Keywords
diffuse leiomyomatosis - extensive myomectomy - longitudinal incision of uterus -
GnRH agonist - MRI - junctional zone
Diffuse Leiomyomatosis
Diffuse leiomyomatosis is an unusual condition in which innumerable small smooth muscle
nodules produce symmetrical enlargement of the uterus. The uterus may be greatly enlarged,
weighting up to 1,000 g. Each nodule ranges from microscopic to 3 cm in size, but
mostly less than 1 cm in diameter. They are composed of uniform, bland, spindled-shaped
smooth muscle cells, and are less circumscribed than typical leiomyoma. Usually, small
nodules occur mainly in the submucosal area, and, therefore, they are recognized as
extensive submucosal myomas by ultrasonography or magnetic resonance imaging (MRI).
Diffuse leiomyomatosis occur in young women at the age of 30's and produce severe
symptoms, such as hypermenorrhea and dysmenorrhea. All of them suffer from iron-deficiency
anemia and also use analgesics during menstruation. They frequently have a past history
undergoing myomectomy. However, traditional surgical approaches by open laparotomy,
laparoscopy, and hysteroscopy usually result in an incomplete myomectomy, and the
patient will complain again of the same symptoms soon after the surgery due to recurrence.
Finally, the patients tend to undergo hysterectomy without childbearing. Thus, diffuse
leiomyomatosis is an important clinical entity and a difficult-to-cure disease in
young women who desires fertility spearing. Gynecologists are asked enthusiastically
by the patient to remove numerous submucosal myomas as complete as possible. In this
text, a novel and radical surgical approach for diffuse leiomyomatosis is described.[1]
Preoperative Evaluation
MRI is absolutely needed to diagnose diffuse leiomyomatosis. T2-weighted image will
disclose numerous small nodules mainly in the junctional zone of the uterine corpus
(Fig. 1A, B). Therefore, this disease is recognized by gynecologists as extensive
submucosal myomas of the uterus. Several nodules may be present in the subserosal
area, but this is not frequent.
Hormonal Treatment before Surgery
It is advised to prescribe gonadotropin-releasing hormone (GnRH) agonist or antagonist
for 3 to 6 months before the surgery. During such hormonal treatment, the uterus and
the nodules become smaller, and the surgery will become much easier. The second MRI
after the hormonal treatment is essential for preoperative planning of the surgery
([Fig. 1C], [D]).
Fig. 1 MRI T2-weighted findings of diffuse leiomyomatosis: nnumerable small nodules are
present in the junctional zone, and protruded into the uterine cavity(A, B). After treatment with four cycles of GnRH agonist, the uterus and myomatous nodules
decrease in size(C, D).(A, C) Sagittal section,(B, D) transverse section.
Tips and Warnings—What is Junctional Zone?
In T2-weighted MRI, the uterine corpus shows the three distinct zonal layers, that
is, the endometrium which is characterized by high-intensity zone along the cavity,
the outer myometrial zone showing relatively high intensity under the serosa, and
the junctional zone with low intensity between the endometrium and the outer myometrium
([Fig. 2]). Actually, the junctional zone is the inner part of myometrium, in which smooth
muscle cells are arranged with more complexity than the outer myometrium. The function
of junctional zone was disclosed by Prof. Kaori Togashi and her collaborators at Kyoto
University, using cine MR imaging.[2] The peristaltic movement of the junctional zone changes dramatically during the
menstrual cycle. The direction of peristalsis occurs from the fundus to downward during
the menstrual period, from the cervix to upward during the periovulatory phase, and
cease during the luteal phase period. This is consistent with the reproductive function
of the uterus in each phase, that is, discharge of the endometrial tissue and blood
in menstruation, support the sperm transport to oviduct, and accept of fertilized
embryo for implantation, respectively.[3] Thus, the peristaltic movement of the junctional zone is essential for reproduction
in the human female. Since diffuse leiomyomatosis is characterized by the occurrence
of numerous nodules in the junctional zone, it will give serious influences to the
reproductive function in women.
Fig. 2 Junctional zone of the uterus: in T2-weighted MRI figures, the uterine corpus is
composed by three different zones. The endometrium appears as the innermost, high-intensity
zone. The outer subserosal zone of the myometrium shows an intermediately high intensity.
The low-intensity zone between the endometrium and the outer myometrium is called
as “junctional zone”, but this is actually the inner part of the myometrium. (This
figure is kindly given by Prof. Kaori Togashi)
1. Opening abdomen.
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2. Tourniquet for hemostasis.
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3. Complete opening of the uterine cavity by deep median incision.
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4. Myomectomy as many as possible.
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5. Closing the uterine cavity by absorbable sutures for three layers.
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6. Application of antiadhesive material.
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7. Closing abdomen.
Explanation of Procedures
General and classical principle for myomectomy described by Dr. Victor Bonney is that
only a minimal number of uterine incisions to remove all myomata should be made. This
was recommended for performing the complete closure of myometrium. According to the
above rule; however, the incision tends to be as small as possible. This should not
be the case in the surgery for diffuse leiomyomatosis, since smaller incision will
miss the occult presence of minute nodules. Thus, the myometrial incision for diffuse
leiomyomatosis should be large enough for complete myomectomy. Here, a novel technique
for extensive myomectomy is presented.
(1) Opening Abdomen and Exploration
Patient is laid in the supine position and urethral catheter is inserted for continuous
bladder drainage. The operator incises the abdominal wall longitudinally from the
pubis toward the umbilicus, then the fascia and peritoneum. The intestines are softly
put upward and maintained with large gauze/sponge, and an appropriate operative field
is obtained by the self-retaining retractor. The operative field is kept moist with
the Ringer solution, and the tissue is handled gently to avoid unnecessary trauma.
(2) Tourniquet for Hemostasis
In order to reduce the blood loss during myomectomy, the soft catheter is applied
as tourniquet for uterine artery at the level of uterine isthmus ([Fig. 3]). To do so, the operator should identify the transparent area of anterior and posterior
leaves of broad ligament, and insert the Pean clamps making the holes for tourniquet.
The tourniquet will be tied tightly enough to occlude the uterine artery.
Fig. 3 Tourniquet for Hemostasis: in order to reduce the blood loss during myomectomy, the
soft catheter is applied as tourniquet for uterine artery at the level of uterine
isthmus. To do so, the operator should identify the transparent area of anterior and
posterior leaves of broad ligament, and insert the Pean clamps making the holes for
tourniquet(A). Then the soft catheter will be tied(B). (Reproduced with permission from Suzuki and Konishi.[1] Copyright © Medical View).
(3) Opening the Uterine Cavity
Deep, median, and longitudinal incision of the uterine corpus is made using the scalpel
([Fig. 4]). Before the incision, the operator should identify the midline that is the midportion
between the isthmic ends of each side of Fallopian tube. The incision is made from
the fundus to downward till the level of isthmus, first anterior wall and then posterior
wall of the uterus. Many myomatous nodules protrude from the cavity and myometrial
wall ([Fig. 5]). Usually, this procedure is accompanied by small amount of bleeding from the myometrial
wall.
Fig. 4 Opening the uterine cavity: deep, median, and longitudinal incision of the uterine
corpus is made using the scalpel. (Reproduced with permission from Suzuki and Konishi.[1] Copyright © Medical View).
Fig. 5 Opening-cavity findings of diffuse leiomyomatosis in the same patient as shown in
[Fig. 1]. Numerous nodules protrude from the cavity and myometrial wall.
(4) Complete Myomectomy
Almost all of myomatous nodules should be removed from the surface of incised myometrial
wall or from the endometrial cavity ([Fig. 6]). More than 95% of macroscopically-detectable nodules can be removed through this
procedure. Blood loss during myomectomy is usually small. It is not necessary for
the operator to concern about the preservation of endometrium. Although considerable
amount of endometrium is removed during the procedure, it will regenerate and soon
recover the normal menstrual cycle. So far, there have been no patients with amenorrhea
or Asherman's syndrome after the surgery.
Fig. 6 Complete myomectomy for diffuse leiomyomatosis in the same patient in [Fig. 5]. Almost all of nodules are removed from the myometrial wall and from the endometrial
cavity.
(5) Closing the Uterine Cavity
When no remaining tumors are macroscopically visible in the uterine wall, it is time
to close the cavity and reconstruct the uterine corpus. Before starting the closing
sutures, the tourniquet is once released to check the presence of heavy bleeding from
the myometrium. Usually, there is no massive bleeding. Reconstruction of the uterine
corpus is performed by the same method as done in the Jones operation for unification
of the bicornuate uterus, using three layers of interrupted sutures with 3–0 or 2–0
Vicryl. The sutures are placed at approximately 5-mm intervals. The most inferior
sutures close to the isthmus should be placed first, and the remainder of the sutures
is then placed, gradually approximating the both sides of wall ([Fig. 7]). Importantly, the first layer for subendometrial sutures should not appear on the
endometrial cavity. In the second layer, the intramural sutures should be tied not
to remain dead spaces. In the third layer for the uterine serosa, the sutures should
be placed beautifully.
Fig. 7 Sutures of the uterine corpus for reconstruction: the first layer sutures should
not appear on the endometrial cavity(A). The third layer sutures for the serosal surface should be placed beautifully(B). (Reproduced with permission from Suzuki and Konishi.[1] Copyright © Medical View).
(6) Application of Antiadhesive Material
After completing the uterine sutures, the operator should check the bleeding from
the uterus, release the tourniquet, and repair the peritoneal holes. Then, the surface
of the uterus is covered by antiadhesive materials, such as Seprafilm, Interceed,
or Adspray.
(7) Closing Abdomen
The abdomen is closed with each sutures for the peritoneum, fascia, and skin. The
operative technique employed should be consistent with the goal of sparing fertility
and the possibility of successful pregnancy.
Postoperative Care and Pregnancy
A period of 3 months of contraception is sufficient before conception. Usually, patients
are prescribed with three cycles of estrogen followed by estrogen–progestin for enhancement
of endometrial regeneration. Active fertile treatment, such as in vitro fertilization-embryo
transfer (IVF-ET) may be needed for conception. If pregnant, the course should be
carefully checked by perinatologist. So far, there have been no experiences of uterine
rupture during pregnancy, but Caesarean section is recommended for safe delivery.
Tips and Warnings—Histopathology of Diffuse Leiomyomatosis
It is very interesting to see the microscopic features of diffuse leiomyomatosis because
we can see the scene of early development of leiomyoma. Actually, there are many microscopic
nodules of hypercellular tumor cells in the subendometrial zone of normal-appearing
myometrium ([Fig. 8]). They blended with each other and merged imperceptibly with the surrounding normal
myometrial smooth muscle cells. Generally, ordinary leiomyomas are composed of mature
smooth muscle cells and immunohistochemically positive for both smooth muscle actin
and caldesmon. In contrast, many of smooth muscle cells in diffuse leiomyomatosis
show hypercellular and immature features, since they have scant cytoplasm positive
for smooth muscle actin but negative for caldesmon but some other cells are positive
for both proteins. Thus, in the minute nodules, we can see the process of differentiation
of smooth muscle cells in the growth of leiomyomas.[4]
Fig. 8 Microscopic features of diffuse leiomyomatosis: hypercellular smooth muscle cells
are irregularly arranged intervening with the surrounding normal smooth muscle cells.
HE section of low magnification(A) and higher magnification(B) showing immature smooth muscle cells, which are immunohistochemically positive for
smooth muscle action(C), but negative for caldesmon(D). HE, hematoxylin–eosin.
Case Presentation: A 27-year-old, nulligravid woman presented with hypermenorrhea and dysmenorrhea.
Her past history was GnRH agonist treatment for leiomyoma at 25 years, laparotomic
myomectomy at 26 years and then hysteroscopic myomectomy at 27 years of age. She was
recently married and desired childbearing. MRI showed numerous small myomatous nodules
in the junctional zone ([Fig. 9]). First, she received four cycles of GnRH agonist treatment, and MRI showed much
decrease in size of uterus and modules. She underwent laparotomy and removal of 90
nodules using the current myomectomy method ([Fig. 10]). Operating time was 3 hours and the blood loss was 200 g. Six months after the
myomectomy, fertile therapy resulted in pregnancy. The course of pregnancy was uneventful,
and a male baby 2,174 g was born by Caesarean section at 36 weeks. There were no ruptures
of the uterine wall, and the myomectomy scar was smooth ([Fig. 11]).
Fig. 9 Case presentation: a 27-year-old woman presented with recurrent hypermenorrhea and
past histories of two surgeries, such as open myomectomy and hysteroscopic myomectomy.
MRI T2-weighted findings of diffuse leiomyomatosis at presentation(A) and after treatment with four cycles of GnRH agonist treatment(B). MRI, magnetic resonance imaging.
Fig. 10 Case presentation: myomectomy findings of diffuse leiomyomatosis in the same patient,
showing the cut section of the uterine corpus (A), the uterine wall after myomectomy (B), and reconstruction of the uterine corpus (C). Six months after the surgery, the patient became pregnant.
Fig. 11 Caesarean section findings of the same patient in [Figs. 9] and [10], showing the anterior view(A) and the posterior view(B) of the uterine corpus just after C-section. Scar of myomectomy is visible, but there
are no ruptures.
