Safety evaluation of immune-cell therapy for malignant tumor in the Cancer Immune-cell Therapy Evaluation Group (CITEG).

BACKGROUND AIMS: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide. METHODS: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation. RESULTS: A total of 3839 patients with malignant tumor were treated with immune-cell therapy, with a median age of 64 years (range, 13-97 years) and a male-to-female ratio of 1:1.08 (1846:1993). Most patients' performance status was 0 or 1 (86.8%) at the first visit, and 3234 cases (84.2%) were advanced or recurrent cases, which accounted for the majority. The total number of administrations reported in CITEG was 31890, of which 960 (3.0%) showed adverse events. The numbers of adverse events caused by treatment were 363 (1.8%) of 19661 administrations of αßT cell therapy, 9 of 845 administrations of γδT-cell therapy (1.1%) and 10 of 626 administrations of natural killer cell therapy (1.6%). The number of adverse events caused by dendritic cell (DC) vaccine therapy was 578 of 10748 administrations (5.4%), which was significantly larger than those for other treatments. Multivariate analysis revealed that αßT cell therapy had a significantly greater risk of adverse events at performance status 1 or higher, and patients younger than 64 years, women or adjuvant immune-cell therapy had a greater risk of adverse events in DC vaccine therapy. Injection-site reactions were the most frequently reported adverse events, with 449 events, the majority of which were associated with DC vaccine therapy. Among all other adverse events, fever (228 events), fatigue (141 events) and itching (131 events) were frequently reported. In contrast, three patients had adverse events (fever, abdominal pain and interstitial pneumonia) that required hospitalization, although they were weakly related to this therapy; rather, it was considered to be the effect of treatment for the primary disease. CONCLUSIONS: Immune-cell therapy for cancer was considered to be a safe treatment without serious adverse events.

Longitudinal shape irregularity of airway lumen assessed by CT in patients with bronchial asthma and COPD.

BACKGROUND: Airway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen. METHODS: Quantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area. RESULTS: Longitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation. CONCLUSIONS: The combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.

Correlation between pathology and neuromelanin MR imaging in Parkinson's disease and dementia with Lewy bodies.

INTRODUCTION: Direct correlation between neuropathological findings and postmortem neuromelanin MR imaging (NmMRI) was performed in the substantia nigra pars compacta (SNc) to clarify the pathological background of the signal changes in normal, Parkinson's disease (PD), and dementia with Lewy bodies (DLB) cases. METHODS: NmMRI of 10 % formalin-fixed autopsied midbrains was performed in three cases (normal control, DLB, and PD) with a 3T imaging system, using a 3D gradient echo T1-weighted sequence with a magnetization transfer contrast pulse. Neuropathological examinations of the midbrains were performed, and the density of neuromelanin-positive neurons (number per square millimeter) was determined. The extent of iron deposition in the midbrain was also evaluated using ferritin immunohistochemistry. Furthermore, we directly correlated the contrast signal ratio in the SNc and the density of neuromelanin-containing neurons. RESULTS: Diffuse hyperintense areas in the SNc reflected well-preserved neuromelanin-containing neurons in the normal control case, whereas an iso-intense area in the SNc showed severe loss of neuromelanin-containing neurons in the DLB and PD cases. Increased signal intensity in the SNc was apparently not influenced by iron deposition. Furthermore, a significant positive correlation between signal intensity and the density of neuromelanin-containing neurons was seen in the SNc. CONCLUSION: Based on the direct correlation between postportem NmMRI and neuropathological findings, signal intensity in the SNc is closely related to the quantity of neuromelanin-containing neurons but is not influenced by iron deposition.

SIRT2 down-regulation in HeLa can induce p53 accumulation via p38 MAPK activation-dependent p300 decrease, eventually leading to apoptosis.

We previously reported that sirtuin 2 (SIRT2), a mammalian member of the NAD+-dependent protein deacetylases, participates in mitotic regulation, specifically, in efficient mitotic cell death caused by the spindle checkpoint. Here, we describe a novel function of SIRT2 that is different from mitotic regulation. SIRT2 down-regulation using siRNA caused apoptosis in cancer cell lines such as HeLa cells, but not in normal cells. The apoptosis was caused by p53 accumulation, which is mediated by p38 MAPK activation-dependent degradation of p300 and the subsequent MDM2 degradation. Sirtuin inhibitors are emerging as antitumor drugs, and this function has been ascribed to the inhibition of SIRT1, the most well-characterized sirtuin that deacetylases p53 to promote cell survival and also binds to other proteins in response to genotoxic stress. This study suggests that SIRT2 can be a novel molecular target for cancer therapy and provides a molecular basis for the efficacy of SIRT2 for future cancer therapy.

Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance.

BACKGROUND: Stromal cells are believed to affect cancer invasion and metastasis. The purpose of this study was to evaluate the distribution of cancer-associated fibroblasts (CAFs) and the incidence of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC), focusing on clinicopathological factors and patient prognosis, as well as cancer invasion. METHODS: The study included 108 patients with OSCC. Anti-α-smooth muscle actin, CD68, and CD163 antibodies were used to identify CAFs and TAMs. CAFs were divided into 4 grades on the basis of staining intensity: negative (0), scanty (1), focal (2), and abundant (3). The most intensive areas of macrophage concentration in each tumor invasive stroma were also evaluated. RESULTS: The cancer specimens were divided into Grade 0/1, Grade 2, and Grade 3 on the basis of CAF grade. In addition, they were divided into low- and high-grade groups on the basis of the number of CD68-positive and CD163-positive macrophages. The latter were significantly increased in the Grade 2 CAF group compared to the Grade 0/1 group (P = 0.009). Kaplan-Meier and multivariate survival analyses revealed that Grade 2 CAFs (P = 0.003) and high CD163-positive macrophage levels (P = 0.007) significantly correlated with a poor outcome in patients with OSCC, and that a high CD163-positive macrophage level was a significant and an independent prognostic factor (P = 0.045). CONCLUSIONS: Cancer-associated fibroblasts and CD163-positive macrophages may be potential prognostic predictors of OSCC.

Fhit, E-cadherin, p53, and activation-induced cytidine deaminase expression in endoscopically resected early stage esophageal squamous neoplasia.

BACKGROUND AND AIM: Abnormal expression of Fragile Histidine Triad (Fhit), E-cadherin and p53 is observed in esophageal squamous cell carcinoma. It has recently been reported that aberrant expression of activation-induced cytidine deaminase (AID) in gastric epithelium leads to the accumulation of nucleotide alterations in the p53 gene. However, little is known about the association between these molecular events and the clinicopathological characteristics of early stage esophageal squamous neoplasia, especially in endoscopically resected tumors. METHODS: Esophageal squamous neoplasias (n = 49) comprising nine cases of low-grade intraepithelial neoplasia (LGIN), 22 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 18 of invasive cancers, were endoscopically resected. Their expression of the tumor-related proteins: Fhit, E-cadherin, p53 and AID was assessed using immunohistochemical methods, and the relationship between protein expression and clinicopathological data was examined. RESULTS: Reduced or absent Fhit and E-cadherin expression was detected in 22% and 0% of LGIN cases, 73% and 14% of HGIN/CIS cases, and 94% and 61% of invasive cancer cases, respectively, showing progressive increases during neoplastic progression (Fhit: P < 0.01, E-cadherin: P < 0.01). Although p53 and AID were overexpressed in these samples, no change in their expression occurred during neoplastic progression. Moreover, p53 expression was not significantly associated with AID expression. CONCLUSIONS: These results indicate that a decrease in Fhit and E-cadherin expression could be related to the development and progression of esophageal squamous neoplasia, and that the expression of p53 was independent of aberrant AID expression in the early stage of esophageal carcinogenesis.

Recent progress in carcinogenesis, progression and management of upper GI cancer: the 21st Hiroshima Cancer Seminar--the 5th Three Universities' Consortium International Symposium, 6 November 2011, International Conference Center Hiroshima.

The 21st Hiroshima Cancer Seminar focused on recent progress of carcinogenesis, progression and management of upper gastrointestinal cancers. ß-Catenin and p120 mediate peroxisome proliferator-activated receptor δ-dependent proliferation induced by Helicobacter pylori in gastric epithelia. Helicobacter pylori CagA plays an important role in stomach carcinogenesis via altered signal transduction and cell polarity by interactions with several host proteins. Inflammation caused by H. pylori infection is responsible for inducing aberrant DNA methylation. The gastric gland mucin-specific αGlcNAc plays dual roles in preventing gastric cancer, inhibition of H. pylori infection and suppression of tumor-promoting inflammation. Information obtained from transcriptome dissection greatly contributes to understanding the molecular character of each mucin phenotype of gastric cancer. The standardized biomarkers will serve as good predictive and prognostic markers for gastric cancer. A microRNA expression profile may be useful for the diagnosis of gastric cancer. Bone marrow-derived mesenchymal stem cells may provide an advantageous microenvironment for re-acquisition of stemness of gastric cancer cells. Recent progress in molecular biology research has enabled the clinical development of molecular targeting agents for gastric cancer, such as trastuzumab. The target molecule-based inhibition of the stromal reaction in the microenvironment may hold promise as an effective anti-tumor therapy. Since robotic surgery is feasible and safe, and provides adequate and precise lymph node dissection, it may be one of the good options for gastric cancer in the near future.

The incidence and significance of retropharyngeal lymph node metastases in hypopharyngeal cancer.

OBJECTIVE: To evaluate the incidence and clinical significance of retropharyngeal lymph node metastasis in hypopharyngeal cancer. METHODS: Pretreatment computed tomography and/or magnetic resonance images of 152 patients treated between 1998 and 2009 were retrospectively reviewed. The prognostic significance of retropharyngeal lymph node metastasis for 116 patients who received definitive treatment was also analyzed. RESULTS: Twelve patients (8%) were radiologically positive for retropharyngeal lymph node metastasis. Tumors originating from the posterior wall showed significantly higher incidence of retropharyngeal lymph node than those originating from other sites (23.8 vs. 5.3%, P = 0.01). The majority of patients with retropharyngeal lymph node involvement experienced distant metastasis. The overall survival rate of patients with retropharyngeal lymph node metastasis was worse than in those lacking retropharyngeal lymph node involvement (0 vs. 68.8% at 2 years, P < 0.01), and so was the cause-specific survival rate (0 vs. 74% at 2 years, P < 0.01). CONCLUSIONS: Patients with hypopharyngeal cancer, especially those with posterior wall tumors, are at high risk for retropharyngeal lymph node involvement. Patients with retropharyngeal lymph node metastasis developed distant metastasis frequently, and showed dismal outcomes.

MicroRNA-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression.

Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell proliferation. Noninvasive optical imaging technologies revealed that intravenous injection of miR-143, but not negative control miRNA, significantly suppressed lung metastasis of 143B (P < 0.01). To search for miR-143 target mRNA in 143B, microarray analyses were performed using an independent RNA pool extracted by two different comprehensive miR-143-target mRNA collecting systems. Western blot analyses revealed that MMP-13 was mostly protein downregulated by miR-143. Immunohistochemistry using clinical samples clearly revealed MMP-13-positive cells in lung metastasis-positive cases, but not in at least three cases showing higher miR-143 expression in the no metastasis group. Taken together, these data indicated that the downregulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 upregulation, suggesting that miRNA could be used to develop new molecular targets for osteosarcoma metastasis.

Efficient establishment of pig embryonic fibroblast cell lines with conditional expression of the simian vacuolating virus 40 large T fragment.

The pig is an important animal for both agricultural and medical purposes. However, the number of pig-derived cell lines is relatively limited when compared with mouse- and human-derived lines. We established in this study a retroviral conditional expression system for the Simian vacuolating virus 40 large T fragment (SV40T) which allowed us to efficiently establish pig embryonic fibroblast cell lines. The established cell lines showed high levels of cell proliferation and resistance to cellular senescence. A chromosome analysis showed that 84% of the cells had the normal karyotype. Transient expression of the Cre recombinase allowed us to excise the SV40T fragment from the genome. The development of this research tool will enable us to quickly establish new cell lines derived from various animals.

Establishment of an antibody specific for AMIGO2 improves immunohistochemical evaluation of liver metastases and clinical outcomes in patients with colorectal cancer.

INSTRUCTION: The human amphoterin-induced gene and open reading frame (AMIGO) was identified as a novel cell adhesion molecule of type I transmembrane protein. AMIGO2 is one of three members of the AMIGO family (AMIGO1, 2, and 3), and the similarity between them is approximately 40% at the amino acid level. We have previously shown that AMIGO2 functions as a driver of liver metastasis. Immunohistochemical analysis of AMIGO2 expression in colorectal cancer (CRC) using a commercially available anti-AMIGO2 mouse monoclonal antibody clone sc-373699 (sc mAb) correlated with liver metastasis and poor prognosis. However, the sc mAb was found to be cross-reactive with all three molecules in the AMIGO family. METHODS: We generated a rat monoclonal antibody clone rTNK1A0012 (rTNK mAb) for human AMIGO2. The rTNK mAb was used to re-evaluate the association between AMIGO2 expression and liver metastases/clinical outcomes using the same CRC tissue samples previously reported with sc mAb. RESULTS: Western blot analysis revealed that a rTNK mAb was identified as being specific for AMIGO2 protein and did not cross-react with AMIGO1 and AMIGO3. The rTNK mAb and sc mAb showed higher AMIGO2 expression, which correlates with a high frequency of liver metastases (65.3% and 47.5%, respectively), while multivariate analysis showed that AMIGO2 expression was an independent prognostic factor for liver metastases (p = 7.930E-10 and p = 1.707E-5). The Kaplan-Meier analyses showed that the rTNK mAb (p = 0.004), but not sc mAb (p = 0.107), predicted worse overall survival in patients with high AMIGO2 expression. The relationship between AMIGO2 expression and poor disease-specific survival showed a higher level of significance for rTNK mAb (p = 0.00004) compared to sc mAb (p = 0.001). CONCLUSIONS: These results indicate that the developed rTNK1A0012 mAb is an antibody that specifically recognizes AMIGO2 by immunohistochemistry and can be a more reliable and applicable method for the diagnostic detection of liver metastases and worse prognosis in patients with high AMIGO2-expressing CRC.

c-Jun N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells.

We previously reported that impaired retinoid signaling causes hepatocellular carcinoma (HCC) through oxidative stress. However, the interaction between oxidative stress and retinoid signaling has not been fully understood. To address this issue, the effects of hydrogen peroxide on the transcriptional activity of RAR/RXR heterodimers, RARα and RXRα proteins and intracellular signaling pathways were examined. The transcriptional activity of RAR/RXR examined by the DR5-tk-Luc reporter assay was significantly suppressed. The RARα protein level began to decrease at 6 h after treatment and declined thereafter. However, RARα mRNA were not changed. Activation of extracellular regulated kinases (ERK), p38, c-Jun N-terminal kinase (JNK) and Akt was observed after treatment of hydrogen peroxide. SP600125, an inhibitor of JNK, reversed the RARα protein level reduced by hydrogen peroxide. Anisomycin, an activator of JNK, reduced RARα protein. Transfection of wild-type JNK-constitutive actively expressing plasmid, but not kinase-negative JNK-expressing plasmid caused reduction of RARα protein. Proteasomal degradation of RARα was observed after anisomycin treatment; however, the mutant RARα, of which phosphorylation sites are replaced with alanines, was not degradated. In hepatitis C virus (HCV)-related human liver tissues, phospho-JNK and RARα reciprocally expressed with the progression of liver disease. Finally, the staining of 8-OHdG and thioredoxin was increased with the disease progression. These data indicate that JNK activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of RARα, suggesting that a vicious cycle between aberrant retinoid signaling and oxidative stress accelerates hepatocarcinogenesis.

Discriminant analysis of native thoracic aortic curvature: risk prediction for endoleak formation after thoracic endovascular aortic repair.

PURPOSE: To determine the association of native thoracic aortic curvature measured from computed tomographic (CT) angiography categorized by discriminant analysis with the development of endoleaks after thoracic endovascular aortic repair (EVAR). MATERIALS AND METHODS: Forty patients (28 men, 12 women; mean age, 74 y; range, 40-89 y) with aortic diseases treated with thoracic EVAR were evaluated. Diseases treated included atherosclerotic aneurysm (n = 27), penetrating atherosclerotic ulcer (n = 4), intramural hematoma (n = 3), mycotic aneurysm (n = 3), and anastomotic pseudoaneurysm (n = 3). Quantitative analysis of native aortic morphology was performed on preprocedural CT angiograms with an original customized computer program, and regional curvature indices in each anatomic segment of the aorta were calculated. Patterns of native thoracic aortic morphology were analyzed by discriminant analysis. The association between the morphologic pattern of the aorta and the presence and type of endoleak was assessed. RESULTS: After leave-one-out cross-validation methods had been applied, the sensitivity, specificity, and accuracy to detect endoleak formation in a new population group by discriminant analysis of the patterns of native aortic curvature were estimated as 84.0%, 58.8%, and 73.8%, respectively. Compared with the no-endoleak group, the type Ia endoleak group had greater curvature at the aortic arch, the type Ib endoleak group had greater curvature at the thoracoabdominal junction, and the type III endoleak group had greater curvature in the midportion of the descending aorta. CONCLUSIONS: Discriminant analysis of native thoracic aortic morphology measured from CT angiography is a useful tool to predict the risk of endoleak formation after thoracic EVAR and should be implemented during treatment planning and follow-up.

Gastric adenocarcinoma with rhabdoid morphology.

Extrarenal rhabdoid tumors (ERRTs) are very rare neoplasms and have been reported in a range of organs, including sixteen cases in the stomach. We describe a woman aged 86 years who had an advanced gastric tumor with lymph node metastasis. The tumor mostly showed a diffuse arrangement with a small glandular region. The tumor cells were non-cohesive and had polygonal morphology with eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm, i.e. they showed rhabdoid features. Immunohistochemically, the rhabdoid tumor cells were strongly positive for cytokeratins and vimentin. However, a candidate tumor suppressor gene of rhabdoid tumors, the INI1 gene, showed no mutations or loss of expression in the tumor cells. Although ERRTs typically have an aggressive clinical course, the patient was still alive without any evidence of recurrence or metastasis at 26 months after surgery. The rhabdoid features of the present case seemed to be a variant of gastric adenocarcinoma.

Genomic profiling of gastric carcinoma in situ and adenomas by array-based comparative genomic hybridization.

Although genomic copy number aberrations (CNAs) of gastric carcinoma at the advanced stage have already been extensively characterized by array comparative genomic hybridization (array CGH) analysis, those of gastric carcinoma in situ (CIS) are still poorly understood. Furthermore, no reports have demonstrated correlations between CNAs and histopathological features of gastric adenoma. In this study, we investigated CNAs of 20 gastric CISs (Vienna category 4.2) and 20 adenomas including seven low-grade adenomas (LGA; Vienna category 3) and 13 high-grade adenomas (HGA; Vienna category 4.1), using oligonucleotide-based array CGH. The most frequent aberrations in CIS were gains at 8q (85%) and 20q (50%), and losses at 5q (50%) and 17p (50%), suggesting that these CNAs are involved in the development of CIS. We found that the pattern of CNAs in HGA was quite different from that in LGA. The most frequent CNAs in HGA were gains at 8q (62%) and 7pq (54%), whereas those in LGA were gain at 7q21.3-q22.1 (57%) and loss at 5q (43%). Interestingly, gains at 8q and 7pq, both of which occurred most frequently in HGA, were not detected in any cases of LGA. Of note, 8q gain was detected most frequently in both HGA and CIS but was undetected in LGA. Since HGA is believed to have a higher risk of progression to invasive carcinoma than LGA, these data suggest that 8q gain is important for the malignant transformation of gastric adenoma.

Cutaneous epithelioid angiomatous nodule arising in capillary malformation.

Cutaneous epithelioid angiomatous nodule (CEAN) represents a rare, benign vascular lesion described by Brenn and Fletcher in 2004. To the best of our knowledge, the development of CEAN in a pre-existing vascular malformation has not been previously reported. A 52-year-old Japanese woman presented with multiple erythematous papules developed on violaceous macule of the right back that had been diagnosed as capillary malformation (CM) in childhood. Histopathological examination of one erythematous papule revealed a relatively well-circumscribed nodule composed mostly of epithelioid cells in the dermis. Abnormal dilated vessels were also identified around the lesion in the dermis, suggesting a CM. Immunohistochemically, the epithelioid cells were positive for CD31 and CD34. Staining for α-smooth muscle actin highlighted pericytes with epithelioid features. These findings were consistent with a diagnosis of CEAN arising in CM. The excised specimens of other erythematous papules revealed pyogenic granuloma (PyG) with focal epithelioid morphology accompanied by CM. We present the first reported case of CEAN arising in CM. Considering the histopathological findings, we speculate that CEAN of our case could be associated with PyG developed in pre-existing CM, and may thus be a variant of PyG with a mostly epithelioid appearance.

Recent progress in carcinogenesis, progression and therapy of breast cancer: the 20th Hiroshima Cancer Seminar--the 4th Three Universities' Consortium International Symposium, October 2010: 31 October 2010, International Conference Center Hiroshima.

The 20th Hiroshima Cancer seminar focused upon breast cancer research and treatment particularly on the mechanism of tumorigenesis and drug resistance and development of novel therapeutics. Several molecules such as retinoblastoma and p16 were raised as key factors in tumorigenesis and invasiveness. Estrogen-related pathways seem to be closely involved in the process. For the tumor lacking hormone receptor and human epidermal growth factor 2, some other mechanisms could be responsible. It seems that MicroRNA 22 directing some putative targets such as SIRT1, Sp1 and CDK6 plays a crucial role in breast tumor growth and metastasis. In addition, ribophorin and the associated molecules might be engaged in breast cancer stemness. Obviously, these molecules provide potential for therapeutic targets. It was also discussed about new drug development such as anti-human epidermal growth factor 2 therapy, anti-angiogenesis, pro-tumor aspects of anti-cancer therapy and application of circulating markers for monitoring, imaging and health-care system. Furthermore, we discussed risk factors, prevention and screening to reduce invasive cancers as well. Throughout the conference, panelists and attendee indicated the importance of translational research and biomarker exploration in order to realize efficient and individualized therapy for breast cancer.

Benign and malignant tumors in Down syndrome: analysis of the 1514 autopsied cases in Japan.

BACKGROUND: Down syndrome is known for its association with neoplasms. The aim of this study was to examine this association. METHODS: We surveyed the association with benign and malignant neoplasms in Down syndrome patients registered in the Annual of Pathological Autopsy Cases of Japan (1974-2000), a database of autopsied cases operated by the Japanese Society of Pathology. RESULTS: In a total of 1514 cases with Down syndrome, there were eight cases with 10 benign tumors (four male and four female) and 104 cases with malignant disorders (61 male, 42 female and one case with unrecorded sex), in which 87 cases with hematopoietic malignancies (83.7%) and 17 cases with solid tumors (16.3%), were identified. The association of gallbladder adenocarcinoma with a benign tumor of the colon was noted in one case, while a further two cases with double benign tumors were confirmed as well. No case with a double malignancy was found. Hematopoietic malignancies (87 cases) included 31 cases (35.6%) with acute myelocytic leukemia, 10 (11.4%) with acute lymphocytic leukemia and two (2.3%) with chronic myelocytic leukemia. The ratio of acute myelocytic leukemia to acute lymphocytic leukemia was 3.1 in the present study. A peak in the age distribution was at 0 years in our data in contrast to the previous data (at 1 year) for myelocytic leukemia. The 17 solid tumors identified included three hepatocellular carcinomas, three extrahepatic cholangiocarcinomas, two gallbladder adenocarcinomas, three brain tumors, and three seminomas. CONCLUSION: We present new associations of benign and malignant tumors with Down syndrome.

Pyothorax-associated lymphoma: imaging findings.

OBJECTIVE: The purpose of this study was to evaluate the radiologic features of pyothorax-associated lymphoma on CT scans and chest radiographs. MATERIALS AND METHODS: Radiographs and CT scans of 21 patients with biopsy-proven pyothorax-associated lymphoma (17 men, four women; median age, 71 years; range 52-77 years) were retrospectively identified. Two readers in consensus analyzed the morphologic imaging features of pyothorax-associated lymphoma and determined their relation to the preexisting chronic empyema cavity. In 13 cases, gallium scans were available and were reviewed. RESULTS: Sixteen patients had a history of artificial pneumothorax therapy for tuberculosis. Pyothorax-associated lymphoma was visualized mainly (71.4% of cases) as extrapulmonary pleural masses on chest radiographs. The CT features included a lenticular (60%) or crescentic (20%) soft-tissue mass located eccentrically at the margin of a coexistent empyema cavity, which was present in all cases. Masses of pyothorax-associated lymphoma were commonly located in the lateral costal pleura (50%) or at the costophrenic angle (30%). The tumor matrix often appeared heterogeneous and contained areas of necrosis (60%). Direct invasion of the chest wall, ribs, lung parenchyma, and abdomen was found in 75%, 50%, 25%, and 25% of patients. Gallium scans, when available, showed marked uptake in 10 of 13 patients (76.9%). CONCLUSION: In patients who have undergone artificial pneumothorax therapy for tuberculosis more than 20 years in the past, a pleural soft-tissue mass adjacent to the margin of a coexistent empyema cavity suggests the presence of pyothorax-associated lymphoma. Knowledge of the typical radiologic findings and locations of pyothorax-associated lymphoma help in the diagnosis of this rare pathologic entity.