European Journal of Obstetrics & Gynecology and Reproductive Biology 80 (1998) 273274

Hyperemesis in late pregnancy - should we think of cancer? A case report

Andreas Hagen*, Christian Becker,, Sanyukta Runkel, Hans K. Weitzel
Department of Obstetrics and Gynecology, University Hospital Benjamin Franklin, Free University of Berlin, Berlin, Germany Received 8 January 1998; received in revised form 20 March 1998; accepted 8 May 1998

Abstract Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specic symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no inuence on the prognosis of gastric cancer patients with hepatic metastases. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: pregnancy; gastric cancer; hepatic metastases

1. Introduction Cancer during pregnancy is rare with a reported incidence of 0,1% [1]. Gastric cancer is most frequent in elderly populations and predominates in males [2]. Therefore information about gastric cancer concomitant with pregnancy is limited.

1.1. Case
A 33 year old primigravida was admitted to our hospital in the 30th week of gestation complaining of persistent vomiting, weight loss, general malaise and recurrent abdominal discomfort over last 3 months. There was no history of gastric or duodenal ulcer. Haematemesis and malena were absent. Routine laboratory parameters were normal with haemoglobin of 12,7 g / dl. Fetal ultrasonography showed normal development correlating to gestational age. Maternal serum tumor markers CA 19-9 and 72-4 were pathologically elevated with 750 kU / l and 70 kU / l respectively. An abdominal ultrasound of the patient revealed four liver lesions distributed over both lobes, morphologically suggesting hemangiomas, though the dif*Corresponding author. Tel.: 149 30 84452591; fax: 149 30 84454141

ferential diagnosis also included hyperechoic metastases. At this stage malignancy of the stomach was suspected and an urgent gastroscopy conrmed the diagnosis showing a large ulcer in the greater gastric curvature that extended from the distal corpus to the antrum and had a suspiciously reddened border. The histology revealed an adenocarcinoma of low differentiation with some signet-ring cells, partially of the intestinal type. The growth fraction was 40%. Helicobacter pylori colonization was detectable. Magnetic resonance tomography (MRT) of abdomen conrmed hepatic metastases. After discussion with medical oncologists, surgeons and the mother, chemotherapy was chosen as rst line of treatment after delivery at 32 weeks. After corticosteroid therapy for fetal lung maturity the patient was delivered of a healthy baby girl via primary caesarean section (weight 1.800 g, APGAR 10 / 10 / 10, UApH 7,32). Histological examination of the placenta showed no evidence of metastases. Using Cytokeratin-19reverse- Transkriptase-PCR malignant cells were detected in maternal peripheral blood, but were absent in fetal blood samples. Chest x-ray, MRT of the head and bone scan were normal. A repeat of abdominal ultrasound on the 7th postoperative day showed progression of liver metastases. Chemotherapy with 5-uorouracil (2400 mg / m 2 Body Surface Area (BSA), day 1 and day 8), leucovorin (500 mg / m 2 BSA, day 1) and cisplatin (50 mg / m 2 BSA, day 1)

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was started on the ninth post operative day after primary wound healing. The patient responded so well to chemotherapy, that only after 2 of 6 planned cycles a second MRT showed a drastic regression of liver metastases as well as of primary tumor. Due to this excellent response the therapeutic strategy was modied and tumor resection was considered to avoid obstruction of gastric passage at a later stage. Billroth II gastrectomy, omentectomy and lymph node dissection were performed 7 weeks after the beginning of chemotherapy. Further cycles of chemotherapy were given post operatively. But after four cycles the patient decided to discontinue the chemotherapy due to severe side effects and increasing weakness. Eight weeks later or seven months after the initial diagnoses the patient died.

2. Discussion This is the rst report of metastatic gastric cancer diagnosed during pregnancy and treated at rst with palliative chemotherapy. The prognosis for a pregnant woman with gastric cancer is altogether very poor. The largest study comes from Japan with 54 patients and shows a one year survival rate of 31,6% [3]. Since surgery does not inuence the long term outcome in gastric cancer patients with hepatic metastases and adequate gastric passage, we decided to administer palliative chemotherapy. In this respect, our therapeutic management differs from that in other known cases, where surgery was the treatment of choice and, in some cases, followed by an adjuvant chemotherapy [4]. It is interesting to see that in all available publications no distant visceral metastases like in our case were described. So we cant compare our management with other cases of locally advanced gastric cancer where surgery alone seems to be the standard. Chemotherapy has here no signicant inuence on the survival rate. Only the stage of disease and the positive lymph nodes are important for the prognosis. Early detection of gastric cancer during pregnancy still remains a dilemma due to rareness of this condition in young women and the frequency of vomiting and nausea mainly in early pregnancy. Therefore diagnosis is very

often delayed and may result in advanced metastatic disease at the time of therapeutic intervention and worsening the clinical outcome. However, if the aforementioned symptoms persist, particularly in late pregnancy other internal differential diagnosis must be considered. Measurement of gastrointestinal tumor markers may be useful in narrowing the diagnosis, as in our case. A gastroscopy seems indicated to exclude a malignant process without risk to the mother or child. The reason for detection of malignant cells in the maternal and fetal blood, using Cytokeratin-19-reverseTranskriptase-PCR, were 12 published cases in the world literature of cancer during pregnancy concomitant with fetal metastases [5]. These patients suffered from malignant melanoma, hematopoietic malignancies and hepatocellular carcinoma. So we think it is necessary to make a careful histological evaluation of the placenta and, if positive, to investigate the extent of tumor cells in the fetal blood. However the search for peripheral tumor cells in maternal blood should be reserved for cases of metastatic disease.

3. Condensation Gastric cancer is rare during pregnancy and diagnosis may be delayed due to attribution of symptoms to pregnancy. The management depends on the clinical stage of the disease as well as on the gestational age.

References
[1] Silverberg E, Lubera J. Cancer statistics, 1989. Cancer 1989;39:3 20. [2] Nesbitt JC, Moise KJ, Sawyers JL. Colorectal carcinoma in pregnancy. Arch Surg 1985;120:636. [3] Ueo H, Matsuoka H, Tamura S, Sato K. Prognosis in Gastric Cancer Associated with Pregnancy. World J Surg 1991;15:2938. [4] Allum WH, Hallissey MT, Kelly KA. Adjuvant chemotherapy in operable gastric cancer, 5 year follow-up rst British stomach group trial. Lancet 1989;1:571. [5] Eltorky M, Khare VK, Osbornr P, Shanklin D. Placenta Metastasis from Maternal Carcinoma. A Report of Three Cases. J Reproductive Med 1995;5:399403.