ROBOTIC PARAGANGLIOMA RESECTION IN A PREGNANT PATIENT

Abstract

Objective:

Functional paragangliomas in pregnancy are rare; however, if not recognized and treated early, they can be life-threatening. New treatment approaches with robotic resection are promising.

Methods:

We present a case of a pregnant female with a paraganglioma which was successfully resected during the second trimester using Da Vinci Xi robotic system. Paraganglioma was diagnosed with plasma and urinary catecholamines and metanephrines, a contrast computed tomography (CT) scan, and confirmed with surgical pathology.

Results:

The patient was initially seen in the emergency room prior to the index pregnancy for nausea, vomiting, and intermittent, left lower quadrant abdominal pain, episodic sweating, palpitations, and anxiety. CT scan of the abdomen and pelvis showed a 4.8 × 4.3 cm heterogeneously enhancing mass in the left retroperitoneum adjacent to the aorta just below the left adrenal gland. She had normal plasma metanephrines but elevated plasma normetanephrines of 7.12 nmol/L (normal, <0.89 nmol/L). Twenty-four-hour urine norepinephrine and catecholamines were elevated to 604 μg (normal, <90 μg/24 hours) and 610 μg (normal, <115 μg/24 hours), respectively. Chromogranin A was elevated to 940 ng/mL (normal, 0 to 95 ng/mL). Paraganglioma was suspected. Doxazosin was started for blood pressure control. The patient became pregnant unexpectedly shortly after. She was managed by a multidisciplinary team. At 18 weeks of pregnancy, she underwent a transabdominal robotic resection of the left retroperitoneal paraganglioma with an excellent outcome.

Conclusion:

Functional paragangliomas in pregnancy are rare but must be recognized and treated early to reduce maternal and fetal complications. An innovative robotic approach should be considered and explored.

INTRODUCTION

Pheochromocytomas and paragangliomas (PPGLs) in pregnancy are rare. Early recognition, diagnosis, and treatment are essential for reducing maternal and fetal complications and mortality (1). Management is aimed at blood pressure control with medication and definitive treatment with surgical resection. Laparoscopic resection is the most common treatment choice if PPGL is diagnosed before the 24th week of pregnancy (1). Reports on robotic resection of PPGLs in general are emerging but are scarce in pregnancy (2,3). There is 1 reported case of robotic resection of pheochromocytoma during the second trimester of pregnancy (4). Here we report the first case (to our best knowledge) of a pregnant woman with a paraganglioma in whom robotic resection was performed in the second trimester with great success.

CASE REPORT

A 33-year-old gravida 4, para 2 female with a past medical history of anxiety and asthma presented to our emergency room with 2 days of nausea, vomiting, and intermittent left lower quadrant abdominal pain. She had diastolic hypertension (blood pressure, 127/96 mm Hg) and was tachycardic (heart rate, 119 beats per minute [bpm]). A contrast computed tomography (CT) scan of the abdomen and pelvis showed a 4.8 × 4.3 cm heterogeneously enhancing mass in the left retroperitoneum adjacent to the aorta, just below the adrenal gland (Fig. 1). On further history taking, the patient reported a 1-year history of episodic sweating, palpitations, and anxiety. Laboratory results revealed normal plasma metanephrines of 0.46 nmol/L (normal, <0.49 nmol/L), but markedly elevated plasma normetanephrines of 7.12 nmol/L (normal, <0.89 nmol/L). Twenty-four hour urine epinephrine and dopamine were normal (<6 μg/24 hours and 218 μg/24 hours, respectively). Urine norepinephrine was elevated to 604 μg/24 hours (normal, <90 μg/24 hours) and urine catecholamines were elevated to 610 μg/24 hours (normal, <115 μg/24 hours). Chromogranin A was elevated to 940 ng/mL (normal, 0 to 95 ng/mL). The patient did not show up at her scheduled endocrine clinic visits until 3 months later. During that visit, her blood pressure was elevated at 154/107 mm Hg and her heart rate was elevated at 119 bpm. Repeat plasma normetanephrines had increased further at 21 nmol/L. Functional paraganglioma was suspected. She was started on doxazosin 1 mg daily with instruction on dose titration for blood pressure control and referred to an endocrine surgeon for surgical intervention. Three weeks later, the patient was found to be pregnant, and she was referred to a high-risk pregnancy clinic. Her case was discussed in a multidisciplinary tumor board. Tumor resection in the second trimester was recommended. Considering the location of tumor and the patient’s pregnancy, the endocrine surgeon, who has performed high-volume laparoscopic and robotic-assisted surgery, elected to use minimally invasive robotic surgery for paraganglioma resection in this pregnant woman.

Fig. 1.

Contrast CT scan of abdomen showed a 4.8 × 4.3 cm heterogeneously enhancing mass in the left retroperitoneum adjacent to the aorta just below the left adrenal gland. CT = computed tomography.

At 18 weeks of pregnancy, the patient was taken to the operating room for robotic paraganglioma resection under general anesthesia using propofol. Her blood pressure was well controlled on doxazosin 2 mg daily prior to the surgery. The patient was placed in the right decubitus position with left side up. Da Vinci Xi robotic system (Intuitive, Sunnyvale, CA) was used to dissect the tumor via transabdominal approach. Normotensive blood pressure goals were achieved (with average blood pressure 120 to 130/70 to 80 mm Hg) using esmolol and nicardipine drip during tumor resection; as well as volume expansion with albumin and plasmalyte, and norepinephrine drip immediately after tumor resection. The surgery was successful; a 5.5 cm (44 g) left retroperitoneal mass was removed. Histology confirmed the diagnosis of paraganglioma with zellballen, positive stains for chromogranin, synaptophysin, and S100 proteins. The procedure time (skin to skin) was 136 minutes, with an estimated blood loss of 250 mL. Repeat plasma normetanephrines improved to normal at 0.56 nmol/L 2 weeks after the surgery. The patient continued to be followed closely at the high risk pregnancy clinic per protocol until delivery. She had no further complications, and underwent a successful spontaneous vaginal delivery of a healthy infant at 39.1 weeks gestational age. Infant APGAR score was 8 at 1 minute and 9 at 5 minutes. She was discharged 48 hours after delivery. Unfortunately, the patient was lost to endocrine follow-up before further genetic workup was completed. Chart review showed the patient was seen in our emergency department 2 years later for ankle pain but without endocrine issues.

DISCUSSION

Pheochromocytomas and paragangliomas (PPGLs) during pregnancy are rare with an estimated incidence of 0.007% (1). Pheochromocytomas are derived from chromaffin cells in the adrenal medulla whereas paragangliomas are derived from the extra-adrenal autonomic ganglia from other areas including the carotid body, jugular foramen, middle ear, posterior mediastinum, abdominal para-aortic region (5). Paragangliomas are less common and make up 19% of PPGLs during pregnancy (6). Functional PPGLs secrete catecholamines which can lead to severe maternal complications including a hypertensive crisis, hemodynamic collapse, pulmonary edema, cerebral hemorrhage and arrhythmia, and fetal complications including hypoxia, intrauterine growth restriction (IUGR), prematurity, and fetal demise (1,7). Fortunately, the maternal mortality rate has now improved to 8 to 9.8% with earlier diagnosis and treatment, compared to 45% prior to 1975 (1,7). Fetal mortality from uncontrolled maternal PPGLs ranges from 12 to 17% (6,7).

Early recognition and diagnosis of PPGLs are crucial for reducing complications. Initial screening for functional PPGLs includes plasma metanephrines or 24-hour urinary catecholamines and metanephrines. False-positive results can be caused by drugs used commonly during pregnancy, including methyldopa, labetalol, and tricyclic antidepressants (5,8,9). Clonidine suppression and glucagon stimulation testing are not recommended in pregnancy due to diagnostic inaccuracy and risks (10). After a positive biochemical screen, the next step is diagnostic imaging (1,5). Magnetic resonance imaging is preferred during pregnancy, with 90 to 100% sensitivity and 70 to 80% specificity (5,8). Contrast CT scans and meta-iodobenzylguanidine scintigraphy are contraindicated in pregnancy due to harmful effects on the fetal thyroid (9,11). Abdominal ultrasound is acceptable but has low sensitivity, especially during the third trimester (8). In our case, the patient became pregnant shortly after the diagnosis of paraganglioma. Genetic consultation and testing should be performed once tumors are diagnosed. Approximately 25 to 30% of patients with PPGLs are found to have a previously undiagnosed inherited disorder or genetic syndrome (8).

Treatment of functional PPGLs in pregnancy involve controlling hypertension with medication and definitive treatment with surgical resection. A multidisciplinary team including obstetrics, endocrinology, surgery, anesthesiology, and neonatology should work together to manage patients. The most common medications are alpha-blockers including phenoxybenzamine, doxazosin, and prazosin (1,6,7,11). Medication should be started at the time of diagnosis and for at least 10 to 14 days before surgery (1). Currently, there are no evidence-based recommendations for an agent of choice in pregnant women. Beta-blockers may be added several days later in combination with alpha-blockers to treat catecholamine induced or reflex tachycardias; however, beta-blocker use is controversial due to concern for IUGR, fetal/neonatal bradycardia, and respiratory suppression (1,6,8).

Surgical resection of the tumor depends on timing of diagnosis, size, and location. If functional PPGLs are diagnosed before the 24th gestational week and less than 6 to 7 cm in size, laparoscopic resection is the most common treatment choice (1). Beyond the second trimester, laparoscopic surgery becomes more difficult due to an enlarged uterus and surgery is frequently delayed until the time of cesarean section or postpartum. Cesarean section has generally been recommended because of increased catecholamine release during vaginal delivery; however, there are case reports of successful vaginal delivery (12,13).

Robotic surgery is a relatively newer approach for resection of PPGLs that allows the surgeon to operate in smaller spaces with more dexterity and precision and with less risk of pneumoperitoneum (1,4,14–16). A recent study showed that anesthesia, procedure times, and cost for robotic adrenalectomy were similar to those of laparoscopic adrenalectomy (14). Reports on robotic resection of PPGLs are emerging but scarce, especially in pregnancy (2,3). There has been 1 case report of successful robotic resection of a pheochromocytoma in the second trimester of pregnancy (4). A minimally invasive approach (laparoscopic or robotic) for resection of a retroperitoneal paraganglioma is often more challenging than for a pheochromocytoma because paragangliomas are usually in the area of the kidney hilum or para-aortic (like in our case). There has been 1 case report of robot-assisted resection of a 7 cm retroperitoneal paraganglioma in a 19-year-old nonpregnant female (3). In our case, an experienced high-volume surgeon explored the option of a robotic approach in a pregnant woman during her second trimester. The transabdominal robotic approach provided advantages such as making it easier to work in tighter spaces, delicate dissection, improved visibility and ergonomics, and is more useful in obese patients and larger tumors (>5.5 cm) in comparison to laparoscopic surgery or posterior retroperitoneoscopic approach (4,15,16). The surgeon in our case was able to resect the paraganglioma using the transabdominal robotic approach with great success.

CONCLUSION

Functional PPGLs during pregnancy are rare. Initial management involves starting alpha-blockers to help manage blood pressure and surgery for definitive treatment. When possible, minimally invasive surgery should be performed during the second trimester. Data on robotic resection of paragangliomas during pregnancy is scarce. To the best of our knowledge, this is the first report of successful resection of paraganglioma in a pregnant woman via a robotic approach. Resection of PPGLs during pregnancy via robot-assisted surgery should be considered when possible and further explored.

Abbreviation

PPGL

pheochromocytoma and paraganglioma