ANTICANCER RESEARCH 36: 2391-2396 (2016)

Accurate Diagnosis of Aortic Invasion in Patients with Lung Cancer

HIDETAKA URAMOTO1,2, YOSHIHITO IIJIMA1, YUKI NAKAJIMA1 and HIROYASU KINOSHITA1

1Division of Thoracic Surgery, Saitama Cancer Center, Saitama, Japan; 2Division of Thoracic Surgery, Kanazawa Medical University, Uchinada, Japan

Abstract. Background: The information regarding the Nevertheless, the information regarding the optimal curative optimal treatment of locally advanced lung tumor for treatment of this subgroup remains limited and appropriate achieving a cure remains limited. This is particularly true for indications pertaining to surgical treatment are still lacking an accurate diagnosis of tumor invasion of adjacent (2). An accurate diagnosis of T4 tumors is particularly structures, especially the aorta. Patients and Methods: warranted because it can be difficult to determine whether Between June 2014 and January 2016, 505 consecutive the tumor invades adjacent structures, especially the aorta (3, patients with chest disease underwent surgery at our 4). Consequently, a certain number of cases that are judged Institution. Among these patients, five (1.0%) with lung to be contraindicated for surgery are expected in clinical tumor were strongly suspected of having aortic invasion. practice to be falsely contraindicated. Therefore, the Their clinical records were retrospectively reviewed to treatment results may be greatly improved by improving the identify factors to accurately diagnose aortic invasion in diagnosis of aortic invasion (2). We herein describe patients with lung cancer. The data on patient characteristics consecutive cases of patients who were strongly suspected of including modern-era clinical imaging, surgical details, and having aortic invasion. The data on patient characteristics, perioperative outcomes were analyzed. Results: The study surgical details, and perioperative outcomes were analyzed. population comprised of four males and one female. The histological types were non-small cell carcinoma lung cancer Patients and Methods in four cases and metastatic carcinoma from renal cell carcinoma in one. No cases were determined to be negative Patients. This study was approved by the Saitama Cancer Center by both computed tomography and magnetic resonance Ethics Committee (H28-538). The pretreatment evaluation imaging. However, an intraoperative assessment showed the included a medical history, physical examination, a complete resectability of lesions without invasion in all cases. blood cell count and analysis of serum chemistry, which included serum electrolytes, liver enzymes, bilirubin, creatinine and Conclusion: The diagnosis of aortic invasion may be coagulation levels. Patients were eligible for this study if they overestimated, although aortic invasion is considered an were suspected of having a resectable tumor. Patients were absolute contraindication to surgical management with excluded if they had contralateral hilar lymph-node metastasis or radical intent. Physicians should pay attention to the a serious pre-existing disease (5). Tumor staging was performed possibility of aortic invasion, even if the angle in contact according to chest radiography, enhanced chest and upper with the tumor indicates a wide field of view, in order to abdomen computed tomography (CT), and bronchoscopy findings. provide a chance for a cure. Fluorodeoxyglucose (FDG)-positron-emission tomographic (PET) scans were used in clinical staging assessments. Magnetic resonance imaging (MRI) of the brain was routinely employed. Lung cancer is the leading cause of cancer-related death Patients underwent a preoperative cardiovascular risk assessment, worldwide (1), and approximately one-third of patients with including electrocardiogram and ultrasound cardiography. The lung cancer are diagnosed with locally advanced disease (2). patients’ records, including their clinical data, preoperative examination results, histopathological findings and TNM stages, were reviewed. When a lung tumor was strongly suspected of demonstrating aortic invasion, we performed chest 3.0-T MRI Correspondence to: Hidetaka Uramoto, Divisions of Thoracic examinations to examine such potential aortic invasion using cine Surgery, Saitama Cancer Center, 780 Komuro, Ina, Kita-adachi-gun, display (6). The evaluation of aortic invasion was performed by a Saitama 362-0806, Japan. Tel: +81 487221111, Fax: +81 Board-certified thoracic radiologist, who was blinded to the 487221129, e-mail: [email protected] operative findings and perioperative outcomes, using a high- resolution 128-detector row CT scanner (7) and cine MRI display Key Words: Aortic invasion, surgery, lung cancer. of the thorax, including sagittal and coronal sections.

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Table I. Characteristics of cases with suspected aortic invasion.

Case Gender Age (years) Diagnosisa Histology Tumor size (cm)

1 M 71 Metastatic tumor Renal cell carcinoma 5.3 2 M 68 IB Adenocarcinoma 3.2 3 M 50 IIIA Large cell carcinoma 4.9 4 F 67 IIIA→IIB (after induction therapy) Non-small cell carcinoma 5.8→2.7 5 M 67 IB Squamous cell carcinoma 4.7

M: Male; F: female. aClinical stage [aortic invasion was diagnosed as negative according to previous experience (4)]

Table II. Summary of the computed tomographic (CT) findings of patients with suspected aortic invasion.

Case CT Point of contact Site Diameter of the tumor Angle (degrees) extension to the aorta (cm)

1 Difficult to judge Arch S1+2 4.3 N/A 2 Difficult to judge Descending S1+2 2.3 90 3 Invasion interpreted as negative Arch S1+2 4.1 N/A 4 Invasion interpreted as negative Descending S6 5.5→2.7 180→180 5 Difficult to judge Arch S1+2 2.5 N/A

N/A: Not applicable.

Surgical technique. The patient was explored through the sixth Table III. Summary of the positron-emission tomographic (PET) and intercostal space using a 12 mm single port (8). An additional magnetic resonance imaging (MRI) findings of patients with suspected working port (12 mm) was used to move the tumor in the lung and aortic invasion. confirm no invasion of the aorta as necessary. After the absence of aortic invasion was confirmed, video-assisted thoracic surgery Case PET (SUV) MRI assisted lobectomy with systematic mediastinal lymph node dissection (en bloc removal of the mediastinal fatty tissue containing 1 8.1 No invasion the lymph nodes) was performed (5). 2 14.5 Invasion suspected 3 19.86 Invasion suspected 4 13.52→ 5.8 Invasion was not completely ruled out Results 5 11.1 Invasion suspected

Patient characteristics. From June 2014 through January SUV: Standardized uptake value. 2016, 505 consecutive chest disease patients underwent surgery at our Institution. Of these, five (1.0%) with lung tumor who were strongly suspected of having aortic invasion were included in this study. The characteristics of these MRI (Figure 1), and no cases were judged to be negative by patients are shown in Table I. The study population both CT and MRI (Table III). After an intraoperative comprised of four males and one female (mean age=64.6 assessment, left upper lobectomy and lymph-nodal dissection years; range=50-71 years). All of the patients were Japanese. was performed in all cases with little difficulty. The average The histological types were non-small cell carcinoma lung operative time and intraoperative blood loss during the cancer in four and metastatic carcinoma from renal cell operation was 140 min and 70 ml, respectively. Postoperative carcinoma in one. The mean diameter of the tumor measured complications occurred in three cases. However, the 30-day 4.8 cm (range=3.2-5.8 cm). Two cases were interpreted as and 90-day mortality rates were both 0% (Table IV). being negative by CT (Figure 1). The mean diameter of the tumor extension to the aorta was 3.7 cm (range=2.3-5.5 cm). Discussion The angle of descending aortic invasion in these two cases was 90 and 180 degrees (Table II). The mean standardized Aortic invasion is considered an absolute technical and uptake value (SUV) of the tumor by PET was 13.4. Three oncological contraindication for surgery (9). Therefore, cases were judged to be suspicious for aortic invasion by making an accurate diagnosis of aortic invasion is

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Figure 1. A: Chest computed tomographic image showing a tumor in the left lower lobe in Case 4. B: Aortic invasion of the left lung tumor was suspected by CT. The left and right images demonstrate CT findings before and after induction treatment, respectively. C: The possibility of invasion was not completely ruled out by a sagittal section on magnetic resonance imaging.

Table IV. Summary of the perioperative factors of patients in this study.

Case Surgical procedure Operative time (min) Blood loss (ml) Postoperative complication (Grade) Stagea

1 Completion LUL +LND 161 278 Hyperkalemia (I) N/A 2 LUL +LND 159 15 None IIA 3 LUL +LND 116 10 Liver dysfunction (II) IIIA 4 LUL +LND 124 12 None IA 5 LUL +LND 138 33 Liver dysfunction (II) IIB

LUL: Left upper lobectomy, LND: lymph nodal dissection, aPathological stage.

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90 degrees of circumferential contact between the tumor and aorta, and the disappearance of mediastinal fat between the tumor and the adjacent mediastinal structures (10). However, some cases without aortic invasion also undergo curative resection (4). Therefore, aortic invasion may be overestimated (6). Furthermore, treatment results may improve following an accurate diagnosis of aortic invasion. Enhanced CT is generally used to determine aortic invasion. However, CT findings have proven to be unreliable for assessing individual cases (10). We previously experienced a case in which the patient had a left lower lobe cancerous lesion measuring 9 cm that was both wide and long, abutting the descending aorta. No clear fat plane was visible between the aorta and the cancer mass. However, an intraoperative assessment indicated the resectability of the lesion without invasion (4). Furthermore, we recently reported the usefulness of easily diagnosing the absence of aortic invasion using cine MRI without the need for specialized software (6). However, the reported patient did not undergo surgical confirmation of the cine MRI findings. Therefore, we herein described the consecutive cases of patients who were strongly suspected of having aortic invasion and underwent operation in this study. No cases were determined to be negative for aortic invasion on both CT and MRI, and either CT or MRI led to diagnosis of aortic invasion in all cases. Additionally, complete resection without the aorta was performed. These findings suggest limitations in current diagnostic imaging for aortic invasion, despite recent advances in diagnostic imaging (11). Thus, surgical resection of some tumors that are strongly suspected of invading the aorta may be carried out. Indeed, all five cases in the present study were ultimately confirmed not to have aortic invasion. There are several limitations associated with this study that must be taken into account when considering the present findings. These include the retrospective nature of the study and the fact that it was carried out at a single institution. Nevertheless, the current results highlight an important issue, as complete resection remains the mainstay among curative modalities. Thus, reduced port-surgery might be considered for intraoperative assessment because some cases may lead to false- positive results, even with advances in clinical imaging, without any obvious findings, such as a narrowed lumen of the aorta. Figure 2. A: Chest computed tomographic image showing a tumor in the left upper lobe in Case 5. B: Aortic invasion of the left lung tumor was suspected. However, aortic invasion was interpreted as being Conflicts of Interests negative by CT, although invasion was suspected by a coronal section on magnetic resonance imaging (C). None declared.

References particularly important for selecting the optimal therapy. 1 Uramoto H, Okumura M, Endo S, Tanaka F, Yokomise H and When tumor invasion spans a great area, abutting the aorta, Masuda M: The 30-day mortality and hospital mortality after then T4 lung cancer as aortic invasion is frequently chest surgery described in the annual reports published by the diagnosed due to there being more than 3 cm of contact Japanese Association for Thoracic and Cardiovascular Surgery. between the tumor and the adjacent mediastinum, more than Gen Thorac Cardiovasc Surg 63: 279-283, 2015.

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2 Uramoto H, Shimokawa H, Hanagiri T, Ichiki Y and Tanaka F: 8 Oka S, Uramoto H and Hanagiri T: Successful extirpation of Factors predicting the surgical outcome in patients with T3/4 thoracic pleural lipoma by single-port thoracoscopic surgery. lung cancer. Surg Today 44: 2249-2254, 2014. Asian J Surg 34: 140-142, 2011. 3 Munden RF, Swisher SS, Stevens CW and Stewart DJ: Imaging 9 Misthos P, Papagiannakis G, Kokotsakis J, Lazopoulos G, of the patient with non-small cell lung cancer. Radiology 237: Skouteli E and Lioulias A: Surgical management of lung cancer 803-818, 2005. invading the aorta or the superior vena cava. Lung Cancer 56: 4 Uramoto H and Kinoshita H: Careful diagnosis of aortic invasion 223-227, 2007. in patients with lung cancer using modern diagnostic imaging. 10 Naidich DP, Webb WR, Muller NL and Krinsky GA: Computed Asian Pac J Cancer Prev 16: 2105, 2015. tomography and magnetic resonance imaging of the thorax. 5 Uramoto H, Akiyama H, Nakajima Y, Kinoshita H, Inoue T, Lippincott Williams & Wilkins, pp. 639, 2007. Kurimoto F, Nishimura Y, Saito Y, Sakai H and Kobayashi K: 11 Venuta F, Rendina EA, Ciriaco P, Polettini E, Di Biasi C, Gualdi The long-term outcomes of induction chemoradiotherapy GF and Ricci C: Computed tomography for preoperative followed by surgery for locally advanced non-small cell lung assessment of T3 and T4 bronchogenic carcinoma. Eur J cancer. Case Rep Oncol 7: 700-10, 2014. Cardiothorac Surg 6: 238-241, 1992. 6 Uramoto H, Kinoshita H, Nakajima Y and Akiyama H: Easy diagnosis of aortic invasion in patients with lung cancer using cine magnetic resonance imaging. Case Rep Oncol 8: 308-311, 2015. 7 Uramoto H, Nozu S, Nakajima Y and Kinoshita H: Possibility of determining the degree of adhesion of the lymph node to the Received February 5, 2016 pulmonary artery preoperatively. J Cardiothorac Surg 10: 101, Revised April 4, 2016 2015. Accepted April 6, 2016

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