Usefulness of low-dose irinotecan for multiple lung metastases of cholangiocellular carcinoma after operation--a case report

We treated a patient in whom low-dose irinotecan therapy was effective for the treatment of multiple lung metastases of cholangiocellular carcinoma after operation. The patient was a 50-year-old man. He underwent extended right hepatectomy for cholangiocellular carcinoma, and multiple lung metastases occurred 8 months after operation. For the treatment of lung metastases, low-dose irinotecan therapy (70 or 40 mg/week) was carried out. Eighteen months after the lung recurrence, he is still alive with a good quality of life, although the lung metastases have progressed. These results suggest that low-dose irinotecan therapy can be effective for lung metastases of cholangiocellular carcinoma.     

Primate neurons show different vulnerability to transient ischemia and response to cathepsin inhibition

Previously, we reported "calpain-induced leakage of lysosomal enzyme cathepsin" as a mechanism of ischemic neuronal death specific for primates. Cathepsin inhibitors such as CA-074 and E-64c were demonstrated to significantly inhibit hippocampal neuronal death. Pyramidal neurons of the hippocampus, Purkinje cells in the cerebellum, and neurons in the caudate nucleus, outer putamen and cortical III, V layers, are known to be vulnerable to ischemia. However, regional differences of the vulnerability and response to neuroprotectants, have not been studied in detail. Here, the monkey brains undergoing transient ischemia were studied to clarify such regional differences by the microscopic counting of surviving neurons. The dead neurons were characterized by eosinophilic coagulation necrosis without apoptotic bodies. The control postischemic brain without treatment showed surviving neurons in caudate nucleus (55.8%), outer putamen (44.4%), cortical III layer (37.8%), CA4 (35.3%), cortical V layer (34.1%), cerebellum (28.2%), CA3 (24.3%), CA2 (16.2%), and CA1 (2.0%). Only the CA1 showed an almost total neuronal loss. In contrast, a single postictal injection of CA-074 or E-64c led to significant inhibition of postischemic neuronal death in all brain regions studied. Overall, more surviving neurons were seen after E-64c treatment than with CA-074: cerebellum, 91.6% vs 85.6%; CA4, 88.6% vs 77.3%; caudate nucleus, 86.1% vs 89.8%; CA2, 83.6% vs 53.0%; outer putamen, 81.3% vs 87.7%; CA1, 80.1% vs 47.4%; CA3, 79.6% vs 60.3%; cortical layer III, 75.5% vs 67.7%; and cortical layer V, 75.0% vs 65.9%, for E-64c and CA-074, respectively. Cathepsin plays a critical role in ischemic neuronal death, and its inhibitors may protect neurons throughout the brain.     

Appearance of rectal varices in extrahepatic portal obstruction after treatment for esophago-gastric varices: a case report

We report a case of rectal varices that developed after endoscopic injection sclerotherapy (EIS) and Hassab's operation for esophageal varices with extrahepatic portal obstruction. A 54-year-old woman was admitted to our hospital in September 1997 for treatment of hematochezia. Emergent colonoscopy revealed tortuous rectal varices with a white plug. Angiography revealed that rectal varices were provided with backward blood flow by the inferior mesenteric vein due to extrahepatic portal obstruction. In this case, previous treatment, EIS and Hassab's operation, for esophago-gastric varices might have inhibited the development of collaterals apart from surface of gastrointestinal tract, such as para-esophageal collateral veins or spleno-renal shunt. Since the thrombus in the extrahepatic portal vein causes strong pressure on inferior mesenteric vein which is connected to the inferior vena cava via the inferior rectal vein, rectal varices might be developed. In this case, it was considered that rectal varices were not treated enough by endoscopic therapy because of regurgitant hyper blood flow against portal venous pressure. Therefore, rectal transection was performed. After the treatment, the patient suffered no further episodes of bleeding from rectal varices.     

Primary lymphoma of bilateral external auditory canals.

We report a rare case of primary lymphoma originating in the bilateral external auditory canals. A 49-year-old man presented with cauliflower-like tumors on both of his external auditory canals. Immunohistopathologic examination and immunoglobulin heavy chain gene rearrangement studies led to a diagnosis of B-cell lymphoma. He had no other systemic involvement. After chemotherapy, total gross tumor removal by surgery was achieved, and no recurrence has been detected during 1 year of follow-up. To our knowledge, this is the third case of malignant lymphoma originating in the external auditory canal to be reported in the literature, and this is the first report that includes immunohistochemical findings of fresh tissue.     

Expression of Amphiregulin, a Novel Gene of the Epidermal Growth Factor Family, in Human Gastric Carcinomas

The expression of mRNA for amphiregulin (AR), a novel gene of the epidermal growth factor family, was examined in 8 human gastric carcinoma cell lines and 32 gastric carcinoma tissues as well as corresponding normal mucosa. Of the 8 gastric carcinoma cell lines, 7 expressed 1.4 kb AR mRNA at various levels. The expression of AR mRNA by TMK-1 and MKN-28 cells was increased by treatment with epidermal growth factor or transforming growth factor α. In surgical cases, all the gastric carcinoma tissues and their adjacent normal mucosa expressed AR mRNA. Interestingly, 20 (62.5%) out of 32 tumors expressed AR mRNA at higher levels than their corresponding normal mucosas (tumor/normal ≥1.2). No obvious correlation was observed between the AR mRNA levels and the histological types or tumor staging of gastric carcinoma. Immunohistochemically, AR protein was localized to the cytoplasm and/or nucleus in tumor cells. These results suggest that AR produced by tumor cells may be involved in the pathogenesis and/or progression of human gastric carcinoma.     

Mitochondrial myopathy,encephalopathy, lactic acidosis,and stroke-like episodes (MELAS) decrease in diastolic left ventricular function assessed by echocardiography

Summary Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are known to be associated with cardiomyopathy. Systolic and diastolic left ventricular functions were assessed by M-mode and Doppler echocardiography in four patients with MELAS and in 14 normal controls. The interventricular septal thickness and left ventricular posterior wall thickness were greater (11.0±1.6 mm vs. 5.8±0.7 mm and 11.0±2.2 mm vs. 5.9±0.8 mm) in patients with MELAS than in a control group. Parameters of systolic left ventricular functions (ejection fraction, shortening fraction, systolic time intervals, and mean Vcf) and left ventricular dimensions were not significantly different between the two groups. To assess the diastolic function, blood flow velocity across the mitral valve was measured by Doppler echocardiography and various indexes were obtained. In patients with MELAS, the impairment of diastolic left ventricular filling was demonstrated by decrease in the following indexes: peak flow velocity in the early passive filling period (E) (0.76±0.10 m/s vs. 0.94±0.09 m/s), integrated velocity for total E (10.2±1.3 vs. 13.0±0.9), the ratio of E and late atrial filling integrated velocities (1.72±0.06 vs. 2.49±0.29).     

Left ventricular preload reserve in preterm infants with patent ductus arteriosus

The left ventricular Frank-Starling response was studied in 15 preterm infants, less than 1500 g birth weight, and in 16 fullterm infants with patent ductus arteriosus. Left ventricular end diastolic volume (LVEDV), stroke volume, and cardiac output were calculated from biplane echocardiographic images with a modified Simpson's rule, and the left ventricular function curve was obtained by standardising with birth weight and body length. In the relationship between LVEDV and stroke volume, the slope of the regression line was significantly milder in preterm than in fullterm infants; however, there was no significant difference in the relationship between LVEDV and cardiac output. The heart rate was significantly higher in preterm than in fullterm infants. Our data indicated that the premature infants had less left ventricular reserve capacity to respond to the increased preload through the left-to-right ductal shunting than the mature ones, and that the high pulse rate made it possible to generate adequate cardiac output in premature infants.     

Atelosteogenesis Type 3: The First Patient in Japan and a Survivor for more than 1 year

We report the first patient of atelosteogenesis type 3 (AO₃) in Japan. The patient had multiple craniofacial abnormalities at birth, including ocular hypertelorism, a flat nasal bridge, micrognathia and a cleft palate. There was rhizomelic shortness of the limbs and a club-foot. The infant had short broad thumbs in the hands similar to those observed in the feet. There were no chromosomal abnormalities. Radiological examination demonstrated striking hypoplasia of the humerus with proximal rounding and distal tapering giving a 'drumstick' appearance, 'S'-shape configuration of the cervical spine, scoliosis and coronal cleft in the thoracolumbar vertebral bodies. The infant experienced recurrent apnea and persistent severe tracheomalacia, which necessitated tracheostomy at 5 months of age. Despite his multiple skeletal deformities and respiratory problems, this patient survived more than 1 year with motorneuronal developmental delay.