We present a rare case of metastatic pancreatic adenocarcinoma diagnosed antepartum. A high index of suspicion must be maintained to diagnose pancreatic cancer during pregnancy. We recommend a thorough history and physical and aggressive pursuit of sensitive imaging in patients with persistent symptoms. If pancreatic adenocarcinoma is diagnosed, a multidisciplinary approach that focuses on patient goals should be undertaken. The effect of pregnancy on tumor growth rates is unknown

Bashir, Showkat

Borum, Marie L.

Davis, Jessica

Wubneh, Helmae

English

PubMed

George Washington University: Health Sciences Research Commons (HSRC)

Himmelfarb Health Sciences Library, The George Washington UniversityHealth Sciences Research CommonsSurgery Faculty Publications Surgery8-1-2016Metastatic Pancreatic Adenocarcinoma DuringPregnancy.Jessica DavisShowkat BashirHelmae WubnehMarie L. BorumGeorge Washington UniversityFollow this and additional works at: https://hsrc.himmelfarb.gwu.edu/smhs_surgery_facpubsPart of the Neoplasms Commons, and the Surgery CommonsThis Journal Article is brought to you for free and open access by the Surgery at Health Sciences Research Commons. It has been accepted for inclusionin Surgery Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contacthsrc@gwu.edu.APA CitationDavis, J., Bashir, S., Wubneh, H., & Borum, M. L. (2016). Metastatic Pancreatic Adenocarcinoma During Pregnancy.. ACG CaseReports Journal, 3 (4). http://dx.doi.org/10.14309/crj.2016.163CASE REPORT | PANCREASMetastatic Pancreatic Adenocarcinoma During PregnancyJessica Davis, MD1, Showkat Bashir, MD1, HelmaeWubneh, MD2, andMarie L. Borum, MD, EdD, MPH11Department of Gastroenterology and Liver Diseases, George Washington University, Washington, DC2Department of Pathology, George Washington University, Washington, DCABSTRACTWe present a rare case of metastatic pancreatic adenocarcinoma diagnosed antepartum. A high index of suspi-cion must be maintained to diagnose pancreatic cancer during pregnancy. We recommend a thorough historyand physical and aggressive pursuit of sensitive imaging in patients with persistent symptoms. If pancreatic ade-nocarcinoma is diagnosed, a multidisciplinary approach that focuses on patient goals should be undertaken. Theeffect of pregnancy on tumor growth rates is unknown.INTRODUCTIONPancreatic cancer is the third leading cause of cancer-related death in the United States.1 Diagnosis of pancreaticadenocarcinoma antepartum is, however, exceedingly rare, with 13 cases published to date.2-14 Of the previouslyreported cases, the mean maternal age at diagnosis is 35.8 years (range, 25–43 years).2-14 Nine of the 13 patientswere diagnosed during their second trimester of pregnancy, with the remaining patients presenting in the third tri-mester. No cases were diagnosed in the first trimester of pregnancy.2-14 Only 5 of the 13 cases were amenable toresection, and in those cases pancreaticoduodenectomy was performed anywhere from 17 weeks gestation to post-partum.2-14 Eight cases reported patient death within 1 year of diagnosis.2-14 The longest documented survival was 16months after diagnosis.2-14 Fetal outcome was largely positive; one case noted elective termination and there wasone spontaneous fetal death, but all other cases reported healthy pregnancies or infants subsequent todiagnosis.2-14CASE REPORTA 34-year-old gravida 1 para 0 woman with past medical history of multiple sclerosis and cholecystectomypresented at 26 weeks gestation with severe abdominal pain and failure to gain weight appropriately inpregnancy. Her family history was remarkable for pancreatic cancer in her mother, who died at age 47. Shedid not smoke or drink alcohol. Admission labs were notable for aspartate aminotransferase (AST) 68 U/L,alanine aminotransferase (ALT) 100 U/L, alkaline phosphatase (ALP) 227 U/L, total bilirubin 0.3 mg/dL, lipase364 U/L, and bile acids 25 mmol/L. Ultrasound showed dilatation of both the common bile duct (CBD) (7.4mm) and pancreatic duct (9.6 mm). Subsequent magnetic resonance cholangiopancreatography (MRCP) dem-onstrated a space-occupying lesion in the pancreatic head with a mildly dilated CBD (Figure 1). The differen-tial diagnosis of the lesion included an inflammatory mass due to acute pancreatitis versus neoplasm. Herfamily history was her only known risk factor for pancreatic cancer. Although her findings were concerning,endoscopic ultrasound was deferred due to the patient’s preference. She was treated for acute pancreatitiswith inflammatory mass with pain control and pancreatic enzyme replacement (pancreatic lipase, 500 U/kgper meal) in an attempt to ameliorate her pain and address any component of pancreatic insufficiency thatmay have contributed to her weight loss.ACG Case Rep J 2016;3(4):e190. doi:10.14309/crj.2016.163. Published online: December 21, 2016.Correspondence:Marie L. Borum, 2150 Pennsylvania Ave, NW Suite 3-405, Washington, DC 20037 (mborum@mfa.gwu.edu).Copyright: © 2016 Davis et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 InternationalLicense. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0.ACG Case Reports Journal / Volume 3 / Issue 4 acgcasereports.gi.org 1ACGCASE REPORTS JOURNALShe returned 1 week later with persistent abdominal pain,weight loss, and emesis. Her liver-associated enzymes weresimilar to her prior admission values with AST 65 U/L, ALT 76U/L, ALP 186 U/L, and total bilirubin 0.4 mg/dL. Her AST,ALT, and ALP remained stable, whereas her total bilirubinrose to 3.0 mg/dL. Given the patient’s preference to avoidinvasive procedures, a second MRCP was performed toreevaluate the previously identified mass in light of herincreased bilirubin. Repeat MRCP was again concerning for apancreatic head mass and increased dilatation of her CBD(Figure 2). Endoscopic ultrasound was performed at 32 weeksgestation and demonstrated a 3.8 x 2.3 cm pancreatic headmass encasing the superior mesenteric vein with celiac andperipancreatic lymphadenopathy (Figure 3). There were noendoscopic luminal findings to explain her emesis. Pathologyon fine-needle aspiration of the pancreatic head mass con-firmed pancreatic adenocarcinoma (Figure 4). Given her fam-ily history and young age at diagnosis, we recommended sheundergo genetic counseling. CA 19-9 was 1 U/mL.C-section was performed 2 days after diagnosis, and a healthymale infant was delivered. Pfannestiel incision allowed directvisualization of pancreatic head mass. The mass was large andfixed with local spread and palpable liver lesions grossly con-sistent with metastases. The patient became jaundiced, andher liver-associated enzymes showed worsening cholestasiswith AST 166 U/L, ALT 171 U/L, ALP 1 102 U/L, and total biliru-bin 13.6 mg/dL. A palliative biliary stent was placed for herworsening jaundice, and her bilirubin trended down. Thepatient opted for supportive care after her delivery.Figure 1. T2-Weighted abdominal magnetic resonance imaging from ini-tial presentation at 26 weeks. (A) Axial view showing a space-occupyinglesion in the head of the pancreas (arrow) with ill-defined margins andinvolvement of the superior mesenteric vein. (B) Coronal view demon-strating a pancreatic head lesion (white arrow) and surrounding edemawith mild dilatation of the CBD (striped arrow) and visualization of graviduterus (yellow arrow).Figure 2. T2-Weighted abdominal magnetic resonance imaging frompresentation at 30 weeks. (A) Axial view showing pancreatic head mass(arrow). (B) Coronal view showing gravid uterus (yellow arrow), pancre-atic head mass (white arrow), significantly increased dilatation of theCBD (striped arrow), and an incompletely characterized hyperintenseliver lesion (dotted arrow) concerning for metastasis.Figure 3. Endoscopic ultrasound of the pancreatic head mass (whitearrow) and portal vein demonstrating enlarged peripancreatic lymphnode (black arrow).Figure 4. Cytology from fine-needle aspiration of the pancreatic headmass confirming adenocarcinoma. Typical glandular type cells occurring(A) in 3-dimensional cohesive groups and (B–E) singly. These markedlyatypical cells are enlarged with overlapping nuclei, chromatin clearingand clumping, increased nuclear to cytoplasmic ratio, and irregular nu-clear borders with focally vacuolated cytoplasm. Papanicolaou stain, 50xmagnification.Davis et al Pancreatic Adenocarcinoma in PregnancyACG Case Reports Journal / Volume 3 / Issue 4 acgcasereports.gi.org 2Unfortunately, she died 4 months after her tissue diagnosis.At most recent follow-up, her son was healthy with reportedlynormal development at 16 months.DISCUSSIONOur case exemplifies the challenges of diagnosis, treatment,and prognosis of pancreatic cancer in the pregnant patient.Early diagnosis is critically important in these patients as itaffects survival and candidacy for surgery. Diagnosis is chal-lenging in the gravid patient, however, as the symptomsof pancreatic cancer—abdominal discomfort, nausea, andvomiting—mimic those of normal pregnancy. Pregnancymasks red flags like unintentional weight loss and abdominalmasses and decreases the sensitivity of noninvasive imagingmodalities. We recommend a careful history and physicalexamination that attends to risk factors for cancer, includingfamily history and tobacco use. Any pregnant patient withpersistent abdominal symptoms despite supportive careshould be screened with imaging modalities. Patients oftenpresent with persistent symptoms and lab abnormalities thatare not proportional to initial imaging findings. This indicatesthat a high index of suspicion for occult malignancy is needed.Although not typically used as a screening tool, CA 19-9 hasthe potential to be useful as a noninvasive test in gravidpatients; it was elevated in 6 cases in the literature, thoughnot in our patient.2-14Once the diagnosis has been made, questions regarding tim-ing and type of therapy arise. Unfortunately, for patients likeours with locally advanced or metastatic disease, surgicalintervention does not improve survival. Palliative chemother-apy and/or supportive care may be offered. For patients whopresent with resectable disease, surgical intervention withpancreaticoduodenectomy has survival benefit. Five antepar-tum cases in the literature presented with resectable disease.Three broad options are available to these patients: immedi-ate surgical intervention, delay of surgery until postpartumstate, or surgery at the earliest age of high fetal viability,approximately 28 weeks.9 The first option offers the highestrisk to the fetus, the second confers the greatest risk to themother, and the third attempts to balance risk of both motherand fetus, potentially at the expense of both.Ultimately, a multidisciplinary approach among high-risk ob-stetrics, surgery, gastroenterology, and the patient herselfwill inform the decision of timing of intervention in thesecases. From a safety perspective, the second trimester isthought to be the optimal time for surgical intervention asthe risk of spontaneous termination is high in the first trimes-ter while access to the pancreas may be limited by the sizeof the uterus in the third trimester.15Prognosis plays a role in therapeutic decision-making as well.Given the paucity of cases available, it is not known if there isa difference in the natural history of pancreatic cancer inpregnant versus non-pregnant patients. There has been spec-ulation that the immunosuppression associated with preg-nancy could increase the aggressiveness of some tumors,and pancreatic cancers have estrogen and progesteronereceptors that could be affected by the gravid state.16Immunohistochemistry was not performed on our patient’stissue to identify the absence or presence of estrogen or pro-gesterone receptors, but this could be an option for futuresimilar cases that may prove informative when making man-agement decisions. As noted above, evaluation of the casesreported thus far in the literature shows that the majority ofcases are not resectable at diagnosis, and, of the 5 cases inwhich the mother survived, only one provided data for longerthan 1 year.DISCLOSURESAuthor contributions: J. Davis wrote and researched themanuscript and is the article guarantor. S. Bashir and MLBorum reviewed the manuscript. H. Wubneh provided the fig-ures and reviewed the manuscript.Financial disclosure: None to report.Informed consent was obtained from the patient's represen-tative for this case report.ReceivedApril 27, 2016;AcceptedSeptember 16, 2016REFERENCES1. National Cancer Institute. SEER Fact Sheets: Pancreas Cancer.http://seer.cancer.gov/statfacts/html/pancreas.html. Updated 2016.Accessed July 25, 2016.2. Gamberdella FR. Pancreatic carcinoma in pregnancy: A case report. AmJObstet Gynecol. 1984;149(1):15–7.3. Porcel JM, Ordi J, Castells L, Farran I. Probable pancreatic cancer ina pre-eclamptic patient. Eur J Obstet Gynecol Reprod Biol. 1992;44(1):80–2.4. Simchuk EJ 3rd, Welch JP, Orlando R 3rd. Antepartum diagnosis of pan-creatic carcinoma: A case report.ConnMed. 1995;59(5):259–62.5. Blackbourne LH, Jones RS, Catalano CJ, Iezzoni JC, Bourgeois FJ.Pancreatic adenocarcinoma in the pregnant patient: Case report andreview of the literature.Cancer. 1997;79(9):1776–9.6. Gojnic M, Boskovic V, Fazlagic A, et al. Pancreatic tumor in a pregnantwoman: A rare case report. Eur J Gynaecol Oncol. 2005;26(2):221–4.7. Marinoni E, Di Netta T, Caramanico L, Tomei B, Moscarini M, Iorio R.Metastatic pancreatic cancer in late pregnancy: A case report andreview of the literature. JMatern Fetal Neonatal Med. 2006;19(4):247–9.8. Su LL, Biswas A, Wee A, Sufyan W. Placental metastases from pancre-atic adenocarcinoma in pregnancy. Acta Obstet Gynecol Scand.2006;85(5):626–7.9. Kakoza RM, Vollmer CM Jr, Stuart KE, Takoudes T, Hanto DW.Pancreatic adenocarcinoma in the pregnant patient: A case report andliterature review. J Gastrointest Surg. 2009;13(3):535–41.10. Onuma T, Yoshida Y, Yamamoto T, Kotsuji F. Diagnosis and manage-ment of pancreatic carcinoma during pregnancy. Obstet Gynecol.2010;116(Suppl 2):518–20.11. Lubner S, Hall B, Gopal D, et al. A 37-year-old pregnant woman with pan-creatic adeno-carcinoma treated with surgery and adjuvant chemother-apy: A case report and literature review. J Gastrointest Oncol. 2011;2(4):258–61.Davis et al Pancreatic Adenocarcinoma in PregnancyACG Case Reports Journal / Volume 3 / Issue 4 acgcasereports.gi.org 312. Perera D, Kandavar R, Palacios E. Pancreatic adenocarcinoma present-ing as acute pancreatitis during pregnancy: Clinical and radiologic mani-festations. J La StateMed Soc. 2011;163(2):114–7.13. Marci R, Pansini G, Zavatta C, et al. Pancreatic cancer with liver metasta-ses in a pregnant patient: Case report and review of the literature. ClinExpObstet Gynecol. 2012;39(1):127–30.14. Papoutsis D, Sindos M, Papantoniou N, Antsaklis A. Managementoptions and prognosis of pancreatic adenocarcinoma at 16 weeks' gesta-tion: A case report. J ReprodMed. 2012;57(3-4):167–70.15. Jabbour N, Brenner M, Gagandeep S, et al. Major hepatobiliary surgeryduring pregnancy: Safety and timing.Am Surg. 2005;71(4):354–8.16. Kreiger N, Lacroix J, Sloan M. Hormonal factors and pancreatic cancerin women.Ann Epidemiol. 2001;11(8):563–7.Davis et al Pancreatic Adenocarcinoma in PregnancyACG Case Reports Journal / Volume 3 / Issue 4 acgcasereports.gi.org 4

Metastatic Pancreatic Adenocarcinoma During Pregnancy.

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