Yoshihiro Shioi

Analysis of cell cycle-related proteins in gastric intramucosal differentiated-type cancers based on mucin phenotypes: a novel hypothesis of early gastric carcinogenesis based on mucin phenotype

BackgroundAbnormalities of cell cycle regulators are common features in human cancers, and several of these factors are associated with the early development of gastric cancers. However, recent studies have shown that gastric cancer tumorigenesis was characterized by mucin expression. Thus, expression patterns of cell cycle-related proteins were investigated in the early phase of differentiated-type gastric cancers to ascertain any mechanistic relationships with mucin phenotypes.MethodsImmunostaining for Cyclins D1, A, E, and p21, p27, p53 and β-catenin was used to examine impairments of the cell cycle in 190 gastric intramucosal differentiated-type cancers. Mucin phenotypes were determined by the expressions of MUC5AC, MUC6, MUC2 and CD10. A Ki-67 positive rate (PR) was also examined.ResultsOverexpressions of p53, cyclin D1 and cyclin A were significantly more frequent in a gastric phenotype than an intestinal phenotype. Cyclin A was overexpressed in a mixed phenotype compared with an intestinal phenotype, while p27 overexpression was more frequent in an intestinal phenotype than in a mixed phenotype. Reduction of p21 was a common feature of the gastric intramucosal differentiated-type cancers examined.ConclusionsOur results suggest that the levels of some cell cycle regulators appear to be associated with mucin phenotypes of early gastric differentiated-type cancers.

Nipple adenoma arising from axillary accessory breast: a case report

Nipple adenoma is a relatively rare benign breast neoplasm, and cases of the disease arising from the axillary accessory breast have very seldom been reported in the English literature. We report a case of nipple adenoma arising from axillary accessory breast including clinical and pathological findings. An 82-year-old woman presented with the complaint of a small painful mass in the right axilla. Physical examination confirmed a well-defined eczematous crusted mass that was 8 mm in size. The diagnosis of nipple adenoma was made from an excisional specimen on the basis of characteristic histological findings. Microscopic structural features included a compact proliferation of small tubules lined by epithelial and myoepithelial cells, and the merging of glandular epithelial cells of the adenoma into squamous epithelial cells in the superficial epidermal layer. Because clinically nipple adenoma may resemble Paget’s disease and pathologically can be misinterpreted as tubular carcinoma, the correct identification of nipple adenoma is an important factor in the differential diagnosis for axillary tumor neoplasms.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1186821489769063

Long-term complete remission of metastatic breast cancer, induced by a steroidal aromatase inhibitor after failure of a non-steroidal aromatase inhibitor.

Patient: Female, 56 Final Diagnosis: Breast cancer Symptoms: Solid mass in the right breast Medication: Exemestane Clinical Procedure: — Specialty: Oncology Objective: Unusual clinical course Background: The efficacy of third-generation aromatase inhibitors for hormone receptor-positive postmenopausal metastatic breast cancer is well established. Although several clinical trials have reported incomplete cross-resistance between different aromatase inhibitors, few cases of complete responses of recurrent metastatic breast cancer occurring after substituting a second aromatase inhibitor have been reported. We here present a rare case of non-steroidal aromatase inhibitor-tolerant metastatic breast cancer with long-term complete remission following substitution of a steroidal aromatase inhibitor. Case Report: We present the case of a 56-year-old Japanese woman who underwent right breast-conserving surgery for breast cancer, TNM staging T1, N0, M0, Stage I. She received adjuvant chemotherapy with 6 cycles of FEC100 and radiation therapy, and then began hormonal therapy with anastrozole. Twelve months postoperatively, computed tomography (CT) revealed multiple lung metastases. Exemestane was substituted for anastrozole. After 3 months of exemestane, CT showed that all lung metastases had completely resolved. Her complete response was maintained for 5 years: she died during a tsunami 6 years after the initial surgery. Conclusions: Substitution of a steroidal for a non-steroidal aromatase inhibitor produced a sustained complete remission in a patient with hormonal receptor-positive postmenopausal recurrent breast cancer. Achieving complete response after switching from a non-steroidal to a steroidal aromatase inhibitor in a hormonal receptor-positive postmenopausal recurrent breast cancer contributed to a higher quality of life for the patient. Further investigation is needed to identify the predictors of long-term remission following such a switch.

Primary retroperitoneal spindle cell liposarcoma: Pathological and immunohistochemical findings

Spindle cell liposarcoma (SCLS) is presently regarded as a rare variant of well‐differentiated liposarcoma (WDLPS), which has the potential for aggressive clinical behavior. WDLPS occurs most frequently in the limbs and retroperitoneum. The most common site of SCLS occurrence is the upper limbs or shoulder girdle. Herein we report the first case of primary retroperitoneal SCLS. A 60‐year‐old Japanese man presented with a right inferior abdominal mass. Complete excision of the mass displayed a yellowish spherical tumor with a well‐circumscribed appearance measuring 98 × 95 mm. Pathological examination of the tumor revealed a neural‐like spindle cell proliferation set in a fibrous background that was associated with an atypical lipomatous component, which usually included lipoblasts. Mitotic cells were scarce. Immunohistochemical analysis demonstrated that lipoblasts were S100 positive, spindle cells were CD34 positive, and both spindle cells and lipoblasts were MDM2 negative. The Ki‐67 labeling index was <2%. At one year follow up, the patient was alive without local recurrence or metastasis. Although the proliferative activity of this tumor did not indicate strong malignancy, retroperitoneal liposarcoma generally has a poor prognosis. Accumulation of cases of SCLS is necessary to facilitate a more accurate evaluation of the pathology and clinical behavior of this tumor.

Autopsy case of acute liver failure due to scrub typhus

Scrub typhus (Tsutsugamushi disease) is an acute febrile disease caused by infection with Orientia tsutsugamushi transmitted by mites. Although patients with scrub typhus commonly display mild liver injury, few die of acute liver failure. We describe herein an autopsy case of acute liver failure due to scrub typhus, which was complicated by disseminated intravascular coagulation and showed rapid progression of liver injury just before death. Histopathological findings revealed submassive hepatocellular necrosis, inflammatory cell infiltration in Glisson’s capsules, and sporadic fibrin thrombi in the hepatic sinusoids. Cause of death was primarily associated with acute liver failure related to disseminated intravascular coagulation.

Effectiveness of neoadjuvant chemotherapy with cisplatin and irinotecan followed by surgery on small-cell carcinoma of the esophagus: A case report

Highlights • Small-cell carcinoma of the esophagus is a rare disease and a poor prognosis.• The optimum treatment strategy for SCCE remains to be established.• We report a case of advanced SCCE achieving a pathologically complete response with preoperative chemotherapy using CDDP and CPT-11, and long-term survival followed by surgery.• Neoadjuvant chemotherapy following esophagectomy could be a useful treatment option.

Stability of cervical esophagogastrostomy via hand-sewn anastomosis after esophagectomy for esophageal cancer

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.

Peripheral vein infusions of amino acids facilitate recovery after esophagectomy for esophageal cancer: Retrospective cohort analysis

Background To investigate the efficacy of amino acid administration via peripheral veins in addition to conventional enteral feeding following esophagectomy. Materials and methods Retrospective analysis of data pertaining to 33 patients with esophageal cancer who underwent radical esophagectomy and satisfied the required nutrition control. Patients were divided into the amino acid group (n = 17) and control group (n = 16). Primary outcomes were albumin (Alb) and prealbumin (PreAlb) levels, urinary 3-methylhistidine/creatinine (3-MeHis/Cre) ratios, nitrogen balance, and weight; postoperative complications were noted as secondary outcomes. Results Alb levels were significantly higher in the amino acid group on postoperative day (POD)-14 (3.4 ± 0.3 vs. 3.1 ± 0.4 mg/dL in the control group, p = 0.018) and at 1 month after surgery (3.8 ± 0.4 vs. 3.5 ± 0.3 mg/dL, p = 0.045). No significant differences were observed in PreAlb and urinary 3-MeHis/Cre rates between the treatment groups. Body weights at 3 months postoperatively were decreased by 6% and 3% in the control and amino acid groups, respectively. Conclusion Peripheral venous administration of amino acids soon after surgical stress is an effective method for nutritional control.

Abstract 1162: Multiple genes on chromosome 17q25 were involved in sporadic esophageal squamous cell carcinoma development

[Background] Tylosis is an autosomal dominant skin disorder that is associated with the early onset of esophageal squamous cell carcinoma (ESCC) in several families. The tylosis esophageal cancer (TOC) gene locus has been mapped to chromosome 17q25.1 using linkage analyses. This region is also frequently lost in sporadic ESCC. [Materials and Methods] Gene expression profiles on 17q25 in tumor samples from 3 ESCC patients were analyzed using RNA-seq. We validated the expression status of candidate genes in samples from 90 ESCC patients using qRT-PCR. Direct sequence, microsatellite LOH analysis, and methylation assay were also performed in the candidate gene, ST6GALNAC1. Mutation profiles of genes on 17q were also evaluated by exome sequence analysis from 144 ESCC patients. [Result] EVPL and ST6GALNAC1 were found to be significantly downregulated in tumor samples using RNA-seq. Significant downregulation of ST6GALNAC1 and EVPL expression in cancer tissues was confirmed by qRT-PCR in 90 ESCC samples. Although direct sequence of ST6GALNAC1 demonstrated missense mutations in 7 out of 46 (15%) cases, these mutations were not tumor specific. ST6GALNAC1 expression was significantly upregulated in 5-aza-dC treatment groups compared with control in the 5 ESCC cell lines. LOH in ST6GALNAC1 gene locus were identified 18 of 27 informative cases (67%). On chromosome 17q, exome sequence revealed that recurrent mutations were observed only in ZNF750 (14.5%) on 7q25.3. Recently, missense mutations in RHBDF2 were identified tylosis familys. However, RHBDF2 mutation was not observed in sporadic ESC samples by exome sequence analysis. [Conclusion] Our results suggest that ST6GALNAC1 is a putative tumor suppressor gene for ESCC. Furthermore, recent studies on tylosis families and our results on sporadic ESC suggest that multiple genes on chromosome 17q25 are involved in ESCC development. Citation Format: Takeshi Iwaya, Suburu Amano, Fumitaka Endo, Yuji Akiyama, Yoshihiro Shioi, Kohei Kume, Satoshi Nishizuka, Chie Ito, Akira Sasaki, Koshi Mimori. Multiple genes on chromosome 17q25 were involved in sporadic esophageal squamous cell carcinoma development. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1162.

Abstract 1159: Downregulation of TMPRSS11B in squamous cell carcinoma

[Background] Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers. The molecular mechanism of ESCC development has not been fully elucidated. [Aim] The aim of this study is to identify responsible genes for ESCC development. [Materials and Methods] Firstly, we performed transcriptome sequence (RNA-seq) analysis of surgically resected tumor and corresponding normal tissues form 3 ESCC patients with different tumor locus, histrogical differentiation, and TNM stage.by RNA-seq analysis: (Case 1) upper thoracic esophagus, well differentiated SCC, TNM, Stage I; (Case 2) middle thoracic esophagus, poorly differentiated SCC, T3N0M0, Stage II; and (Case 3) lower thoracic esophagus, moderately differentiated SCC, T3N1M0, Stage III. Next, we validated the expression status of the candidate gene in 64 clinical samples and 10 ESCC cell lines (KYSE150, KYSE270, KYSE410, KYSE450, KYSE510, TE1, TE6, TE8, TE9, and TE10) using quantitative real-time PCR (qRT-PCR). [Results] In RNA-seq analysis, 34 genes showed more than 30-fold decrease in tumor samples compared to normal tissues, and the most downregulated gene was transmembrane protease serine 11B (TMPRSS11B). Amon these 34 genes, other 5 genes of TMPRSS11 family (TMPRSS11A, TMPRSS11BNL, TMPRSS11D, TMPRSS11E, and TMPRSS11F) were included. qRT-PCR analysis revealed that TMPRSS11B expression in ESCC samples were lower than those in normal samples (p Citation Format: Suburu Amano, Takeshi Iwaya, Satoshi Nishizuka, Kohei Kume, Chie Ito, Yuji Akiyama, Yoshihiro Shioi, Fumitaka Endo, Akira Sasaki. Downregulation of TMPRSS11B in squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1159.