Portal site metastasis of invasive mesothelioma after diagnostic thoracoscopy in a dog

Brigitte A. Brisson Department of Clinical Studies, Ontario Veterinary College, University Guelph, Guelph, ON N1G 2W1, Canada.

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Felipe Reggeti Department of Pathobiology, Ontario Veterinary College, University Guelph, Guelph, ON N1G 2W1, Canada.

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Dorothee Bienzle Department of Pathobiology, Ontario Veterinary College, University Guelph, Guelph, ON N1G 2W1, Canada.

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Abstract

Case Description—A 10-year-old Golden Retriever evaluated because of recurrent pericardial and pleural effusion underwent thoracoscopy with biopsy of the pleura and mediastinum.

Clinical Findings—Before thoracoscopy, 5 L of serosanguinous fluid was removed from the pleural cavity via thoracocentesis. During thoracoscopic exploration, it was observed that the parietal pleura and mediastinum were covered by miliary white to tan nodules 1 to 3 mm in diameter. Biopsy specimens were obtained, and partial pericardiectomy was performed. Portal sites were closed routinely. Cytologic evaluation of the pleural fluid revealed high protein concentration and cellularity, with cellular changes consistent with an exfoliating carcinoma. Results of bacterial culture were negative.

Treatment and Outcome—Carboplatin was administered via intracavitary instillation, and prednisone was administered orally. Twenty-one days later, 1 firm, irregularly shaped 6.5 × 3-cm mass and 4 smaller masses were detected in the area of the left thoracic wall where the cannula had been inserted during thoracoscopy. Histologic analysis of tissue from the masses collected at necropsy confirmed that they were malignant tumors with similar appearance to the pleural mesothelioma and immunohistochemical staining properties identical to those of the primary tumor.

Clinical Relevance—Although thoracoscopy is associated with less postoperative pain, shorter hospitalization times, and faster patient recovery than sternotomy procedures, complications are also possible with minimally invasive endoscopic surgery. Portal site metastasis can develop from contamination of portal sites with cells on instruments or cannulas or via leakage of effusion fluid. Although rare, this potential complication should be discussed with owners prior to performing the procedure.

Abstract

Case Description—A 10-year-old Golden Retriever evaluated because of recurrent pericardial and pleural effusion underwent thoracoscopy with biopsy of the pleura and mediastinum.

Clinical Findings—Before thoracoscopy, 5 L of serosanguinous fluid was removed from the pleural cavity via thoracocentesis. During thoracoscopic exploration, it was observed that the parietal pleura and mediastinum were covered by miliary white to tan nodules 1 to 3 mm in diameter. Biopsy specimens were obtained, and partial pericardiectomy was performed. Portal sites were closed routinely. Cytologic evaluation of the pleural fluid revealed high protein concentration and cellularity, with cellular changes consistent with an exfoliating carcinoma. Results of bacterial culture were negative.

Treatment and Outcome—Carboplatin was administered via intracavitary instillation, and prednisone was administered orally. Twenty-one days later, 1 firm, irregularly shaped 6.5 × 3-cm mass and 4 smaller masses were detected in the area of the left thoracic wall where the cannula had been inserted during thoracoscopy. Histologic analysis of tissue from the masses collected at necropsy confirmed that they were malignant tumors with similar appearance to the pleural mesothelioma and immunohistochemical staining properties identical to those of the primary tumor.

Clinical Relevance—Although thoracoscopy is associated with less postoperative pain, shorter hospitalization times, and faster patient recovery than sternotomy procedures, complications are also possible with minimally invasive endoscopic surgery. Portal site metastasis can develop from contamination of portal sites with cells on instruments or cannulas or via leakage of effusion fluid. Although rare, this potential complication should be discussed with owners prior to performing the procedure.

Laparoscopic and thoracoscopic procedures have been performed with increasing frequency in small and large animal veterinary medicine during the past 5 years. Minimally invasive techniques have been developed, and the number of procedures performed in client-owned animals is increasing rapidly. Thoracoscopy is used diagnostically to perform biopsies and therapeutically for performing partial pericardiectomy, lung lobectomy, correction of persistent aortic arch, and thoracic duct ligation.1–4 Although minimally invasive surgery has few reported complications and is associated with better postoperative patient comfort, potential complications exist. In humans, metastasis of neoplasia to the abdominal wall or subcutis at the site of portal insertion after diagnostic or therapeutic oncologic procedures has been reported.5–10 To the authors' knowledge, such apparent tumor invasion after laparoscopic or thoracoscopic surgery has not previously been reported in the veterinary literature. In the present report, portal site metastasis associated with thoracoscopy in a dog with mesothelioma is described.

A 10-year-old neutered male Golden Retriever with a history of exercise intolerance and recurrent pleural and pericardial effusion was examined by the surgical service at the Ontario Veterinary College Veterinary Teaching Hospital. Thoracocentesis and pericardiocentesis performed 4 months prior to admission had resulted in resolution of all clinical signs. At the time of initial examination at the Veterinary Teaching Hospital, 420 mL of bloody, turbid fluid was removed via pericardiocentesis at the right fourth intercostal space. Cytologic assessment of the pericardial fluid at that time revealed high cellularity (9.5×109 nucleated cells/L) and protein concentration (28 g/L). Anisocytosis, karyomegaly, enlarged nucleoli, and occasional mitotic figures were observed, supporting a diagnosis of a malignant neoplasm such as hemangiosarcoma exfoliating into the pericardial space. Because a cardiac mass was not evident on cardiac ultrasonography and no abnormalities were detected on abdominal ultrasonography, thoracotomy and pericardiectomy were recommended but declined by the owners.

Four months later, the dog was readmitted with a 2-week history of exercise intolerance and pleural effusion. Thoracocentesis performed at the right fourth intercostal space yielded drainage of 5 L of serosanguinous fluid. Other than a small volume of pleural effusion fluid, thoracic radiographs and cardiac and abdominal ultrasononography revealed no clinically important abnormalities. A CBC and serum biochemical profile revealed mild anemia (Hct, 0.38 L/L; reference limits, 0.39 to 0.56 L/L), neutrophilia (10.9×109 cells/L; reference limits, 2.9 to 10.6×109 cells/L), monocytosis (1.5×109 cells/L; reference limits, 0.0 to 1.1 ×109 cells/L), and thrombocytosis (467×109 platelets/L; referencelimits, 117 to 418×109 platelets/L). Changes in serum biochemical values included hyponatremia (129 mmol/L; reference limits, 140 to 154 mmol/L), hypochloremia (99 mmol/L; reference limits, 104 to 119 mmol/L), hyperkalemia (7.0 mmol/L; reference limits, 3.8 to 5.4 mmol/L), hyperphosphatemia (2.37 mmol/L; reference limits, 0.90 to 1.85 mmol/L), and hypermagnesemia (1.3 mmol/L; reference limits, 0.7 to 1.0 mmol/L). Those changes were considered to result from chronic illness and body cavity effusion and were partially corrected by IV administration of a balanced electrolyte solution.a To further investigate the cause of persistent effusion, thoracoscopic exploration was performed by use of single-lung intubation (right lung) while the dog was positioned in dorsolateral recumbency with the right side down. A 5-mm transdiaphragmatic portal for the camera was inserted, and 3 additional 5-mm instrument portals were placed along the ventrolateral aspect of the left thoracic wall in the second, fifth, and seventh intercostal spaces. Exploration revealed that the parietal pleura and mediastinum had irregular surfaces with focal areas of fibrosis and ulceration. Miliary white to tan nodules ranging in size from 1 to 3 mm in diameter were observed over the entire parietal pleura and mediastinum (Figure 1). A small volume of residual pleural effusion was noticed. No abnormalities were observed on the lung surface. Pleural fluid was aspirated and submittedfor cytologic examination and bacterial culture. Multiple biopsy specimens were obtained from the thoracic wall and mediastinum, and a partial pericardiectomy (4×4-cm pericardial window) was performed. Specimens were removed through cannulas in the fifth and seventh intercostal spaces without use of a specimen bag. Portal sites were closed routinely in an interrupted suture pattern with 2-0 monofilament glycomer 631b used to appose the muscle and subcutaneous tissues and 3-0 monofilament polypropylenec used to appose the skin. Residual air was drained from the thoracic cavity with an 18-gauge, over-the-needle catheter and extension set. Postoperative analgesia consisted of administration of an IV fentanyl constant rate infusion (1 to 2 mg/kg [0.5 to 0.9 mg/lb] per hour) for 15 hours after surgery. Recovery from anesthesia was uncomplicated. One day after surgery, a seroma (diameter, 5 cm) was noticed at the level of the most ventral portal incision (centered over the seventh intercostal space on the ventrolateral aspect of the left side of the thorax). A compression bandage was applied to prevent further extension of the seroma into the surrounding tissues. Cytologic evaluation of the pleural fluid collected at surgery revealed high protein concentration (30 g/L) and high cellularity (84.7 ×109 nucleated cells/L) with cellular changes consistent with an exfoliating carcinoma. Results of bacterial cultures were negative.

Figure 1—
Figure 1—

Endoscopic images of white to tan miliary neoplastic nodules along the mediastinal tissues (A) and fibrotic plaques along the thoracic wall (B) in a dog that developed portal site metastasis of mesothelioma 21 days after thoracoscopy.

Citation: Journal of the American Veterinary Medical Association 229, 6; 10.2460/javma.229.6.980

Histologic and immunohistochemical evaluation of mediastinal, pleural, and pericardial tissues revealed an invasive mesothelioma and pericardial fibrosis (the microscopic features of which have been reported11). Carboplatin (275 mg/m2 in 250 mL of saline [0.9% NaCl] solution instilled into the pleural cavity) was administered 24 hours after thoracoscopy, and the dog was discharged with instructions for the owners to orally administer prednisone (0.5 mg/kg [0.2 mg/lb], q 24 h). Twenty-one days later, a second dose of intracavitary carboplatin was administered (300 mg/m2 in 250 mL of saline solution) after 1 L of serosanguinous fluid was drained from the right side of the thorax. At that time, a 6.5×3-cm firm, irregular mass was observed on the ventrolateral portion of the left thoracic wall over the sixth through eighth ribs (Figure 2). Four additional masses, approximately 0.5 cm in diameter each, were palpable along the periphery of the larger mass. None of the masses seemed painful on palpation. Biopsy of the larger mass was recommended but declined by the owner. The dog was readmitted 10 days later (32 days after surgery) because of dyspnea and signs of discomfort. Physical examination at that time revealed tachypnea (100 breaths/min), tachycardia (125 beats/min), and mild cyanosis. Lung sounds were muffled bilaterally. Thoracocentesis on the right side of the thorax yielded 2.5 L of serosanguinous fluid. Palpation of the subcutaneous thoracic mass indicated that the size had increased to approximately 8×4 cm; distinct smaller masses were no longer palpable along the periphery of the larger mass. Carboplatin treatment was discontinued, and prednisone treatment was continued. Thoracocentesis was performed weekly at the referral clinic, but the dog was euthanized 1.5 months after thoracoscopy because of progressive deterioration. A complete postmortem examination was not performed; however, histologic evaluation of samples of the subcutaneous masses collected after euthanasia confirmed that they were malignant tumors with similar appearance to the pleural mesothelioma (Figure 3) and with immunohistochemical staining properties identical to those of the primary tumor.11

Figure 2—
Figure 2—

Photograph of the same dog as in Figure 1. Notice the mass that developed on the ventrolateral aspect of the left thoracic wall over the sixth to eighth ribs 21 days after thoracoscopy. Cranial is to the left.

Citation: Journal of the American Veterinary Medical Association 229, 6; 10.2460/javma.229.6.980

Figure 3—
Figure 3—

Photomicrograph of a section of the subcutaneous mass that developed at the thoracoscopy portal site in the same dog as in Figures 1 and 2. Notice the nests of mesothelioma cells surrounded by fibrous tissue below the subcutaneous fatty tissue. H&E stain; bar = 100 mm. The inset image is a higher magnification of neoplastic mesothelial cells arranged in clusters and rows. H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 229, 6; 10.2460/javma.229.6.980

Discussion

Tumor cell implantation at trocar insertion sites has been reported within days to months of abdominal and thoracic procedures for potentially curable neoplastic lesions in humans.5,7,8,12,13,d Since a 1978 report5 of portal site metastasis after laparoscopy in a patient with ovarian cancer, portal site metastasis has been reported in association with laparoscopic surgery of the gastrointestinal,14,15 genital,9,10 and urinary16 tracts. The rate of occurrence and mechanism by which portal site metastasis develops are unknown at this time. Although it has been reported17,18,d that the rate of portal site metastasis appears to be low (approx 1%), similar to rates reported in association with open abdominal procedures,13,19,d recurrence rates have been as high as 6.7% to 28% after diagnostic or therapeutic laparoscopy for malignant disease in humans. This discrepancy may be related to the terminology used to describe lesions. In 1 report,20 the term port site recurrence was used to describe patients that developed a mass at a portal site and to exclude patients that developed disease at a portal site after widespread neoplastic disease (carcinomatosis) was diagnosed. It is thought that patients with carcinomatosis are more likely to develop extension of the primary disease to the portal site rather than a true metastatic spread.

Experimental studies have revealed that intact peritoneum is resistant to tumor cell implantation21 but that free neoplastic cells appear to attach to injured portal tissue sites and grow more readily in traumatized and healing tissues.22,23 The same mechanisms likely apply to pleural surfaces. Factors thought to contribute to the development of portal site metastasis include patient debilitation,24 preexisting peritoneal metastases or disseminated disease,13 contamination of the cannula with highly exfoliative tumor cells by repeated passage of contaminated instruments,25,26 contamination of portal incisions during unprotected specimen removal,25 and surgical invasion of the tumor and excessive tumor manipulation.25 The contributing role of the chimney effect, by which expulsion of insufflation gas droplets through or around the cannula may contribute to contamination of the portal incision sites, is well described.23,25–27 However, the role of insufflation-mediated tumor dissemination is controversial because portal site contamination by tumor cells has also been reported in instances when mechanical retraction rather than insufflation was used for organ visualization.26 Insufflation was not performed in the dog of this report because unlike with laparoscopy, neither insufflation nor mechanical wall retraction is required for thoracoscopy. Tumor tissue manipulation, repeated instrument movement through the cannulas, and removal of tissue specimens were performed in the dog of this report and could have facilitated contamination of the cannulas and portal sites with tumor cells. The use of a specimen collection bag may have reduced the risk of contamination related to specimen retrieval through cannulas.

Portal site metastasis after thoracoscopic procedures appears to be rare in humans.7,12,28–31 Chen et al31 reported an incidence of < 1% in a study in which 1,069 cases of thoracic malignancy that arose after thoracoscopic procedures were reviewed. In that study,31 portal site metastases were associated most commonly with advanced intrathoracic disease, pleural effusion, and diffuse pleural metastasis (carcinomatosis). Similarly, ascites has also been reported to increase the risk of portal site metastasis in humans,5,32 a sequela thought to result from postoperative leakage of tumor cell–contaminated fluid through gravitydependent portal incisions.20,32 The dog in the present report had pleural effusion at the time of thoracoscopic exploration and developed a seroma after the procedure at 1 instrument portal site (the site of the future portal site metastasis). Cytologic examination of pleural fluid collected at surgery confirmed the presence of numerous tumor cells in the effusion, supporting the suspicion that leakage of effusion through 1 or more portal sites contributed to spread of tumor cells to the thoracic wall and rapid development of a subcutaneous mass after surgery. Careful suctioning of pleural or abdominal effusion fluid is advisable to decrease the risk of postoperative leakage and contamination. In addition, careful closure of thoracic wall incisions should be performed to decrease postoperative leakage through cannula incision sites. In the dog of this report, an attempt was made to close the muscular and subcutaneous tissues with a single cruciate suture placed at each portal site. It is possible that imperfect tissue apposition resulting from excessive subcutaneous adipose tissue contributed to postoperative leakage. Rapid accumulation of pleural fluid and disseminated pleural cavity neoplasia may also have contributed to contamination and invasion of the portal sites after thoracoscopy, possibly resulting in extension of the disease as opposed to metastasis.

The advantages of thoracoscopy over thoracotomy in dogs are primarily related to the minimally invasive nature of the former procedure, which is associated with less postoperative pain, shorter hospitalization times, and faster patient recovery. In this instance, had thoracoscopy not been possible, a sternotomy procedure would likely have been performed because there was no evidence of localized or lateralized disease. Sternotomy procedures are associated with lengthy convalescence periods and the potential for complications that can markedly decrease patients' quality of life, especially if life expectancy is short. In this dog, thoracoscopic exploration and biopsy enabled accurate diagnosis and initiation of chemotherapy within 24 hours of surgery and discharge from the hospital 1 day after thoracoscopy. Moreover, the development of portal site metastasis in this dog likely did not affect the clinical course of disease given that intrathoracic disease was advanced and rapid recurrence of pleural effusion had already developed at the time of diagnosis. Similarly, the clinical course of disease in humans with advanced intra-abdominal neoplasia does not appear to be affected by development of portal site metastasis.13

To the authors' knowledge, this is the first case of portal site metastasis reported in animals. The case illustrates that complications are possible with minimally invasive endoscopic surgery, which otherwise has many advantages over conventional surgical approaches. Portal site metastasis can develop from contamination of portal sites with instruments or cannulas during an endoscopic procedure or via leakage of ascitic or pleural effusion fluid. Although rare, this potential complication should be discussed with owners prior to performing diagnostic or therapeutic procedures.

a.

Plasma-Lyte A, Baxter Corp, Mississauga, ON, Canada.

b.

Biosyn, Tyco Health Care Group Canada Inc, St Laurent, QC, Canada.

c.

Surgipro, Tyco Health Care Group Canada Inc, St Laurent, QC, Canada.

d.

Anderson DN, Driver CP, Miller SS. ‘Port recurrence’ after laparoscopic surgery: the AESGBI experience (abstr). Minim Invasive Ther Allied Technol 1996;5:100.

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