Microwave ablation for treatment of hepatic neoplasia in five dogs

Toni Yang Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Gainesville, FL 32611.

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J. Brad Case Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Gainesville, FL 32611.

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Sarah Boston Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Gainesville, FL 32611.

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Michael J. Dark Department of Infectious Diseases and Pathology, College of Veterinary Medicine, Gainesville, FL 32611.

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Beau Toskich Department of Radiology, College of Medicine, University of Florida, Gainesville, FL 32610.

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Abstract

CASE DESCRIPTION 5 dogs between 9 and 11 years of age were evaluated for treatment of primary (n = 2) or metastatic (3) hepatic neoplasia.

CLINICAL FINDINGS Patients were evaluated on an elective (n = 3) or emergency (2) basis. Two dogs with primary hepatic neoplasia were evaluated because of lethargy and inappetence. One dog was referred after an enlarged anal sac was detected via palpation per rectum during a routine physical examination. Two dogs were evaluated on an emergency basis because of lethargy and weakness, and hemoabdomen in the absence of a history of trauma was detected. All 5 dogs underwent thoracic radiography and abdominal ultrasonography, with CT performed in both dogs with primary hepatic neoplasia. All dogs had preoperative evidence of abdominal neoplasia, and none had evidence of thoracic metastasis.

TREATMENT AND OUTCOME All dogs underwent ventral midline laparotomy and had diffuse hepatic neoplasia that precluded complete resection. Locoregional treatment with MWA was applied to hepatic lesions (0.5 to 2.5 cm diameter) without procedural complications. Histopathologic diagnoses were biliary adenocarcinoma (n = 1), hemangiosarcoma (2), hepatocellular carcinoma (1), and apocrine gland adenocarcinoma (1).

CLINICAL RELEVANCE MWA is being increasingly used as an adjunct in the surgical treatment of human patients with primary and metastatic liver disease. Results of the present small case series suggested that MWA is feasible and potentially effective as an adjunctive treatment for appropriately selected dogs with nonresectable hepatic tumors. Further investigation is indicated.

Abstract

CASE DESCRIPTION 5 dogs between 9 and 11 years of age were evaluated for treatment of primary (n = 2) or metastatic (3) hepatic neoplasia.

CLINICAL FINDINGS Patients were evaluated on an elective (n = 3) or emergency (2) basis. Two dogs with primary hepatic neoplasia were evaluated because of lethargy and inappetence. One dog was referred after an enlarged anal sac was detected via palpation per rectum during a routine physical examination. Two dogs were evaluated on an emergency basis because of lethargy and weakness, and hemoabdomen in the absence of a history of trauma was detected. All 5 dogs underwent thoracic radiography and abdominal ultrasonography, with CT performed in both dogs with primary hepatic neoplasia. All dogs had preoperative evidence of abdominal neoplasia, and none had evidence of thoracic metastasis.

TREATMENT AND OUTCOME All dogs underwent ventral midline laparotomy and had diffuse hepatic neoplasia that precluded complete resection. Locoregional treatment with MWA was applied to hepatic lesions (0.5 to 2.5 cm diameter) without procedural complications. Histopathologic diagnoses were biliary adenocarcinoma (n = 1), hemangiosarcoma (2), hepatocellular carcinoma (1), and apocrine gland adenocarcinoma (1).

CLINICAL RELEVANCE MWA is being increasingly used as an adjunct in the surgical treatment of human patients with primary and metastatic liver disease. Results of the present small case series suggested that MWA is feasible and potentially effective as an adjunctive treatment for appropriately selected dogs with nonresectable hepatic tumors. Further investigation is indicated.

An 11-year-old neutered male Cocker Spaniel (dog 1) was evaluated because of a left anal sac mass that had initially been detected by the referring veterinarian 3 months previously during a routine physical examination. Laboratory testing at that time revealed leukocytosis, which prompted empiric treatment with ciprofloxacin for a week prior to referral. At the time of referral, no abnormalities other than the left anal sac mass were noted on physical examination. Thoracic radiographs were obtained, and findings were unremarkable. Abdominal ultrasonography revealed scant peritoneal effusion, medial iliac lymphadenomegaly, and multiple splenic nodules measuring up to 1.9 cm in diameter. The left anal sac was large (2.9 × 2.6 cm), lobulated, heterogeneous, and hypoechoic. Results of cytologic examination of fine-needle aspirates obtained from the spleen and left anal sac were consistent with a diagnosis of AGAC. The dog underwent left anal sacculectomy, exploratory laparotomy, medial iliac lymphadenectomy, and splenectomy.

During exploratory laparotomy, multiple (n = 10) nodules involving several liver lobes were detected. The nodules ranged from 0.5 to 1.8 cm in diameter and were sharply excised (2 nodules) or ablated (8 nodules) with a single 17-gauge, 15-cm triaxial MWA probea applied at 40 W for 1.5 to 3 minutes, depending on lesion size. Of the 2 sharply excised nodules, 1 was excised following ablation to determine postablation histopathologic appearance. The dog recovered from surgery without apparent complications, and adjuvant chemotherapy was declined by the owner. Histologic examination of the left anal gland, left medial iliac lymph node, spleen, and 2 hepatic nodules confirmed the diagnosis of metastatic AGAC. Histologic examination of an ablated section of liver confirmed complete destruction of the neoplastic nodule (Figure 1).

Figure 1—
Figure 1—

Photomicrographs of a hepatic nodule excised from an 11-year-old neutered male Cocker Spaniel (dog 1) with metastatic AGAC (A) and of a second nodule excised after undergoing MWA (B). H&E stain; bars = 500 μm.

Citation: Journal of the American Veterinary Medical Association 250, 1; 10.2460/javma.250.1.79

Five months after surgery, the dog was examined by the University of Florida Small Animal Emergency Service because of a 1-week history of diarrhea and tenesmus. Laboratory testing including serum biochemical analysis revealed hypercalcemia (15 mg/dL; reference range, 8.9 to 11.4 mg/dL). Palpable sublumbar lymph nodes and a nodular mass just ventral and to the left of the colon were noted on rectal examination. Thoracic radiography revealed no evidence of pulmonary metastasis. Abdominal ultrasonography showed an enlarged left medial iliac lymph node causing ventral displacement of the colon as well as multiple hypoechoic liver nodules up to 1.1 cm in diameter. Cytologic examination of a fine-needle aspirate of the left medial iliac lymph node indicated metastatic AGAC. Results of cytologic examination of a fine-needle aspirate of 1 liver nodule were compatible with a diagnosis of hepatocellular hyperplasia with mild neutrophilic and lymphocytic inflammation but no evidence of metastasis. Fluid therapy and treatment with furosemide (2 mg/kg [0.9 mg/lb], IV, q 8 h) resulted in a decrease in the serum ionized calcium concentration from 2.0 to 1.5 mmol/L (reference range, 1.18 to 1.35 mmol/L). Further evaluation and treatment, including CT, lymphadenectomy, anal sac mass resection, and adjuvant chemotherapy, were discussed but declined by the owner; discharge and palliative care were elected. At the time of discharge, the dog was hyporexic with persistent dyschezia. Tramadol (2.8 mg/kg [1.3 mg/lb], PO, q 8 to 12 h), prednisone (1.1 mg/kg [0.5 mg/lb], PO, q 24 h), and omeprazole (1.1 mg/kg, PO, q 24 h) were prescribed with a recheck recommended at 7 days; however, the dog was lost to further follow-up.

A 9-year-old sexually intact male Scottish Terrier (dog 2) was referred for evaluation and treatment of hepatic and urinary bladder masses, which were diagnosed 1 week previously when the dog was examined by the referring veterinarian because of inappetence and lethargy of 4 days’ duration. Laboratory testing during that visit revealed high serum ALP and ALT activities (ALP, 3,347 U/L [reference range, 8 to 160 U/L]; ALT, 245 U/L [reference range, 18 to 121 U/L]). A urinalysis revealed isosthenuria (urine specific gravity, 1.008). On initial examination at the University of Florida, the dog was bright, alert, and responsive. Abnormalities noted were a grade I/VI left apical systolic heart murmur, cranial abdominal organomegaly, and a mildly enlarged prostate. Contrast-enhanced CT revealed a right divisional, lobular, and cavitated hepatic mass measuring 7.4 × 7.8 × 7.0 cm (length × width × height). A hepatic nodule measuring 0.4 cm in diameter was evident in the left lateral liver lobe. There was focal (1.8 × 1.3 × 0.8-cm) thickening of the dorsal aspect of the urinary bladder apex and mild prostatomegaly. Results of cytologic examination of fine-needle aspirates of the bladder and liver masses were consistent with diagnoses of transitional cell carcinoma and hepatocellular carcinoma, respectively. Serum biochemical analysis revealed high ALP (1,903 U/L; reference range, 8 to 114 U/L), ALT (1,459 U/L; reference range, 18 to 64 U/L), and aspartate aminotransferase (431 U/L; reference range, 15 to 52 U/L) activities. The dog underwent exploratory laparotomy, right middle and quadrate liver lobectomy, partial cystectomy, and MWA of five 5-mm- to 1-cm-diameter liver nodules at 40 W for 1.5 to 3 min/nodule. The dog recovered from surgery without apparent complications and was discharged from the hospital 2 days later. Histologic examination of surgical biopsy specimens confirmed the diagnoses of transitional cell carcinoma of the bladder and biliary adenocarcinoma of the liver.

Two days after discharge, the dog was readmitted to the hospital on an emergency basis because of incisional dehiscence secondary to a surgical site infection. The surgical wound subsequently healed following surgical wound revision and antimicrobial treatment. Follow-up abdominal ultrasonography 1 month after surgery revealed no abnormalities of the liver or urinary bladder. The dog commenced adjuvant chemotherapy (toceranib phosphate,b 2.5 mg/kg [1.1 mg/lb], PO, every Monday, Wednesday, and Friday for 3 weeks). A recheck serum biochemical analysis 2 months after surgery (1 month after the start of chemotherapy) revealed ALP activity of 1,485 U/L (reference range, 5 to 160 U/L) and ALT activity of 162 U/L (reference range, 18 to 121 U/L). Abdominal ultrasonography 3 months after surgery revealed large hepatic lymph nodes. Toceranib phosphate chemotherapy had been discontinued by the owner some time between 1 and 2 months after the medication had been started because of perceived adverse effects (recurrent anorexia and lethargy). The dog had received 2 doses of piroxicamc (0.25 mg/kg [0.11 mg/lb], PO, q 24 h) some time between 2 and 3 weeks after starting chemotherapy, but this was also discontinued by the owner because of concerns about melena. At the 5-month recheck evaluation, abdominal ultrasonography revealed multiple nodules measuring up to 0.8 cm in diameter near the trigone of the urinary bladder, but no hepatic nodules were seen. Piroxicam (0.25 mg/kg, PO, q 24 h) was again recommended to address the progression in bladder disease. Twelve months after surgery, the dog was reportedly clinically normal. No abnormalities with urination were reported by the owner. The dog had been intermittently receiving piroxicam (0.25 mg/kg, PO, q 24 h) as well as multiple vitamin and herbal supplements. Eighteen months after surgery, the owner suspected hematuria and brought the dog to its referring veterinarian. Urinalysis confirmed hematuria, and sediment evaluation revealed large sheets of transitional epithelial cells. The dog was referred to the University of Florida for further diagnostic testing. On physical examination, the dog's previously diagnosed heart murmur had progressed to grade III/VI. Discomfort was elicited on abdominal palpation, during which a mass was felt in the caudal aspect of the abdomen. Red-tinged urine was noted to be dripping from the dog's penis. Serum biochemical analysis revealed ALT activity of 110 U/L (reference range, 18 to 64 U/L) and ALP activity of 1,348 U/L (reference range, 8 to 114 U/L). Thoracic radiographs were negative for pulmonary metastatic disease. Abdominal ultrasonography revealed a severe increase in size and extent of the previously noted urinary bladder mass, which now extended around approximately 75% of the circumference of the urinary bladder wall. There was mildly progressive hepatomegaly with margins consistent with prior liver resection; no distinct hepatic nodules or masses were observed. Administration of vinblastine (2 mg/m2, IV, q 7 d) and meloxicam (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) was started, but the owner elected to discontinue chemotherapy after 2 doses of vinblastine and 2 days of meloxicam administration because of intermittent inappetence and melena. The dog was last assessed 21 months after surgery and, at that time, had intermittent clinical signs associated with recurrent urinary tract infections. Abdominal ultrasonography revealed that both the liver and urinary bladder masses were static.

A 9-year-old neutered male Yorkshire Terrier (dog 3) in an obtunded state with a 4-day history of progressive weakness and lethargy was examined by the emergency service. Results of a CBC performed earlier that day by the referring veterinarian included an Hct of 21.8% (reference range, 37.0% to 55.0%). On physical examination, the dog was laterally recumbent; had pale mucous membranes, tachycardia, and tachypnea; and had a distended abdomen with a palpable fluid wave. One unit of packed RBCs was administered at the time of initial examination owing to the dog's critical status. Abdominal ultrasonography revealed numerous 0.6- to 2.1-cm-diameter hepatic nodules as well as a large, cavitated splenic mass and a moderate volume of peritoneal effusion. Thoracic radiography revealed no evidence of metastasis. The patient subsequently underwent exploratory laparotomy and splenectomy, liver biopsy, and MWA (45 to 60 W for 2 minutes) of the 6 largest liver nodules identified on ultrasonography, including 1 that was actively hemorrhaging (Figure 2). The dog recovered well from surgery with no apparent complications. Results of histologic examination of surgical specimens from the spleen and liver were compatible with a diagnosis of hemangiosarcoma. Two weeks after surgery, the dog commenced adjuvant chemotherapy with doxorubicind (1 mg/kg [0.45 mg/lb], IV, q 3 wk), with diphenhydraminee (0.25 mg/kg, SC, prior to doxorubicin), maropitantf (1 mg/kg, SC, prior to doxorubicin), ondansetrong (0.8 mg/kg [0.36 mg/lb], PO, q 24 h), metronidazoleh (12 mg/kg [5.5 mg/lb], PO, as needed), and Yunnan Baiyaoi (48 mg/kg [21.8 mg/lb], PO, q 12 h) also administered. Three months after surgery, abdominal ultrasonography revealed a well-defined, round, hyperechoic, 8-mm-diameter nodule in the corticomedullary region of the left kidney. The liver contained multiple nodules, similar to results of preoperative abdominal ultrasonography. Thoracic radiography revealed no evidence of pulmonary metastasis. Toceranib phosphate (1.9 mg/kg [0.86 mg/lb], PO, q 48 h) was added to the treatment protocol because of evidence of progressive metastatic disease. One week later, the dog was reexamined because of weakness, obtundation, and melena. Despite emergency resuscitation and 2 blood transfusions, the dog died 3 months after the initial surgery.

Figure 2—
Figure 2—

Photograph of intraoperative MWA antenna placement in a hepatic nodule in a 9-year-old neutered male Yorkshire Terrier (dog 3) with hemangiosarcoma. Notice the coagulative necrosis.

Citation: Journal of the American Veterinary Medical Association 250, 1; 10.2460/javma.250.1.79

An 11-year-old neutered male Australian Shepherd (dog 4) was examined because of an acute onset of lethargy and a history of a large solitary right liver mass diagnosed 2 weeks previously at a referring specialty hospital. Serum biochemical analysis at that time revealed ALT activity of 1,399 U/L (reference range, 18 to 121 U/L). On abdominal ultrasonography, the hepatic mass measured 5.5 cm in width and 8.5 cm in length. Multiple nodules in the left lateral liver lobe were also detected. Results of cytologic analysis of fine-needle aspirates of the mass were inconclusive but suggestive of hepatocellular carcinoma. Contrast-enhanced CT revealed a right-sided cavitated and variably contrast-enhancing multilobular mass and mild hepatic lymphadenomegaly. Hypoattenuating splenic nodules measuring 0.5 to 1.5 cm in diameter were also evident. At initial examination at the University of Florida, the dog was quiet and alert. The only abnormality noted on physical examination was organomegaly on palpation of the cranial aspect of the abdomen. The dog underwent exploratory laparotomy; right medial, quadrate, and partial left lateral liver lobectomies; splenectomy; cholecystectomy; and MWA (65 W for 2 to 3 minutes) of 2 liver nodules in the left middle liver lobe measuring 1.1 and 2.2 cm in diameter. A cholecystectomy was performed because the gallbladder was adhered to the hepatic masses. The dog recovered from surgery without complications and was discharged 2 days later. Histologic examination of the gallbladder and central liver mass confirmed a diagnosis of hepatocellular carcinoma with a surgical margin of 0.5 cm. Histologic examination of the spleen and left lateral liver mass indicated hemangioma and nodular hyperplasia, respectively. Four days after surgery, the owner reported that the dog was doing well at home. Recheck ultrasonographic examination was recommended every 3 months for a year and every 6 months thereafter. Three months after surgery, abdominal ultrasonography did not reveal any abnormalities. At the time of the last follow-up 10 months after surgery, the dog was doing well at home with only occasional mild signs of gastrointestinal upset treated by the owner with over-the-counter antacids.

An 11-year-old neutered male Golden Retriever (dog 5) was referred for evaluation on an emergency basis after developing hemoabdomen in the absence of a history of trauma. The dog had a 24-hour history of lethargy, poor appetite, and 1 episode of vomiting. On physical examination, signs of pain were elicited during abdominal palpation and a mass was appreciable in the cranial aspect of the abdomen. A fluid wave was also palpable. Abdominal radiography revealed loss of serosal detail and splenomegaly. A CBC indicated a PCV of 26.3% (reference range, 37.3% to 61.7%) and total solids concentration of 5.0 g/dL (reference range, 5.2 to 8.2 g/dL). Abdominocentesis was performed; PCV of the abdominal fluid was 29%, and total solids concentration was 4.6 g/dL. There was no evidence of pulmonary metastasis on thoracic radiographs. Abdominal ultrasonography revealed moderate peritoneal effusion and a poorly defined, heterogeneous, 4.5 × 4.2-cm-diameter, hyperechoic left divisional hepatic mass. Additional multifocal, round, poorly defined, hypoechoic, and hyperechoic nodules measuring up to 1.5 cm in diameter were evident within the left and right divisions of the liver. Generalized splenomegaly was also noted with rounded margins and multifocal, poorly defined, hypoechoic nodules of up to 7.9 cm in diameter.

The patient underwent exploratory laparotomy; prior to surgery, 1 U of packed RBCs was administered. Splenectomy; partial lobectomies of the left lateral, right lateral, and right medial liver lobes; and MWA of a 2.5-cm-diameter nodule in the caudate lobe at 65 W for 3 minutes were performed. The dog recovered from surgery without apparent complications and was discharged 2 days later. Histologic examination of spleen and hepatic specimens confirmed a diagnosis of hemangiosarcoma. Adjuvant chemotherapy was recommended but declined by the owner.

Four days after surgery, the dog was evaluated on an emergency basis after it chewed out the staples at the cranial aspect of the laparotomy incision. The surgical incision went on to heal without further complications following appropriate wound management. Two weeks after surgery, the owner reported that the dog was clinically normal with progressive improvement in appetite and a normal demeanor. Frequent and inappropriate urination on the bedding was reported. Diagnostic testing to investigate the urinary issues and adjuvant chemotherapy for the hemangiosarcoma were discussed and declined by the owner. The dog was euthanized by the referring veterinarian 45 days after surgery because of owner concerns related to quality of life.

Discussion

Hepatic neoplasia in dogs can be either primary or metastatic in origin. Primary hepatic neoplasia is uncommon, accounting for 0.6% to 1.5% of all neoplasms in dogs.1 Metastatic spread to the liver is common, with 30.6% to 36.8% of dogs with primary nonhepatic neoplasia reportedly developing secondary liver tumors.2 For dogs with primary neoplasia of the liver, surgical resection is generally thought to yield the best results in terms of curative intent. In a report3 of 48 dogs with hepatocellular carcinoma, the authors concluded that tumor-related mortality rate for dogs that were not treated surgically was 15.4 times the rate for dogs that underwent surgery. In human patients, both metastatic colorectal and primary hepatocellular neoplasia are common.4,5 Surgical resection is considered the standard of care and is associated with a better prognosis and longer survival times.4,5 However, many dogs and humans with liver tumors are not surgical candidates, often because of high tumor burden, tumor location, compromised liver function, involvement of adjacent vasculature, or some combination of these factors.6,7 As a result, several locoregional treatments have been developed, including MWA, RFA, cryotherapy, percutaneous ethanol injection, transarterial chemoembolization, transarterial radioembolization, laser ablation, irreversible electroporation, and, more recently, transportal radioembolization.8–11 The most commonly used locoregional ablative treatment in human patients has been RFA8; however, there has been increasing interest in MWA, along with clinical evidence that it is an equivalent or possibly superior technique.6,8,12–14

The basis of MWA lies in the generation of controlled thermal energy through an antenna to a focal area of tissue, resulting in tumor cell death. With MWA, heat is produced by means of rapid oscillation of an electromagnetic field generating polar molecular friction. This is in contrast to RFA, which relies on electrical impedance within inherently conductive tissues. The predominant advantage of using an electromagnetic field is production of a heat zone in a more rapid, homogenous, and predictable manner. In addition, MWA can be performed concurrently with multiple probes to best match tumor morphology.6 Radiofrequency ablation requires an electrical current, which may result in an inconsistent ablation zone as desiccated tissues immediately adjacent to the electrode create a barrier of low conductivity (increased impedance), resulting in an unreliable distribution of tissue necrosis.6,12 Radiofrequency ablation also appears more susceptible to the heat-sink effect, a phenomenon that involves the attenuation of thermal energy from target tissues because of the cooling effect of adjacent vasculature.15,16 In 1 experimental study,16 histopathologic analysis of the livers of 7 Yorkshire pigs that underwent MWA of areas in variable proximity to hepatic veins was performed, and the authors concluded that no to minimal heat-sink effect occurred.

The 3 main components of an MWA system include a generator, a power source, and antennas, also referred to as probes. Most of the currently available systems also incorporate a cooling system that creates a continuous circulation of either fluid or compressed gas through the antenna shaft.12 The generators are most commonly set at either 915 MHz or 2.54 GHz according to FCC regulations.12 The incorporation of a cooling system helps prevent proximal probe heating and subsequent thermal damage to adjacent tissues that are not part of the target lesion. The design of the antenna is most commonly linear.12 For all 5 patients for the present report, MWAj was performed via an open surgical approach. Both direct, with the MWA probe inserted into the center of the nodules, and no-touch, with the probe aligned in contact with the surface of capsular lesions without puncture, applications were performed. The mean thermocouple temperatures within the targeted tissues ranged from 110° to 130°C. Tract cauterization to > 70°C was performed when direct puncture was used. The MWA settings were chosen according to manufacturer recommendations on the basis of the size of the lesions and on the basis of previous ex vivo and in vivo research involving cattle, pigs, and dogs.17–19

All 5 patients in the present case series had diffuse hepatic neoplasia that precluded complete surgical resection. The characteristics of the liver make it well suited to application of MWA.12 With limited options available for treatment of unresectable hepatic neoplasia and high morbidity associated with intraoperative hemorrhage in dogs with compromised liver function, targeted application of thermal necrosis with an added coagulative benefit by use of a technique such as MWA becomes intriguing. Although we have demonstrated feasibility of hepatic MWA in dogs, further study is necessary to determine whether disease-free or survival benefits exist for dogs with specific hepatic neoplasms treated locoregionally with MWA. We also note that histologic examination was not performed on every liver nodule that was treated in the patients of this report. Considering that prediction of malignancy on the basis of the presence of a nodule with or without cytologic examination is challenging, it is possible that MWA was applied to benign lesions as well as malignant ones in these dogs. However, this is to be expected given the nature of the MWA modality, and intraoperative decision making was necessary for nodules that may not have previously undergone fine-needle aspiration or been detected on preoperative diagnostic imaging. Ideally, intraoperative histopathologic evaluation of frozen sections or immediate cytologic evaluation would have been performed prior to ablation.

Two dogs in the present case series (dogs 2 and 4) had no hepatic abnormalities noted on postoperative ultrasonographic examinations. Previous studies20–22 have found that ultrasonography has a low sensitivity for detection of hepatic parenchymal lesions. In a study20 of 371 dogs, for instance, the sensitivity of ultrasonography for detection of hepatic metastasis was only 56%. Human patients treated by means of MWA undergo postablation diagnostic imaging to assess ablation zones and monitor for tumor recurrence with contrast-enhanced CT or magnetic resonance imaging as standard modalities, which have supplanted ultrasonography.23 We suggest that for the dogs of this report, it is possible postablation lesions may have been undetected at follow-up because of the limitations of ultrasonography.

Hepatic metastases from AGAC (dog 1) and hemangiosarcoma (dogs 3 and 5) were treated with MWA in this report. Hypercalcemia and distant metastases at the time of diagnosis of AGAC have been reported as factors associated with a poor prognosis in dogs.24,25 In 1 study,25 dogs with either hypercalcemia or metastasis had a median survival time of 6 months, compared with 11.5 months for dogs without hypercalcemia and 15.5 months for dogs without metastasis. In 2 studies,24,26 no significant differences in survival times were reported when dogs received adjuvant chemotherapy as part of the treatment protocols. Similarly, in a recent study27 evaluating survival time for dogs with primary splenic hemangiosarcoma, clinical stage was the most important prognostic factor associated with survival time. These associations between the presence of distant metastases and shorter survival times coupled with a lack of significant prolongation of survival time with adjuvant chemotherapy suggest that MWA, which is a direct locoregional treatment modality for dogs with hepatic metastases, warrants further investigation as an adjunct to established treatments.

In the present report, dogs 2 and 4 had primary hepatic neoplasms with multiple, additional smaller liver nodules. In dogs, hepatocellular carcinoma is the most common primary liver tumor and is divided into 3 subtypes: massive, nodular, and diffuse.28 Whereas it has been reported previously that 61% of hepatocellular carcinomas are massive, defined as being isolated to a single liver lobe and thus potentially resectable, nodular and diffuse hepatocellular carcinomas, which reportedly accounted for 29% and 10% of hepatocellular carcinomas in 1 series,28 encompass multiple liver lobes and are usually nonresectable. Results of 1 study3 demonstrated that median survival time for dogs treated with surgery was > 1,460 days, compared with 270 days for dogs treated medically. In the same study, the major intraoperative complication was hemorrhage. The use of MWA may provide a locoregional surgical solution for treatment of some nonresectable hepatic neoplasms and, because of its coagulative properties, might be especially useful for patients with nonresectable hemorrhaging masses such as dog 3 of this report.

No intraoperative or postoperative complications associated with the application of MWA were observed in the dogs described in the present report. Several studies13,29,30 of human patients with hepatic neoplasia have found MWA to be equally as effective and safe, compared with RFA, on the basis of local tumor control and overall survival rates, with the advantages of shorter ablation time and fewer applications per lesion. The rate and nature of major complications that have been noted are comparable with those for patients treated with RFA, ranging between 0% and 8% and including hemorrhage, abscess, biliary tract injury, and tumor seeding.14

Although MWA in adult human patients is well documented, there is a paucity of literature reporting the implementation of ablation techniques as treatment for malignant or benign hepatic lesions in human pediatric patients. A major limiting factor is the inherently small liver volume in pediatric patients, leading to concerns of damage to the central bile ducts and thrombosis in major branch vessels. This is of particular consideration when multiple ablations are required, resulting in larger volumes of coagulation necrosis. In the present report, most dogs required more than 1 ablation. No notable short- to intermediate-term adverse effects on liver function or clinical manifestations of liver failure or biliary obstruction were observed, despite the high volumes of ablation, compromised liver tissues, geriatric status of the patients (age, 9 to 11 years), and, in 2 of the 5 dogs (dogs 2 and 3), adjunctive chemotherapy. As such, we believe there is translation potential in the use of dogs with naturally occurring hepatic neoplasia as a model for implementation of MWA in human pediatrics.

Results of the present small case series suggested that MWA is a feasible and potentially effective treatment option for certain nonresectable hepatic tumors in dogs. Clinical benefits of MWA for specific liver tumors in dogs are unknown, and prospective investigation is indicated. In human patients, the application of MWA has been achieved with ultrasound-guided, laparoscopic, and CT-guided methods.13,31,32 Implementation in other organs with differing tissue composition such as lung, kidney, and bone has been reported to be effective and safe.33–35 We have recently reported the feasibility of a laparoscopic approach for MWA in dogs, but clinical evidence is minimal.36 The application of MWA via ultrasound or CT guidance also deserves clinical investigation in veterinary patients.36

Acknowledgments

Presented in part at the 12th Annual Meeting of the Veterinary Endoscopy Society, Santa Barbara, Calif, April 2015.

ABBREVIATIONS

AGAC

Apocrine gland adenocarcinoma

ALP

Alkaline phosphatase

ALT

Alanine aminotransferase

MWA

Microwave ablation

RFA

Radiofrequency ablation

Footnotes

a.

Certus 140 2.45-GHz Ablation System, NeuWave Medical, Madison, Wis.

b.

Palladia, Zoetis Inc, Florham Park, NJ.

c.

Feldene, Pfizer Animal Health, New York, NY.

d.

Adriamycin, Bedford Laboratories, Bedford, Ohio.

e.

Benadryl, Parkedale Pharmaceuticals Inc, Rochester, Mich.

f.

Cerenia, Zoetis Inc, Kalamazoo, Mich.

g.

Zofran, GlaxoSmithKline, Research Triangle Park, NC.

h.

Flagyl, Pfizer Animal Health, New York, NY.

i.

Yunnan Baiyao, Yunnan Baiyao Group Co Ltd, Yunnan, China.

j.

Certus PR15 Ablation Probe, NeuWave Medical, Madison, Wis.

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