A review of tumour lysis syndrome with targeted therapies and the role of rasburicase

What is known and Objective: Tumour lysis syndrome (TLS) is an oncologic emergency with potentially devastating consequences classically associated with cytotoxic chemotherapy. In recent years, molecularly targeted drugs have assumed an increasingly important role in cancer therapeutics. The possibility of TLS is often overlooked in this setting. Rasburicase, a recombinant urate oxidase, is remarkably effective in treating hyperuricemia, thought to be central to the pathogenesis of renal injury in TLS. Our objective is to review the literature on TLS especially as it pertains to targeted therapies and summarize current knowledge and provide future directions regarding the role of rasburicase in the management of TLS. Methods: A MEDLINE search was conducted using PubMed and the keyphrase ‘tumor lysis syndrome’ to identify articles describing TLS with a broad range of novel anti‐cancer agents. Meeting abstracts were also reviewed. Additionally, the biomedical literature was searched using the keyword ‘rasburicase’. Results and Discussion: Tumour lysis syndrome has been described with nearly every class of ‘targeted therapy’. This is not surprising as any drug causing death of cancer cells by any mechanism may lead to TLS in the appropriate setting. Although there is a wealth of evidence suggesting that rasburicase is extremely effective in correcting hyperuricemia, prospective trials showing that it improves hard outcomes such as acute renal failure, need for dialysis and mortality are lacking. Furthermore, much lower doses and durations of therapy than approved appear to be effective in controlling hyperuricemia, potentially leading to enormous cost savings. What is new and Conclusion: Any effective cancer therapy can lead to TLS. Physicians should consider the risk of TLS on a case‐by‐case basis and determine appropriate prophylaxis. The role of rasburicase continues to evolve. Randomized controlled trials evaluating clinically relevant outcomes are needed.     

Single-dose rasburicase for tumour lysis syndrome in adults: weight-based approach

Background: The optimal rasburicase dose for adult patients has not been determined. Objective: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. Method: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome‐associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. Result: Twenty‐one patients received rasburicase with an average first dose of 0·15 ± 0·03 mg/kg. The drug dosing was calculated based on the patients’ ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89·7 ± 9·0% from the baseline through the first 24 h after a single rasburicase dose (11·4 ± 4·5 mg/dL vs. 1·4 ± 1·4 mg/dL, respectively, P < 0·001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer’s recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24–72 h after the single rasburicase dose were not significantly different from baseline (1·8 mg/dL vs. 2·3 mg/dL, respectively, P = 0·14). Conclusion: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia‐associated nephrotoxicity. From our experience, a single dose of 0·15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h.     

Chronic myelomonocytic leukaemia after platinum-based therapy for non-small cell lung cancer: case report and review of the literature

Chronic myelomonocytic leukaemia (CMML) is a preleukaemic condition with myeloproliferative features, and classified as a part of myelodysplastic syndrome (MDS). Other than alkylating agents and topoisomerase II inhibitors, there is less evidence that chemotherapeutic drugs are associated with therapy-related CMML, acute leukaemia or MDS. We present a patient who developed CMML within 2 years of platinum-based chemotherapy for a metastatic non-small cell lung cancer. He received a cumulative dose of 240 mg/m(2) of cisplatin, and 1123 mg/m(2) of carboplatin before developing CMML. The cytogenetic study revealed trisomy 8. This is the first reported case that links platinum-based therapy with development of CMML with trisomy 8. Although the relationship between platinum therapy and the development of CMML is difficult to assess due to combinational nature of therapy in most cases, physicians should consider the possibility of CMML in patients with symptoms or signs suggestive of haematologic malignancy after platinum therapy.     

Tumor lysis syndrome after starting treatment with Gleevec in a patient with chronic myelogenous leukemia

Chronic myelogenous leukemia (CML) is one of the myeloproliferative disorders. It accounts for 15–20% of all leukemias in adults. The mainstay of diagnosis is the detection of Philadelphia chromosome or one of its products. Tyrosine kinase inhibitors changed the paradigm of treating such disease with the good responses. However, they do have side effects. In our case we will report tumor lysis syndrome happening after starting Imatinib myselate. We did a literature review and looked all the cases that documented this complication.     

牙源性颗粒细胞瘤1例报道并文献复习

目的 探讨牙源性颗粒细胞瘤的病理组织学特点、诊断及鉴别诊断。方法 应用光镜、免疫组化对1例牙源性颗粒细胞瘤手术切除标本进行组织学观察。结果 其组织学特点是大量的颗粒细胞排列紧密，周围有多个散在的牙源性上皮条索和团块，有的团块中央可见均质状嗜酸性物。vimentin、CKl9和S-100呈不同程度的阳性反应。结论 牙源性颗粒细胞瘤是一种罕见的肿瘤，根据组织学特点，结合免疫组化染色，可以做出明确诊断。     

Intersection syndrome: a case report and review of the literature

Intersection syndrome is a condition that should be differentiated from DeQuervain’s stenosing tenosynovitis, as there are many subtle differences in treatment and prognosis. We present a case of intersection syndrome, describing its characteristic clinical and anatomic features, and highlighting differences in the areas of diagnosis and treatment relative to the better known DeQuervain’s tenosynovitis.     

Marked hyperuricemia with acute renal failure: need to consider occult malignancy and spontaneous tumour lysis syndrome

Spontaneous tumour lysis syndrome (TLS) is an extremely uncommon cause for acute renal failure (ARF). ARF presenting with hyperkalemia, hyperuricemia and hyperphosphatemia should lead to further work up for occult haematological malignancy. We describe two cases of lymphoma presenting with ARF secondary to spontaneous TLS. The ARF in the first case appeared to be due to intravenous volume depletion but eventually lead to the diagnosis of gastric lymphoma. The second patient is interesting as he is probably the first reported case of lymphoma with HIV infection presenting as spontaneous TLS. Early diagnosis and prompt renal replacement therapy does not necessarily reverse the ARF.     

Tumor lysis syndrome: A clinical review

Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders,use of uric acid lowering agents and dialysis in refractory cases.     

超声诊断胆道闭锁脾脏畸形综合征1例

患儿男,3个月,主因"自生后黄疸进行性加重,大便色浅近白色,小便进行性颜色加深"就诊.查体见腹壁静脉曲张.超声见:肝脏呈水平横位,大部分位于左上腹,右肋下未及.肝脏被膜欠光滑,内部回声粗糙.肝脏内门脉血管纤细.第一肝门位置偏左,于此处反复探查可见一外形僵硬的胆囊,大小2.3 cm×0.4 cm×0.5 cm.胆囊内壁不光滑呈"小波浪"状.禁食与喂奶2 h后两次探查胆囊的大小形态均未见明显改变.     

Laparoscopic approach in the treatment of splenic angiolipomatous hamartoma: the first report of a case

Angiolipomatous hamartoma is a benign mesenchymal proliferation of unknown aetiology. Only a few cases have been documented in the published literature. This current case report describes a 57-year-old female patient who was hospitalized for an assessment of a previously radiologically-verified splenic lesion and further treatment. The patient had been surgically treated 10 years previously; a lobectomy of the superior left pulmonary lobe had been performed in order to remove a verified tumour lesion. A complete radiological examination was undertaken, which verified a spleen of a size that was within the physiological range, with a centrally-located lobular tumour lesion. Given the risk of splenic rupture, as well as the fact that the lesion’s aetiology was still undetermined, and finally the fact that differential diagnostics indicated the possibility of a metastasis, the patient was treated surgically. Laparoscopic splenectomy, in the treatment of splenic diseases, even rare ones such as this, is not a novelty. Indeed, it needs to be applied as the standard approach, with the well-known benefits that the minimalized approach offers.     

Fryns syndrome: case report and review of the literature

Fryns syndrome (FS) is a rare malformation. We report a case of FS referred to our clinic at 27 weeks' gestation with a diagnosis of congenital diaphragmatic hernia. Sonographic examination of the fetus revealed a left-sided diaphragmatic hernia, pulmonary hypoplasia, and a median orofacial cleft. The diagnosis of FS was made after exclusion of chromosome aberrations and delivery of the fetus. Macroscopic inspection revealed a coarse face (hypertelorism and broad and flat nasal bridge, anteverted nostrils, median cleft lip/palate, poorly shaped auricles with attached earlobes, facial hirsutism), a narrow thorax, nail hypoplasia, and hypoplastic, widely spaced nipples.     

Nutcracker syndrome accompanied by hypertension: a case report and literature review

Nutcracker syndrome (NCS) refers to characteristic clinical symptoms that develop secondary to the nutcracker phenomenon (NCP), defined as compression of the left renal vein between the superior mesenteric artery and the aorta. A 22-year-old Chinese man presented with a 2-year history of hypertension and left flank pain after activity; his blood pressure fluctuated within 130–150/90–100 mmHg without treatment. He had microscopic hematuria (2+) and increased plasma renin activity. The findings of both color Doppler ultrasound and computed tomography angiography were consistent with a diagnosis of NCS. The patient had no history of familial hypertension or special medications. Secondary hypertension-related examinations showed no significant abnormalities. After placement of an endovascular stent in the left renal vein, normal blood flow resumed and the collateral circulation was reduced. Both the hypertension and flank pain were alleviated within 3 days after the intervention and did not reappear during the following 11 months. NCP/NCS accompanied by hypertension is very rare. The possibility of NCP/NCS should be considered when secondary hypertension cannot be explained by other factors. The mechanism by which hypertension is caused by NCP/NCS is rather complex and deserves further investigation.     

Short QT syndrome: a case report and review of literature

The short QT syndrome has been recently recognised as a genetic ion channel dysfunction. This new clinical entity is associated with an incidence of sudden cardiac death, syncope, and atrial fibrillation in otherwise healthy individuals. The distinctive ECG pattern consists of an abnormally short QT interval, a short or even absent ST segment and narrow T waves. A 30-year-old resuscitated woman with short QT syndrome is described together with an example of the classic ECG characteristics. A short-coupled variant of torsade de pointes was reveal on Holter recordings. The implantable cardioveter defibrillator seems to be the therapy of choice to prevent from sudden cardiac death. Quinidine proved to be efficient in prolonging the QT interval and rendering ventricular tachyarrhythmias non-inducible in patients with a mutation in KCNH2 (HERG). Our preliminary data suggest amiodarone combined with beta-blocker may be helpful in treating episodes of polymorphic ventricular tachycardia for patients with an unknown genotype. Because the short QT syndrome often involves young patients with an apparently normal heart, it is imperative for physicians to recognize the clinical features of the short QT syndrome in making a timely correct diagnosis.     

Atraumatic splenic rupture in a patient treated with rivaroxaban: A case report and a narrative review

Atraumatic splenic rupture (ASR) is a rare condition mostly associated with neoplastic, infectious, and inflammatory diseases. ASR associated with drug treatment is even rarer. In this case report, we highlight an unusual complication of the direct oral anticoagulant rivaroxaban. A 64‐year‐old male patient was admitted to the emergency department with complaints of faintness and diffuse abdominal cramps. The patient had no history of recent trauma. Clinical examination revealed hemodynamic instability with a moderate response to filling and mild abdominal discomfort on palpation. His medical history included chronic hypertension, constipation, and recent atrial flutter ablation. The patient was taking amiodarone, bisoprolol, atorvastatin, and rivaroxaban. Splenic rupture was diagnosed several hours later on contrast‐enhanced abdominal computed tomography scan. Massive blood transfusions and emergency laparotomy for splenectomy were performed. Anatomopathological analysis did not reveal any neoplastic, inflammatory, or infectious causes. The patient was successfully discharged from the intensive care unit 3 days later. Clinicians must consider the possibility of ASR as a complication of rivaroxaban in patients with abdominal tenderness and hemodynamic instability. Unfortunately, clinical presentation is not always typical of a ruptured spleen. Delayed diagnosis can be life threatening or fatal. Splenectomy via laparotomy remains the best therapeutic option in cases of splenic rupture in unstable patients on direct oral anticoagulants.     

Deferasirox in a refractory anemia after other treatment options: case report and literature review

Deferasirox, represents an effective iron chelator drug in lower risk myelodysplastic syndromes. Reduction in oxidative stress is responsible of the hematologic improvement but further explanation may impact on its benefit. Biological and clinical studies are necessary to better define mechanisms of action, assess toxicities, and predicting factors of response.     

Gitelman综合征1例及文献复习

<正>Gitelman综合征(GS)是一种常染色体隐性遗传的失盐性肾小管疾病,以"五低一高"和代谢性碱中毒,即低血钾、低血镁、低血氯、低尿钙、偏低血压和肾素-血管紧张素-醛固酮系统(RAAS系统)活性增高为典型临床表现[1]。临床上该病较为少见,易漏诊、误诊。现报道南京医科大学第二附属医院诊治的1例GS。1 病历资料患者,女,50岁,已婚,汉族,江苏高邮人,因"反复乏力、头晕1年"于2019年2月11日入院。患者1年前因急性胃肠炎腹泻     

Mercury as a cause of membranous nephropathy and Guillain–Barre syndrome: case report and literature review

Secondary renal involvement in chronic exposure to metallic mercury is well known. Mercury also causes central nervous system damage and demyelinating polyneuropathy. Here, we describe a case of a patient with daily exposure to mercury in skin lightening cream and hair dyes who was diagnosed with Guillain–Barre syndrome and then developed nephrotic syndrome because of membranous neuropathy. By reviewing the literature describing mercury-associated diseases, we found that mercury components have an immunomodulatory activity, which is also involved in both peripheral neuropathy and glomerulonephritis.