Acute liver failure as the initial manifestation of acute leukaemia

Abstract: Background/Aims: Haematological malignancies seldom cause clinically significant liver disease. Acute liver failure as the initial manifestation of acute leukaemia is very rare and carries a very poor prognosis. Methods/Results: Three cases of acute liver failure secondary to acute leukaemia are described. Each case presented initially as acute liver failure of uncertain cause. Specific treatment for the leukaemia was instituted; however, all three patients died as a consequence of the liver failure. We describe the clinical course and relevant investigations of these patients and discuss possible mechanisms of acute liver failure in this setting. Conclusion: Acute leukaemia presenting as acute liver failure has a very poor prognosis. Although a rare cause of acute liver failure, it should be considered in any patient presenting with acute liver failure with prodromal symptoms and a raised peripheral white cell count, lactate dehydrogenase and uric acid.     

Roux-en-Y drainage of a pancreatic fistula for disconnected pancreatic duct syndrome after acute necrotizing pancreatitis

Background

After acute necrotizing pancreatitis (ANP), a pancreatic fistula may occur from disconnected pancreatic duct syndrome (DPDS) where a segment of the pancreas is no longer in continuity with the main pancreatic duct.

Aim

To study the outcome of patients treated using Roux-Y pancreatic fistula tract-jejunostomy for DPDS after ANP.

Methods

Between 2002 and 2011, patients treated for DPDS in the setting of endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopanreatography (MRCP) documented main pancreatic duct disruption with Roux-Y pancreatic fistula tract-jejunostomy.

Results

In all, seven patients with DPDS were treated. The median age was 62 years (range 49–78) and five were men. The cause of ANP was gallstones (2), alcohol (1), ERCP (1) and idiopathic (3). Pancreatic necrosectomy was done in six patients. Time from onset of pancreatitis to fistula drainage was 270 days (164–365). Pancreatic fistulae arose from DPDS in the head/neck (4) and body/tail (3). Patients had a median fistula output of 140 ml (100–200) per day before surgery. The median operative time was 142 min (75–367) and estimated blood loss was 150 ml (25 to 500). Patients began an oral diet on post-operative day 4 (3–6) and were hospitalized for a median of 7 days (5–12). The median follow-up was 264 days (29–740). Subsequently, one patient required a distal pancreatectomy. After surgery, three patients required oral hypoglycaemics. No patient developed pancreatic exocrine insufficiency.

Conclusion

Internal surgical drainage using Roux-en-Y pancreatic fistula tract-jejunostomy is a safe and definitive treatment for patients with DPDS.     

Acute myeloid/T‐lymphoblastic leukaemia (AMTL): a distinct category of acute leukaemias with common pathogenesis in need of improved therapy

Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T‐lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T‐lymphoid lineages, such as myeloperoxidase and CD3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia (AML) harbour hallmarks of T cell development, such as T‐cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T‐ALL), including WT1, PHF6, RUNX1 and BCL11B. This proposed diagnostic entity overlaps with early T cell precursor (ETP) T‐ALL and T cell/myeloid mixed phenotype acute leukaemias (MPALs), and also includes a subset of leukaemias currently classified as AML with features of T‐lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches.     

老年患者急性心肾综合征的危险因素及预后分析

目的 对老年急性心肾综合征（acute cardiorenal syndrome,ACRS）患者的危险因素及预后进行分析.方法 回顾性分析312例住院期间发生急性心力衰竭（acute heart failure,AHF）的老年患者的临床资料[其中164例合并急性肾损伤（acute kidney injury,ACRS）（ACRS组）,148例未合并AKI（非ACRS组）].结果 312例AHF患者中,13.1％住院期间死亡,Charlson并发症评分≥3分、住院期间发生ACRS和住院期间需要透析治疗是AHF患者死亡的危险因素（OR =4.723,P=0.041;OR =6.096,P=0.008;OR=18.743,P＜0.001）.52.56％的AHF患者发生ACRS,估算肾小球滤过滤（estimated glomerular filtration,eGFR）＜60 mL/（min· 1.73 m2）、使用利尿药是AHF患者住院期间发生ACRS的危险因素（OR=2.239,P=0.025;OR =2.555,P=0.001）;eGFR、血清白蛋白（Mbumin,ALB）是AHF患者住院期间发生ACRS的保护因素（OR=0.968,P＜0.001;OR=0.907,P=0.007）.23.2％的ACRS患者死亡,住院期间透析是ACRS患者住院期间死亡的危险因素（OR=10.407,P＜0.001）;使用β受体阻断药、使用利尿药是ACRS患者住院期间死亡的保护因素（OR=0.312,P=0.011;OR=0.345,P=0.040）.结论 老年患者ACRS发生率高、预后差.基础eGFR和ALB浓度降低以及使用利尿药可能使老年AHF患者发生ACRS的风险增加.并发症多、住院期间发生ACRS、住院期间需要透析治疗均是老年AHF患者不良预后的危险因素.     

Secondary acute lymphoblastic leukaemia is constitutional and probably not related to prior therapy

Very little is known about secondary acute lymphoblastic leukaemia (s‐ALL). This retrospective analysis studied a cohort of s‐ALL patients treated at a single centre between 1994 and 2013, while comparing therapy‐associated ALL (t‐ALL) and antecedent malignancy ALL (am‐ALL) patients. Thirty‐two patients with s‐ALL were identified. The overall incidence was 9·4% among ALL adults while T‐cell s‐ALL was rare (12% of s‐ALLs). The median time interval between two malignant diagnoses was 5·3 years (range: 0·1–28). In contrast to previous reports, most of the s‐ALLs were CD10 +  and without KMT2A (MLL) abnormalities. The overall survival (OS) rates of the entire cohort at 12 and 24 months from ALL diagnosis was 49% and 25%, respectively. Most patients (n = 23, 72%) received prior chemo‐/radio‐therapy for their first malignancy (t‐ALL) and only 9 (28%) did not (am‐ALL). No significant difference was found in the incidence of B‐/T‐ lineage ALL, extramedullary disease, blood count, and the rate of Philadelphia‐positive ALL, nor in the rates of complete remission (P = 0·55) and OS (P = 0·97). This similarity, together with high incidence of family malignancy in both groups, raise the possibility that s‐ALL patients may have an inherent predisposition to malignancies and a history of previous therapy may be of lesser importance in the pathogenesis of s‐ALL.     

Liver biopsy features of acute hepatitis C compared with hepatitis A,B, and non-A,non-B,non-C

ABSTRACT— The diagnosis of acute hepatitis C (AHC) often can only be suspected because current serologic tests remain negative for over 3 months. Because histologic features might provide useful clues, we reviewed 85 liver biopsy specimens from 85 patients with acute viral hepatitis, comparing 22 cases of AHC with 23 cases of acute hepatitis A (AHA), 30 cases of acute hepatitis B (AHB), and 10 cases of acute hepatitis non-A, non-B, non-C (AHNC). AHC was characterized by dense portal lymphoid aggregates (7 cases) and Poulsen-Christoffersen-type cholangitis (8 cases); these lesions were not found in any other type of acute viral hepatitis, and thus appeared to be diagnostic. Sinusoidal inflammatory infiltrates also were common in AHC, particularly in biopsy specimens obtained during the early phase of the disease. These inflammatory infiltrates did not appear to affect adjacent hepatocytes. Necrosis in AHC usually was spotty and accompanied by mixed inflammatory cells. In AHNC, necrosis was also spotty but, as an added feature, pigmented macrophages predominated in them. In AHA, necrosis was predominantly periportal, whereas in AHB, severe zone-3 necrosis predominated. Fatty changes were predominantly microvesicular; they were common in AHC but were also found in other groups. Collectively, the described histologic features allowed diagnosis of AHC in biopsy specimens with reasonable confidence. However, histologic findings failed to predict the prognosis in individual cases.     

重症胰腺炎合并ARDS的诊断治疗

目的探讨重症胰腺炎（SAP）并发成人呼吸窘迫综合症（ARDS）的诊断和治疗。方法对我院近10年收治的72例重症胰腺炎（SAP）其中并发成人呼吸窘迫综合症38例进行回顾性临床总结，分析其血气PaO2／FiO2、Qs／Qt等与诊断和治疗的关系。结果重症胰腺炎（SAP）并发ARDS的发生率52．77％（38／72）．在及时合理治疗原发病的基础上，均给予机械通气，平均6．5天，机械通气24h后血气分析显示PaO2为（94．85±12．25）mmHg，PaO2为（34．4±7．05）mmHg，Qs／Qt值为5．25％±6．85％，全组死亡10例，放弃治疗3例，死亡率26．31％。结论重症胰腺炎（SAP）在及时处理原发病的基础上，对并发的ARDS进行早期诊断和治疗，正确使用呼吸机，防治并及时处理其它并发症，是降低病死率的有效措施。     

善得定治疗急性胰腺炎的体会

作者对比观察了善得定对急性胰腺炎的治疗作用，其剂量为0.1-0.15mg，每4－6h一次，皮一注射。在85例水肿型胰腺炎中，15例应用善得定治疗。结果显示，善得定治疗组转手术率显著低于非善得定组（P＜0．05），未合并感染的12例坏死性胰腺炎均采取非手术治疗，其中3例应用善得定治疗，其合并症全部消失，明显优于对照组。合并感染的67例坏死性胰腺炎均予以手术治疗，病情严重的14例，用善得定治疗，结果显示可减少并发症及其严重度。     

An unusual case of CD4+ CD7+ CD56+ acute leukemia with overlapping features of type 2 dendritic cell (DC2) and myeloid/NK cell precursor acute leukemia

Type 2 dendritic cell (DC2) acute leukemia has been recently described. We report here an unusual case of a 17-yr-old adolescent with overlapping features of DC2 and myeloid/NK cell precursor acute leukemia as defined by Suzuki et al. The patient presented with lymphadenopathy and hepatosplenomegaly without extranodal manifestations in skin or elsewhere. The morphologic, cytochemical and immunophenotypic features were compatible with those described in DC2 acute leukemia, with co-expression of CD4, CD56 and CD123 antigens. The novel markers BDCA-4 and BDCA-2 considered specific for DC2s were co-expressed. However, bright CD7 positivity along with a dim expression of CD33 (57%) and CD117 (27%) were also noted. Additionally, there was bright expression of NG2 monoclonal antibody 7.1, a frequent finding in myeloid/NK cell precursor acute leukemia. The interpretation of the immunophenotypic profile leads to the hypothesis on the existence of borderline cases between DC2 and myeloid/NK cell precursor acute leukemia. Still, other hypotheses can not be overlooked, such as the possibility for a kind of variant monoblastic leukemia or of another rare entity of acute unclassified leukemia.     

Trefoil factor-2, an early predictor for acute gastrointestinal injury in patients with acute pancreatitis

Acute gastrointestinal injury (AGI) is commonly present in patients with acute pancreatitis (AP). It is often difficult to predict gastrointestinal function in the early stage due to lack of reliable markers. We aimed to assess whether early plasma trefoil factor 2 (TFF-2) is a potential predictor for AGI.Fifty one patients were included for the onset of AP (from developing abdominal pain) within 72 hours in this prospective observational single-center study from January 2013 to July 2015. Among them 23 patients were classified as mild, 17 as moderately severe, and 11 as severe according to 2012 Atlanta classification. Plasma samples were collected only once at admission to the ICU. Twenty samples of healthy adults were also collected as control. The TFF-2 levels were determined by using a human TFF-2 enzyme-linked immunoassay. AGI grades from 1st to 7th day after admission were observed.The plasma TFF-2 levels among AP patients in early stage were significantly higher than healthy controls (766.41 ng/mL vs 94.37 ng/mL, P < .0001). The correlations between TFF-2 levels and AGI grades from 1st to 4th day after admission were positive (r = 0.47, 0.43, 0.42, 0.40 respectively, P < .05). As a predictor of acute gastrointestinal failure, plasma TFF-2 was superior to others: Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, procalcitonin, C-reactive protein, serum calcium. In addition, TFF-2 increased along with the severity of AP (r = 0.554, P < .0001) and associated with Acute Physiology and Chronic Health Evaluation II, sequential organ failure assessment, C-reactive protein, serum calcium.The plasma TFF-2 levels were increased in patients in early stage of AP and correlated with AGI grades and disease severity in our study. TFF-2 might be a potential predictor for acute gastrointestinal failure in patients with AP.     

重症急性胰腺炎当前应关注的问题

<正>在重症急性胰腺炎治疗发展史上,不同时期会有不同问题被关注,这并不是疾病本质有什么变化,而是专科医师对其认识在逐步加深,正如一个覆盖着纱巾的少女,在纱巾被揭开的过程中她的容貌渐渐展现在人们的面前,其实,这并非是美丽少女有什么变化,只是纱巾被揭开的程度不同而已。在两百年以前的Senn及Moynihan时代,治疗急性胰腺炎     

Drug induced acute pancreatitis: Does it exist?

As the incidence of acute pancreatitis continues to rise, establishing the etiology in order to prevent recurrence is important. Although the etiology of acute pancreatitis is not difficult in the majority of patients, almost a quarter of patients are initially labeled as having idiopathic acute pancreatitis. When confronted with a patient with acute pancreatitis and no clear etiology defined as an absence alcoholism, gallstones(ultrasound and/or MRI), a normal triglyceride level, and absence of tumor, it often appears reasonable to consider a drug as the cause of acute pancreatitis. Over 100 drugs have been implicated by case reports as causing acute pancreatitis. While some of these case reports are well written, many case reports represent poorly written experiences of the clinician simply implicating a drug without a careful evaluation. Over-reliance on case reports while ignoring randomized clinical trials and large pharmacoepidemiologic surveys has led to confusion about drug induced acute pancreatitis. This review will explain that drug induced acute pancreatitis does occur, but it is rare, and over diagnosis leads to misconceptions about the disease resulting in inappropriate patient care, increased litigation and a failure to address the true entity: idiopathic acute pancreatitis.     

Single agent thalidomide in patients with relapsed or refractory acute myeloid leukaemia

Thalidomide is a putative anti-angiogenesis agent that has significant anti-tumour activity in haematological malignancies with increased bone marrow angiogenesis, including multiple myeloma (MM) and myelodysplastic syndromes (MDS). Increased levels of the mitogen for angiogenesis, vascular endothelial growth factor (VEGF), correlate with worse survival in acute myeloid leukaemia (AML). A phase II trial of thalidomide was conducted in patients with relapsed- or refractory-AML previously treated with cytarabine-containing regimens. A total of 16 patients with refractory- or relapsed-AML were treated with thalidomide 200-800 mg orally daily (median dose 400 mg daily) for a median of 27 d (range, 3-94 d). Overall, one patient (6%) achieved complete remission (CR) lasting for 36 months, and two patients had a transient reduction in marrow blasts from 8% and 7% to less than 5% in both cases. There was no correlation between reduction in levels of angiogenesis markers and response. Toxicities related to thalidomide were significant, and precluded dose escalation beyond 400 mg orally daily in most patients. Although there appears to be some evidence of biological activity, single agent thalidomide is not an optimal choice of therapy for salvaging patients with relapsed- or refractory-AML. Thalidomide analogues with more potent immunomodulatory activities and more favourable toxicity profiles may offer more promise as anti-AML therapy.     

Aggressive polychemotherapy for acute myelofibrosis

Acute myelofibrosis is a rare and still ill-defined disease. Based on morphological observation, immunophenotyping and ultrastructural analysis, we support the assumption that acute myelofibrosis is a malignant disorder mainly of the megakaryocytic lineage and is closely related to acute megakaryocytic/blastic leukaemia. Consequently, the 11 patients reported here were treated with aggressive polychemotherapy with combinations including daunorubicin and cytosine arabinoside and 6-thioguanin or VP16-213. 4 complete remissions, 2 partial remissions and 1 minor response were observed. Duration of aplasia was not significantly prolonged. These findings indicate that the use of aggressive polychemotherapy is feasible in acute myelofibrosis and results in a significant number of remissions.