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Gynecologic Oncology 91 (2003) 429 – 434
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Case Report
Laparotomy wound recurrence of endometrial carcinoma Victor Macias,a,b,* Barbara Baiotto,c Jose´ Pardo,a Fernando Mun˜oz,b and Pietro Gabrieleb a
Department of Radiotherapy, Hospital General de Catalunya, c/Gomera s/n, 08190 Sant Cugat del Valles, Barcelona, Spain b Department of Radiotherapy, Istituto per la Ricerca e la Cura del Cancro, 10060 Candiolo, Turin (Italy) c Department of Medical Physics, Istituto per la Ricerca e la Cura del Cancro, 10060 Candiolo, Turin (Italy) Received 5 March 2003
Abstract Background. Most endometrial cancer relapses are either pelvic or distant metastases. Recurrences in the laparotomy scar are extremely rare, as to our knowledge this is only the sixth reported case and the first treated with brachytherapy. We also present a review of the literature with an emphasis on radiation therapy treatment. Case. A 64-year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for IIIA endometrial adenocarcinoma, followed by systemic chemotherapy and pelvic external-beam radiotherapy. Three years later, a recurrence in the laparotomy scar was resected and additional chemotherapy was administered. A solitary mass in the abdominal wound was then found 4 years after that and was reirradiated by combining external-beam radiation therapy and interstitial brachytherapy after complete resection. Histology of the abdominal wall implants was very similar to that of the primary tumour. Conclusion. Laparotomy wound recurrence (LWR) for endometrial cancer usually appears as a solitary mass that grows slowly without concomitant failure sites a few years after hysterectomy. In these six patients there is no common histology pattern that could suggest predictive factors for LWR. Common postoperative irradiation does not deliver sufficient a dose to the anterior abdominal wall to prevent this kind of failure. © 2003 Elsevier Inc. All rights reserved. Keywords: Endometrial cancer; Recurrence; Radiotherapy; Brachytherapy
Introduction
Case report
Endometrial cancer is the most commonly diagnosed gynecologic neoplasm [1]. Most endometrial cancer relapses are either pelvic or distant metastases and occur within the first 2 years after hysterectomy [2]. Recurrences in the laparotomy wound are extremely rare as, to our knowledge, only five cases have been previously reported [3–7]. This case is presented with a review of previous similar cases, possible mechanisms for this type of spread and an analysis of radiation therapy treatment.
R.M., a 64-year-old white female, gravida 1, with noninsulin-dependent diabetes and hypercholesterolemia, was operated on for eventration in November 1994, when a left ovarian mass was suspected. An abdominal CT-scan showed increased uterus dimensions with hypodense content and a 5 ⫻ 4 ⫻ 5 cm anexus mass, without increased lymph nodes. Chest X-ray was normal. Ca 125 and Ca 19.9 levels were 54 Ul/ml (normal ⬍ 35 UI/ml) and over 240 UI/ml (normal ⬍ 37 UI/ml), respectively. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy through midline infraumbilical incision in January 1995. Pelvic lymphadenectomy was not performed. Pathology examination revealed a uterus weighing 100 g with a 7.5 cm uterine cavity completely occupied
* Corresponding author. Fax: ⫹34-93-589-26-18. E-mail address:
[email protected] (V. Macias). 0090-8258/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2003.07.001
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Fig. 1. Abdominal CT scan showing the first laparotomy wound recurrence (small node) in 1998.
by an exophytic necrosed mass involving the cervical canal. On microscopy, a G2 endometrial adenocarcinoma with focal squamous metaplasia was seen to have infiltrated more than half the myometrium with the involvement of the cervix and the left Fallopian tube os. Focal ovarian endometriosis in the right parametrium was observed. Vaginal and parametrial resection margins were free of disease. Peritoneal washings were positive to neoplastic cells. It was staged as pT3a N0 M0, stage IIIA (FIGO). Serum tumoral markers returned to normal levels. Systemic chemotherapy consisting of three cycles of adryamicin with cisplatinum was administered between April and July. Six weeks later, the pelvis was irradiated to a dose of 50 Gy in 2 Gy/day fractions using four 10 ⫻ 15 cm obliqued fields of 1.5 MV photons. The patient was free of disease until February 1998, when an abdominal CT scan detected two cystic nodes localized at the level of the top of the laparotomy scar measuring 7 ⫻ 5 ⫻ 1.5 cm (Fig. 1). There was no evidence of intraabdominal recurrence or distant metastases. Ca 19.9 serum level increased to 113 Ul/ml, whereas Ca125 was
normal. The histological examination of the resected nodes confirmed the presence of adenocarcinoma with similar characteristics to the initial tumour (adenocarcinoma with squamous metaplasia) infiltrating subcutaneous fat and scar connective tissue. Serum markers decreased to normal levels. The patient was treated with adjuvant systemic chemotherapy using the same schema as before. In November 2001, the patient was referred to our institution when diagnosed with a second abdominal scar recurrence. The mass, measuring 10 ⫻ 12 cm, had infiltrated the abdominal wall without involving adjacent intraperitoneal organs such as the colon or the small intestine (Fig. 2). No abdominal lymph nodes or metastases were detected. Ca 19.9 and Ca 125 increased to 683 and 43 UI/ml respectively. The tumour was completely removed, although resection margins were considered microscopically affected. Histological examination showed adenocarcinoma similar to that previously described. Serum markers decreased to normal levels. Four months later, the patient underwent externalbeam radiotherapy in the scar using a direct field of 12 MeV
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Fig. 2. Second recurrence in the laparotomy scar (2001).
electrons produced by a linear accelerator. The dose delivered was 36 Gy in 2-Gy/day fractions over 4 weeks. Nine days afterwards, an implant of interstitial brachytherapy (BT), CT-guided, was performed (Fig. 3). Under sedation and local anaesthesia 11 vectors were placed into the fat of the anterior abdominal wall crossing the scar. Then a second CT scan was made for dosimetry purposes and a 3D isodose plan was prepared. Finally, plastic implant catheters were connected to an afterloading computer-controlled machine with a high-dose-rate iridium-192 source. The radiation time was 14 min for each fraction. The delivered dose was 20 Gy in four daily fractions of 5 Gy over 1 week. Total prescribed dose (EBRT ⫹ BT) to the scar and 4.5 cm surrounding tissues was estimated to be 64 Gy. Catheters were gently removed immediately after the last session, without anaesthesia. Treatment was very well tolerated without analgesics or other drugs and interference with normal activities was minimum. To date, 7 months after completion of the BT, skin hyperpigmentation is the only
sequel of the two radiotherapy treatments. Abdominal CT scan and ultrasounds show no abnormality. Discussion The characteristics of endometrial cancer patients with reported laparotomy wound recurrence (LWR) are summarized in Table 1. How cancer cells implant themselves in the laparotomy wound and grow in situ is not known. Despite the common presence of cancer cells intraperitoneally, as proved in positive peritoneal washings, the implantation and growth of cells in the abdominal wound is very rare. The long diseasefree interval and the solitary recurrence in the abdominal scar without other concomitant metastases in most cases suggest that the recurrence could be due to cells being implanted directly in the wound and then growing slowly, rather than being spread via blood or lymphatic vessels from the initial tumour. Unlike LWR, skin metastases of endo-
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Fig. 3. Abdominal CT scan showing isodose curves of the brachytherapy treatment. Prescribed dose was 20 Gy to 85% isodose curve (light blue). Scar is completely involved in the 50% isodose curve (yellow). Notice that small parts of the small intestine are placed between the 50 and 30% (green) isodose curves.
metrial cancer outside the laparotomy wound appear as multiple firm nodules that grow quickly in various body sites with coexistent metastasis in different organs. This reflects a generalised spread through lymphatics and blood vessels. There are two possible mechanisms to explain how malignant cells reach the abdominal wound: (1) Penetrating the thickness of the uterine wall or the Phallopian tube to spread intraperitoneally through the laparotomy wound. Deep myometrial invasion or positive peritoneal washings to atypical cells were assessed in all patients except one, whose data were not available. (2) Spilling through the cervical os at the moment of hysterectomy and implanting directly in the incision during the surgical act. They will remain viable or not depending on factors such as the immune status of the patient. Two of six patients with LWR had concomitant failures, in vagina [3] and paraaortic lymph nodes [4]. The presence of cancer in these sites shows an unusual dissemination for endometrial cancer. It may be explained, as suggested by
Espinos et al. [4], by blockage of lymph vessels with the possibility of retrograde flow or formation of alternative channels, both caused by the patient’s age or the surgical treatment. With regard to overall survival, the patient with LWR and concomitant abdominal lymph nodes died 3 months after diagnosis. There is no available data from the patient with concomitant vaginal metastasis. Three of four patients with isolated LWR, including the present case, had no evidence of disease 3 years (16 – 47 months) after implant resection. The other patient developed lung metastases 2 years after the primary treatment with no abdominal scar recurrence. These data suggest that when the laparotomy scar is the unique initial failure site, a disease-free interval of at least a few years can be expected and treatment must be realized with curative intent. All of the 6 patients were treated in a different way, including mass resection, external-beam radiotherapy (alone or postoperative), BT, chemotherapy, and hormonal therapy. Due to the rarity of this
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Table 1 Characteristics of endometrial cancer patients with laparotomy wound recurrence Author
Agea (years)
Treatment of PT
pT stageb (Grade)
P washings
DFI (years)
Concomitant recurrence sites
Treatment of LWR
RT dose/DPF (Gy)
Follow-upc (months)
Chapman (1988)
65
RT
NA
NA
7
Vagina
CT ⫹ PG
NA
NA
Espinos (1993)
77
TAH-BSO ⫹ EBRT␣ ⫹ BT
pT1c (G2-3)
⫺
1 month
Paraaortic lymph nodes
EBRT ⫹ PG
43␣ 24
Deceased (3)
Curtis (1994)
50
TAH-BSO ⫹ P32W ⫹ PG
pT1b (G1)
⫹
1.5
None
Resection ⫹ EBRT
55.8/1.8
Lung metastasis (24)
Kotwall (1994)
65
TAH-BSO
pT1c (G1-2)
⫹
7
None
Resection
0
NED (⬎15)
Khalil (1998)
58
TAH-BSO ⫹ EBRT
pT1c (G1-2)
⫺
5
None
Resection ⫹ PG
55/NA
NED (48)
Present case
56
TAH-BSO ⫹ CT ⫹ EBRT
pT3a (G2)
⫹
3
None
Resection ⫹ CT (1st recurrence) Resection ⫹ EBRT ⫹ BT ⫹ PG (2nd recurrence)
50/NA
NED (11)
6.5
36/2 (EBRT) 20/5 (BT)
a
Age at diagnosis of primary endometrial carcinoma; PT, primary tumour; RT dose, radiation therapy dose either in initial treatment or in recurrence treatment; TAH-BSO, total abdominal hysterectomy with salpingo-oophorectomy; EBRT, external-beam radiation therapy; BT, Brachytherapy; P32W, intraperitoneal 32P washings; CT, chemotherapy. b T-stage, primary tumour extent, according to UICC, 5th edition; NA, not available; DFI, disease-free interval from the primary treatment; AWR, abdominal wall recurrence; PG, progestin; DPF, dose per fraction. c Follow-up, follow-up since scar implant resection; NED, no evidence of disease.
clinical presentation it has not been possible to establish the optimal treatment combination. In the absence of metastasis, surgery may be performed as initial treatment if the abdominal mass seems resectable. Postoperative EBRT can be administered in solitary LWR to avoid a second abdominal scar recurrence as in the case we are reporting. We suggest a dose of about 70 –75 Gy focused on the abdominal wound, which is similar to the curative treatment of vaginal cuff scar recurrence [8]. Given the documented reduction of tumour volume, even with moderate doses [4], EBRT with concomitant hormonal therapy (medroxyprogesterone acetate) may be used in palliative and preoperative treatments. Irradiation of the pelvis after hysterectomy is a common practice to prevent locoregional failures of endometrial cancer. A dose to 45–50 Gy is considered sufficient to treat microscopic disease [8]. As shown in Table 1, three patients were irradiated after hysterectomy, but developed the wound implant 1.5–5 years afterwards. Possible reasons for these failures are as follows: 1. The aim of postoperative radiation therapy of endometrial cancer is to “sterilise” the possible microscopic residual disease at the level of the tumour bed, pelvic lymph nodes, and vaginal cuff scar. At the same time, to avoid significant toxicity, rectum, bladder, skin, and femoral heads have to be protected as much as possible. As a result of these goals, the usual standard technique consists of four isocentric beams at 0°, 90°, 180°, and 270° gantry angles to
the pelvis using megavoltage photons. With this beam arrangement, higher doses are placed in the centre of the pelvis while sensitive organs are irradiated under tolerance limits. Reviewing dose distribution in a random group of patients with endometrial cancer treated with the described technique in our institution, the laparotomy wound is underdosed, receiving around 60% or less of prescribed dose (Fig. 4). 2. On the other hand, the cranial border of the radiation fields are usually positioned at the level of the fourth and fifth lumbar vertebrae to permit the irradiation of external iliac lymph nodes while minimising the exposure of the small intestine. However, as reported by Khalil et al. [7], the cranial part of the laparotomy incision is sometimes above L5 level, so it is not included in the irradiation fields. In our opinion, the current radiation therapy plan should not be modified because the acute and chronic toxicity, mainly intestinal, to be expected would be greater than the theoretical benefit of preventing this rare type of spread. When the laparotomy scar has to be irradiated after previous radiotherapy of the pelvis, as in the present case, the technique explained above cannot be used again, because the small intestine has already received 50 Gy. This dose corresponds to the tolerance dose to keep the probability of severe chronic toxicity from therapeutic irradiation under 5% [9]. Electron beams or BT, thanks to its short dose falloff, allow this goal to be obtained. In the case we are reporting the combination of a direct electron beam and then
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Fig. 4. Abdominal CT scan showing isodose curves of a standard beam arrangement in the postoperative irradiation of endometrial carcinoma patients. Gantry angle beams are 0° (beam 1), 90°, 180°, and 270° (beam 4). Common prescribed dose is 45–50 Gy to the ICRU point, i.e., the intersection of the four beams, which corresponds to 100%. Lymphatic regions are included to the 95% isodose curve (yellow). The laparotomy scar receives less than 60% of the prescribed dose (60% isodose curve in light blue, outer elliptic isodose line).
interstitial BT achieved the best dose distribution. To date, neither acute toxicity (except a mild skin reaction) nor chronic toxicity has been assessed. Considerations about serum level of Ca 19.9 in LWR are not available. In the present case, Ca 19.9 increased clearly when recurrence was present and diminished to normal level after treatment. This marker is being used in the patient’s follow-up in order to obtain an early diagnosis of recurrence.
References [1] American Cancer Society (ACS). Cancer facts and figures—1998. Atlanta, GA: ACS, 1998. [2] Perez CA, Bedwinek JM, Breaux SR. Patterns of failure after treatment of gynecologic tumours. Cancer Treat Symp 1983;2:217.
[3] Chapman GW, Fabacher P, Thompson H. Incisional recurrence of endometrial carcinoma. J Nat Med Assoc 1988;80:350. [4] Espinos J, Garcia-Patos V, Guiu XM, Delgado E. Early skin metastasis of endometrial carcinoma: case report and review of literature. Cutis 1993;52:109. [5] Curtis MG, Hopkins MP, Cross B, Tantri MD, Jenison EL, Rehmus E. Wound seeding associated with endometrial cancer. Gynecol Oncol 1994;52(3):413–5. [6] Kotwall CA, Kirkbride P, Zerafa AE, Murray D. Endometrial cancer and abdominal wound recurrence. Gynecol Oncol 1994;53(3):357– 60. [7] Khalil AM, Chammas MF, Kaspar HJ, Shamseddine AI, Seoud MA. Case report: endometrial cancer implanting in the laparotomy scar. Eur J Gynaecol Oncol 1998;19(4):408 –9. [8] Chao KSC, Perez CA, Brady LW 1999. Radiation oncology: management decisions. Philadelphia: Lippincott-Raven p. 513– 4. [9] Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21(1): 109 –22.
