Prognostic impact of splenomegaly on survival of Chinese with primary myelofibrosis

Predicting survival in persons with primary myelofibrosis (PMF) is typically based on the International Prognostic Scoring System (IPSS), the Dynamic IPSS (DIPSS) or the DIPSS-Plus. These scoring systems use clinical and laboratory data developed predominately in persons of European descent. Splenomegaly is not a prognostic variable in any of these scoring systems. Recently, we reported differences in clinical and laboratory features between Chinese vs. persons of European descent with PMF. Based on this we developed a modified prognostic model to predict survival of Chinese subjects in which splenomegaly is an independent favorable prognostic factor. In the current study, we analyzed data from 874 Chinese with PMF including 495 with splenomegaly. Subjects with splenomegaly had significantly higher hemoglobin concentrations (P < 0.001), higher levels of WBCs (P < 0.001), platelets (P < 0.001), excess blood blasts (≥1%; P = 0.012), less RBC-transfusion-dependence (P < 0.001) and lower DIPSS risk distribution (P = 0.024). Frequency of JAK2^V617F (62% vs. 50%; P = 0.003) was also different. In univariate analyses subjects without splenomegaly had briefer survival (median, 64 mo [95% CI, 43–85] vs. 110 mo [95% CI, 67–153]; P < 0.001). In multivariate analyses, splenomegaly was a favorable prognostic correlate of survival independent of DIPSS risk-cohort (hazard ratio [HR] = 1.445; [95% CI, 1.101–1.895]; P = 0.008). Our data suggest including splenomegaly improves the predictive accuracy of the prognostic model to estimate survival of Chinese with PMF.     

Increased immunohistochemical expression of YKL-40 in the spleen of patients with portal hypertension

YKL-40 has been identified as a growth factor in connective tissue cells and also a migration factor in vascular smooth muscle cells. To a large extent, the increase of serum YKL-40 is attributed to liver fibrosis and asthma. However, the relationship of the expression and clinical/prognostic significance of YKL-40 to the splenomegaly of patients with portal hypertension is unclear. In the present study, the expression of YKL-40 was studied by immunohistochemistry in 48 splenomegaly tissue samples from patients with portal hypertension and in 14 normal spleen specimens. All specimens were quickly stored at -80°C after resection. Primary antibodies YKL-40 (1:150 dilution, rabbit polyclonal IgG) and MMP-9 (1:200 dilution, rabbit monoclonal IgG) and antirabbit immunoglobulins (HRP K4010) were used in this study. The relationship of clinicopathologic features with YKL-40 is presented. The expression of YKL-40 indicated by increased immunochemical reactivity was significantly up-regulated in splenomegaly tissues compared to normal spleen tissues. Overexpression of YKL-40 was found in 68.8% of splenomegaly tissues and was significantly associated with Child-Pugh classification (P = 0.000), free portal pressure (correlation coefficient = 0.499, P < 0.01) and spleen fibrosis (correlation coefficient = 0.857, P < 0.01). Further study showed a significant correlation between YKL-40 and MMP-9 (correlation coefficient = -0.839, P < 0.01), indicating that YKL-40 might be an accelerator of spleen tissue remodeling by inhibiting the expression of MMP-9. In conclusion, YKL-40 is an important factor involved in the remodeling of spleen tissue of portal hypertension patients and can be used as a therapeutic target for splenomegaly.     

Liver involvement in Gaucher disease: A practical review for the hepatologist and the gastroenterologist

Gaucher disease (GD), a rare lysosomal storage disorder caused by deficient glucocerebrosidase activity and consequent accumulation of glycosphingolipids in the mononuclear phagocyte system, may progress to disabling and potentially life-threatening complications when left undiagnosed and untreated. Unfortunately, because of non-specific signs and symptoms and lack of awareness, patients with type 1 GD, the most common non-neuropathic variant, frequently experience diagnostic delays. Since splenomegaly and thrombocytopenia are the dominant clinical features in many GD patients leading to first medical contact, the hepatologist and the gastroenterologist need to be aware of this condition. Liver involvement has been reported in the majority of GD patients, and comprises hepatomegaly, with or without liver enzymes alteration, fibrosis/cirrhosis, portal hypertension, focal liver lesions, and cholelithiasis. Moreover, GD is associated with several biochemical alterations of potential interest for the hepatologist and the gastroenterologist, including hypergammaglobulinemia, hyperferritinemia and metabolic abnormalities, that may lead to misdiagnoses with chronic liver diseases of common etiology, such as primary hemochromatosis, autoimmune liver diseases or nonalcoholic fatty liver disease. This comprehensive review, based on the collaborative experience of physicians managing patients with GD, provides practical information on the clinical, histological and radiological hepatic manifestations of GD aiming at facilitating the diagnosis of GD for the hepatologist and the gastroenterologist.     

TYPE I GAUCHER DISEASE IN CHILDREN WITH AND WITHOUT ENZYME THERAPY

This retrospective study describes the course of 56 children with non-neuronopathic Gaucher disease who presented at <16 years and were followed at 6- to 12-month intervals for 3-9 years. Massive splenomegaly and height retardation marked those who required treatment. Enzyme replacement significantly increased hemoglobin levels; platelet counts were divergent at presentation and follow-up, regardless of therapy. Among treated patients there was a significant reduction in liver and spleen index volumes, and a significant increase in height z-scores. None of the children required splenectomy or developed lung involvement. Many patients diagnosed due to large-scale screening were very mildly affected and remain untreated.     

Splenectomy in Myelofibrosis: Indications,Efficacy, and Complications

Splenomegaly, which may range from a few centimeters below the left costal border to massive dimensions, is one of the most characteristic features in patients with advanced myelofibrosis (MF). Splenectomy may offer an effective therapeutic option for treating massive splenomegaly in patients with MF, and especially in cases of disease refractory to conventional drugs, but it is associated with a number of complications as well as substantial morbidity and mortality. Whether splenectomy should be performed before allogeneic hematopoietic stem-cell transplantation is also controversial, and there is a lack of prospective randomized clinical trials that assess the role of splenectomy before hematopoietic stem-cell transplantation in patients with MF. Although splenectomy is not routinely performed before transplantation, it may be appropriate in patients with massive splenomegaly and related symptoms, so long as the higher risk of graft failure in such cases is taken into account. This review aims to describe the efficacy, indications, and complications of splenectomy in patients with MF; and to evaluate the long-term impact of splenectomy on patient survival and risk of disease transformation.     

Laparoscopic spleen-preserving distal pancreatectomy with and without splenic vessel preservation: The role of the Warshaw procedure

Background/objectivesLaparoscopic spleen-preserving distal pancreatectomy (LSPDP) for low-grade malignant pancreas tumors was recently demonstrated. Although the procedure with splenic vessel preservation (SVP) is optimal for LSPDP, SVP is not always possible in patients with a large tumor or a tumor attached to splenic vessels. This study aimed to analyze the safety of two procedures: LSPDP without SVP, known as the Warshaw technique (lap-WT), and LSPDP with SVP (lap-SVP).MethodsSeventeen patients who underwent a lap-WT and seven patients who underwent a lap-SVP were investigated retrospectively.ResultsThe median follow-up duration was 45 (range 17–105) months. In the lap-WT and lap-SVP patients, the sizes of the tumors were 5 (1.3–12) and 1.5 (1–4) cm; the operative times were 304 (168–512) and 319 (238–387) min; the blood loss was 210 (5–3250) and 60 (9–210) gr; the length of the postoperative hospital stay was 15 (8–29) and 18 (5–24) days; the peak platelet counts were 37.2 (14.6–65.2) and 26.4 (18.8–41) × 10⁴/μL, and splenomegaly was observed in 10 (59%) and three (43%) patients, respectively. In both procedures, there was no local recurrence. In the lap-WT group, splenic infarctions were seen in four (24%) patients and perigastric varices were seen in two (12%) patients. All of these patients were observed conservatively.ConclusionsBoth the lap-WT and lap-SVP were found to be safe and effective, and in cases in which the tumor is relatively large or close to the splenic vessels, lap-WT can be used as the more appropriate procedure.     

Hypersplenism and thrombocytopenia after exposure to ustekinumab in a patient with Crohn’s disease

Crohn’s disease can be characterized as a chronic inflammatory state causing various clinical presentations and long-term risks that should be considered when determining the optimal therapeutic strategy. To date, while a few case reports have been available regarding ustekinumab-induced thrombocytopenia, none are available regarding hypersplenism. We describe a 33-year-old woman who developed only Ileocolonic Crohn’s disease on ustekinumab due to failure of anti-TNF with septic shock and thrombocytopenia. Abdominal computed tomography revealed hepatosplenomegaly, parasacral collection, and fistulization. The patient was transferred to the intensive care unit and managed accordingly. Various treatment modalities were attempted, but none of them improved her platelet count. Our case report demonstrates that ustekinumab may induce hypersplenism and subsequently thrombocytopenia and should be considered a potential cause of low platelet count.     

原发性骨髓纤维化伴巨脾患者脾切除术前后血常规动态观察

目的探讨原发性骨髓纤维化(PMF)伴巨脾患者脾切除术对血常规的影响。 方法对1例PMF伴巨脾患者脾切除术前后的血常规等指标进行动态观察,并对切除的巨脾进行组织学检查。 结果患者术后呼吸困难、腹胀、纳差等症状明显好转。血常规结果示：白细胞明显升高,中性粒细胞百分比下降,淋巴细胞百分比升高,红细胞数变化相对较小,血红蛋白术后早期由于自体脾血回输升高,继之基本平稳,血小板变化最显著,术后明显减少,第5天最低仅10×10⁹/L,后逐渐恢复正常。组织学检查可见脾脏出现骨髓化倾向。 结论PMF伴巨脾行脾切除后血常规改变明显,脾脏出现了部分代替骨髓造血的组织学改变,脾切除后机体血细胞计数逐渐恢复正常。对PMF伴脾脏巨大导致影响呼吸和消化功能的患者应予以切除脾脏。     

Laparoscopic splenectomy for histiocytic sarcoma of the spleen

Primary histiocytic sarcoma of the spleen is a rare but potentially lethal condition. It can remain asymptomatic or only mildly symptomatic for a long time. An 81-year-old woman presented with an extremely enlarged spleen. She suffered from progressive anemia and required a red blood cell transfusion once a month. Although computed tomography, ultrasonography, and magnetic resonance imaging were performed for diagnosis, a confirmed diagnosis was not obtained. Her enlarged spleen compressed her stomach, and she suffered from gastritis and a sense of gastric fullness just after meals. She underwent laparoscopic splenectomy for therapeutic and diagnostic purposes. Her post-operative course was uneventful. After surgery, her red blood cell and platelet counts increased markedly. The tumor was diagnosed as splenic histiocytic sarcoma. Post-surgical chemotherapy was not performed, and the patient died of liver failure due to liver metastasis 5 mo after surgery. Laparoscopic splenectomy is minimally invasive and useful for the relief of symptoms related to hematological disorders. However, in cases of an enlarged spleen, optimal views and working space are limited. In such cases, splenic artery ligation can markedly reduce the size of the spleen, thus facilitating the procedure. The case reported herein suggests that laparoscopic splenectomy may be useful for the treatment of splenic malignancy.     

门静脉高压症183例脾切除的治疗体会

目的总结门静脉高压症脾切除的治疗经验。方法回顾性分析我院2006年1月至2009年12月门静脉高压症脾切除的183例患者的临床资料。结果无手术死亡病例,无术后脾蒂血管出血,无胰漏、胃底及结肠损伤等严重并发症。术后主要并发症包括左膈下脓肿1例、肺部感染5例、左侧胸腔积液7例、大量腹水9例、门静脉系统血栓形成21例,均经保守治疗后治愈。结论脾动脉的妥善处理、脾周韧带及粘连的解剖分离、脾蒂血管的正确处理以及脾窝创面的彻底止血是门静脉高压症脾脏切除的关键。