Spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid

BACKGROUND: Tumors of the so-called intrathyroidal epithelial thymoma type are a rare group of thyroid neoplasm tumors. Of this type of tumor, spindle epithelial tumor with thymus like differentiation (SETTLE) has been reported only 17 times in English literature. METHODS: An 18-year-old woman was initially seen with a 6-cm left thyroid mass that was resected with a left thyroidectomy. Histopathologic features of the excised left thyroid tumor together with an immunohistochemistry and electron microscopy led us to a diagnosis of SETTLE. RESULTS: Most of the specimen was composed of highly cellular spindle cells that formed intersecting and streaming fascicles. The spindle cells showed both vimentin immunoreactivity and cytokeratin immunoreactivity but no immunoreactivity for thyroglobulin or calcitonin. Electron microscopic examination of the spindle cells demonstrated prominent cytoplasmic tonofilaments, desmosomes, and basal lamina consistent with epithelial cell origin. DNA content analysis by flow cytometry revealed DNA diploidy. CONCLUSIONS: SETTLE of thyroid gland is an extremely rare entity. A review of the literature reveals that SETTLE has distinctive morphologic features and an immunohistochemical profile.     

Intradural extramedullary ganglioneuroma associated with multiple hamartoma syndrome

A 51-year-old woman presented with a rare completely intradural and extramedullary spinal ganglioneuroma associated with multiple hamartoma syndrome and manifesting as complaints of neck pain and dizziness persisting for 8 months. Magnetic resonance imaging of the spinal cord revealed an intradural extramedullary lesion at the C1 level. She underwent right suboccipital craniectomy and C1-2 hemilaminectomy to remove the tumor. Histological examination confirmed ganglioneuroma. She also suffered from multiple facial trichilemmomas, thyroid goiter, multiple polyposis of the gastrointestinal tract, and pulmonary hamartoma indicating multiple hamartoma syndrome. These benign neoplasms were treated conservatively.     

Laparoscopic Nephrectomy,Ex Vivo Repair,and Autotransplantation for a Renal Artery Aneurysm: Report of a Case

A 57-year-old woman was hospitalized with a left renal artery aneurysm (RAA). The aneurysm measured 35 mm in diameter and was located at the renal artery bifurcation. We performed a laparoscopic nephrectomy using a retroperitoneal approach and performed an ex vivo repair of the renal artery. The reconstructed kidney was then autotransplanted at the left iliac fossa. The patient's postoperative course was uneventful. A laparoscopic nephrectomy and ex vivo repair are both considered to be effective for treating complex RAA.     

Proximal oblique-domed osteotomy of the first metatarsal for the treatment of hallux valgus associate with flat foot: effect to the correction of the longitudinal arch of the foot

Introduction Flat foot and/or metatarsal primus varus are the major causes of hallux valgus, and it is important to correct these deformities in order to prevent the recurrence of this condition. We demonstrate the clinical and radiological assessment of the correction of hallux valgus, metatarsal primus varus, and flat foot after proximal oblique-domed osteotomy of the metatarsus with distal soft tissue reconstruction. Materials and methods Twenty-seven feet of 22 patients with moderate or severe hallux valgus who had undergone proximal oblique-domed osteotomy were studied. After the adductor hallucis tendon was cut at the attachment of the proximal phalanx and at the sesamoid bone, the osteotomy was performed 3 cm dorsal-distal to the metatarsocuneiform joint to transfer distal fragment approximately 5 mm in the plantar direction, and rotated laterally decreasing the first–second intermetatarsal angle to 5 degrees. Results The mean AOFAS score was 54.1 ± 2.8 points at pre-operation and 92.8 ± 4.8 points at the most recent follow-up (P < 0.0001). Significant improvement was seen between the hallux valgus angle (P < 0.0001), first–second intermetatarsal angle (P < 0.0001), first–fifth intermetatarsal angle (P < 0.0001), talar pitch (P = 0.0032), and calcaneal plantar angle (P = 0.0327) before surgery and at one year after surgery. The average improvement of the talar pitch and calcaneal plantar angle was 2.6 ± 1.4 and 2.4 ± 1.5 degrees, respectively. Conclusion This study suggest that proximal oblique-domed osteotomy of the metatarsal as a surgical procedure for the treatment of moderate or severe hallux valgus with flat foot can be recommended to correct the longitudinal arch of the foot and the first–second intermetatarsal angle.     

Minimum incision endoscopic nephrectomy for giant hydronephrosis

Five consecutive patients with symptomatic giant hydronephrosis underwent minimum incision endoscopic nephrectomy. The originally huge renal specimen was retroperitoneally mobilized using both of endoscopy and direct vision, without the use of trocar ports or gas insufflation, via a single minimum incision that narrowly permitted extraction of the specimen. The specimen was successfully extracted from the incision in all patients. Technically, proper deflation of the hydronephrotic sac facilitates mobilization and enables extraction of the specimen. Median (range) size of incision, operative time, and estimated blood loss were 4 cm (3-5), 205 min (156-222), and 210 mL (110-350), respectively. No patient required blood transfusion or encountered operative complications. Postoperative convalescence was short and uneventful; all patients resumed oral intake and ambulance on the day following surgery, and were physically dischargeable from hospital after 2-3 postoperative days. Thus, this technique is a feasible, minimally invasive and safe procedure for symptomatic giant hydronephrosis.     

Improved accuracy in predicting the presence of Gleason pattern 4/5 prostate cancer by three-dimensional 26-core systematic biopsy

OBJECTIVES: To evaluate whether three-dimensional 26-core (3D26) prostate biopsy improves the accuracy in predicting the presence of Gleason pattern 4/5 cancer compared with extended transrectal 12-core (TR12) or transperineal 14-core (TP14) biopsy schemes. METHODS: We studied 143 consecutive men in whom prostate cancer was diagnosed by the 3D26 biopsy and who underwent radical prostatectomy (RP) without neoadjuvant treatment. All histologic grading was reevaluated by a single pathologist according to the 2005 International Society of Urological Pathology Consensus Conference on Gleason Grading. Cancer grade was categorized into high grade (Gleason pattern 4/5 cancer present) and non-high grade (absent) in both biopsy and RP specimens. Since TR12 and TP14 biopsy schemes represent subsets of the 3D26 biopsy, we could compare these schemes directly in an identical patient cohort. RESULTS: There was a grade agreement between 3D26 biopsy and RP in 132 (92.3%) cancers. Grade concordance between biopsy and RP was significantly better in 3D26 biopsy than in TR12 (83.5%, p=0.025) biopsy. Risk of underestimation of cancer grade by 3D26 biopsy (26.5%) was significantly lower than that by TP14 (51.4%, p=0.034). Grade concordance between 3D26 biopsy and RP was not according to clinical variables including prostate volume, clinical stage, prostate-specific antigen (PSA), and PSA density. CONCLUSIONS: We demonstrated that the 3D26 biopsy can accurately predict the presence of Gleason pattern 4/5 cancer on RP specimens with a high concordance rate of 92.3%, a value significantly higher than that between extended TR12 biopsy and RP specimens.     

Effect of the XIAP inhibitor Embelin on TRAIL-induced apoptosis of pancreatic cancer cells

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in a wide variety of tumor cells, while it has no toxicity for the majority of normal cells.Therefore, TRAIL may be a suitable agent for anticancer therapy. We previously reported that a number of pancreatic cancer cell lines show resistance to TRAIL-induced apoptosis via overexpression of XIAP and FLIP. The present study was conducted to further examine TRAIL-based therapeutic strategies by aiming to restore functional apoptotic pathways in resistant pancreatic cancer cells. METHODS: In various pancreatic cancer cell lines, TRAIL-induced apoptosis was evaluated in the presence or absence of an XIAP-inhibitor (Smac peptide). Second, TRAIL-induced apoptosis was evaluated in TRAIL-resistant AsPC-1 cells with or without FLIP antisense. Third, the combined effect of Smac peptide and FLIP antisense was tested, and the activation of apoptosis-related caspases and poly (ADP-ribose) polymerase was evaluated. Finally, TRAIL-induced apoptosis was evaluated in the presence or absence of FLIP antisense and an XIAP inhibitor (embelin). RESULTS: Smac peptide enhanced TRAIL-induced apoptosis in a dose-dependent manner for several pancreatic cancer cell lines, but showed no effect on TRAIL-resistant AsPC-1 cells. Smac peptide alone had no influence on cell viability. TRAIL-induced apoptosis was restored in TRAIL-resistant AsPC-1 cells by exposure to FLIP antisense, which suppressed the expression of FLIP. The effect of TRAIL was augmented by the combination of FLIP antisense and Smac peptide. Similarly, TRAIL-induced apoptosis was restored by the combination of FLIP antisense and embelin. Activation of apoptotic caspases and cleavage of poly (ADP-ribose) polymerase was observed after sensitization of TRAIL-resistant pancreatic cancer cells. CONCLUSIONS: Pancreatic cancer cells gain resistance to TRAIL-induced apoptosis via expression of the antiapoptotic proteins XIAP and FLIP. Smac peptide and FLIP antisense could restore the apoptotic effect of TRAIL. An XIAP inhibitor, embelin, enhanced the effect of TRAIL in the presence of FLIP antisense. These findings may provide useful information for the development of TRAIL-based therapeutic strategies by restoring functional apoptotic pathways in resistant pancreatic cancer cells. In addition, a low molecular weight XIAP inhibitor like embelin could be a lead compound for the development of effective XIAP inhibitors.     

Allogeneic chimerism established with a mixture of low dose bone marrow cells and splenocytes in sublethally irradiated mice

BACKGROUND: Allogeneic chimerism has been established in graft-accepting recipients and the donor cells in the host may act in a major way to facilitate the induction of tolerance. In this study, we examined the effects of allogeneic chimerism after injecting donor bone marrow cells (BMCs) mixed with splenocytes (SPLCs) to the sublethally conditioned recipients. METHODS: In BALB/c(H-2(d)) to B6(H-2(b)) combination, B6 recipients were irradiated at 7.5 Gy and were injected a mixture of donor BMCs and SPLCs intravenously. On day 90 after injection, the degree of chimerism in peripheral blood lymphocytes (PBL) and in the splenocytes was checked by flow cytometry. RESULTS: In groups which were injected varying BMCs, when > 45 x 10(6) BMCs were injected into B6, a large percentage of donor cells were detected in PBL and in the spleen. In contrast, when < 30 x 10(6) BMCs were injected into B6, only a small percentage of donor cells were detected. In the groups which were injected 3 x 10(6) BMCs with varying SPLCs, when > 10 x 10(6) SPLCs were added, a large percentage of donor cells were detected in PBL and SPLCs, but a small percentage of donor cells were detected with the addition of < 3 x 10(6) SPLCs. A high percentage of chimeric mice showed donor specific tolerance in vitro, mixed lymphocyte responses, and in vivo, skin grafting. In contrast, only a small percentage of chimeric mice showed no donor specific tolerance by skin grafting. CONCLUSION: These findings suggested that even a low dose of BMCs can establish a state of allogeneic chimerism and donor specific tolerance if combined with SPLCs.     

Vascular-Resident CD169-Positive Monocytes and Macrophages Control Neutrophil Accumulation in the Kidney with Ischemia-Reperfusion Injury

Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169⁺ monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169⁺ cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169⁺ monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169⁺ cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C^lo monocytes into CD169⁺ cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C^lo subset of CD169⁺ monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169⁺ monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.     

Expression of anti-apoptotic protein, Bcl-2, in liver regeneration after a partial hepatectomy

BACKGROUND: Although Bcl-2 is well known to have anti-apoptotic activities in vitro and in vivo, the role of Bcl-2 relating to liver regeneration remains controversial. The aim of this study was to document the effect of Bcl-2 expression on liver regeneration in rats undergoing a partial hepatectomy. MATERIAL AND METHODS: Adult male Wistar rats (n = 4/group) at 72 h before undergoing a 70% partial hepatectomy (PH) were administered 1 x 10(9) plaque-forming units of adenovirus vector encoding either human Bcl-2 (group 1) or LacZ (group 2) intravenously and were sacrificed at 0, 12 h, and at 1, 2, 3, 7, 14, and 21 days postoperatively. In group 3, normal saline was injected instead of adenovirus vector. Liver regeneration was monitored by measuring the restituted liver mass and proliferating cell nuclear antigen (PCNA) immunostaining. The incidence of apoptosis in the liver was analyzed by the immunohistochemical detection of single-stranded DNA at 14 and 21 days postoperatively. RESULTS: The restituted liver mass showed significantly higher values in group 1 (26.1 +/- 7.2%) than in group 2 (14.7 +/- 6.8%) and 3 (13.6 +/- 5.0%) at 1 day after PH (P < 0.05). The PCNA labeling index was significantly higher in group 1 (47.2 +/- 9.9%) than in groups 2 (19.0 +/- 7.8%) and 3 (19.2 +/- 15.2%) at 1 day after a partial hepatectomy (P < 0.05). The hepatocyte growth factor (HGF) mRNA expression was significantly lower in group 1 than in group 2 at 12 h after PH (P < 0.05). The number of single-stranded DNA-positive cells decreased significantly more in group 1 (5.67 +/- 1.53 positive cells/10 fields per tissue) than those in group 2 (18.33 +/- 7.57 positive cells/10 fields per tissue) at 14 days after PH. CONCLUSIONS: These results thus indicated that an overexpression of anti-apoptotic protein Bcl-2 does not necessarily have an anti-apoptotic effect on liver regeneration but appears to have a pro-proliferative effect in the early phase of liver regeneration.