"Have you seen such a patient? He was in his youth and for no reason, he suddenly became several centimeters shorter in one year and felt uncomfortable all over. He went through many hospitals for several years and spent a lot of money, but he could not be cured. Instead, he became heavier and heavier, and his height became shorter and shorter, but he couldn't find the real root cause." As soon as we met, Professor Liu Yong raised questions to the reporter.
"In fact, many of these patients have an extremely rare disease called tumor hypophosphorus osteomyelitis, or hypophosphatemia, referred to as TIO for short. It is caused by a small tumor that may be the size of a soybean and does not know where it is hidden." Professor Liu Yong introduced, "There are currently less than 1,000 cases of this disease worldwide, with outstanding clinical manifestations, including progressive bone pain, limb fatigue, limited movement, shortening of height, pathological fractures, etc., which seriously affect the patient's quality of life. In the early stage of the disease course, it is often misdiagnosed as ankylosing spondylitis, primary osteoporosis, spinal degeneration, etc. If the surgery can be completely removed after accurate and localization, hypophosphatemia can be effectively corrected, the symptoms can be significantly improved, and the patient can return to normal life."
So far, many doctors and patients have insufficient cognition of tumor hypophosphorus osteomyelitis, and the diagnosis process is very difficult. It takes more than five years for patients to go from illness to diagnosis. Not only that, the occult and changeable tumor location and the small tumor body also add many difficulties to the diagnosis and treatment of the disease. The first case of tumor hypophosphorus osteomalacia in China was reported in 1974 by Professor Zhang Xiaoqian, a famous internal scientist at Peking Union Medical College Hospital. Currently, Peking Union Medical College Hospital has become the world's largest comprehensive diagnosis and treatment center for tumor hypophosphorus osteomalacia.
As a center for diagnosis and treatment of difficult and rare diseases, the Department of Endocrinology, Nuclear Medicine, , orthopedics, pathology, radiology, laboratory and other departments of Peking Union Medical College Hospital worked diligently to make outstanding contributions to the improvement of TIO's clinical diagnosis and treatment level. In 2021, TIO's international diagnosis and treatment consensus was organized and compiled by scholars such as Professor Xia Weibo of the Department of Endocrinology of Peking Union Medical College Hospital and Professor Huo Li of the Department of Nuclear Medicine, along with experts from Europe, America, Japan, and South Korea. Professor Liu Yong, chief physician of orthopedics at Peking Union Medical College Hospital, and his team have been engaged in orthopedic surgery for TIO since 2012. So far, more than 300 cases have been completed, the number of surgeries in the world. Liu Yong admitted that many TIO patients have no experience in surgical treatment, no precedent for reference, and the literature cannot find out, "How to treat the patient's treatment effect and bring a better prognosis to the patient? The methods are all figured out by the whole team sitting together, one by one."
Professor Liu Yong, chief physician of orthopedics at Peking Union Medical College Hospital, discussed the diagnosis and treatment plan with his team. Photo by Wang Ying, Beijing News reporter
Customizes a more suitable surgical plan for patients
In clinical practice, Liu Yong encountered a TIO patient who was only 30 years old. Her tumors widely invaded the left knee joint. This situation is rare because most TIO patients have very small tumors. She has been diagnosed by several other hospitals with synovitis and tendon sheath giant cell tumor . She has undergone 3 surgeries before and after. After seeing the patient's medical records, Liu Yong was also in trouble. Tumors are widely distributed in the joints, and tumors are spread throughout the distal femur, proximal tibia, intra-articular and surrounding soft tissues. Generally, amputation is required to ensure that the tumor is completely removed, so that the blood phosphorus can return to normal.
"But she is only 30 years old and is not married yet. What should she do after amputation? Or after the tumor is removed, the patient will install a prosthesis. On the one hand, it is a question whether the legs can survive after installing the prosthesis, because blood vessels and nerves are wrapped in the tumor. Will the blood vessels and nerves be damaged during the tumor removal process? In addition, if the tumor is not removed cleanly and the patient's blood phosphorus level does not return to normal levels, he may still face amputation in the end. This will not only solve the pain, but also bring economic losses. These issues must be considered."
After considering multiple plans, Liu Yong and his team consulted, negotiated, and discussed many times and finally decided to try to help the patient save his legs first, and at the same time avoid unnecessary economic expenses.So, after removing the bones, joints and soft tissue containing the tumor, they did not immediately install the prosthesis. Instead, they temporarily filled the part of the lower limb defect with bone cement to observe whether the nerves and blood vessels remained intact after the operation and whether the lower limbs could survive. At the same time, they observed the recovery of blood phosphorus levels to determine whether the tumor was removed completely. "In the end, the patient's blood phosphorus was normal and the calf could be preserved. We will perform the surgery to place artificial joint for the patient." Liu Yong said happily.
There is also a 28-year-old patient with the tumor located on the tibial platform close to the articular cartilage, and the tumor is relatively small. According to conventional ideas, it is inevitable to remove part of the tibial platform and joint surface when removing the tumor, and artificial joint replacement is performed after removal. However, considering that although artificial joints can be used for many years in theory, they will actually face many problems such as loosening and infection after several years of activity. "This is an important issue for a young man in his twenties. No matter how good the artificial joint is, it is not as good as the original one."
So, Liu Yong's team thought of a new way - percutaneous puncture + bone cement filling and killing. "Bone cement is a polymer compound. During the solidification process, bone cement can produce high temperatures of more than 60 degrees. Injecting bone cement into the tumor body, on the one hand, high temperature can 'kill' tumor cells, and on the other hand, it can also destroy the blood flow of the tumor body. This method is a minimally invasive surgery, which can be done under local anesthesia. Not only is the cost very low, but the trauma is very small. There is no need to destroy the bones and no need to replace artificial joints. It can be put into the ground immediately after the operation." The same minimally invasive method was also used by Liu Yong's team to treat TIO tumors in special parts such as femoral head , femoral neck, sacral , and thus they also innovatively carried out several "first international surgeries".
Among the more than 300 patients treated by Liu Yong's team, in addition to those located in the bones of the limbs, some tumors are located in the spinal region and soft tissues. Especially the spinal region has a complex structure, and tumor removal may bring risks such as spinal instability, reduced spinal mobility, and nerve damage. According to the patient's tumor size and location, Liu Yong's team also designed different surgical plans and successfully cured many patients.
targets one of the difficulties in surgery, that is, it is difficult to accurately locate the tumor during surgery, and Liu Yong's team is also constantly trying to solve these problems. "Although the location of the tumor was discovered through CT, nuclear magnetic field, nuclide imaging and other images, it is another matter during the operation to accurately find the tumor and completely remove it. The bones at the growth of the tumor are almost the same as normal bones. If too much is cut, the bones will be broken, and less is cut, the tumor will not be removed completely, and the patient's blood phosphorus will not rise, and the symptoms will not be relieved." Liu Yong said that with the development of artificial intelligence technology, combining with real technology will help the precise positioning and complete resection of the tumor in the operation. "We are still exploring now. We have used this technology to complete several surgeries from around 2018." Professor Liu Yong, chief physician of orthopedics at Peking Union Medical College Hospital. Photo by Wang Ying, Beijing News reporter
Multidisciplinary collaboration helps rare disease diagnosis and treatment
patients with tumor hypophosphorus osteomyelitis can get a clear diagnosis and reasonable treatment, which can be said to be a lucky thing.
The pathogenic tumor of tumors with tumor hypophosphorus osteomalacia will affect the phosphorus excretion function of the kidneys and cause phosphorus to be excreted in large quantities. Calcium and phosphorus are precisely the very important inorganic salt required for bone metabolism. If there is insufficient phosphorus in the body, calcium metabolism will also occur, and patients will experience varying degrees of osteoporosis . If you suffer from this disease, patients will be tortured by inexplicable pain in the whole body, weak limbs, limited movement, and pathological fractures due to severe osteoporosis and shorten their height. In severe cases, height can be shortened by five or six centimeters a year, or even more than ten centimeters, seriously affecting the quality of life. However, since many people do not understand this disease, delayed diagnosis often occurs and patients cannot receive timely treatment.
The growth location of tumors caused by tumor hypophosphorus osteomyelitis does not have a specific range. The human subcutaneous tissue, limb bones, joints, spine, soft tissue, palms, toes, mouth, internal organs, etc. may all be the growth locations of this tumor.Most of the time the tumor is very small, even the size of a soybean, and it is necessary to combine a variety of diagnostic methods, including ultrasound examination, whole-body magnetic resonance examination, 99Tcm-labeled hydrazine-based octreo-SPECT, 68Ga-DOTA-TATE PET/CT, etc., to determine the location of the tumor. "The growth location of many tumors is difficult to detect when ordinary imaging examinations are performed. Special nuclide imaging and PET/CT are required to detect occult tumors. It is difficult for hospitals to diagnose and treat the disease without these equipment." Liu Yong said.
"Generally speaking, it takes an average of nearly 5 years for patients to get sick to diagnose. When patients come to our hospital, from examination to finalizing the location of the tumor, it is about two or three months. It is not only a department for patients with oncology hypophosphorus osteomyelitis to receive reasonable treatment. The multidisciplinary collaboration model of Peking Union Medical College Hospital has great help in the diagnosis and treatment of the disease, covering decades of hard work by colleagues in multiple departments such as endocrinology, radiology, nuclear medicine, pathology, otolaryngology, dentistry, orthopedics, etc. And efforts are inseparable from the strong support of all aspects of the hospital. "Liu Yong introduced that patients usually suspect that they may be tumor hypophosphorus osteomyelitis after medical history inquiry and various examinations in the endocrinology department, and then they will determine the doctor's judgment after various imaging examinations. After a series of examinations, the location of the tumor is finally determined. According to the location of the tumor, the patient will be assigned to different surgical departments (such as orthopedics, otolaryngology, dentistry, etc.), and the pathologist is also required to finally determine whether the resection tissue is a pathogenic tumor.
The diagnosis and treatment of tumor hypophosphorus osteomyelitis can also be regarded as individualized diagnosis and treatment. Liu Yong told reporters that from the qualitative localization diagnosis of patients, including clinical symptoms, duration of disease, lesion location, etc., to the discussion of surgical plan, pathology determination, postoperative follow-up, etc., the entire process cannot be completed by any department alone, and involves collaboration of multiple disciplines.
"There are not many reported cases around the world with tumor low phosphorus osteomalacia, and the low disease awareness rate is one reason. During routine physical examinations, many people see that the blood phosphorus level is low and they will not consciously go for further examinations. The clinical manifestations of the disease may also be mistaken for treatment as a common orthopedic disease. I hope more people can understand this disease and benefit more patients." Liu Yong said.
Beijing News reporter Liu Xu
proofreading Lu Qian
