Itsuro Nagae

Direct measurement of the extravasation of polyethyleneglycol-coated liposomes into solid tumor tissue by in vivo fluorescence microscopy

Abstract The extravasation of liposomes of different sizes into solid tumors after i.v. injection was visualized by in vivo fluorescence microscopy in mouse neuroblastoma C-1300-bearing mice. Liposomes composed of distearoylphosphatidylcholine/cholesterol (1/1 molar ratio) and 6 mol% distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared. The PEG-coated liposomes were fluorescently labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) as a liposome marker or with doxorubicin (DXR) as an aqueous-phase marker. Liposomes with an average diameter of 100–200 nm showed the greatest tumor accumulation. With time after injection of DiI-labeled liposomes, the tumor interstitial fluorescence intensity increased. Most fluorescent spots were located outside and around the vessel wall, indicating extravasation of intact liposomes. The perivascular distribution was heterogeneous. We also obtained the same fluorescence localization pattern with DXR released from extravasated liposomes after injection of DXR-encapsulated liposomes. No fluorescence from extravasated liposomes was detected in normal s.c. tissue; the fluorescent spots were observed only in the vessel wall. Our results indicate that small-size long-circulating liposomes are able to traverse the endothelium of blood vessels in tumors and extravasate into interstitial spaces. Moreover, encapsulated drug was released from extravasated liposomes in the tumor.

Primary omental-mesenteric myxoid hamartoma of the mesoappendix incidentally detected after abdominal trauma in a child: report of a case.

A 14-year-old boy was brought to our hospital with abdominal pain and nausea after suffering a blow to the abdomen. A mass was felt in the right hypogastrium, and the patient was hospitalized for possible hematoma resulting from the abdominal trauma. Initially, we treated him conservatively and observed his course, but on the 20th day after trauma, enhanced computed tomography showed that the area of strong enhancement in the tumor was unchanged. Superior mesenteric angiography showed findings indicative of a pseudoaneurysm caused by the trauma, and surgery was performed 26 days after the injury. Laparotomy revealed a tumor with a clear boundary, thought to originate in the mesoappendix, without any sign of pseudoaneurysm. Histopathological examination confirmed that the tumor was an omental-mesenteric myxoid hamartoma. The patient had an uneventful postoperative course and was discharged from hospital on the 12th day after surgery. More than 5 years have elapsed since the operation and no sign of recurrence or metastasis has been recognized.

Liposome Drug Delivery System for Murine Neuroblastoma

PURPOSE The effects of liposome-infused doxorubicin on C-1300 murine neuroblastoma were studied. The liposome surface was covered with polyethylene glycol to avoid migration toward the reticuloendothelial system and to prolong its presence in the bloodstream. Liposome-infused doxorubicin hydrochloride (DXR), an anthracycline was used as an anticancer antibiotic substance. METHODS Each A/J mouse was transplanted with 1 x 10(5) C-1300 murine neuroblastoma cells subcutaneously in the thigh. The experiment was conducted when the maximum tumor dimension was 1 cm. The control group was given only physiological saline solutions, the second group was given DXR alone, and the third group received liposome-infused DXR (Lip-DXR). The survival and doubling times were measured. One, 12, and 24 hours after the injection, the DXR concentration in the cardiac tissues was measured for statistical comparison. RESULTS The survival time of the mice was found to be 27+/-5.10 days in the control group, 31.40+/-3.15 days in the DXR group, and 43.86+/-2.13 days in the Lip-DXR group. The Lip-DXR group showed the longest survival time. The tumor-doubling time was found to be 9.07+/-2.30, 10.75+/-3.49, and 19.80+/-3.26 days, for each group, respectively. When comparing the DXR concentration in the heart tissues, the Lip-DXR-administered mice showed significantly lower DXR accumulation in the cardiac tissues after 1 and 12 hours than the DXR-administered mice. CONCLUSION This study proved that liposome-infused DXR could be used effectively on murine neuroblastoma (C-1300 tumor cell model) and may reduce the incidence of cardiac toxicity as compared with DXR alone.

Biliary atresia with cartilage formation

Extrahepatic biliary atresia (EHBA) is an infl ammatory obliteration of the extrahepatic biliary system and usually an isolated anomaly that is an acquired and progressive disease. There are a number of theories about the pathogenesis of BA, which include occult viral infections, morphological defect and vascular insults. 2 Reovirus type 3 is one of the candidates of the pathogenesis of BA because of serological reactivation and localization of particles in the porta hepatis. Cytomegalovirus (CMV) has been also associated with EHBA in previous case reports. 3 We report a rare case of EHBA associated with cartilage formation and CMV infection.

A case of tubular adenoma developing after bladder augmentation: Case report and literature review

Highlights • We report a rare case of adenoma that developed after sigmoidocolocystoplasty.• There were 11 cases of oncogenesis after bladder augmentation in the literature, including our case.• We recommend routine surveillance cytoscopy and cytology for patients after bladder augmentation, although this remains controversial.

Sigmoidocolocystoplasty for neurogenic bladder reviewed after 20 years

BACKGROUND/PURPOSE We report the current status of patients who underwent augmentation cystoplasty (AC) at least 20years previously. METHODS Surgical history, incidence of urinary tract infection (UTI) and bladder stones, vesicoureteral reflux (VUR), urine cytology, renal function, a colon cancer tumor marker (carcinoembryonic antigen: CEA), and patient outcomes were assessed. RESULTS Forty patients who underwent AC (mean age: 34.4years; mean follow-up time: 24.3years) were analyzed. Mean age at AC was 11years. Incidence of bladder stones was 30%. There were no incidences of carcinoma after AC, and CEA levels were not increased. Ureteral reimplantation (URI) was performed in 21 patients. URI performed at the same time as AC was successful in 14 cases (93%) and unsuccessful in 1 (7%) because of persistent VUR. UTI developed after AC in only 1 patient (2.5%) with persistent VUR. This patient required unilateral nephrectomy 18years after the AC because of repeated UTIs. Thirty-four patients (85%) were employed, and 4 (10%) were married. Two of the 19 female patients (11%) had experienced pregnancy and delivery. Five patients (13%) had mental disorders. CONCLUSION Ultra long-term follow-up suggests that AC is a safe procedure with manageable sequelae, although some mental health issues remain. TYPE OF STUDY Case series with no comparison group. LEVEL OF EVIDENCE Level IV.