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We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pappor2sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

An 84-year-old man visited our hospital with epigastralgia.Levels of hepatic and biliary enzymes and CRP were elevated, as detected by a blood test.On a CT scan, a swollen gallbladder with stones was detected.The patient was admitted to the hospital with a diagnosis of Grade I acute cholecystitis.Conservative treatment was continued with antibiotic administration and the patient was discharged from the hospital with improvement on day 6 after admission.Three months later, the patient underwent laparoscopic cholecystectomy.In the gallbladder, a 45×45 mm tumor was found.Upon pathological examination, diffuse proliferation of lymphocyte-like heterotypic cells and subserosal invasion were observed.Immunohistochemistry results were negative for MUM1 and positive for CD10 and Bcl6 markers.A malignant diffuse large B-cell lymphoma was diagnosed.We experienced a case of malignant lymphoma of the gallbladder diagnosed after surgery for acute cholecystitis, which we herein report with literature consideration.

Summary Objective Multiple endocrine neoplasia type 1 (MEN1) is less well recognized in Asian countries, including Japan, than in the West. The clinical features and optimal management of MEN1 have yet to be clarified in Japan. The aim of this study was to clarify the clinical features of Japanese patients with MEN1. Design/Patients We established a MEN study group designated the ‘MEN Consortium of Japan’ in 2008, and asked physicians and surgeons to provide clinical and genetic information on patients they had treated. Of 680 registered patients, 560 were analysed. Measurements Clinical and genetic features of Japanese patients with MEN1 were examined. Results Primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumours (GEPNET), and pituitary tumours were seen in 94·4%, 58·6% and 49·6% of patients, respectively. The prevalence of insulinoma was higher in the Japanese than in the West (22%vs 10%). In addition, 37% of patients with thymic carcinoids were women, while most were men in western countries. The MEN1 mutation positive rate was 91·7% in familial cases and only 49·3% in sporadic cases. Eight novel mutations were identified. Despite the availability of genetic testing for MEN1, the application of genetic testing, especially presymptomatic diagnosis for at-risk family members appeared to be insufficient. Conclusions We established the first extensive database for Asian patients with MEN1. Although the clinical features of Japanese patients were similar to those in western countries, there were several characteristic differences between them.

This study aimed to analyse whether age, metastasis, extrathyroidal invasion and size (AMES) risk definition is valuable for Japanese patients with differentiated thyroid carcinoma (DTC). Methods: Two hundred and fifteen Japanese DTC patients (43 men, 172 women; mean age, 51.0 years; mean follow-up, 102 months) treated surgically at our institutions between 1981 and 2001 were retrospectively analysed. Clinicopathological features were compared between high-risk and low-risk patients by AMES criteria. Various risk factors were also evaluated for each group of patients. Results: There were 57 high-risk and 158 low-risk patients. Recurrence and mortality rates were 43.9% and 24.6% in high-risk patients and 7.6% and 0.6% in low-risk patients, respectively (p < 0.0001). Disease-specific survival rates at 5, 10 and 15 years were 84.3%, 74.0% and 63.5% in high-risk patients and 100%, 100% and 98.3% in low-risk patients, respectively (p < 0.0001). Univariate analysis revealed that curative resection, local recurrence and distant metastasis were risk factors for mortality in the high-risk group. Multivariate analysis revealed that curative resection (hazard ratio [HR], 4.68; 95% confidence interval [CI], 1.23-17.83; p = 0.024) and distant metastasis (HR, 4.79; 95% CI, 1.24-18.40; p = 0.023) were significantly related to mortality in high-risk patients. Conclusion: AMES can identify high-risk and low-risk Japanese patients. Distant metastasis and curative resection are prognostic factors for disease-specific death.

We report a rare case of a solitary metachronous metastasis of renal clear cell carcinoma (RCC) presenting as a thyroid tumor 19 years after a nephrectomy. Our search of the English-language literature found only sporadic reports of late RCC metastases to the thyroid. Fine-needle aspiration biopsy of the thyroid tumor was not accompanied with thyroglobulin (Tg) staining, leading us to initially suspect a primary follicular thyroid carcinoma. The patient, a 77-year-old man, underwent a total thyroidectomy with modified neck dissection. Histological examination confirmed the tumor to be RCC metastasis, and immunohistochemical analysis revealed that both Tg and thyroid transcription factor-1 (TTF-1) were negative in the tumor cells. Thus, the possibility of late RCC metastasis to the thyroid should be considered, even in a patient with a remote history. Furthermore, TTF-1 is useful for identifying thyroid metastatic carcinomas.

背景:甲状腺びまん性硬化型乳頭癌は, 若い女性に好発し, 臨床的・病理学的に通常の乳頭癌と鑑別すべき特徴を有するまれな腫瘍である. 今回われわれはその1例を経験したので報告する.症例:31歳, 女性. 右甲状腺腫瘤を主訴とし当院受診. 橋本病が疑われ, 甲状腺穿刺吸引細胞診が施行された. 細胞診では一般的な乳頭癌での細胞所見に加え, 多数のリンパ球が背景に出現し, 扁平上皮化生様異型細胞, 砂粒小体形成が認められた. びまん性硬化型乳頭癌が強く疑われ, 甲状腺全摘出術および頸部廓清術が施行された. 甲状腺右葉は明らかな結節を形成することなく線維化を伴ってびまん性に腫大していた. 組織学的には右葉を主体に, 線維化やリンパ濾胞形成を伴うリンパ球浸潤を背景とし, 核溝やすりガラス状核を呈する異型細胞が乳頭状, 濾胞状, 一部充実性に増生していた. 扁平上皮化生様変化, 砂粒小体形成を伴う甲状腺内微小転移巣やリンパ管侵襲を認めた. リンパ節転移が高頻度にみられた.結論:細胞診でも, びまん性硬化型乳頭癌の特徴とされる高度のリンパ球浸潤, 砂粒小体, 扁平上皮化生様変化がみられ, 触診所見, 画像情報等の臨床情報を加味することにより細胞診での推定は可能と考えられた.

Multiple endocrine neoplasia type 1 (MEN1) is less well recognized in Asian countries, including Japan, than in the West. The clinical features and optimal management of MEN1 have yet to be clarified in Japan. The aim of this study was to clarify the clinical features of Japanese patients with MEN1.We established a MEN study group designated the 'MEN Consortium of Japan' in 2008, and asked physicians and surgeons to provide clinical and genetic information on patients they had treated. Of 680 registered patients, 560 were analysed.Clinical and genetic features of Japanese patients with MEN1 were examined.Primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumours (GEPNET), and pituitary tumours were seen in 94·4%, 58·6% and 49·6% of patients, respectively. The prevalence of insulinoma was higher in the Japanese than in the West (22%vs 10%). In addition, 37% of patients with thymic carcinoids were women, while most were men in western countries. The MEN1 mutation positive rate was 91·7% in familial cases and only 49·3% in sporadic cases. Eight novel mutations were identified. Despite the availability of genetic testing for MEN1, the application of genetic testing, especially presymptomatic diagnosis for at-risk family members appeared to be insufficient.We established the first extensive database for Asian patients with MEN1. Although the clinical features of Japanese patients were similar to those in western countries, there were several characteristic differences between them.

Herein, we report two extremely rare cases of differentiated thyroid carcinoma (DTC) with extended tumor thrombus or mediastinum lymph node metastasis (LNM) involving the superior vena cava (SVC), causing SVC syndrome. Both of these patients were successfully treated with radical resection and reconstruction of the SVC using autologous tissue instead of an expanded polytetrafluoroethylene (ePTFE) graft. The left brachiocephalic vein was used to reconstruct the SVC in a papillary thyroid carcinoma patient with mediastinum LNM and a pericardial patch was used in a follicular thyroid carcinoma patient with tumor thrombus. Our search of the English-language literature found sporadic reports of SVC resection with reconstruction by vascular graft (ePTFE), interposed between the brachiocephalic vein and the right atrium. However, SVC reconstruction using autologous tissue in thyroid carcinoma has not been reported to date. To our knowledge, this is the first report describing such an unusual technique in DTC patients.

Background To examine the outcomes and risk factors in pediatric differentiated thyroid carcinoma (DTC) patients who were defined as TNM stage I because some patients develop disease recurrence but treatment strategy for such stage I pediatric patients is still controversial. Methods We reviewed 57 consecutive TNM stage I patients (15 years or less) with DTC (46 papillary and 11 follicular) who underwent initial treatment at Ito Hospital between 1962 and 2004 (7 males and 50 females; mean age: 13.1 years; mean follow-up: 17.4 years). Clinicopathological results were evaluated in all patients. Multivariate analysis was performed to reveal the risk factors for disease-free survival (DFS) in these 57 patients. Results Extrathyroid extension and clinical lymphadenopathy at diagnosis were found in 7 and 12 patients, respectively. Subtotal/total thyroidectomy was performed in 23 patients, modified neck dissection in 38, and radioactive iodine therapy in 10. Pathological node metastasis was confirmed in 37 patients (64.9%). Fifteen patients (26.3%) exhibited local recurrence and 3 of them also developed metachronous lung metastasis. Ten of these 15 achieved disease-free after further treatments and no patients died of disease. In multivariate analysis, male gender (p = 0.017), advanced tumor (T3, 4a) stage (p = 0.029), and clinical lymphadenopathy (p = 0.006) were risk factors for DFS in stage I pediatric patients. Conclusion Male gender, tumor stage, and lymphadenopathy are risk factors for DFS in stage I pediatric DTC patients. Aggressive treatment (total thyroidectomy, node dissection, and RI therapy) is considered appropriate for patients with risk factors, whereas conservative or stepwise approach may be acceptable for other patients.

The mitotic spindle assembly checkpoint (MSAC) genes are responsible for preventing chromosome missegregation. MSAC gene expressions have been reported to be associated with tumor cell proliferation or unfavorable cancer behavior. The present study was conducted to preliminary investigate the MSAC gene expressions in thyroid neoplasms.Expression levels of MSAC genes (hBUB1, hBUBR1, hBUB3 and hMAD2) were evaluated in 9 follicular thyroid adenomas (FAs), 9 follicular thyroid carcinomas (FTCs), 21 papillary thyroid carcinomas (PTCs), 5 anaplastic (undifferentiated) thyroid carcinomas (ATCs) and 3 adjacent normal thyroid tissues (NTs) by real-time quantitative RT-PCR. These gene expressions were compared between undifferentiated thyroid carcinomas (ATCs) and differentiated thyroid carcinomas (DTCs) and between advanced DTCs and non-advanced DTCs. DTCs included PTCs and FTCs. Advanced DTCs were defined as carcinoma with aggressive nature such as extrathyroid extension, distant metastasis, recurrence or death from the disease.MSAC gene expressions varied in different thyroid tumors and fell in the order of ATC, DTC (PTC and FTC), FA and NT Carcinomas had higher expression compared to adenoma or normal tissue. hBUB1, hBUBR1 and hMAD2 expressions in ATCs were significantly higher than those in DTCs (p0.005). hBUBR1 and hMAD2 expressions in advanced DTCs were significantly higher than those in non-advanced DTCs (p0.05).The MSAC genes were overexpressed in thyroid carcinomas with aggressive nature. Further studies are required to clarify the relationship between the MSAC gene expressions and thyroid cancer behavior.

Although all tumor, node, metastasis system (TNM) stage IVA papillary thyroid carcinomas (PTCs) do not seem to behave equivalently as a result of various tumor and node stages, to our knowledge, subclass evaluation has never been attempted. We reviewed 119 stage IVA PTC patients who underwent initial thyroidectomy with modified neck dissection as curative surgery at our institution (33 male patients, 86 female patients; age 61.6 years; follow-up 87.7 months). These patients were divided into groups A (T1–3N1b; n = 79), B (T4aN0–1a; n = 9), and C (T4aN1b; n = 31). Outcomes were compared between the groups. The rates of recurrence (P

To examine lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC) according to clinicopathological features and outcomes associated with the nodal status.We reviewed 231 patients with PTC (or =1.0cm) who underwent initial thyroidectomy with modified neck dissection. LNM was examined in the central and lateral compartment and risk factors for disease-free survival (DFS) were evaluated. Nodal status and outcomes were further evaluated in four subgroups, 19 older patients (or =45years old) with palpable lymphadenopathy (PLA) and 134 without PLA, and 11 younger patients (45years old) with PLA and 67 without PLA, because multivariate analysis revealed that age (p0.05, Hazard ratio (HR) 3.51) and PLA (p0.0001, HR 14.9) were risk factors for DFS.Central and lateral LNM were found in 176 and 151 patients. Seventeen exhibited skip metastasis. Recurrence and disease death occurred in 23 and 5. In analysis of the four subgroups, recurrence was significantly frequent in older patients with PLA than in younger patients with PLA or older patients without PLA (8/19 vs. 3/11 or 12/134). Younger patients without PLA did not exhibit recurrence.Prognosis is worse in older patients with PLA. Such patients should be treated carefully with a considerable treatment strategy.

Background GLUT10 (gene symbol SLC2A10) is a facilitative glucose transporter within the type 2 diabetes (T2DM)-linked region on chromosome 20q12-13.1. Therefore, we evaluated GLUT10 as a positional candidate gene for T2DM in Caucasian Americans. Methods Twenty SNPs including 4 coding, 10 intronic and 6 5' and 3' to the coding sequence were genotyped across a 100 kb region containing the SLC2A10 gene in DNAs from 300 T2DM cases and 310 controls using the Sequenom MassArray Genotyping System. Allelic association was evaluated, and linkage disequilibrium (LD) and haplotype structure of SLC2A10 were also determined to assess whether any specific haplotypes were associated with T2DM. Results Of these variants, fifteen had heterozygosities greater than 0.80 and were analyzed further for association with T2DM. No evidence of significant association was observed for any variant with T2DM (all P ≥ 0.05), including Ala206Thr (rs2235491) which was previously reported to be associated with fasting insulin. Linkage disequilibrium analysis suggests that the SLC2A10 gene is contained in a single haplotype block of 14 kb. Haplotype association analysis with T2DM did not reveal any significant differences between haplotype frequencies in T2DM cases and controls. Conclusion From our findings, we can conclude that sequence variants in or near GLUT10 are unlikely to contribute significantly to T2DM in Caucasian Americans.

Background: Matrix metalloproteinases are Zn2+- and Ca2+-dependent endopeptidases secreted by many cells. Expression of the matrix metalloproteinase 9 (MMP9) gene is increased in a variety of renal diseases. Several genetic studies have associated MMP9 with end-stage renal disease (ESRD). Methods: In this study, 2.2 kb of the promoter region and all 13 exons (3.3 kb) of MMP9 genomic DNA were scanned for polymorphisms. Genetic associations between MMP9 polymorphisms and renal disease were evaluated. Results: Eleven single-nucleotide polymorphisms (SNPs; 4 promoter, 6 coding region, and 1 3′ untranslated region [UTR]) were identified in Caucasians and 19 SNPs (11 promoter, 8 coding region, 1 3′ UTR) were identified in African Americans. A previously identified highly polymorphic (CA)n repeat in the promoter region of MMP9 also was evaluated. We found 15 alleles in Caucasians and 14 alleles in African Americans. Allele frequencies, genotypes, and 3-marker haplotypes were compared between patient and control populations. Differences were not observed using single-locus analyses. Two haplotypes that included the (CA)n repeat allele in African-American patients with type 2 diabetic nephropathy (T2DM/ESRD) showed borderline significant differences. Dichotomizing the (CA)n repeat distribution showed that shorter alleles in Caucasian cases were associated with ESRD using an additive disease-predisposing model (P = 0.05). Analysis of the (CA)n repeat in expanded sets of subjects showed strong evidence for an association of shorter alleles with ESRD in Caucasians (P = 0.00012) and suggested a similar trend in African Americans with T2DM/ESRD (P = 0.086) and subjects without T2DM/ESRD (P = 0.047). Conclusion: This comprehensive analysis of MMP9 and renal disease suggests a possible role for the (CA)n repeat in renal disease, consistent with previous reports.

Recent linkage studies and association analyses indicate the presence of at least one type 2 diabetes susceptibility gene in human chromosome region 20q12-q13.1. We have constructed a high-resolution 6.0-megabase (Mb) transcript map of this interval using two parallel, complementary strategies to construct the map. We assembled a series of bacterial artificial chromosome (BAC) contigs from 56 overlapping BAC clones, using STS/marker screening of 42 genes, 43 ESTs, 38 STSs, 22 polymorphic, and 3 BAC end sequence markers. We performed map assembly with GraphMap, a software program that uses a greedy path searching algorithm, supplemented with local heuristics. We anchored the resulting BAC contigs and oriented them within a yeast artificial chromosome (YAC) scaffold by observing the retention patterns of shared markers in a panel of 21 YAC clones. Concurrently, we assembled a sequence-based map from genomic sequence data released by the Human Genome Project, using a seed-and-walk approach. The map currently provides near-continuous coverage between SGC32867 and WI-17676 ( approximately 6.0 Mb). EST database searches and genomic sequence alignments of ESTs, mRNAs, and UniGene clusters enabled the annotation of the sequence interval with experimentally confirmed and putative transcripts. We have begun to systematically evaluate candidate genes and novel ESTs within the transcript map framework. So far, however, we have found no statistically significant evidence of functional allelic variants associated with type 2 diabetes. The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region.