A case of esophageal small-cell carcinoma responding to chemotherapy with CTP-11

After examination of a 64-year-old man with dysphagia who consulted our hospital, a diagnosis was made an esophageal small-cell carcinoma. This tumor had infiltrated the aorta and upon further examination another carcinoma, trachial adenosquamous cell carcinoma was found. We judged this case to be inoperable. At first, 2 courses of systemic chemotherapy were administered by CDDP but this therapy had little effect. We know that CPT-11 is effective in the treatment of lung small-cell carcinoma, leading us to a decision to use CPT-11 for the second systemic chemotherapy. As a result of 8 courses, the tumor minification rate was 64% with PR. After completing 13 courses, the patient could ingest any type of food. We observed grade 2 leukopenia as the only side effect. The patient survived for 1 year and 10 months after beginning the initial treatment. He transferred to another hospital for laser therapy for his trachial carcinoma. The patient died of brain metastasis. To date the treatment of patients with esophageal small-cell carcinoma with chemotherapy using CPT-11 has not been reported. We suggest that CPT-11 is an effective therapy in improving the condition of patients QOL with esophageal small-cell carcinoma.     

Oxalato-platinum or 1-OHP, a third-generation platinum complex: an experimental and clinical appraisal and preliminary comparison with cis-platinum and carboplatinum

A new platinum complex, oxalatoplatin or l-OHP, which, at the same metal dose in experimental tests is as efficient as cisplatin, and is more so at a lower metal dose than carboplatin; which is as efficient in human tumors of the testis and ovary as these other analogs, and more so in melanoma and breast cancer; which is not nephrotoxic, cardiotoxic or mutagenic, and hardly hematotoxic and neurotoxic, is described and compared with the above-mentioned platinum complexes. Combined with 5Fu, it induces a high number of remissions in colorectal cancer, and has brought about cures in inoperable gastric cancers. Combined with carboplatin, it has resulted in a high proportion of cures in L1210-carrying mice, which no other two-by-two combination of these complexes has achieved.     

Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT).

The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective delivery of relatively high concentration of 10B compounds to malignant tumor tissue. This study focuses on a new tumor-targeting drug delivery system for BNCT that uses small (less than 200 nm in diameter), unilamellar mercaptoundecahydrododecaborate (BSH)-encapsulating, transferrin (TF)-conjugated polyethyleneglycol liposomes (TF-PEG liposomes). When TF-PEG liposomes were injected at a dose of 35 mg 10B/kg, we observed a prolonged residence time in the circulation and low uptake by the reticuloendothelial system (RES) in Colon 26 tumor-bearing mice, resulting in enhanced accumulation of 10B into the solid tumor tissue (e.g., 35.5 microg/g). TF-PEG liposomes maintained a high 10B level in the tumor, with concentrations over 30 microg/g for at least 72 h after injection. This high retention of 10B in tumor tissue indicates that binding and concomitant cellular uptake of the extravasated TF-PEG liposomes occurs by TF receptor and receptor-mediated endocytosis, respectively. On the other hand, the plasma level of 10B decreased, resulting in a tumor/plasma ratio of 6.0 at 72 h after injection. Therefore, 72 h after injection of TF-PEG liposomes was selected as the time point of BNCT treatment. Administration of BSH encapsulated in TF-PEG liposomes at a dose of 5 or 20 mg 10B/kg and irradiation with 2 x 10(12) neutrons/cm2 for 37 min produced tumor growth suppression and improved long-term survival compared with PEG liposomes, bare liposomes and free BSH. Thus, intravenous injection of TF-PEG liposomes can increase the tumor retention of 10B atoms, which were introduced by receptor-mediated endocytosis of liposomes after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. These results suggest that BSH-encapsulating TF-PEG liposomes may be useful as a new intracellular targeting carrier in BNCT therapy for cancer.     

Unusual Liver Carcinomas with Sarcomatous Features: Analysis of Four Cases

We recently examined the clinicopathological and immunohistochemical features of four cases of primary hepatic carcinoma with sarcomatoid elements. Three of the four patients had associated ordinary hepatocellular carcinoma (HCC) and one had a sarcomatoid carcinoma with no apparent elements of HCC. The presenting symptoms were high fever and hypochondralgia in three patients, and right hypochondralgia without a high fever in one. The preoperative diagnoses were liver abscess in two patients, HCC in one, and cholangioma in one. Preoperative imaging showed necrotic change or abscess formation in the tumors. The sarcomatous elements showed a positive reaction to vimentin in three patients, but the ordinary HCC cells did not. Macroscopically, the tumors appeared as a single nodule with pericapsular growth. The prognoses of these patients were poor due to the early development of intrahepatic or distal metastases. We conclude that symptoms such as a high fever or hypochondralgia are characteristics of these tumors and that they may be histogenetically derived from a dedifferentiation of HCC, although no elements of HCC were found in one of our cases. Received: June 9, 2000 / Accepted: November 20, 2000     

Signet-Ring Cell Carcinoma of the Ampulla of Vater: Report of a Case

An 83-year-old man was admitted to our hospital complaining of general fatigue, fever, and obstructive jaundice. Percutaneous transhepatic bile duct drainage was performed. Gastroduodenal fiberscopy revealed carcinoma of the ampulla of Vater, and early gastric cancer was suspected. A pancreatoduodenectomy with lymph node dissection was performed. Although a biopsy specimen from the gastric lesion was suspected to be well-differentiated adenocarcinoma, no cancerous lesion was found in a specimen resected from the stomach. The histopathologic findings of the ampullary lesion were compatible with a diagnosis of signet-ring cell carcinoma. This is a rare lesion, and a review of the literature revealed only three previous similar cases. Received: May 1, 2001 / Accepted: March 5, 2002 RID="*" ID="*" Reprint requests to: N. Eriguchi (address 1)     

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.     

Guide to diagnosing primary pancreatic lymphoma, B-cell type: immunocytochemistry improves the diagnostic accuracy of endoscopic ultrasonography-guided fine needle aspiration cytology

Primary pancreatic lymphoma (PPL) is a rare disease with <1%of extranodal non-Hodgkin's lymphoma arising in the pancreas. This report provides immunocytochemical information on PPL that would be valuable for making differential diagnoses between PPL, pancreatic neuroendocine tumor, acinar cell carcinoma, and pancreatic ductal cancer. A 68-year-old woman had a chief complaint of abdominal pain. Fine needle aspiration cytology (FNAC)was performed. The FNAC smear showed moderate cellularity,with a small to moderate number of irregular cells and lymphocytes.No epithelial tumor clusters or abundant mucoid background were seen. The cells were scattered with pleomorphism and showed irregular nuclear shapes with finely granular chromatin,an increased nuclei–cytoplasm ratio, and prominent nucleoli.Cytologically, PPL was suspected with Papanicolaou staining but definite diagnosis was not made. Therefore, the specimen was destained, immunocytochemically examined for leukocyte common antigen (LCA), and PPL was suspected again. Numerous tumor cells were found in the surgical sample and tumor cells were positive for CD20 and negative for CD45RO. Based on these findings,the tumor was diagnosed as PPL, B-cell type. The preoperative FNAC smear that was examined for LCA was then reexamined for CD20, CEA, and Synaptophysin. As a result, the tumor cells were positive for LCA and CD20, whereas they were negative for CEA and Synaptophysin. Taking these findings together with the cytopathologic findings, this specimen was reconfirmed as PPL. Immunocytochemical examination for LCA and CD20 is useful in the identification of malignant pancreatic lymphoma, B-cell type.     

Chronic hemodialysis patients with visceral obesity have a higher risk for cardiovascular events

The risk of cardiovascular disease is substantially high in hemodialysis patients. The risk factors for cardiovascular disease in dialysis patients include age, malnutrition, duration of dialysis, diabetes mellitus and hyperphosphatemia. However, it is not clear whether cardiovascular disease is associated with abdominal obesity in dialysis patients. The aim of the present study was to clarify the relationship among visceral fat area and cardiovascular complications in chronic dialysis patients. Area of visceral fat was measured using computed tomography scan in 94 patients. The abdominal aortic calcification index (ACI), blood lipid profile and complication of cardiovascular disease were evaluated in these patients. Compared to patients with smaller visceral fat area (<100 cm2), those with larger visceral fat area (≥100 cm2) showed significantly higher cardiovascular complication and higher serum levels of triglyceride and significantly lower serum levels of HDL-cholesterol. Patients with larger visceral fat area and longer duration of dialysis showed severer calcification by ACI analysis, and showed higher incidences of ischemic heart disease. This study suggested that chronic dialysis patients with higher visceral fat area have a higher risk for vascular events, especially ischemic heart disease.