Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma.

BACKGROUND: To examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma. PATIENTS AND METHODS: A multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes. RESULTS: Among 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001). CONCLUSION: Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Effects of MgADP on length dependence of tension generation in skinned rat cardiac muscle.

The effect of MgADP on the sarcomere length (SL) dependence of tension generation was investigated using skinned rat ventricular trabeculae. Increasing SL from 1.9 to 2.3 microm decreased the muscle width by approximately 11% and shifted the midpoint of the pCa-tension relationship (pCa(50)) leftward by about 0.2 pCa units. MgADP (0.1, 1, and 5 mmol/L) augmented maximal and submaximal Ca(2+)-activated tension and concomitantly diminished the SL-dependent shift of pCa(50) in a concentration-dependent manner. In contrast, pimobendan, a Ca(2+) sensitizer, which promotes Ca(2+) binding to troponin C (TnC), exhibited no effect on the SL-dependent shift of pCa(50), suggesting that TnC does not participate in the modulation of SL-dependent tension generation by MgADP. At a SL of 1. 9 microm, osmotic compression, produced by 5% wt/vol dextran (molecular weight approximately 464 000), reduced the muscle width by approximately 13% and shifted pCa(50) leftward to a similar degree as that observed when increasing SL to 2.3 microm. This favors the idea that a decrease in the interfilament lattice spacing is the primary mechanism for SL-dependent tension generation. MgADP (5 mmol/L) markedly attenuated the dextran-induced shift of pCa(50), and the degree of attenuation was similar to that observed in a study of varying SL. The actomyosin-ADP complex (AM.ADP) induced by exogenous MgADP has been reported to cooperatively promote myosin attachment to the thin filament. We hereby conclude that the increase in the number of force-generating crossbridges on a decrease in the lattice spacing is masked by the cooperative effect of AM.ADP, resulting in depressed SL-dependent tension generation.

Necrotic changes in prolactinomas after long term administration of bromocriptine.

Six prolactinoma patients were studied endocrinologically and their tumors were examined histologically after long term bromocriptine therapy. In patient 1 with a large prolactinoma, a marked reduction in size and a remarkable decrease in elevated serum PRL levels occurred after bromocriptine treatment for 8 months. The histological findings consisted of two components, i.e. shrunken island-like cell nests and acellular spaces. Some degenerative and necrotic tumor cells, hyaline substance, and fibrosis were observed with light and electron microscopy in these acellular spaces. Island-like cell nests consisted of atrophic cells having disproportionally scanty cytoplasm. The same histological findings were observed in four other patients. However, in another patient whose tumor decreased in size only slightly during bromocriptine therapy, the specimen had few acellular spaces. Thus, long term bromocriptine treatment of patients with prolactinomas may result in necrosis of some adenoma cells in some patients.

Late vasospasm of the inferior epigastric artery graft.

We report a case of vasospasm of a free inferior epigastric artery graft at 5-year angiographic follow-up after coronary artery bypass grafting. Although the cause of spasm was not clear, the graft was viable and had a vasoconstrictor profile similar to a gastroepiploic artery graft at long-term follow-up.

Relationship between myocardial cation content and injury in reperfused rat hearts treated with cation channel blockers.

A role for K+ and Ca2+ channel blockers in cardiac contractile dysfunction and myocardial ionic imbalance was examined in isolated rat hearts with 35-min ischemia and 60-min reperfusion. The K+ channel blockers glibenclamide (1-30 microM) and sematilide (1-30 microM), Ca2+ channel blockers diltiazem (0.1-3 microM) and nicardipine (0.03-1 microM) and fast Na+ channel blocker tetrodotoxin (0.01-0.3 microM) were delivered for the last 3-min pre-ischemia. Ischemia-induced increase in Na+ content was attenuated by diltiazem and tetrodotoxin at all concentrations employed and by nicardipine at 0.3 microM, whereas the ischemia-induced loss of K+ was suppressed partially by glibenclamide and sematilide and almost completely by the two drugs in combination. Left ventricular developed pressure of untreated hearts did not recover upon reperfusion, which was associated with increases in myocardial Na+ and Ca2+ contents and decreases in K+ and Mg2+ contents. Glibenclamide and sematilide neither enhanced the post-ischemic recovery of left ventricular developed pressure nor affected cation changes during reperfusion. Diltiazem enhanced the recovery of left ventricular developed pressure and attenuated imbalance of the myocardial Na+ during ischemia and of all myocardial cations examined during reperfusion. The effects of nicardipine on these parameters were small. Tetrodotoxin enhanced the recovery of left ventricular developed pressure and reversed the imbalance of all myocardial cations examined during reperfusion in a concentration-dependent manner. The results suggest that blockade of transmembrane flux of K+ during ischemia plays a minor role in the improvement of post-ischemic contractile recovery, rather blockade of transmembrane flux of Na+ attenuates the ischemia and reperfusion injury.

Proton magnetic resonance spectroscopy of brain tumors: an in vitro study.

The ability of proton magnetic resonance spectroscopy (1H MRS) to diagnose brain tumors was investigated using in vitro high-resolution spectra. Fifty-eight surgically excised samples of brain tumors (12 glioblastomas, 4 anaplastic astrocytomas, 6 astrocytomas, 12 meningiomas, 6 neurinomas, 4 chordomas, 3 craniopharyngiomas, 2 pituitary adenomas, 2 malignant lymphomas, 1 ependymoma, 1 medulloblastoma, and metastatic brain tumors including 3 pulmonary adenocarcinomas, a hepatocellular carcinoma, and a renal cell carcinoma) and 4 nontumorous lobectomized brains were examined by in vitro 1H MRS. N-Acetyl-aspartate was demonstrated in normal tissues but could not be detected in nonneuroectodermal tumors. Total creatine was decreased in all brain tumors in comparison with normal brain tissues, but was relatively higher in neuroectodermal tumors than in other brain tumors. Choline-containing compounds were present in all tumors except craniopharyngioma, and their concentrations were particularly high in a metastatic brain tumor from hepatocellular carcinoma. The concentration of glycine was high in neuroectodermal tumors, whereas that of taurine was high in medulloblastoma, pituitary adenoma, and renal cell carcinoma. Alanine was increased in meningioma, glioma, and pituitary adenoma. Neurinoma had the largest inositol content among the tumors examined. Thus each type of brain tumor exhibited a characteristic MR spectrum. These data suggested that in vivo 1H MRS might provide clinically useful information about tumor metabolism and aid in the differential diagnosis of tumors. Although excellent anatomical localization of tumors can be readily obtained by MR imaging, MRS may provide additional information in cases in which the differential diagnosis of tumors by MR imaging is difficult.

Immunohistochemical heterogeneity of type 1 blood group antigen expressions in testicular germ cell tumors.

The immunohistochemical expression of type 1 blood group antigens (type 1 BGAs) was analyzed for 30 cases of testicular germ cell tumors (TGCTs), using monoclonal antibodies against DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b) (Le(b)). DU-PAN-2 was expressed very frequently in all of the embryonal carcinomas (ECs). CA19-9 expression was demonstrated in 53% of ECs, but the number of positive cells was generally smaller than that for DU-PAN-2. CA19-9-negative ECs tended to show a higher number of DU-PAN-2-positive cells compared to CA19-9-positive ECs, and ECs in which DU-PAN-2 was more strongly expressed showed a relatively frequent expression of CA19-9. In 36% of seminomas and 56% of yolk sac tumors (YSTs), DU-PAN-2 was weakly expressed, and the positive cells were few in number. Little or no expression of CA19-9 was demonstrated in seminomas and YSTs. Regarding Le(a) and Le(b), the expressions were found to be limited to teratomas at a frequency of 57% and 86%, respectively, with the exception of one EC positive for Lea and one YST positive for Leb. Eighty-six percent of teratomas showed expressions of DU-PAN-2 and CA19-9. DU-PAN-2 was also seen in some intratubular malignant germ cells. The antibodies used were all negative for choriocarcinomas, syncytiotrophoblastic giant cells, and normal testicular tissues. The antigen expressions were predominantly observed on the surface of tumor cells developing luminal structures. In conclusion, although CA19-9 was relatively specific for ECs, it should be emphasized that ECs were rather characteristic of extensive DU-PAN-2 expression. Particularly in CA19-9-negative ECs, a combined analysis of DU-PAN-2 and CA19-9 would be helpful in confirming the histopathologic diagnosis of TGCTs. The clinical significance of DU-PAN-2 in ECs as a tumor marker remains to be clarified. Le(a) and Le(b) expressions were thought to be related to the differentiation or maturation rather than to the malignant transformation in TGCTs.

Parietal cephalocele: clinical importance of its atretic form and associated malformations.

In this study of atretic cephaloceles, the authors have considered the pedunculated or sessile type of cephalocele and also small nonpedunculated scalp defects developing in the vertex midline. Parietal cephaloceles were found in 15 infants (10 boys and five girls), and accounted for 37.5% of all cephaloceles. They consisted of four encephaloceles, six meningoceles, and five atretic cephaloceles. The clinical and morphological characteristics of parietal cephaloceles were investigated and compared with those arising at other locations. Parietal cephaloceles carried a much less favorable prognosis than those in the occipital region, regardless of the type of cephalocele; they were associated with cerebral malformations more frequently and were more severe than occipital cephaloceles. Grave congenital anomalies were found in 87% of patients with parietal cephalocele, and only two patients (neither of whom had any other malformation) attained normal development. Brain malformations were closely related to the site from which the cephalocele issued, and dorsal cyst malformation was found in eight patients with parietal cephalocele. Two types of atretic cephaloceles were found, each in a different location. The first type was an alopecic lesion occurring in the parietal midline; all five patients with this type had dorsal cyst malformations and none developed normally. The second type was a nodular lesion developing at the occipital midline, not associated with cerebral anomalies; all five patients with this type showed normal development. The pathogenesis of atretic cephaloceles and their associated intracranial malformations are discussed.

Motif 2 in adenosine kinase homologous ginseng polypeptide showed affinity to D-ribose by capillary zone electrophoresis and surface plasmon resonance.

Affinity capillary electrophoresis (ACE) and surface plasmon resonance (SPR) were applied to the analysis of anti-lipolytic acidic tetradecapeptide from Panax ginseng roots. The ginseng polypeptide (GPP) and modified GPPs were chemically synthesized and their affinity to D-ribose and adenosine was examined by ACE and SPR. GPP had affinity to D-ribose and adenosine and the binding constants (Kb) to GPP were calculated by both methods (Kb = 1.04 x 10(4) mol-1 to D-ribose by ACE and Kb = 1.91 x 10(4) mol-1 to adenosine by SPR). Most of the modified GPPs lost their affinity to D-ribose and adenosine through substitution or rearrangement of the amino acids.

Clinicopathological studies of esophageal carcinoma in achalasia: analyses of carcinogenesis using histological and immunohistochemical procedures.

Achalasia of the esophagus is a benign disease caused by dyskinesia of the lower esophagus and cardia and is presumed to be a premalignant lesion leading to an increased risk of squamous cell carcinoma. We analyzed six surgically or endoscopically resected carcinomas among 54 cases of esophageal achalasia using histological and immunohistochemical procedures. The mean interval between the diagnosis of achalasia and carcinoma was 21.5 years. Four of the six cases were superficial early-stage cancers whilst the other two were advanced cancers invading the adventitia. Histological mapping of the resected esophageal specimens demonstrated marked hyperplastic changes of stratified squamous epithelium and multiple foci of dysplastic changes. The squamous cell carcinomas showed well-differentiated type with low-grade atypia, closely associated with dysplastic foci. Immunohistochemical staining for p53, p21, p16 and epidermal growth factor receptor suggested that the dysplastic epithelium was a borderline lesion between hyperplasia and in situ carcinoma. Our observations suggested that esophageal food stasis induces chronic hyperplastic esophagitis and eventually malignant transformation of esophageal epithelial cells, associated with dysplasia-carcinoma sequence.

Renal expression of insulin-like growth factor-l in acute renal failure: a preliminary report.

Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.

Binding shift assay of parvalbumin, calmodulin and carbonic anhydrase by high-performance capillary electrophoresis.

Shifts in mobility caused by binding of Ca2+ to calmodulin and parvalbumin were studied using high-performance capillary electrophoresis in a Tris-glycine buffer, rather than conventional polyacrylamide gel electrophoresis which requires larger amounts of sample and longer assay time. A Zn(2+)-binding protein, carbonic anhydrase, also showed a partial shift in mobility following Zn(2+)-binding.

A method to reduce thrombogenicity of a graft for small diameter arterial substitution seeded with autologous venous tissue fragments.

The authors successfully applied a method to accelerate endothelialization by tissue fragmentation to a small diameter fabric vascular prosthesis. Tissue fragment seeded grafts showed rapid healing of the neointima. The thrombogenicity of the collagen fibrils in the fragments, however, caused major problems when the method was applied to small diameter grafts: the positively charged collagen fibrils aggregated the negatively charged platelets. The authors masked the fibrils electrostatically with heparin molecules, which are negatively charged. A canine jugular vein was resected, minced into tissue fragments, and suspended in the heparin solution; it then was sieved through the wall of a fabric prosthesis. The grafts (4 mm internal diameter and 3.5 cm in length) were implanted into both carotid arteries of six dogs (12 grafts). Tissue fragment seeded grafts without heparin also were implanted into six dogs. As a control, preclotted fabric grafts were implanted into six dogs (12 grafts). These grafts occluded within 1 week, whereas all the masked grafts were patent without thrombi. In vitro examination of heparin release revealed that approximately 92% of heparin in the graft was released during the first 5 hr, but approximately 6% remained after 25 hr. These results indicate that the method is applicable to small diameter arterial grafts.

Proton magnetic resonance spectroscopy of astrocytic tumors: an in vitro study.

Water-soluble metabolites extracted from 20 astrocytic tumors (11 glioblastomas, 3 anaplastic astrocytomas, and 6 low-grade astrocytomas) and four normal brains were measured qualitatively and quantitatively using in vitro high-resolution proton magnetic resonance (1H-MR) spectroscopy. MR spectra from tumors exhibited characteristic patterns according to malignancy, presumably reflecting the metabolism of gliomas. Concentrations of choline-containing compounds, inositol, alanine, and glycine increased according to the malignancy, while that of total creatine decreased. In particular, glycine concentration was very high in glioblastoma, and an immunohistochemical study using anti-glycine antibody demonstrated that glycine was mainly distributed in glioma cells, not in proliferative endothelial cells. The ratios of choline-containing compounds and glycine to total creatine are useful parameters for grading gliomas, and the ratio of glycine to total creatine is useful for the differential diagnosis of glioblastoma from metastatic tumor. Such indications appearing in in vivo 1H-MR spectroscopy might provide clinically useful information on tumor metabolism and malignancy, and help assess the effects of radiation therapy and chemotherapy on gliomas.

Intracranial pressure responses during hyperbaric oxygen therapy.

The responses of intracranial pressure (ICP) to hyperbaric oxygen (HBO) therapy and arterial gas pressures were investigated. ICP was measured through a ventricular or spinal drainage catheter in patients with brain tumor or cerebrovascular disease. Changes in ICP, heart rate (HR), arterial blood pressure (ABP), and transcutaneous partial pressure of carbon dioxide (PtcCO2) or oxygen (PtcO2) were recorded continuously during air or 100% O2 breathing at 1 and 2.5 atmospheres absolute (ATA). HR and PtcCO2 decreased and mean ABP was unchanged during HBO inhalation. ICP was reduced at the beginning and tended to increase gradually during HBO inhalation. The change from air to O2 without altering respiratory frequency and volume caused a gradual increase of ICP and PtcCO2 with a transient ICP reduction in an artificially respirated patient. Intentionally reduced respiration to maintain PtcCO2 at the value at 2.5 ATA with air caused the ICP to return to near the value at 2.5 ATA with air even during HBO inhalation. These findings suggest that reduced ICP is initially due to direct cerebral vasoconstriction caused by hyperoxia and is maintained mainly by induced hypocapnia during HBO inhalation. Care is required when giving HBO therapy to patients with a high ICP and/or who are respirated artificially.

Repeated intracerebral hemorrhage associated with impaired platelet aggregation--report of two cases.

The authors report two cases of hypertensive intracerebral hemorrhage (ICH) repeated at the same site within 1 or 2 days causing death in a 53-year-old male and a 48-year-old female. In both cases, platelet aggregation was significantly impaired. Acquired platelet dysfunction may be important in the expansion of hemorrhage in patients with repeated hypertensive ICH. In such cases administration of normal platelets may be required to prevent devastating hemorrhage.

Venous angioma: follow-up study and therapeutic considerations.

Ten patients with cerebral venous angioma (VA) were followed up for 12 to 106 months. Seven VAs were found as a result of intracerebral hemorrhage and the others were found incidentally. Among three VAs cauterized or partially excised, one disappeared but two were unchanged on follow-up angiography. Another VA, treated by irradiation following evacuation of the hematoma, gradually reduced in size on angiography. In the remaining six VAs treated conservatively, follow-up angiography demonstrated no visible change. During the follow-up period, bleeding from VA was encountered in one patient who had previously suffered from intracerebral hemorrhage. Prevention of bleeding from VA is considered important; however, complete extirpation of VA is difficult since the resectable area of normal brain parenchyma including the VA is very limited. From our experience, radiation therapy is believed to be useful when VA is considered to carry the risk of hemorrhage.

Influence of boiling water treatment on surface roughness and surface microstructure of set gypsum (dental stone).

The influence of boiling water treatment on the surface roughness and surface microstructure of set gypsums was investigated. Typical surfaces before and after immersion in boiling water were compared by means of SEM observation, the Knoop hardness test, and a surface roughness test. The surfaces of set gypsums were rougher than that of an acrylic resin plate, and after immersion in boiling water, highly roughened surfaces and thinner crystal bodies were observed on each specimen under SEM. The knoop hardness of set gypsums was considerably lowered after boiling water immersion. That of die stones was the same or lower than set dental stones. The results showed that even brief immersion in boiling water had profound effects on the dental stone cast, resulting in rougher surfaces and lower hardness of set gypsums.

[Barbiturate therapy in 16 cases with intracranial lesion with special reference to the indication and limitation].

The effects and indications of barbiturate therapy for brain protection, and prevention and reduction of the intracranial hypertension were investigated using an ultrashort acting barbiturate, thiamylal, in sixteen cases with intracranial lesions. Final outcome of the treatment revealed 8 good recoveries which were actively administered thiamylal during operation or immediately after. On the other hand, four cases, whose intracranial pressures (ICPS) of over 40 mmHg could not be controlled suffered brain death. Barbiturate therapy was not effective for brain protection of primary damaged lesions. It is concluded that barbiturate therapy may provide a satisfactory reduction of the intracranial hypertension in cases during the early postoperative stage or of under 40 mmHg initial ICP.

[Arteriovenous malformation associated with meningioma].

A case of arteriovenous malformation (AVM) associated with a meningioma is reported. A 28-year-old woman was hospitalized for generalized convulsion. CT scan and right carotid angiogram revealed AVM in the right parietal lobe extending to the wall of the lateral ventricle. At the time of surgery an intraventricular meningioma attached to the choroid plexus was found in the excised cavity of the AVM. It is suggested that the meningioma might have been caused by chronic irritation due to an increased blood flow in the arteries supplying the AVM, because the AVM and the meningioma exist in the same lesion and share the same blood supply.