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Year : 1999  |  Volume : 9  |  Issue : 2  |  Page : 69-71
Case report : Nebulization chemotherapy for lymphangitis carcinomatosa

Department of Radiotherapy and Oncology, Kasturba Medical College, Manipal-576719, Karnataka, India

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Keywords: Lymphangitis Carcinomatosa, Nebulization Chemotherapy

How to cite this article:
Ramkumar S, Fernandes DJ. Case report : Nebulization chemotherapy for lymphangitis carcinomatosa. Indian J Radiol Imaging 1999;9:69-71

How to cite this URL:
Ramkumar S, Fernandes DJ. Case report : Nebulization chemotherapy for lymphangitis carcinomatosa. Indian J Radiol Imaging [serial online] 1999 [cited 2021 Jan 22];9:69-71. Available from:
Lymphangitis carcinomatosa is a rare, aggressive and often fatal form of pulmonary metastases [1]. Although treatment modalities used for lymphangitis vary, no form of treatment has consistently had any impact on survival.

We report on a primary breast cancer patient with lymphangitis carcinomatosa who was treated using a unique technique: nebulization chemotherapy, in addition to systemic chemotherapy and supportive care in order to achieve rapid, sustainable improved response.

Nebulization chemotherapy involves inhalation of ultrasonically aerosolized particles of a chemotherapeutic drug 5-F­luorouracil (5-FU), using an ultrasonic nebulizer. This technique was first used in inoperable lung cancer [2] and allows direct and prolonged action of high concentration 5- FU on tumor tissue. Since 5-FU is directly incorporated and metabolized in the respiratory tract, it is possible to deliver a localized high concentration of the drug to the tumor tissue with minimal systemic absorption, resulting in higher tumor response, with minimal systemic side effects.

   Case Report Top

A forty-eight-years-old premenopausal woman with infiltrating duct carcinoma breast stage Illa, status post mastectomy and axillary sampling, bilateral oopherectomy, and adjuvant loco-regional radiotherapy presented on November 27, 1995 with a one month history of progressively worsening breathlessness, orthopnea and dry cough. She was on Tamoxifen 20 mg/day since September 1994. Physical examination was remarkable except for scattered bilateral rhonchi and diminished breath sound intensity in the left infrascapular and infraaxillary regions.

The chest radiograph revealed bilateral reticulonodular opacities and a left sided pleural effusion Arterial blood gas analysis showed pCO2 33.6 mm Hg. p02 63 mm of Hg and pH 7.4 Sputum was negative for AFB. sterile on culture. Pleural fluid was negative for malignancy on exfoliative cytology. Serum chemistries were within reference range. Bone scan was negative for osseous metastases. An ultrasonogram of the abdomen did not reveal hepatic metastases. A diagnosis of lymphangitis carcinomatosa with left sided pleural effusion and Type I respiratory failure was made [Figure - 1].

Systemic antibiotics intravenous aminophylline nebulized salbutamol and steroids were started Concurrently. she was also administered systemic chemotherapy with 5-Fluorouracil, Epirubicin and Cyclophosphamide. As there was no response to treatment and her dyspnea continued to worsen, nebulization chemotherapy with 5-Fluorouracil was commenced. A loading dose of 5­Fluorouracil 500 mg with solvent (bisolvon 2 ml) was delivered using an ultrasonic nebulizer. The ultrasonically aerosolized drug was inhaled for approximately 20 minutes. In order to prevent mucositis, the oral cavity was rinsed with tap water after completion of inhalation to remove excess 5-FU. Nebulization chemotherapy was continued for five days (500 mg on day #1; 250 mg/day on days #2 through #5).

Marked clinical improvement occurred within 12 hours of nebulization chemotherapy. Shortness of breath and cyanosis was resolved. Examination of the thorax and lungs revealed minimal scattered rhonchi. The pulse oximeter recorded near normal (97%) oxygen saturation.

After five days of nebulization chemotherapy, all other medications (nebulizer salbutamol, ipravent and steriods, intravenous bronchodilators and steriods) were tapered off and discontinued. The patient was discharged after a week. Symptomatic improvement persisted on subsequent return. A follow-up chest radiograph revealed near complete regression of the disease [Figure - 2].

Further chemotherapy consisted of eight courses of three-weekly systemic Epirubicin and Cyclophosphamide along with nebulization chemotherapy using 5-FU. A total of fourteen grams of 5-FU were delivered by nebulization. Chemotherapy by nebulization was discontinued after six courses. In May 1996 she developed bone metastases in the left humerus and ribs. Her pulmonary disease status remained status quo. She received palliative local radiotherapy to the left shoulder. Further therapy was declined. The patient passed away in August 1996.

   Discussion Top

First described by Gabriel Andral in 1829 in a patient with uterine cancer [3], lymphangitis carcinomatosa is most commonly associated with cancers of the lung, breast, stomach, and cervix [4],[5],[6].

Lymphangitis carcinomatosa is caused by tumor cell infiltration of septa], peri-vascular and peri-bronchial lymphatics [7]. Dyspnea and cough are frequent and often occur before changes in the chest radiographs Radiologic changes appear as dyspnea becomes progressively worse and these are related to the dilatation of the lymphatic channels. Pleural effusion is common.

Radiologic appearances were first described by Kerley et al. and include thin lines several centimeters in length radiating from the hila, transverse lines about 3 cm in length at the lung bases and extending into the pleura and a fine meshwork throughout the lung giving a reticular pattern [5]. All three types of Kerley lines should be sought for, in the diagnosis of lymphangitis carcinomatosa.

Microscopically, the lungs present a characteristic appearance. They appear firm, airless, edematous and often partly collapsed due to associated pleural effusions, with the pleural lymphatic channels outlined by the growth. In a majority of patients, pulmonary metastases result from blood-borne emboli [4],[7].

Lymphangitis carcinomatosa is rapidly progressive and fatal. Most series report a mean survival rate of two months (range three days to seven months) [1],[4],[5],[7]. Our patient had a good subjective and objective response and survived for nine months. The most important point to be noted from this modality of treatment was that the quality of life was greatly improved and maintained with minimal discomfort to the patient and without any major side effects. This may not be possible by other modalities.

Nebulization chemotherapy was introduced by Tatsumura et al in the treatment of inoperable non-small lung cancer [2]. Aerosolized particles of the chemotherapeutic drug, 5-Fluorouracil along with a solvent were delivered using an ultrasonic nebulizer through the mouth. 5­FU administered by nebulization accumulates mainly in the trachea, bronchi and regional nodes. Nebulization allows direct and prolonged action of high concentration of 5-Fluorouracil on the tumor tissue. Tatsumura et al have shown that more than 50% of particles (5-FU) with a 1­$ micron diameter reach the alveoli. This study also demonstrated negligible systemic absorption of 5-FU [2].

Jet nebulizers deliver particles of a mass with a median diameter of 6 micron while those from ultrasonic nebulizers. have a median diameter of 2.8 micron. Furthermore, ultrasonic nebulizers deliver approximately eight times the amount of drug/solution to the lower airway when compared to a jet nebulizer [8].

The nebulized drug is retained for a considerably longer period in tumor tissue than in normal tissue resulting in high antitumor activity with negligible or no systemic adverse effects. Oral stomatitis has been described with 5-FU by nebulization chemotherapy. However this can be avoided by moistening the oral cavity with milk before and by tap water gargling after the nebulization treatment [2]. Nebulization chemotherapy appears to be effective in achieving rapid early response and along with systemic chemotherapy and supportive care can be used in treating lymphangitis carcinomatosa.

   References Top

1.Harold JT. Lymphangitis carcinomatosa of the lungs.Q J Med 1952; 21: 353.  Back to cited text no. 1  [PUBMED]  
2.Tatsumura T, Koyama S, Tsujimoto M, Kitagawa M, Kagamimori S. Further study of nebulization chemotherapy, a new chemotherapeutic method in the treatment of lung carcinomas: fundamental and clinical. Br J Cancer 1993; 68: 1146-1149.  Back to cited text no. 2  [PUBMED]  
3.Doyle L, Gabriel Andral (1797-1876) and the first reports of lymphangitis carcinomatosa. J R Soc Med 1989; 82: 491-93.  Back to cited text no. 3    
4.Janower ML and Blennerhassett JB. Lymphangitic spread of metastatic cancer to the lung. Radiol 1971; 101: 267.  Back to cited text no. 4    
5.Yang S and Lin C. Lymphangitis carcinomatosis of the lungs. The clinical significance of its roentgenologic classification. Chest 1972; 62: 179.  Back to cited text no. 5    
6.Weisbrod GL, Stoneman HR and Tao LC. Diagnosis of diffuse malignant infiltration of lung (Lymphangitis carcinomatosis) by percutaneous fine-needle aspiration biopsy. J Can Ass Rad 1985; 36: 238.  Back to cited text no. 6    
7.Spencer H. Pathology of the lung, 3 d ed. Vol. 2. Belfast: Pergamon Press, 1977: 1000-1002.  Back to cited text no. 7    
8.Woldorf J. Mist therapy reconsidered, an evaluation of the respiratory deposition of labeled water aerosols produced by jet and ultrasonic nebulizer. Pediatrics 1969: 43: 799-808.  Back to cited text no. 8    

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S Ramkumar
5, 10th Cress Road, Prasanth Nagar, Bangalore 79, Karnataka
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