Today's Veterinary Practice

MAY-JUN 2014

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| LymPh Node CyToLogy Today's Veterinary Practice May/June 2014 22 tvpjournal.com Figure 4. Squamous cell carcinoma metasta- sis to a lymph node: the abundant population of small lymphocytes in the background con- firms lymph node origin, but the large, angular epithelial cells with abundant cytoplasm do not belong in a lymph node under any circumstance; note the occasional lymphoblast and plasma cell. Cour- tesy Dr. Natalie Hoepp Figure 5. View (2×) of a sectioned histologic specimen of a lymph node showing the limitations of needle aspirates: On the left side of the image, the node is effaced with a neoplastic cell popula- tion, but the right side of the specimen shows a reactive lymph node population. Needle aspiration can miss a neoplastic population, and histopathology is recommended if there is clinical concern. Courtesy Dr. Tamara Hancock Figure 6. Melanophag- es, containing abun- dant dark pigment, can be seen in areas of chronic inflammation and other nonneoplastic pathology in draining lymph nodes. However, the more lightly granulated cell on the lower right (ar- rows) is a melanocyte, which should not be present in a lymph node and, therefore, is consistent with lymph node metastasis. Courtesy Dr. Erin Burton 5 mg/mL Solution for Injection Non-steroidal anti-inflammatory drug for use in dogs and cats only Caution: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Warning: Repeated use of meloxicam in cats has been associated with acute renal failure and death. Do not administer additional injectable or oral meloxicam to cats. See Contraindications, Warnings, and Precautions for detailed information. Description: Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class. Each mL of this sterile product for injection contains meloxicam 5.0 mg, alcohol 15%, glycofurol 10%, poloxamer 188 5%, sodium chloride 0.6%, glycine 0.5% and meglumine 0.3%, in water for injection, pH adjusted with sodium hydroxide and hydrochloric acid. Indications: Dogs: Metacam (meloxicam) Solution for Injection is indicated in dogs for the control of pain and inflammation associated with osteoarthritis. Cats: For the control of postoperative pain and inflammation associated with orthopedic surgery, ovariohysterectomy and castration when administered prior to surgery. Contraindications: Dogs and cats with known hypersensitivity to meloxicam should not receive Metacam Solution for Injection. Additional doses of meloxicam or other NSAIDs in cats are contraindicated, as no safe dosage for repeated NSAID administration has been established (See Animal Safety). Do not use meloxicam in cats with pre-existing renal dysfunction. Warnings: Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. For IV or SQ injectable use in dogs. All dogs and cats should undergo a thorough history and physical examination before administering any NSAID. Appropriate laboratory testing to establish hematological and serum biochemical baseline data is recommended prior to, and periodically during use of any NSAID in dogs and cats. For subcutaneous (SQ) injectable use in cats. Do not use IV in cats. When treating cats: do not administer a second dose of meloxicam. Do not follow the single, one-time dose of meloxicam with any other NSAID. Do not administer Metacam Oral Suspension following the single, one-time injectable dose of meloxicam. Do not repeat the single, one-time dose of meloxicam in cats or dogs. Owners should be advised to observe their dogs and cats for signs of potential drug toxicity. Precautions: The safe use of Metacam Solution for Injection in cats younger than 4 months of age or dogs younger than 6 months of age, cats or dogs used for breeding, or in pregnant or lactating females has not been evaluated. Use a syringe of appropriate size to ensure precise dosing. As a class, cyclo-oxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Dogs and cats that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be carefully approached and monitored. NSAIDs may inhibit the prostaglandins that maintain normal homeostatic function. Such anti-prostaglandin effects may result in clinically significant disease in patients with underlying or preexisting disease that has not been previously diagnosed. Anesthetic drugs may affect renal perfusion; approach concomitant use of anesthetics and NSAIDs cautiously. Appropriate monitoring procedures should be employed during all surgical procedures. The use of perioperative parenteral fluids is recommended to decrease potential renal complications when using NSAIDs in cats. If additional pain medication is needed after the single one-time dose of meloxicam, a non-NSAID class of analgesic may be necessary. In one study 1 , one cat in each NSAID treatment group had increased intraoperative hemorrhage. Since NSAIDs possess the potential to induce gastrointestinal ulcerations and/or perforation, concomitant use of meloxicam with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. The use of another NSAID is not recommended. Consider appropriate washout times when switching from corticosteroid use or from one NSAID to another in dogs and cats. As a single use product in cats, meloxicam should not be followed by additional NSAIDs or corticosteroids. The use of concomitantly protein-bound drugs with Metacam Solution for Injection has not been studied in dogs and cats. Commonly used protein-bound drugs include cardiac, anticonvulsant and behavioral medications. The influence of concomitant drugs that may inhibit metabolism of Metacam Solution for Injection has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy. The effect of cyclo-oxygenase inhibition and the potential for thromboembolic occurrence or a hypercoagulable state has not been studied. Adverse Reactions: Dogs: A field study involving 224 dogs was conducted wherein 109 were administered meloxicam and 115 were administered a placebo. Based on the results of this study, GI abnormalities, such as vomiting (31 dogs), soft stools/ diarrhea (15 dogs), bloody stool (1 dog), and inappetance (3 dogs) were the most common adverse reactions associated with the administration of meloxicam. Dogs may have experienced more than one episode of the adverse reaction during the study. In foreign suspected adverse drug reaction (SADR) reporting, adverse reactions related to meloxicam administration included: auto-immune hemolytic anemia (1 dog), thrombocytopenia (1 dog), polyarthritis (1 dog), nursing puppy lethargy (1 dog), and pyoderma (1 dog). Adverse reactions reported post-approval were: Gastrointestinal (vomiting, diarrhea, melena, gastrointestinal ulceration), urinary (azotemia, elevated creatinine, renal failure), neurological/behavioral (lethargy, depression), hepatic (elevated liver enzymes), and dermatologic (pruritus). Cats: A field study involving 138 cats was conducted. Of the 72 cats receiving Metacam Solution for Injection, six cats (8.3%) experienced post-treatment elevated serum blood urea nitrogen (BUN) levels. The pre-treatment values were in the normal range. Of the 66 cats in the butorphanol treatment group, no cats experienced post-treatment elevated serum BUN levels. Nine cats (12.5%) receiving Metacam Solution for Injection had post-treatment anemia. Four cats (6.1%) in the butorphanol treatment group had post-treatment anemia. Twenty-four hours after the injection with Metacam Solution for Injection, one cat experienced pain upon palpation of the injection site. In studies used for the foreign approval of Metacam Solution for Injection in cats, lethargy, vomiting, inappetance, and transient pain immediately after injection were noted. Diarrhea and fecal occult blood have also been reported. Adverse reactions reported post-approval were: Urinary (azotemia, elevated creatinine, elevated phosphorus, renal failure), gastrointestinal (anorexia, vomiting, diarrhea), neurological/behavioral (lethargy, depression), and hematologic (anemia). Acute renal failure and death have been associated with the use of meloxicam in cats. Information for Dog and Cat Owners: Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with NSAID intolerance. Adverse reactions may include vomiting, diarrhea, lethargy, decreased appetite and behavioral changes. Dog and cat owners should be advised when their pet has received a meloxicam injection. They should contact their veterinarian immediately if possible adverse reactions are observed, and DOG OWNERS should be advised to discontinue Metacam therapy. Effectiveness: Dogs: The effectiveness of Metacam Solution for Injection was demonstrated in a field study involving a total of 224 dogs representing various breeds, all diagnosed with osteoarthritis. This placebo-controlled, masked study was conducted for 14 days. Dogs received a subcutaneous injection of 0.2 mg/kg Metacam Solution for Injection on day 1. The dogs were maintained on 0.1 mg/kg oral meloxicam from days 2 through 14. Dogs showed clinical improvement with statistical significance in lameness, weight-bearing, pain on palpation, mobility, ability to rise, limping, and overall improvement after 14 days of meloxicam treatment for all variables. Cats: The effectiveness of Metacam Solution for Injection was demonstrated in a masked field study involving a total of 138 cats representing various breeds. This study used butorphanol as an active control. Cats received either a single subcutaneous injection of 0.3 mg/kg Metacam Solution for Injection or 0.4 mg/kg butorphanol prior to onychectomy, either alone or in conjunction with surgical neutering. Pain assessment variables evaluated by veterinarians included additional pain intervention therapy, gait/lameness score, analgesia score, sedation score, general impression score, recovery score, and visual analog scale score. Additionally, a cumulative pain score, which was the summation of the analgesia, sedation, heart rate and respiratory rate scores was evaluated. A palpometer was used to quantify the pain threshold. A substantial number of cats required additional intervention in the 0–24 hour postsurgical period, with the majority of these interventions taking place within the first hour. Therefore, the percentage of cats in each group that received one or more interventions was designated as the primary assessment variable. The median number of interventions was one per cat in the meloxicam group and two per cat in the butorphanol group and this difference was statistically significant (p=0.0021). The statistical evaluation supports the conclusion that the meloxicam test article is non-inferior to the butorphanol active control. The number of interventions administered to the meloxicam group was less than the butorphanol group at 1, 3, 5, 8, 12, and 24 hours post-surgery. Cats receiving Metacam Solution for Injection showed improvement in the pain assessment variables. Reference: 1. Slingsby LS, Waterman-Pearson AE. Comparison between meloxicam and carprofen for postoperative analgesia after feline ovariohysterectomy. J Small Anim Pract . 2002;43(7):286–289. Manufactured for: Boehringer Ingelheim Vetmedica, Inc. St. Joseph, MO 64506 U.S.A. US Patent 6,184,220 Metacam is a registered trademark of Boehringer Ingelheim Vetmedica GmbH, licensed to Boehringer Ingelheim Vetmedica, Inc. 601307L-05-1006 M601502-00 Code 601311 02/2014 NADA 141-219, Approved by FDA Metacam ® (meloxicam) cytes, it can sometimes be difficult to determine with certainty whether the aspirated structure actually was a lymph node. In most cases, the sample contains small numbers of metastatic cells mixed with lymphocytes (Table 4, page 21). Diagnosis based on cytology of a metastatic lymph node— even before the primary tumor is located—is not uncommon. One example is oral tumors: because owners do not routinely look inside their dogs' mouths, they may present the pet because a mass was noted in the mandibular region (Figure 4). Early metastasis can be challenging, because its presence can cause some degree of reactivity in the node (Figure 5) or, if metastasis to lymph nodes has occurred, in regions of the node that are not sampled by fine-needle aspiration. Lymph node biopsy or removal for histopathology should be performed if there is concern for metastasis based on size or shape of a lymph node that cannot be confirmed on cytology. (Continued on page 76) 4 5 6 TVP_2014-0506_Lymph Node Cytology.indd 22 5/24/2014 10:39:02 AM

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