Lost in the Fog

Lost in the Fog was a racing phenom in 2005, winning 10 of 11 and the Eclipse Award Sprint Championship (sidebar). But his early 2006 lackluster racing history brought him back to racehorse reality — or something else was affecting him and foreshadowing a more serious problem that ultimately claimed his life.

His discomfort the week of Aug. 14 sent out a red flag, and trainer Greg Gilchrist vanned Lost in the Fog an hour-and-a-half east from Golden Gate Fields to University of California-Davis' (UC-Davis) Veterinary Medical Teaching Hospital.

Mild colic to rare lymphoma

At first thought to be suffering mild colic, further tests and a biopsy revealed a large cantaloupe-size lymphoma mass on Lost in the Fog's spleen. According to Gary Magdesian, DVM, dipl. ACVIM, dipl. ACVECC, dipl. ACVCP, chief of Equine Critical Care Medicine at UC-Davis, rectal palpation was the initial suspicion about the spleen being enlarged.

Lost in the Fog: This racing phenom's career was cut short with the diagnosis of lymphoma. University of California-Davis clinicians devised the treatment strategy which extended the stallion's life until Sept. 17 when the decision was made to euthanize.

An abdominal ultrasonography revealed a large splenic mass and splenomegaly. The next day, the team performed an ultrasound-guided biopsy of the splenic mass, which revealed lymphosarcoma.

By week's end, using abdominal laparoscopy, Larry Galuppo, DVM, Dipl. ACVS, chief of Equine Surgery, found two additional abdominal masses. One — about the size of an egg — was in the ligament that suspends the spleen within the abdomen. The second was a very large mass at the base of Lost in the Fog's spine. Results revealed abdominal lymphosarcoma with splenic involvement, which was determined to be inoperable, terminal cancer.

"He's been running with this thing inside him in every race he ran this year," Gilchrist says. "It shows you what kind of warrior this horse is. I've never had a horse that comes close to this."

Unmasking the ultrasound: The image clearly depicts Lost in the Fog's splenic involvement.

A tumor is operable if it is localized in a structure that can be removed (e.g. ovary, uterus, segment of resectable intestine, spleen, liver lobe, etc). If the tumor has infiltrated tissue, that because of location and/or encasement of major vessels, nerves or non-removal organs (e.g. heart, etc.), it is, for practical purposes, inoperable. As in people, surgery can attempt to reduce the tumor load if suitable adjunct treatments are available (radiation, chemo, etc.).

As in the case of Lost in the Fog, internal masses that are determined to be lymphoma are likely part of the generalized or multicentric form of lymphoma, multiple internal masses," states Fairfield T. Bain, DVM, MBA, Dipl. ACVIM, ACVP, ACVECC of Woodside Equine Clinic, Ashland, VA.

Lymphoma is a disease of middle-aged horses, reported mostly common in the 4- to 10-year-old age group. The cause remains unknown; no viral cause has been found as it has in other animals and some forms of the disease in humans.

The most common signs associated with lymphoma are weight loss, usually associated with intestinal involvement or the effects of cancer on the body's metabolism.

Lymphoma can involve a variety of areas of the body, both in the abdomen and in the chest cavities, as well as skin nodules or around the eyelids. Lost in the Fog, though he presented with extensive internal tumors, showed no signs of debilitating disease.

According to John Robertson, VMD, PhD, director for the Center for Comparative Oncology, Virginia Tech CVM, horses usually present with "a relatively short history within weeks to months of growth of firm nodules on the head, neck and chest," with other variable clinical signs that include anorexia, inability or unwillingness to work, depressed, fever, dyspnea and weight loss. Some horses with primary cutaneous lymphosarcoma "show no signs other than multiple, non-painful swellings in the skin or subcutis and peripheral lymphadenopathy."

Lost in the Fog showed none of these signs, as he raced, seemingly healthy, other than his poor racing performance. Until his discomfort the week of Aug. 14, it is assumed he had presence of lymphoma for several months without obvious clinical signs.

The long-term prognosis for lymphoma is usually poor. The treatment rationale is to shrink the tumor enough so it can be removed surgically.

Lymphoma is rare in the horse, so blood work rarely provides a specific diagnosis, but does often show secondary effects such as evidence of inflammation, anemia and alterations in the serum proteins. Some immunoglobulins (specifically IgM) are lowered in some lymphoma patients. Diagnosis of internal forms of lymphoma, such as the case with Lost in the Fog, is usually made by imaging, with ultrasound being most important.

The specific diagnosis is made by microscopic examination of a needle aspirate or biopsy of a mass. Further study of the cell types using immunohistochemistry will likely help characterize the tumor and help determine its cause and how it will respond to treatment.

"My experience reflects germ cell tumors as being the most common aggressive intra-abdominal tumor in otherwise healthy looking young (3-6 yrs) horses (still rare though)," says Claude Ragle, DVM, dipl. AVCS, Washington State University CVM. "Diagnosis can be a challenge from biopsy only. Even though the aggressive biologic behavior of the tumor is evident, getting the "fine print" of the cell type and origin can be frustrating."

Peter Moore, BVSc, Ph.D., dipl. ACVP, lymphoma pathologist specialist, definitively typed the tumor as a B-cell lymphoma using clonality and cell surface markers that only he has antibodies for in horses. The histopathology report states, "The diagnosis of B-cell lymphoma was based upon the positive immunoreactivity with CD11a (leukocyte marker), CD21 (B-cell marker), and CD79a (B-cell marker) on sections of frozen tissue and the results of clonality (clonal rearrangement of IGH - immunoglobulin heavy chain gene). The sample was negative for T-cell markers on frozen sections (CD3, CD4 and CD8)."

Splenic involvement

The fact that Lost in the Fog's lymphoma primarily involved the spleen (considered Stage IV) is of interest to his lack of performance and to the issues involved with his treatment.

The spleen, situated against the left abdominal wall, just caudal to the stomach, is a unique organ that involves blood filtration as well as acting as an immune organ. The equine spleen also serves as a reservoir for blood cells.

"The horse spleen is a giant bag of extra blood," explains Kenneth McKeever, Ph.D., FACSM, associate professor, Equine Science Center, Rutgers University. "When the horse runs, its spleen contracts (as the muscles surrounding the spleen contract) and forces a fresh supply of oxygen-rich red blood cells into its blood stream, effectively pumping extra oxygen into its cardiovascular system virtually on demand."

When at rest, about 35 percent of the horse's total blood volume is comprised of red blood cells. Horses increase their red blood cell numbers to more than 65 percent of blood volume during a race. This greatly increases the horse's racing ability to carry needed oxygen.

With splenic involvement, it is no wonder. Lost in the Fog ran out of gas in his last several races.

Not only was he probably experiencing severe discomfort with the jockey perched on his back (because of the tumor along his spine), but his spleen's ability to dump red blood cells for extra oxygen and energy during racing performance also was probably impaired.

When the primary splenic mass was first found, splenectomy was contemplated. Clinical splenectomy in the horse is rare and more commonly performed for research. Several are done every year for USDA research projects with WSU and the University of Idaho, and at Iowa State University's College of Veterinary Medicine. Splenectomy is challenging because of the large size of the horse's spleen, the location within the abdomen, and the fact that it is a blood-storing organ and has a propensity toward hemorrhage.

According to Reinertson, who has done several, it is best performed by resection of the left 16th rib and incision of the diaphragm. The large size of Lost in the Fog's spleen (with tumor involvement) would have made it even more difficult. Ideally, selection of subjects "who were healthy but had easily palpable ribs significantly increased the ease of performing the splenectomy, decreased the duration of the surgical procedure and decreased the incidence of postoperative complications."

The long-term prognosis with lymphoma is usually very poor. Treatment with combinations of chemotherapy agents has provided some improvement in the form of suppression of the disease for varying periods of time. Horses with lymphoma limited to the skin may survive much longer than those with internal involvement.

"We are trying to shrink the tumors," Gilchrist says prior to the euthanasia. If they can shrink them significantly, possibly they can be removed surgically.

Upon arriving at Golden Gate Fields, Fog was put on mild pain medication and dexamethasone to try and decrease tumor mass size. After about two weeks, blood work and ultrasound revealed no changes, and the decision was made to begin several weeks of chemotherapy treatments. The chemotherapy, to be done at UC-Davis, consists of up to six sessions, three weeks apart. The horse will go to the university for the treatments and return home to Golden Gate.

"Chemotherapy is a rational treatment for any multicentric malignancy," states Robertson, "though no successful medical treatment of this tumor exists (in horses)." According to veterinary literature, although methotrexate and dexamethasone have been tried for short periods, and have reduced the size of lesions for short time periods, animals were eventually euthanized when tumors re-grew.

Though veterinary oncologists have insufficient clinical data to state that chemotherapy treatment of lymphoma is ineffective, Robertson believes that "more aggressive therapy administered for longer periods of time may show some benefit in individual horses."

Fortunately, effects of chemotherapy in the horse are not as dramatic in the horse as they are in the human (hair loss, etc). The hair cell growth cycle includes the growing (anagen) stage, the resting (telogen) stage and the transitional (catagen) stage. At the end of the telogen stage, the hair falls out. Chemotherapy drugs kill all rapidly growing cells, and so the hair bulb cells are vulnerable. In humans, chemotherapy drugs weaken or kill developing hair, though in the horse, for some unknown reason, this does not occur.

The cause of the lack of alopecia response to chemotherapy in the horse is unknown, though Bain speculates that it might be because of the physiology of the growth cycle of the equine hair cells, or to a lack of effect of the drugs used.

Even though the horse's hair coat is unaffected, monitoring of the blood work is most important since these drugs will affect rapidly dividing cells, usually those in the bone marrow, resulting in a low white blood cell count, which creates a susceptibility to secondary infections (pneumonia, diarrhea). The spectre of laminitis loomed as well.

On Aug. 23, Lost in the Fog was walked and given some of the carrots and apples that had been left for him by his many fans.

The horse's health took a turn for the worse, however. Lost in the Fog was humanely euthanized on Sept. 17.

While at University of California-Davis, Lost in the Fog was attended to by a team of veterinarians. Assisting primary overseer Dr. Gary Magdesian, in addition to Dr. Larry Galuppo, are Mary Beth Whitcomb, DVM, Head Equine Ultrasound; Julie Dechant, DVM, MS, DACVS; Dr. Alain Theon, DVM, MS, DACVR, Chief of Equine Radiation and Medical Oncology; and residents Johnathan Anderson, BVM&S; Carrie Finno, DVM; and Emily Haggett, BVSc.

Those that worked with Lost in the Fog pointed out that his heart was key to his treatment.

"The fact that he is bright and bold despite his medical condition," Magdesian says, "is probably the same quality that allowed him to become such a great racehorse."

Investigating cancer

Take the Reins Foundation, Inc. is a private foundation dedicated to funding new research, study, diagnosis, prevention and treatment of cancer in horses.

The Foundation was established in recognition and remembrance of Chili, a favored Thoroughbred that came to the Center of Comparative Oncology at Virginia Tech. Chili was the first horse on a clinical trial of a novel treatment for malignant melanoma. This clinical trial was done in collaboration with scientists at the Comprehensive Cancer Center at Wake Forest University. Chili died of complications from multicentric malignant melanoma in October 2005. The foundation was established to continue the fight that was inspired by Chili's case to try to develop new therapies for a devastating form of cancer that routinely kills horses (and people).

Those people who knew Chili "have put their faith in us to study, to learn to fight cancer with relentless determination and not to accept defeat," states Dr. John Robertson, director, Center for Comparative Oncology, Virginia Tech College of Veterinary Medicine.

Take the Reins Foundation President Karen Witter, says that "the Foundation seeks to help provide funds necessary to engage the personnel, resources and facilities required to carry out the task, primarily by designated gifts and by donations from private donors, grants, corporate sponsors, memberships and contributions from the general public."

Current research at the Center for Comparative Oncology, sponsored in part by the Take The Reins Foundation includes:

• Developing a serum profiling test to diagnose malignant melanoma in horses and to monitor therapy

• Phase I-II clinical trial of a novel botanical oil for treatment of poorly resectable malignant melanomas

• Development of two new drugs for treatment of melanoma and squamous cell carcinoma, including a novel photodynamic molecule

• Search for key gene mutations that lead to transition of locally growing to infiltrative malignant melanomas

• Studies of advanced laser devices to remove infiltrative tumors.

For additional information visit www.takethereins.info or contact Robertson at the Virginia Tech College of Veterinary Medicine.

'Versatile, relaxed and collected;' Lost in the Fog fondly remembered

Lost in the Fog posed in the winner's circle, majestic, relaxed and collected. He had just demolished his foes in the Grade 2 Riva Ridge, on the June 11, 2005, Belmont Stakes day undercard. He was visibly cool, as he had been in the paddock, though it was a muggy 85-degree New York day, and all the other horses were in a full sweat.

"He's a pretty cool customer. He likes his job," noted trainer Greg Gilchrist. "He's your typical surfer kinda dude," said jockey Russell Baze, smiling. "Not too much ever shook him up."

This was his seventh in a string of 10 straight career wins, including the Grade 1 King's Bishop at Saratoga, the Sunshine Millions Dash, the Carry Back, and the Grade 2 Swale, flying at triple-digit Beyer speed figures each time. In 2005, he went coast-to-coast six times to earn the Eclipse Sprint Championship, earning $844,500, though he faltered in his last race, losing the Breeder's Cup Sprint.

Gilchrist purchased Lost in the Fog (Lost Soldier-Cloud Break) for 85-year-old owner Harry Aleo, at the Ocala FL 2YO in training sale. "He was born with a lot of ability, that's obvious," Gilchrist said. "He's good-looking, but there are probably better, bigger, more imposing figures than him; but when you put the total horse together, he's just so well balanced. His movements are fluid, there is no wasted action, everything is all going forward. When you work him, it's amazing, he really doesn't look like he's going anywhere until you look at the stopwatch, and you go, 'Wow, he's really going that fast!' "

Lost in the Fog set a Turf Paradise track record at 6 1/2 furlongs as a 2-year-old in his second start, on Dec. 26, 2004, when he won the Arizona Juvenile by 14 3/4 lengths in 1:13.55. As a 3-year-old, Fog set the Golden Gate track record on May 15, 2005, in a 10-length victory in the Golden Bear Stakes in 1:07.32.

During his 3YO campaign, it was both his ability to travel well and perform at an incredible level that really impressed Gilchrist. "It seemed like he really loved it," he says. The objective was "to keep him sound and keep him happy," then he would perform well. It was not easy, when running in as many quality races a horse has to be 100 percent. "When you take a blood count on Fog, I have never trained a horse that carries a blood count (PCV) that he does. It's almost off the charts—it's unbelievable."

After his successful year, Gilchrist sent him to Ocala to languish out the winter for a little R&R, away from the rigors of racing, and a shot of rejuvenation in the Florida sun.

During 2005, Lost in the Fog seemed just that, unbeatable. Early in 2006, a noticeable chink seemed to appear in his armor. In his first outing, at his home Golden Gate Fields, Fog lost by more than three lengths to Carthage. He came back, winning the Aristides at Churchill Downs on June 3. But on July 15, on his return to Calder Racecourse in Miami, he was a badly beaten, finishing ninth.

"It was unusual that although he got bumped a little bit at the start, and though he was running comfortably, half way around the turn I had nothing," Baze stated. "It was just real unusual, even in the Breeder's Cup (October 2005), he got me to the eighth pole, before he ran out of steam that day. It was very unusual for him not to show me any kind of run at all, that early in a race."

Quarter crack problems and foot soreness were thought to be the source of his early 2006 racing setbacks, but his lack of response in the Smile at Calder raised concerns. In early August Gilchrist and Oleo decided to retire him to stud. Once lymphoma was found, it significantly changed the plan.

Lost in the Fog was vanned back to his home stall at Golden Gate Fields, where he spent time with the people who cared for him most — his groomer, trainer and especially his owner, Harry Aleo.

"My heart goes out to Harry," said jockey Russell Baze. "He has to be hurting pretty bad right now. This is a very important animal to him; he really got connected with this horse."

Baze has ridden many incredible horses, with similar victories, but he has a special bond with Lost in the Fog.

"He is a special horse. He was a real easy horse (to ride), he made my job very easy," says Baze.

Fast, yet relaxed is how this Thoroughbred was described.

"He'd be cruising on the lead, maybe going 22 (seconds/quarter-mile), while every other horse would be struggling to go that fast, but he'd just be going along with his ears pricked, doing it very easily," Baze proudly exclaimed.

Horses with his talent, temperament and athleticism, that are able to ship all over the country and run on several different track surfaces, are rare.

Fog is a playful, studdish horse.

"Anyone that has ever handled him has a mark on them, a 'Lost in the Fog' tattoo," Gilchrist remarks. "His worst habit is that he will bite. If he thinks he can get you, he will."

He would bite you if given a chance," echoes Baze. "On the track, he never got excited or antsy going into the gate, but he wasn't above taking a bite out of the pony, or the pony-girl or the groom or anybody that would get within reach. He wasn't real mean about it, he'd just every now and then reach over and remind everybody that he was a stallion."

Everyone within Thoroughbred racing became enamored of him. Lost in the Fog was a champion. He was powerful, efficient. He moved amazingly fast across the racetrack. Those close to him and his fans will miss him on the racetrack, though Thoroughbred racing was lucky to have him while it did.