Appropriate duration of postoperative oral adjuvant chemotherapy with HCFU for colorectal cancer

We conducted a joint study of different duration of drug administration for oral adjuvant chemotherapy using camphor (HCFU) with patients having advanced colorectal cancer who underwent curative resection. The patients were randomly divided into 2 groups, according to length of HCFU administration (6-month group and 2-year group), and followed up for 5 years postoperatively. In total, 239 patients were originally enrolled, out of which 155 were chosen as subjects for this study. There was significant difference in the overall cumulative 5-year survival rate between the short-term group and the long-term group (78.1% vs 89.6%). Between the respective subgroup that was defined by tumor location (colon or rectum), no differences were observed, but there was significant difference in the subgroup that was defined by the presence/absence of lymph node metastasis (59.4% vs 83.9%). It appears that oral adjuvant chemotherapy with HCFU is more effective when administered for 2 years than for 6 months.     

Ewing's sarcoma

Ewing's sarcomas account for 6.8% of all primary malignant bone tumors and are probably a neurogenic, undifferentiated, high-grade malignancy, which usually affects the bones of children 5-15 years of age. Pain and swelling are the most common symptoms. Increase of CRP and erythrocyte sedimentation rate, leucocytosis, and anemia are frequently seen. Radiologically, they show permeative bone destruction on plain radiographs. When arising in the diaphysis of long bones, laminated, "onion-skin" periosteal reaction is seen. The tumor shows muscle density on CT, iso-signal intensity on T1-weighted MR images, and high signal intensity on T2-weighted MR images. Intramedullary invasion and skip lesions can be detected on MR images. Histologically, the tumor is uniformly composed of sheets of small round cells closely packed and without any matrix product. Glycogen granules are demonstrated in the cytoplasm by periodic acid-Schiff (PAS) and diastase reactions. Immunohistochemically, Ewing's sarcomas are positive for vimentin and MIC-2 gene product (CD99). Reciprocal translocation, i.e., t(11;22) (q24;q12), is seen in the tumor cells. EWS/FLI-1 fusion gene can be demonstrated, which can be a complementary method in diagnosing this tumor. Because Ewing's sarcomas are chemosensitive and radiosensitive, they are treated by a combination of chemotherapy, surgery, and radiotherapy. Neoadjuvant chemotherapy consists of preoperative chemotherapy and postoperative chemotherapy. Preoperative chemotherapy aims at eradicating distant micrometastasis, reducing the primary tumor volume, and evaluating the efficacy of the chemotherapeutic agents. Surgery is performed as a local treatment by excising the tumor using the wide procedure. If surgery is impractical, curative radiotherapy is performed instead of excision. When surgery is performed without complete wide procedure, adjuvant radiotherapy is carried out to eradicate the residual tumor cells. Postoperative chemotherapy aims to eradicate the distant micrometastasis. Recently, myeloablative, high-dose chemotherapy followed by autologous bone marrow transplantation is being attempted for poor-prognosis patients and good results have been reported.     

Indication and limitation of endoscopic surgery against urological cancer

Endoscopic surgery in the urological field begins with cystoscopy and transurethral resection, and it develops into laparoscopic surgery. The indication of laparoscopic surgery for a malignant tumor also gradually expands. It is virtually impossible to search for urological cancer using laparoscopic procedures. In particular, out laparoscopic nephrectomy for renal cancer and transurethral resection for bladder cancer used widely in Japan. In the future, laparoscopic partial nephrectomy and the laparoscopic procedure for adrenal cancer and prostate cancer are considered to become widespread.     

Comparison of treatment methods for hepatocellular carcinoma--based on JIS score

It is well known that prognosis of patients with hepatocellular carcinoma (HCC) depends not only cancer spread, but also on liver disease stage. The Japan Integrated Staging (JIS) scoring system, which combines TNM stage and Child-Pugh stage, is superior to CLIP Score in the discriminatory ability of the prognosis in 3,934 patients with HCC. Therefore, it is also useful in the comparison of the treatment results between treatment modalities or between institutions. It is thus recommended that the JIS score be used in the comparison of treatment results of patients with HCC.     

Genome-wide cDNA microarray analysis of gene expression profiles in pancreatic cancers using populations of tumor cells and normal ductal epithelial cells selected for purity by laser microdissection

To characterize molecular mechanism involved in pancreatic carcinogenesis, we analysed gene-expression profiles of 18 pancreatic tumors using a cDNA microarray representing 23,040 genes. As pancreatic ductal adenocarcinomas usually contain a low proportion of cancer cells in the tumor mass, we prepared 95% pure populations of pancreatic cancer cells by means of laser microbeam microdissection, and compared their expression profiles to those of similarly purified, normal pancreatic ductal cells. We identified 260 genes that were commonly upregulated and 346 genes that were downregulated in pancreatic cancer cells. Because of the high degree of purity in the cell populations, a large proportion of genes that we detected as upregulated or downregulated in pancreatic cancers were different from those reported in previous studies. Comparison of clinicopathological parameters with the expression profiles indicated that altered expression of 76 genes was associated with lymph-node metastasis and that of 168 genes with liver metastasis. In addition, expression levels of 30 genes were related to the recurrence of disease. These genome-wide expression profiles should provide useful information for finding candidate genes whose products might serve as specific tumor markers and/or as molecular targets for treatment of patients with pancreatic cancer.     

Multiple myeloma complicated by autoimmune hemolytic anemia

A 57-year-old man was admitted with severe anemia and hypergamma globulinemia. After a diagnosis of multiple myeloma and autoimmune hemolytic anemia was made, chemotherapy rapidly decreased the M-protein level and improved his anemia with normalization of the direct Coombs test. The immunoglobulin binding to the patient's red cells was immunoglobulin G kappa chain like the myeloma M-protein. However, monoclonal immunoglobulin G derived from short-term culture of the patient's bone marrow mononuclear cells did not bind to a panel of red cells. Therefore, the relationship between the M protein produced by his myeloma cells and hemolysis remained unclear.     

Cortical activation in area 3b related to finger movement: an MEG study

To evaluate cortical activation reflecting sensory feedback after finger movement, we recorded movement-related cerebral fields (MRCFs) following voluntary finger movement and somatosensory evoked fields for mixed (median) and pure cutaneous (radial) nerve stimulations (mSEFs and rSEFs) in six normal subjects. Equivalent current dipoles for movement-evoked field 1 (MEF1) in MRCFs and the component (70m) obtained in mSEFs, not clearly in rSEFs, were similarly distributed in each subject. They were located in area 3b, but both mean locations were significantly (p < 0.01) medial to N20m in mSEFs. MEF1 and 70m reflect similar cortical activities related to finger movement and have the same neuronal generator in area 3b, which is different from that of N20m.     

Expression of BRI,the normal precursor of the amyloid protein of familial British dementia,in human brain

Familial British dementia (FBD) is characterized neuropathologically by deposition of a unique amyloid-forming protein, ABri. It is a fragment of an abnormal form of a precursor protein, BRI. In FBD, BRI is elongated by 11 amino acids due to a point mutation that prevents recognition of the normal stop codon. We have investigated the expression of normal BRI in non-FBD cases. Three antibodies were raised against sequences of BRI and were used for immunoblotting and immunohistochemistry. Each of these antibodies detected a band at approximately 35 kDa by Western blotting. In postmortem human brain tissues, BRI was detected as fine granules in the neuronal cytoplasm. Pyramidal neurons in CA3 and CA4 of the hippocampus as well as Purkinje cells in the cerebellar cortex were most intensely stained for BRI. Such a distribution of neurons strongly expressing BRI parallels the reported occurrence of ABri deposits in patients with FBD. In pathological cases, BRI was detected in dystrophic neurites in senile plaques, around lesions in ischemic cases, in torpedo and glumose changes in the cerebellum, Lewy neurites, ballooned neurons, and neurons generally in hypoxic cases. These results suggest that BRI is transported in neuronal processes and is possibly involved in some role in nerve terminals. While a physiological role of BRI in brain remains to be determined, the behavior of BRI in diverse brain lesions appears to be somewhat analogous to that of amyloid precursor protein, which is the source of the -amyloid protein of Alzheimers disease.     

Hippocampal volume and first major depressive episode after cancer diagnosis in breast cancer survivors

OBJECTIVE: Patients experiencing their first major depressive episode after receiving a diagnosis of cancer are frequently seen in clinical oncology settings; however, little is known about the neurobiological basis of the first episode. In previous studies, a smaller hippocampus than in healthy comparison subjects has been observed in patients with a history of recurrent and prolonged major depressive episodes. The purpose of the present study was to investigate whether there is an association between hippocampal volume and a first major depressive episode after cancer diagnosis in cancer survivors. METHOD: The subjects were 68 female cancer survivors who had undergone breast cancer surgery 3 or more years earlier (mean interval=4.3 years, SD=0.9). The hippocampal volume and delayed recall function of the 17 cancer survivors who had their first major depressive episode after receiving their cancer diagnosis and the 51 with no history of major depressive episode at any time during their lives were measured by magnetic resonance imaging and the Wechsler Memory Scale-Revised, respectively. RESULTS: The mean duration of the major depressive episode after cancer diagnosis was 11.9 weeks (SD=14.2). There were no significant differences in left or right hippocampal volume or in delayed recall function between the cancer survivors with and without a major depressive episode after cancer diagnosis. CONCLUSIONS: First major depressive episodes after cancer diagnosis in female cancer survivors do not appear to be associated with hippocampal volume. However, a longitudinal study with healthy comparison subjects is needed to draw a definite conclusion.