Background
The present study analyzed biliary tract cancer patients registered from 2008 to 2013 in Japan and evaluated the outcomes of biliary tract cancer.
Methods
A total of 18,606 patients were ...registered from 2008 to 2013. Cases were analyzed with regard to patient survival according to contiguous extent of the primary tumor (T), node metastasis, and tumor stage using the 3rd English edition of the Japanese classification of the biliary tract cancers.
Results
Five‐year survival rates were 39.8% for gallbladder cancer, 24.2% for perihilar bile duct cancer, 39.1% for distal bile duct cancer, and 61.3% for ampullary region cancer. Significant differences were observed between newly introduced subdivisions in the new Japanese classification for all tumoral sites except gallbladder cancer. The survival rate in patients with #13a metastasis was significantly higher than in patients with distant lymph node metastasis.
Conclusions
The new Japanese classification adopted the 7th edition of staging system developed by the Union for International Cancer Control staging system. However, numerous aspects of these classification systems remain unvalidated. The present analysis demonstrated the significance of a proportion of T factor subdivisions and classifications of regional lymph nodes in cases of gallbladder cancer in the new Japanese classification.
Highlight
Ishihara and colleagues conducted a registry study to determine the outcomes of biliary tract cancer and to validate the new Japanese classification based on the UICC staging system 7th edition. Of particular note, survival rates were significantly higher in patients with #13a metastasis than in those with distant lymph node metastasis.
Giant cell tumor of bone (GCTB) is a locally aggressive bone tumor that frequently shows local recurrence and occasionally shows malignant transformation to high-grade sarcoma. Histologically, ...conventional GCTB is composed mainly of three types of cells: mononuclear neoplastic cells with an osteoblastic precursor phenotype, mononuclear histiocytic cells, and osteoclast-like multinucleated giant cells. These cells interact with each other via the RANKL-RANK axis and other mechanisms for tumor formation. The vast majority of GCTBs were recently revealed to harbor
H3F3A
p.G34W mutation, and a minor subset have
H3F3A
p.G34L, p.G34M, p.G34R, or p.G34V mutation. H3.3 G34W mutant-specific immunohistochemistry is a highly sensitive and specific surrogate marker for
H3F3A
p.G34W mutation in GCTB and thus useful for differential diagnoses of histological mimics. H3.3 mutant-specific immunohistochemistry has also contributed to the understanding of the bone-forming ability of neoplastic cells of GCTB and the remarkable new bone formation after treatment with denosumab, an inhibitor of RANKL. In primary and secondary malignant GCTBs, the
H3F3A
gene allele can be preserved or lost with malignant transformation.
Myxoid liposarcoma (MLS) accounts for 20%‐30% of liposarcoma and the round cell component (RCC) is believed to be a specific poor prognostic factor. However, the RCC assessment criteria are vaguely ...defined and, therefore, are inconsistently employed by pathologists. In this study, we modified and applied two established grading systems to evaluate nuclear atypia (namely, the World Health Organization/International Society of Urological Pathology and the Fuhrman grading in renal cell carcinoma) in 64 MLS cases. Detailed software‐based assessments of the morphology and the cellularity were performed. DNA mutation analysis, comprehensive mRNA expression analysis, and immunohistochemistry were also performed. Our findings revealed that the high–nuclear‐grade group according to the modified Fuhrman grading system exhibited a significantly poor disease‐free survival (hazard ratio: 4.43; 95% confidence interval: 0.9‐22.6; p = 0.047). On the other hand, the cellularity was significantly higher in the modified Fuhrman high‐grade group (p = 0.010 at the percentage of the hypercellular area; p = 0.003 at the maximum cell density) but did not qualify per se as a poor prognostic factor in the survival analyses. Furthermore, the modified Fuhrman high‐grade group significantly expressed the cell cycle–related genes (such as FOXM1, PLK1, and CDK1). In conclusion, our analyses suggest that an evaluation focusing on nuclear morphology (rather than on cellular density) can be more reliable in predicting the MLS prognosis.
The evaluation focusing on nuclear morphology (rather than on cellular density) can be more reliable in predicting the myxoid liposarcoma (MLS) prognosis. Modified Fuhrman grading is useful for the morphology evaluation. The high–nuclear‐grade group significantly expressed the cell cycle–related genes (such as FOXM1, PLK1, and CDK1).
The yips, an involuntary movement impediment that affects performance in skilled athletes, is commonly described as a form of task-specific focal dystonia or as a disorder lying on a continuum with ...focal dystonia at one end (neurological) and chocking under pressure at the other (psychological). However, its etiology has been remained to be elucidated. In order to understand sensorimotor cortical activity associated with this movement disorder, we examined electroencephalographic oscillations over the bilateral sensorimotor areas during a precision force task in athletes with yips, and compared them with age-, sex-, and years of experience-matched controls. Alpha-band event-related desynchronization (ERD), that occurs during movement execution, was greater in athlete with yips as compared to controls when increasing force output to match a target but not when adjusting the force at around the target. Event-related synchronization that occurs after movement termination was also greater in athletes with yips. There was no significant difference in task performance between groups. The enhanced ERD is suggested to be attributed to dysfunction of inhibitory system or increased allocation of attention to the body part used during the task. Our findings indicate that sensorimotor cortical oscillatory response is increased during movement initiation in athletes with yips.
Adenocarcinoma (ADC) is the most frequent histological type of lung cancer and comprises the majority of lung cancers in non‐smokers. Thus, genetic factors responsible for ADC susceptibility need to ...be determined to establish efficient ways of preventing the disease. The OGG1 gene, encoding a glycosylase for 8‐hydroxyguanine, an oxidatively damaged promutagenic base, has the polymorphism Ser326Cys, and OGG1‐326Cys protein was indicated to have a lower ability to prevent mutagenesis than the OGG1‐326Ser protein. Case‐control studies to date suggest that the OGG1‐326Cys allele is associated with a higher risk for several types of cancers, including overall lung cancer. However, the contribution of this polymorphism to lung ADC risk is unclear. In the present study, the OGG1‐Ser326Cys polymorphism was assessed for association with lung ADC risk using a case‐control study of a Japanese population consisting of 1097 cases and 394 controls. Odds ratios (OR) of the 326Cys allele carriers increased in a dose‐dependent manner with allele number (P for the trend test = 0.04). The OR of homozygotes for the 326Cys allele was increased significantly when homozygotes for the 326Ser allele were used as a reference (OR = 1.5, 95% confidence interval CI = 1.0–2.1, P = 0.04). Furthermore, the overall OR for lung ADC of the Cys/Cys homozygotes out of a total of 1925 ADC patients and 3449 controls from six case‐control studies reported up to the present were 1.43 (95% CI = 1.11–1.84, P = 0.0045). These results indicate that OGG1‐326Cys functions as a risk allele for lung ADC development. (Cancer Sci 2006; 97: 724–728)
Background
It is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is ...synonymous with “abnormal junction of the pancreaticobiliary ductal system”, “anomalous arrangement of pancreaticobiliary ducts”, “anomalous union of bilio-pancreatic ducts”, etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually.
Biliary carcinogenesis
The most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic.
K-ras
gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of
p53
gene and overexpression of
p53
protein are also found in the cancerous and noncancerous lesions. These changes are called “hyperplasia–carcinoma sequence”.
Treatment
Total excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.
Introduction: Tumor size is an important factor in determining the appropriate clinical management of intradural-extramedullary schwannoma. A tumor volume reduction may be achieved by conservative ...targeted therapy instead of invasive surgery if a molecular event related to tumor size is discovered. Insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an oncofetal tumor-associated antigen that is expected to be a target for immunotherapy, was focused on in this study.Methods: The IMP3 status was assessed by immunohistochemistry in 64 samples of intradural-extramedullary schwannoma, and the correlation between IMP3 expression and tumor size was evaluated.Results: Immunohistochemically, high IMP3 expression was observed in ~85% of schwannomas. The maximum tumor diameter of the high IMP3 expression group was significantly larger than that of the low IMP3 expression group (34.3 mm vs 18.5 mm, p=0.002). The receiver operating characteristic curve demonstrated that a maximum tumor diameter of 24 mm was a predictable factor for IMP3 expression (sensitivity, 0.7; 1−specificity, 0.2; area under the curve, 0.82).Conclusions: Upregulated IMP3 expression was associated with large tumor size, suggesting a possible therapeutic approach.
The histological definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is quite difficult because the morphological features are not specific and no useful immunohistochemical ...marker has been identified. Loss-of-function mutations in EED or SUZ12, which encode the core subunit of polycomb repressive complex 2 (PRC2), were reported in MPNSTs, and the mutations were shown to cause inactivation of PRC2, leading to loss of trimethylation of histone H3 at lysine 27 (H3K27me3). Immunohistochemistry of H3K27me3 is expected to be a specific marker for MPNSTs. We evaluated immunohistochemical expression of H3K27me3 in MPNSTs with heterologous components and metachronous cases of MPNSTs. Among 145 MPNST samples, 50 (34.5%) showed complete loss of staining, and 45 (31.0%) showed partial loss of staining. Regarding the backgrounds of MPNSTs, 43 patients of neurofibromatosis type 1 (NF-1)-associated MPNST demonstrated 19 (44.2%) complete and 12 (27.9%) partial loss of H3K27me3. Among MPNSTs with heterologous component, almost all of MPNSTs with epithelioid differentiation (8/9 samples, 88.9%) retained H3K27me3, and malignant Triton tumors without epithelioid component lacked H3K27me3 at high rate (91.7%). Five of 20 metachronous MPNST cases showed significantly reduced expression of H3K27me3 between primary and later-occurring tumors, but in some cases increased expression of H3K27me3 in the clinical course (such as complete loss to partial loss) was observed. If the tumors are recurrent or metastatic, H3K27me3 expression should be reduced or at least maintained because loss of H3K27me3 is due to genetic mutation of EED or SUZ12. MPNSTs, especially those associated with NF-1, can occur in heterochronous and multiple patterns, and the identification of increased expression of H3K27me3 during a patient’s clinical course can be helpful for determining whether the tumors are heterochronous, multiple or not. As heterochronous and multiple tumors may show lower malignancy compared to recurrent or metastatic tumors, favorable prognosis may be expected when H3K27me3 expression is increased.
Background/Purpose
The results from the Japanese Biliary Tract Cancer Statistics Registry from 1988 to 1998 were reported in 2002. In the present study, we report here selectively summarized data as ...an overview of the 2006 follow-up survey of the registered cases from 1998 to 2004 for information bearing on problems with the treatment of cancer of the biliary tract.
Methods
A total of 5,584 patients were registered from 1998 to 2004. The site of cancer was the bile duct in 2,732 patients, the gallbladder in 2,067, and the papilla of Vater in 785. Those cases were analyzed with regard to patient survival according to the extent of tumor invasion (pT), the extent of lymph node metastasis (pN) and the stage.
Results
The five-year survival rate after surgical resection was 33.1% for bile duct cancer, 41.6% for gallbladder cancer, and 52.8% for cancer of the papilla of Vater. For hilar or superior bile duct cancer, the 5-year survival rate was lower with an increase in the pT, pN and f stage, except pT3 vs. pT4, pN1 vs. pN2 and stage III vs. stage IVa. For middle or distal bile duct cancer, the 5-year survival rate was lower with increase in pT, pN and f stage, except pT2 vs. pT3, pN2 vs. pN3, stage II vs. stage III and stage III vs. stage IVa. For gallbladder cancer, the 5-year survival rate was lower with increase in pT, pN and f stage. For cancer of the papilla of Vater, the 5-year survival rate was lower with increase in pT, pN and f stage, except pT1 vs. pT2, pN1 vs. pN2, and stage III vs. stage IVa.
Conclusions
In the present study, the outcomes of surgical treatment were better than that of the previous report from Japan and foreign countries. The pT, pN and stage of gallbladder cancer are well defined. However, there were no significant differences in some groups of those of bile duct cancer and cancer of the papilla of Vater.
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