实体瘤溶解综合征

肿瘤溶解综合征是血液系统肿瘤治疗中常见的并发症,但在实体瘤中较少见,其发病隐匿,极易误诊、漏诊,预后差.实体瘤溶解综合征典型的临床特征为高尿酸血症、高钾血症、高磷血症和低钙血症,并发症主要为急性肾功能衰竭和心律失常.对高危患者进行预防性干预、早期诊断和积极治疗是改善预后的关键.本文回顾既往文献报道的87例实体瘤溶解综合征,对其发病情况、预防和治疗进行综述.     

Acute tumor lysis syndrome in a hemodialysis patient with diffuse large B cell lymphoma

Acute tumor lysis syndrome (TLS) is a life-threatening complication of cancer therapy requiring prompt recognition and aggressive management. It occurs particularly in patients with lymphoproliferative disease during potent myelosuppressive therapy. To our knowledge, acute TLS in end-stage renal disease (ESRD) patients with malignancy is extremely rare and has never been reported in English literature. We report the first case of acute TLS in an ESRD woman with diffuse large B cell lymphoma after chemotherapy. Aggressive treatments with daily hemodialysis and allopurinol rather than hydration benefit the patient. There is neither optimal therapy in treating ESRD patients with TLS nor adequate guidelines for how to adjust the chemotherapy drug in hemodialysis patients. This case provides our experience to clinician how to treat acute TLS in ESRD patients.     

Acute tumor lysis syndrome in solid tumors—a case report and review of the literature

PURPOSE: Tumor lysis syndrome (TLS) is a potential complication in cancer therapy. It may occur in highly sensitive tumors, especially in childhood cancers and acute leukemias, whereas it is rare in the treatment of adult solid tumors. TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia following massive lysis of malignant cells. Complications include acute renal failure and metabolic acidosis. We report the first case of TLS during chemotherapy in a patient with metastatic medulloblastoma, together with a review of the literature regarding the occurrence of TLS in patients with solid tumors. METHODS: Data regarding clinical and biochemical parameters were extracted from the actual patients' files. Reports of TLS in the English language literature up to 2002 were identified by searching Medline. RESULTS: A 23-year old male with metastatic medulloblastoma received chemotherapy with cisplatin and etoposide due to massive extracerebral manifestations including metastases to the liver, mediastinal lymph nodes and bone marrow metastases. The patient developed classical signs of TLS on the second day of chemotherapy, including acute renal failure. A 17-fold increase in plasma LDH up to 87608 U/l was observed together with a 4-fold increase in plasma creatinine. The patient was treated with aggressive hydration, allopurinol and repeated hemodialysis. During the following days the patient improved and the biochemical markers all returned to normal. REVIEW. Reviewing the literature, a total of 45 patients with solid tumors who developed TLS have been reported. Most of the patients presented with metastatic, therapy-sensitive disease. Although preventable in practically 100% of patients, TLS is a potentially fatal complication, and in this material the mortality rate was one in three. Risk factors included increased LDH, hyperuricemia and pretreatment azotemia. CONCLUSIONS: TLS is only rarely associated with treatment of solid tumors. Precautions should be taken to avoid this potentially fatal complication in (chemo)therapy of solid tumors, especially in therapy-sensitive tumors presenting with bulky, metastatic disease and preexisting risk factors, including azotemia, elevated LDH and hyperuricemia. Prophylactic treatment to avoid TLS includes allopurinol, hydration prior to treatment and alkalization of the urine. Urate oxidase (rasburicase) is now beginning to replace allopurinol as a more effective way of reducing hyperuricemia and thereby the risk of TLS.     

The management of tumor lysis syndrome

The manifestation of tumor lysis syndrome (TLS) occurs when the destruction of tumor cells releases breakdown products that overwhelm the excretory mechanisms of the body. A cardinal sign is hyperuricemia, leading to uric acid nephropathy. Other signs are hyperkalemia, hyperphosphatemia and secondary hypocalcemia. Conventional management of TLS consists of aggressive intravenous hydration, diuretic therapy, urinary alkalization, and inhibition of urate production by high-dose allopurinol. Urate oxidase has been used in the management of patients at risk for TLS and recently the recombinant urate oxidase rasburicase was developed. Several data indicate that rasburicase is effective and well tolerated in the prevention and treatment of chemotherapy-induced hyperuricemia. Treatment options of hyperkalemia include sodium polystyrene sulfonate, hypertonic glucose and insulin, loop diuretics, and bicarbonate. Treatment of hyperphosphatemia reduces dietary phosphate intake and includes phosphate binders such as aluminum hydroxide and aluminum carbonate. When recurrent hypocalcemia is present, a continuous intravenous infusion of calcium gluconate can be initiated. Hemodialysis should be considered for every patient with excessively elevated uric acid, phosphate and/or potassium and in those patients with acute renal failure to control urinary volume and manage uremia.     

原发性肝癌行肝动脉化疗栓塞术后的并发症及其分析

目的 探讨原发性肝癌行经导管肝动脉化疗栓塞术(TACE)后的严重并发症,分析其原因和防治方法.方法 对573例原发性肝癌患者行TACE 1252次,针对术后发生的并发症进行影像学及化验检查,总结发生严重并发症的原因及其治疗、预防措施.结果 共发生上消化道出血3例,肝衰竭4例(其中死亡1例),肺栓塞1例,栓塞性胆囊炎4例,肝性脑病2例,胃穿孔后死亡1例,胆汁瘤2例.结论 原发性肝癌经TACE治疗后出现的严重并发症与患者术前肝功能较差、门静脉高压、术中化疗栓塞药物量大、药物返流及异位栓塞等有关.重视术前病例的选择,术中规范操作,尽可能超选择插管给药,术后加强护肝治疗和保护胃黏膜治疗,密切注意病情变化,可减少或防止TACE后严重并发症的发生.     

Tumour lysis syndrome in children: experience of last decade

The strategy against tumour lysis syndrome (TLS) had been hyperhydration, urine alkalinization, and allopurinol. Recently, rasburicase was added to the armament against this life-threatening condition. In Korea, rasburicase is used as a rescue therapy for cases with allopurinol-resistant hyperuricemia, because of the restriction by the National Health Insurance. We reviewed our experiences to re-assess the risk factors of TLS and the efficacy of rasburicase. Medical records were retrospectively reviewed for 396 children who were diagnosed as positive with acute leukemia and non-Hodgkin lymphoma between the years 2000 and 2009. The risk factors for TLS were analyzed statistically, and those before and after the availability of rasburicase were compared. Sixty eight patients (17.2%) had TLS. Multivariate analysis showed that pre-chemotherapy hypophosphatemia was a risk factor for TLS, in addition to the known risk factors of hyperuricemia and high lactate dehydrogenase concentration. The availability of rasburicase as a rescue therapy did not negate the importance of uric acid as a risk factor of TLS. Rasburicase as a second line treatment for intractable hyperuricemia was not effective in reducing the incidence of TLS. Pre-chemotherapy hypophosphatemia was a significant independent risk factor for TLS.     

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents

Tumor lysis syndrome (TLS) is an uncommon but potentially life‐threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B‐cell lymphoma‐2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.

Implications for Practice

Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.     

Diagnosis, prevention and treatment of renal lesion in extracorporeal shock wave lithotripsy

The diagnosis and treatment of 120 patients with urolithiasis were made. The following examinations were made: the study of immune status and lipid peroxidation, detection of selective proteinuria, leukocyte migration inhibition reaction with autoantigens obtained from the tissues of the renopelvic segment providing additional information about renal parenchyma and immune system. The patients were divided into two groups: 70 patients of the study group received pre-, intra- and postoperative preventive pharmacotherapy, while 50 patients of the control group received standard therapy. It is shown that preventive measures in the patients of the study group aimed at raising resistance of the kidney to the shock wave and prevention of infectious-inflammatory process evidence for necessity of the above measures not only before extracorporeal shock wave lithotripsy, but also in intra- and postoperative periods.     

Erectile dysfunction following radical therapy for prostate cancer.

With the earlier detection of prostate cancer and the increasing demand for treatment of organ-confined dizease, quality of life issues are becoming more important. Development of erectile dysfunction (ED) following radical therapy is a particular concern, and occurs in perhaps a third of patients treated by radiotherapy and 30-70% of patients treated by radical prostatectomy. Although it is assumed that the ED relates to damage to the nerves subserving erection, this view has been questioned recently and in at least a proportion of patients the cause appears to be vascular. Despite the likely cause of their ED, all patients presenting with ED after treatment for prostate cancer should undergo assessment by history and examination to ensure that there are no other correctable risk factors. Patients can then be considered for a number of treatment options, and currently sildenafil (Viagra, Pfizer) is usually used as first-line therapy assuming there are no contraindications, such as severe ischaemic heart disease or nitrate therapy. Sildenafil improves erectile function in 70% of patients with ED post-radiotherapy, but appears less effective in men after radical prostate surgery with a response rate of 40-50%. Other treatment options include self-injection or intra-urethral administration of alprostadil, and some patients are happy to use a vacuum erection device. Finally, if all else fails, patients may be suitable for penile implant surgery.     

Clinical approach to infection in patients with hematologic malignancy]

Patients with hematologic malignancy are susceptible to infection because of the disease process and its treatment. Profoundly granulocytopenic patients are at increased risk of developing Pseudomonas aeruginosa bacteremia, often with a fatal outcome. Therapy with one or two anti-pseudomonal beta-lactam antibiotics and an aminoglycoside in combination that were effective in vitro against the infecting organism proved to be superior, by one-week survival, to therapy with either one in vitro effective beta-lactam or aminoglycoside or inadequate drugs. On the other hand, treatment with granulocyte colony-stimulating factor had no significant association with longer survival, although a favorable outcome was well correlated with an increase in the granulocyte count during therapy. An active mycobacteriosis was documented in 2% of all patients with hematologic malignancy. Dissemination occurred in half of them. The prognosis of tuberculosis was depended mainly on early diagnosis and treatment, while that for the atypical variety was largely influenced by the underlying disease. The frequency of deep fungal infection in patients with acute leukemia at autopsy increased progressively from 10% in 1970-1974 to 38% in 1983-1986, but it decreased somewhat to 29% in 1987-1989 after the introduction of empiric amphotericin B therapy in 1986. Early empiric antifungal therapy should therefore be started in granulocytopenic patients with fever refractory to antibacterial therapy, because of unreliability of the current serodiagnosis. A total protective isolation for patients undergoing bone marrow transplantation (BMT) was associated with a reduced incidence of pneumonia, especially due to Aspergillus, and to a lesser extent, bacteremia. Cytomegalovirus pneumonia complicating BMT continues to have a poor prognosis, although the frequency has gradually been decreasing with the introduction of effective preventive measures. An early diagnosis and treatment as well as preventive measures is thus necessary for infection control in patients with hematologic malignancy.     

Current concepts of treatment strategies in advanced or recurrent ovarian cancer

Ovarian cancer is the fifth most common cause of death from cancer in women. The standard first-line treatment for advanced ovarian cancer is a combination of paclitaxel and carboplatin or carboplatin alone. Sequential single-agent therapy is of particular interest in patients with symptom-free disease progression. Age, performance status and treatment preferences of the respective patient are further decisive factors which should be taken into account when selecting single or combination therapy. Second-line treatment depends, for instance, on the duration of response to first-line platinum therapy, previous treatment regimens used, tolerability, the patient's performance status and preference of a particular treatment, and cost-effectiveness. If tumor recurrence occurs within 6 months following platinum-based therapy, other agents such as paclitaxel, pegylated liposomal doxorubicin, topotecan or gemcitabine should be used. If the tumor recurs after 6 months, a combination therapy of platinum and paclitaxel has proven to be the most effective. Reasonable options in progressive disease are treatment with platinum, either alone or combined with other agents, especially investigational compounds.     

Management of tumor lysis syndrome in adults

Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS. However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. With the increased intensity and efficacy of cancer therapies, novel approaches for the management of TLS are needed. Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion. A recombinant form of urate oxidase, rasburicase, is now registered for the treatment and prevention of TLS. This review provides an overview of rasburicase development and discusses the impact of rasburicase in the prevention and management of TLS.     

Spontaneous tumor lysis syndrome in a patient with cholangiocarcinoma

Tumor lysis syndrome (TLS) is a potentially deadly complication of tumors or their treatment. This syndrome consists of a constellation of laboratory parameters such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and clinical complications such as seizures, acute renal insult, cardiac dysrhythmias and death. TLS is especially common in patients with hematological malignancies with rapid cellular turnover rates such as acute lymphocytic leukemia and Burkitt lymphoma, but is very rare in patients with solid tumors. However, it is essential to keep in mind that solid tumors can also lead to TLS. We present a case of a 66-year-old African American male with metastatic cholangiocarcinoma complicated by the development of spontaneous TLS. TLS has never been reported in a patient with cholangiocarcinoma.     

Management of tumor lysis syndrome in adults

Spontaneous or treatment-induced tumor lysis syndrome (TLS) can cause significant morbidity and potential mortality. Vigorous hydration, alkalinization and inhibition of uric acid synthesis with allopurinol are the most frequently used methods for treatment and prevention of TLS. However, this approach fails to prevent renal insufficiency in up to 25% of high-risk patients. With the increased intensity and efficacy of cancer therapies, novel approaches for the management of TLS are needed. Unlike allopurinol, urate oxidase promptly reduces the existing uric acid pool, prevents accumulation of xanthine and hypoxanthine and does not require alkalinization, facilitating phosphorus excretion. A recombinant form of urate oxidase, rasburicase, is now registered for the treatment and prevention of TLS. This review provides an overview of rasburicase development and discusses the impact of rasburicase in the prevention and management of TLS.     

Bortezomib-induced tumor lysis syndrome in multiple myeloma

Tumor lysis syndrome (TLS) is exceedingly rare in multiple myeloma because of the relatively slow proliferation and response of the malignant cells. Bortezomib is a novel agent that inhibits proteasome and has shown activity against multiple myeloma. We report 8 episodes of TLS seen in 7 patients with bortezomib therapy, with or without dexamethasone, among 496 patients treated on 3 phase II multicenter studies. Biochemical abnormalities resolved with supportive therapy in 6 patients (including hemodialysis in 2) but proved fatal in 1. Clinicians should be alert for TLS in patients with myeloma with significant disease burden treated with bortezomib because of the potential for rapid onset of cell lysis with this agent.     

食管及贲门癌手术少见并发症临床分析

  目的  总结食管及贲门癌手术少见并发症的诊断及治疗体会,吸取其诊断失误、治疗失败的教训。  方法  回顾性分析少见并发症的发病原因、临床诊断、处理方法、预防措施及其中治疗失败的相关因素。  结果  治愈及死亡分别为10例及8例（除外已报道的8例）。  结论  1）该文所述的并发症虽然少见,但临床上时有发生,若处理不当,常造成严重后果;2）对主动脉食管固有支撕脱性损伤的喷射状出血,术者要沉着、冷静,只要处理方法正确,损伤口均可以修补成功;3）右胸径路是预防奇静脉损伤的关键措施;4）吻合口腹内瘘的患者,若早期漏出感染物包裹于膈下,容易延误诊断;5）吻合口主动脉瘘,关键在于预防;6）警惕术后肺动脉栓塞的发生,提高其防治意识;7）胸胃纵隔疝若不及时处理,预后较差。      

Recombinant urate oxidase for prevention of hyperuricemia and tumor lysis syndrome in lymphoid malignancies

Hyperuricemia is a common manifestation of lymphoid malignancies at diagnosis or after the start of chemotherapy. When accompanied by other metabolic abnormalities and/or organ failure, hyperuricemia may be a manifestation of tumor lysis syndrome (TLS). Patients at particularly high risk of such complications include those with acute lymphoblastic leukemia and advanced stage non-Hodgkin's lymphoma. Conventional measures to prevent hyperuricemia and TLS are comprised of hydration, alkalinization of body fluids, and administration of allopurinol. Although these measures are usually effective in preventing or managing hyperuricemia, approximately 20% of patients at high risk of TLS require dialysis, and many cannot receive chemotherapy as planned. Rasburicase, a recombinant form of the enzyme urate oxidase, has recently become available and may further reduce the morbidity of hyperuricemia and TLS. In this review, we provide an overview of hyperuricemia and TLS and discuss the impact of rasburicase in the overall management of these complications.     

Transoral laser surgery for laryngeal cancer: outcome, complications and prognostic factors in 275 patients

AIM: Curative treatment options for laryngeal carcinoma include primary radiation therapy, open surgical techniques and transoral laser surgery (TLS). In the last decade, TLS has become an important tool in the treatment of laryngeal cancer and has become the standard approach in many institutions. The aim of this study was to review the experience of a single center institution with TLS for early and advanced laryngeal cancer. METHODS: We retrospectively analyzed 275 patients who underwent TLS in regard to the survival outcome and surgical complications. RESULTS: The 5-year disease-free survival estimate was 90.3% and the 10-year disease-free survival estimate was 88.2%. The 5-year larynx preservation rate estimate was 88.2% and the 10-year larynx preservation rate estimate was 87.3%. The disease-free survival was significantly worsened by the variables T and N (p=0.0003; p<0.001, respectively). Two percent of all patients required intraoperative tracheostomy and the rate of minor postoperative complications was 17%. There were no fatal complications. CONCLUSIONS: We conclude that TLS is a valid treatment method for early laryngeal carcinoma. Selected cases of advanced carcinomas may also benefit from TLS.     

Treatment of relapses in juvenile acute lymphoblastic leukemia]

Recurrence of childhood acute lymphoblastic leukemia occurs in about 30-50% and indicates irresistable progression of the disease. While systemic (= hematologic) relapse is due to drug resistance of leukemic cells, pharmacologic barriers may be responsible for local relapses as meningeal involvement, leukemic ophthalmopathy or testicular infiltration. L-asparginase seems to be an important component of drug combinations for re-induction therapy for systemic relapse. Following reinduction therapy modification of continuation therapy is necessary. Local relapses require local treatment, i.e. radiotherapy and e.g. intrathecal drug application. Local relapse is almost always followed by hematologic relapse. Therefore, intensification of systemic therapy is also recommended. Prevention of these relapses is much more important and probably more successful than treatment. Therefore, initial therapy should include preventive measures for pharmacologic sanctuaries.     

Tumor lysis syndrome after treatment with gemcitabine for metastatic transitional cell carcinoma

Tumor lysis syndrome is a set of life threatening complication that can arise from treatment of high tumor burden, drug sensitive, and rapidly proliferating neoplasm particularly of hematological origin. It is rarely described in patients with solid tumors. We report the first case of tumor lysis syndrome in a man with metastatic renal pelvic transitional cell carcinoma after gemcitabine treatment. Despite aggressive therapy, he died 2 weeks after TLS was diagnosed. Our experience demonstrates that administration of gemcitabine for metastatic renal pelvic transitional cell carcinoma may induce acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and prompt initiation of appropriate therapeutic measures.