Primary retroperitoneal spindle cell liposarcoma: Pathological and immunohistochemical findings

Spindle cell liposarcoma (SCLS) is presently regarded as a rare variant of well‐differentiated liposarcoma (WDLPS), which has the potential for aggressive clinical behavior. WDLPS occurs most frequently in the limbs and retroperitoneum. The most common site of SCLS occurrence is the upper limbs or shoulder girdle. Herein we report the first case of primary retroperitoneal SCLS. A 60‐year‐old Japanese man presented with a right inferior abdominal mass. Complete excision of the mass displayed a yellowish spherical tumor with a well‐circumscribed appearance measuring 98 × 95 mm. Pathological examination of the tumor revealed a neural‐like spindle cell proliferation set in a fibrous background that was associated with an atypical lipomatous component, which usually included lipoblasts. Mitotic cells were scarce. Immunohistochemical analysis demonstrated that lipoblasts were S100 positive, spindle cells were CD34 positive, and both spindle cells and lipoblasts were MDM2 negative. The Ki‐67 labeling index was <2%. At one year follow up, the patient was alive without local recurrence or metastasis. Although the proliferative activity of this tumor did not indicate strong malignancy, retroperitoneal liposarcoma generally has a poor prognosis. Accumulation of cases of SCLS is necessary to facilitate a more accurate evaluation of the pathology and clinical behavior of this tumor.     

Effect of colestimide therapy for glycemic control in type 2 diabetes mellitus with hypercholesterolemia

Colestimide is a new anion-exchange resin used to lower serum cholesterol in Japan. Because of its excellent compliance, colestimide can replace cholestyramine. To clarify the effect of colestimide on glycemic controls, colestimide (3 g/day) or pravastatin (10 mg) was given orally to patients with type 2 diabetes treated with oral hypoglycemic agents or insulin who had low-density lipoprotein (LDL) cholesterol levels exceeding 3.6 mmol/l. In the colestimide groups, fasting plasma glucose concentrations had decreased significantly from 8.5 +/- 1.4 to 7.7 +/- 1.5 mmol/l at 3 months (P<0.05), as had glycated hemoglobin (HbA1c) from 7.7 +/- 0.7% to 6.8 +/- 0.5%, for an 8% reduction (P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin group. Total cholesterol and LDL-cholesterol decreased significantly (P<0.01) with either medication, with similar reduction rates for both drugs. Doses of oral hypoglycemic agents and insulin did not change during the study, and body weight remained stable. Considering that patients with type 2 diabetes often have hyperlipidemia, colestimide therapy may have a clinically useful dual action in such patients.     

Increased expression of cyclooxygenase-2 correlates with resistance to radiation in human prostate adenocarcinoma cells

PURPOSE: Cyclooxygenase-2 functions as a survival factor by protecting cells from apoptosis. We analyzed cyclooxygenase-2 expression in LNCaP-COX-2 and LNCaP-Neo cell lines treated with irradiation. MATERIALS AND METHODS: LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 500 microM celecoxib and a dose response curve was generated. A clonogenic assay was performed in which cells were subjected to irradiation (0 to 6 Gy) with or without celecoxib. Cyclooxygenase-2 protein and other relevant proteins were measured by immunohistochemistry Western blot analysis after irradiation and celecoxib treatment. RESULTS: The 2 studied cell lines experienced cytotoxic effects of celecoxib in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to radiation therapy than LNCaP-Neo cells. Furthermore, the addition of celecoxib sensitized LNCaP-Neo and LNCaP-COX-2 cells to the cytocidal effects of radiation. Moreover, cyclooxygenase-2 over expression was associated with the over expression of pAkt and carbonic anhydrase. In this cell line irradiation alone was associated with increased expression of cyclooxygenase-2 and carbonic anhydrase. Combination therapy with irradiation and celecoxib down-regulated cyclooxygenase-2, pAKT and carbonic anhydrase. LNCaP-Neo cells expressed carbonic anhydrase and pAkt. Irradiation of these cells increased carbonic anhydrase and pAkt expression. Combination therapy with irradiation and celecoxib down-regulated carbonic anhydrase and pAkt. CONCLUSIONS: Cyclooxygenase-2 expression is also associated with pAkt and carbonic anhydrase expression. Down-regulation of cyclooxygenase-2 by celecoxib is associated with decreased expression of cyclooxygenase-2, pAkt and carbonic anhydrase, and eventual radiation sensitization, which is a phenomenon that may have clinical usefulness.     

Surgical treatment for liver cancer. Current issues

Surgical treatment of hepatocellular carcinoma (HCC) has developed remarkable for several reasons. The surgical mortality rates of patients with HCC after hepatectomy have decreased due to appropriate criteria for surgery, refined surgical techniques and improvement in the pre- and postoperative management. In preoperative management, refinements in liver function tests and strategies for esophageal varices, and the induction of preoperative portal vein embolization have contributed favorably to the outcome after hepatectomy for HCC. Furthermore, hepatectomy has been technically refined by various vascular control methods and liver transection devices based on the realization that surgical anatomical information also plays a major role in improving surgical outcome. Also concomitant splenectomy with hepatectomy might extend the criteria for surgery in HCC patients with hypersplenism. Therefore, hepatectomy is a safe therapeutic approach that could bring about a favorable outcome in patients with HCC. Nowadays transplantation is one of the therapeutic options for HCC patients, even in Japan. Herein the surgical treatment of HCC in Japan is reviewed and current issues in the surgical treatment of HCC are discussed.     

Increased apoptosis of circulating T cells in myelodysplastic syndromes

The mechanism of T cell lymphopenia in myelodysplastic syndromes (MDS) is unknown. We investigated apoptosis in freshly isolated and cultured lymphocytes; the latter were used to detect cells not yet apoptotic but destined for apoptosis. Apoptosis increased in both fresh and cultured T cells in MDS compared with those from healthy controls. Furthermore, in lymphopenic MDS patients the lymphocyte count correlated negatively with the degree of T cell apoptosis. MDS T cells showed increased Fas expression. However, in MDS but not in controls, the degree of T cell apoptosis was independent of the Fas expression level, and exogenous anti-Fas antibodies did not modulate T cell apoptosis. Mechanisms other than the Fas–Fas ligand pathway may induce T cell apoptosis in MDS.     

Laterality of Swallowing in Healthy Subjects by AP Projection Using Videofluoroscopy

Although anteroposterior projections in videofluoroscopic examination of swallowing (VF) provide clinically important information, the laterality of swallowing in healthy subjects has not been examined fully to date. One hundred sixty-seven healthy volunteers were prospectively studied. The subjects were asked to swallow 5 ml of barium solution three times while X-ray images were taken that showed the pathway of the solution from the pharynx into the esophagus to assess the laterality of swallowing. We classified patterns of swallowing into three types according to passage in the pharyngoesophageal segment as indicated by width: RD (right-side-dominant flow), LD (left-side-dominant flow), and NL (no laterality in flow). Fifty-eight percent of the subjects were classified as NL, 35% as LD, and 7% as RD. The ratio of types in women was NL:LD:RD = 7:2:1. There were no significant differences among the groups according to age. Although classifications in young men (age = 20–30 years) tended to be the same as in women regardless of age, ratios of LD tended to increase with age; 71% of elderly adults (age = 51–75 years) were classified as LD. These results demonstrate laterality in normal swallowing and will be helpful in determining treatment strategies for the patients with dysphagia.     

Different apoptotic regulation of TRAIL-caspase pathway in HBV- and HCV-related hepatocellular carcinoma

Human hepatocellular carcinoma (HCC) appears to be strongly associated with apoptosis and its breakdown may be involved in the occurrence of HCC. Like the Fas/Fas-L system, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) transduces apoptosis in a number of cancers; it is also a clinical candidate for cancer therapy. To examine its applicability in future therapy, the apoptotic pathway through TRAIL was investigated in HBV- and HCV-related HCC that have different mechanisms of hepatocarcinogenesis. Caspase-3 activity and the expression of four types of TRAIL receptor mRNAs were quantitated in tumor and contiguous non-tumor tissues obtained from 27 patients with HCC (HBV-related in 10; HCV-related in 17). The expression of caspase-3 and TRAIL receptors was also examined immunohistochemically. A significantly positive correlation was observed between caspase-3 activity and TRAIL-R1, -R2. Caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue were significantly lower than those in non-tumor tissue in HBV-related HCC. Some HCV-related HCC cases, however, demonstrated elevated caspase-3 activity and TRAIL-R1, -R2 expression in tumor tissue. HBV-related HCC demonstrated significantly suppressed caspase-3 activity, signifying apoptosis. Both TRAIL-R1 and -R2 showed coefficient correlation with caspase-3 activity, and were strongly associated with apoptosis in human HCC.