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Ann Thorac Surg 2009;88:1745-1748. doi:10.1016/j.athoracsur.2009.08.010
© 2009 The Society of Thoracic Surgeons
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Original Articles: General Thoracic

Clinical Outcome After Pulmonary Resection for Lung Cancer Patients on Hemodialysis

Toshiro Obuchi, MD*, Wakako Hamanaka, MD, Yasuhiro Yoshida, MD, Jun Yanagisawa, MD, Daisuke Hamatake, MD, Takeshi Shiraishi, MD, Akinori Iwasaki, MD

Department of Thoracic, Breast, Endocrine, and Pediatric Surgery, Fukuoka University Hospital, Fukuoka, Japan

Accepted for publication August 6, 2009.

* Address correspondence to Dr Obuchi, Jonan-ku, Nanakuma, 7 chome, 45-1, Fukuoka, 814-0180, Japan (Email: tobuchi{at}fukuoka-u.ac.jp).


   Abstract
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 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: The number of operations for patients with malignant tumors receiving long-term hemodialysis has been increasing; however, there are only few reports about pulmonary resection for the patients with lung cancer.

Methods: Between 1995 and 2009, 11 hemodialysis patients (6 men, 5 women; mean age, 66.4 years) with non-small cell lung cancer underwent pulmonary resection at our institution. We retrospectively evaluated their postoperative clinical outcomes and long-term results.

Results: The underlying kidney conditions included nephrosclerosis in 3, diabetic nephropathy in 3, glomerulonephritis in 1, and polycystic kidney in 1; 3 patients had undergone nephrectomy. The median duration of hemodialysis preoperatively was 5.0 years. Three patients had been treated for previous carcinoma. The histopathologic diagnoses were adenocarcinoma in 9 patients and squamous cell carcinoma in 2. Procedures included lobectomy in 9, pneumonectomy in 1, and wedge resection in 1. There were no in-hospital deaths. Postoperative morbidity included 2 cases of pneumonia and 1 of chylothorax. At the time of our investigation, 6 patients were dead; 2 of cancer and 4 of noncancer causes. The overall 5-year survival rate of 11 patients was 28.0%.

Conclusions: Hemodialysis is not a contraindication to lung resection, despite the high morbidity rate. Surgical treatments, including lobectomy, remain one of effective treatments for patients on hemodialysis with lung cancer.


   Introduction
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 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Owing to technologic progress made in hemodialysis, the number of patients in a long-term hemodialysis has been increasing; therefore, it is reasonable to assume that the number of hemodialysis patients with lung cancer in need of pulmonary resection should increase [1–3]. However, only few reports have detailed the clinical outcomes after pulmonary resection for hemodialysis patients with non-small cell lung cancer [4–6]. As such, we evaluated the clinical outcomes and long-term results of these patients.


   Patients and Methods
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 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
This study protocol was examined and approved by the department Research Review Board. Before the operation, we had obtained a written consent from all patients giving us permission to perform research using their data, with an understanding that their privacy would be protected. The board concluded that this study does not violate patient privacy and approved the consent form.

Between January 1995 and January 2009, 11 patients (6 men, 5 women) with non-small cell lung cancer who were also receiving hemodialysis underwent lung resection at our institution. We retrospectively reviewed their data, and their characteristics are reported in Table 1. The median preoperative duration of hemodialysis was 5.0 years (range, 0.5 to 23 years), with a mean duration of 6.7 years.


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  		Table 1 Patient Characteristics
 
Pulmonary resections were performed through a posterolateral thoracotomy or using the video-assisted thoracic surgical (VATS) technique, which are the standard procedures in our institution.

In all patients, hemodialysis through the shunt was routine 3 days a week, on Tuesday, Thursday, and Saturday, using heparin sodium. All operations were performed on Wednesday so that the patients underwent hemodialysis on the day before the operation and the day after. No additional hemodialysis was done on the operative day. For the perioperative hemodialysis, nafamostat mesylate was used instead of heparin sodium until the chest drainage tube was removed and hemostasis was confirmed. For priming the circuit of hemodialysis, 20 mg of nafamostat mesylate was used, and 30 mg/h of nafamostat mesylate was continuously added into the circuit during hemodialysis.

Antibiotics were routinely given intravenously, intraoperatively, and postoperatively. We administered 1 gram/d of an antibiotic such as piperacillin, cefazolin, or cefotiam. On the operative day, the antibiotic was intravenously dripped at the start of the operation. Postoperatively, the antibiotic was given for a few days.

We investigated the 11 patients in terms of respiratory functions, serum levels of urea nitrogen and creatinine, underlying kidney condition, histology, status of lung cancer and history, comorbidity, history of smoking, surgical procedure, operative time, volume of intraoperative blood loss, duration of postoperative thoracic drainage, duration of postoperative hospitalization, postoperative complication, patient prognosis, and cause of death.

Data for the 11 patients were statistically analyzed using StatMate software (ATMS Inc, Tokyo, Japan). Using this software, we plotted Kaplan-Meier curves.


   Results
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 Abstract
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 Patients and Methods
 Results
Comment
 References
 
The mean duration of follow-up was 995.6 days (range, 106 to 4975 days). The mean serum levels of urea nitrogen and creatinine after hemodialysis were 29.4 mg/dL and 4.0 mg/dL, respectively.

The underlying kidney conditions included nephrosclerosis in 3 patients, diabetic nephropathy in 3, glomerulonephritis in 1, and polycystic kidney in 1 (Table 2). In addition, 3 patients had undergone nephrectomy. The histologic diagnosis was adenocarcinoma in 9 patients and squamous cell carcinoma in 2. Although preoperative clinical stage was evaluated to be IA or IB for all patients, the postoperative pathologic stages of cancer were determined as IA in 6 patients, IB in 3, IIB in 1, and IIIA in 1.


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  		Table 2 Preoperative Characteristics of the 11 Hemodialysis Patients
 
Treatment history revealed that 3 patients had already been treated for previous primary carcinoma, comprising colon carcinoma in 2 and renal carcinoma in 1. Also, 6 patients were current smokers at the time of admission.

Procedures included lobectomy in 9 patients, pneumonectomy in 1, and wedge resection for a tiny localized adenocarcinoma, Noguchi type B, in 1. Operations were done through posterolateral thoracotomy in 7 patients and by VATS in 4. The operative time and the intraoperative blood loss are reported in Table 3. The mean duration of postoperative thoracic drainage was 4.2 days, and the mean duration of postoperative hospitalization was 15.6 days. There were no hospital deaths. Postoperative complications included pneumonia in 2 patients and chylothorax in 1. The morbidity rate was 27.3%.


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  		Table 3 Postoperative Characteristics of the 11 Hemodialysis Patients
 
Six patients had died at the time of the investigation. Two died of lung cancer and the remaining 4 died of noncancer causes such as acute myocardial infarction or subarachnoid hemorrhage. The overall 5-year survival rate was 28.0% (Fig 1), and the 5-year survival rate for stage I patients was 37.5% (Fig 2).


Figure 1
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  		Fig 1. Kaplan-Meier curves show overall survival after pulmonary resection for hemodialysis patients with non-small cell lung cancer. The 5-year survival rate was 28.0%.

 

Figure 2
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  		Fig 2. Long-term survival after pulmonary resection is shown for hemodialysis patients with stage I lung cancer. The 5-year survival rate was 37.5%.

 

   Comment
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 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
Patients receiving hemodialysis have been reported to have a potentially higher risk of cancer, and they undergo more operations in their lifetime than others [2–4]. Maisonneuve and colleagues [3] reported high risks associated with cancer of the kidney, bladder, and endocrine organs in patients undergoing hemodialysis, but no increase in the incidence of cancer of the lung, colon or rectum, breast, and stomach. Kantor and colleagues [5] also reported that no increase in the number of patients with lung cancer was found in hemodialysis patients, so the relative risk for these patients was 0.8. However, patients receiving hemodialysis are generally thought to have weakened anticancer immune systems [4]. In fact, 3 patients (27.3%) in our study had a treatment history of another primary carcinoma. It is unclear whether this rate of double cancer (27.3%) in our limited experience has some clinical meaning, but this rate seems relatively high.

At our institution, the patients on hemodialysis could safely undergo even major lung resections with our usual procedures, under strict patient selection. It was reasonable that the mean volume of intraoperative blood loss was about 150 grams, and the mean duration of thoracic drainage was about 4 days. We think that perioperative usage of nafamostat mesylate, which is an ultra-short-acting anticoagulant agent used in hemodialysis, is more effective than heparin sodium in controlling intraoperative and postoperative bleeding, as Tsuchida and colleagues [6] also reported. The administration of hemodialysis with nafamostat mesylate instead of heparin sodium did not negatively affect hemostasis perioperatively for the present 11 patients.

A high morbidity rate after pulmonary resection for patients on hemodialysis has been reported [6]. We found complications in 3 of 11 patients. For 2 of those 3 patients, complications of pneumonia resulted in prolonged durations of postoperative hospital stays. The 27.3% morbidity rate in our series was high, even though no fatal complications occurred. Thus, hemodialysis patients undergoing lung resection should be closely monitored postoperatively for symptoms of complications such as pneumonia.

Japan is one of the countries with the longest life expectancy at birth in the world, and because the elderly population is increasing as whole, the number of elderly patients with lung cancer has been increasing. Currently, lobectomies are being performed even on extremely elderly patients, such as octogenarians, provided that they are in good performance status, the curability is appropriate, and their quality of life is not negatively affected [7].

Our study included an 89-year-old patient who underwent lobectomy through a posterolateral thoracotomy. Although it is generally difficult to evaluate the operative indication of someone who is as old as this patient, it is also difficult to choose other methods of treatment, such as chemotherapy or best supportive care, in the case like this patient, who had early-stage cancer and was in good performance status. Radiotherapy is also a treatment option, but it is not easy to choose radiotherapy when a better curability can be expected from surgery. Although lung wedge resection is usually a good surgical treatment option, depending on the location of tumor, lobectomy was the only option in this patient. Generally, lobectomy has its advantage in the low recurrence rate after the procedure, with simple postoperative follow-up and without the need for continuous treatments, especially for those with stage I lung cancer. With respect to our 89-year-old patient, the reason why we performed lobectomy was that first, he was healthy for his age and expressed a strong desire to have lobectomy over other options. Second, the average life span of 89-year-old Japanese men is 4.70 years. In fact, he was discharged 12 days after lobectomy without any complications. At least in this case, we think lobectomy was one of reasonable options.

In our limited study, the 5-year survival rate was 28.0% for the 11 hemodialysis patients with lung cancer undergoing pulmonary resection and 37.5% for the 9 patients with stage I lung cancer. Although it is problematic to make a simple comparison between our results and the results of patients not receiving hemodialysis [8], it is still necessary to find a clinical meaning from our results. One possible explanation is that arteriosclerosis, which is largely a cardiovascular disease, has a great effect on morbidity and mortality for hemodialysis patients [9]. Ohtake and colleagues [9] reported that cardiac death accounts for almost 40% of total deaths among hemodialysis patients, and coronary angiography showed significant coronary artery stenosis in 53.3% of 30 asymptomatic chronic kidney disease patients at the start of hemodialysis.

Among the many complications induced by long-term hemodialysis are infections, chronic heart failure, and arteriosclerosis of cerebral and cardiac arteries. In fact, 4 of the 6 deaths in our study were of noncancer causes, including arteriosclerosis. The prognosis for those patients after lung resection might have been influenced by their underlying complications. Nevertheless, surgical treatments are still effective for treating lung cancer.

In conclusion, our study revealed that hemodialysis is not a contraindication to lung resection, despite high morbidity rate; surgical intervention is still an effective treatment for patients on hemodialysis with lung cancer. In our limited study, however, we were unable to refer to differences in effectiveness between surgical intervention and radiotherapy [10] or between lobectomy and limited lung resection [11]. We think that further studies are needed to establish the therapeutic tactics for hemodialysis patients with lung cancer, especially early-stage cancer.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Pinson CW, Schuman ES, Gross GF, et al. Surgery in long-term dialysis patients: Experience with more than 300 cases Am J Surg 1986;151:567-571.[Medline]
  2. Cuckovic C, Djukanovic L, Jankovic S, et al. Malignant tumors in hemodialysis patients Nephron 1996;73:710-712.[Medline]
  3. Maisonneuve P, Agodoa L, Gellert R, et al. Cancer in patients on dialysis for end-stage renal disease: an international collaborative study Lancet 1999;354:93-99.[Medline]
  4. Ciriaco P, Casiraghi M, Melloni G, et al. Pulmonary resection for non-small-cell lung cancer in patients on hemodialysis: clinical outcome and long-term results World J Surg 2005;29:1516-1519.[Medline]
  5. Kantor AF, Hoover RN, Kinlen LJ, et al. Cancer in patients receiving long-term dialysis treatment Am J Epidemiol 1987;126:370-376.[Abstract/Free Full Text]
  6. Tsuchida M, Yamato Y, Aoki T, et al. Complications associated with pulmonary resection in lung cancer patients on dialysis Ann Thorac Surg 2001;71:435-438.[Abstract/Free Full Text]
  7. Togashi K, Koike T. Surgical treatment for patients aged 80 years or older with primary lung cancer and differences in outcomes according to sex Kyobu Geka 2008;61:347-351.[Medline]
  8. Asamura H, Goya T, Koshiishi Y, et al. A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers J Thorac Oncol 2008;3:46-52.[Medline]
  9. Ohtake T, Kobayashi S, Moriya H, et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: an angiographic examination J Am Soc Nephrol 2005;16:1141-1148.[Abstract/Free Full Text]
  10. Qiao X, Tullgren O, Lax I, Sirzén F, Lewensohn R. The role of radiotherapy in treatment of stage I non-small cell lung cancer Lung Cancer 2003;41:1-11.[Medline]
  11. Chamogeorgakis T, Ieromonachos C, Georgiannakis E, Mallios D. Does lobectomy achieve better survival and recurrence rates than limited pulmonary resection for T1N0M0 non-small cell lung cancer patients? Interact Cardiovasc Thorac Surg 2009;8:364-372.[Abstract/Free Full Text]



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