Clonal growth of hepatitis B virus-integrated hepatocytes in cirrhotic liver nodules.

A total of 83 cirrhotic nodules (pseudolobules) individually collected from 11 cirrhotic livers of hepatitis B virus carrier patient were analyzed for the frequency and mode of hepatitis B virus integration as well as histological features. Southern blot analysis disclosed discrete bands at higher molecular weight region in 26 of 83 nodules (31.3%), indicating a clonal growth of hepatocytes with viral integration. Considerable variation (0-75%) existed in the positive rates for discrete bands in nodules among livers. Molecular cloning revealed the sequence flanking an integrated viral sequence to be host DNA and thus confirmed true integration. Histological analysis, however, did not reveal any neoplastic-appearing foci of growth within nodules, despite the fact that the detection sensitivity would predict clones of more than 10(5) cells to give rise to clonal integration patterns on Southern blot analysis. The question of whether clonal expansion of hepatocytes reflects any viral integration-associated growth advantage and/or a preneoplastic condition awaits future studies.     

A histopathological analysis of five cases of adenomatous hyperplasia containing minute hepatocellular carcinoma.

We present five cases of adenomatous hyperplasia (AH) containing minute hepatocellular carcinoma (HCC) in cirrhotic liver. All the patients were Japanese, four males and one female, ranging in age from 60 to 80 years. Two of the specimens were obtained at surgery and the others at autopsy. The AH specimens ranged from 2.0 to 3.0 cm in diameter, and the maximum diameter of HCC foci in the AH was 2.0 cm. Histologically, apart from the HCC foci, the AH specimens showed intrinsic atypia, suggesting preneoplastic change. These features included an increase of both cellularity and the nucleo-cytoplasmic ratio, distortion of cord structure and pseudoacinar formation. All of the AH specimens contained typical portal triads. Details of diagnostic imaging were also obtained in four cases. The findings of the present study support the possibility that AH with intrinsic atypia is a preneoplastic lesion of HCC. The sequence of "adenomatous hyperplasia with intrinsic atypia-HCC foci" would thus represent part of the early phase of hepatocarcinogenesis in humans.     

Calcium pump expression in human bone and soft tissue tumours

Ninety-one cases of human bone and soft tissue tumours were studied for calcium pump expression by strepto-avidin-biotin immunohistochemical staining with a monoclonal antibody against sarcoplasmic reticulum calcium-ATPase (mAb6F5). Two out of 5 cases of embryonal rhabdomyosarcoma, 1 out of 5 cases of biphasic synovial sarcoma, 4 of 4 cases of chordoma and all of 3 chondrosarcoma cases were positive for mAb6F5. Although this novel monoclonal antibody can be used as a marker of myogenic tumours, the present positive result for endoplasmic reticulum calcium-ATPase (calcium pump) in other tumours including chordoma, chondrosarcoma and synovial sarcoma indicates a wider immunoreactivity. The findings further suggest that intracellular calcium may play an important role in cell proliferation and/or differentiation.     

Benign clear cell tumor of the lung in an 8-year-old girl

A case of "benign clear cell tumor of the lung" occurred in an 8-year-old girl. The tumor was a solid well-circumscribed mass, measuring 1 cm in diameter. Histologically, it consisted of polygonal cells intermingled with large, thin-walled vessels. Glycogen was scarce in paraffin sections; however, electron microscopic observation revealed a large amount of glycogen. Intracytoplasmic filaments were not observed, but scattered pinocytotic vesicles and plaquelike densities along the plasma membrane were found.     

Dedifferentiated chondrosarcoma of the rib with a malignant mesenchymomatous component: An autopsy case report

A rare variant of dedifferentiated chondrosarcoma wlth malignant mesenchymomatous component in a 57-year-old male is reported. The patient presented with a posterior mediastinal mass arising from the left eighth and ninth ribs showing well differentiated, low-grade chondrosarcoma. Five years later, local recurrence occurred and an excised specimen also showed the same histological features as the primary tumor. Another 6 years later, the tumor recurred and metastasized to the multiple organs, the patient dying 4 months later. Autopsy revealed that the recurrent and metastatic tumors showed malignant mesenchymomatous 'dedifferentiation' of chondrosarcoma composed of rhab domyosarcoma, angiosarcoma, chondrosarcoma, osteosarcoma, and leiomyosarcoma, in addition to fibrosarcomatous areas. Although the less differentiated component of dedifferentiated chondrosarcoma usually shows the histological features of malignant fibrous histiocytoma and fibrosarcoma, multilineage differentiation can occur in that component. The phenomenon of 'dedifferentiation' in chondrosarcoma and the relationship to and distinction from malignant mesenchymoma of soft tissue and bone are discussed.     

Adrenoceptor-mediated effects on calcium channel currents are antagonized by 5′-(N-ethyl)-carboxamido-adenosine in guinea-pig atrial cells

Summary In guinea-pig atrial myocytes, the effects of the adenosine analogue 5-(N-ethyl)-carboxamido-adenosine (NECA) in the presence of isoprenaline (ISO) on Ca²⁺ channel activity were analyzed. Single Ca²⁺ channel currents were recorded from cell-attached patches by application of several hundred 100 ms depolarizing steps. Under control conditions, burstlike activity of channel openings during some depolarizing steps were followed by variably long periods of quiescence (blank sweeps). During superfusion with ISO (100 nmol/l), ensemble-averaged (mean) current was increased by about 150%. The underlying mechanism was found to be a significant increase in the channel availability, defined as the ratio of current-containing sweeps to the total number of sweeps. In addition, the ISO-induced reduction of blank sweeps was combined with slightly but not significantly higher values of the open probability in the current-containing sweeps. Open time and shut time histograms could be fitted by single and double exponential curves, respectively, which remained rather unaffected in the presence of ISO; accordingly, mean open time and mean shut time of the channel were not significantly changed by ISO. After the addition of NECA (1 mol/l) in the presence of ISO, the ISO-induced increase in mean current was abolished. This effect of NECA on mean current was due to a reduction of the channel availability and a slight decrease in the open probability. The purinoceptor blocking agent 8-phenyltheophylline (10 mol/l) antagonized the inhibitory action of NECA on the ISO-induced increase in Ca²⁺ channel activity. These results indicate that -adrenoceptor-induced changes in Ca²⁺ channel activity are counteracted by stimulation of, presumably, A₁ adenosine receptors. This may be explained by the fact that purinoceptors, beside their stimulating action on K⁺ channels, mediate an additional inhibitory effect on the adenylate cyclase system in the atrium. Subsequently, purinoceptor activation reverses the ISO-induced increase in Ca²⁺ channel activity due to a reduction in cAMP content leading to a decrease in the number of phosphorylated Ca²⁺ channels. Send offprint requests to U. Jahnel at the above address     

Association of Loss of Heterozygosity at the p53 Locus with Chemoresistance in Osteosarcomas

Although the osteosarcoma is considered to be among the most chemosensitive malignancies and preoperative chemotherapy is commonly applied, an appreciable proportion of cases are in fact quite insensitive. Predictive markers for chemosensitivity are therefore desirable in order to develop effective treatment strategies. Thirty-two cases of conventional osteosarcomas treated at the Cancer Institute Hospital, Tokyo, were analyzed. The sensitivity to preoperative chemotherapy was investigated with reference to loss of heterozygosity (LOH) at the 17p13 ( p 53) and 13q14 ( Rb ) loci and expression of the cell-cycle associated proteins, p53, Rb, p21/Waf-1, mdm-2 and Ki-67, as detected immunohistochemically. LOH was detected by analyzing polymerase chain reaction products at marker microsatellite loci. The efficacy of chemotherapy was evaluated both radiologically and histologically. LOH at p 53 or Rb loci was seen in 54% (13/24) and 58% (14/24) of cases, respectively. Only 15% of osteosarcomas with LOH at the p 53 locus were sensitive to preoperative chemotherapy, as compared to 64% of tumors without such loss ( P <0.05). A similar but much less distinct tendency was observed with LOH at the Rb locus. No relationship was evident between chemosensitivity and immunohistochemical staining patterns for p53, Rb, p21/Waf-1, mdm-2 or Ki-67. The results suggest that p 53 gene deletion, but not the other parameters investigated, may be useful for predicting chemoresistance of osteosarcomas.     

Chromosome spreading techniques for primary gastrointestinal tumors

The requirement for well spread out chromosomes for the cytogenetic analysis of primary gastrointestinal tumors led us to develop new techniques. These techniques involved two main procedures: (1) preliminary incubation with culture medium in the presence of collagenase, Dispase, and colcemid, for 3h, and (2) treatment with an extremely hypotonic solution (0.044 M KCl) for 30 min. The techniques were applied to 11 gastrointestinal malignancies (including 1 early gastric cancer and 1 metastatic liver lesion of colon cancer) and significant increases (P<0.01) in the number of metaphases of analyzable karyotypes were obtained, compared with a previous method in which the standard hypotonic molarity of KCL (0.075 M) was employed. The mean value for metaphase numbers of the analyzable karyotypes was 37.0±3.7% in the 5 gastric cancers and 44.7±4.8% in the 5 colon cancers and 1 metastatic lesion. These values were three times and more than twice, respectively, the values obtained by the previous method. A fluorescence in situ hybridization (FISH) study was carried out on one cologenic tumor, the α-satellite centromere-specific probe 17 being used. Deletion of the long arm of chromosome 17 was demonstrated. The method proposed here could yield a sufficient number of metaphases without the use of tissue culture that might cause alteration of karyotype. It can be employed with small biopsy specimens and in studies utilizing the FISH technique.     

Pipeline flow diversion with adjunctive coil embolization for internal carotid artery aneurysms following an intradural component: results in 46 consecutive aneurysms from a Japanese single-center experience

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6 mm; median neck width, 6.3 mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (<?10 mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥?10 mm) aneurysms (P?=?.024). The median clinical follow-up was 22 months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively.

     

The topoisomerase II alpha gene status in primary breast cancer is a predictive marker of the response to anthracycline-based neoadjuvant chemotherapy

This study aimed at evaluating the usefulness of topoisomerase II alpha (TOP2A) for predicting the effect of anthracycline-based neoadjuvant chemotherapy in breast cancer. The TOP2A status was examined using fluorescent in situ hybridization (FISH) in 14 pre-chemotherapeutic breast cancer tissues, and was also assessed by immunohistochemistry (IHC) in 14 pairs of pre- and post-chemotherapeutic breast cancer specimens. TOP2A gene aberration by IHC tended to show a correlation with pathological responses but this was not statistically significant (p=0.060). On the other hand, the low TOP2A/CEP17 ratio correlated with good pathological responses (p=0.012). TOP2A overexpression was not significantly associated with response (p=0.580). Our results thus suggest that the TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer.