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Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer.Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers.Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification.Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Malignancy arising in fibrous dysplasia (FD) is rare. Approximately 100 cases have been reported so far, and osteosarcoma is the most common malignancy. We report a case of osteosarcoma in a 33-year-old Japanese man with monostotic FD of the right proximal femur from the age of 16 years. Histologically, relatively well-differentiated osteosarcoma was found in the FD lesion. Immunohistochemically, the FD was negative for p53 or MDM2, and the MIB-1 index was less than 1%, whereas the osteosarcoma was positive for both p53 and MDM2, and the MIB-1 index was up to 15%. The FD and osteosarcoma were negative for CDK4. Fluorescent in situ hybridization assay showed no amplification of the MDM2 gene, indicating that the osteosarcoma was a conventional osteosarcoma, not an intraosseous well-differentiated type. The original cell of malignancy in FD is unclear. Malignancy can be potentially derived from dysplastic cells in the area of the FD or cells in the adjacent normal tissues. GNAS gene mutation has recently been reported for fibrous dysplasia and the mutation is highly specific to fibrous dysplasia among fibro-osseous lesions including osteosarcoma. In this case, point mutations of GNAS were found in the FD and osteosarcoma but not in the adjacent normal tissues, suggesting that osteosarcoma was derived from the spindle cells of FD. This is the first report to clearly show that osteosarcoma is derived from the spindle cells in fibrous dysplasia (FD).

At times, surgeons face various difficulties in the treatment of patients who require surgical therapy. The patients' general conditions as well as their will and religion can sometimes interfere with the implementation of the best therapeutic option. For instance, the presence of cardiac disease, respiratory disease, or cognitive impairment often can difficult the decision-making process when determining the optimal therapeutic strategies. Pregnancy is not a pathological condition, but it can complicate the decision-making process with respect to choosing the best treatment for pregnant patients who require surgery. Non-obstetric surgery in pregnant patients is relatively common, although it requires a prudent selection of anesthetic drugs, surgical methods and analgesic agents. Additionally, it is a well-known religious practice that Jehovah's Witnesses refuse to receive blood transfusions, and thus, their surgical management can be challenging. Giant cell tumor of bone (GCTB) is classified as a benign bone tumor, but it is locally aggressive. Standard treatment for GCT is

Background Proximal tibial reconstruction following wide resection in both malignant and benign tumors presents difficulties mainly due to both patellar tendon reconstruction and high risk of infection. The purpose of this study is to determine the efficacy of a new technique using a mesh for extensor reconstruction. Methods We retrospectively reviewed nine consecutive patients who underwent resection of the proximal tibia with prosthetic reconstruction and reconstruction of the extensor using a mesh between 2009 and 2012. The surgical technique included the attachment of the mesh to the tibial component with a band of meshes looped over the patella and a gastrocnemius flap for coverage. Results One patient had an above-the-knee amputation due to infection. Eight patients were followed up for 33 months (range, 20–50). In the eight patients, extensor lag had a mean of 5° (range, 0 to 20). Active flexion had a mean of 96.25° (range, 80 to 120) and ISOLS scores had a mean of 21/30 (range, 18 to 26). All patients were able to ambulate without crutches at the latest follow-up. Conclusion Extensor lag was significantly less compared to previous reports. No complications were observed in eight patients. Utilization of the mesh for extensor reconstruction after the proximal tibial resection is a simple, reliable and successful method. Level of evidence Therapeutic level IV.

Background Endoprosthetic reconstruction of the proximal humerus is one of the standard procedures after resection of tumors of the proximal humerus and has been considered a reliable method to reconstruct the proximal humerus in recent reports. However, instability of the shoulder joint caused by loss of the rotator cuff and deltoid muscle function is often observed after such an endoprosthetic reconstruction. Methods We performed the endoprosthesis suspension method with polypropylene monofilament knitted mesh. This suspension method, by which the endoprosthesis is suspended from the bone structure, was used after resection of tumors in 9 patients. We assessed postoperative stability of the shoulder joint by comparing these patients with 12 patients who underwent the conventional surgical technique, by which the mesh-wrapped endoprosthesis is attached only to soft tissue. Results In radiographic and physical evaluation, 4 of the 12 patients in the soft tissue reconstruction group showed shoulder joint instability. No patient in the suspension method group showed subluxation of the humeral prosthesis. The mean shoulder flexion was 35° and 65° and the mean shoulder abduction was 40° and 40° for the soft tissue reconstruction group and the suspension method group, respectively. Discussion Shoulder joint subluxation sometimes occurs because of elongation of the attached soft tissue in the conventional reconstruction with mesh, whereas no shoulder joint subluxation occurs after endoprosthetic reconstruction in the suspension method because the bone structure has no leeway for elongation. Excellent stability of our new method enables exercise of the surgical shoulder at an early stage, leading to improved range of shoulder joint motion.

Objective: In Japan, pazopanib has been made available to soft tissue sarcoma patients, also to patients histologically diagnosed as ineligible for the international Phase 3 study (PALETTE). However, clinical evidence for the use of pazopanib in PALETTE-ineligible patients is currently insufficient. Methods: We retrospectively reviewed medical records of soft tissue sarcoma patients treated with pazopanib at our institute. By pathological review, the patients’ eligibility for the PALETTE was evaluated and the differences in their responses to pazopanib and incidences of adverse events were investigated. Results: From November 2012 to August 2014, a total of 47 patients received pazopanib, 38 (81%) of whom were histologically eligible for the PALETTE, and 9 of whom (19%) were not. The median follow-up time was 7.5 months (range 1.4–20.3 months). An objective response was observed in both groups, but the patients’ survival tended to be longer in the PALETTE-eligible patients; median progression-free survival was 4.5 months vs. 2.9 months (P= 0.15) and overall survival was 10.7 months vs. 7.8 months (P = 0.55), though these differences were not statistically significant. There were no significant differences in the incidence of adverse events by PALETTE eligibility, but dose skipping or dose reduction was more likely to be observed in PALETTE-ineligible patients. Conclusion: Pazopanib is tolerable to soft tissue sarcoma patients ineligible for the PALETTE and some of them respond to pazopanib, but the prognoses of patients ineligible for the PALETTE might be worse than those of PALETTE-eligible patients. The indication of pazopanib for soft tissue sarcoma patients with PALETTE-ineligible histologies should be decided carefully.

Giant cell tumor (GCT) is classified as a benign bone tumor, but it is locally aggressive, and sometimes metastasizes in a benign state. In addition, malignant transformation occurs once in a while. Most of the secondary malignancies in GCT occur after treatment of benign GCT that has included radiation therapy [1, 2]. As a cytogenetic characteristic of GCT, telomeric associations (tas) were reported [3, 4]. Tas may generate dicentric chromosomes (dic) and chromatoid breakagefusion-bridges, which lead to chromosomal instability and tumorigenesis [5, 6]. Recently, the relationship between cytogenetic abnormalities and clinical behavior in GCT has begun to be elucidated. For example, the DNA ploidy pattern may predict the recurrence potential of GCT, chromosomal abnormalities superimposed on tas are responsible for an aggressive clinical course [7], and centrosome amplification may be useful in predicting the clinical behavior of GCT [8]. Here we report a case of secondary malignancy in GCT. Malignant transformation occurred in a relatively early period, and any radiation therapy was not administered to the primary lesion. Malignant transformation was demonstrated not only by histopathological study but also by cytogenetic analysis. The recurrent tumor, which was a secondary malignancy in GCT, had a near-triploid karyotype with multiple structural abnormalities as observed in pleomorphic sarcoma, while the primary benign GCT had a near-diploid karyotype with tas and dic.

Guidelines suggest that followup for low-grade soft tissue sarcomas should be every 3 to 6 months for 2 to 3 years and then annually, and for high-grade sarcomas every 3 to 6 months for 2 to 5 years, then every 6 months for the next 2 years, and then annually. However, there is only very limited evidence to support these strategies.In a population of patients treated surgically for soft tissue sarcomas, we evaluated the (1) timing of diagnosis of local recurrences after sarcoma excision; (2) timing of diagnosis of distant metastases; and (3) the difference in those parameters based on tumor size and grade.Patients diagnosed with soft tissue sarcomas and who underwent surgical excision between 1978 and 2008 were retrospectively reviewed. Age, histologic diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, tumor location, and size were reviewed at a mean of 6 years (range, 1 month to 30 years). We met with patients every 3 months for 5 years, every 6 months for 10 years, and then annually until 15 years after surgery. Eight hundred sixty-seven patients with a median age at diagnosis of 52 years were eligible for analysis. The incidence of local recurrence and metastases was calculated for every 2-year period and presented per 1000 person-years.Ninety-eight patients (11%) developed local recurrence at a median time of 19 months; 90% of patients who had local recurrences had them within 7.1 years, and 95% occurred by 8.6 years. One hundred ninety-eight patients (23%) developed distant metastases at a median time of 12 months; 90% of patients who developed metastases developed them by 4.2 years and 95% did so by 7.3 years. High-grade tumors had a higher incidence of local recurrence and metastases in first 2 years, whereas low-grade tumors recurred at a constant rate throughout the followup period.Followup beyond 10 years does not yield a sufficient number of local recurrences or metastases to warrant further monitoring.Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Lymph node metastases in patients with soft tissue sarcomas are rare and these metastases are frequently associated with certain histologic subtypes. The survival is believed to be poor if lymph node metastases occur and the potential benefit of lymphadenectomy is unclear.We determined whether lymph node metastases affect overall survival with regard to the status of lymphadenectomy, histologic subtypes, isolated or systemic metastasis, and the timing of presentation of lymph node metastases.We retrospectively reviewed all 871 patients diagnosed with soft tissue sarcomas between 1983 and 2008 to determine whether they had lymph node metastases at diagnosis or subsequently and whether they had lymphadenectomy for treatment. Overall survival was assessed and the effect of prognostic variables was examined by a log rank test.Forty-nine of the 871 patients (6%) had lymph node metastases. The estimated 5-year survival rate for the group of 49 patients with lymph node metastases was 27%. Those who had lymphadenectomy had better survival at 1.5 years although there was no difference between those who did not undergo lymphadenectomy at 5 years. Patients with nonrhabdomyosarcoma had better overall survival than patients with rhabdomyosarcoma. Timing of development of lymph node involvement and whether lymph node metastases were an isolated site did not affect the overall survival.Overall survival of patients with lymph node metastases was related to histologic subtypes and patients with nonrhabdomyosarcoma had better survival than those with rhabdomyosarcoma. Resection of the metastatic lymph node did not improve long-term survival of patients with soft tissue sarcomas.Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Background: In treatment of tumors, we usually reconstruct after resection of the entire femur using only metallic modular endoprostheses among many procedures and defined it as a total femur replacement. We studied the interrelation between the preservation of rectus femoris and the functional outcome after total femur replacement. Methods: We rated the functional outcomes of 21 patients who underwent total femur replacement. We categorized the subjects into 2 groups: group A (rectus femoris preserved) and group B (rectus femoris unpreserved). We examined them based on the Mann-Whitney U test between the 2 groups in average through the Musculoskeletal Tumor Society functional scores. Results: The average score of group A was 20 of 25 (11–25; 80%), whereas the average score of group B was 10 of 25 (4–13; 40%). There was significant difference between the groups (P = 0.00168877). Conclusion: We found that the preservation of rectus femoris is imperative for achieving the favorable functional outcome in total femur replacement.

Well-differentiated liposarcoma (WD) acquires fully malignant potential when the histological progression named dedifferentiation occurs. This progression is supposed to occur in a time-dependent manner but this is still a debated issue. Clinically, the prediction of dedifferentiation for WD is very important from the therapeutic point of view. To identify genes that are predictive of dedifferentiation and to understand the mechanism of dedifferentiation, we investigated clinical information of 50 cases and studied the gene expression profiles of 36 lipomatous tumors using cDNA microarray. The clinical study showed that the dedifferentiation did not always seem to occur in a time-dependent manner. Interestingly, from the gene expression study, unsupervised hierarchical clustering analysis of well-differentiated lesions obtained from dedifferentiated liposarcoma (DD) cases that were indistinguishable from WD pathologically showed a clearly distinct gene expression pattern from WD. Using the pattern-matching program, 1687 genes including 487 known genes were identified, which discriminated WD cases from well-differentiated lipomatous lesions obtained from DD cases. These results suggest that the dedifferentiation may arise from different types of WD that could be distinguished from gene expression profiling but could hardly be classified by the pathological studies.

Background. The role of surgical intervention for the treatment of small round cell sarcoma of bone, has become important. However, there have been few reports concerning the surgical safety margin for this disease. An appropriate surgical margin should be discussed in relation to the effects of preoperative treatment, local recurrence rate, and prognosis.

We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and extra-osseous region of the right distal femur. Histologically, the tumor consisted of epithelioid mononuclear cells and they looked like to have abundant eosinophilic cytoplasm reminiscent of hepatic tissues. In some areas, however, typical histologic features of TSGCT were observed. Electron microscopy revealed that the eosinophilic cytoplasm-like substance was intercellular fibrinous material surrounding the mononuclear tumor cells. Immunohistochemically, mononuclear tumor cells and multinucleate giant cells were positive for CD68 (Kp1) and some of the mononuclear tumor cells were also positive for desmin. Finally, we made the diagnosis of hepatoid TSGCT.

BackgroundSoft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature.Case presentationA case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she developed sciatic nerve palsy from the carcinoma metastasis directly to the nerve. Operative resection and Histological examination revealed poorly differentiated adenocarcinoma, the same as her primary site adenocarcinoma.ConclusionsSciatica is usually caused by a herniated disc or spinal canal stenosis. Sciatic nerve palsy may be caused by nondiscogenic etiologies that may be either intrapelvic or extrapelvic. It is important to image the entire course of the nerve to distinguish these etiologies quickly. The longer the nerve compression the less likely a palsy will recover. Surgery is a good intervention that simultaneously obtains a tissue diagnosis and decompresses the nerve.

Rotationplasty is one treatment option for femoral bone sarcomas in skeletally immature patients. This procedure can also be used to save failed limb salvage procedures such as infected prostheses and failed bone grafts in adults. Rotationplasty is only rarely indicated, and the surgical complications and risk factors for failure of the procedure that might influence the treatment or patient choices have not been well described.We retrospectively reviewed 19 patients who underwent rotationplasty focusing on surgical indications, surgical procedures such as the type of rotationplasty, and whether vessels were sacrificed and reconstructed with vascular anastomosis or preserved. Risk factors for failure of rotationplasty were categorized into either early or late postoperative complications.Thirteen of 19 rotationplasties were done for patients diagnosed with primary sarcoma, 3 patients for unplanned excisions of sarcomas, and 3 patients for infection. Two of 19 patients did not have sufficient circulation resulting in amputation. Six of 19 patients underwent vascular anastomoses, and all of these anastomoses were successful. Three patients had multiple operations for infection before rotationplasty, and one patient's treatment failed so an amputation was required. As late complications, one patient had delayed bone union and one had postoperative infection that healed after removal of plate fixation. Two patients had malrotation of the tibia that resolved with revision surgery. One patient had a skin ulcer that healed with conservative treatment. One patient who had an unplanned excision had a hemipelvectomy for non-union 11 months after rotationplasty.Rotationplasty was successfully accomplished in 16 of the 19 patients (84 %) with sarcomas, unplanned excision of sarcomas or infection. Vascular anastomosis did not increase the risk of rotationplasty failure in our series. Patients appeared to have a higher risk of failure of rotationplasty after multiple operations, possibly because of inflammation around the vessels. The surgeon should be aware of the higher potential risk and consider vascular anastomosis for these patients.

Patients with local recurrence of soft-tissue sarcomas have a poor overall survival. High-grade, soft-tissue sarcomas in deep locations may have a poorer prognosis regarding local recurrence than low-grade sarcomas or those located superficially. Although previous reports evaluated tumors at various depths, it is unclear what factors influence recurrence of deep, high-grade sarcomas.We therefore determined whether possible risk factors (tumor size, location, histologic subtype, unplanned excision, local recurrence at presentation, metastasis at diagnosis, surgical procedure, surgical margin, and adjuvant treatments) influenced local recurrence of deep, high-grade, soft-tissue sarcomas.We retrospectively reviewed 433 patients with deep, high-grade, soft-tissue sarcomas surgically treated between 1985 and 2005. For each patient, we reviewed tumor size, location, histologic subtype, unplanned excision, local recurrence at presentation, metastasis at diagnosis, surgical procedure, surgical margin, and adjuvant treatments and determined the effect of each prognostic variable on local recurrence. The minimum followup was 1 month (median, 51 months; range, 1-305 months).Forty-seven patients had local recurrence at a median of 10.7 months. Local recurrence at presentation, metastasis at diagnosis, and positive margins independently predicted local recurrence. No other factors independently predicted local recurrence.Unplanned excisions did not increase the rate of local recurrence of deep, high-grade, soft-tissue sarcomas if treated appropriately. Aggressiveness of tumor represented by metastasis or local recurrence at presentation may be a risk for local recurrence.Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Pasteurized bone (PB) is recycled bone. The pasteurization has a tumor cell-killing effect wit retention of initial strength. However, few reports have been published on its long-term course; thus, in this study, we evaluated the long-term course of use of PB and examined appropriate reconstruction methods.We reviewed 27 cases in which reconstructive surgery using PB was performed between 1990 and 2002. Of these, we excluded 12 fatal cases and 1 case in which follow-up was discontinued. Therefore, our final analysis consisted of 14 cases with an average follow-up period of 165 months. The reconstruction methods used were: osteoarticular graft in 6 cases, composite graft with prosthesis in 3 cases, intercalary graft in 1 case, and reconstruction using PB from the pelvis in 4 cases.The PB survived in 7 of the 14 cases. Five and 10-year survival of the PB was 78.6 and 47.6%, respectively. Three of the 6 osteoarticular cases failed because of late-onset absorption or infection of the PB. For patients with composite graft or intercalary graft, long-term survival was achieved when small amounts of PB were used. For patients with pelvic grafts, long-term survival was achieved in a case of P1 pelvis, but large PB grafts on small bone-junction surfaces were not successful in the long term. On the basis of these results, we were able to achieve successful long-term results with small PB grafts on large bone-junction surfaces.To prevent bone absorption and achieve long-term survival of PB, it is important to use a small PB graft and create a large surface area of contact with normal bone. These factors are advantageous to PB survival and to gaining limb function.

Previously, using microarray and real-time RT-PCR analysis, we established that HOXB2 is an adverse prognostic indicator for Stage I lung adenocarcinomas. HOXB2 is one of the homeobox master development-controlling genes regulating morphogenesis and cell differentiation.The molecular functions of HOXB2 were analyzed with a small interfering RNA (siRNA) approach in HOP-62 human non-small cell lung cancer (NSCLC) cells featuring high HOXB2 expression. Matrigel invasion assays and microarray gene expression analysis were compared between the HOXB2-siRNA cells and the control cells.The Matrigel invasion assays showed attenuation of HOXB2 expression by siRNA to result in a significant decrease of invasiveness compared to the control cells (p = 0.0013, paired t-test). On microarray gene expression analysis, up-regulation of many metastasis-related genes and others correlating with HOXB2 expression was observed in the control case. With attenuation of HOXB2 expression, downregulation was noted for laminins alpha 4 and 5, involved in enriched signaling, and for Mac-2BP (Mac-2 binding protein) and integrin beta 4 amongst the genes having an enriched glycoprotein ontology.HOXB2 promotes invasion of lung cancer cells through the regulation of metastasis-related genes.

The aim of this study was to analyze epidemiological and clinical data of patients with aneurysmal subarachnoid hemorrhage (SAH) in the Yaeyama islands, an isolated subtropical region of Japan. A total of 94 patients (31 men and 63 women, mean age 57.3 years) were diagnosed as having non-traumatic SAH during a 13-year period from 1989 to 2002. The age-and sex-adjusted annual incidence rate of SAH was 17.4 per 100,000 population. The incidence of SAH was the highest in August. Seventy-nine patients were hospitalized within 24 hours after onset of SAH. Seventeen patients were transferred by helicopter. The Hunt and Kosnik grade was I in 29 patients (30.9%). The CT Fisher group was 3 in 42 patients (44.7%). Ruptured aneurysm was detected in 78 patients (saccular type in 70 patients, small size in 49 patients, and internal carotid artery in 28 patients). Rebleeding occurred in 20 patients (21.3%). Symptomatic vasospasm occurred in 26 patients (27.7%). Acute and chronic hydrocephalus occurred in 25 (26.6%) and 22 (23.4%) patients respectively. A total of 120 neurosurgical operations were performed in 70 patients (operation for ruptured aneurysm in 62, early operation in 39). A total of 42 operative complications occurred in 29 patients. Fifty-one patients (54.3%) had a good outcome. The number of full-time neurosurgeons did not influence the performance of neurosurgical operation and outcome. In conclusion, epidemiologically, the high incidence of SAH in August is unusual. Patients with aneurysmal SAH in the Yaeyama islands have common clinical characteristics and undergo standard neurosurgical treatment.

Background Outcomes of patients with lung adenocarcinomas can be predicted to some extent from the pathologic stage (p-stage). Although all attempts are made to fully remove cancer lesions, still a number of p-stage I patients without metastatic disease at the time of surgery develop recurrences and die of cancer. It is thus very important to identify p-stage I patients who are at risk of recurrence. Methods Previously, using microdissected samples, we identified metastasis-related genes. Using real-time reverse-transcriptase polymerase chain reaction analysis, we investigated the transcriptional levels of the top metastasis-related genes using 96 independent test lung adenocarcinoma samples and investigated their correlations with the prognosis. Results and Conclusions We document evidence that p-stage I patients with HOXB2 up-regulation have a worse prognosis than those with HOXB2 down-regulation ( p = 0.0065), whereas the HOXB2 status has no prognostic significance for p-stage II–IV patients. Comparing tumors and corresponding normal lung tissue, we confirmed HOXB2 up-regulated lesions to have much higher HOXB2 expression than the corresponding normal tissue. Confirmation with a larger number of samples is needed, with further research to clarify the molecular functions of HOXB2.

Recent microarray expression studies support the hypothesis that metastatic potential is acquired early in tumorigenesis and that most tumor cells have the potential to metastasize. To assess this possibility, we investigated invasive lung adenocarcinomas, which characteristically display morphological heterogeneity with a less malignant appearance at the periphery as a model. In lymph node-positive lesions, gene expression profiles were compared among moderately differentiated components with an aggressive appearance, peripheral well-differentiated components with a less malignant appearance, and patient-matched lymph node metastases. We also compared these with node-negative lung adenocarcinomas, which are morphologically indistinguishable from node-positive tumors. Striking similarities were observed between pairs of primary and metastatic tumors, even within primary well-differentiated components. We generated a 75-gene signature separating primary lung adenocarcinomas according to lymph node status. Hierarchical clustering using this gene set identified a distinct independent group composed of node-positive cases, clearly separate from node-negative tumors and normal lung tissue. The results suggest that the metastatic signature is maintained throughout progression, implying that the entirety of a primary tumor, including the morphologically less malignant components, might have metastatic potential. This finding has profound clinical implications. In the future, the metastatic potential of tumors may be predicted by biopsy, helping to avoid unnecessary lymph node dissection in low-risk patients.

Numerous genes whose expression is controlled by complex regulatory networks are involved in the development and progression of each cancer,and those genes will be the key factors for determining each characteristic of the tumor. The recent development of DNA microarray and related technologies provides an opportunity to perform more detailed characterization( profiling) of individual tumor cells. Indeed, the gene expression profile of a tumor provides a unique molecular portrait or signature that can be correlated with clinical behavior and drug responsiveness. The development of personalized( or customized) medicine and molecularly targeted drugs is enthusiastically awaited based on the results of research examining genomic diversity such as SNPs( single nucleotide polymorphisms), gene expression profiling with DNA microarrays, and analysis of protein expression and interactions.

There are many kinds of wide excision or wide resection, which are methods to remove the tumor with surrounding tissues. The curability of wide resection depends on the range and characteristics of the normal surrounding tissues. The fascia, periosteum and perivascular sheath act as barriers against invasion of tumors. Therefore, evaluation of the surgical margin is essential in surgery for malignancy. Some sarcomas characteristically show invasive growth patterns while others have a discrete border. Causes of the local recurrence are 1) insufficient surgical margin, 2) skip metastasis, 3) tumor thrombus, and 4) lymph node metastasis. The so-called "Safety surgical margin" is the margin that prevents local recurrence due to insufficient surgical treatment. Local recurrence due to other causes can not be treated by surgery alone as chemotherapy is also required. For example, the infiltrative type of malignant fibrous histiocytoma requires a curative procedure. On the other hand, non-infiltrative types of sarcoma or high-grade sarcoma, which are good responders to preoperative treatment, are locally controlled by an adequate wide margin procedure. When the tumor is close to the bone, main vessels and/or nerves, it is sometimes very difficult to preoperatively decide whether or not to sacrifice these important organs. A new surgical method, "In Situ Preparation (ISP)," is a useful method to solve such problems. ISP makes it possible to evaluate the surgical margin without contamination. And additional procedures including alcohol soaking or pasteurization can be achieved according to the surgical margin. Because ISP can prevent overtreatment, the number of our cases that require resection of the nerves or vessels have decreased. After a wide resection, there have been many possible complications, including infection, deep venous thrombosis, loosening of prosthesis, skin necrosis, and arterial occlusion. Once postoperative complications occur, patients must remain in the hospital for a long time. To prevent this, the preservation of normal tissue, meaning reduction of surgical margin, is important.

The number of known mRNA transcripts in the mouse has been greatly expanded by the RIKEN Mouse Gene Encyclopedia project. Validation of their reproducible expression in a tissue is an important contribution to the study of functional genomics. In this report, we determine the expression profile of 57,931 clones on 20 mouse tissues using cDNA microarrays. Of these 57,931 clones, 22,928 clones correspond to the FANTOM2 clone set. The set represents 20,234 transcriptional units (TUs) out of 33,409 TUs in the FANTOM2 set. We identified 7206 separate clones that satisfied stringent criteria for tissue-specific expression. Gene Ontology terms were assigned for these 7206 clones, and the proportion of `molecular function' ontology for each tissue-specific clone was examined. These data will provide insights into the function of each tissue. Tissue-specific gene expression profiles obtained using our cDNA microarrays were also compared with the data extracted from the GNF Expression Atlas based on Affymetrix microarrays. One major outcome of the RIKEN transcriptome analysis is the identification of numerous nonprotein-coding mRNAs. The expression profile was also used to obtain evidence of expression for putative noncoding RNAs. In addition, 1926 clones (70%) of 2768 clones that were categorized as “unknown EST,” and 1969 (58%) clones of 3388 clones that were categorized as “unclassifiable” were also shown to be reproducibly expressed.

The colloidal osmotic and hydrostatic pressure of chronic subdural hematomas were measured with a manometer in 35 patients. Manometric measurement showed an increase in the hematoma fluid corresponding to 5% of the total hematoma volume. The maximum colloidal osmotic pressure of the hematoma fluid, as measured with a transducer, was 23 ± 12 mmHg (mean ± standard deviation). Hemorrhage occurs continuously or intermittently within a subdural hematoma, accompanied by red cell hemolysis and hemoglobin degradation. The colloidal osmotic pressure within a subdural hematoma is higher than that in plasma or cerebrospinal fluid, so that the hematoma is able to absorb water through semipermeable membranes or capillaries. However, since the absorption force can transport only 5% of the hematoma volume, the colloidal osmotic pressure is a contributory process rather than a primary etiologic factor.

沖繩肉用ヤギの飼養実態を調査するとともに沖繩在来型,日本本土より移入された日本ザーネン種およびこれら以外の肉用一般型総計1,459頭について外部形態的遺伝形質と体型(783頭)を調査した.また体各部位間の表型相関をも求めた.外部形態的遺伝形質は毛色,肉髯,毛髯,角,副乳頭および間性の6形質とし,約4ヶ月齢以上の雌雄について調査した.雌の体型は,1才以上で,かつ1産以上の個体について体高,斜体長,体重など13部位を測定した.体尺測定は沖繩県下の9つの島で行った.1) 飼養方式は舎内けい留が最も一般的である.しかし島によっては舎内での放し飼い,放牧,けい牧,牧柵を設置せず半野生状態のまま放牧する方式などがみられた.2) 有色で,角,毛髯,副乳頭を持ち,肉髯を欠く個体をすべて在来型とした.肉用一般型およびザーネン種における5つの外部形質の出現割合をみるとそれぞれ有色(13,0%),肉髯(29,47%),有角(61,35%),副乳頭(37,12%),毛髯(雌68,83%,雄86,100%)であった.間性は肉用一般型のみに1.3%出現していた.3) 雌の体尺測定の平均値は,在来型,肉用一般型,ザーネン種で体高はそれぞれ52,57,69cm,斜体長58,63,75cm,胸囲67,74,87cm,体重22,31,51kgであった.測定した13部位すべてについて3タイプ間に有意差があった.4) 体各部位間の表型相関は,肉用一般型においては,すべての部位間で高い有意の相関係数が得られた.これに対し,ザーネン種では有意でない相関係数もあり,また一部の形質間を除き,肉用一般型より表型相関係数は低かった.5) 枝肉歩留について食肉センターにおいて調査した成績では雌48%,雄53%であった.ヤギ肉の利用はヤギ汁とサシミが一般的である.

The authors report the role of local inflammatory mechanisms in outer membranes to define the physiopathogenesis of the chronic subdural hematoma enlargement. The outer membranes in 20 adult patients of chronic subdural hematoma were investigated by means of light and electron microscopy. Microscopically, perivascular small hemorrhage and hemosiderin as well as fibroblasts, hemosiderin-laden macrophages, eosinophiles and plasma cells were found around the sinusoidal channels. Perisinusoidal hemorrhage, especially red blood cells were, usually, separated from the hematoma cavity by the fibrous layer. Several sinusoids could be seen coalesced to form multiple small cavities in outer membranes, with a fibroblast like lining. Such small hemorrhagic cavities, although not often, may rupture to communicate with the hematoma cavity. Ultrastructurally, the endothelial cells of sinusoids were rich in organelles, especially rough E.R., free ribosomes, mitochondrias, pinocytotic vesicles, and endothelial specific bodies. The site of vascular leakage was identified in several sinusoids as an endothelial gap, in the range of 1-8 μ in diameter, presumably formed by separation at intercellular junctions. Perivascular exudation of plasma lead to destruct the extracellular matrix of the sinusoidal layer. Extensive accumulations of endogenous amorphous material and irregularly arranged thin collagen fibers showed interstitial edema. Fibroblasts manufacture tropocollagen molecules within the activated rough E.R., which are then secreted onto the cell surface and gradually polymerized into visible microfibrils and collagen fibers. Interstitial edema, ultimately, disappears in the fibrous layer. The fibrous layer is generally characterized by numerous collagen fibers, fibroblasts, serum proteins and only a few capillaries, some of which show direct openings into the hematoma cavity. Some perivascular edematous fluid in the sinusoidal layer may pass through the fibrous layer into the hematoma cavity. Under scanning electron microscopy, red blood cells and fibrin strands or sheets were seen especially around the outlets of the fibrous layer capillaries. The results indicate that outer membranes, once developed, enlarge chronic subdural hematoma by ruptures of small hemorrhagic cavities formed in outer membranes, direct hemorrhage from the fibrous layer capillaries, and exudation of perisinusoidal edematous fluid into the hematoma cavity.

✓ A case of focal cerebral syphilitic gumma of the right temporal lobe is reported. Angiography showed moderate focal hypervascularity with stretched vessels, and irregularity of the vessel walls. Plain computerized tomography revealed an area of low density that enhanced strongly after intravenous administration of contrast medium.

e21527 Background: After the approval of pazopanib for the treatment of STS, pneumothorax was reported as an unexpected adverse event during pazopanib treatment. However, the incidence and risk fac...

Background Giant cell tumor of bone is an osteolytic, usually benign, tumor characterized by the infiltration of osteoclast-like giant cells. The receptor activator of nuclear factor kappa-B ligand pathway has been shown to play a key role in the pathogenesis of giant cell tumor. Treatment for refractory, recurrent, or metastatic giant cell tumor remains challenging. A monoclonal antibody to receptor activator of nuclear factor kappa-B ligand, denosumab, offers promise in these patients. Tartrate-resistant acid phosphatase 5b, a bone resorption marker, is secreted from osteoclasts and this marker is reported to be high in patients with giant cell tumor of bone. We investigated the effects of denosumab and the usefulness of a tartrate-resistant acid phosphatase 5b as a monitoring marker in the management of a refractory giant cell tumor of bone. Case presentation A 41-year-old Japanese male with right ischiac pain was diagnosed with a giant cell tumor in his right ischium. Since the tumor extended to the acetabulum, there was a possibility that en bloc resection might significantly impair function of the hip joint and curettage could cause massive bleeding. Therefore, denosumab therapy (120 mg, administered 3 times every 4 weeks) was performed before radical surgery. The giant cell tumor of bone was treated with denosumab successfully. No adverse reaction was noted. Tartrate-resistant acid phosphatase 5b secretion was measured in the patient’s serum to monitor the response to denosumab, and a rapid normalization of the marker was observed after the first denosumab administration. Conclusion This case suggests that denosumab therapy might be an option for treating refractory giant cell tumor of bone, and that tartrate-resistant acid phosphatase 5b might be an early marker with which to monitor the efficacy of denosumab therapy for refractory giant cell tumor.