Sorafenib plus partial splenic embolism for treatment of hepatocellular carcinoma Barcelona stage C combined with hypersplenism: a case series.

BACKGROUND: Sorafenib is mainly used to treat patients with hepatocellular carcinoma (HCC) Barcelona Clinic Liver Cancer (BCLC) stage C, many of whom also have severe cirrhosis. However, hypersplenism and digestive tract hemorrhage are common complications of cirrhosis, which increase the risk and difficulty of treatment. METHODS: Nineteen patients with HCC BCLC stage C with hypersplenism were treated with sorafenib plus partial splenic embolism at Chongqing University Cancer Hospital, Chongqing, China, between January 2015 and June 2018. We analyzed the therapeutic effect and clinical safety of this treatment in these patients. RESULT: Hypersplenism was rectified in all patients. The incidence rates of hemorrhage and myelosuppression were 0%, and the mean survival time was 11.2 months. CONCLUSION: Sorafenib plus partial splenic embolism could relieve hypersplenism and prolong survival in patients with BCLC stage C HCC.

Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism.

BACKGROUND: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. METHODS: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13). RESULTS: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). CONCLUSIONS: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

ß-Blocker therapy ameliorates hypersplenism due to portal hypertension in children.

BACKGROUND/PURPOSE: Thrombocytopenia due to hypersplenism precludes percutaneous liver biopsy in many cases of chronic liver disease (CLD). The aim of this study was to assess the efficacy of propranolol in correcting platelet counts (>100,000/mm(3)) to ensure percutaneous liver biopsy in children with CLD. METHODS: From January 2005 to December 2012, 51 consecutive children (mean age 11.5 ± 3.0 years, 34 boys) with CLD who needed liver biopsy but could not be done due to hypersplenism-related thrombocytopenia (platelets <100,000/mm(3) and/or total leukocyte counts <4,000/mm(3) with splenomegaly) were recruited and given a 4-week trial of long-acting propranolol (1.5-2 mg/kg/day). Hemodynamic parameters and splenic artery hemodynamics by Doppler ultrasound were recorded before and after the propranolol trial. Response to therapy was defined as improvement of platelet counts to ≥10(5)/mm(3). RESULTS: Thirty-two (62.7%) children responded to propranolol therapy and their mean platelet counts increased from 57.5 ± 13.0 × 10(3) to 140.7 ± 43.3 × 10(3)/mm(3), p = 0.0001. Liver biopsy could be done in 29. While comparing responders with non-responders, baseline spleen size (7.4 ± 3.3 vs. 12.7 ± 4.5 cm, p = 0.0001) and platelet counts (57.5 ± 13.0 × 10(3) vs. 39.5 ± 14.5 × 10(3), p = 0.0001) were found to be significant. ROC curve suggested a cut-off value of ≤8.5 cm of spleen and ≥53,000 platelets as predictors of response. With propranolol, mean arterial pressure and spleen size reduced (p < 0.05) and splenic artery resistance increased significantly (p = 0.005) in responders. CONCLUSIONS: Propranolol corrects thrombocytopenia and makes liver biopsy possible in almost two-thirds of cases by reducing splenic sequestration through splenic artery vasoconstriction. The baseline spleen size and platelet counts determine the effectiveness of therapy. A trial of ß-blocker is worth carrying out in cases where liver biopsy is contraindicated due to hypersplenism-related thrombocytopenia.

Treatment of suspected hyper-reactive malarial splenomegaly (HMS) in pregnancy with mefloquine.

Malaria infections in pregnancy are associated with adverse outcomes for both mother and child. There are few data on hyper-reactive malarial splenomegaly, an aberrant immunological response to chronic or recurrent malaria in pregnancy. This retrospective assessment reviewed the impact of mefloquine treatment on pregnant women with suspected hyper-reactive malarial splenomegaly in an area of low malaria transmission in the 1990s, showing significant reductions in spleen size and anemia and anti-malarial antibody titers without any notable negative effect on treated women or their newborns.

Interleukin-11 administration normalizes the platelet count in a hypersplenic cirrhotic patient.

We report the successful administration of interleukin-11 (IL-11 or oprelvekin), a promoter of megakaryocyte maturation, to a 54-year-old male Jehovah's Witness with hepatic cirrhosis and hypersplenic thrombocytopenia requiring surgery for symptomatic interstitial cystitis. This observation suggests that oprelvekin might be crucial in the acute management of certain types of hypersplenic thrombocytopenias.

Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis.

A 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m2 and increased each month by 10 mg/m2. It was then administered by continuous infusion until June 2000, starting at 20 mg/m2/d and tapering by 5 mg/m2 every 2 weeks to a final daily dose of 5 mg/m2/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis.

Positive effect of granulocyte-colony stimulating factor on erythropoiesis in humans.

We studied the effects of granulocyte-colony stimulating factor (G-CSF) on human erythropoiesis in vivo. Changes in the peripheral blood were analyzed in 9 subjects; 3 healthy volunteers, 3 patients with pancytopenia and hypersplenism and 3 patients with chronic renal failure and severe anemia being treated with hemodialysis. We monitored erythropoiesis according to the number of highly fluorescent cells (HFC) present in the peripheral blood after staining with Auramine 0. These cells are relatively immature reticulocytes that contain much RNA. All subjects received recombinant human G-CSF at a daily dose of 100 micrograms/m2 administered intravenously for 3 to 5 days. Plasma erythropoietin was measured in patients receiving dialysis before and several times after its administration. The number of HFC increased significantly in all subjects. In 1 of 3 patients receiving dialysis, the plasma erythropoietin increased transiently but insignificantly. These findings show that G-CSF affects human erythropoiesis in vivo, but that the mechanism of its effect did not involve an increase in plasma erythropoietin.

Ultrasound-guided percutaneous injection of ethanolamine oleate for hypersplenism. An experimental study in dogs.

In order to evaluate a possible therapy for hypersplenism, an experiment with animals was done. In nine dogs, 0.6 ml/kg body weight of 5% ethanolamine oleate was injected percutaneously into the spleen under ultrasound guidance. The injection was repeated three times at intervals of 1 week. Three dogs each were killed at 1, 4, and 8 weeks after the final injection. All dogs tolerated the procedure well and lived until they were killed. The platelet count and leukocyte count increased after the injections, and remained higher than the pretreatment level until death. This effect probably is due to depressed splenic function. The autopsy showed 40% of the spleen to be infarcted with complete destruction of the normal structure. No serious complications occurred. In addition, injection of ethanolamine oleate in six fully heparinized dogs showed that there was little risk of hemorrhage. Ultrasound-guided percutaneous injection of ethanolamine oleate might be a simple and effective therapy for hypersplenism.

[Acute myeloblastosis in von Jaksch-Luzet syndrome]. / Myéloblastose aiguë au cours du syndrome de von Jaksch-Luzet.

A 7 month-old infant of Italian origin, who was given a vitamin-D deficient diet developed a Von Jaksch-Luzet syndrome with more than 20% myeloblasts in the bone marrow. Plasma levels of vitamin D metabolites wer low and parathormone levels were high. A low dose of vitamin D3 (2,000 IU cholecalciferol/day) resulted in the recovery of a normal phosphocalcic balance and in the disappearance of myeloblastosis.

Splenomegaly in sarcoidosis.

The clinical records of 32 patients with sarcoidosis associated with splenomegaly were reviewed. The results of this study disclosed that when compared with a matched control population without splenomegaly, patients with splenomegaly had evidence of more extensive extrathoracic sarcoidosis. In contrast, there was no difference in the degree of pulmonary involvement between patients with or without splenomegaly. Of the 32 patients with splenomegaly, seven (20%) had evidence of hypersplenism and five (16%) had abdominal symptoms. These abnormalities occurred only in patients with greatly enlarged spleens. Considering splenomegaly, we suggest that corticosteroids are indicated in the management of only large spleens and not of smaller spleens, unless there are other specific indications.

The effect of intravenous injection of ethyl palmitate emulsion on sequestration of thermally damaged erythrocytes in rats with experimentally induced hypersplenism, and in normal rats.

The authors attempted at experimental elimination of sequestration function of the spleen in Wistar rats using an i.v. injection of ethyl palmitate emulsion, both in "hypersplenic" animals being long-term applied i.p. methyl cellulose solution, and in control rats. In the rats clearance of 51Cr-labelled and thermally damaged erythrocytes from blood was examined and their sequestration in the spleen and liver followed. The ethyl palmitate injection resulted in both experimental groups in a significant decrease of the erythrocyte counts sequestrated in the spleen, and significant prolongation of the elimination half time for thermally damaged erythrocytes from the blood.