Huge Spleen Research Articles

Asymptomatic huge spleen mass.

Asymptomatic huge spleen mass.

Abstract 120: Compartmentalized functions of epidermal growth factor receptor (EGFR) in tumorigenesis and malignant phenotypes

Abstract Previous studies demonstrated that nuclear EGFR is associated with malignancy and resistance to tyrosine kinase inhibitor (TKI). To decipher the cellular compartmentalized functions and underlying mechanism of EGFR, we generated EGFR mutants at nuclear translocation signal (NLS) and nuclear export signal (NES). The results showed that EGFR NLS mutant with decreased nuclear translocation sensitized the cancer cells to TKI and impaired invasiveness and stemness of the cancer cells. In contrast, EGFR NES mutant with increased nuclear accumulation promoted aggressiveness of the cancer cells including TKI resistance. Next, we generated genetically engineered mouse model (GEMM) to validate the resulting phenotypes of the EGFR mutants. To this end, CRISPR-Cas9-mediated genome editing approach was used for generating EGFR mutant knock-in mouse, which harbors an internalization-deficient mutation (EGFRLL/AA), pro-nuclear (NES) mutation (EGFRL749P(S)) and the dual mutations. Upon EGF stimulation nuclear EGFR (nEGFR) accumulation in the hepatocytes from EGFRL749P heterozygous mice was increased. Conversely, a significant reduction of nEGFR was observed in the hepatocyte from EGFTRLL/AA homozygous mice. We found that germline expression of EGFRL749P(S) gave rise to deficiency in breeding. However, EGFRLL/AA mutant mice displayed no gross abnormal even in homozygous offspring, suggesting that depletion of nEGFR has no significant phenotype. We failed to generate homozygotes of EGFR NES mutant mice due to embryonic lethality. Of note, the female and male founders and F1 EGFRL798P(S) mice developed tumors with huge spleen. The IHC staining results indicated that the infiltrating lymphocytes in liver, stomach and kidney were B cells. The latency of the B cell lymphomagenesis was from 17 to 23 months, and tumor incidence of F1 offspring of EGFRL749P(S) knock-in mice was 10 of 15 (66.7%). These findings indicated that single allele mutation in EGFR NES domain is capable of driving lymphomagenesis, suggesting that the EGFR NES mutant possesses a strong oncogenic activity. Surprisingly, by searching database of EGFR mutation in human tumors (Cosmic database https://cancer.sanger.ac.uk/cosmic ), we noticed that among the somatic mutations in EGFR gene the gene amplification represents only small part of the gene alternations in human cancers, and EGFR L747P and L747S mutation occur in the lung cancer patients with intrinsic TKI resistance. In addition, the majority of human B lymphocyte originated tumors harboring EGFR NES mutation are also heterozygotes. Cosmic database shows that somatic mutations at the EGFR NES region occur in the patients with plasma cell lymphoma. Taken together, our findings suggest that nEGFR contributes to malignant potential of the tumors and EGFR with NES mutation is a tumor driver. Citation Format: Lei Nie, Junwei Hou, Yu-Yi Chu, Ying-Nai Wnag, Li-Chuan Chan, Longfei Huo, Paul Chiao, Shao-Chun Wang, Mien-Chie Hung, Michael Wang. Compartmentalized functions of epidermal growth factor receptor (EGFR) in tumorigenesis and malignant phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 120.

The usefulness of modified splenic hilum hanging maneuver in laparoscopic splenectomy, especially for patients with huge spleen: a case-control study with propensity score matching.

Although Laparoscopic splenectomy (LS) have been proven to the standard operation for removal of spleen, the rate of conversion to open surgery is still higher than those of other laparoscopic surgeries, especially for huge spleen. In order to reduce the rate of conversion to open surgery, we had developed LS using modified splenic hilum hanging (MSHH) maneuver: the splenic pedicle was transected en bloc using a surgical stapler after hanging splenic hilum with an atraumatic penrose drain tube. Between January 2005 and December 2019, we retrospectively assessed 94 patients who underwent LS. MSHH maneuver was performed in 37 patients (39.4%). We compared the intra- and postoperative outcomes between patients with or without MSHH maneuver. To adjust for differences in preoperative characteristics and blood examination, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 29 patients per group. Predictive factors of conversion from LS to open surgery were elucidated using the uni- and multi-variate analyses. After the propensity score matching, blood loss (268ml vs. 50ml), the rate of conversion to open surgery (27.6% vs. 0%), and postoperative hospital stays (15days vs. 10days) were significantly decreased in patients with MSHH maneuver, respectively. Among 94 patients, 19 patients (20.2%) underwent conversion to open surgery. In multivariate analysis, spleen volume (SV) and LS without MSHH maneuver were independent predictive factors of conversion to open surgery, respectively. Additionally, cut-off value of SV for conversion to open surgery was 802ml (sensitivity: 0.684, specificity: 0.827, p < 0.001). LS using MSHH maneuver seems to be useful surgical technique to improve intraoperative outcomes and reduce the rate of conversion from LS to open surgery resulting in shorten postoperative hospital stay.

Isolated Giant Primary Splenic Hydatid Cyst in a 10-Year-Old Boy: A Case Report

Hydatid cyst (HD) disease is a parasitic infection produced by cysts containing the larval stage of Echinococcus granulosus. It occurs worldwide, but its prevalence is higher in the rural communities of some developing countries like Yemen, where sheep and cattle raising constitute a crucial component of the agricultural industry. This zoonotic disease spreads due to close contact humans with sheep and dogs. The most involved organs with HC are the liver and lungs. However, other organs may also foster it, such as the spleen, with an incidence rate of between 0.5% and 6%. To the best of our knowledge, primary involvement of the spleen by HC is very rare, and a few cases with isolated spleen HC in children were reported. In this study, a ten-year-old boy with a huge primary splenic HC is reported with chief chief complaint of pain and non-tender bulging in his abdomen’s left upper quadrant. A 20×16×18 cm splenic cystic mass was detected by ultrasonography (US) and confirmed by abdominal computed tomography (CT) scan without macroscopic involvement in other organs. Total splenectomy was carried out for hem. Pathological examinations revealed cystic hydatidosis. We describe this case of an isolated huge spleen HC, which was successfully treated with total splenectomy, focusing on the management and outcome of this disease.

The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion

目的探讨24个月内疾病进展（POD24）对伴骨髓侵犯的脾边缘区淋巴瘤（SMZL）患者总生存的影响，比较POD24与非POD24患者的临床特征。方法回顾性分析2002年1月至2017年1月中国医学科学院血液病医院收治的有治疗指征且经过正规治疗的伴骨髓侵犯的SMZL患者，选取随访时间足以对POD24进行判断的患者（排除因非进展因素发生死亡的患者），进行预后评估及临床特征比较。结果共入组患者106例，中位年龄57（25～79）岁。①临床特征：全部患者均有骨髓侵犯和脾肿大，其中巨脾59.4％（63/106），肝大14.8％（15/101）；复杂核型22.7％（18/79），13q缺失5.1％（4/78），11q缺失1.3％（1/72），17p缺失2.5％（2/80），12号染色体三体（CEP12）7.5％（4/53）。②生存分析：单因素分析提示POD24、HGB<100 g/L以及CEP12为与总生存相关的不良预后因素；多因素分析提示仅POD24有独立预后意义［HR＝20.116（95％CI 2.226～181.820），P＝0.008］。③亚组分析：POD24患者较非POD24患者起病时纵隔淋巴结肿大的发生率（63.6％对18.9％，P＝0.005）及复杂核型发生率（50.0％对17.9％，P＝0.024）明显增高；腹腔淋巴结肿大、贫血、血小板减少、白蛋白下降以及乳酸脱氢酶增高的发生率在POD24患者中更高，与非POD24患者相比差异无统计学意义（P>0.05）。结论POD24为影响伴骨髓侵犯的SMZL患者总生存的独立预后不良因素，起病时伴纵隔淋巴结肿大及复杂核型的患者发生POD24比例更高。

PB2207 EARLY SPLEEN RESPONSE IS A GOOD PROGNOSTIC FACTOR OF RUXOLINIB OUTCOME IN PATIENTS WITH MYELOFIBROSIS

Background:Ruxolitinib(RUXO) improves long‐term prognosis in patients(pts) with primary or post‐polycythemia/post‐thrombocythemia myelofibrosis(MF). The most patients experience spleen response. Meanwhile there are a few data how the speed of spleen response in MF affects RUXO treatment outcome.Aims:Evaluate prognostic significance of early spleen response on results of RUXO treatment in patients with MF and assess the factors associated with spleen response.Methods:In the multicenter real world ptactice study 42 patients (male 18, 43%) with MF and spleen data available at least at 3 months were included. Median age at the time of RUXO initiation was 55(25‐75)yrs. Median time from MF diagnosis to RUXO was 52(2‐346)mos. Median time on RUXO was 29 (4‐81)mos. Spleen response(SR) was assessed by palpation. Median spleen length before RUXO was 19(5‐33 cm) with massive spleen &gt;10 cm in the most pts ‐ 36(86%). Constitutional symptoms had 40(95%) of pts. DIPSS score was low, inter‐1 or inter‐2/high in 1(3%), 23(59%) and 15(38%) of 39 evaluable pts.Results:Spleen length reduction at 3mos was: &lt;25% in 13(31%)(Group 1), 25‐&lt;50% in 14(33%) (Group 2) and ≥50% in 15(36%)(Group 3) pts. At 6 mos 3/12(25%) and 3/14(21%) evaluable pts from Gr1 and Gr2 improved their SR. Some more pts from these groups experienced spleen reduction later, but mainly in case of RUXO dose elevation. SR, assessed according to IWG‐MRT criteria, was 13/42(31%) and 17/41(41,5%) in evaluable pts at 3mos and 6 mos, respectively. In all groups a few pts lost their SR. RUXO was stopped in 11(26%) pts, mainly due to disease progression or/and death. Depth of sSR significantly correlated with overall survival. All pts of Gr3 remained alive, whereas 7/29(24%) pts dead in Gr2 and Gr3 overall(p = 0,021). Less pts in Gr3 had huge spleen(&gt;20 cm), blasts 1% or more, low hemoglobin and were treated with low RUXO dose. There were equal symptoms burden in in different groups (Table 1).Summary/Conclusion:The majority of pts respond to RUXO. Depth of SR at 3 mos significantly influenced RUXO long term outcome – all pts with &gt;50% of spleen reduction at 3 mos are alive. It seems that pts with higher dose of RUXO, no periferal blasts, less spleen size and higher hemoglobin level are more responded to RUXO. Larger cohort of pts is needed to confirm statistical significance of this data.image

Splenectomy in sickle cell haemoglobinopathies

Background: Sickle cell disease is one of the common haemoglobinopathies in the world. Among its various clinical presentations, splenic complications are associated with high morbidity and substantial mortality, the only effective preventive strategy for which is prophylactic splenectomy. The aim of the present study was to observe the safety and effectiveness of splenectomy to prevent frequent requirement of hospitalizations, blood transfusions and splenic complications in patients of sickle cell disease.Methods: The study was carried out in 72 patients of SCD with splenomegaly who underwent splenectomy for some indication in the surgery department of VSSIMSAR, Burla during the period from October 2016 to September 2018. Their preoperative baseline hematological parameters and frequency of transfusion requirement was compared with postoperative status.Results: Of these 72 SCD patients, 49 (68.7%) patients had repeated requirement of blood transfusion and hypersplenism, 22 (30.5%) patients had history of one or more episodes of splenic sequestration crises, one patient had splenic abscess. After splenectomy the mean increase in haemoglobin level, TLC and TPC was respectively 2.83±0.9 gm%, 1.7±0.8 lac/cmm and 2726±1618/cmm. Operative mortality was 0%. None of the patients required any blood transfusion and no major postoperative complications during 6 months follow up period.Conclusions: The morbidity of the patients of SCD in terms of repeated hospitalizations, blood transfusion, living with a huge spleen, accompanying symptoms and its complications can be effectively minimized by the elective splenectomy. With good preoperative preparation and post-operative management, splenectomy in SCD patients is a safe procedure with minimal risk of post-operative complications.

Copper and anesthesia − a surprising connection

A 28-year-old female presented with complaints of fever with chills and dizziness on and off for the last 3 months. On admission, she was investigated and found to have anemia and thrombocytopenia. On examination, the patient was pale and had a palpable huge spleen. Past history revealed a diagnosis of Wilson’s disease 15 years ago. This disease, due to altered copper metabolism, may influence the conduct and outcome of anesthesia secondary to abnormalities in hemopoietic, cardiovascular, connective tissue, immune, and nervous systems. In this study, we present a patient, a diagnosed case of Wilson’s disease, with massive splenomegaly posted for splenectomy under general anesthesia and the concerns involved therein.

Electronic Poster Presentations, Maternal Fetal Medicine

Electronic Poster Presentations, Maternal Fetal Medicine

Non-cirrhotic portal hypertension – Concept, diagnosis and clinical management

Non-cirrhotic portal hypertension (NCPH) is mainly related to vascular disorders in the portal system, granuloma formation with periportal fibrosis or genetic alterations affecting the hepatobiliary system. For the diagnosis of the so-called idiopathic NCPH, it is essential to rule out chronic liver diseases associated with progression to cirrhosis as viral hepatitis B and C, alcoholic and non-alcoholic fatty liver, autoimmune disease, hereditary hemochromatosis, Wilson's disease as well as primary biliary cirrhosis and primary sclerosing cholagitis. This mini review will focus on the most common types of NCPH, excluding the idiopathic NCPH. Primary Budd-Chiari syndrome, characterized by obstruction of hepatic venous outflow, must be distinguished from sinusoidal obstruction syndrome, a cause of portal hypertension associated with exposure to toxic plants or therapeutic agents. Noninvasive imaging methods usually help the diagnosis of both Budd-Chiari syndrome and portal thrombosis, the later a relatively frequent cause NCPH. Clinical presentation and management of these vascular disorders are evaluated. Schistosomiasis, a worldwide spread endemic parasitic disease, may evolve to severe forms of the disease with huge spleen and gastroesophageal varices due to presinusoidal portal hypertension. Although management of acute upper gastrointestinal bleeding is similar to that of cirrhosis, prevention of rebleeding differs. Instead of portosystemic shunt procedures, the esophagogastric devascularization with splenectomy is the accepted surgical alternative. Its association with endoscopic therapy is suggested to be the best option for PH due to schistosomiasis. In conclusion, the prompt diagnosis of the disorder leading to non-cirrhotic portal hypertension is essential for its correct management.

A case of wandering spleen

Wandering spleen is a rare entity characterized by huge spleen with laxity of the splenic ligaments, absence of peritoneal attachments and presence of long pedicles. We herein present a case of a 42-year-old female with wandering spleen that presented to our clinic with intermittent abdominal pain associated with an abdominal lump.

Chronic Myeloid Leukemia Presenting with Visual and Auditory Impairment in an Adolescent: An Insight to Management Strategies

A 15-year-old girl presented with progressive deterioration in vision and hearing over 1 week. A huge spleen was palpated below the left costal margin laying down to inguinal region. Blood count showed hyperleukocytosis with a white blood cell count of 455 × 10(9)/l. Peripheral smear yielded myeloid precursor cells with basophilia. Bone marrow aspiration revealed a blast count of 5% morphologically and 4% by flow cytometry. Fundoscopic examination revealed bilateral retinal exudates, edema and hemorhages. Partial sensorioneural hearing loss was also detected on the right ear. The diagnosis of chronic myeloid leukemia was confirmed by positive t(9;22) by RT-PCR. After commencing on hydroxyurea and intrathecal methotrexate-prednisolone, progressive improvement in hearing and vision was obtained. In our brief report, we aimed to emphasize rare presentation with visual and hearing impairment of chronic myeloid leukemia during childhood, especially in "chronic phase".

Fatal splenic rupture caused by an atypical malignant lymphoma in a Holstein cow

Summary Postmortem examination of a 5.5-year-old Holstein cow with history of sudden death showed a very huge spleen (120 × 45 × 10 cm) associated with severe haemoperitoneum. Histopathological findings included extensive infiltration of medium to large sized lymphocytic and lymphoblastic cells with small amounts of cytoplasm, round nuclei with coarsely granular chromatin in the spleen, and limited foci of similar cellular infiltration in the liver. This case was diagnosed as a fatal splenic rupture caused by an atypical malignant lymphoma.

Indication for Splenectomy in the Era of Living-Donor Liver Transplantation

Although end-stage liver disease (ESLD) is often associated with splenomegaly and thrombocytopenia, splenectomy is not necessary in liver transplantation (OLT) except in special situations. In this paper, we examined the indications for splenectomy in the era of living-donor living transplantation. Six of 46 patients underwent splenectomies. Among them, one received a cadaveric graft. Three splenectomies were performed at 6, 7, and 44 days after OLT because of a huge spleen, massive ascites, or impaired liver function. The other two patients received simultaneous splenectomy during OLT to prevent rejection of ABO-incompatible grafts with a positive anti–T-cell test; and one, for postoperative therapy of hepatitis C. All six patients had a good response to splenectomy. We concluded that splenectomy may be indicated for recipients with severe thrombocytopenia, small-for-size syndrome, ABO incompatibility with positive anti–T/B-cell tests and post-OLT therapy for hepatitis C.

Autoimmune lymphoproliferative syndrome; a case report.

Autoimmune lymphoproliferative syndrome is a disorder of lymphoid system regulation characterized by chronic splenomegaly, lymphadenopathy and autoimmune phenomena especially immune-mediated cytopenias. The hallmark of the disease is the presence in peripheral blood and lymphoid tissue of increased numbers of a normally rare T lymphocyte subset, usually referred to as "double-negative" T cells. Here the authors report a 16-year-old boy when he was first hospitalized for diffuse petechiae, purpura and epistaxis at 9 years of age. One year later,he was readmitted for high fever and recurring cytopenia. On examination several enlarged, nontender lymph nodes involving cervical and submandibular areas and a huge spleen were detected. Lymph node biopsy was performed two times. According to flowcytometry of peripheral blood and immunophenotyping of lymph node tissues which revealed increased numbers of CD3+CD4-CD8- T-lymphocytes autoimmune lymphoproliferative syndrome was suggested for him. Autoimmune lymphoproliferative syndrome should be considered in differential diagnosis of any patient with unexplained Coomb's positive cytopenias, hypergammaglobulinemia, generalized lymphadenopathy and splenomegaly. The confirmation of the diagnosis should be based upon genetic analysis and detection of the affected genes involved in fas pathway.

Recurrent infections and bilateral uveitis in a patient with CD8 deficiency.

CD8 deficiency is a rare primary immunodeficiency with low or absent peripheral CD8 cells which results from TAP deficiency, Zap 70 deficiency and CD8 alpha gene mutation.We report a 14 year old female who presented with a history of recurrent pneumonia, bronchiectasis, otitis, severe varicella, herpetic lesions of mouth, bilateral uveitis, and cataract formation since the age of 8 years.She had growth failure, a huge spleen and moderate clubbing. In immunologic workup, humoral and phagocytic systems were normal. DTH response to candida, PPD and DT were negative but LTT response to PHA mitogen was normal. HLA typing showed normal class I expression. Flowcytometry of peripheral blood showed CD8: 0 to 2% (absolute count, 0-60 cells/mm3) with increased CD4/CD8 ratio on several occasions.Diagnosis of this patient cannot be HLA class I deficiency (TAP1 or TAP2), because class I expression had been normal. It is possible to be Zap -70 deficiency or CD8 alpha gene mutation. Bilateral uveitis in our patient was a unique presentation which might have resulted because of immune dysregulation in CID.

A CASE OF PRIMARY MYELOFIBROSIS SUSPECTED OF TERMINATING IN LEUKEMIA AFTER SPLENECTOMY

We experienced a case of primary myelofibrosis (PMF) suspected of terminating in leukemia after splenectomy. A 70-year-old man who was in hospital because of chronic anemia and thrombocytopenia was diagnosed as having primary myelofibrosis (PMF) on close examination. Thereafter, left lateral abdominal pain and appetite loss appeared and abdominal ultrasonography and CT scan revealed the giant spleen. Because of unsuccessful blood transfusions for his anemia and oppressed symptoms of the stomach due to the huge spleen, a splenectomy was carried out. After the splenectomy, the platelet count increased but no remission of anemia was attained. Five months later, WBC increased to 136, 700/mm3 and the percentage of myeloblast in peripheral blood increased to 78.0%, and then the patient died. So we suspected that it was terminated in leukemia after the splenectomy. A few cases have been reported that primary myelofibrosis terminated in leukemia after splenectomy, and splenectomy may have a risk to enhance the characteristic of primary myelofiblosis as “myeloproliferative disorders”. We have to be more considerate of indication about surgical therapy for primary myelofibrosis.

Serum laminin P1 in idiopathic myelofibrosis and related diseases

The serum concentration of laminin P1 antigen was determined in 32 patients with various myeloproliferative disorders, including 19 patients with idiopathic myelofibrosis. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured concomitantly in 27 patients. Serial laminin measurements were carried out in 25 patients. The median serum laminin concentration in patients with acute disease, i.e. acute myelofibrosis and patients in a transforming disease phase was significantly higher (1.58 U/ml; range 1.15–2.07) as compared with patients with chronic disease (1.02 U/ml; range 0.75–1.76; p= 0.012) and healthy control subjects (1.13 U/ml; range 0.75–1.67; p = 0.00015). In individual patients serum laminin covariated closely with serum PIIINP, the leucocyte count and LDH. The median serum laminin concentration in patients with a huge spleen was significantly lower than in the patient group with a normal spleen size/previous splenectomy. Pronounced splenomegaly was particularly prevalent in patients with chronic disease implicating splenic enlargement as a significant extrahepatic site of laminin uptake/degradation in myeloproliferative disorders.

A CASE REPORT OF SPLENECTOMY IN A PATIENT WITH SPLENIC INFARCTION COMBINED WITH PRIMARY MYELOFIBROSIS (PMF)

This paper describes a case of primary myelofibrosis (PMF) associated with splenic infarction which was treated by splenectomy. A 58-year-old man who had been diagnosed as PMF 1.5 years before was admitted to the hospital because of splenomegaly, left hypochondralgia, high fever and marked decrease in peripheral platelet (1-2×104/μl). Abdominal CT scan and RI scintigraphy indicated multiple splenic infarction. Splenectomy was performed because his symptoms were aggravated. After the operation hypochondralgia and fever disappeared and the patient was discharged from the hospital on 30th postoperative day. For severe thrombocytopenia, administration of “platelet concentrate” during perioperative period contributed to preventing hemorrhagic diathesis, and the huge spleen 2330g in weight could be easily resected with only 300g of intraoperative bleeding without complications. Some authors have reported that splenectomy in PMF patients is much riskier than that in other diseases. We suppose that splenectomy in PMF patients may be recommended not to improve hematological findings, but to relieve severe symptoms due to splenic infarction like this case.

Long-term follow-up of partial splenectomy in Gaucher's disease

Seven children with Gaucher's disease who underwent partial splenectomy were followed for 7 to 8 years. None of the children had systemic sepsis or symptoms related to liver enlargement. Bone crisis occurred in only two children who had experienced bone crisis prior to partial splenectomy. This contrasts with the development of bone crises in five of six children who underwent total splenectomy at a similar age and who had previously been free of bone symptoms. Partial splenectomy should be regarded as a temporary solution in the treatment of hypersplenism and the mechanical compression related to the huge spleen. In 71% of the patients, massive enlargement and a severe to moderate degree of pancytopenia occurred again after 3 to 8 years; total splenectomy was required in three patients.