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Ann Thorac Surg 2005;79:1409-1411
© 2005 The Society of Thoracic Surgeons


Case report

A Direct Measurement of Serum Amylase Levels Produced by Lung Cancer

Mitsuaki Sakai, MD*,a, Shigemi Ishikawa, MD, PhDb, Tatsuo Yamamoto, MD, PhDb, Masataka Onizuka, MD, PhDb, Yuzuru Sakakibara, MD, PhDb, Masayuki Noguchi, MD, PhDc

a Department of Thoracic Surgery, Tsukuba Gakuen Hospital, Tsukuba, Ibaraki, Japan
b Department of Surgery, Institute of Clinical Medicine, Tsukuba, Ibaraki, Japan
c Department of Pathology, Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Ibaraki, Japan

Accepted for publication October 16, 2003.

* Address reprint requests to Dr Sakai, Tsukuba University Hospital, Department of Thoracic Surgery, Amakubo 2-1-1, Tsukuba City, Ibaraki Prefecture 305-8576, Japan
misakai-ths{at}umin.ac.jp


    Abstract
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 Abstract
 Introduction
 Comment
 References
 
The production of amylase by lung cancer has been previously diagnosed pathologically or immunohistochemically, or it has been confirmed by a decrease in serum levels after resection. It is possible to directly probe the continuous production of amylase by collecting samples from the inflow and outflow vessels of lung cancer. We herein describe an intraoperative measurement in which the amylase level in the pulmonary lobar vein was 3 times greater than that in the superior vena cava which was 6 times greater than the normal range. The venous level of amylase returned to a normal range after resection.


    Introduction
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 Abstract
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Hyperamylasemia is one of the rare complications of lung cancer. Previous pathologic or biochemical studies support the existence of a mechanism in which lung cancer tissue can produce amylase [1, 2]. In an immunohistochemical study, the amylase levels in lung cancer tissue were higher than those in normal lung tissue [3]. Conversely, other studies have shown that inflammatory or normal lung tissue could also produce amylase [1, 4] and that increased amylase positive-staining in lung cancer tissue did not correlate with hyperamylasemia [5]. Because these studies were pathologic or biological studies and were not specific to amylase-producing lung cancer, it is important to evaluate serum amylase levels directly from blood samples in pre- and post-lung tumor vessels to clarify the location of amylase secretion and to verify continuous amylase secretion.

We herein report a case of amylase-producing lung cancer in intraoperative measurement of serum amylase levels was performed from vessels of pre- and post-tumor.

A 58-year-old man was admitted to our hospital complaining of a persistent dry cough for 2 months. Physical examination on admission revealed clubbed fingers and spinal scoliosis. Laboratory data showed hyperamylasemia that was 1,255 U/L in serum (normal, < 109 U/L) and 1,552 U/L in urine (normal, < 450 U/L). Amylase isozyme analysis using electrophoresis showed that the salivary types were dominant (98%) compared with the pancreatic type (2%). No abnormality in the salivary glands or pancreas was confirmed by computed tomography or ultrasonography. Moreover, the patient had no hematological signs of macroamylasemia or renal insufficiency. Serum carcinoembryonic antigen and cyfra 21-1 were elevated to 13.9 ng/mL (normal, < 5.0 ng/mL) and 5.9 ng/mL (normal, < 2.0 ng/mL), respectively. Chest roentgenogram revealed a mass shadow at the left lung field on admission. Chest computed tomographic scan revealed a 65 x 60 mm tumor in the left lower lobe with left interlobular lymph node swelling (Fig 1). Based on the histologic diagnosis of the transbronchial biopsy specimen as lung cancer of the left lower lobe (nonsmall cell lung cancer, cT2N1M0, stage IIB), a left thoracotomy was performed. The tumor was located in the left lower lobe without pleural effusion, but involved the interlobar pulmonary artery. Intraoperatively we collected blood samples to measure serum amylase levels from the left inferior pulmonary vein, the superior vena cava, and the left radial artery at the same time by means of direct puncture using a fine needle. The amylase level of the left inferior pulmonary vein (2,331 U/L) was higher than those of the superior vena cava (912 U/L) and the left radial artery (993 U/L) (Fig 2). The proportion of each amylase isozyme pattern in the sample serum from the left inferior pulmonary vein was similar to that from the superior vena cava and from the left radial artery. We performed a left pneumonectomy after measurement. Histopathologic diagnosis of the resected specimen was a moderately to poorly differentiated adenocarcinoma (40 mm in diameter) having a partially pleomorphic carcinoma component with pleural invasion and mediastinallymph node metastasis. The pathologic stage was stage IIIA (T2N2M0).



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Fig 1. Chest computed tomography reveals a tumor with atelectasis in the left lower lobe.

 


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Fig 2. Serum amylase levels of intraoperative samples. The amylase level of the left inferior pulmonary vein (LIPV) was greater than those of the superior vena cava (SVC) and the left radial artery (LRA). The amylase isozyme pattern of the LIPV was similar to those of the SVC and the LRA. The normal isozymes of salivary and pancreatic amylase are S1 and P1, respectively. The abnormal types of salivary gland isozymes are S2, S3, and S4.

 
An immnohistochemical study was carried out using polyclonal sheep amylase antibodies raised against human salivary amylase (Biogenesis Ltd, Poole, UK). A positive-staining reaction appeared in the tumor tissue, especially in the cytoplasm and cell membrane of the tumor cells (Fig 3A), and in contrast, normal lung tissue of the left lower lobe and upper lobe also showed slightly positive reactions (Fig 3B).



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Fig 3. (A) An immnohistochemical study shows a positive-staining reaction in cytoplasm and the cell membrane of the tumor cells. (B) Normal lung tissue shows a slight positive-staining reaction in both the left upper and lower lobes.

 
The postoperative course was uneventful. The serum amylase levels and the amylase isozyme patterns returned to a normal range within 3 days postoperatively. The patient was discharged on postoperative day 18. Since then the patient has been clinically free of any evidence of recurrence and his serum amylase levels have been within a normal range for 1 year.


    Comment
 Top
 Abstract
 Introduction
 Comment
 References
 
An association between hyperamylasemia and lung cancer was first reported by Weiss and colleagues [6]. Although it is believed that lung cancer can produce amylase, it is difficult to make a preoperative diagnosis of amylase-producing lung cancer, because we cannot evaluate amylase secretion from lung cancer tissue directly. Previous case reports made clinical diagnoses by exclusion or a decrease in serum amylase after treatment [3, 7]. To the present, no specific clinicopathologic feature of amylase-producing lung cancer has been apparent when compared with other lung cancers not producing amylase. The major clinical characteristics of amylase-producing lung cancer are the dominant salivary type, elevation of amylase isozyme, and no findings of disease which causes an increase of the serum amylase except lung cancer [2, 3, 5]. The major histologic type of amylase-producing lung cancer is adenocarcinoma [2, 7]. Previous studies have shown amylase production using pathologic or biochemical techniques such as the amylase activity in the supernatant from homogenized tumor tissue, immunohistochemical staining, Northern blot analysis, and electron microscopic analysis [1, 2, 5, 7]. Because these techniques are indirect measurement methods, it is important to prove a high level serum amylase level in pulmonary circulation by direct measurement.

We were able to find a high level of amylase release by measuring samples collected from the left inferior pulmonary vein that was a drainage vein from the tumor tissue. Immnohistochemically, we could also confirm the amylase production. The positive-staining reaction against the human amylase of the tumor tissue was homogeneous, and it was stronger than that of the adjacent lung tissue. Moreover, the staining reaction of the normal lung tissue was similar and weak in the left upper lobe and in the left lower lobe where the tumor was located. This result, in conjunction with the serum assay, suggests that lung cancer can produce amylase and release it into circulation, which results in different levels of serum amylase between the left inferior pulmonary vein and the superior vena cava.

The serum amylase levels for the diagnosis of lung cancer and follow-up after treatment can be applied as a tumor marker. However, the clinical efficacy of this tumor marker may be controversial because some previous studies have shown that the synthesized amylase level in the tumor tissue does not correlate with hyperamylasemia [2, 5].

The direct measurement of serum amylase was simple, and it is useful to measure the amylase levels intraoperatively to clarify the location of amylase production.


    References
 Top
 Abstract
 Introduction
 Comment
 References
 

  1. Seyama K, Nukiwa T, Takahashi K, Takahashi H, Kira S. Amylase mRNA transcripts in normal tissues and neoplasms: the implication of different expressions of amylase isogenes. J Cancer Res Clin Oncol. 1994;120:213–220[Medline]
  2. Tomita N, Matsuura N, Horii A, et al. Expression of alpha-amylase in human lung cancers. Cancer Res. 1988;48:3292–3296[Free Full Text]
  3. Tsukawaki M, Izawa M, Yoshida M, et al. A case of amylase-producing lung cancer. Intern Med. 1992;31:60–63[Medline]
  4. Hayashi Y, Fukayama M, Koike M, Nakayama T. Amylase in human lungs and the female genital tract. Histochemical and immunohistochemical localization. Histochemistry. 1986;85:491–496[Medline]
  5. Lenler-Petersen P, Grove A, Brock A, Jelnes R. Alpha-amylase in resectable lung cancer. Eur Respir J. 1994;7:941–945[Abstract]
  6. Weiss M, Edmonton HAK, Wertman M. Elevated serum-amylase associated with bronchogenic carcinoma. Am J Clin Pathol. 1951;21:1057–1061[Medline]
  7. Martin PC, Sarma DP. Amylase-producing lung cancer. J Surg Oncol. 1982;21:30–32[Medline]




This Article
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Right arrow Lung - cancer


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