journal name: international journal of hepatobiliary and

Manuscript Accepted Early View Article

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Early View Article: Online published version of an accepted article before publication in the

final form.

Journal Name: International Journal of Hepatobiliary and Pancreatic Diseases (IJHPD)

Type of Article: Case Report

Title: Adrenal Cortical Carcinoma with Pulmonary Emboli: A Unique Presentation of a

Rare Tumor with Extensive Tumor Thrombus and Inferior Vena Cava Extension

Authors: Hoylan T. Fernandez, Peter T. W. Kim, Giuliano Testa

doi: To be assigned

Early view version published: March 18, 2016

How to cite the article: Fernandez H T, Kim P T W, Testa G. Adrenal Cortical Carcinoma

with Pulmonary Emboli: A Unique Presentation of a Rare Tumor with Extensive Tumor

Thrombus and Inferior Vena Cava Extension. International Journal of Hepatobiliary and

Pancreatic Diseases (IJHPD). Forthcoming 2016.

Disclaimer: This manuscript has been accepted for publication. This is a pdf file of the

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TYPE OF ARTICLE: Case Report 1

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TITLE: Adrenal Cortical Carcinoma with Pulmonary Emboli: A Unique Presentation 3

of a Rare Tumor with Extensive Tumor Thrombus and Inferior Vena Cava Extension 4

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AUTHORS: 6

Hoylan T. Fernandez1, MPH, Peter T. W. Kim1, Giuliano Testa1, MBA 7

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AFFILIATIONS: 9

1MD, From the Annette C. and Harold C. Simmons Transplant Institute, Baylor 10

University Medical Center, Dallas, Texas. 11

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CORRESPONDING AUTHOR DETAILS 13

Hoylan T. Fernandez, MD 14

Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical 15

Center, 3500 Gaston Avenue, Dallas, TX 75246 United States 16

Phone number: 214-820-2050; 17

Email: [email protected]. 18

Fax: 214-818-6491 19

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Short Running Title: IVC Reconstruction for Adrenal Cortical Carcinoma 21

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Guarantor of Submission : The corresponding author is the guarantor of 23

submission. 24

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35

ABSTRACT 36

37

Introduction 38

Adrenal cortical carcinoma (ACC) is rare, and presenting symptoms vary widely 39

depending on functional or non- functional endocrine status. These tumors are most 40

commonly treated with surgical resection and post-operative mitotane administration. 41

42

Case Report 43

This is an unusual presentation of a 23 year old female with no significant past 44

medical history, admitted to the hospital with syncope and dyspnea. CTA 45

demonstrated extensive bilateral pulmonary embolisms, with an associated 16cm 46

assumed right lobe hepatic mass with suprahepatic vena cava tumor thrombus 47

extension beyond the level of the hepatic veins. The patient underwent a complete 48

resection of the right adrenal mass, with inferior vena cava resection, thrombectomy, 49

and placement of caval interposition graft without the use of bypass. Pathology was 50

consistent with adrenal cortical carcinoma. 51

52

Conclusion 53

This case of an adrenal cortical carcinoma, with a rare presentation of bilateral 54

pulmonary embolisms, was treated with a surgical R0 resection. This included a 55

right adrenalectomy with IVC resection and interposition graft. Tumors with IVC 56

involvement and tumor thrombus can be treated with surgical resection and IVC 57

grafting, without the use of bypass. 58

59

Keywords: inferior vena cava, adrenalectomy, adrenal cortical carcinoma 60

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66

INTRODUCTION 67

Adrenal cortical carcinoma (ACC) is an extremely rare condition, with an incidence of 68

1 to 2 per million populations [1–5]. Patients may present with symptoms of steroid 69

surplus such as Cushing’s syndrome, virilization, hirsutism, or oligomenorrhea. In 70

atypical cases, presentations may include hypertension or electrolyte disturbances 71

associated with hyperaldosteronism. However, nonfunctioning tumors may present 72

with abdominal or back pain and vague gastrointestinal symptoms. These are 73

extremely aggressive tumors requiring a complete R0 resection and adjuvant 74

treatment with mitotane. Large-vessel invasion has been demonstrated as a poor 75

prognostic indicator, with a <30% 3-year survival rate.2,3 Resection of ACC with caval 76

extension and tumor thrombus has been described previously and has required a 77

cavotomy for thrombus removal or venous patch, conducted with the use of cardiac 78

bypass or veno-veno bypass [4,5]. This report describes a right ACC with rare 79

presentation of initial bilateral pulmonary embolisms and with suprahepatic vena 80

cava tumor thrombus extension above the level of the hepatic veins. The patient 81

required a right adrenalectomy, inferior vena cava (IVC) resection, thrombectomy, 82

and IVC replacement with composite graft, conducted without the use of bypass. 83

84

CASE REPORT 85

A 23-year-old woman with no significant past medical history was admitted to the 86

hospital with dyspnea and syncope. The admitting laboratory values included: Na 87

141meq/L, Cr 0.79mg/dL, glucose 129mg/dL, troponin 0.412ng/mL, D dimer 88

10.4ug/mL FEU, lactate 2mmol/L. A computed tomography scan of the head was 89

normal. However, a computed tomography angiogram of the chest demonstrated 90

extensive bilateral pulmonary emboli in the right and left main pulmonary arteries, 91

with extension into lobar, segmental, and subsegmental branches. Doppler 92

ultrasound of the lower extremities was negative for venous thrombosis. An 93

echocardiogram showed significant right atrial and ventricular dilation with markedly 94

reduced systolic function but preserved ejection fraction and a well-circumscribed 95


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mass in the IVC consistent with thrombus. She was treated with tissue plasminogen 96

activator and continuous heparin infusion. 97

Ultrasound of the abdomen revealed a 16-cm mass thought to arise from the right 98

hepatic lobe with a 5-cm IVC thrombus. On subsequent magnetic resonance 99

imaging, a 16.6-cm mass was noted in the right upper quadrant adjacent to the 100

posterior right hepatic lobe with extension into the intrahepatic IVC and prominent 101

tumor thrombus extending just distal to the right atrium (Figure 1A–1C). Urine 102

metanephrine and normetanephrines were negative, but the free cortisol level was 103

elevated. Her dehydroepiandrosterone level was significantly elevated, while her 104

morning cortisol level was within normal limits. Tumor activity was negative for 105

adrenocorticotropic hormone, alpha-fetoprotein, and carbohydrate-associated 106

antigen 19-9. A transjugular biopsy of the tumor thrombus was attempted; however, 107

a large multilobular filling defect in the IVC was noted extending beyond the level of 108

the hepatic veins, resulting in an 80% stenosis (Figure 1D). Percutaneous biopsy 109

was consistent with ACC, with positive immunohistochemistry staining for inhibin and 110

MART-1 but negative staining for adrenocorticotropic hormone. 111

The tumor was arising from the right adrenal gland with multiple enlarged venous 112

collaterals enveloping the surface and adherent to the inferior aspect of the liver with 113

no apparent tumor infiltration of the liver or kidney. There was clear tumor infiltration 114

of the IVC and thrombus extending from the suprarenal cava to the level of the 115

hepatic veins (Figure 2A). 116

The liver was mobilized off of the right diaphragm and IVC. The right kidney was 117

spared by dissecting the tumor from the adrenal, with preservation of the right renal 118

vein. The adrenal mass was completely mobilized from the retroperitoneum. Total 119

vascular exclusion of the liver was performed by circumferential dissection of the 120

infrahepatic suprarenal cava, and the suprahepatic vena cava just below the hepatic 121

veins. Vascular clamps were positioned at the supra and infrahepatic caval positions, 122

ensuring the suprahepatic clamp was placed superior to the thrombus. The right 123

adrenal gland and IVC was removed en bloc (Figure 2B). A polyester composite 124

graft (Hemashield Gold 22 mm- Maquet Getinge Group) was used to reconstruct the 125

IVC in an end-to-end fashion (Figure 2C, 2D). Once the suprahepatic caval 126


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anastomosis was completed, the clamp was moved below the hepatic veins to allow 127

for early reperfusion of the liver and to aid with overall hemodynamics. 128

Pathology was consistent with an 18-cm, 928-g right ACC with IVC and liver capsule 129

invasion. The margins were negative, with no evidence of perineural invasion. The 130

patient did well postoperatively with no immediate complications and was discharged 131

on a steroid taper. She commenced treatment with mitotane as an adjuvant therapy 132

and therapeutic lovenox for treatment of her pulmonary emboli. 133

134

DISCUSSION 135

Adrenal cortical carcinoma is an extremely rare disease, whose incidence has been 136

reported at 0.78 per million, though other sources may report a higher incidence. It 137

has been noted to be more prevalent in women, occurring either in childhood or in 138

the fourth or fifth decade. They may be glucocorticoid, androgen, estrogen, or 139

aldosterone producing. However, in rare cases these masses may not produce 140

hormones, appear clinically inactive, and are found incidentally. Symptoms of 141

inactive tumors may include abdominal or back pain, fever, weight loss, or may have 142

no apparent clinical symptoms associated with their presence. 143

Diagnosis of ACCs involves both hormonal work up and imaging studies. If 144

glucocorticoid production is suspected, the following should be performed: 145

dexamethasone suppression test, 24 hr urinary cortisol, serum cortisol, and serum 146

ACTH. In the case of androgen or estrogen production a serum DHEA-S, 17-OH 147

progesterone, androstenedione, testosterone, and a 17β estradiol should be 148

obtained. In cases of aldosterone production serum potassium, and an 149

aldosterone/renin ratio are required. A pheochromocytoma should be excluded in 150

the work up. In regards to imagine, CT or MRI offer high specificity, and a PET scan 151

may be helpful in identification of metastatic disease. The presence of tumor 152

thrombus may require Doppler ultrasound, or echocardiography to define the 153

margins of extension. Pursuing a biopsy is discouraged as hormonal work up and 154

imaging are sufficient for diagnosis, and may create the risk of metastasis. However, 155

if the mass is not amenable to surgical intervention, a biopsy may be required for 156

diagnostic purposes to dictate appropriate medical therapy. 157

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By definition, an ACC with tumor thrombus is classified as a T4 tumor, and stage III 159

cancer. In most cases, these tumors are amenable to surgical resection and come 160

with a high (60-80%) risk of recurrence even with a complete resection. 161

Thrombectomy is performed with the aid of IVC cross clamping, hepatic vascular 162

exclusion, or the use of cardiopulmonary bypass, determined by the margins of 163

thrombus extension. In some cases, replacement of the IVC by use of a vascular 164

graft may be necessary if the thrombus has invaded the vascular wall, or cannot be 165

easily removed, and should be performed if an R0 resection is anticipated. Adjuvant 166

therapy with mitotane is recommended and radiotherapy may be considered. Large 167

vessel invasion independently represents a poor prognostic factor, and confers an 168

inferior disease free survival as well as overall survival. Imaging with CT, and in 169

some cases PET, is recommended every 3 months for at least 2 years. Overall 170

prognosis is poor with a 5 year survival rate of <35% in complete resections, and 171

<10% in incomplete resections. Median survival for stage III cases with large vessel 172

invasion are thought to be approximately 9 months, with a significantly decreased 173

disease specific survival with the presence of tumor thrombus. 174

Surgical resection is the current standard of care in the treatment of ACC, with 175

extent of resection dictated by local invasion of surrounding organs and large vessel 176

invasion. A small number of case reports, case series, and reviews have described 177

resection of ACCs with caval extension and caval tumor thrombus requiring 178

cavotomy or limited IVC resection with emphasis on radical resection and requiring 179

cardiac or veno-veno bypass. While long term prognosis of these progressed ACCs 180

remains poor due to delayed diagnosis, frequent presence of advanced disease, and 181

lack of effective adjuvant treatment, the best management available is complete 182

surgical resection. 183

This case illustrates the use of radical resection with removal of suprahepatic vena 184

cava tumor thrombus above the level of the hepatic veins and composite graft 185

placement without the use of bypass. 186

187

CONCLUSION 188

An R0 resection and large-vessel venous reconstruction of these extensive 189

adrenalcortical carcinomas can be achieved without the aid of cardiac or veno-veno 190


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bypass. Imaging is imperative in pre-operative planning, and a multi-disciplinary 191

team approach may be necessary. 192

193

ABBREVIATIONS 194

ACC, adrenal cortical carcinoma; IVC, inferior vena cava 195

196

CONFLICT OF INTEREST 197

There is no conflict of interest to report, including manuscript preparation or funding 198

by a commercial organization. 199

200

AUTHOR’S CONTRIBUTIONS 201

Hoylan T. Fernandez – Substantial contributions to conception and design, 202

acquisition of data, analysis and interpretation of data, drafting the article, revising 203

it critically for important intellectual content, final approval of the version to be 204

published 205

Peter T. W. Kim – Analysis and interpretation of data, revising it critically for 206

important intellectual content, final approval of the version to be published 207

Giuliano Testa- Analysis and interpretation of data, revising it critically for important 208

intellectual content, final approval of the version to be published 209

210

REFERENCES 211

1. Libé R. Adrenocortical carcinoma (ACC): diagnosis, prognosis, and 212

treatment. Front Cell Dev Biol 2015; 3:45. 213

2. Gaujoux S, Brennan MF. Recommendation for standardized surgical 214

management of primary adrenocortical carcinoma. Surgery 2012; 152:123-215

32. 216

3. Turbendian HK, Strong VE, Hsu M, Ghossein RA, Fahey TJ 3rd. 217

Adrenocortical carcinoma: the influence of large vessel extension. Surgery 218

2010; 148:1057-64. 219

4. Chiche L, Dousset B, Kieffer E, Chapuis Y. Adrenocortical carcinoma 220

extending into the inferior vena cava: presentation of a 15-patient series and 221

review of the literature. Surgery 2006;139:15-27. 222


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5. Ochi T, Tanji N, Shimamoto K, Ikeda T, Toshino A, Yokoyama M. 223

Application of cardiopulmonary bypass for resection of renal cell carcinoma 224

and adrenocortical carcinoma extending into the right atrium. Int J Urol 225

2006; 13:202-5. 226

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FIGURE LEGENDS 228

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Figure 1: Magnetic resonance imaging demonstrating (A)- the right adrenal mass 230

involving the IVC with tumor thrombus; (B)- the origin arising from the right adrenal; 231

(C)- a coronal view showing IVC extension to the level of the hepatic veins; and (D)- 232

a venogram demonstrating IVC thrombus with resulting stenosis 233

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Figure 2: Surgical photos: (A) - right adrenal tumor in situ, with liver rotated medially 235

to expose the IVC; (B)- right adrenal tumor after removal; (C)- composite graft 236

reconstruction of the IVC due to tumor involvement; (D)- completion of IVC graft 237

reconstruction 238

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FIGURES 255

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Figure 1: Magnetic resonance imaging demonstrating (A)- the right adrenal mass 259

involving the IVC with tumor thrombus; (B)- the origin arising from the right adrenal; 260

(C)- a coronal view showing IVC extension to the level of the hepatic veins; and (D)- 261

a venogram demonstrating IVC thrombus with resulting stenosis 262

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Figure 2: Surgical photos: (A) - right adrenal tumor in situ, with liver rotated medially 278

to expose the IVC; (B)- right adrenal tumor after removal; (C)- composite graft 279

reconstruction of the IVC due to tumor involvement; (D)- completion of IVC graft 280

reconstruction 281

journal name: international journal of hepatobiliary and

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