Toshisuke SAITO, M.D.,* Mitsuyoshi NAGAE, M.D., PhD.*
* Hiroo Medical Clinic (Gynecology clinic), Yokohama, Japan.

Corresponding author: Toshisuke Saito, MD,
Hiroo Medical Clinic, 5-20 Ichiba-shimocho, Tsurumi-ku, Yokohama 230-0024, Japan.
Office Phone: +81-45-505-4149. Fax: +81-45-505-4750
E-mail: hiroo@ca.mbn.or.jp

Sources of financial support: none
Author contributions: TS has considerable experience in uterine cancer surgery and has extensively studied pelvic surgery. He developed the procedure described in this paper and has performed it successfully numerous times.

MN worked as an assistant surgeon under TS. He worked with TS to improve the procedure and contributed many valuable comments to this paper.

Condensation:

Treatment for adenomyosis involving the separation of the uterus into three layers and removing the affected layer: reports of six deliveries in five patients.

Conservative surgery for patients with adenomyosis: Technique and results
Toshisuke SAITO, M.D., Mitsuyoshi NAGAE, M.D., PhD.

Abstract

Objective: To describe conservative surgical treatment of adenomyosis as developed at out institution and report postoperative results, including those of successful pregnancies and deliveries.

Study design: Retrospective review and statistical analysis of records for first 138 patients with pathologically confirmed adenomyosis who were treated with the new, conservative procedure. We explain this procedure in detail with illustrations. Obstetricians have reported to us that five women with adenomyosis achieved six successful deliveries after treatment. We report their cases.

Results: We have performed more than 4,000 procedures on patients with myoma, adenomyosis, or both. Nearly all patients with adenomyosis had relief from preoperative symptoms and exhibited improved laboratory results following surgery. At least 6 deliveries from 5 patients are known.

Conclusions: Conservative surgical treatment of adenomyosis, even severe cases, is safe and effective; preservation of reproductive ability is possible with this technique.

Key words: adenomyosis, conservative surgery, pregnancy, delivery,laser,endometriosis

Introduction.

Adenomyosis, a common gynecological disease of women of reproductive age, typically presents with symptoms ranging from hypermenorrhea to infertility. Uterine myoma, adenomyosis and endometriosis often coexist. Medical management of endometriosis-associated pain has been well established1) 2), as well as surgical treatment including recent laparoscopic laser ablation3). In Japan, medical treatment of adenomyosisis is limited to gonadotropin-releasing hormone agonist in severe cases. However examining the histories of present illness of more than 4,000 cases at our clinic, simple total hysterectomy has been advised for the more severe cases. We developed a new surgical treatment that conserves the uterus; we describe this technique, which not only has enabled complete relief of symptoms in almost all of our patients but has also resulted in at least six successful deliveries. We report the cases of successful pregnancy and delivery of which we are aware.

Patients and Methods

Patients. We examined records of the first 600 inpatients diagnosed by our clinic (September 1988 - September 1991) with myoma and/or adenomyosis that required surgery. Of this total, only 138 cases had the diagnosis of adenomyosis confirmed by postoperative pathological examination. Before visiting our clinic, all 138 had been advised by doctors in other hospitals that only simple total hysterectomy was available as treatment. The patients ranged in age from 27 to 50 years (mean±SD = 41.1±5.6), with mean parity of 0.84±1.05 (SD), and mean gravida of 1.81±1.71 (SD). These 138 cases were examined statistically.

Preoperative evaluation and preparation. All patients were given preoperative general examinations including magnetic resonance imaging (MRI), computerized tomography (CT), ultrasonography (US), and measurement of serum CA-125, as well as tested for cancer of the uterine cervix and endometrium. All MRI scans were performed under conditions of T2 weighting and SE of 2200/100. During operation, no blood transfusions or hematinic medications were given to the 138 patients except under emergency conditions

After vaginal washing, a 30-cc silicone rubber indwelling catheter was inserted into the endometrial lumen and inflated as much as possible with an indigo carmine and physiologic saline solution. This served to facilitate observation of the endometrium during surgery and to pressurize it afterward.

Surgical procedure. During the study period of 1988 through 2007, our clinic used a Pfannenstiel’s incision if possible, on patients subsequently diagnosed with myoma and/or adenomyosis. Surgical orientation for our procedure was based on results of preoperative MRI and intra-abdominal palpation. The uterine fundus, adnexa, ureters, bladder, colon and other organs were carefully examined and manually separated when adhesions were found. As a general rule, the fundus was pinched out of the abdomen and a tourniquet with rubber tubing was applied to the cervix beneath the adnexa.

Starting with either the anterior or posterior portion of the uterus body, dependent on where tissue was hypertrophic, the fundus was incised longitudinally along the median, avoiding critical sections. Figure 1 shows the incision made parallel to the serosal plane, leaving approximately 5 mm of myometrial tissue for the outer C layer (serosal side). Incision of the endometrium was avoided except in the unusual case of accidental perforation. (The illustration shows the inside boundary of the endometrium solely for illustration purposes.)

Deepening the incision, the median layer B (myometrium) was abscissed in cuneiform fashion while the elasticity of the balloon was checked with fingers to confirm tissue thickness. The abscission was performed so that approximately 5 mm remained for the inner layer A (endometrial side). In patients exhibiting extraordinary deformation or enlargement, 5 mm was preserved on both the inner and outer layer, taking particular care to avoid perforation of the outer layer while removing as much of the affected median layer as possible. Attention should be paid to keep the isthmus of Fallopian tube intact, in order to prevent postoperative tubal infertility.

When the endometrium seemed to be unaffected, no further tissue was removed. In many cases, removal of excessive endometrial tissue in large adenomyosis lesions depended on whether the patient desired preserve the option of pregnancy. We were careful to avoid endometrial perforation, particularly if the patient wished to become pregnant after surgery.

To conserve the uterus, important tissue such as oviducts, ovary cardinal ligaments and the bladder had to be protected from damage. Blood flow was secured, and dead space was eliminated during abscission and formation. For this purpose, extraneous portions of the outer layer were eliminated longitudinally. The same surgical procedure was repeated for the contralateral portion of the uterus.

Ablation was applied bidimensionally with CO2 laser (300 Hz scanner mode; output 6?18W; pulse 100?1800 ?s; Nidek, Inc. COL-1040SH) to the endometrial boundary, principally over the outer surface of the inner layer A and inner surface of the outer layer C. Defocused laser ablation was also used to remove lesions of the adnexa, oviduct and cervix, where removal with standard scalpel and scissors was difficult.

In cases where the endometrium was perforated, a running suture was applied. The outer layer was closed with interrupted suturing, followed by fine suturing. To minimize the risk of dead space, the inner layer was pulled tight to make close contact with the outer layer. The rubber tourniquet was removed when suturing was finished.

The indwelling catheter was left pressurized for 24 hours for angiopressure and then removed.

Before the abdominal cavity was closed, it was washed with a 0.9% saline solution and medicated with antibiotics (Fosfomycin). A Relia Vac Suction Kit tube (C.R. Bard, Inc. USA) was inserted and left in place for three days.

Statistical analysis. Pre- and postoperative values for CA-125, red blood cell count, hemoglobin, and hematocrit for the first 138 patients whose data were retrieved was analyzed with use of a two-tailed sign test.

General Results and Case Reports

Since this treatment was first developed, nearly all of our patients have had relief of their preoperative symptoms. Table I shows results for the first 138 patients whose data were analyzed. Doctors in charge of delivery by caesarean section have reported to us that five of our patients had successful pregnancy and childbirth after surgery. The five cases are presented below.

Case 1 was a 33-year-old nulliparous woman who was diagnosed with myoma after a spontaneous abortion at two months of gestation. After her diagnosis was given at a university hospital based on MRI results and she was advised that simple total hysterectomy was her only treatment option, she came for a consultation to our clinic. After undergoing surgery in April 1996, she delivered a 3,056 g boy in March 1998 by cesarean section. Figure 6 shows pre- and postoperative MRI scans. The removed tissue weighed 75 g; pathological examination confirmed adenomyosis.

Case 2 was a 27-year-old gravida 0 woman with a history of dysmenorrhea since age 20 years. At age 21, she was treated with gonadotropin-releasing hormone agonist but discontinued treatment due to severe side effects. She then underwent laparoscopy, after which she was informed that surgery was not possible. Our procedure, performed in July, 2001, removed 145 g of tissue. Pathological examination confirmed adenomyosis. Figure 7 shows pre- and postoperative MRI scans. She delivered a 2,814 g boy in November 2003 and a 2,328 g boy in January 2007.

Case 3, a 38-year-old gravida 0 woman, visited a large hospital at which myoma was diagnosed. Treatment with gonadotropin-releasing hormone agonist was advised, but she refused. After undergoing surgery at our clinic in August 2003, her menstruation stopped. Ultrasound examination revealed that she was pregnant, and she was hospitalized in a university hospital. She was transferred to another university hospital, where she delivered a 2,300 g girl by caesarean section in August 2006. Severe postpartum bleeding led to simple total hysterectomy. Figure 8 shows her pre- and postoperative MRI scans. The tissue removed during her procedure at our clinic weighed 171 g; pathological examination confirmed adenomyosis.

Case 4, a 37-year-old gravida 0 woman with a congenitally anomalous septate uterus, had experienced dysmenorrhea and hypermenorrhea for 10 years. Adenomyosis was diagnosed; more recently, she reported severe abdominal pain and constipation. She was treated gonadotropin-releasing hormone agonist, but her symptoms failed to improve. She was advised that the only treatment option available was simple total hysterectomy. At our clinic, surgery in October 2003 removed tissue weighing 558.1 g. Pathological examination confirmed adenomyosis. Figure 9 shows her pre- and postoperative MRI scans. She delivered a 2,940 g girl in June 2005.

Case 5, a 39-year old gravida 0 woman, was hospitalized for hypermenorrhea, dysmenorrhea and anemia. She was treated with gonadotropin-releasing hormone agonist for six months, but experienced severe side effects that included headache and dizziness. At age 32, she was diagnosed with myoma. At age 34, she became pregnant but had a spontaneous abortion early in the pregnancy. After undergoing our procedure in September 1997, she became pregnant by in vitro fertilization ? embryo transfer. She delivered a 1,506 g boy in March 2002. Figure 10 shows her pre- and postoperative MRI scans. The tissue removed weighed 341 g; pathological examination confirmed adenomyosis.

Discussion

A common treatment for severe adenomyosis is gonadotropin-releasing hormone agonist administered for a maximum of six months. Side effects are often severe. If treatment fails, simple total hysterectomy is typically advised. Relief of secondary dysmenorrhea caused by adenomyosis can be ensured after hysterectomy but less invasive approaches can be tried initially4). The authors observed that the myometrium hardened by adenomyosis could be removed, preserving the rest of the uterus. Our technique was created by separating the uterine wall into three layers and resecting only the affected myometrium.

Use of this treatment method is further supported by reports of abdominal pregnancies resulting in successful childbirth5), which indicate that the uterus itself is not necessary for implantation and fetal development, as delivery can be performed by caesarean section. The endometrium is suitable for implantation and fetal growth. The serosal side plays a protective role in fetal growth, and the normal myometrium supports vaginal delivery and postpartum involution.

In seeking to raise pregnancy and delivery rates for patients with adenomyosis or myoma, factors such as the patient’s reproductive ability (including age) and timeliness of treatment are important. The number of oocytes in the ovary peaked at 20th gestational week in utero and decreases gradually4). Noyes et al described the cyclic histologic changes in human endometrium, which proved in an orderly response to cyclic hormonal production by the ovaries6). On the other hand, precise analysis on relationship between age and menstruation, age group at 25-34 years showed the greatest stability and efficacy of ovarian activity7), which agree with the general understanding of fertility. Endogenous opioid peptides are making the mechanism of reproduction clear8). In most of our cases, patient’s age and severity of adenomyosis were not appropriate for pregnancy and delivery. Other important factors relate to how the surgical procedure is performed, and we discuss those limitations and considerations here: Since our cases were very severe, the rate of achieving pregnancy is about 1%, however in adenomyosis, mass size usually ranges from the size of a fist to a child’s head, younger patient age is expected to increase success rate significantly. The most intact endometrium is found in the lower part of the uterus, and it is possible for implantation to occur here. As a result, efforts should be made to preserve as much of the inner layer A as possible in this area. Nevertheless, as in the case of Case 3, severe uncontrollable bleeding may occur postpartum, requiring hysterectomy.

Removal of the outer tissue layer after abscissing the affected median layer may result in problems. The removal of too much of the outer layer may disrupt uterine enlargement such that fetal growth results in spontaneous abortion. This aspect of the surgery requires further analysis for refinement.

We were advised of the six successful deliveries by the doctors in charge. We believe that more of our patients probably achieved pregnancy but did not notify us because of their impression that our hospital might charge fees related to subsequent pregnancy following surgery (it does not). Some patients also perceive their pregnancy as a matter of course. As a result, we believe the number of successful deliveries is probably higher than reported here.

This is the first report on this surgical method. In spite of its relative novelty as a treatment option, at least five patients with severe adenomyosis who underwent this procedure were able to achieve successful pregnancy and delivery. Our five cases were extremely severe cases of adenomyosis but for typical cases of adenomyosis, safely perform this conservative surgery.

Acknowledgments

All pathological analyses were performed by Dr. Toshiko Nakajima, FALCO Biosystems Ltd., 17-1 Tai-nishiarami Kumiyama-cho, Kuze-gun, Kyoto 613-0036, Japan.

References

1. Mahutte NG, Arici A. Medical management of endometriosis-associated pain. Obstet Gynecol Clin N Am 2003; 30; 133-150.
2. Ling FW, For the pelvic pain study group. Randomized controlled trial of depot Leurpolide in patients with chronic pelvic pain and clinically suspected endometriosis. Obstet Gynecol 1999; 93:51-58.
3. Donnez J, Squifflec J. Laparoscopic excision of deep endometrosis. Obstet Gynecol Clin N A 2004; 31; 567-580.
4. Berek JS. Berek & Novak’s Gynecology. Philadelphia (PA): Lippincott Williams & Wilkins; 2007.
5. France JT, Jackson P. Maternal plasma and urinary hormone levels during and after a successful abdominal pregnancy. Br J Obstet Gynecol 1980; 87:　356-362.
6. Noyes RW, Hertig AT, Rock J. Dating the endometrial biopsy. Fertil Steril 1950; 1:3-25.
7. Collet ME, Wertenberger GE, Fiske VM. The effect of age upon the pattern of menstrual cycle. Fertil Steril 1954; 5: 437-448.
8. Gindoff PR, Ferin M. Brain opioid peptides and menstrual cyclicity. Semin Reprod Endocrinol 1987; 5: 125-133.

Figure legends

｜Japanese｜HOME｜