericin B: Fungizone®). It is important to use the
medication for 1 to 2weeks because mycelium
may remain even after symptoms improve [3].
Other
symptoms Common signs
Periodontitis, stomatitis,
redness, pain
Fig. 20.4 Microscopic image of Candida mycelium. The
presence of mycelium indicates that Candida is
pathogenic
References
1. Yuzawa K. Japanese transplantation registry 2017
annual report. Japanese J Transplant. 2018;53(2/3):79;
(in Japanese).
2. The Japan Society for Hematopoietic Cell
Transplantation. Guidelines for hematopoietic cell
transplantation GVHD. 4
56: 1–77, 2018; (in Japanese). https://www.jstct.or.jp/
uploads/les/guideline/01_02_gvhd_ver04.pdf.
3. Noguchi T.Oral candida not cured (Khoku Candida
ga Naoranai). Medicina 8. Tokyo: Igaku Shoin; 2017.
p.1426–31; (in Japanese).
th
ed. JSHCT monograph,
Соседние файлы в папке Библиотека им академика М.И. Перельмана