Nami Yamashita

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients.

Molecular mechanisms regulating the hormone sensitivity of breast cancer

Breast cancer is a heterogeneous disease. Approximately 70% of breast cancers are estrogen receptor (ER) positive. Endocrine therapy has dramatically improved the prognosis of ER‐positive breast cancer; however, many tumors exhibit de novo or acquired resistance to endocrine therapy. A thorough understanding of the molecular mechanisms regulating hormone sensitivity or resistance is important to improve the efficacy of and overcome the resistance to endocrine therapy. The growth factor receptor signaling pathways, particularly the phosphatidylinositol 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway can mediate resistance to all forms of endocrine therapy. In contrast, FOXA1 transcription factor is a key determinant of ER function and endocrine response. Intriguingly, a link between hormone resistance induced by the PI3K/Akt/mTOR pathway and the function of FOXA1 has been suggested. In this review, we focus on the PI3K/Akt/mTOR pathway and functions of FOXA1 in terms of the molecular mechanisms regulating the hormone sensitivity of breast cancer.

Bowel obstruction due to sciatic hernia

incarcerated sciatic hernia, and she underwent emergency operation ( fig. 2 ). The operation was performed using the transgluteal approach ( fig. 3 ). The sciatic hernia was repaired by suturing the piriformis muscle and the gluteus maximus muscle, without bowel resection because there was no evidence of ischemic change. She was discharged on the 14th postoperative day without any trouble. A 72-year-old woman showed massive ascites and sciatic hernia, which was composed solely of ascites, on computed tomography (CT) done in February 2005 as part of a regular follow-up for liver cirrhosis at Aso Iizuka Hospital. Surgical intervention was not chosen as there was no sign of visceral herniation ( fig. 1 ). This patient subsequently presented with abdominal distension in May 2005. CT revealed small bowel obstruction due to Published online: June 23, 2008

Technical Improvement of Total Pharyngo-Laryngo-Esophagectomy for Esophageal Cancer and Head and Neck Cancer

AbstractPurposeTotal pharyngo-laryngo-esophagectomy (PLE) is highly invasive, and the subsequent reconstruction is difficult. The purpose of this study was to clarify the techniques that can decrease the surgical stress and allow for safe reconstruction after this operation. MethodsThe surgical method and clinical outcomes of total PLE were reviewed in 12 patients with either cervicothoracic esophageal cancer or double cancer of the esophagus and pharynx. Microscopic venous anastomosis was principally performed, and arterial anastomosis was added, if needed.ResultsA narrow gastric tube was used in ten patients, including two patients who underwent free jejunal interposition, while the colon was used as the main reconstructed organ in two other patients. Staged operations were performed in three high-risk patients. All six patients treated after 2010 were able to undergo thoracoscopic and/or laparoscopic surgery. No critical postoperative complications developed, although minor anastomotic leakage developed in two patients who were successfully treated conservatively.ConclusionWhen performing PLE, it is important to decrease the surgical stress and ensure a reliable reconstruction by adopting techniques that are appropriate for each case, such as thoracoscopic and laparoscopic surgery, staged operations, microvascular anastomosis, and muscular flaps.

Differential impact of the expression of the androgen receptor by age in estrogen receptor–positive breast cancer

We evaluated the expression of the androgen receptor (AR) to determine its significance in breast cancer. AR expression levels were analyzed in 250 invasive breast cancers by immunohistochemistry and any association with the clinicopathological features was evaluated. AR expression was higher in estrogen receptor (ER)‐positive cases than in ER‐negative cases (P < 0.0001). AR expression was associated with ER level, and it increased with age in ER‐positive cases. The cut‐off value was determined to be 75% (Cancer Res. 2009;69:6131–6140), and AR expression was considered to be high in 155 (62%) cases. High AR expression significantly correlated with lower nuclear grade (P < 0.0001), ER and progesterone receptor (PR) positivity (P < 0.0001 and P = 0.0022), HER2 negativity (P = 0.0113), lower Ki67 index (P < 0.0001) and a longer disease‐free survival (DFS) and distant metastasis‐free survival (DMFS) (P = 0.0003 and 0.0107). This association between a high AR expression and a good DFS and DMFS was significant for ER‐positive tumors (P < 0.0001 and P = 0.0018); however, no association existed between AR expression and prognosis for ER‐negative tumors. In patients ≤51 years old, a high AR expression level significantly correlated with a better prognosis, but this was not significant in patients who were 50 or younger. Multivariate Cox hazard analyses revealed AR expression to be independently associated with a good prognosis in overall patients (HR 0.46, P = 0.0052) and in the ER‐positive cohort (HR 0.34, P = 0.0009). AR expression is associated with a less aggressive phenotype and a good prognosis in patients with ER‐positive breast cancer. This is considered to be a specific phenomenon for postmenopausal breast cancer patients.

Surgical strategies for esophageal cancer associated with head and neck cancer

Esophageal cancer is frequently associated with squamous cell carcinoma in the head and neck. Both cigarette smoking and alcohol consumption are risk factors for multiple cancers of the head and neck, as well as the esophagus. Routine screening and close follow-up for second cancers are important in patients with esophageal cancer or head and neck cancer. For this purpose, endoscopy with Lugol’s staining, as well as narrow-band imaging combined with magnifying endoscopy, is a powerful tool for the early detection of esophageal cancer. Multimodal therapy is essential for patients with double cancers. When considering surgical treatment, the curability of both cancers must be carefully evaluated. If both tumors are potentially curable, each lesion should be treated individually. In patients with metachronous double cancers, the prior treatment of the first primary carcinoma often affects the treatment of the second cancer. Close cooperation among medical staff members is essential for complicated surgeries for double cancers. Techniques that are appropriate for each case must be adopted, such as careful dissection, staged operations, muscular flaps and microvascular anastomosis.

Chondroblastic osteosarcoma arising from the pleura: Report of a case

Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura.

Epithelial Paradox: Clinical Significance of Coexpression of E-cadherin and Vimentin With Regard to Invasion and Metastasis of Breast Cancer

Background E‐cadherin and vimentin are regarded as major conventional canonical markers of the epithelial–mesenchymal transition. It is commonly assumed that E‐cadherin is uniformly lost during the process of epithelial–mesenchymal transition. Breast tumor cells typically invade as a cohesive multicellular unit in a process called collective invasion. The aim of this study was to reveal the clinical importance of the expression pattern of E‐cadherin and vimentin in breast cancer. Methods E‐cadherin and vimentin protein expression was evaluated by immunohistochemistry in 176 invasive breast cancer samples. Among these, E‐cadherin and vimentin expression were evaluated in the set of primary site and metastatic lymph nodes in 65 cases. In addition, E‐cadherin and vimentin expression were analyzed by confocal laser scanning microscopy to see E‐cadherin and vimentin localization in the breast cancer cells. Results Both at the primary site and metastatic lymph nodes, both E‐cadherin– and vimentin‐positive tumors had the worst disease‐free and overall survival among all cases. In addition, E‐cadherin and vimentin protein is colocalized within the same tumor cells in a human breast cancer specimen. Conclusion Our present data suggest the existence of an aggressive subpopulation in the primary tumor nest of breast cancer. Micro‐Abstract E‐cadherin and vimentin are regarded as major conventional canonical markers of epithelial–mesenchymal transition. Both E‐cadherin– and vimentin‐positive tumors had the worst prognosis among all cases. Further, E‐cadherin and vimentin protein is colocalized within the same tumor cells, suggesting the existence of an aggressive subpopulation in the primary tumor nest of breast cancer.

Protein Expression of Programmed Death 1 Ligand 1 and HER2 in Gastric Carcinoma

Objectives: Programmed death 1 (PD-1) is an immunoinhibitory receptor and has been identified as a new target for immunotherapy in cancer. Here we report the expression of PD-1 ligand 1 (PD-L1) in surgically resected gastric cancer. Materials and Methods: We examined formalin-fixed tumor samples from 144 gastric cancer patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1. Human epidermal growth factor receptor 2 (HER2) expression and phosphatase and tensin homolog (PTEN) loss of heterozygosity were investigated in these patients. RNA interference was used to downregulate HER2 expression, and PD-L1 protein expression was assessed by flow cytometry using the gastric cancer cell line MKN45. Results: Overexpression of PD-L1 was significantly correlated with tumor invasion (p = 0.011) and associated with poor survival. The number of PD-L1-positive cases increased according to the HER2 score in clinical samples. siRNA-mediated downregulation of HER2 significantly decreased PD-L1 protein expression in MKN45 cells. Conclusions: PD-L1 expression was associated with poor survival of gastric cancer, and HER2 signaling affects the expression of PD-L1 in gastric cancer. In gastric cancer, PTEN and HER2 are potential candidate biomarkers for developing human antibodies that block PD-L1.

Expression of APOBEC3B mRNA in primary breast cancer of Japanese women

Recent studies have identified the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B (APOBEC3B) as a source of mutations in various malignancies. APOBEC3B is overexpressed in several human cancer types, including breast cancer. In this study, we analyzed APOBEC3B mRNA expression in 305 primary breast cancers of Japanese women using quantitative reverse transcription-PCR, and investigated the relationships between the APOBEC3B mRNA expression and clinicopathological characteristics, prognosis, and TP53 mutations. The expression of APOBEC3B mRNA was detected in 277 tumors and not detected in 28 tumors. High APOBEC3B mRNA expression was significantly correlated with ER- and PR-negativity, high grade and high Ki67 index. The APOBEC3B mRNA expression was highest in the triple-negative and lowest in the hormone receptor-positive/HER2-negative subtypes. The TP53 gene was more frequently mutated in the tumors with high APOBEC3B mRNA expression. High APOBEC3B mRNA expression was significantly associated with poor recurrence-free survival in all cases and the ER-positive cases. These findings were almost consistent with the previous reports from the Western countries. In conclusion, high APOBEC3B mRNA expression was related to the aggressive phenotypes of breast cancer, high frequency of TP53 mutation and poor prognosis, especially in ER-positive tumors.