Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer

Purpose: Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer. Methods: Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed. Results: High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis. Conclusions: Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients

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Prognostic value of tropomyosin-related kinases A, B, and C in gastric cancer.

PURPOSE: Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer. METHODS: Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed. RESULTS: High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis. CONCLUSIONS: Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients.

A prospective study of total plasma cell-free DNA as a predictive biomarker for response to systemic therapy in patients with advanced non-small-cell lung cancers.

BACKGROUND: While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for systemic therapy response. PATIENTS AND METHODS: We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6-12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal-Wallis and Kaplan-Meier estimates. RESULTS: A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93-1.20, P = 0.41] or OS (HR = 1.04, 95% CI 0.93-1.17, P = 0.51), neither were changes in cfDNA. CONCLUSIONS: In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing.

Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy: reliable results following long-term follow-up.

BACKGROUND: To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. METHODS: From January 1999 to March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. RESULTS: Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83-1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. CONCLUSIONS: Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.

Statins inhibit tumor progression via an enhancer of zeste homolog 2-mediated epigenetic alteration in colorectal cancer.

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin-mediated antiproliferative effects depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27(KIP1) expression in the resected CRC by immunohistochemical staining and resulted in the significantly better prognoses both in overall survival (p = 0.02) and disease free survival (p < 0.01) compared to patients without statin intake. Statins may inhibit tumor progression via an EZH2-mediated epigenetic alteration, which results in survival benefits after resected CRC. Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC.

Distal pancreatectomy using a no-touch isolation technique.

BACKGROUND AND AIMS: Distal pancreatectomy is the only effective treatment for cancers of the pancreatic body and tail. The recurrence rate after DP has remained high. In an effort to over-come this problem, we developed a no-touch surgical technique for DP. This is a pilot study to see if distal pancreatectomy can be technically done using a no-touch surgical technique with-out deteriorating the post-operative prognosis. PATIENTS AND METHODS: From November 2000 through May 2011, 16 pancreatic ductal adeno-carcinoma patients have been operated on using a no-touch technique by a single operator. We described the surgical technique, and we reported our preliminary experience. During the procedure, the pancreatic body and tail is neither grasped nor squeezed by the surgeon. And all drainage vessels from the pancreatic body and tail are ligated and divided during the early phase of the operation. Furthermore, for improved dissection of the retroperitoneal tissue (rightward and posterior margins), we use a hanging and clamping maneuver and dissection behind Gerota's fascia. RESULTS: In the current series, the posterior and rightward resection margins were free in all patients, although seven were positive for anterior serosal invasion. The post-operative prognosis was not deteriorated with this technique. CONCLUSION: No-touch distal pancreatectomy technique may have some theoretical advantages, which merit future investigation in randomized controlled trials.

Contributions of FASN and SCD gene polymorphisms on fatty acid composition in muscle from Japanese Black cattle.

The fatty acid synthase (FASN) and stearoyl-CoA desaturase (delta-9-desaturase) (SCD) genes affect fatty acid composition. This study evaluated the contributions of polymorphisms of these genes on fatty acid composition in muscle in two different populations: 1189 and 1058 Japanese Black cattle from the Miyagi and the Yamagata populations respectively. We sampled intramuscular fat from the longissimus thoracis muscle in the Miyagi population and from the trapezius muscle in the Yamagata population. The collective contributions of FASN and SCD polymorphisms to total additive genetic variance for oleic acid were 13.46% in the Miyagi population and 16.29% in the Yamagata population and to phenotypic variance were 5.45% and 6.54% respectively. Although the individual effects of FASN and SCD polymorphisms on fatty acid composition were small, overall gene substitution may effectively improve fatty acid composition. In addition, we found that gene polymorphism contributions of fatty acids varied by population even in the same breed.

Effect of the C-terminal domain of Vibrio proteolyticus chitinase A on the chitinolytic activity in association with pH changes.

AIMS: To reveal the cause of the difference in activity of chitinase A from Vibrio proteolyticus and chitinase A from a strain of Vibrio carchariae (a junior synonym of Vibrio harveyi), we investigated the pH-dependent activity of full-length V. proteolyticus chitinase A and a truncated recombinant corresponding to the V. harveyi form of chitinase A. METHODS AND RESULTS: After overexpression in Escherichia coli strain DH5α, the full-length and truncated recombinant chitinases were purified by ammonium sulphate precipitation and anion exchange column chromatography. Chitinase activity was measured at various pH values using α-crystal and colloidal chitins as the substrate. The pH-dependent patterns of the relative specific activities for α-crystal chitin differed between the full-length and truncated recombinant chitinases, whereas those for colloidal chitin were similar to each other. CONCLUSION: The difference in the activity of V. proteolyticus chitinase A and V. harveyi chitinase A might be partly due to a change in the pH dependence of the chitinase activities against α-crystal chitin, resulting from C-terminal processing. SIGNIFICANCE AND IMPACT OF STUDY: The present results are important findings for not only ecological studies on the genus Vibrio in association with survival strategies, but also phylogenetic studies.

Distribution and species composition of juvenile and adult scombropids (Teleostei, Scombropidae) in Japanese coastal waters.

Two scombropid fishes, Scombrops boops and Scombrops gilberti, are closely related and commercially important species in Japan. These species are often confused in commercial markets because of their morphological similarity. In this study, scombropid specimens collected from various Japanese coastal waters were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and phylogenetic analysis of the 16S rRNA gene in mitochondrial DNA. These analyses showed that all the scombropid specimens collected from localities in the Sea of Japan were identified as S. boops, whereas those from the Pacific Ocean included two species, S. boops and S. gilberti. Almost all juvenile (<200 mm standard body length, S(L)) S. gilberti originated from the Pacific coastal waters of the northern Japan, whereas adults (>400 mm S(L)) were found only in deep water off the Izu Peninsula to the Izu Islands. This suggests that S. gilberti might migrate extensively during its life cycle. In addition, differences in the number of specimens and the distribution between the two species suggest that S. gilberti is less abundant than S. boops in Japanese waters.

Phenotypic variation in Lactococcus lactis subsp. lactis isolates derived from intestinal tracts of marine and freshwater fish.

AIMS: We compared phenotypic characteristics of Lactococcus lactis subsp. lactis derived from different sources including the intestinal tract of marine fish and freshwater fish, and cheese starter culture. METHODS AND RESULTS: In the phylogenetic analysis based on partial 16S rRNA gene nucleotide sequences (1371 bp), freshwater fish-, marine fish- and cheese starter culture-derived strains were identical to that of L. lactis subsp. lactis previously reported. Fermentation profiles determined using the API 50 CH system were similar except for fermentation of several sugars including l-arabinose, mannitol, amygdalin, saccharose, trehalose, inulin and gluconate. The strains did have distinct levels of halotolerance: marine fish-derived strains > cheese starter-derived strain > freshwater fish-derived isolate. CONCLUSIONS: Lactococcus lactis subsp. lactis showed extensive diversity in phenotypic adaptation to various environments. The phenotypic properties of these strains suggested that L. lactis subsp. lactis strains from fish intestine have additional functions compared with the cheese starter-derived strain that has previously described. SIGNIFICANCE AND IMPACT OF THE STUDY: The unique phenotypic traits of the fish intestinal tract-derived L. lactis subsp. lactis might make them useful as a probiotics in aquaculture, and contribute to the development of functional foods and novel food additives, since the strains derived from fish intestines might have additional functions such as antibacterial activity.

Smoking-related changes in the background lung of specimens resected for lung cancer: a semiquantitative study with correlation to postoperative course.

AIMS: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking-related interstitial lung disease. METHODS AND RESULTS: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers (P < 0.01) with lower lobe predominance. There were significant correlations (P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone (P < 0.01). CONCLUSIONS: AEF is an important smoking-related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important.

Novel ecological niche of Cetobacterium somerae, an anaerobic bacterium in the intestinal tracts of freshwater fish.

AIMS: This study was conducted to clarify the taxonomic status of Bacteroides type A strains with high vitamin B(12)-producing ability that is widely distributed in the intestinal tracts of freshwater fish. METHODS AND RESULTS: Seventeen strains of Bacteroides type A isolated from five fish species were all rod-shaped and gram-negative. The strains were positive for esculin hydrolysis, nitrate reduction, resistance to bile, acid phosphatase, and negative for the production of catalase and urease and the susceptibility to vancomycin. The G+C content of DNA from the 17 strains was 29 x 1-31 x 9 mol%, and 16S rDNA sequence analysis revealed a close phylogenetic relationship between Bacteroides type A strains and Cetobacterium somerae sharing 99 x 7-100% sequence similarity. In addition, strains were capable of producing vitamin B(12) at a rate of 1 x 82-13 x 98 ng ml(-1) in 48 h. CONCLUSION: Phenotypic and phylogenetic characteristics indicated that all isolates previously classified as Bacteroides type A strains belong to C. someare. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided the important finding of novel niche of vancomycin-resistant bacteria such as C. somerae in the intestinal tract of freshwater fish.

Purification and characterization of Vibrio parahaemolyticus extracellular chitinase and chitin oligosaccharide deacetylase involved in the production of heterodisaccharide from chitin.

A chitin-degrading bacterial strain, KN1699, isolated from Yatsu dry beach (Narashino, Chiba Prefecture, Japan), was identified as Vibrio parahaemolyticus. Treatment of powdered chitin with crude enzyme solution prepared from the supernatant of KN1699 cultures yielded a disaccharide, beta-D-N-acetylglucosaminyl-(1,4)-D-glucosamine (GlcNAc-GlcN), as the primary chitin degradation product. The extracellular enzymes involved in the production of this heterodisaccharide, chitinase (Pa-Chi; molecular mass, 92 kDa) and chitin oligosaccharide deacetylase (Pa-COD; molecular mass, 46 kDa), were isolated from the crude enzyme solution, and their hydrolysis specificities were elucidated. These studies confirmed that (1) Pa-Chi hydrolyzes chitin to produce (GlcNAc)(2) and (2) Pa-COD hydrolyzes the acetamide group of reducing end GlcNAc residue of (GlcNAc)(2). These findings indicate that GlcNAc-GlcN is produced from chitin by the cooperative hydrolytic reactions of both Pa-Chi and Pa-COD.

Immune modulation and expression of cytokine genes in rainbow trout Oncorhynchus mykiss upon probiotic feeding.

This study elucidates the immune modulation including the expression of cytokine genes following dietary administration of three selected probiotic bacteria--Lactobacillus rhamnosus, Enterococcus faecium and Bacillus subtilis to fish, rainbow trout Oncorhynchus mykiss. They were fed for 45 days on either a basal control diet or one of the three probiotic diets containing the specific bacteria in freeze-dried form at a density of 10(9)CFUgfeed-1. The non-specific immune parameters examined--superoxide anion production by the head kidney leukocytes and the alternate complement activity of serum was improved by probiotic feeding. Besides this, the relative gene expressions of interleukin-1beta1, tumor necrosis factor 1 and 2 and transforming growth factor-beta were up regulated in the spleen and the head kidney. The comparatively better performance of E. faecium could possibly be linked to their suitable ambient temperature conditions. Thus, probiotic bacteria delivered in feed exerts its influence on the immune system of fish, both at cellular and molecular levels.

Identification of intestinal bacteria from Japanese flounder (Paralichthys olivaceus) and their ability to digest chitin.

AIMS: The aim of the present study was to clarify the taxonomic status of intestinal bacteria isolated from Japanese flounder (Paralichthys olivaceus) and describe their ability to digest chitin. METHODS AND RESULTS: Phylogenetic analysis based on 16S ribosomal DNA (rDNA) sequences showed that 82 representative isolates were closely related to three major species of marine vibrios, Vibrio scophthalmi-Vibrio ichthyoenteri group (41 isolates), Vibrio fischeri (39 isolates) and Vibrio harveyi (two isolates), with similarities of 97.2-99.8%, 96.4-100% and 98.6-99.5% respectively. These findings indicate that V. scophthalmi-V. ichthyoenteri group is indigenous to the intestinal tract of Japanese flounder. Moreover, the ability of 82 isolates to digest chitin was examined using the agar plate method and PCR amplification of the chiA gene. The two V. harveyi isolates and 36 of 41 V. scophthalmi-V. ichthyoenteri isolates digested chitin and were chiA PCR positive, whereas all 39 V. fischeri isolates digested chitin but were chiA PCR negative. CONCLUSIONS: Intestinal bacteria from Japanese flounder were mainly composed of Vibrio scophthalmi-V. ichthyoenteri group and V. fischeri. Taken together, the results showed that 81 of 82 isolates could digest chitin. However, only 38 of these isolates possessed a chiA homologue which could be identified by PCR. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study shows that Japanese flounder harbours bacteria of the V. scophthalmi-V. ichthyoenteri group, and these results are similar to what has been found for turbot (Scophthalmus maximus).

Purification and characterization of chitinases from Clostridium sp. E-16 isolated from the intestinal tract of the South American sea lion (Otaria flavescens).

AIMS: This study was undertaken to examine the properties of chitinases purified from Clostridium sp. E-16, an intestinal bacterium of the South American sea lion (Otaria flavescens). We also elucidated the taxonomic status of this bacterium to better understand the role of intestinal anaerobic bacteria in marine animals. METHODS AND RESULTS: Two chitinases were purified with ammonium sulfate precipitation, affinity chromatography and preparative electrophoresis from culture supernatant fluid from Clostridium sp. E-16. Molecular mass was estimated to be 77 kDa for chitinase 1 and 98 kDa for chitinase 2 by SDS-PAGE. Optimum pH of both purified chitinases was between 5.0 and 7.0. Chitinase 1 was inhibited with Cu(2+), Fe(2+), Hg(2+) and Zn(2+), while chitinase 2 was inhibited with Fe(2+). Phylogenetic analysis using 16S ribosomal DNA (rDNA) sequences and phenotypic characterization revealed that Clostridium sp. E-16 was closely related to Clostridium baratii. CONCLUSIONS: It is likely that chitinases from C. baratii or a C. baratii-like bacterium play an important role in degradation of chitin in the intestinal tract of the South American sea lion and in marine environments. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of chitinase purification and characterization from a marine Clostridium strain.

Immune responses in rainbow trout Oncorhynchus mykiss induced by a potential probiotic bacteria Lactobacillus rhamnosus JCM 1136.

This study was undertaken to examine the effect of supplementing a suggested probiotic bacteria Lactobacillus rhamnosus JCM 1136 in feed on immune response and gut flora composition of rainbow trout Oncorhynchus mykiss. The probiotic bacteria were incorporated into a commercial feed to constitute two experimental diets containing either 10(9) or 10(11) colony forming unit of live bacteria/g of feed while a third diet without the bacterial supplement served as the control diet. The diets were offered to rainbow trout (75g average weight) in triplicate tanks for 30 days. Fish were sampled at 10, 20 and 30 days after commencement of the feeding trial to determine the proportion of the given probiont in the gut microflora composition and the nonspecific humoral and cellular immune responses on the 30th day. The relative proportion of the probiont increased with the feeding duration in the intestine, but not in the stomach. The proportion of L. rhamnosus in the stomach corresponded to the intake levels while no such relation existed in the intestine. The serum lysozyme and complement activities were significantly greater in fish fed the higher level of probiont compared with the control fish. The phagocytic activity of head kidney leucocytes also showed similar tendencies. These observations indicate the potential immuno-regulatory role of probiotic organisms in rainbow trout.

Induced radioactivity in CU targets produced by high-energy heavy ions and the corresponding estimated photon dose rates.

Irradiation experiments were performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility, National Institute of Radiological Sciences. The radioactive spallation products in a thick Cu target were obtained for Ar(230, 400 MeV per nucleon), Si(800 MeV per nucleon), Ne(100, 230, 400 MeV per nucleon), C(100, 230, 400 MeV per nucleon), He(100, 230 MeV per nucleon), p(100, 230 MeV) ions. The gamma-ray spectra from irradiated Cu samples inserted into the composite Cu target were measured with a high-purity germanium (HPGe) detector. From the gamma-ray spectra, we obtained the spatial distribution of radioactive yields of spallation products of 40 nuclides in the Cu sample in the Cu target. From the spatial distribution of radioactive yields, we estimated the residual activity and photon dose induced in the Cu target. The residual activity and photon dose become larger with the increase in projectile energy per nucleon and the range of the projectile beam for the same projectile energy per nucleon.

Clinical and immunohistochemical characteristics of benign giant cell tumour of bone with pulmonary metastases: case series.

PURPOSE: Giant cell tumour of bone with pulmonary metastases is rare. However, some patients die of pulmonary metastases, and histological examination cannot distinguish between benign tumour and malignant metastases. In this study, we present clinical and immunohistochemical findings associated with giant cell tumour of bone with pulmonary metastases. METHODS: Five patients with benign giant cell tumour of bone with pulmonary metastases (one man and 4 women) were studied. Patients' ages ranged between 20 and 23 years (mean age, 21.8 years). Tumours were in the distal femur in 2 cases, and in the proximal tibia, distal tibia, and lumbar spine in one case each. The tissue specimens from primary tumours, recurrent tumours, and pulmonary metastases were studied using immunohistochemical techniques. RESULTS: Three of the 5 primary tumours were of the spontaneous regression or growth cessation type, or the continuously slow-growing type, showing 4.2% to 6.2% of positive cells for Ki-67 after immunohistochemical staining. However, 2 patients with the rapid-growing type of disease died of pulmonary metastases; their primary, recurrent, and metastatic tumour specimens contained 9.0% to 11.5% of positive cells for Ki-67. CONCLUSION: Three of the 5 primary tumours had a benign clinical pattern and immunohistochemistry. Two of the 5 patients died of pulmonary metastases, which had an aggressive clinical pattern and a high prevalence of positive cells in Ki-67. Examination of Ki-67 should be carried out for aggressive type of giant cell tumour.

Surgical management of malignant soft tissue tumours in patients aged 65 years or older.

OBJECTIVE: With the aim to determine the most effective treatment for primary malignant musculoskeletal tumours in patients aged 65 years or older, we reviewed cases of low- and high-grade neoplasms, surgical margins, surgical methods, and the prognoses of elderly and aged patients at our institution. METHODS: Records of 25 patients aged 65 years or older who had malignant soft tissue tumours from December 1986 to February 1997 were reviewed. Low- and high-grade neoplasms accounted for 8 and 17 patients, respectively. 11 patients were aged 65 to 69 years, while 14 were 70 years or older. Surgical margins were wide in 19 cases, marginal in 4, and intralesional in 2. Reconstruction was done using 6 musculocutaneous flaps and/or 4 vessel grafts. As adjuvant therapy, radiotherapy was used in 5 cases and chemotherapy in 3. There was no recurrence in patients with wide surgical margins (determined on the basis of gross inspection of the excised tumour and the cut surface); but there was recurrence in 4 patients with marginal margins, and one patient with intralesional margin. Two patients with intralesional, 4 with marginal, and 2 with wide margins, died from recurrence at the primary site and metastasis, or from metastasis without recurrence at the primary site. RESULTS: Follow-up periods ranged from 4 months to 180 months (mean, 91.6 months). The overall 5-year survival rate was 79.6%; for low- and high-grade neoplasms, the figures were 100% and 69.7%, respectively; for those aged 65 to 69 years and in their 70's or older, the figures were 90.9% and 70.1%, respectively. CONCLUSION: For geriatric patients, wide surgical margins are required to manage both low- and high-grade neoplasms, in order to avoid multiple surgeries.