Surgical and combined treatment of patients with Klatzkin's tumor.

Surgery as being a preferential method of treatment of patients with cholangiocarcinoma is associated with high complications and mortality levels while demonstrating poor long-term outcomes. Optimization of preoperative management and improvement of the results of surgical treatment for patients with proximal extrahepatic bile duct carcinoma. From January 1998 to December 2013 surgical treatment was performed in 36 patients (19 males, 17 females) with Klatzkin's tumor, from whom 10 patients obtained postoperative chemotherapy. Bismuth-Corlette type III-IV tumor stage was determined in 30 (83.3%) patients. Portal vein resection was performed in 13 (36.1%) patients. 27 (75.5%) patients underwent R0 resection. Postoperative mortality rate consisted 16.7%, complications were revealed in 87.1% of cases. 6 (16.7%) patients required additional surgery and interventional procedures were performed in other 20 (55.5%) patients to fix postoperative complications. Overall 5-year survival rate in R0-resection group was 40.1%, median - 29 months. In postoperative chemotherapy group overall 3-year survival rate was 66.7% which was twice higher than in surgery group but the difference was not statistically significant (p=0.35). The improvement of short-term outcomes of surgical treatment for patients with Klatzkin's tumor requires optimization of preoperative management and detailed adherence of surgical techniques. Combination of surgery with postoperative chemotherapy showed the trend to improvement of overall survival.

In vitro cell growth stimulated by recombinant human cytokines can help to diagnose transient leukemia in neonates.

BACKGROUND/PURPOSE: In a previous study, we demonstrated that in vitro cell growth stimulated by human placental conditioned medium distinguished between transient leukemia (TL) and congenital acute myeloid leukemia (AML) in neonates. We then sought to determine whether the application can be expanded if in vitro cell growths are stimulated by recombinant human cytokines including granulocyte-macrophage colony-stimulating factor (rhGM-CSF), interleukin-3 (rhIL-3), stem cell factor (rhSCF) and thrombopoietin (rhTPO). METHODS: Eight neonates with features indistinguishable from AML were studied. Seven patients had Down syndrome and the eighth a normal phenotype. Bone marrow or peripheral blood mononuclear cells (MNC) were cultured in the presence of rhGM-CSF+rhIL-3+rhSCF or of rhTPO alone. After incubation, granulocyte-macrophage colony-forming units (CFU-GM)-derived colonies and clusters were scored on an inverted microscope. Colony-forming units-megakaryocyte (CFU-MK)-derived colonies were counted with an in situ CD61 immunostained dish. Liquid suspension cultures of MNC were stimulated by rhGM-CSF and/or rhTPO. RESULTS: CFU-GM-derived colonies and clusters from bone marrow and peripheral blood MNC revealed normal patterns in seven patients. RhTPO-stimulated megakaryocyte colony formation was normal in one patient. Cytospin smears of liquid suspension cultures all showed good myeloid or megakaryocytic maturation consistent with TL rather than AML. One neonate died on the 2nd day of life, but in the seven remaining patients, blasts disappeared from the peripheral blood within 10 months. Among four patients followed long-term, one developed myelodysplastic syndrome at 21 months. This child was given tailored chemotherapy and had a disease-free survival>20 months. CONCLUSION: In vitro cell growth stimulated by recombinant human cytokines can help to diagnose TL in neonates.

Hematopoietic progenitor cells increase remarkably in the peripheral blood of children with infection.

BACKGROUND: Peripheral blood (PB) of children with viral infection had remarkable increase in colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colonies and clusters. The authors sought to investigate the hematopoietic changes in children with infection. METHODS: The CFU-GM-derived colonies and clusters, burst-forming unit-erythroid (BFU-E)-derived colonies, and colony-forming unit-megakaryocyte (CFU-MK)-derived colonies assays and methylcellulose and/or agarose culture of PB were performed in 25 controls and 42 infected patients. Hematopoietic cell assays and cell culture of bone marrow (BM) were performed in 28 controls and 12 infected patients. RESULTS: The PB controls had very few CFU-GM-derived colonies and clusters. The PB of infected children had many more CFU-GM-derived colonies and clusters. In addition, PB of infected children had abundant BFU-E-derived colonies and CFU-MK-derived colonies, whereas, from BM there were no statistical differences in the numbers of CFU-GM-derived colonies and clusters, BFU-E-derived colonies, and CFU-MK-derived colonies between infection group and control group. The numbers of CFU-GM-derived colonies and clusters were greater in PB of bacteria-infected patients than those in PB of non-bacteria-infected patients. CONCLUSIONS: PB of infected children had increased numbers of colonies, especially in the bacteria-infected group.

Enhancing insecticidal efficacy of baculovirus by early expressing an insect neurotoxin, LqhIT2, in infected Trichoplusia ni larvae.

LqhIT(2), an insect specific neurotoxin from the venom of Leiurus quinquestriatus hebraeus, has been demonstrated to improve insecticidal efficacy of Autographa californica nuclear polyhedrosis virus (AcMNPV). A polyhedrin-positive recombinant AcMNPVvAcP(hsp70)EGFP/P(pag90)IT(2) was engineered for larvae to express the enhanced green fluorescence protein (EGFP) and LqhIT(2) under the control of P(hsp70) and P(pag90) promoters, respectively. This would allow a visual observation of the viral infection and an improvement of the insecticidal efficacy. The insecticidal activity of this recombinant baculovirus, a wild type AcMNPV and four other recombinant baculoviruses, was evaluated and compared in terms of mortality, body weight, median lethal time (LT(50)), and median lethal concentration (LC(50)). Insecticidal efficacy was unaltered when treated with vAcP(hsp70)EGFP, moderately improved when infected by vAcP(10)IT(2) (a P(10)-promoted LqhIT ( 2 ) gene), and significantly elevated when treated with vAcP(pag90)IT(2) or vAcP(hsp70)EGFP/P(pag90)IT(2). No apparent difference was observed in insecticidal efficacy when additional EGFP was expressed as a visible marker. These results suggest that recombinant AcMNPV vAcP(hsp70)EGFP/P(pag90)IT(2) may be used as an effective insecticide against Trichoplusia ni and other lepidopterous insect pests.

Neuroblastoma with expression of erythropoietin resulting in erythrocytosis.

We report the detection of erythropoietin mRNA in the tumor from a patient with neuroblastoma and erythrocytosis. A 2-year-old girl with neuroblastoma presented with hemoglobin 21.3 g/dL, red blood cells 8.03 x 1012/L, and hematocrit 0.641. The serum erythropoietin level was 26.54 mU/mL. The hemoglobin, hematocrit, and serum erythropoietin level were within normal ranges 3 months after surgical excision of the tumor. RT-PCR analysis showed that erythropoietin mRNA expression in the tumor tissue was as high as that of normal renal tissue. These results conclusively demonstrated that the tumor was the site of the ectopic erythropoietin production.

Clinical significance of cell differentiation in hepatocellular carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma is commonly found in Asian countries and prognosis still remains unsatisfactory due to recurrence after surgical tumor resection. METHODOLOGY: We try to demonstrate the recurrence and survival time in 99 surgical patients grading by tumor cellular differentiation from surgical specimen. RESULTS: The rates of well, moderate, and poor differentiation were encountered in 21 cases (21.2%), 61 cases (61.6%) and 17 cases (17.7%), respectively. Small tumor (< 3 cm) was found in only one (5.9%) in the poor differentiation group and 38.1% and 37.7% in the well and moderate differentiation groups. Capsular invasion was found in 13 (61.9%), 39 (63.9%) and 7 (41.1%) in the well, moderate and poor differentiation group, respectively. We found 41.9% (18/43) and 22.4% (13/58) to be tumor free in capsule invasion (-) and (+) after a period of 18.1 and 29.9 months, respectively. However, the recurrent time was 10.6 and 11.3 months, respectively with no significant difference (p > 0.05). Vascular invasion was more frequent in the poor differentiation group (76.5%) than the well (23.8%) and moderate (60.7%) differentiation groups (P < 0.05). We found 23.5% (4/17) and 35% (21/60) to be tumor free but the recurrence time was 6.5 and 14.1 months for the vascular invasion (-) and (+), respectively. The residual median survival times were 6.5 and 14 months after recurrence, respectively. The tumor recurrence rates were 52.7% (11/21), 52.4% (32/61), and 35.5% (6/17) and recurrence times were 11.7, 11.9, and 4.5 months for the well, moderate and poor differentiation group respectively totally. The recurrence time of young age group (< 39 years old) was shorter than the others and there was no patient of well differentiation less than 40 years old. The recurrence time was shorter in the poor differentiation group but there was no significant difference according to age group. The median survival times were 22.2, 22.9, and 9.5 months for each group, respectively. CONCLUSIONS: Differentiation of hepatocellular carcinoma cell had a clinical significance and was found to be positively correlated with the invasive proclivity. The median survival time was longer in both the well and moderate differentiation group, but not in the poor differentiation group. The clinical data revealed that the extended operations performed upon the patients with poor differentiation effected the recurrence time but not the survival time.

The synergistic effect of thrombopoietin in erythropoiesis with erythropoietin and/or IL-3 and myelopoiesis with G-CSF or IL-3 from umbilical cord blood cells of premature neonates.

The authors sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with other cytokine(s) on burst-forming unit-erythroid (BFU-E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony formations from cord blood of premature neonates. Cord blood nonadherent mononuclear cells (MNC) from normal premature neonates were cultured in a methylcellulose system. When cultured with 1 x 10(4) MNC/mL, erythropoietin (EPO) 2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 100 ng/mL, the addition of TPO to EPO gave rise to more BFU-E-derived colonies (p = .000). The addition of TPO to EPO + IL-3 gave rise to more BFU-E-derived colonies (p = .002) also. TPO synergizes erythropoiesis from cord blood of premature neonates. Likewise, the addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies (p = .000) also. TPO synergizes myelopoiesis from cord blood of premature neonates. Thus, TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord blood of premature neonates.

The synergistic effect of thrombopoietin in erythropoiesis with erythropoietin and/or IL-3 and myelopoiesis with G-CSF or IL-3 from umbilical cord blood cells of full-term neonates.

The authors sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with other cytokines on burst-forming unit-erythroid (BFU-E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony formations from cord blood. Cord blood nonadherent mononuclear cells (MNC) from normal full-term neonates were cultured in a methylcellulose system. When cultured with 5 x 10(4) MNC/mL, erythropoietin (EPO) 2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 400 ng/mL (experiment 1), the addition of TPO to EPO gave rise to more BFU-E-derived colonies (p = .002). The addition of TPO to EPO + IL-3 gave rise to more BFU-E-derived colonies (p = .006) also. TPO synergizes erythropoiesis from cord blood. When cultured with IL-3 50 ng/mL, granulocyte colony-stimulating factor (G-CSF) 25 ng/mL, and/or TPO 400 ng/mL, the addition of TPO to IL-3 gave rise to more CFU-GM-derived colonies (p = .002). The addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies (p = .002) also. TPO synergizes myelopoiesis from cord blood. Thus, TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord blood. In the identical conditions of culture, cord blood had significantly greater BFU-E-derived or CFU-GM-derived colony formation than bone marrow (in a previous report by the authors) did. When cultured under conditions similar to those of experiment 1, but with 1 x 10(4) cord blood MNC/mL and TPO 100 ng/mL (experiment 2), results similar to those in the experiment 1 also revealed that TPO has synergistic effects on erythropoiesis and myelopoiesis from cord blood. In every individual assay, the numbers of BFU-E-derived or CFU-GM-derived colonies in experiment 1 were significantly higher than those in experiment 2.

Mitral annulus velocity in the evaluation of left ventricular diastolic function in atrial fibrillation.

This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function in patients with atrial fibrillation. Atrial fibrillation is the most common sustained arrhythmia encountered in clinical practice. The clinical usefulness of conventional Doppler indexes is limited in atrial fibrillation because of the altered left atrial pressure and loss of synchronized atrial contraction. Mitral inflow and mitral annulus velocities were measured simultaneously with tau in 27 patients with nonrheumatic atrial fibrillation at the cardiac catheterization laboratory. Among deceleration time of mitral inflow, peak mitral inflow velocity (E), and peak diastolic mitral annulus velocity (E), only E correlated with tau (r = 0.51, P =.007). Prolonged tau (>/=50 ms) could be predicted by E <8 cm/s with a sensitivity of 73% (16 of 22) and a specificity of 100% (5 of 5). The E/E ratio correlated with left ventricular filling pressure (r = 0.79, P <.001). The E/E ratio of >/=11 could predict elevated left ventricular filling pressure (>/=15 mm Hg) with a sensitivity of 75% (9 of 12) and a specificity of 93% (14 of 15). Mitral annulus velocity is useful in the detection of impaired left ventricular relaxation and estimation of filling pressure even in patients with atrial fibrillation.

Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function.

OBJECTIVES: This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function. BACKGROUND: Mitral inflow velocity recorded by Doppler echocardiography has been widely used to evaluate left ventricular diastolic function but is affected by other factors. The mitral annulus velocity profile during diastole may provide additional information about left ventricular diastolic function. METHODS: Mitral annulus velocity during diastole was measured by Doppler tissue imaging (DTI) 1) in 59 normal volunteers (group 1); 2) in 20 patients with a relaxation abnormality as assessed by Doppler mitral inflow variables (group 2) at baseline and after saline loading; 3) in 11 patients (group 3) with normal diastolic function before and after intravenous nitroglycerin infusion; and 4) in 38 consecutive patients (group 4) undergoing cardiac catheterization in whom mitral inflow velocity and tau as well as mitral annulus velocity were measured simultaneously. RESULTS: In group 1, mean +/- SD peak early and late diastolic mitral annulus velocity was 10.0 +/- 1.3 and 9.5 +/- 1.5 cm/s, respectively. In group 2, mitral inflow velocity profile changed toward the pseudonormalization pattern with saline loading (deceleration time 311 +/- 84 ms before to 216 +/- 40 ms after intervention, p < 0.001), whereas peak early diastolic mitral annulus velocity did not change significantly (5.3 +/- 1.2 cm/s to 5.7 +/- 1.4 cm/s, p = NS). In group 3, despite a significant change in mitral inflow velocity profile after nitroglycerin, peak early diastolic mitral annulus velocity did not change significantly (9.5 +/- 2.2 cm/s to 9.2 +/- 1.7 cm/s, p = NS). In group 4, peak early diastolic mitral annulus velocity (r = -0.56, p < 0.01) and the early/late ratio (r = -0.46, p < 0.01) correlated with tau. When the combination of normal mitral inflow variables with prolonged tau (> or = 50 ms) was classified as pseudonormalization, peak early diastolic mitral annulus velocity < 8.5 cm/s and the early/late ratio < 1 could identify the pseudonormalization with a sensitivity of 88% and specificity of 67%. CONCLUSIONS: Mitral annulus velocity determined by DTI is a relatively preload-independent variable in evaluating diastolic function.

[Occurrence of tertian malaria in a male patient who has never been abroad].

Malaria is estimated to have a worldwide incidence of more than 100 million clinical cases and approximately 1 million deaths per year. Korea, although previously known as an endemic area of tertian malaria (Plasmodium vivax), has been considered free from malaria as there had been no report on indigenous cases since 1984. Recently, however, we experienced an indigenous case of P. vivax infection in a young man who had never been abroad. The patient was a 23-year-old Korean soldier with 18-day history of recurrent fever and chill lasting 4 to 8 hours on alternative days since mid-July 1993. He had lived in Changwon, Kyongsangnam-do, before entering barracks located in Paju-gun, Kyonggi-do on June 1992, and had never been out of Korea. He had no history of blood transfusion nor parenteral use of drugs. The peripheral blood smears showed typical ring forms, trophozoites, and gametocytes of P. vivax, in addition to mild anemia and thrombocytopenia. After confirmation of the diagnosis, he was treated with hydroxychloroquine and primaquine. Follow-up blood smears no more revealed malaria parasites. It is not certain whether the present case is due to a resurgence of indigenous malaria or a secondary infection from introduced malaria. Whichever the source of infection the domestic occurrence of malaria cycle in Korea should be a warning sign in public health point of view.