It’s comforting to know there is "Hope".
Ilona and Bill
If you are attending the North American Veterinary Conference this week be sure to stop by and see Dr. Craig Clifford on Saturday January 17 for Clinical Application of Immunotherapeutics in Veterinary Oncology.
Cally, a 14-year-old, spayed female, domestic shorthair cat, presented to the Oncology Service at HopeVS for consultation for recently diagnosed gastrointestinal large cell lymphoma. Cally had a 1-month history of weight loss and progressively worsening appetite. She also had 2-3 days of hematemesis and pica. She was taken to the primary care vet where routine blood work and abdominal x-rays were found to be normal. Abdominal ultrasound was recommended which revealed a mass effect in the stomach and enlarged gastric lymph nodes, aspirates confirmed large cell lymphoma upon cytology review by a pathologist.
Lymphoma, a cancer of the immune system, is one of the most common cancers diagnosed in cats. Feline lymphoma may occur in various anatomic forms, with gastrointestinal being one of the most common forms(1, 2). Feline gastrointestinal lymphoma is divided into three main forms based on cell size, immunophenotype, and mucosal architecture(2). Enteropathy-associated T-cell lymphoma (EATCL) Type II is most often a small cell lymphoma which is confined to the mucosal layer of the small intestines and generally carries a good prognosis with an average survival time of 29 months when treated with steroids and Chlorambucil. The second main form is EATCL Type I, a large cell lymphoma in approximately 60% of cases, occurring in the submucosal and muscularis layers of the small intestine. This form of lymphoma carries a poor prognosis with average survival time of 1.5 months when treated with multiagent chemotherapy protocol. The third main form is B cell gastrointestinal lymphoma, a large cell form in 100% of cases, occurring in the submucosal and muscularis layers of the stomach, ileum and ileocecocolic junction. This form of lymphoma carries a poor prognosis with the average survival time of 3.5 months when treated with multiagent chemotherapy protocols.
Treatment of choice for feline large cell lymphoma is multiagent chemotherapy protocol, often L’CHOP or L’COP-based protocols are used(1). These protocols alternate L’asparaginase, vincristine (or vinblastine), cyclophosphamide, +/- doxorubicin. Steroids (prednisone or prednisolone) are incorporated into the chemotherapy protocol.
As outlined above, cats with gastric lymphoma, such as Cally, may have an estimated survival time of 3-4 months with L’CHOP protocol(2). In Cally’s case ultrasound results revealed a gastric mass and enlarged gastric lymph nodes. No ultrasound abnormalities were noted in other regions of the gastrointestinal tract. Cytology confirmed large cell lymphoma. Histopathology was recommended to further evaluate cellular characteristics, mucosal architecture, and immunophenotype; however Cally’s owners declined surgical biopsies. We recommended L’CHOP treatment protocol and serial ultrasound exams to monitor tumor response to treatment. In addition to traditional treatment for the cancer, we discussed incorporating acupuncture into Cally’s protocol, with the goal of reducing potential chemotherapy and tumor-induced nausea, improve appetite, and support the immune system(3).
Human and veterinary studies have demonstrated the benefit of acupuncture for conditions including: pain(3-6), immune dysregulation and inflammation(7-8), and nausea(9-10). In 1998, the National Institutes of Health (NIH) published a consensus report summarizing research findings which confirmed positive benefit on the effectiveness of acupuncture for chemotherapy-induced nausea as well as post-operative pain secondary to tumor removal in people(11). This report sparked major interest in acupuncture as a compliment to physician-based Western Medicine. Since 1998 there has been a surge in funding to support research evaluating the molecular mechanisms and the clinical benefits of acupuncture(12). As more and more positive research is published, Western medicine practitioners are gaining confidence in using this modality as a tool in their tool-belt. It is not surprising that the top tier, world-renowned U.S. Cancer Institutes such as, Dana-Farber in Boston, Sloan-Kettering in New York, and MD Anderson in Houston, all have integrative medicine programs closely associated with their Cancer Centers.
Research from physician-based medicine supports the use of this modality for the human oncology patient. Three of many studies were chosen to be summarized here. The first study is a three-armed, randomized, prospective clinical trial published in The Journal of the American Medical Association(10). Women with high grade mammary carcinoma, treated with high-dose myeloablative chemotherapy, were randomly assigned to three separate groups: anti-emetic alone, anti-emetic with electroacupuncture, anti-emetic with acupuncture at non-therapeutic locations on the body. The study found that women in the anti-emetic with electroacupuncture group had significantly less vomiting episodes compared to women in the two other groups (anti-emetic alone and anti-emetic with non-therapeutic acupuncture)(10).
The second study, published in The Journal of Supportive Care in Cancer evaluates the effectiveness of acupuncture at alleviating nausea in children with solid tumors who were receiving high dose chemotherapy(13). Eleven children were studied for a total of 22 chemotherapy cycles. The children were divided into two groups: group 1 received anti-emetic along with acupuncture and group 2 received anti-emetic alone. The amount of anti-emetic therapy used by each patient was documented (baseline and any additional needed) as well as a daily diary of emesis episodes, nausea scores and changes in body weight. The benefits of acupuncture with respect to the reduction of additional antiemetic medication were observed. The study found that acupuncture enabled patients to experience reduced levels of nausea and vomiting during chemotherapy.
The third study published in The Journal of Alternative and Complementary Medicine, investigated the effect of acupuncture on white blood cell count and absolute neutrophil count in patients with ovarian cancer receiving myelosuppressive chemotherapy(14). Patients received therapeutic acupuncture versus non-therapeutic acupuncture while undergoing chemotherapy. Acupuncture was given 2–3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. White blood cell count, absolute neutrophil count and plasma granulocyte colony-stimulating factor (G-CSF ) were assessed weekly for one month. Results indicated that the median white blood cell count in the therapeutic acupuncture group was significantly higher than in the non-therapeutic acupuncture group after adjusting for baseline value, (8600 cells/μL, range: 4800–12,000 versus 4400 cell/μL, range: 2300–10,000) (p = 0.046). In addition the incidence of grade 2-4 leukopenia was less in the therapeutic acupuncture arm than in the non-therapeutic acupuncture arm (30% versus 90%; p = 0.02). The median leukocyte nadir, neutrophil nadir, and recovering absolute neutrophil counts were all higher but not statistically significantly different (p = 0.116–0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. In conclusion a clinically relevant trend of higher WBC values during one cycle of chemotherapy was observed in patients with ovarian cancer receiving therapeutic acupuncture during myelosuppressive chemotherapy. This suggests a potential myeloprotective effect of acupuncture.
In veterinary medicine, there are multiple research reports demonstrating the benefit of acupuncture at alleviating pain(3, 15-19) and nausea(9) for the veterinary patient. There is however, a paucity of data evaluating the benefits of acupuncture for the veterinary oncology patient. The good news is that there is data in the human literature which supports acupuncture as a beneficial adjunct therapy to traditional treatment for the cancer patient. By applying what we know from human medicine to the veterinary patient, veterinarians are able to further develop the field, embark on potential clinical research projects to help improve the scientific database, and most importantly, provide well rounded care for our cancer patients.
Cally went on to receive the L’CHOP protocol in which she received chemotherapy weekly along with acupuncture. Most common acupuncture points used include: Bai-Hui, GV 14, BL 23/20/21/17, ST 36. The goal of these acupuncture points was to reduce potential chemotherapy and tumor-induced nausea, improve appetite, and balance the immune system. After the first month of chemotherapy, a recheck ultrasound confirmed strong partial remission based on smaller tumor size. Cally was continued on this therapy. During the course of her disease and treatment she never experienced low white blood cell counts and had only intermittent regurgitation of hairballs but no vomiting and no pica. We continued to monitor the tumor response via serial ultrasound exams every 8-10 weeks. Eight-months after initial diagnosis she presented with acute onset of vomiting. Ultrasound exam confirmed progression of disease in the form of another gastric mass, which occurred within a short time frame as ultrasound exam 4-weeks prior revealed normal stomach wall thickness. Due to the severity of clinical symptoms associated with the relapse lymphoma, the clients declined further treatment and elected humane euthanasia.
In summary, Cally experienced low level of side effects from the tumor and from chemotherapy treatment as well as a longer than anticipated remission period with gastric lymphoma. She tolerated acupuncture treatment well. This case report demonstrates that acupuncture may be used in conjunction with chemotherapy in the feline patient with large cell lymphoma.
Submitted by: Kate Vickery, VMD, MS, DACVIM (Oncology), CVA
- Hematopoietic Tumors: Feline Lymphoma and Leukemia. Vail, DM. In:Withrow MacEwen Small Animal Clinical Oncology. eds. Saunders. 2013. 638.
- Feline Gastrointestinal Lymphoma: Mucosal Architecture, Immunophenotype, and Molecular Clonality. Veterinary Pathology Moore PF, et al. 2012 Jul;49(4):658-68. http://www.ncbi.nlm.nih.gov/pubmed/21505197
- The Validity of Acupuncture in Veterinary Medicine. Am J Trad Chinese Vet Med. Xie Huisheng, et al. 7(1): 35-43. http://people.tamu.edu/~etebeaux/ode/techwrite/Validity%20of%20Acupuncture.pdf
- Analgesic Effect of Electroacupuncture in Post-Thoracotomy Pain: A Prospective Randomized Trial. Annals Thoracic Surgery. Wong RH, et al. 2006. 81: 2031-36. http://www.sciencedirect.com/science/article/pii/S0003497505023696
- Randomized, Blinded, Sham-Controlled Trial of Acupuncture for the Management of Aromatase Inhibitor-Associated Joint Symptoms in Women with Early-Stage Breast Cancer. Journal Clinical Oncology. Crew KD, et al. 2010. 28: 1154-60. http://jco.ascopubs.org/content/28/7/1154.short
- Molecular Mechanisms Underlying the Effects of Acupuncture on Neuropathic Pain. Neural Regeneration Ju Z, et al. 2013. Sept 5; 8(25): 2350-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4146043/
- Effects of Acupuncture on Leucopenia, Neutropenia, NK, and B cells in Cancer Patients: A Randomized Pilot Study. Evid Based Complement Alternat Med. Pais I, et al. 2014. 217397. http://www.hindawi.com/journals/ecam/2014/217397/
- IL-10 Cytokine Released from M2 Macrophages is Crucial for Analgesic andAnti-inflammatory Effects of Acupuncture in a Model of Inflammatory Muscle Pain. Molecular Neurobiol da Silva MD, et al. 2015. 51(1): 19-31. http://porteiras.s.unipampa.edu.br/gpfin/files/2014/06/IL-10-Cytokine-Released-from-M2-Macrophages-Is-Crucial-for-Analgesic-and-Anti-inflammatory-Effects-of-Acupuncture-in-a-Model-of-Inflammatory-Muscle-Pain.pdf
- Effects of Maropitant, Acepromazine, and Electroacupuncture on Vomiting Associated with Administration of Morphine in Dogs. J Am Veterinary Medical Assoc. Koh RB, et al. 244 (7): 820. http://avmajournals.avma.org/doi/abs/10.2460/javma.244.7.820
- Electroacupuncture for Control of Myeloablative Chemotherapy-Induced Emesis: A Randomized Controlled Trial. J Am Medical Assoc. Shen J, et al. 2000. 284: 2755-61. http://jama.jamanetwork.com/article.aspx?articleid=193319&resultclick=1
- NIH Consensus Conference. Acupuncture. J Am Medical Assoc. 1998. 280: 1518-24. http://www.ncbi.nlm.nih.gov/pubmed/?term=NIH+Consensus+Conference.+Acupuncture.+J+Am+Medical+Assoc.+1998
- The Value of Acupuncture in Cancer Care. Hematology Oncology Clinics North Am. Lu W, Dean-Clower E, et al. 2008. 22(4): 631. http://www.sciencedirect.com/science/article/pii/S0889858808000580
- Acupuncture Against Chemotherapy-Induced Nausea and Vomiting in Pediatric Oncology. Supportive Care in Cancer. Reindl, T., et al. 2006. 14(2):172. http://link.springer.com/article/10.1007/s00520-005-0846-
- Acupuncture for Chemotherapy-Induced Neutropenia in Patients with Gynecologic Malignancies: A Pilot Randomized, Sham-Controlled Clinical Trial. The J of Comp and Alt Med. Lu, W., et al. 2009, 15(7): 745-753. http://online.liebertpub.com/doi/abs/10.1089/acm.2008.0589
- Effectiveness of Electroacupuncture Analgesia Compared with Opioid Administration in a Dog Model: Pilot Study. British J Anaesthesia. Groppetti, D., et al. 2011. 107: 612 http://bja.oxfordjournals.org/content/107/4/612.short
- Comparison of Decompressive Surgery, Electroacupuncture, and Decompressive Surgery followed by Electroacupuncture for the Treatment of Dogs with Intervertebral Disk Disease with Long-Standing Severe Neurologic Deficits. JAVMA. Joaquim, et al. 2010. 236 (11):1225 http://avmajournals.avma.org/doi/abs/10.2460/javma.236.11.1225
- Outcome of 119 dogs and cats treated at the acupuncture unit of the Faculty of Veterinary Medicine and Animal Science of the University of São Paulo State. Brazilian J Veterinary Research and Animal Science. Angeli, et al. 2005. 42 (1): 68. http://www.revistas.usp.br/bjvras/article/viewFile/26456/28239
- Evaluation of electroacupuncture treatment for thoracolumbar intervertebral disk disease in dogs. JAVMA. Hayashi, et al. 2007. 231 (6): 913 http://avmajournals.avma.org/doi/abs/10.2460/javma.231.6.913
Odin is a 6-year-old, neutered, male Great Dane who presents for ongoing management of a presumed osteosarcoma of the left distal tibia. He is systemically healthy and the primary complaint is related to pain, swelling, and lameness in this limb. At this time, his owners are interested in pursuing alternatives to amputation for controlling Odin’s pain. Five months ago he received a single fraction of Cyberknife therapy to this lesion and has since been treated with chemotherapy and pamidronate. He initially did well with a special brace for support of this limb, but recently has become too painful to tolerate the brace and his mobility has significantly decreased. The limb remains intact with no evidence of fracture on radiographs. Current pain therapy includes Rimadyl, tramadol, and acupuncture which he has tolerated well but is becoming less effective.
On examination, there is an enlarged area just above the left tarsus. This is significantly painful to palpation with hyperesthesia/allodynia of the upper thigh and lumbar epaxial musculature. He refuses to stand without significant aid and will not place weight on or lie on his left side. No other areas of pain are identified.
Amputation was discussed but declined in favor of palliative care. Goals for pain management are multifactorial but center around the ability to improve mobility in this large dog to enable the owner to care for him and allow fitting and use of the brace in order to help avoid fracture.
Partly due to the severity of his presentation, but also due to the need to rapidly restore some mobility due to his large size, a hospitalized “pain vacation” was elected for Odin in addition to adjustments to his long-term analgesic protocol. A “pain vacation” consists of an aggressive and multimodal injectable treatment for 12-24 hrs. Medications are designed to treat pain related to the direct lesion while also dramatically calming central hypersensitivity to pain. The goal is to achieve a rapid and potentially long lasting “reset” of central pain centers while also achieving more rapid control of hypersensitivity surrounding the lesion itself.
Odin was hospitalized and treated with lidocaine, ketamine, and dexmedetomidine as IV constant rate infusions. No loading doses were used. Lidocaine and ketamine were titrated to their desired doses over the first hour. Dexmedetomidine was titrated to achieve a relaxed, conscious, non-anxious patient. A single dose of methadone was given initially to offset the pain of hospital manipulations and IV catheter placement. Infusions of lidocaine, ketamine, and dexmedetomidine were continued for 12 hours.
Odin became rapidly more comfortable during treatment. By the end of the infusion period, he was able to lie comfortably on and have the affected limb palpated. He was able to stand with aid. He tolerated all medications well and was discharged without incident. At 4 weeks follow-up Odin continued to be significantly more comfortable. He is able to toe touch and balance on the affected limb and comfort continues to be maintained with oral medications.
Lidocaine blocks sodium channels in central and peripheral nerve cell membranes that play roles in acute and persistent pain hypersensitivity. It may also inhibit calcium channels involved in chronic pain conditions. IV dosing in dogs is generally well tolerated with common adverse effects including loss of appetite, nausea, and vomiting.
Ketamine is a non-competitive antagonist at excitatory NMDA receptors. Activation and upregulation of NMDA-R occur with ongoing neuronal depolarization, as in this case of an ongoing painful lesion, and leads to increased excitatory neurotransmission and hypersensitivity. Decreasing these responses can produce sustained increases in comfort and response to more traditional medications. Adverse effects may include tachyarrhythmias, agitation, and nausea.
Dexmedetomidine is an alpha-2 adrenoceptor agonist which produces analgesia via changes in calcium ion communication through sensory pathways in the peripheral and central nervous systems. It is a useful adjunct when titrated to low doses producing mild sedation and anxiolysis and may have a role in reducing central pain hypersensitivity. Adverse effects may include bradyarrhythmias, nausea, and vomiting.
While not a substitute for traditional palliative options in painful cancer, a multimodal “pain vacation” can be an effective adjunct in extending quality of life and achieving rapid improvement in painful states while allowing traditional therapies to resume or maintain effectiveness.
Submitted by Jeff Wilson, DVM, DACVAA, CVMA
Facing the holiday season for the first time following the loss of your beloved companion animal can be extremely challenging. The holidays represent a time for joy and reflection, but when you have lost your pet, you might feel unable to celebrate, because your lap or the space next to you is empty. Participating in traditional family activities is an ongoing reminder of what is missing from your life.
The following recommendations serve as a guide to help you through the holidays, while taking into consideration, grief is a unique and individual experience:
Acknowledge the Pain
Grieving the loss of a pet is agonizing at any time of the year and the holidays tend to intensify feelings of loneliness and sorrow. You may feel pressured to mask your true feelings, but pretending you are not brokenhearted will only hurt in the long run. Ultimately, embracing the sadness will lead you out of the pain. Grief comes as a result of love and is a tribute to the remarkable relationship you shared with your companion animal.
Treasure the Memories
While your pet’s physical presence is gone, the love, memories, and lessons learned will always be with you. Do not be afraid to remember favorable times with your pet, as this can be a source of comfort while experiencing extreme heartache. Reflecting upon and taking inventory of the gifts received from your faithful companion animal sparks the healing process. One way to honor the relationship between you and your pet is to acknowledge how your life has been changed for the better.
Revise Holiday Traditions
For many, pets are a vital part of the holiday celebrations and it is almost impossible to comprehend the fact they will not be here this year. Although people have individual needs, try to resist the impulse to avoid the holidays altogether. The goal is to make the holidays work for you in less than ideal circumstances. If you typically entertain guests or host family festivities, you may want to consider going out to dinner with family and friends.
The holidays are difficult for children, because they are experiencing sadness due to the loss, but at the same time feel the excitement of the impending celebration. Communicate with children to let know it is okay to have fun without feeling guilty. With regard to modifying holiday traditions, keep in mind children depend on the familiarity of annual rituals, since it provides them with a sense of security. Before finalizing the holiday plans, listen to what is important to your children and try to incorporate their hopes and wishes into the celebration.
Establish a New Ritual
When a daily routine was centered on the relationship with a pet, the death can also be profoundly disruptive to one’s sense of home, safety, purpose, and identity. Find a way to incorporate your pet into a new holiday tradition by keeping their memory alive during the holiday season and beyond. In the matter of developing a new ritual, consider lighting a remembrance candle during the holiday dinner, decorating a tree ornament with your pet’s picture, creating a picture book or video, and sharing notable stories about your companion animal with family and friends. Remember the love that you shared and make a difference in your pet’s honor by giving back, in terms of volunteering or donating at a local animal shelter.
Engage in Social Support
The need for support may be the greatest in the midst of the holiday season. Be honest with how you are truly feeling with the people you love and give them the opportunity to be there for you. After the loss of a pet, reaching out to family and friends can be a daunting task. If you know someone who is grieving over the loss of a pet, do not wait for an invitation for help, but show up and lend support by being present. Reassure your loved one that the sadness may fade, but the relationship will never end.
Practice Self Care
Grieving is an exhausting process and the pain invades all parts of your life, which is why you must allow your mind and body to take a break from dealing with the complicated thoughts and emotions. Plan an activity that brings a moment of comfort and joy that will allow you to take a well-needed breath. Schedule the holiday around supportive family and friends, but balance it with quiet time as well. Try to streamline your life as much as possible in relation to the holiday preparations. Most importantly, be kind to yourself and recognize your pain is entirely appropriate.
My wish for you this holiday season is that you find peace in your heart and hope in new beginnings.
Jennifer Durn is a welcome addition to the Hope Team and she is heading up our Support Services Program. The program has been incorporated into the framework of Hope Veterinary Specialists and offers a unique advantage to clients who might find a sounding board beneficial during challenging circumstances. The Hope team acknowledges the incredible relationship between the clients and their ever-faithful companion animals and is dedicated to reinforcing the bond through our high standard of care and service. The Support Services Program at Hope VS is free of charge and is coordinated by Jennifer Durn, MSW, LSW. Support is provided in person, over the phone, and through email.
Visit http://www.pavetfoundation.org/henryscupboard.aspx to help donate today!