Circulating nucleosomes as a potential cancer biomarker in dogs with splenic nodular lesions.

Splenic nodular lesions in dogs can be either benign or malignant. They might be discovered incidentally or, in case of rupture, they may lead to hemoabdomen. Nevertheless, splenectomy followed by histopathology is essential for diagnosis and to prevent rupture. Yet, this invasive procedure might be postponed for dogs with benign splenic nodular lesions. Conversely, owners may opt for euthanasia over surgery for malignancies with poor prognosis like hemangiosarcoma. Thus, anticipating diagnosis with non-invasive biomarkers is crucial for proper patient management. In this prospective study, plasma samples were collected from 66 dogs with histologically confirmed splenic nodular lesions. A canine-specific ELISA kit was applied to assess nucleosome concentration, with histopathology of the spleen serving as the gold standard. Nucleosome concentration was found to be significantly higher in dogs with malignant splenic nodular lesions, particularly in those with hemangiosarcoma and other malignancies. The presence of hemoabdomen, more prevalent in dogs with splenic malignancy, also resulted in increased plasmatic nucleosome concentrations. Plasma nucleosomes could serve as a biomarker for detecting malignant splenic nodular lesions in dogs. More research is needed to understand how nucleosome concentration relate to disease stage and prognosis in dogs with hemangiosarcoma.

Evaluation of clopidogrel, hypercoagulability, and platelet count in dogs undergoing splenectomy for splenic masses.

Dogs that had splenectomy are predisposed to fatal thrombotic conditions, and thrombocytosis is a risk factor for post-splenectomy hypercoagulability. However, in veterinary medicine, there are no specific therapeutic approaches for managing this hypercoagulability. This study aimed to determine the preventive effect of clopidogrel on post-operative hypercoagulability during the first 2 weeks post-splenectomy in dogs with splenic masses. This study included 12 dogs that had splenectomy. Seven dogs received no treatment (group A), and five were treated with clopidogrel (group B). Clopidogrel was loaded at 10 mg/kg on day 2 and continued at 2 mg/kg until day 14. Blood samples were collected on the day of surgery and 2, 7, and 14 days after splenectomy in both groups. In group B, thromboelastography (TEG) was performed on the same days. In group A, there was significant elevation of platelet counts on days 7 (p = 0.007) and 14 (p = 0.001) compared to day 0. In group B, the platelet counts were significantly elevated on day 7 (p = 0.032) but no significant difference was found on day 14 compared to day 0. Platelet counts on day 14 were significantly higher in group A than in group B (p = 0.03). The lower platelet counts were correlated with alterations in TEG parameters, and no significant differences were found in the K and α-angle values at all postoperative assessment points compared to day 0. Our study suggests that clopidogrel may reduce post-operative thrombocytosis and hypercoagulability in dogs that undergo splenectomy for splenic masses.

Strobilanthes crispus bioactive subfraction inhibits tumor progression and improves hematological and morphological parameters in mouse mammary carcinoma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Locally known as 'pecah batu', 'bayam karang', 'keci beling' or 'batu jin', the Malaysian medicinal herb, Strobilanthes crispus (S. crispus), is traditionally used by the local communities as alternative or adjuvant remedy for cancer and other ailments and to boost the immune system. S. crispus has demonstrated multiple anticancer therapeutic potential in vitro and in vivo. A pharmacologically active fraction of S. crispus has been identified and termed as F3. Major constituents profiled in F3 include lutein and ß-sitosterol. AIM OF THE STUDY: In this study, the effects of F3, lutein and ß-sitosterol on tumor development and metastasis were investigated in 4T1-induced mouse mammary carcinoma model. MATERIALS AND METHODS: Tumor-bearing mice were fed with F3 (100 mg/kg/day), lutein (50 mg/kg/day) and ß-sitosterol (50 mg/kg/day) for 30 days (n = 5 each group). Tumor physical growth parameters, animal body weight and development of secondary tumors were investigated. The safety profile of F3 was assessed using hematological and histomorphological changes on the major organs in normal control mice (NM). RESULTS: Our findings revealed significant reduction of physical tumor growth parameters in all tumor-bearing mice treated with F3 (TM-F3), lutein (TM-L) or ß-sitosterol (TM-ß) as compared with the untreated group (TM). Statistically significant reduction in body weight was observed in TM compared to the NM or treated (TM-F3, TM-L and TM-ß) groups. Histomorphological examination of tissue sections from the F3-treated group showed normal features of the vital organs (i.e., liver, kidneys, lungs and spleen) which were similar to those of NM. Administration of F3 to NM mice (NM-F3) did not cause significant changes in full blood count values. CONCLUSION: F3 significantly reduced the total tumor burden and prevented secondary tumor development in metastatic breast cancer without significant toxicities in 4T1-induced mouse mammary carcinoma model. The current study provides further support for therapeutic development of F3 with further pharmacokinetics studies.

Laparoscopic splenectomy for solitary splenic metastasis in a patient with ovarian cancer with a long disease-free interval: a case report.

BACKGROUND: In general, splenic metastasis of epithelial ovarian cancer is considered a terminal stage resulting in widespread metastasis. Solitary splenic metastasis of epithelial ovarian cancer is rare in patients with post-treatment ovarian cancer with long disease-free intervals. CASE PRESENTATION: We report a case of a 62-year-old Japanese woman who presented with elevated serum cancer antigen 125 due to a solitary splenic metastasis of ovarian cancer. She underwent primary open cytoreduction including resection of the right ovarian cancer and postoperative chemotherapy, followed by secondary open cytoreduction and additional postoperative chemotherapy. The disease-free interval was more than 5 years after the additional postoperative chemotherapy. She did not complain of any symptoms and there were no abnormal findings except for elevated cancer antigen 125. However, computed tomography and magnetic resonance imaging revealed a tumor of 6.5 × 4.5 cm in her spleen, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography showed no other metastatic lesions. Laparoscopic splenectomy was performed as tertiary cytoreduction with a diagnosis of a solitary splenic metastasis. Her elevated cancer antigen 125 immediately decreased to within the normal range after the splenectomy. On microscopic examination, the tumor was grade 3 endometrioid adenocarcinoma localized in the spleen, consistent with the previous grade 3 endometrioid adenocarcinoma ovarian cancer. CONCLUSIONS: Elevated cancer antigen 125 is useful for early detection of metastasis of ovarian cancer. Computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography-computed tomography are useful to evaluate whether splenic metastasis of ovarian cancer is solitary, and laparoscopic splenectomy is safe and feasible for a solitary splenic metastasis.

Metastatic Recurrent Hepatocellular Carcinoma Post Liver Transplant With Marked Pretransplant Elevation of Alpha Fetoprotein and No Evidence of Primary Neoplasm.

Determinants of hepatocellular carcinoma recurrence posttransplant include hepatic tumor burden, presence of vascular invasion, and serum alpha-fetoprotein level. However, the significance of marked alpha-fetoprotein elevation in cirrhosis, in the absence of a hepatic mass lesion on imaging studies, is unclear and no longer qualifies for a Model for End-Stage Liver disease exception for transplant listing in the United States. We report a case of posttransplant metastatic recurrent hepatocellular carcinoma in a patient with marked elevation of alpha-fetoprotein pretransplant without imaging evidence of primary hepatic tumor before or after transplant or histopathologic evidence of neoplasm in the explant. This report underscores the significance of marked alpha-fetoprotein elevation in the setting of cirrhosis, even in the absence of a liver lesion, as it may identify a subset of patients with microvascular invasion and microscopic tumor cell dissemination placing them at high risk of posttransplant recurrence. Longer follow-up may be considered in these patients pretransplant to optimize outcomes by lowering posttransplant recurrence risk.

Intravenous immunoglobulin-induced acute thrombocytopenia.

BACKGROUND: Intravenous immunoglobulin (IVIG) has known efficacy in various hematologic conditions, including immune thrombocytopenic purpura. STUDY DESIGN AND METHODS: We present the clinical course of a patient with splenic marginal zone lymphoma, who developed acute thrombocytopenia on three consecutive episodes, with nadir counts of 27 × 109 , 50 × 109 , and 9 × 109 /L, upon administration of Intratect IVIG for hypogammaglobulinemia. An immunofluorescence test applying flow cytometry and monoclonal antibody immobilization of platelet antigens (MAIPA) assay were used to evaluate the reaction between IgG present in the IVIG preparations and the patient's or healthy donors' platelets (PLTs). RESULTS: A strong direct binding reaction was observed between the patient's PLTs and Intratect IgG using both methods. A similar reaction failed to materialize with controls. Binding was not antigen specific according to MAIPA. CONCLUSIONS: This is the first reported case of thrombocytopenia as a possible adverse effect of IVIG.

Clinicopathological features of primary splenic follicular lymphoma.

Follicular lymphoma (FL) is a low-grade lymphoma that is usually characterized by generalized lymphadenopathy. Extranodal invasion by FL generally involves the bone marrow, skin, and duodenum; splenic infiltration often occurs in the advanced stages. However, primary splenic FL is very rare. Hence, few studies have been performed on splenic FL, and its clinicopathological features have not been established. This study aimed to investigate the clinicopathological features of primary splenic FL, as compared to nodal FL. We analyzed 17 patients diagnosed with primary splenic FL and 153 control patients with systemic FL. Hepatitis C virus (HCV)-positive status was significantly more common in patients with splenic FL than in the control patients (p = 0.02). Ann Arbor stage III or IV (p = 0.0003) and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) (p = 0.03) were significantly less common in patients with splenic FL than in the control patients; however, the overall and progression-free survival curves were not significantly different between the groups. Among the 17 patients with splenic FL, the progression-free survival was significantly worse in patients who underwent splenectomy without receiving postoperative chemotherapy than in those who did (p = 0.03). These results suggest that primary splenic FL should be considered different from systemic FL; accordingly, its management should also be conducted differently.

Significance of cytological smear evaluation in diagnosis of splenic mast cell tumor-associated systemic mastocytosis in a cat (Felis catus).

An 8-year-old cat was presented with vomiting and weight loss. Histopathology and cytology revealed systemic mastocytosis, a rare condition and a clinical challenge. This case emphasizes the significance of cytological evaluation of smears in diagnosis of mastocytosis and in confirmation in biopsy specimens.

Signification de l'évaluation d'un frottis cytologique dans le diagnostic d'une mastocytose systémique chez un chat(Felis catus)associée à une tumeur des mastocytes spléniques. Un chat âgé de huit ans a été présenté avec des vomissements et une perte de poids. L'histopathologie et la cytologie ont révélé une mastocytose systémique, une affection rare et difficile sur le plan clinique. Ce cas met en lumière l'importance de l'évaluation cytologique des frottis pour le diagnostic de la mastocytose et la confirmation pour les spécimens de biopsie.(Traduit par Isabelle Vallières).

Case report of primary splenic angiosarcoma with hepatic metastases.

Primary splenic angiosarcoma (PSA) is the most unusual type of malignancy with early multifocal metastasis through hematogenous spread. PSA is generally believed to originate from splenic sinusoidal vascular endothelium with a high rate of metastasis and to have a poor prognosis. Its etiology and pathogenetic mechanisms have not yet been clearly described. Thus far, only approximately 200 cases have been reported. PSA has variable symptomatology with the potential to present with life-threatening complications. The diagnosis of PSA is challenging; and often late. PSA should be considered in the differential diagnosis of patients with splenomegaly and anemia of unknown etiology. Surgical treatment with splenectomy is considered the only curative intervention for potential long-term disease-free survival. Early diagnosis and treatment are very important. It is important that clinical doctors improve the understanding of PSA. Herein, we report one rare case of PSA with hepatic metastases, along with a review of the current literature.

Hepatosplenic T-cell lymphoma with aberrant expression of serum ß-HCG: a case report.

BACKGROUND: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of hematologic malignancies frequently presenting at advanced stage of diagnosis. METHODS: We report a case of PTCL with an uncommon and aggressive onset with disseminated intravascular coagulation (DIC). RESULTS: Laboratory findings revealed an aberrant expression of ß subunit of human chorionic gonadotropin (ß-HCG). Other than for determination of pregnancy, ß-HCG is regularly found as a tumor marker in germ cell tumors with trophoblastic differentiation and its aberrant expression has been reported in the literature in other neoplastic conditions only in the context of case reports. CONCLUSIONS: In hematologic malignancies, ß-HCG expression has been described only in sporadic cases. Awareness of this feature could avoid diagnostic delay in such an aggressive disease.

Big endothelin-1 as a tumour marker for canine haemangiosarcoma.

Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA.

Serum vascular endothelial growth factor in dogs with haemangiosarcoma and haematoma.

Splenic haemangiosarcomas are frequently seen in dogs. Because of their bad prognosis differentiation from other benign splenic lesions are of prognostic importance. However, because haemangiosarcoma is a tumour of the vascular system, it was hypothesised that vascular endothelial growth factor (VEGF) might play a major role in tumour growth and might thus be increased in the blood of affected dogs. The aim of this study was to investigate the clinical relevance of differences in serum VEGF concentrations between dogs with splenic haemangiosarcomas and those with non-malignant splenic lesions (haematomas) and healthy subjects using a canine ELISA. Serum VEGF levels were significantly higher in dogs with splenic masses compared with healthy dogs, but did not differ significantly between dogs with haemangiosarcomas and haematomas. VEGF has a potential clinical utility as a diagnostic marker for dogs with splenic lesions but may not be useful to differentiate among the various splenic lesions.

Schistocytes, echinocytes, iron deficiency anemia, and thrombocytopenia - hematologic manifestations of splenic angiosarcoma.

Splenic angiosarcoma is a rare and aggressive malignancy with an incidence of less than one per million and a fatality rate over 90%.  Early diagnosis is of great importance for optimal management.  Here, we report the case of a patient with splenic angiosarcoma who presented with prominent schistocytes, echinocytes, thrombocytopenia, and iron deficiency anemia, which in combination with radiographic evidence of a splenic mass, raised the suspicion for angiosarcoma and resulted in a prompt surgical intervention with curative intent. Resolution of the hematologic findings following splenectomy suggests that patients with this malignancy should be monitored for recurrent hematologic abnormalities as they may herald recurrence of the disease. We present a literature review on the hematologic manifestations that is associated with this malignant disease.