Early response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201Tl-chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin in human bladder cancer cells and human leukocytes.

The uptake and retention of single photon tracers in irradiated tumour cells was observed in an attempt at the early evaluation of the effect of radiation. T24 human bladder cancer cells were exposed to a single dose of 10 Gy or 20 Gy or a fractionated dose of 10 Gy (2 Gy for 5 days). The uptake of 201Tl chloride, 99Tcm-sestamibi and 99Tcm-tetrofosmin was observed by incubating in vitro for 60 min. The retention of the tracers was observed at 60 min after changing the incubation medium for a tracer-free medium. Uptake per culture well of all tracers in the cells exposed to 20 Gy declined as viable cell number decreased, but uptake per cell increased progressively. Uptake per cell of all tracers in the cells exposed to either a single dose or a fractionated dose of 10 Gy also increased, while a delay in growth was observed. The retention of these tracers decreased during this period and recovered thereafter. A binding assay with purified human leukocytes indicated that assessment with 99Tcm-sestamibi and 99Tcm-tetrofosmin is influenced by inflammatory cells. In conclusion, the effect of radiation may be underestimated if assessed by tracer uptake alone because of the increase in tracer uptake in viable irradiated cells. Observation of the retention of tracers may provide additional information.     

Primary smooth muscle tumor of the liver encasing hepatobiliary cystadenoma without mesenchymal stroma.

We describe a 59-year-old Japanese woman with a large mass of her liver encasing cystic components. Radiologic imaging showed the mass to be hypervascular, and surgical resection disclosed a white tumor. The solid portion was immunohistochemically characterized as a smooth muscle tumor. The cystic components were multilocular and lined with columnar epithelium, consistent with a hepatobiliary cystadenoma. The epithelium strongly stained for CA19-9. The subepithelial space was occupied by collagenous connective tissue interspersed with a small number of spindle-shaped cells. The cystic lesions lacked the mesenchymal stroma between the epithelium and connective tissue layer. There have been no previous reports of a hepatic smooth muscle tumor encasing a hepatobiliary cystadenoma. Because of the pathogenesis of the cystadenoma, it is possible to assume that the smooth muscle tumor also arose from the cells composing the biliary duct in association with the development of the cystadenoma.     

Acute and chronic effects of hyperosmolality on mRNA and protein expression and the activity of Na-K-ATPase in the IMCD.

We investigated acute and chronic effects of hyperosmolality on mRNA and protein expressions of Na-K-ATPase alpha and beta isoforms and Na-K-ATPase activity in the rat inner medullary collecting duct (IMCD). Incubation of IMCD in hypertonic medium for 30 min reduced the Na-K-ATPase activity by 50%. The Na-K-ATPase activity of dehydrated rats measured in isotonic medium was decreased, and incubation in hypertonic medium did not further decrease the activity. Incubation of IMCD in hypertonic medium for 6 h did not change alpha(1) mRNA. In contrast, dehydration decreased alpha(1) subunit mRNA and protein and beta(1) protein expressions without changing beta(1) mRNA. These data show (1) that acute hyperosmolality decreases Na-K-ATPase activity in IMCD without changing alpha(1) and beta(1) mRNA and (2) that 2 days of dehydration decreased Na-K-ATPase activity by reducing alpha(1) and beta(1) proteins. Thus, the mechanisms for the inhibition of the Na-K-ATPase activity in IMCD is different between acute and chronic exposure to hyperosmolality.     

Proposal on the extent of lymph node dissection for gallbladder carcinoma.

BACKGROUND/AIMS: To evaluate the value of performing extended regional lymph node dissection for gallbladder carcinoma, the mode of recurrence after curative resection was analyzed. METHODOLOGY: Records of 45 patients who underwent surgical resection for gallbladder carcinoma from 1973 to August 1997 were reviewed. RESULTS: Thirty-three cases underwent a curative resection and 12 received a non-curative resection. Among the 32 patients who survived the curative resection, cancer recurred in 7 with lymph node metastasis, whereas recurrence was found in only 1 of the remaining 25 patients without lymph node metastasis (p < 0.0001). At the 1st diagnosis of recurrence in these 8 patients, lymph node recurrence was detected in 7, and the site of recurrence was limited to the lymph nodes, which were confined to the peripancreatic region and the interaortocaval nodes near the left renal vein in 4 cases. CONCLUSIONS: In view of the site of the metastatic lymph nodes and the lymphatic drainage system of the gallbladder, it was considered that lymph node dissection was inadequate in 5 of the 8 patients and that 2 might have been cured by extended regional lymph node dissection, including complete resection of the retroportal, posterior pancreatoduodenal, right celiac and interaortocaval nodes.     

Decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, influence recurrence and survival of patients with resectable extrahepatic bile duct carcinoma.

This study was undertaken to identify potential abnormalities of p27(Kip1) and cyclin D1 expression in extrahepatic bile duct carcinomas and to assess the prognostic significance of p27(Kip1) and cyclin D1 levels for patients with this disease. Decreased p27(Kip1) expression (<50% nuclei staining) and cyclin D1 overexpression (>5% nuclei staining) was observed immunohistochemically in 19 (56%) and 23 (68%) of the 34 tumors examined, respectively. Both decreased p27(Kip1) and cyclin D1 overexpression were associated with relapse (P =.0005 for p27(Kip1) and P =.0004 for cyclin D1). Kaplan-Meier curves showed that both decreased p27(Kip1) and cyclin D1 overexpression correlate significantly with shortened survival rates (for p27(Kip1), P =.0419 and P =.002 for overall and disease-free survival; for cyclin D1, P =.0392 and P =.0021 for overall and disease-free survival). Cox regression model analyses identified decreased p27(Kip1) and cyclin D1 overexpression as independent markers predicting death from relapse (P =.0371, risk ratio: 3.891 for p27(Kip1); P =.0429, risk ratio: 8.31 for cyclin D1). Decreased p27(Kip1) was associated with cyclin D1 overexpression (P =.0202), and coincident abnormalities of the 2 proteins occurred in 16 of the 34 (47%) tumors, indicating that extrahepatic bile duct carcinoma progression may require synchronous dysfunction of p27(Kip1) and cyclin D1 in about half of patients. Patients with tumors showing coincident abnormalities of p27(Kip1) and cyclin D1 showed even more frequent recurrence than patients with an alteration in only 1 of the 2 proteins. In conclusion, decreased p27(Kip1) expression and cyclin D1 overexpression, alone and in combination, predict poor prognosis in patients with resectable extrahepatic bile duct carcinoma.     

Rotational cine cholangiography: evaluation for use in diagnosing bile duct carcinoma.

OBJECTIVE: We evaluated the usefulness of rotational cine cholangiography in the preoperative diagnosis of bile duct carcinoma. SUBJECTS AND METHODS: Rotational cine cholangiography was performed in both the transverse and cephalad anterior oblique planes in 60 patients with obstructive jaundice. Using strict diagnostic criteria, the capability of this technique to detect the confluence of the right hepatic duct and the left hepatic duct, the right anterior segmental duct and the right posterior segmental duct, and the left medial segmental duct was investigated. The angle at which the confluence was revealed was also investigated. In 26 patients with resected bile duct carcinomas, the preoperative diagnosis of cancer spread obtained using this procedure was compared with the histopathologic findings. RESULTS: Overall detectabilities of the confluences of the right hepatic ducts and left hepatic ducts, the right anterior segmental ducts and right posterior segmental ducts, and the left medial segmental ducts were 97.6%, 87.0%, and 93.1%, respectively. The angles of the confluences of the right hepatic ducts and left hepatic ducts and of the right anterior segmental ducts and right posterior segmental ducts were widely distributed: on the other hand, those of the left medial segmental ducts were distributed mainly from 0 degrees to 20 degrees . The accuracies of diagnosis of cancer invasion were 91.7% in the common hepatic ducts, 100% in the right hepatic ducts, 91.7% in the left hepatic ducts, 100% in the right anterior segmental ducts, 83.3% in the right posterior segmental ducts, and 100% in the left medial segmental ducts. CONCLUSION: Rotational cine cholangiography is reliable not only in detecting the confluence of the bile ducts but also in diagnosing the longitudinal extent of cancer spread along the bile duct wall.     

Partial Seizure with Aphasic Speech Arrest Caused by Watching a Popular Animated TV Program

On the evening of December 16, 1997, about 700 children across Japan were hospitalized because of convulsive seizures or vomiting experienced while watching a popular animated TV program that included blue and red stimuli that alternated at 12 flashes per second. In one case, an 11-year-old girl developed a hallucination in the right visual field and a subsequent cramp on the right side of her face, with aphasic speech arrest. She had no history of seizures. Her electroencephalogram (EEG) showed normal background activity and no epileptiform discharges. Intermittent photic stimulation provoked a photoparoxysmal response. Her main clinical manifestation was a TV-induced left occipital lobe seizure spreading toward the left inferior frontal lobe. This suggested a functional link from the occipital lobe to the frontal operculum.     

Percutaneous bowel drainage for jaundice due to afferent loop obstruction following pancreatoduodenectomy: Report of a case

(Received for publication on July 9, 1998; accepted on Mar. 11, 1999)     

Long-term toxicity and carcinogenicity study of cyclamate in nonhuman primates.

Twenty-one monkeys (cynomolgus, rhesus, African green) were fed cyclamate (100 mg/kg and 500 mg/kg) in the diet five times per week from a few days after birth and continuing for up to 24 years. Malignant tumors were diagnosed in three 24-year-old cyclamate monkeys; these were metastatic colon carcinoma (rhesus; 500 mg/kg), metastatic hepatocellular carcinoma (cynomolgus; 500 mg/kg), and a small, well differentiated adenocarcinoma of the prostate (cynomolgus; 100 mg/kg). Benign tumors were found at necropsy in three females; these were adenoma of the thyroid gland (rhesus; 100 mg/kg) and two cases of leiomyoma of the uterus (rhesus; 100 mg/kg and 500 mg/kg). No tumors were detected in an age-matched control group of 16 monkeys. Examination of the testes revealed complete testicular atrophy in one of the old cyclamate monkeys, and focal germ cell aplasia (Sertoli-only tubules) in two other cyclamate monkeys. Focal spermatogenic interruption (maturation arrest) at various germ cell levels mixed with normal spermatogenesis was observed in both the cyclamate-treated and the control monkeys, all of which were over 20 years old. Measurements of terminal cyclohexylamine concentrations showed that three of the males dosed with cyclamate at 500 mg/kg were high converters, with plasma concentrations comparable to the levels that produce testicular atrophy in rats. However, only one of the three high converters showed histologic evidence of irregular spermatogenesis. The overall conclusion is that the testicular abnormalities and the sporadic cases of different malignancies found after more than 20 years of dosing do not provide clear evidence of a toxic or carcinogenic effect of sodium cyclamate in monkeys.     

Kinetic Analysis of the Interaction between Recombinant Human FcRIα and Serum IgEs from Allergic Patients

Binding of IgE to the high-affinity IgE receptor (FcεRI) is the essential event for allergic reaction. Although there are many reports on binding kinetics between myeloma IgE and FcεRI, little is known about the kinetics between heterogeneous polyclonal IgE in the serum and FcεRIα. To elucidate the binding characteristics of heterogeneous serum IgE, we measured kinetic parameters of binding between IgE from allergic patients and a recombinant ectodomain of the human FcεRIα subunit by real-time interaction analysis based on surface plasmon resonance. Purified IgE monomer from the plasma of allergic patients displayed kinetics for the interaction with FcεRIα similar to those of myeloma IgE. In the case of crude IgE samples from allergic patients, one of seven specimens showed significantly higher affinity than highly purified IgE, suggesting that it is possible for IgEs in this specimen to form complexes of higher molecular weight.