Long-term outcome of vincristine-aspirin-ticlopidine (VAT) therapy for vascular tumors associated with Kasabach-Merritt phenomenon.

BACKGROUND: . This study aimed to clarify the combinatorial treatment effect of agents as aspirin and ticlopidine associated with vincristine in the management of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenic coagulopathy that occurs in the presence of an enlarging vascular tumor such as kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). PROCEDURE: . A retrospective review was conducted of medical records of all children with diagnosis of KHE or TA associated with KMP treated with vincristine-aspirin-ticlopidine (VAT) therapy at two different institutions in the same country from 1994 to 2011. Clinical features, response to VAT therapy and outcomes were recorded. RESULTS: . Eleven patients (mean age 11 months, range 0-36), including seven females (64%) and four males (36%), were identified. Seven patients underwent incisional biopsy and two different histologies were found, KHE in four patients and TA in three patients. Tumors were located in the head and neck (n = 5), chest wall (n = 2), arm (n = 2) and retroperitoneum (n = 2). Mean platelet level was 10,200/mm(3) (range 4,000-21,000). A plaque-like lesion with ecchymosis was the most common cutaneous manifestation (63%). All patients underwent VAT therapy. Mean duration of treatment was 3.9 months for vincristine, 13.9 months for aspirin, and 13.4 months for ticlopidine. All patients are alive with a mean follow-up of 4.5 years (range, 2-17). CONCLUSIONS: . Antiaggregant therapy is helpful in combination with vincristine in the treatment of KMP associated with KHE and TA. Prognosis is excellent if severe thrombocytopenia is controlled despite failure in reduction of tumor size.

Disseminated intravascular large B cell lymphoma with slowly decreasing high-density lipoprotein cholesterol.

Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal large B cell lymphoma in the lumina of small vessels. Low high-density lipoprotein cholesterol (HDL-C) is associated with sepsis, malignancy, and death. Recent evidence suggests an inverse relationship between HDL-C and non-Hodgkin lymphoma. We report the case of a 71-year-old female who presented with decreasing HDL-C for years prior to diagnosis of IVLBCL. The patient developed nonspecific symptoms, including dizziness, gait instability, fatigue, tinnitus, and weight loss. Although malignancy was high on the differential, no diagnosis was made antemortem. The diagnosis of disseminated intravascular large B cell lymphoma was made postmortem in multiple organ systems. The presentation of IVLBCL is nonspecific and misleading. To our knowledge this is the second known case report of low HDL-C preceding diagnosis of IVLBCL, but the first case documenting low HDL-C years prior to diagnosis.

A patient with intravascular lymphoma presenting with cerebral infarction and a high serum MPO-ANCA level.

A 74-year-old woman presented with multiple brain infarctions, an inflammatory reaction, and a high serum titer (414 U/ml) of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) with no hematological abnormalities. After the inflammation and ANCA titers were resolved with steroid therapy for suspected microscopic polyangiitis, hemophagocytic syndrome developed. Biopsies revealed non-Hodgkin's intravascular lymphoma (IVL). The flare of IVL with negative serum ANCA suggested that the initial high serum MPO-ANCA had not originated from tumor cells.

Evaluation of GLUT1, IGF-2, VEGF, FGF 1, and angiopoietin 2 in infantile hemangioma.

INTRODUCTION: Infantile hemangioma (IH) is a common vascular tumor in children. It is reported that IHs are associated with immunochemical markers such as vascular endothelial growth factor (VEGF)-A, glucose transporter isoform 1 (GLUT1), and insulin-like growth factor-2 (IGF-2). MATERIAL AND METHODS: This cross-sectional study focused on pediatric patients with IH. A total of 46 patients (mean age 14.2±21.9 months) with IH and 45 healthy controls (mean age 21.8±15.08 months) were enrolled. Demographic data, clinical findings, and laboratory parameters were recorded. Blood samples were collected. Serum GLUT1, IGF-2, VEGF-A, fibroblast growth factor 1 (FGF1), and angiopoietin 2 levels were assessed by enzyme-linked immunosorbent assay. RESULTS: Serum GLUT1, IGF-2, and VEGF-A levels were significantly higher in patients with IH than in healthy controls (8.80±4.07pg/mL vs. 5.66±4.34pg/mL, 281.10±84.12pg/mL vs. 234.19±75.38pg/mL, 1196.99±389.34pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.026, p=0.030, and p=0.036). Serum GLUT1, IGF-2, and VEGF-A levels in patients with complicated hemangioma were significantly higher than in healthy controls (9.69±3.94pg/mL vs. 5.66±4.34pg/mL, 289.94±83.18pg/mL vs. 234.19±75.38pg/mL, 1276.22±388.24pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.017, p=0.022, and p=0.011). Serum GLUT1, IGF-2, and VEGF-A levels in patients with hemangioma receiving propranolol treatment were significantly higher than in healthy controls. Serum FGF1 levels were higher in patients with IH, complicated hemangioma, and hemangioma receiving propranolol treatment than in healthy controls but the difference was not statistically significantly. CONCLUSION: Serum GLUT1, IGF-2, and VEGF-A levels were positively correlated with disease severity in patients with hemangioma, for example, in complicated hemangioma and hemangioma requiring propranolol treatment. However, further research on larger and different age subgroups is warranted to assess these markers.

Predictor for histological microvascular invasion of hepatocellular carcinoma: a lesson from 229 consecutive cases of curative liver resection.

BACKGROUND: Microscopic vascular invasion is an important risk factor for recurrent hepatocellular carcinoma (HCC), even after curative liver resection or orthotopic liver transplantation. To predict microscopic portal venous invasion, the following two questions were examined retrospectively: Is it possible to detect microvascular invasion preoperatively? What are the characteristics of a group of early HCC recurrences even with no microvascular invasion? METHODS: Study 1 included 229 patients with HCC who underwent curative liver resection between 1991 and 2008; 127 had HCC without microscopic portal venous invasion, and 52 had HCC with microscopic portal venous invasion (MPVI). These two distinct groups were analyzed with regard to various clinicopathologic factors. Subsequently, we specifically investigated if HCCs <5 cm with vascular invasion (n = 32) have some characteristics that would allow detection of latent microvascular invasion. Study 2 included 127 HCC patients without MVPI; 42 had a recurrence within 2 years, and 85 patients were recurrence-free for at least 2 years. These two distinct groups were analyzed with regard to various clinicopathologic factors. RESULTS: HCC diameter of >5 cm, the macroscopic appearance of HCC, and high levels of preoperative des-gamma-carboxyprothrombin are significant prognostic factors in identifying microvascular invasion of HCC. The strongest predictor of early recurrence (within 2 years) was the serum alpha-fetoprotein level in patients without clear microvascular invasion. CONCLUSIONS: Tumor size, macroscopic appearance, and high tumor marker levels are important elements in identifying the group of patients with a low HCC recurrence rate after curative liver resection.

Upper arm life-saving amputation of a 12 day-old neonate due to extensive vascular tumor of the upper extremity.

Vascular tumors in neonates are mostly benign; however, locally aggressive voluminous forms may destabilize the hemodynamics of a neonate. Herein, we present an unusual case of a neonatal giant vascular tumor in the right upper extremity, causing a consumption coagulopathy and acute deterioration of vital signs. The patient required mechanical ventilation, inotropic support, and administration of blood products by the seventh day. Vascular embolization attempts failed to improve the general condition of the patient. Due to the deteriorating and life-threatening general condition of the patient, amputation around the upper arm level occurred under emergency conditions on the twelfth day. The patient's hemodynamic parameters were regained immediately, with neither inotropic agents nor blood products required after the second postoperative day. Clinical and pathological diagnosis revealed kaposiform hemangioendothelioma. Patient monitoring proceeded until the age of 15 months, with no local recurrence around the stump or soft tissue coverage complications. Therefore, since other treatment options failed, the early amputation decision was life-saving.

Classification of cutaneous intravascular breast cancer metastases based on immunolabeling for blood and lymph vessels.

BACKGROUND: Intravascular breast cancer metastases to the skin can have several clinically distinct manifestations. Carcinoma telangiectoides, which presents as an erythematous patch with prominent telangiectasias or lymphangioma circumscriptum-like lesions, is a rare manifestation of cutaneous metastatic breast cancer and has been proposed to spread via dermal blood vessels. Carcinoma erysipelatoides, which presents as an erysipelas-like patch or plaque, has been proposed to spread via lymphatics. Clinical variants with nodular lesions that show tumor cells within vessels and in the extravascular space are seen more commonly. It has not been demonstrated conclusively whether dermal blood vessels or whether dermal lymph vessels are principally involved in these clinically distinct forms of cutaneous breast cancer metastases. OBJECTIVES: We sought to determine if carcinoma telangiectoides affects predominantly dermal blood vessels and if carcinoma erysipelatoides affects predominantly dermal lymph vessels. METHODS: Serial sections of biopsy specimens from patients with a characteristic clinical presentation of carcinoma telangiectoides and carcinoma erysipelatoides were labeled for cytokeratin to identify malignant cells. Subsequently, these sections were labeled for CD31 (a marker for blood and lymph vessels) and podoplanin (a marker for lymph vessels, but not for blood vessels), to differentiate blood vessels from lymph vessels in these sections. RESULTS: Sections from carcinoma telangiectoides showed malignant tumor cells strictly within dermal blood vessels, but not in lymph vessels. In contrast, sections from carcinoma erysipelatoides showed malignant tumor cells strictly in dermal lymphatics. LIMITATIONS: We used typical clinical cases to demonstrate the distinct involvement of blood and lymph vessels in these variants of cutaneous metastatic breast cancer. A larger case series is needed to confirm these findings. CONCLUSIONS: Immunolabeling for CD31 and podoplanin of cutaneous lesions of metastatic breast cancer confirms the spread of tumor cells predominantly via lymphatics in carcinoma erysipelatoides and predominantly via blood vessels in carcinoma telangiectoides.

Successful management of steroid-resistant vascular tumors associated with the Kasabach-Merritt phenomenon using sirolimus.

Vascular tumors associated with Kasabach-Merritt phenomenon (KMP) are life-threatening and the mortality is as high as 10-30%. Steroids are considered the primary choice for drug therapy. However, there are many steroid-resistant cases. In the present study, analyzed data are presented to support the use of sirolimus in clinical practise for the treatment of corticosteroid-resistant vascular tumors with KMP in eight infants between June 2015 and April 2017 in a single hospital. The time to initial response was 6.8 ± 2.7 days. The average stabilization time for the platelet count was 19.1 ± 8.5 days. At the time of publication, the average duration of sirolimus treatment was 14.1 ± 4.0 months, and the average time for sirolimus treatment as a single agent was 12.6 ± 4.2 months. The side-effects were tolerable and included oral ulcer, fever, pain, skin rash and transient ascension of serum transaminase and cholesterol. Our study indicated that sirolimus therapy is an effective and safe method for the treatment of corticosteroid resistant vascular tumors associated with KMP in infants.

Intravascular lymphoma - a rare cause of hemolytic anemia and neurologic disorders.

Intravascular lymphoma is an uncommon and often overlooked form of non-Hodgkin's lymphoma characterized by extensive proliferation of lymphoid cells within the lumina of small and medium-sized vessels. Clinical symptoms of the disease are variable and often nonspecific, mostly neurologic in nature. With an aggressive course, intravascular lymphomatosis has a poor prognosis and is rarely diagnosed ante mortem. We describe here a 76-year-old woman with the clinical diagnoses of hemolytic anemia and progressive lethargy where intravascular lymphomatosis turned out as the underlying cause of the disease.

Intravascular large cell lymphoma associated with hypoalbuminemia.

We report here a 71-yr-old Japanese woman who presented with severe anasarca and hypoalbuminemia. She had a postmortem diagnosis of intravascular large B-cell lymphoma, which is a rare type of lymphoma characterized by an intravascular proliferation of lymphoma cells. Severe generalized edema was thought to be attributed to vascular and/or lymphatic obstruction due to proliferation of lymphoma cells within the lumina and/or an increase in catabolism induced by tumor proliferation.

[Portal vein thrombosis after splenectomy in childhood: report of 4 cases]. / Thrombose portale après splénectomie chez l'enfant: à propos de 4 observations.

Portal vein thrombosis is a major complication of splenectomy. Its frequency is underestimated because of asymptomatic cases. Mesenteric occlusion with intestinal infarcts is the first cause of mortality. Secondarily, in the absence of repermeabilisation, a portal hypertension can occur. We present in this study 4 cases of portal vein thrombosis in childhood. Portal vein thrombosis is frequent (8% of splenectomies) and may be asymptomatic. Doppler postoperative surveillance is justified. Thrombocytosis seems to be a determinant factor. Early diagnosis and treatment may reduce lethal outcome.

Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer.

BACKGROUND AND AIM: The significance of serum levels of transforming growth factor (TGF)-beta1 in the development of gastric cancer is unclear. The purpose of this study is to determine whether serum TGF-beta1 correlated with the clinicopathological findings of patients with gastric cancer. METHODS: Transforming growth factor-beta1 levels in the serum of 275 gastric cancer patients and 275 gender- and age-matched healthy controls were measured with enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. RESULTS: The mean level of serum TGF-beta1 of gastric cancer patients (15.9 +/- 5.9 ng/mL) was significantly higher than that (13.9 +/- 7.4 ng/mL) of healthy controls (P < 0.01). The odds ratio for the subjects in the highest quartile (16.7 ng/mL or more) was 4.03 (95% confidence interval, 2.14-7.58), as compared with that for the subjects in the lowest quartile (0-9.5 ng/mL). Patients with venous invasion compared to those without venous invasion had significantly elevated serum TGF-beta1 (17.3 +/- 7.2 vs 15.0 +/- 5.1 ng/mL; P = 0.04). There were no statistically significant differences between the two groups categorized by histological type, lymph node metastasis and distant metastasis. Logistical regression analysis showed that venous invasion was significantly correlated with elevated serum TGF-beta1 levels (P = 0.02). CONCLUSIONS: The present study showed that an elevated serum TGF-beta1 level may be significantly correlated with venous invasion in gastric cancer patients.