Clinicopathological features of gastric metastasis from breast cancer in three cases.

The common sites for metastases from breast cancer are lymph nodes, bone, lung, liver, and brain. Gastrointestinal (GI) metastasis is rarely found or diagnosed in patients with breast cancer. This report presents three cases of gastric metastasis from breast cancer. Case 1 was a 42-year-old female diagnosed with gastric metastasis after mastectomy with axillary lymph node dissection for invasive lobular carcinoma of the left breast. Case 2 was a 54-year-old female who was diagnosed to have invasive lobular carcinoma of the left breast with systemic bone and gastric metastasis. Case 3 was a 54-year-old female who was diagnosed to have bilateral invasive ductal carcinoma of the breast with simultaneous bone and gastric metastasis. The immunohistochemical statuses for estrogen receptor, progesterone receptor, mammaglobin, and gross cystic disease fluid protein-15 (GCDFP-15) between the primary and gastric metastatic lesions were all well matched. All three cases were treated with systemic chemotherapy, hormone therapy or both, without surgical intervention for gastric lesions. Two patients with disseminated disease died 27 and 58 months after diagnosis of gastric metastasis, while one patient without organ metastasis is still alive at 56 months after diagnosis. It is important to make a correct diagnosis by distinguishing gastric metastasis from breast cancer in order to select the optimal initial treatment for systemic disease of breast cancer.

The clinical benefit of high-dose toremifene for metastatic breast cancer.

INTRODUCTION: Toremifene(TOR)is a selective estrogen receptor modulator(SERM). A high dose of 120 mg TOR(HD-TOR) has been used for recurrent breast cancer in Japan, but there is still insufficient evidence regarding the efficacy of HD-TOR. PATIENTS AND METHODS: HD-TOR was administered for recurrent or metastatic breast cancer between January 2003 and May 2012. The primary end point of the study was the tumor response rate. Bone metastasis cases were excluded from the efficacy analysis, but were included in the safety population. RESULTS: A total of 21 patients registered in the study and the 2 patients with bone metastasis only were excluded from the efficacy analysis. The median follow-up period was 8. 3 months. None of the patients in the study had a CR, 4 had a PR(21. 1%), 9 had SD(47. 4%), and 6 had PD(31. 6%). Eight of the 9 SD cases had a long-term SD. The ORR was 21. 1% and the CB rate was 63. 2%. The median TTP of CB cases was 18. 3 months. None of the patients discontinued treatment because of a grade 3 or grade 4 adverse effects. CONCLUSION: In summary, the current study showed that HD-TOR may lead to a CB for recurrent breast cancer in first- or second-line treatment rather than thirdline. In particular, HD-TOR may give a benefit in highly endocrine-sensitive cases.

Periostin promotes chronic allergic inflammation in response to Th2 cytokines.

Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with αv integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or αv integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.

Lymphadenectomy along the left recurrent laryngeal nerve by a minimally invasive esophagectomy in the prone position for thoracic esophageal cancer.

BACKGROUND: A thoracoabdominal esophagectomy for esophageal cancer is a severely invasive procedure. A thoracoscopic esophagectomy may minimize injury to the chest wall and reduce surgical invasiveness. Conventional thoracoscopic procedures are performed in the left lateral-decubitus position. Recently, procedures performed in the prone position have received more attention because of improvements in operative exposure or surgeon ergonomics. However, the efficacy of the prone position in an aggressive thoracoscopic esophagectomy with an extensive lymphadenectomy has not been fully documented. METHODS: We successfully performed a thoracoscopic esophagectomy with a three-field extensive lymphadenectomy in 43 esophageal carcinoma patients in the prone position from December 2007 to December 2009. We describe our procedures with the patients in the prone position, focusing especially on a lymphadenectomy along the left recurrent laryngeal nerve where the nodes are frequently involved and precise dissection is technically challenging. To determine further the advantages of this position, we retrospectively compared surgical outcomes in 43 patients to those of 34 patients who underwent a thoracoscopic esophagectomy in the left lateral decubitus position as a historical control from January 2006 to November 2007. RESULTS: It was easier to explore the operative field around the left recurrent laryngeal nerve during a thoracoscopic esophagectomy in the prone position. The mean duration of the aggressive thoracoscopic procedure in the prone position was 307 min, which was significantly longer than in the left lateral decubitus position, but the total estimated blood loss in the prone position was significantly lower. There was no difference in the incidence of postoperative complications between the two procedures. CONCLUSIONS: A thoracoscopic esophagectomy in the prone position is technically safe and feasible and provides better surgeon ergonomics and better operative exposure around the left recurrent laryngeal nerve during an aggressive esophagectomy.

Case report of pseudoaneurysm caused by core needle biopsy of the breast.

We treated a patient with a pseudoaneurysm caused by core needle biopsy (CNB), in which both the cancer and the aneurysm were excised by breast conservation therapy. A 51-year-old woman attended a local hospital because of a 25-mm mass in the upper outer quadrant of the right breast. CNB was performed, and brisk bleeding occurred at the biopsy site. Immediate hemostasis was achieved with direct manual compression. CNB detected fatty tissue, and a diagnosis could not be made. When she presented at our hospital 6 weeks later, there was a 25-mm pulsating mass at the biopsy site. Color-flow Doppler US and dynamic MRI showed a breast tumor and pseudoaneurysm formation. For the purpose of diagnosis and treatment of the breast tumor and pseudoaneurysm, lumpectomy of the right breast was performed. Histological diagnosis was papillotubular carcinoma and pseudoaneurysm. Although this condition is relatively rare, it is important to be aware of the possibility of complications, such as pseudoaneurysms, which require treatment.

[A case of recurrent breast cancer with bone marrow metastasis treated with weekly paclitaxel therapy].

A 44-year-old woman with bone marrow metastasis from breast cancer was treated with weekly paclitaxel therapy. She underwent radical mastectomy for right breast cancer (T2N1M0, Stage II B) in April 2003, and was then treated with hormonal therapy (leuprorelin). In November 2005, she received radiation for bone metastasis in thoracic and lumbar vertebrae, and bisphosphonate therapy was performed. Additional hormonal therapy (tamoxifen) was administered for progressive bone metastasis. However, in September 2006, pancytopenia was recognized and bone marrow metastasis was diagnosed by bone biopsy. Disseminated intravascular coagulation (DIC) developed, so she was given weekly paclitaxel therapy with blood transfusion and G-CSF injection. Improvement of pancytopenia and tumor markers was recognized temporarily, and but 3 months later the tumor markers increased again. Four months after introduction of chemotherapy, she died of gastrointestinal hemorrhage.

Activation of protein kinase C delta induces growth arrest in NPA thyroid cancer cells through extracellular signal-regulated kinase mitogen-activated protein kinase.

Protein kinase C (PKC) is a family of serine-threonine kinases that regulate many cell processes. To study the role of PKCdelta in thyroid cancer cells, we used a replication-deficient adenovirus (PKCdeltaAdV), to tightly control PKCdelta expression. In NPA cells, activation of wild-type (WT) PKCdelta with phorbol 12-myristate 13-acetate (PMA) induced an arrest in cell growth at G(1) phase, which was itself inhibited by the PKCdelta inhibitor rottlerin. Furthermore, overexpression of a dominant negative PKCdelta did not induce G(1) arrest. These findings strongly suggested that PKCdelta induced cell growth arrest in NPA cells. We investigated the mechanism of G1 arrest by examining G(1)-related proteins and mitogen-activated protein kinase (MAPK) by Western blotting. After activation of WTPKCdelta with PMA, cyclin E expression and retinoblastoma protein (Rb) phosphorylation decreased; the expression of p27(Kip1) increased and the phosphorylation of extracellular signal-regulated kinase (ERK) MAPK decreased. These results indicated that the activation of PKCdelta induced cell growth arrest in NPA cells, through an ERK MAPK-p27(Kip1)-cyclin E-pRb pathway. PKCdelta may therefore be an effective molecular target for novel therapy in thyroid cancer.

Axillary lymph node recurrence of papillary thyroid microcarcinoma: report of a case.

We report a case of axillary lymph node recurrence of thyroid papillary microcarcinoma (PMC) in a 51-year-old woman who had undergone thyroidectomy with lymph node dissection 5 years earlier. We performed residual thyroid resection with cervical and bilateral axillary lymph node dissection, and pathological examination revealed well-differentiated papillary carcinoma, with partial poor differentiation. Postoperative radioiodine therapy was ineffective, and the patient died of systemic dissemination of the recurrence 8 months after her second operation. The positive cell rates of proliferating cell nuclear antigen and Ki-67 were clearly higher in the recurrent lymph nodes than in the primary thyroid tumor, suggesting increased cell proliferation in the recurrent lymph nodes. Thyroid papillary carcinoma rarely recurs in the axillary lymph nodes, but its possibility must be kept in mind, especially in patients with remarkable cervical lymph node metastasis and those who undergo extensive lymph node dissection.

Adult-type ganglioneuroblastoma in the adrenal gland treated by a laparoscopic resection: report of a case.

A case of ganglioneuroblastoma in the adrenal gland of a 50-year-old man is reported. The patient was incidentally found to have a nonfunctioning tumor in the right adrenal gland. The tumor, measuring 4.5 cm, was successfully removed using laparoscopy. Histologically, the tumor was diagnosed to be a ganglioneuroblastoma. Immunohistochemically, a few MIB-1-positive cells and no S-100 protein-positive cells were observed. There has been no evidence of recurrence for 2.5 years to date after the operation. Adrenal ganglioneuroblastoma is extremely rare in adults, and only seven such cases have been previously reported in the literature.

Mutated p53 gene encodes a nonmutated epitope recognized by HLA-B*4601-restricted and tumor cell-reactive CTLs at tumor site.

Mutations of p53 gene occur in approximately 50% of human cancers, and accumulated p53 protein may be an appropriate target molecule to use for cancer immunotherapy. Indeed, mutated or nonmutated p53-derived peptides can induce HLA class I-restricted and tumor cell-reactive CTLs in vitro. However, to our knowledge, evidence that p53-derived peptides are truly recognized by CTLs at tumor sites has not yet been obtained. This study revealed that a mutated p53 gene encoded a nonmutated nonapeptide recognized by a HLA-B46-restricted and tumor cell-reactive CTL line that was established from T cells infiltrating a colon cancer lesion with the p53 mutation. This p53 peptide, at amino acid positions 99-107, had the ability to induce HLA-B46-restricted and peptide-specific CTLs reactive to tumor cells with the p53 mutation from the peripheral blood mononuclear cells of cancer patients, but not from those of healthy donors. These peptide-induced CTLs did not react to either HLA-B46(+) tumor cells without the p53 mutation or to HLA-B46(+) phytohemagglutinin-blastoid cells. These results provide a scientific basis for the development of p53-directed specific immunotherapy for HLA-B46(+) cancer patients.