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Open Access

Management of appendiceal pseudomyxoma peritonei diagnosed during pregnancy

World Journal of Surgical Oncology20097:48

https://doi.org/10.1186/1477-7819-7-48

Received: 22 April 2009

Accepted: 19 May 2009

Published: 19 May 2009

Abstract

Background

The incidence of cancer during pregnancy is approximately 1 in 1000. The most common types encountered during pregnancy are cervical, breast and ovarian. Epithelial tumors of the appendix on the other hand are rare and account for only approximately 1% of all colorectal neoplasms; the occurrence of this neoplasm during pregnancy is extremely rare.

Case Presentation

The medical history of a 30 year old woman diagnosed at 17 weeks gestation with an appendiceal mucinous tumor with large volume pseudomyxoma peritonei was presented. Her pregnancy was preserved and she had an early vaginal delivery of a healthy baby at 35 weeks. At 2 1/2 weeks postpartum the patient underwent extensive cytoreductive surgery and intraperitoneal chemotherapy. She remains disease-free 5 years after her initial diagnosis. A literature review of this clinical situation and a discussion of treatment plans were presented.

Conclusion

The management of an appendiceal tumor with pseudomyxoma peritonei diagnosed during pregnancy requires full knowledge of the natural history of this disease to achieve a balance of concern for maternal survival and fetal health.

Background

Epithelial tumors of the appendix are rare, accounting for approximately 1% of all colorectal neoplasms [1]. The tumor can range in presentation from a malignant mucocele found at routine appendectomy, to a ruptured high grade appendiceal malignancy with large volume pseudomyxoma peritonei [2]. During pregnancy, cancer occurs in approximately 1 in 1000 women, with the most common types being cervical, breast and ovarian [3]. There are only a few reports of appendiceal tumors occurring during pregnancy. Management of malignancy during pregnancy is challenging, requiring a balance of concern for maternal survival and fetal health and well-being. The management plan, which may require induced abortion, is determined by the stage of pregnancy and the predicted behavior of the cancer. We present here the medical history of a patient having an appendiceal mucinous tumor with large volume pseudomyxoma peritonei syndrome during pregnancy and the treatments she had at our institution. A review of the literature regarding this clinical situation and a discussion of treatment options are presented.

Case presentation

A 30 year old primagravid woman at 17 weeks gestation was found on routine prenatal ultrasound to have a complex right ovarian mass. She underwent surgery and was found to have a ruptured appendiceal mucinous neoplasm with a large volume pseudomyxoma peritonei syndrome. The right ovary and appendix were removed and an omental biopsy was performed. The final pathology confirmed a well-differentiated mucinous adenocarcinoma of appendiceal origin. She recovered without incident from this surgery and was referred for assessment to the Washington Hospital Center at 26 weeks gestation. In consultation with the patient and her obstetrician it was decided to preserve the pregnancy and schedule an early vaginal delivery at 35 weeks gestation.

Following an uncomplicated vaginal delivery of a healthy baby, she underwent a staging CT. It showed no evidence of metastases within the liver parenchyma or outside of the peritoneal cavity. A large volume of mucinous cancer was imaged beneath right and left hemidiaphragm and in the pelvis. Small bowel except for the terminal ileum was spared. Preoperative tumor markers revealed an elevated CEA at 68.2 ng/mL (normal 0–5 ng/mL), CA-125 of 177 units/mL (normal 0–35 units/mL) and CA 19-9 of 361 units/mL (normal 0–37 units/mL).

At 2 1/2 weeks after delivery, the patient underwent an abdominal exploration followed by cytoreductive surgery. She had thick, densely packed tumor covering most of the parietal peritoneal surface, with an especially large volume of disease in the lesser omentum, omental bursa and surrounding the porta hepatis. The stomach and the small bowel except for the terminal ileum were spared. An extensive cytoreduction surgery was performed including total anterior parietal peritonectomy and resection of tumor in the abdominal wall scar, greater and lesser omentectomy with stripping of the omental bursa, right and left upper quadrant peritonectomies including total diaphragm stripping bilaterally, splenectomy, electroevaporation of tumor on liver capsule, cholecystectomy, and a right hemicolectomy including the distal 15 cm of terminal ileum. A total pelvic peritonectomy with abdominal hysterectomy, left salpingo-oophorectomy and rectosigmoid colon resection was performed. The peritoneal cancer index score was 28 (out of a maximum of 39), and the cytoreduction was scored as complete (residual tumor less than 2.5 mm) [4]. Intraoperative intraperitoneal heated chemotherapy was administered through the open coliseum technique, with 15 mg/m2 mitomycin C at 41.5°C for 90 minutes. A Tenckhoff catheter and Jackson-Pratt drains were inserted for early postoperative intraperitoneal 5-fluorouracil chemotherapy [5]. Following completion of the hyperthermic intraoperative intraperitoneal chemotherapy an ileocolic and colorectal anastomosis was performed. The total operating time was 9 hours, and the blood loss was estimated at 350 mL, with 2 units of packed red blood cells and 4 units of fresh frozen plasma administered during the operation.

On postoperative day 1 through 5, 900 mg intraperitoneal 5-fluorouracil in 1.5% dextrose peritoneal dialysis solution was administered daily for 23 hours. The patient developed uncomplicated neutropenia on postoperative day 16, with neutrophil count of 0.9 × 103/uL and a total leukocyte count of 1.3 × 103/uL, which was treated successfully with granulocyte colony stimulating factor. On postoperative day 18 she was diagnosed with a left lower extremity deep venous thrombosis and was treated with intravenous heparin which was converted to warfarin prior to discharge from the hospital. She had a postoperative ileus requiring nasogastric drainage for 2 weeks and received total parenteral nutrition during this time. She was discharged in good condition on postoperative day 24.

Three weeks following surgery her tumor marker levels decreased with CEA at 0.5 ng/mL, CA 125 at 92.1 units/mL, and CA 19-9 at 10.6 units/mL. CA 125 normalized by 2 months post-operatively.

After recovery from surgery, she was treated with the Xelox regimen (Xeloda 1000 mg/m2 bid for 14 days then 7 day rest and oxaliplatin 130 mg/m2 intravenous over 90 minutes on day 1) for 8 cycles over 24 weeks.

In follow-up at five years after, the patient and her child are in good condition. She has had two episodes of transient small bowel obstruction treated conservatively. On her most recent clinical, radiologic and biochemical assessment at 5 years after her initial diagnosis she remains disease-free.

Discussion

Pseudomyxoma peritonei syndrome is a rare disease registered as number 843 by the National Organization for Rare Disorders [6]. To our knowledge there is only one previous report of a disseminated appendiceal tumor occurring during pregnancy [7]. Our case of pseudomyxoma peritonei presenting in early pregnancy highlights some interesting challenges in the management of cancer in pregnancy. In this case, as in most other cancers occurring during pregnancy, there is a paucity of evidence to guide the clinician in optimal management. Maternal health and timely treatment of the malignancy is balanced by health and safety of the fetus, as many treatment interventions, including abdominal surgery, radiation, and chemotherapy, are known to be harmful to the fetus. Therefore during pregnancy, in addition to the stage and prognosis of the cancer, the stage and value of the pregnancy must also be considered.

For cancer diagnosed during the latter part of pregnancy, an optimal decision often involves a negligible delay in definitive treatment following an early delivery at about 34 weeks gestation when the risk to the premature infant is quite low. During the first trimester the fetus is most susceptible to teratogenic effects; x-rays and most chemotherapeutic agents are contraindicated. Also, spontaneous abortion is common. A long delay in treatment of an aggressive cancer is often unacceptable to the woman and her treating physicians, and a recommendation for termination of the pregnancy must be considered. During the second trimester, as in our patient, abdominal surgical procedures have the lowest risk of spontaneous abortion or premature labor. Additionally, many chemotherapeutic agents have been successfully used in the second and third trimester. Plain radiographs and even abdominal CT scans pose minimal risk to the fetus at this stage of the pregnancy. With increasing experience with abdominal MRI, this is becoming the recommended imaging modality for pregnant women with appendiceal or other gastrointestinal malignancy.

In our patient the appropriate diagnostic surgical evaluation, an appendectomy, was made at the safest time, during the second trimester. Unexpectedly at laparotomy, a diagnosis of large volume pseudomyxoma peritonei from a ruptured appendiceal mucinous carcinoma was made. The natural history of pseudomyxoma peritonei was then considered to guide our management [8]. As described by Ronnett and coworkers pseudomyxoma peritonei describes mucinous intraabdominal tumors usually of appendiceal origin with a broad spectrum of aggressiveness. The low grade appendiceal mucinous tumors (disseminated peritoneal adenomucinosis) usually have a slowly progressive course over several years. The clinical entity with the non-invasive disease is referred to as pseudomyxoma peritonei syndrome. In contrast mucinous carcinomatosis from poorly differentiated cancers of the appendix usually with signet ring morphology have an aggressive behavior, progress rapidly, and carry a worse prognosis. Well-differentiated appendiceal mucinous adenocarcinoma with pseudomyxoma peritonei, as in our patient, is a less aggressive disease, shows a less rapid progression and an intermediate prognosis.

With all appendiceal mucinous neoplasms the prognosis is dependent not only on the histologic grade of the tumor but also the completeness of cytoreduction score [9]. The volume of intraabdominal tumor as assessed by the peritoneal cancer index has no impact on prognosis [9, 10]. In this patient a delay in definitive treatment undoubtedly allowed an increase in tumor volume to occur. However, since the cytoreduction was complete, minimal compromise in the prognosis was expected.

In a review of the literature, there have been 7 previous reports of appendiceal mucinous tumors occurring during pregnancy in the absence of pseudomyxoma peritonei syndrome [7, 1116]. Six were appendiceal mucinous tumors confined to the appendix and one non-mucinous appendiceal adenocarcinoma with peritoneal carcinomatosis (Table 1). In one case, the diagnosis was made in the third trimester and an early delivery was carried out prior to definitive treatment. In one case the diagnosis was made at the time of Cesarean section at term. Four patients presented with an acute abdomen and the diagnosis of appendicitis, with the correct diagnosis being revealed at laparotomy. One of these patients elected to have a therapeutic abortion prior to reoperation for a right hemicolectomy, one patient had a right hemicolectomy at initial operation at 26 weeks gestational age and went on to deliver at term, and the remaining two were treated with appendectomy. The final patient was diagnosed in very early pregnancy at the time of a spontaneous abortion, and underwent surgical treatment 3 months later after progression of disease was revealed on imaging.
Table 1

Case reports of appendiceal epithelial (mucinous) tumors during pregnancy.

Reference and year

Diagnosis

Gestational age at presentation

Clinical presentation

Initial treatment of appendiceal tumor

Definitive treatment of appendiceal tumor

Management and outcome of pregnancy

Patient outcome and follow-up

Haase (current case)

Well-differentiated mucinous adenocarcinoma with pseudomyxoma peritonei syndrome

17 weeks

Incidental finding on routine prenatal ultrasound

Laparotomy, right salpingo-oophorectomy, appendectomy, omental biopsy

Complete cytoreductive surgery with HIPEC and EPIC after delivery, and adjuvant chemotherapy

Early induction and vaginal delivery of healthy baby at 35 weeks

5 years, no recurrence

Sebire

2000 [7]

Moderately-differentiated appendiceal adenocarcinoma with peritoneal carcinomatosis and liver metastases

29 weeks

Lower abdominal pain and vomiting

Diagnostic workup of metastatic disease (liver biopsy)

Palliative debulking (omentectomy, appendectomy, left oophorectomy) at time of Cesarean section. Adjuvant 5-FU, epirubicin and carboplatin

Cesarean section at 30 weeks, healthy baby

6 months post treatment clinically well but residual tumor in right iliac fossa and liver

Gallo

2001 [11]

Well-differentiated mucinous cystadenocarcinoma

38 weeks

Incidental finding at Cesarean section

Appendectomy at time of Cesarean section

Right hemicolectomy after radiographic metastatic workup

Cesarean section at 38 weeks

5 years, no recurrence

Donnenfeld

1986 [12]

Perforated mucinous appendiceal adenocarcinoma

31 weeks

Acute abdomen,

Appendectomy

Right hemicolectomy 9 days postpartum

Early induction and vaginal delivery of healthy baby at 33 weeks

30 day follow up no complications

Morgan

2004 [13]

Well-differentiated mucinous adenocarcinoma, negative peritoneal washings

26 weeks

Acute abdomen

Right hemicolectomy

No further treatment

Vaginal delivery of healthy baby at term

36 months, no recurrence

Zeteroglu

2003 [14]

Mucinous appendiceal cystadenocarcinoma

21 weeks

Acute abdomen

Appendectomy

Right hemicolectomy, omentectomy

Terminated at 21 weeks

1 year, no recurrence

Casey

2003 [15]

Perforated mucinous cystadenoma

21 weeks

Acute abdomen

Appendectomy

No further treatment

miscarriage

Discharged well 4 days after surgery

Kalu

2005 [16]

Mucinous adenoma with mucocele

5 weeks

Incidental ultrasound finding at time of vaginal bleeding

Observation with serial imaging (follow-up ultrasound 3 months)

Appendectomy 3 months later when mass doubled in size

Spontaneous abortion at 6 weeks

Discharged well 4 days after surgery

HIPEC: heated intraperitoneal chemotherapy

EPIC: early postoperative intraperitoneal chemotherapy

5-FU: 5-fluorouracil

Based on our case and the previous case reports, it appears reasonable to carry out a diagnostic surgical evaluation of a mucinous appendiceal tumor during pregnancy, ideally in the second or third trimester. If a patient presents with an acute abdomen from a ruptured mucinous tumor, initial surgery should consist of a complete appendectomy and mesoappendectomy, and biopsy of omental or peritoneal tumor deposits. Since the rate of lymph node positivity in appendiceal mucinous neoplasms is less than 5%, more extensive surgery involving a right hemicolectomy at the time of initial diagnosis is not warranted and poses undue risk to the mother and fetus [17]. Definitive management of moderate or low grade appendiceal cancer with pseudomyxoma peritonei should be delayed until after delivery, as extensive cytoreduction and intraperitoneal chemotherapy would be impossible and contraindicated during pregnancy. It is reasonable to have the delivery at an earlier date, 34–35 weeks gestation, in order not to further delay treatment of appendiceal adenocarcinoma (Table 2). The method for childbirth is important if the delivery is to occur prior to definitive cytoreduction. A vaginal delivery is required. A Cesarean section is contraindicated. An abdominal incision for Cesarean section will allow for mucinous cancer cells to implant and progress within the abdominal incision and parametrial tissues. This would potentially compromise the completeness of cytoreduction and the likelihood of a curative result [18]. If a Caesarian section is necessary for obstetrical reasons, a midline incision should be used, which can be excised with subsequent cytoreductive surgery. Stage for stage, one would postulate that pregnant cancer patients with pseudomyxoma peritonei may have similar outcomes as non-pregnant patients. With optimal management including complete cytoreduction and intraperitoneal chemotherapy, patients with pseudomyxoma peritonei from well-differentiated appendiceal mucinous carcinoma will have a 15-year survival of 50% [9].
Table 2

Suggested management strategy for pseudomyxoma peritonei syndrome occurring during pregnancy.

 

Aggressive Malignancy

Low-Moderate Grade Malignancy

Week of Pregnancy

Diagnostic Tests

CRS + HIPEC

Diagnostic Tests

CRS + HIPEC

0–12

Unsafe

Consider pregnancy termination

Unsafe

Delay treatment to 35 weeks

13–27

Safe

Consider pregnancy termination

Safe

Delay treatment to 35 weeks

28–40

Safe

Delay treatment to 35 weeks

Safe

Delay treatment to term

(CRS = cytoreductive surgery, HIPEC = hyperthermic intraperitoneal chemotherapy)

Koops and colleagues wrote about pseudomyxoma peritonei syndrome diagnosed in women who were attempting pregnancy (Koops A, Smeenk RM, Zoetmulder FAN, Hoek A. Pseudomyxoma peritonei and pregnancy. Report of two cases, unpublished data). They recommend that definitive treatment of the appendiceal tumor be delayed to allow pregnancy to occur if the disease was minimally aggressive. In patients with progressive disease their experience with delay led to an advanced, untreatable disease state.

Conclusion

In patients with slow or moderate advance of disease, the pregnancy (or pregnancy wish) should be allowed to proceed to a vaginal delivery. In patients with a rapid progression, termination of the pregnancy and definitive treatment may be necessary to protect the mother.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Abbreviations

CEA: 

carcinoembryonic antigen

CA 19-9: 

cancer antigen 19-9

CA 125: 

cancer antigen 125

CT: 

computed tomography.

Declarations

Authors’ Affiliations

(1)
Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto
(2)
Program in Peritoneal Surface Malignancy, Washington Cancer Institute, Washington Hospital Center

References

  1. Moran BJ, Cecil TD: The etiology, clinical presentation, and management of pseudomyxoma peritonei. Surg Oncol Clin N Am. 2003, 12: 585-603. 10.1016/S1055-3207(03)00026-7.View ArticlePubMedGoogle Scholar
  2. Sugarbaker PH: New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome?. Lancet Oncol. 2006, 7: 69-76. 10.1016/S1470-2045(05)70539-8.View ArticlePubMedGoogle Scholar
  3. Donegan WL: Cancer and pregnancy. CA Cancer J Clin. 1983, 33: 194-214. 10.3322/canjclin.33.4.194.View ArticlePubMedGoogle Scholar
  4. Jacquet P, Sugarbaker PH: Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res. 1996, 15: 49-58.Google Scholar
  5. Sugarbaker PH: The Washington Cancer Institute experience in the management of carcinomatosis, peritoneal mesothelioma, and sarcomatosis. Curr Res in Cancer. 2007, 1: 13-54.Google Scholar
  6. Sugarbaker PH: Current concepts of the pseudomyxoma peritonei syndrome: A benign tumor, often a needless fatal outcome. J Rare Diseases. 1997, 3: 5-18.Google Scholar
  7. Sebire NJ, Osborn M, Darzi A, Farthing A, Goldin RD: Appendiceal adenocarcinoma with ovarian metastases in the third trimester of pregnancy. J R Soc Med. 2000, 93: 192-193.PubMed CentralPubMedGoogle Scholar
  8. Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM: Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis: A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to "pseudomyxoma peritonei.". Am J Surg Pathol. 1995, 19: 1390-1408.View ArticlePubMedGoogle Scholar
  9. Sugarbaker PH, Chang D: Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol. 1999, 6: 727-731. 10.1007/s10434-999-0727-7.View ArticlePubMedGoogle Scholar
  10. Sugarbaker PH, Jablonski KA: Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995, 221: 124-132.PubMed CentralView ArticlePubMedGoogle Scholar
  11. Gallo JL, Martinez-Ossa R, Ferrer G, Camara M: Mucinous appendiceal cystadenocarcinoma and pregnancy. Am J Perinatol. 2001, 18: 155-157. 10.1055/s-2001-14531.View ArticlePubMedGoogle Scholar
  12. Donnenfeld AE, Roberts NS, Losure TA, Mellen AW: Perforated adenocarcinoma of the appendix during pregnancy. Am J Obstet Gynecol. 1986, 154: 637-638.View ArticlePubMedGoogle Scholar
  13. Morgan DR, Fernandez CO, DeSarno C, Mann WJ: Adenocarcinoma of the appendix in pregnancy: a case report. J Reprod Med. 2004, 49: 753-755.PubMedGoogle Scholar
  14. Zeteroglu S, Kotan C, Ozen S, Goktolga U: Mucinous appendicular cystadenocarcinoma during pregnancy. A case report. J Reprod Med. 2003, 48: 831-833.PubMedGoogle Scholar
  15. Casey RG, Tan M, Salman R, Ryan J, Gillen P: Acute abdomen in pregnancy due to mucinous cystadenoma of the appendix. J Obstet Gynaecol. 2003, 23: 566-567. 10.1080/0144361031000156564.View ArticlePubMedGoogle Scholar
  16. Kalu E, Croucher C: Appendiceal mucocele: a rare differential diagnosis of a cystic right adnexal mass. Arch Gynecol Obstet. 2005, 271: 86-88. 10.1007/s00404-004-0663-5.View ArticlePubMedGoogle Scholar
  17. Gonzalez-Moreno S, Sugarbaker PH: Right hemicolectomy does not confer a survival advantage in patients with mucinous carcinoma of the appendix and peritoneal seeding. Br J Surg. 2004, 91: 304-311. 10.1002/bjs.4393.View ArticlePubMedGoogle Scholar
  18. Sugarbaker PH: Peritoneum as the first-line of defense in carcinomatosis. J Surg Oncol. 2007, 95: 93-96. 10.1002/jso.20676.View ArticlePubMedGoogle Scholar

Copyright

© Haase et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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