Challenges in the management of adenocarcinoma of ampulla of Vater in pregnancy: A case report and review of literature
Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
Department of General Surgery, King Fahad Specialist Hospital, Dammam, Saudi Arabia
⁎Corresponding author. a.qattan.94@gmail.comHighlights
- •Ampullary adenocarcinoma is a rare entity during pregnancy.
- •Diagnosing ampullary adenocarcinoma in pregnancy can be quite challenging, as the symptoms may overlap with the physiological changes of pregnancy. Furthermore, the diagnostic modalities’ invasiveness & the associated radiation exposure that might harm the fetus.
- •The best treatment modality for resectable tumors is in the form of surgery (i.e.; pancreaticoduodenectomy) that is possible during pregnancy. Yet challenging as its important to choose the appropriate time of surgery to insure the viability of the fetus without risking the progression of the disease.
- •Another challenge that might be encountered is intra-operatively, due to the bulkiness of the uterus which makes such a procedure even more difficult to preform safely & successfully.
Abstract
Introduction
Ampullary adenocarcinoma is a rare entity during pregnancy. It accounts for 0.5% of all gastrointestinal malignancies. The best treatment modality for resectable tumors with the best reported outcome is surgical resection in the form of pancreaticoduodenectomy (Whipple procedure). In this case report, we discuss the challenges in the management of ampullary adenocarcinoma in a pregnant patient.
Case presentation
We report a case of 22 years old pregnant women who presented with vague abdominal pain and jaundice at the 28th week of gestation. Endoscopic retrograde cholangiopancreatography (ERCP) showed a stricture around the ampulla and distal common bile duct (CBD). The CBD was stented and a biopsy was taken. Histopathology revealed: an invasive adenocarcinoma. The patient was managed by elective pancreaticoduodenectomy after induction of vaginal delivery at the 34th week of gestation.
Conclusion
Diagnosing and managing ampullary adenocarcinoma in pregnant patients in their 3rd trimester is challenging. Yet, a delayed viable delivery followed by a definitive surgery in the form of pancreaticoduodenectomy offers the best outcomes for both the mother & fetus in case of early stage disease.
1Introduction
This work has been reported in line with the SCARE criteria [1].
Ampullary adenocarcinoma is a malignant tumor originating from the ampulla of Vater and it accounts for 0.5% of all gastrointestinal (GI) malignancies [2]. Ampullary adenocarcinoma is rare entity during pregnancy [3]. The best treatment modality for resectable tumors providing the best outcome is a complete surgical resection in the form of pancreaticoduodenectomy (Whipple procedure) [4]. Here, we report a case of 22 years old pregnant female at 28th week of gestation and its challenges in diagnosis and management & a review of literature.
2Case presentation
We report a case of a 22 years old pregnant female medically free, referred to us from her Obstetrician when she was complaining of abdominal pain and jaundice. Abdominal US confirmed a single intrauterine pregnancy at 28th week of gestation with appropriate growth for date and showed dilated intrahepatic ducts otherwise it was inconclusive due to the gravid uterus (Fig. 1). Her blood investigations showed a picture of cholestatic jaundice, and all other labs were within normal. So, we decided to proceed with a Magnetic resonance cholangiopancreatography (MRCP) which showed dilatation of both of the CBD (measuring 0.9 cm) & pancreatic duct, as well as an ampullary mass measuring 2 cm (Fig. 2). Later on, Endoscopic retrograde cholangiopancreatography (ERCP) with shielding of the abdomen to protect the fetus from radiation revealed an ampullary and distal CBD strictures. A punch biopsy was taken & the CBD was stented. The histopathology came as invasive adenocarcinoma & full metastatic work up was done and did not reveal any metastatic lesions. So, surgery was the best available option with the best possible outcome but we were reluctant to delay the surgery to ascertain the viability of the fetus. At 34th week of gestation induction of labor was done, both mother and the baby did well and were discharged home on 2nd day postpartum. The mother was readmitted one week later & full body CT scan repeated & there was no vascular invasion or distant metastasis.
Therefore, we proceeded with pancreaticoduodenectomy. A laparotomy incision was done, intraoperative examination of the abdomen revealed; a palpable mass at the ampulla of Vater and the stent was felt in the CBD and duodenum, a bulky uterus as the patient was still in the postpartum period. There was no vascular invasion, peritoneal deposits or any other distant metastasis. For the pancreatojejunostomy anastomosis, a two-layer end-to-side duct-to-mucosa approach was adopted. The pancreatic duct was stented to divert the pancreatic secretions away from the anastomosis. Then the hepaticojejunostomy was done in an end-to-side fashion followed by the gastrojejunostomy.
The Patient had uneventful postoperative course and was discharged 1 week after her surgery. Histopathology came as poorly differentiated invasive adenocarcinoma of ampulla of Vater with negative resection margins. Three out of thirteen lymph nodes revealed metastatic involvement so she received six cycles of adjuvant chemotherapy which she tolerated well. Upon 6 years follow up, computed tomography (CT) and positron emission tomography (PET) scans were normal with no evidence of recurrence.
3Discussion
Patients with periampullary tumors can present with wide variety of gastrointestinal symptoms. The most commonly is obstructive jaundice 2ry to CBD obstruction. In other cases, they can present with biliary colic along with constitutional symptoms especially in adenocarcinoma compared to other types of GI malignancies [5].
We reviewed published articles concerning periampullary & pancreatic malignant tumors that has been diagnosed during pregnancy & confirmed by histopathology in the English literature. To the best of our knowledge, only 41 cases have been reported (Table 1) and our case is the 42nd. Porcel et al. published the first case of adenocarcinoma of ampulla of Vater in pregnant woman at 3rd trimester in 1992 [6]. Upon our review (N = 41), the common age of presentation that was found in the literature was during the 30 s in contrast to our case, where the patient presented to us at the age of 22 years old. The most common histopathological type was found to be adenocarcinoma (18 cases), followed by mucinous cystic neoplasm (16 cases), neuroendocrine neoplasms (3 cases), Solid-pseudopapillary neoplasms (3 cases) and 1 case had anaplastic.Author Histology Patient age Clinical presentation Gestation at presentation (trimester/ weeks) Diagnosis method Gestation for Surgery (trimester/ weeks) Complications Smithers et al. [12] MCN – – 1st (7) – 1 st (8) Tumor ruptured Baiocchi et al. [13] MCN – – 3rd – Postpartum None reported Porcel et al. [6] Adenocarcinoma 43 epigastric pain,
Upper lumbar backache, nausea and vomiting.3rd (28) Aspiration cytology – severe pre-eclampsia, HELLP syndrome, left axillar venous thrombosis, Pancreatic metastasis
Mother death 35 days post-partumOlsen et al. [14] MCN – – 1st (6) – 2nd (18) None reported Simchuk et al. [15] Adenocarcinoma – – 2nd (16) – 2nd (16) metastases Sciscione et al. [16] Neuroendocrine 37 Incidentally US finding (pancreatic mass) 2nd (19) – 2nd (20) Fetal death Blackbourne et al. [17] Adenocarcinoma 32 back pain, nausea, emesis, and dark urine 2nd (14) Intraoperative FNA 2nd (17) No complications Ganepola et al. [18] MCN 37 Abdominal pain 1st (4) Frozen section 2nd (23) No complications Lopez-Tomassetti et al. [19] MCN 26 abdominal
pain and hyperemesis2nd (20) Histological analysis of resected mass 2nd (20) No complications Kato et al. [20] MCN 33 abdominal distention 2nd (15) MRI- Intraoperative ultrasound 2nd (20) Pre-op IUGR Marinoni et al. [8] Adenocarcinoma 38 Epigastric pain 3rd (27) Biopsy by ERCP Postpartum Mother death 50 days post-partum Lin Lin Su et al. [21] Adenocarcinoma 37 intermittent epigastric pain 2nd (22) Ultrasound-guided liver biopsy
confirmed metastatic poorly differentiated adenocarcinoma,
Consistent with a pancreatic primary.2nd Termination of pregnancy Ishikawa et al. [22] MCN 33 Epigastric mass 2nd (17) MRI Postpartum No complications Al Adnani et al. [23] Adenocarcinoma 27 Prenatal care: HTN, fallen fetal growth 3rd (30) Pancreatic biopsy – IUGR, placental metastasis,
Mother death 3 moths postpartumHerring et al. [24] MCN 34 Accidental finding of abdominal mass during routine follow up 1st (3) Histological analysis of resected mass 2nd (17) No complications Ozden et al. [25] MCN 32 Epigastric pain 3rd (36) Histological analysis of resected mass 3rd (36) Tumor rupture Wiseman et al. [26] MCN 32 LUQ pain with palpable mass 2nd (15) MRI- US guided drainage 2nd (16) Pre-op Intractable nausea Hakamada et al. [27] Anaplastic 38 Incidentally US finding 1st trimester, 1st pregnancy MRI- US 2nd trimester, 2nd pregnancy Intractable nausea, upper GI bleed (pre-op), local recurrence (post-op) Ikuta et al. [28] MCN 30 Left hypochondrial pain 1st (10) CT, - US guided drainage Post-abortion Missed abortion Kamphues et al. [29] Neuroendocrine 32 Arterial HTN 2nd (19) US, MRI 2nd (19) Splenic vein thrombosis renal artery compression (intra-op) Kamphues et al. [29] Neuroendocrine 35 Vomiting, weight loss 2nd (16) Needle biopsy 2nd (18) No complications Kakoza et al. [11] Adenocarcinoma 40 Epigastric pain, nausea, vomiting 2nd (24) Duodenal mucosal biopsy Postpartum Liver metastasis, mother death 6 months post-op Asciutti et al. [30] MCN Epigastric pain + mass 2nd (23) – Postpartum Pancreatitis Onuma et al. [31] Adenocarcinoma 32 frequent uterine
contractions3rd (30) CT, Histological analysis of resected mass 3rd (34) Pre-op Gastric perforation Naganuma et al. [32] MCN 32 threat of premature labor 3rd (33) CT, Histological analysis of resected mass 3rd (34) Tumor rupture, local recurrence 6 months pos-op Perera et al. [7] Adenocarcinoma 25 Epigastric pain, nausea,
One episode of emesis2nd (20) MRCP, ERCP No surgery, underwent chemotherapy Mother Death Lubner et al. [33] Adenocarcinoma 37 nausea, vomiting,
back pain, acholia, and dark colored urine2nd (16) EUS with FNA 2nd (18) Death 12 months post diagnosis Marci et al. [34] Adenocarcinoma 36 Epigastric pain, vomiting, weight loss 3rd (35) US, CT Postpartum (PRE-OP) Acute renal failure Feng et al. [35] SPNs 26 Incidentally abdominal mass by US 2nd (14) US, MRI, needle biopsy 2nd (14) 3rd postoperative day pancreatic fistula occurred Boyd et al. [36] MCN 21 abdominal distention and fullness 1st (10) CT, MRI 2nd (20) No complications Boyd et al. [36] Adenocarcinoma 29 Emesis, epigastric pain 3rd (37) US, CT Postpartum 2 weeks post-op PE, iliac & femoral veins thrombosis, DIC, multiorgan system failure & death. Boyd et al. [36] Adenocarcinoma 37 right upper back pain, nausea and vomiting, alcoholic stools, and dark urine 2nd (17) US, ERCP, FNA 2nd (19) 4 months post-op liver metastasis, 1-year post-op death. Liu et al. [37] Adenocarcinoma 31 weight loss and progressive, positional dyspnea 3rd trimester US, CT, PET scan 3rd (34) Ovarian cyst rupture,
(post-op) Pleural effusion, ascitesTsuda et al. [38] MCN 28 Referred as case of abdominal tumor 1st (9) US, MRI, 2nd (18) Mild glucose intolerance post-op. Tica et al. [39] MCN 27 abnormal sonogram 3rd (29) MRI postpartum No complications Huang et al. [40] SPNs 29 Epigastric pain, backache, nausea, and vomiting 2nd (19) US, MRI 2nd (19) Tumor rupture MacDonald et al. [41] SPNs 23 Incidentally abdominal mass by US 2nd (14) US, MRI 2nd (18) No complications Labarca-Acosta et al. [42] Adenocarcinoma 35 Vomiting, pain in the left epigastrium and hypochondrium, general weakness and weight loss. 16 weeks Fine-needle biopsy – Maternal death Aker et al. [43] Adenocarcinoma 27 Right upper quadrant pain, nausea,and vomiting. 2nd (26) ascites cytology Post-partum Fetal death
Metastasis to placenta, hepatic, supraclavicular lymph nodeDavis et al. [44] Adenocarcinoma 34 abdominal pain and failure to gain weight appropriately in pregnancy. 2nd (26) Pathology
on fine-needle aspiration of the pancreatic head mass confirmed
pancreatic adenocarcinoma– Death 4 months after C-section Aynioglu et al. [45] Adenocarcinoma 36 recurrent severe abdominal pain radiating to the back, jaundice,
nausea, and vomiting.3rd (28) Histopathological analysis Post-partum No complication
In case of pregnancy, diagnosing of ampullary adenocarcinoma can be challenging. The way it does that is by making alarming symptoms of malignancy through the physiological changes of pregnancy. As jaundice can develop frequently in the 3rd trimester due to benign intrahepatic cholestasis, which can be misleading initially as in our case. Furthermore, other symptoms that adenocarcinoma of ampulla of Vater cause like abdominal discomfort, nausea & vomiting also can happen in normal pregnancy. Another challenge is that the gravid uterus that decreases the sensitivity of non-invasive imaging modalities [5]. The reported cases demonstrate a variety of gestational ages at presentation, which indicated a clinical difficulty in diagnosis. Unlike our case, most of the reported cases presented at 2nd trimester.
There are different radiological modalities that can aid in obtaining a confirmatory diagnosis and staging of ampullary carcinoma but not all of these can be used freely during pregnancy such as ERCP or CT scan, due to the risk of radiation exposure to the fetus [7]. The main diagnostic modalities for pregnant women are ultrasonography and MRCP. The ultrasonography is mainly used to identify the presence of biliary dilation & obstruction while MRCP can visualize the mass [8].
In our case, the MRCP revealed an ampullary mass measuring 2 cm with no vascular involvement. ERCP is used during pregnancy for diagnosis by obtaining a biopsy, stenting for biliary draining and to prepare the patient for surgery or if the tumor is not operable. To minimize the risk radiation exposure to the fetus the patient should have a lead shield in place as we did in our case. Biochemically, an elevated carbohydrate antigen 19-9 (CA 19-9) level may help to guide the diagnosis towards an ampullary adenocarcinoma [4]. Nevertheless, US and MRCP were the main diagnostic modalities reported in the literature.
Management wise, surgical resection is usually done by a Whipple procedure (Pancreaticoduodenectomy) followed by an adjuvant therapy is the standard of care for early stage disease. Such surgery carries a risk of many complications. One important complication to consider is pancreatic fistula or leak with a reported incidence ranging from 2 to 40% [9].
To decrease the risk of such complication, intraoperatively a pancreatic duct stent can be used. Adaptation of this technique to protect the anastomotic site & decrease the chance of any leak have led good to outcome of such procedure in some centers [10].
Surgical intervention is challenging in pregnant patients, the appropriate time to intervene depends on the gestational age at the time of diagnosis and the stage of the disease. The challenges that might be encountered in first trimester, is the risk of spontaneous abortion and the best strategy is to abort the pregnancy. While in the second trimester induced delivery can’t be applied as gestational age is not compatible with life and it is the most dangerous time to put the patient on chemotherapy. In the third trimester, the large size of the uterus is another challenge especially intraoperatively [11].
In our patient, the obstetrician induced labor at week 34 of gestation & Whipple procedure was done afterwards and the major challenge was a presence of a bulky uterus during the surgery.
4Conclusion
Obtaining a diagnosis of ampullary adenocarcinoma in pregnant patients in their third trimester & managing them can be challenging due to; 1) the overlapping symptoms between it & the physiological changes of pregnancy, 2) the limitation of using the appropriate diagnostic modalities in order to avoid radiation exposure to the fetus, 3) the intraoperative technical difficulties 2ry to the gravid uterus. Yet, a delayed viable delivery followed by a definitive surgery in the form of pancreaticoduodenectomy is still achievable with a multi-disciplinary approach & good perioperative preparation in early stage disease.
Conflicts of interest
None.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Ethical approval
Case reports are exempted from ethical approval according to our institution policies.
Consent
Written informed consent was obtained from the patient for publication of this case report.
Registration of research studies
N/A.
Guarantor
Dr. Mohammed Saad Alqahtani.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Acknowledgment
None.