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Ann Thorac Surg 1995;60:599-602
© 1995 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Surgical Treatment of Lung Cancer in Patients With Human Immunodeficiency Virus

Division of Cardiothoracic Surgery, University of Miami/Jackson Memorial Medical Center, and the Veterans Administration Medical Center, Miami, Florida

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
Background. Since January 1986, more than 20 patients have been seen at the University of Miami/Jackson Memorial Medical Center and the Miami Veterans Administration Medical Center with concurrent human immunodeficiency virus infection and bronchogenic carcinoma. Four of these patients were treated surgically with curative intent.

Methods. The histories, records, operative reports, and pathology reports of the 4 patients were reviewed.

Results. The 4 surgically treated patients had stage I T1 N0 M0 lung cancer. Three patients had T4 cell counts of less than 200/µL and were managed by lobectomy. These patients died 5, 3, and 5 months postoperatively. More recently, a fourth patient had a T4 cell count of 963/µL and was treated with wedge resection. He is currently alive 12 months postoperatively.

Conclusions. It is concluded that surgically treated patients with lung cancer, human immunodeficiency virus infection, and T4 cell counts lower than 200/µL have high mortality and morbidity. Although it may be best to base surgical intervention on the stage of the patient's human immunodeficiency virus infection, further analysis is essential to determine which subgroup of human immunodeficiency virus–positive patients, if any, would benefit from surgical treatment of lung cancer.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
Acquired immunodeficiency syndrome (AIDS) was first recognized in 1981 after reports to the Centers for Disease Control of Pneumocystis carinii pneumonia and Kaposi's sarcoma in homosexual men [1–3]. Human immunodeficiency virus (HIV), a retrovirus, was soon shown to be the agent responsible for AIDS [4, 5]. This virus eventually leads to a state of immunodeficiency with infected patients prone to both infectious and malignant complications. Certain malignancies including Kaposi's sarcoma and malignant lymphoma have clearly been shown to occur with increased frequency in AIDS patients [6–8]. With other malignancies such as bronchogenic carcinoma, the relationship is not yet clear [9–12].

Of all malignancies, bronchogenic carcinoma represents the most frequent cause of death in both men and women [13]. Some studies [9, 10, 12] have suggested an increased incidence of bronchogenic carcinoma in young patients with HIV; others [11] have questioned this relationship.

Since January 1986, more than 20 patients have been seen at the University of Miami/Jackson Memorial Medical Center and the Miami Veterans Administration Medical Center with concurrent HIV infection and bronchogenic carcinoma. Four of these patients were treated surgically with curative intent. We report the outcome in this group of patients and speculate on the conclusions to be drawn.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
The histories, records, operative reports, and pathology reports of all patients at the University of Miami/Jackson Memorial Medical Center and the Miami Veterans Administration Medical Center who were infected with HIV and who underwent surgical intervention for bronchogenic carcinoma with curative intent were reviewed. There were 4 such patients.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
Patient 1
A 41-year-old man was admitted on March 12, 1986, for resection of a new right upper lobe nodule 2 cm in diameter. He had been treated for pleural tuberculosis in 1982 with INH (isoniazid) and rifampin. He had smoked two packs of cigarettes a day for 20 years and drank one six-pack of beer a day.

On March 13, 1986, he underwent right upper lobectomy for a 2 x 1 x 1-cm adenocarcinoma arising in a scar (Fig 1). All nodes were negative, making this tumor a T1 N0 M0 stage I adenocarcinoma of the lung. A soft nodular lesion in the superior segment of the right lower lobe was excised as well and interpreted on frozen section as ``pneumonitis.'' Subsequent study revealed this lesion to be focal Pneumocystis carinii infection (Fig 2).

View larger version (81K): [in this window] [in a new window]   Fig 1. . (Patient 1.) Computed tomographic scan. The arrow denotes a 2 x 1 x 1-cm adenocarcinoma arising in a scar in the right upper lobe.

View larger version (78K): [in this window] [in a new window]   Fig 2. . (Patient 1.) Computed tomographic scan. The arrow denotes a soft nodular lesion in the superior segment of the right lower lobe. Subsequent study revealed this lesion to be focal Pneumocystis carinii infection.

The patient returned to the hospital on August 6, 1986, with small-bowel obstruction requiring exploratory laparotomy and lysis of adhesions. This procedure was complicated by sepsis and respiratory failure, and the patient died on August 17, 1986.

Patient 2
A 40-year-old HIV–positive man with a history of Pneumocystis pneumonia was seen with a 3-cm enlarging coin lesion. The T4 cell count on December 12, 1989, was 102/µL. On December 19, 1989, he underwent a right upper lobectomy. Pathologic examination revealed right upper lobe scar adenocarcinoma, a T1 N0 M0 stage I cancer.

The postoperative course was complicated by abdominal distention and severe ileus. Sigmoidoscopy was performed on January 8, 1990. The ileus eventually resolved, and the patient was discharged on January 17, 1990, postoperative day 29. He died on March 30, 1990, of pneumonia and respiratory arrest.

Patient 3
A 45-year-old man with a history of chronic pancreatitis, peptic ulcer disease, smoking, and alcohol consumption was seen with a productive cough, and a chest roentgenogram revealed a left lower lobe nodule. On March 22, 1991, he had a forced expiratory volume in 1 second of 3.28 L, 89% of predicted. On May 31, 1991, he underwent a left lower lobectomy for a 1.5 x 1.5 x 1.5 cm well-differentiated adenocarcinoma. Lymph nodes were not involved, thus making this a T1 N0 M0 stage I lung cancer. The patient did well postoperatively and was discharged on June 5, 1991, postoperative day 5.

The patient returned to the hospital on June 25, 1991, with a temperature of 39.7°C and lymphadenopathy. On June 26, he was found to be HIV positive by enzyme-linked immunosorbent assay and Western blot. On July 1, the T4 cell count was 99/µL and on July 7, 128/µL. Results of a bone marrow biopsy on July 9 were consistent with lymphoma. On July 15, the biopsy specimen from a left inguinal lymph node revealed malignant lymphoma of the large-cell immunoblastic type. The patient was offered chemotherapy but declined and left the hospital on July 16, 1991.

He was rehospitalized twice-from August 30 to September 9 for treatment of volume depletion, severe hyponatremia, atypical mycobacterial pneumonia, and sepsis and again on October 11, with fever, active tuberculosis, liver failure, and sepsis. He was discharged to hospice on October 16, 1991, in terminal condition.

Patient 4
A 53-year-old man was admitted with alcoholic pancreatitis on November 11, 1993, and a chest roentgenogram revealed a 1.5-cm left upper lobe nodule. On December 4, 1993, he was found to be HIV positive by enzyme-linked immunosorbent assay and Western blot. On December 10, 1993, a computed tomography–guided biopsy of the left upper lobe nodule was done, and the specimen revealed cellular evidence of adenocarcinoma. On December 14, 1993, the T4 cell count was 963/µL. The patient's pancreatitis eventually resolved, and on December 28, 1993, he underwent bronchoscopy, mediastinoscopy, and left thoracotomy with a generous wedge resection of the lingular mass. Final pathologic study revealed a 1.5-cm infiltrating, poorly differentiated squamous carcinoma with negative nodes, a T1 N0 M0 stage I cancer.

Postoperatively the patient did well and was discharged on January 4, 1994, postoperative day 7. He is currently alive 12 months after resection.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
In 1990, it was estimated that 1 person in every 250 people in the United States was infected with HIV [14]. More than 99.9% of infections begin with viral transmission through sexual contact, blood exposure, or perinatal transmission. In adults, patients experience an ``acute retroviral syndrome'' 2 to 6 weeks after viral transmission. This syndrome is clinically similar to infectious mononucleosis and is associated with high-grade viremia [15]. The acute retroviral syndrome resolves spontaneously. Seroconversion occurs usually 6 to 12 weeks after initial exposure, and patients enter a period of clinical latency known as ``chronic asymptomatic HIV infection,'' which may last 5 to 15 years. Constitutional symptoms then develop, and patients enter a stage of ``symptomatic HIV disease.'' Finally, patients progress to AIDS, which is characterized by the presence of opportunistic infections and malignancies characteristic of severe cell-mediated immunodeficiency [16].

T-helper cells are T lymphocytes that play a crucial role in cell-mediated immunity and are infected and destroyed by HIV. Also known as CD4 cells, these cells are gradually depleted during the period of chronic asymptomatic HIV infection (Fig 3). Healthy adults average 1,000 CD4 cells/µL of blood with a normal range of 600 to 1400/µL [17–19]. The acute retroviral syndrome is characterized by a temporary decline in CD4 cell count followed by a return toward normal. Then, during the latent period of chronic asymptomatic HIV infection, the CD4 cell count begins to gradually decrease over several years. Patients infected with HIV experience a decline in CD4 cell count of 30 to 80 µL/y [20]. Constitutional symptoms usually begin to develop when the CD4 cell count approaches 300/µL. The average CD4 cell count seen in patients with serious opportunistic infections is 50 to 100/µL [15]. The Centers for Disease Control now stages HIV infection according to CD4 cell count: stage I is greater than or equal to 500/µL; stage II, 200 to 499/µL; and stage III, less than 200/µL [21]. As of 1992, a CD4 cell count of less than 200/µL defines AIDS whether or not opportunistic infections or malignancies are present [21].

View larger version (27K): [in this window] [in a new window]   Fig 3. . Natural history of human immunodeficiency virus (HIV) infection and CD4 cell counts. The white arrows denote our patients who died 5, 3, and 5 months after operation. The curved black arrow denotes our patient currently alive 12 months after operation. (Adapted by permission of the New England Journal of Medicine [1993;328:327–35].)

Several studies [9, 10, 12] have recently reported an association between HIV infection and bronchogenic carcinoma. These studies suggest that lung cancer in HIV patients presents at a younger age and is associated with a more fulminant course with shortened survival. Adenocarcinoma is reported as the preponderant cell type.

We [25] recently reported our experience with a total of 23 patients with HIV infection and lung cancer seen between January 1986 and July 1991. These patients were noted to be younger than other patients with lung cancer, had adenocarcinoma as a preponderant histologic type, and had a median survival of only 3 months with a range of 1 month to 10 months. Here we report the results of surgical treatment with curative intent of 4 HIV–infected patients with T1 N0 M0 stage I lung cancer. Three patients had T4 cell counts lower than 200/µL and were managed by lobectomy. These patients had complicated postoperative courses and died 5, 3, and 5 months postoperatively. More recently, a fourth patient with a T4 cell count of 963/µL was treated with wedge resection. He is currently alive 12 months postoperatively. Coincidentally, the patient with the longest survival in our larger previous series of 23 patients also had the highest CD4 cell count (968/µL).

Patients with stage I lung cancer have an overall 5-year survival rate of 60% to 70%, and those with T1 N0 M0 lesions have an overall 5-year survival rate of 68.5% to 83% [26]. In this series, the overall 1-year survival rate for HIV–infected patients with stage I T1 N0 M0 lung cancer is only 25%, and the 1-year survival rate is 0% for those with CD4 cell counts of less than 200/mm³.

Although experience with the surgical management of HIV–infected patients with lung cancer is limited, certain conclusions can be drawn. Surgical management of patients with lung cancer, HIV infection, and T4 cell counts of less than 200/µL can have high mortality and morbidity. Further analysis is essential to determine which subgroup of HIV–positive patients, if any, would benefit from standard surgical treatment of lung cancer.

One possible approach would be to base the recommendation for surgical treatment on the stage of the patient's HIV infection. Using this approach, patients with CD4 counts of greater than 500/µL would be considered appropriate candidates for resection with curative intent by the same criteria as patients without HIV infection. Patients with CD4 cell counts between 200/µL and 500/µL might be considered for limited resection. Finally, those with CD4 cell counts of less than 200/µL could be considered for palliative nonoperative management. Whether this approach proves to be reasonable in the management of HIV–infected patients with bronchogenic carcinoma awaits further experience and analysis.

It is unlikely that a single institution will have a large enough experience to develop specific treatment recommendations. Consequently, a survey of experience in the surgical treatment of lung cancer in HIV–infected patients is being undertaken. It is requested that information concerning surgical treatment of these patients be shared by completing and forwarding the survey (Appendix 1).

	Appendix 1. Survey: Surgical Treatment of Lung Cancer in Patients With Human Immunodeficiency Virus

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
DIRECTIONS: Please fill out one sheet for each patient undergoing operation and return sheet to:

• Richard J. Thurer, MD
  
• Division of Cardiothoracic Surgery (R-114)
  
• University of Miami School of Medicine
  
• PO Box 016960
  
• Miami, FL 33101
  

Surgeon's Name: ____________________

Phone Number: ______________________

Institution: ________________________

Total Number of HIV—Infected Patients Undergoing Operation for Lung Cancer: _________________

Number of This Patient: __________________

PATIENT INFORMATION:
Date of Birth: _________________________

Preoperative CD4 (T4) Counts: ___ ___ ___ ___

Preoperative CD8 (T8) Counts: ___ ___ ___ ___

Date Measured: ____ ____ ____ ____

Date of Operation:____________________

Surgical Procedure:_____________________

Tissue Diagnosis (Cell Type):________________

Tumor Size:_______cm Diameter Circle One: T1 T2 T3 T4

Node Status: N0 N1 N2 N3

Metastatic Disease: M0 M1

Tumor Stage:________________________

Postoperative CD4 (T4) Counts: ___ ___ ___ ___

Postoperative CD8 (T8) Counts: ___ ___ ___ ___

Date Measured: ____ ____ ____ ____

OUTCOME:
Intraoperative Death: ______ Yes ______ No

30-Day Mortality: ________ Yes ______ No

Currently Alive: ________ Yes ______ No

Date of Last Follow-up_________________

Date of Death:_____________________

Cause of Death:______________________

Please describe perioperative and postoperative compli cations.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 
Presented at the Poster Session of the Thirty-first Annual Meeting of The Society of Thoracic Surgeons, Palm Springs, CA, Jan 30–Feb 1, 1995.

Address reprint requests to Dr Thurer, Division of Cardiothoracic Surgery (R-114), University of Miami School of Medicine, PO Box 016960, Miami, FL 33101.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Appendix 1. Survey: Surgical... References

 

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20. Bartlett JG. A decade of HIV infection. In: Wilson SE, Williams RA, eds. Surgical problems in the AIDS patient. New York: Igaku-Shoin Medical Publishers, 1994:1–16.
21. Centers for Disease Control. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults.MMWR 1992;41(RR-17):1–19.[Medline]
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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Richard J. Thurer Jeffrey P. Jacobs Fred W. Holland, II Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thurer, R. J. Articles by Cintron, J. R. Search for Related Content PubMed PubMed Citation Articles by Thurer, R. J. Articles by Cintron, J. R.