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Persistent cough - A rare presentation of hepatocellular carcinoma
Respiratory Medicine Case Reports 24 (2018) 103–104
Contents lists available at ScienceDirect
Respiratory Medicine Case Reports journal homepage: www.elsevier.com/locate/rmcr
Case report
Persistent cough - A rare presentation of hepatocellular carcinoma a,∗
a
b
O.G. Sandahl , O. Hilberg , F. Rasmussen , A. Løkke a b
T
a
Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Nørrebrogade 44, 8800 Aarhus C, Denmark Department of Radiology, Aarhus University Hospital, Nørrebrogade 44, 8800 Aarhus C, Denmark
A B S T R A C T
Coughing is a very common condition, accounting for frequent visits in general practice. In this case report, we found the cause of persisting cough to be hepatocellular carcinoma, located in close proximity to the diaphragm. After the tumor had been treated with chemoembolization the coughing disappeared. After the common causes for persistent cough has been ruled out, the clinician could consider other, rarer, conditions as the cause of the coughing, including affection of the diaphragm.
Coughing is one of the most common causes of visits in general practice, accounting for up to 40% [1,2]. Coughing is generally defined as acute, subacute or persistent. Persisting cough as defined by lasting more than 8 weeks [1], may be caused by several pathologies. Cough may be a manifestation of any lung and bronchial disease. The most common causes of coughing are smoking, treatment with ACE-inhibitors, GERD (gastroesophageal reflux disease), asthma, chronic bronchitis and upper airway cough syndrome (UACS) due to a variety of rhinosinus conditions [3,4]. Each cough occurs through the stimulation of a complex reflex arc composed of 3 pathways, the afferent pathway, the efferent pathway and the cough center. The cough center is stimulated via the vagus nerve [5]. The diaphragm is involved in this arc via both afferent and efferent neurogenic pathways. These pathways can stimulate entities that touch or displace the nerves involved. Pathology of the diaphragm can therefore lead to increased coughing. A 60-year-old male was referred to the Lung Cancer Out-patient Clinic, due to persistent cough for 5 months. He had a history of diabetes mellitus type 2, chronic kidney disease and gout. He had no history of smoking, nor a history of alcohol abuse. There was no weight loss, fever or other B-symptoms. He had no history of allergy. There was no history of treatment with ACE-inhibitors, nor was there symptoms of GERD or UACS. Test of lung function showed reduced FEV1 (1.84L, 56%) and FVC (2.20L, 53%) in a restrictive pattern with a FEV1/FVC ratio of 0.84 and showed no sign of asthma or chronic obstructive lung disease. Blood test showed elevated alkaline phosphatase (412 U/l), but normal amylase, alanine transaminase and bilirubin. White blood count was normal at 7.0 10ˆ9/l. Hemoglobin (Hgb) was normal at 10.2 mmol/ l.
∗
A CT scan of the chest and upper abdomen showed a 4.5 cm × 6.0 cm focal liver lesion in the cranial part of the right lobe of the liver. No abnormalities in the thoracic cavity were found. Further examinations and treatment were made at the Department of Hepatology and Gastroenterology. CT of the liver confirmed the inhomogeneous solid lesion in segment 4/8 of the liver. The lesion was located very near the diaphragm. A liver biopsy revealed the lesion to be hepatocellular carcinoma, stage T1N0M0, Child-Pugh A, score 5. The patient was still suffering; from coughing at this point. The patient was treated with two series of chemoembolization (Figs. 1 and 2 – before and after treatment). Chemoembolization is first line non-curable treatment for HCC, aiming to extend life and to potentially downstage the tumor to permit transplantation or resection. Two months after the chemoembolization the patient was feeling well and the coughing had disappeared. Renewed test of lung function now showed improvement, with FEV1 (2.35L, 76%), FVC 3.92 (91%) and an obstructive FEV1/FVC ratio of 0.66. The restrictive pattern shown before chemoembolization could be caused by the tumors close proximity to the diaphragm. In this case story presented, we believe that the persistent cough was caused by the hepatocellular carcinoma's very close proximity to the diaphragm, possible affecting the neurogenic pathways or the cough center via the vagal nerve, although possible systemic secretion from the carcinoma causing coughing cannot be completely ruled out. After the tumor had been treated with chemoembolization the coughing disappeared. According to international guidelines, in nonsmokers, with normal chest x-ray, and no ongoing treatment with ACEinhibitors, the diagnostic approach should focus on detecting and treating GERD, UACS, asthma or chronic bronchitis. These conditions can be seen alone or in combination with each other [3].
Corresponding author. E-mail address: [email protected] (O.G. Sandahl).
https://doi.org/10.1016/j.rmcr.2018.04.013 Received 11 October 2017; Received in revised form 19 April 2018; Accepted 21 April 2018 2213-0071/ © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Respiratory Medicine Case Reports 24 (2018) 103–104
O.G. Sandahl et al.
Fig. 1. CT of the liver before chemoembolization, with arrow pointing to the tumor.
Fig. 2. CT of the liver after chemoembolization, with arrow showing complete necrosis of the tumor.
One case-report has previously described hepatocellular carcinoma as the rare cause of dyspnea, but coughing was not present in that case [6]. This case-report describes as the first hepatocellular carcinoma as a possible cause for persisting cough. We acknowledge that the improvement of cough with chemoembolization doesn't prove causality, however we believe the case illustrates that when normal diagnostic approach to persisting cough has been completed without success, it can be worth investigation other avenues, including affection of the diaphragm.
therapy, Am. Rev. Respir. Dis. 141 (1990) 640–647. [2] R.S. Irwin, M.H. Baumann, D.C. Bolser, L.P. Boulet, S.S. Braman, C.E. Brightling, K.K. Brown, B.J. Canning, A.B. Chang, P.V. Dicpinigaitis, R. Eccles, W.B. Glomb, L.B. Goldstein, L.M. Graham, F.E. Hargreave, P.A. Kvale, S.Z. Lewis, F.D. McCool, D.C. McCrory, U.B. Prakash, M.R. Pratter, M.J. Rosen, E. Schulman, J.J. Shannon, C. Smith Hammond, S.M. Tarlo, S.M. Tarlo, American College of Chest Physicians (ACCP): diagnosis and management of cough executive summary: ACCP evidencebased clinical practice guidelines, Chest 129 (1 Suppl) (2006) 1S–23S. [3] R. Melvin, M.D. Pratter, FCCP: Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines, Chest 129 (1 suppl) (2006) 59s–62s. [4] R.S. Irwin, W.M. Corrao, M.R. Pratter, Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy, Am. Rev. Respir.Dis 123 (1981) 413–417. [5] Mario Polverino, Francesca Polverino, Marco Fasolino, Filippo Andò, Antonio Alfieri, Francesco De Blasio, Anatomy and neuro-pathophysiology of the cough reflex arc, Multidiscip. Respir.Med. 7 (2012) 5. [6] V.M. Novotný, V.P. van der Hulst, P.A. van der Wouw, J.L. Blaauwgeers, P.H. Frissen, An unusual presentation and way to diagnose hepatocellular carcinoma, Neth. J. Med. 62 (7) (2004 Jul-Aug) 254–256.
References [1] R.S. Irwin, F.J. Curley, C.L. French, Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific
104
Contents lists available at ScienceDirect
Respiratory Medicine Case Reports journal homepage: www.elsevier.com/locate/rmcr
Case report
Persistent cough - A rare presentation of hepatocellular carcinoma a,∗
a
b
O.G. Sandahl , O. Hilberg , F. Rasmussen , A. Løkke a b
T
a
Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Nørrebrogade 44, 8800 Aarhus C, Denmark Department of Radiology, Aarhus University Hospital, Nørrebrogade 44, 8800 Aarhus C, Denmark
A B S T R A C T
Coughing is a very common condition, accounting for frequent visits in general practice. In this case report, we found the cause of persisting cough to be hepatocellular carcinoma, located in close proximity to the diaphragm. After the tumor had been treated with chemoembolization the coughing disappeared. After the common causes for persistent cough has been ruled out, the clinician could consider other, rarer, conditions as the cause of the coughing, including affection of the diaphragm.
Coughing is one of the most common causes of visits in general practice, accounting for up to 40% [1,2]. Coughing is generally defined as acute, subacute or persistent. Persisting cough as defined by lasting more than 8 weeks [1], may be caused by several pathologies. Cough may be a manifestation of any lung and bronchial disease. The most common causes of coughing are smoking, treatment with ACE-inhibitors, GERD (gastroesophageal reflux disease), asthma, chronic bronchitis and upper airway cough syndrome (UACS) due to a variety of rhinosinus conditions [3,4]. Each cough occurs through the stimulation of a complex reflex arc composed of 3 pathways, the afferent pathway, the efferent pathway and the cough center. The cough center is stimulated via the vagus nerve [5]. The diaphragm is involved in this arc via both afferent and efferent neurogenic pathways. These pathways can stimulate entities that touch or displace the nerves involved. Pathology of the diaphragm can therefore lead to increased coughing. A 60-year-old male was referred to the Lung Cancer Out-patient Clinic, due to persistent cough for 5 months. He had a history of diabetes mellitus type 2, chronic kidney disease and gout. He had no history of smoking, nor a history of alcohol abuse. There was no weight loss, fever or other B-symptoms. He had no history of allergy. There was no history of treatment with ACE-inhibitors, nor was there symptoms of GERD or UACS. Test of lung function showed reduced FEV1 (1.84L, 56%) and FVC (2.20L, 53%) in a restrictive pattern with a FEV1/FVC ratio of 0.84 and showed no sign of asthma or chronic obstructive lung disease. Blood test showed elevated alkaline phosphatase (412 U/l), but normal amylase, alanine transaminase and bilirubin. White blood count was normal at 7.0 10ˆ9/l. Hemoglobin (Hgb) was normal at 10.2 mmol/ l.
∗
A CT scan of the chest and upper abdomen showed a 4.5 cm × 6.0 cm focal liver lesion in the cranial part of the right lobe of the liver. No abnormalities in the thoracic cavity were found. Further examinations and treatment were made at the Department of Hepatology and Gastroenterology. CT of the liver confirmed the inhomogeneous solid lesion in segment 4/8 of the liver. The lesion was located very near the diaphragm. A liver biopsy revealed the lesion to be hepatocellular carcinoma, stage T1N0M0, Child-Pugh A, score 5. The patient was still suffering; from coughing at this point. The patient was treated with two series of chemoembolization (Figs. 1 and 2 – before and after treatment). Chemoembolization is first line non-curable treatment for HCC, aiming to extend life and to potentially downstage the tumor to permit transplantation or resection. Two months after the chemoembolization the patient was feeling well and the coughing had disappeared. Renewed test of lung function now showed improvement, with FEV1 (2.35L, 76%), FVC 3.92 (91%) and an obstructive FEV1/FVC ratio of 0.66. The restrictive pattern shown before chemoembolization could be caused by the tumors close proximity to the diaphragm. In this case story presented, we believe that the persistent cough was caused by the hepatocellular carcinoma's very close proximity to the diaphragm, possible affecting the neurogenic pathways or the cough center via the vagal nerve, although possible systemic secretion from the carcinoma causing coughing cannot be completely ruled out. After the tumor had been treated with chemoembolization the coughing disappeared. According to international guidelines, in nonsmokers, with normal chest x-ray, and no ongoing treatment with ACEinhibitors, the diagnostic approach should focus on detecting and treating GERD, UACS, asthma or chronic bronchitis. These conditions can be seen alone or in combination with each other [3].
Corresponding author. E-mail address: [email protected] (O.G. Sandahl).
https://doi.org/10.1016/j.rmcr.2018.04.013 Received 11 October 2017; Received in revised form 19 April 2018; Accepted 21 April 2018 2213-0071/ © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Respiratory Medicine Case Reports 24 (2018) 103–104
O.G. Sandahl et al.
Fig. 1. CT of the liver before chemoembolization, with arrow pointing to the tumor.
Fig. 2. CT of the liver after chemoembolization, with arrow showing complete necrosis of the tumor.
One case-report has previously described hepatocellular carcinoma as the rare cause of dyspnea, but coughing was not present in that case [6]. This case-report describes as the first hepatocellular carcinoma as a possible cause for persisting cough. We acknowledge that the improvement of cough with chemoembolization doesn't prove causality, however we believe the case illustrates that when normal diagnostic approach to persisting cough has been completed without success, it can be worth investigation other avenues, including affection of the diaphragm.
therapy, Am. Rev. Respir. Dis. 141 (1990) 640–647. [2] R.S. Irwin, M.H. Baumann, D.C. Bolser, L.P. Boulet, S.S. Braman, C.E. Brightling, K.K. Brown, B.J. Canning, A.B. Chang, P.V. Dicpinigaitis, R. Eccles, W.B. Glomb, L.B. Goldstein, L.M. Graham, F.E. Hargreave, P.A. Kvale, S.Z. Lewis, F.D. McCool, D.C. McCrory, U.B. Prakash, M.R. Pratter, M.J. Rosen, E. Schulman, J.J. Shannon, C. Smith Hammond, S.M. Tarlo, S.M. Tarlo, American College of Chest Physicians (ACCP): diagnosis and management of cough executive summary: ACCP evidencebased clinical practice guidelines, Chest 129 (1 Suppl) (2006) 1S–23S. [3] R. Melvin, M.D. Pratter, FCCP: Overview of common causes of chronic cough: ACCP evidence-based clinical practice guidelines, Chest 129 (1 suppl) (2006) 59s–62s. [4] R.S. Irwin, W.M. Corrao, M.R. Pratter, Chronic persistent cough in the adult: the spectrum and frequency of causes and successful outcome of specific therapy, Am. Rev. Respir.Dis 123 (1981) 413–417. [5] Mario Polverino, Francesca Polverino, Marco Fasolino, Filippo Andò, Antonio Alfieri, Francesco De Blasio, Anatomy and neuro-pathophysiology of the cough reflex arc, Multidiscip. Respir.Med. 7 (2012) 5. [6] V.M. Novotný, V.P. van der Hulst, P.A. van der Wouw, J.L. Blaauwgeers, P.H. Frissen, An unusual presentation and way to diagnose hepatocellular carcinoma, Neth. J. Med. 62 (7) (2004 Jul-Aug) 254–256.
References [1] R.S. Irwin, F.J. Curley, C.L. French, Chronic cough. The spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific
104