A case of intraductal tubulopapillary neoplasm of pancreas with severe calcification,a potential pitfall in diagnostic imaging

We experienced a case of intraductal tubulopapillary neoplasms (ITPN) of the pancreas with severe calcification, which complicated image diagnosis. A pancreas head tumor was detected in a Japanese female in her 50s. Early enhancement by contrast‐enhanced CT and coarse calcification suggested a neuroendocrine tumor, although the obstruction and dilation of the main pancreatic duct appeared to be an intraductal tumor. An endoscopic ultrasound‐guided fine needle aspiration biopsy specimen revealed adenocarcinoma tissue. Pancreaticoduodenectomy was performed, and the patient has been well without evidence of recurrence for over 10 months. Pathological examination on the resected specimen revealed that the tumor showed papillary and tubulo‐cribriform growth patterns. Together with typical immunohistochemical results, the final diagnosis of ITPN was made. Characteristically, this case showed extensive calcification of both psammoma body‐type and non psammoma body‐type with foamy macrophage aggregation. This is the first report of ITPN with two types of calcification and macrophage. Since calcification might be one of the characteristic histological findings in ITPN as shown in our case, the possibility of ITPN should be also considered when calcification is detected in pancreatic lesions by various imaging modalities.     

Adenosquamous Carcinoma of the Gallbladder: A Clinicopathological, Immunohistochemical and Flow-cytometric Study of Twenty Cases

Twenty patients (7.4%) with adenosquamous carcinoma of the gallbladder were selected from 271 surgically resected gallbladder cancers. The 20 patients were composed of 8 men and 12 women with a mean age of 66.9 years. Histologically, all twenty tumors showed an abrupt transition between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) areas, and well differentiated AC was also found in the peripheral area of the tumor. A histochemical and immunohistochemical study using alcian blue, periodic acid-Schiff, cytokeratins, involculin and tissue polypeptide antigen disclosed a different nature of the two components. DNA heterogeneity between the components was detected in 5 of 7 cases by flow cytometry. The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC areas (mean 20.55%) was larger than that of the AC areas (mean 11.40%) ( P =0.0029), which indicated that the SCC areas had a greater proliferative capacity than AC areas. These results suggest that the SCC component of adenosquamous carcinoma of the gallbladder arose by a stepwise molecular progression of the pre-existing AC. Furthermore, the prognosis of adenosquamous carcinomas of the gallbladder (mean survival: 10 months) in the advanced stage (pTNM 2–4) was less favorable than those of papillary and well differentiated AC (mean survival: 99 months and 86 months) ( p <0.0001).     

Title aggregation patterns of argyrophilic nucleolar organizer regions induced by 5-fluorouracil in the nuclei of MCF-7 human breast cancer cells

The effects of tamoxifen and 5-fluorouracil (5-FU) on the patterns of argyrophilic nucleolar organizer regions (AgNORs) in MCF7 human breast cancer cells were studied. Tamoxifen and 5-FU both inhibited the growth of MCF-7 cells by 18% by day 3 of culture, but each had different effects on the AgNORs. Whereas no significant changes were induced by tamoxifen, effects on the AgNORs of MCF-7 cells by 5-FU were dramatic: 5-FU treatment changed the pattern of AgNORs, reducing the number of satellites by aggregation, typically to a single aggregation around nucleoli in a sphenoidal fashion. We named these morphological changes: fluorouracil induced AgNOR aggregations (FAA). Following treatment with 500 ng/ml 5-FU, FAA developed rapidly, AgNORs forming two or three aggregates in 24% (6 h), 24% (12 h), 40% (24 h) and 34% (48 h) of cells, compared to a control rate of 14%. Single large aggregate was rarely found in untreated cultures but after 6, 12, 24 and 48 h treatment with 500 ng/ml 5-FU, AgNORs had formed a single aggregate in 6, 8, 16 and 22% of cells, respectively. FAA were observed at a concentration of 100 ng/ml 5-FU; 48 h treatment resulted in cells in which two or three aggregates were increased by 24% and a single aggregate by 16%. These large single aggregates were larger than nucleoli stained by Papanicolau staining.     

Bilateral carotid stenting for bilateral carotid artery stenosis improved vascular dementia

We report a case of bilateral internal carotid artery (ICA) stenosis treated with stenting. A 78-year-old man suffered from vascular dementia and left hemiparesis, and, by magnetic resonance angiogram (MRA), was diagnosed as having bilateral ICA stenosis. Cerebral angiogram showed severe, bilateral ICA stenosis (right; 88%, left; 93%) and xenon single photon emission tomography (SPECT) showed severely decreased cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). We performed bilateral carotid angioplasty with self-expanding stents. Both CBF and CVR were improved bilaterally after the operation. The patient was discharged without neurological deficits. Carotid stenting may be an alternative treatment for severe ischemia caused by severe, bilateral ICA stenosis.     

Failure of endoscopic removal of common bile duct stones due to endo-clip migration following laparoscopic cholecystectomy

We report herein an extremely rare complication; namely, endo-clip migration into the common bile duct, following laparoscopic cholecystectomy, that occurred in a 57-year-old man. He underwent laparoscopic cholecystectomy, but postoperative bile leakage occurred from the cystic duct stump and he was treated by conservative drainage for 1 month. Five years later, he complained of vomiting and pain in the right hypochondrium, and he was admitted for investigations of jaundice and liver dysfunction. Computerized tomography scanning of the abdomen and endoscopic retrograde cholangiography revealed that several calculi, with six endo-clips as nuclei, had migrated into the biliary tract. Endoscopic removal of the calculi following endoscopic sphincterotomy, using a basket catheter, was unsuccessful, and it was therefore necessary to remove the basket catheter surgically. The mechanism of endo-clip migration and the method for removing the endo-clips are briefly discussed. Received: September 21, 2001 / Accepted: February 8, 2002     

Roles of brain prostaglandin E2 and thromboxane A2 in the activation of the central sympatho-adrenomedullary outflow in rats

This study addressed the question whether proximal and distal guinea pig tracheal segments respond differently to contractile agents. Using a perfused trachea set-up, histamine, KCl or the cyclo-oxygenase inhibitor, indomethacin, could be administered selectively to the mucosa (at the inside) or the serosa (at the outside) of the tracheal segments. Proximal parts contracted significantly more (40-60%) than distal parts when 1 mM histamine was administered to the mucosal or serosal side or when KCl (50 mM) was added to the serosal side. When histamine was administered to the mucosal side of epithelium-denuded segments, the contractions were twice as high in proximal than in distal parts (3057 vs. 1526 mg). Inhibition of tracheal cyclo-oxygenase with indomethacin at the mucosal side increased proximal and distal reactivity to mucosally administered histamine to the same extent. Serosal administration of indomethacin, however, increased histamine reactivity only in proximal segments (from 2690 to 5180 mg). In the latter segments, subsequent administration of histamine to the serosal side further increased the contraction, while serosal histamine in the absence of serosal indomethacin produced a relaxation (net difference of 4672 mg). In conclusion, the higher intrinsic contractility of proximal tracheal segments is counteracted by serosal cyclo-oxygenase products.     

Granulocyte-colony stimulating factor enhances chimeric antibody Nd2 dependent cytotoxicity against pancreatic cancer mediated by polymorphonuclear neutrophils

Nd2 is a monoclonal antibody against pancreatic cancer. We have previously reported that human/mouse chimeric antibody Nd2 (c-Nd2) can induce antibody-dependent cell-mediated cytotoxicity (ADCC) with peripheral blood mononuclear cells (PBMs) as effectors. In this study, we investigated whether c-Nd2 can induce ADCC with poly-morphonuclear neutrophils (PMNs) as effector cells and the effects of granulocyte-colony stimulating factor (G-CSF) in enhancing this cytotoxicity. Cytotoxicities for pancreatic cancer cell line, SW1990 were dose-dependently increased by c-Nd2 during co-culture with PMNs and these cytotoxicities were significantly suppressed by the addition of neutralizing antibodies against CD16, which is Fcgamma receptor expressed on PMN membranes. PMNs treated with G-CSF significantly enhanced in vitro ADCC activity against SW1990 induced by c-Nd2. The in vivo growth of subcutaneously transplanted SW1990 tumor in nude mouse was significantly inhibited by i.p. administration of c-Nd2 compared to control (non-specific IgG1). In addition, this inhibitory effect was enhanced by the combination of c-Nd2 and G-CSF. Immunohistochemical study with anti-mouse neutrophil elastase antibody demonstrated strong infiltrations of PMNs into and around the transplanted tumor, treated with c-Nd2 and G-CSF. These results suggest that PMNs play an important role in c-Nd2 inducing ADCC and that combination immunotherapy of c-Nd2 with G-CSF may have clinical applications in the treatment of patients with pancreatic cancer by enhancing ADCC.