Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: A Histological Assessment of 365 Patients in Japan

Background  A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. Methods  A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. Results  The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). Conclusions  Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.     

Selective hepatic vascular exclusion for the hepatic resection of HCC

BACKGROUND/AIMS: Selective hepatic vascular exclusion (SHVE) is an effective technique for the control of bleeding in major hepatic resections. Outcomes of the procedures of the SHVE group were compared with the non-SHVE group. METHODOLOGY: A retrospective study was carried out of 312 hepatic resections performed over a period of 10 years. The cases in this study were limited to Child's classification A, because of the rate of Child A in the SHVE group (n=82) was significantly higher than that within the non-SHVE group (n=158) (93% vs. 71%; p < 0.001). Preoperative factors, like age, gender, tumor size, intraoperative blood loss, operation time, and the postoperative course of the two groups were compared for both groups. RESULTS: The SHVE group showed significantly less blood loss, necessary blood transfusion, and a significant rate of severe postoperative complications. The rate of segmentectomy and subsegmentectomy in the SHVE group was higher than in the non-SHVE group, and the rate of partial hepatectomy and lobectomy in the non-SHVE group was higher than that in the SHVE group. Although the more difficult operations were performed in the SHVE group than in the non-SHVE group, there was no significant difference in the postoperative hospital stays in both groups. CONCLUSIONS: The SHVE technique is effective for bleeding control in major liver resections.     

Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi

Fusicoccins are a class of diterpene glucosides produced by the plant-pathogenic fungus Phomopsis amygdali. As modulators of 14-3-3 proteins, fusicoccins function as potent activators of plasma membrane H(+)-ATPase in plants and also exhibit unique biological activity in animal cells. Despite their well studied biological activities, no genes encoding fusicoccin biosynthetic enzymes have been identified. Cyclic diterpenes are commonly synthesized via cyclization of a C(20) precursor, geranylgeranyl diphosphate (GGDP), which is produced through condensation of the universal C(5) isoprene units dimethylallyl diphosphate and isopentenyl diphosphate by prenyltransferases. We found that (+)-fusicocca-2,10 (14)-diene, a tricyclic hydrocarbon precursor for fusicoccins, is biosynthesized from the C(5) isoprene units by an unusual multifunctional enzyme, P. amygdali fusicoccadiene synthase (PaFS), which shows both prenyltransferase and terpene cyclase activities. The functional analysis of truncated mutants and site-directed mutagenesis demonstrated that PaFS consists of two domains: a terpene cyclase domain at the N terminus and a prenyltransferase domain at the C terminus. These findings suggest that fusicoccadiene can be produced efficiently in the fungus by using the C(5) precursors, irrespective of GGDP availability. In fact, heterologous expression of PaFS alone resulted in the accumulation of fusicocca-2,10 (14)-diene in Escherichia coli cells, whereas no product was detected in E. coli cells expressing Gibberella fujikuroi ent-kaurene synthase, another fungal diterpene cyclase that also uses GGDP as a substrate but does not contain a prenyltransferase domain. Genome walking suggested that fusicoccin biosynthetic enzymes are encoded as a gene cluster near the PaFS gene.     

Combined coronary artery re-operation and pulmonary resection for hemoptysis

We present a 59-year-old woman who underwent combined pulmonary resection for bronchiectasis with massive, recurrent hemoptysis and redo coronary artery bypass. She had previously been hospitalized four times for massive hemoptysis. She had also undergone coronary artery bypass and had symptomatic severe graft disease. We performed simultaneous right middle lobectomy and redo triple bypass. At surgery, lobectomy was performed before heparinization, then redo bypass was performed using on-pump cardiopulmonary bypass. The postoperative course was uneventful.     

Huge brain abscess and invasive pulmonary disease by fungal infection during chemotherapy for infantile acute myeloid leukemia

The authors encountered a 7-year-old girl with a huge brain abscess and invasive pulmonary lesion due to fungus, who had been treated for acute myelogenous leukemia (AML). Although she was administered voriconazole to prevent fungal infection, she developed partial seizure and paralysis of the left side because of the huge brain abscess. Fungus culture and serum fungal markers, including Aspergillus antigen, were all negative. She underwent drainage and surgical resection of necrotic tissue after antifungal agents, including liposomal amphotericin B (L-AMB). Resection pathology revealed localized fungal infection, suspected as due to zygomycosis. The cerebral lesion reduced after the operation and the pulmonary lesion also vanished. We discontinued AML treatment because of the severe fungal infection; however, she has remained in continuous remission. Although Lipo-AMPH and itraconazole are comparatively effective for zygomycosis, progressive disseminated zygomycosis is extremely intractable. Our case underlines the feasibility and successful application of combined conventional antifungal agents and surgical resection in such a patient.     

Small-cell lung carcinoma produces salivary-type amylase: a case report with review

A 53-year-old woman diagnosed with small-cell lung carcinoma (SCLC) was referred to our hospital because of general malaise and inappetence. Serum amylase levels were drastically elevated at 13,920 IU/l, with the salivary type dominating. She suffered multiple liver metastases and presented with disseminated intravascular coagulation (DIC). She succumbed to progressive malaise one month after admission. The amylase level was increased to 18,630 IU/l just before her death. Necropsy of the right supraclavicular lymph node confirmed SCLC with partial necrosis. Immunohistological analysis revealed that the SCLC produced salivary-type amylase. A rare case of salivary-type amylase-producing SCLC with a futile outcome was reported with review of the previous literature.     

Effects of PMX-DHP treatment for patients with directly induced acute respiratory distress syndrome

Endotoxin-removal direct hemoperfusion column containing polymyxin B immobilized fibers (PMX-DHP) is an effective procedure for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS). We investigated retrospectively the effects and appropriate timing of PMX-DHP induction for directly induced ARDS in 38 patients. PMX-DHP was carried out twice for two hours. Blood pressure, heart rate (HR) and PaO(2)/FIO(2) (PF) ratio, leukocytes, platelets, endotoxin, inflammatory cytokines and clusters of differentiated peripheral neutrophils and monocytes were measured before and after PMX-DHP. Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores and lung injury scores (LIS) were determined at the time of starting PMX-DHP. The underlying causes of ARDS were pneumonia in 29 patients and aspiration pneumonia in 9 patients. The patients were divided into Survivors (n = 21) and Nonsurvivors (n = 17). Mortality was 45% at 30 days after PMX-DHP. The APACHE II and SOFA scores and the LIS were not significantly different between the two groups. The time from the onset of ARDS to the start of PMX-DHP was significantly delayed between the two groups. PMX-DHP significantly improved the PF ratio, HR and systolic blood pressure in the Survivors compared to the Nonsurvivors. The function of active monocytes in the peripheral blood was significantly suppressed after PMX-DHP. This early induction of PMX-DHP is indicated for directly induced ARDS. In the Nonsurvivors, this delay could have led to undesirable responses to oxygenation and circulation after PMX-DHP.     

Spasm induced by protection balloon during carotid artery stenting

Purpose The PercuSurge system is a distal balloon embolic protection device used for carotid artery stenting (CAS). We performed a retrospective study on the prognosis and clinical effects of spasms induced by the PercuSurge GuardWire system (PercuSurge-induced spasm). Materials and methods We performed CAS in 118 carotid stenoses using the PercuSurge system. Of the 118 procedures, 31 (26.3%) of the patients experienced PercuSurge-induced spasm, and all underwent postoperative follow-up studies by cerebral angiography and antiplatelet treatment. Results On follow-up angiograms obtained a mean of 5.2 months (range 3–10 months) after CAS, all 31 PercuSurge-induced spasms had disappeared, and no delayed stenosis was found at the sites where the spasms had occurred. No ischemic events due to the spasms occurred during a mean follow-up of 13 months (range 3–32 months). Conclusion In the hands of physicians experienced in endovascular surgery, CAS using the PercuSurge system is a safe method with which to treat patients with carotid stenosis. Our study demonstrated that PercuSurge-induced spasms had no morphological or clinical adverse effects.     

The sinusoidal pressure during ischemia-reperfusion injury in perfused mouse liver pretreated with or without L-NAME

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver. MATERIALS AND METHODS: Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). RESULTS: In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h. CONCLUSIONS: Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.     

Rapid quantitative analysis of magnesium stearate in pharmaceutical powders and solid dosage forms by atomic absorption: Method development and application in product manufacturing

The distribution of magnesium stearate (MgSt) in tablet granule has a significant impact on the compression process. A rapid quantitative method for evaluating magnesium stearate content by atomic absorption was established. The MgSt was extracted from the granule in 0.1 mol/L nitric acid and the resulting free magnesium ion quantitated by atomic absorption. The total analysis time was significantly shortened in comparison to the previously used sample ignition method.