Mitsuhiko Iwamoto

Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas

DCs are the most potent antigen‐presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation‐specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti‐CD1a antibody for immature DCs and an anti‐CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a+ TIDCs, and 82 (63.1%) samples contained CD83+ TIDCs. The number of CD83+ TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF‐β, whereas the number of CD1a+ TIDCs was not. Kaplan‐Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83+ TIDCs with longer relapse‐free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83+ TIDCs was significantly better than that of patients with fewer CD83+ TIDCs. Multivariate analysis revealed that CD83+ TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.

A novel method using the VIO soft-coagulation system for liver resection

BACKGROUND The VIO soft-coagulation system (SCS) is a new device for tissue coagulation. The current study evaluated the efficacy of the SCS when used for liver resection. METHODS The 252 patients were divided into 2 groups; in 155 patients (conventional group), liver transection was performed using an ultrasonic dissector and saline-coupled bipolar electrocautery for hemostasis. In 97 patients (SCS group), the SCS was used instead of bipolar electrocautery. RESULTS The median blood loss and surgical time were less in the SCS group than in the conventional group (350 vs 640 mL, P = .0028; 280 vs 398 min, P < .0001). No significant differences were found in postoperative complications between the SCS group (32.0%) and the conventional group (40.6%). The risk factors for bleeding were nonuse of the SCS (P = .0039), macroscopic vascular invasion of the hepatic tumors (P = .0088), and collagen type IV value in the sera >200 (P = .0250) on multivariate analysis. In a subgroup analysis, in the collagen type IV value >200 subgroup, the tumor diameter >5 cm subgroup, and the inflow nonocclusion subgroup, use of the SCS decreased surgical bleeding (P = .0120, P = .0126, and P = .0032, respectively) and surgical time (P = .0001, P < .0001, and P = .0036, respectively) compared with the conventional group. Furthermore, even in the major hepatectomy group, the SCS use decreased surgical time (P < .0001). CONCLUSION The SCS is an effective and safe device for decreasing surgical time and surgical bleeding without increasing the rate of bile leakage and causing other complications.

Hepatobiliary Cystadenoma Combined with Multiple Liver Cysts: Report of a Case

Abstract Hepatobiliary cystadenomas are rare benign tumors with malignant potential. They are almost always solitary lesions accompanied by multilocular cysts in the liver, and are difficult to differentiate from cystadenocarcinoma, despite the diagnostic modalities available. This report describes a case of hepatobiliary cystadenoma with multiple cysts in the left hepatic lobe, diagnosed by magnetic resonance imaging in a 48-year-old woman. Abdominal computed tomography revealed only multiple cystic lesions in the left lobe, but cholangiography via a nasogastric biliary drainage tube combined with percutaneous transhepatic cholangiography showed a stenotic region with fine irregularity in the left lateral posterior segmental bile duct and left lateral anterior segmental bile duct. Hepatobiliary cystadenocarcinoma with multiple liver cysts was suspected. We performed left hepatectomy, and microscopic examination confirmed a diagnosis of hepatic cystadenoma with multiple liver cysts. There was no nuclear atypia or mitosis in the epithelium of the locus, which was constructed of simple columnar-to-cuboidal epithelium with basal nuclei. The patient is well without recurrence more than 4 years after surgery.

Breast Conserving Surgery Using Volume Replacement with Oxidized Regenerated Cellulose: A Cosmetic Outcome Analysis

We evaluated the cosmetic outcome of volume replacement with oxidized regenerated cellulose (ORC) after breast‐conserving surgery (BCS) and also examined factors that may have influenced the results. Ninety‐four patients who underwent BCS with ORC replacement between January 2010 and August 2012 participated in this study. The cosmetic outcomes of these patients were evaluated using scores based on the criteria of the Japan Breast Cancer Society. We evaluated cosmetic scores with regards to several clinical factors and the occurrence of complications after this procedure. The mean score of the cosmetic outcome of all patients was 9.5 points of 12 points. Thirty‐seven patients were categorized as “Excellent,” 34 were “Good,” 22 were “Fair,” and 1 was “Poor.” Patient age, body mass index, weight of the specimen, and ORC amount were not significantly different between patients with favorable cosmetic scores and those without. However, the weight of the removed specimen was slightly higher in patients with an unfavorable cosmetic score. Although acute dermatitis and eczema was observed in 15% and 3% of patients, all of them were improved with conservative treatment. Cosmetic scores were significantly higher in patients without complications than in patients with complications. In conclusion, ORC replacement after BCS is a simple and reliable procedure. The selection of indication and prevention of complications are important for obtaining a better cosmetic outcome. This is the first report to cosmetically evaluate a relatively large number of patients that have undergone ORC replacement after BCS.

Phase II Study of Neoadjuvant Anthracycline- Based Regimens Combined With Nanoparticle Albumin-Bound Paclitaxel and Trastuzumab for Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer

UNLABELLED We treated patients with operable human epidermal growth factor receptor 2-positive breast cancer with neoadjuvant anthracycline regimens followed by nanoparticle albumin-bound paclitaxel plus trastuzumab. Of the 44 patients, 49% achieved a pathologic complete response (pCR). The pCR rate was 36% and 71% in the patients with estrogen receptor-positive and -negative cancer, respectively. Neoadjuvant therapy using this combination appears to be effective and safe. Introduction: Neoadjuvant chemotherapy plus trastuzumab. INTRODUCTION Neoadjuvant chemotherapy plus trastuzumab results in a 30% to 50% pathologic complete response (pCR) rate in human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been associated with improved therapeutic outcomes. Thus, the pCR rate can be useful in evaluating novel agents in this patient population. Nanoparticle albumin-bound (nab)-paclitaxel (PTX) can reduce the toxicity of PTX while maintaining its efficacy. The present study evaluated the activity and safety of nab-PTX as a neoadjuvant treatment of HER2(+) breast cancer. PATIENTS AND METHODS We treated patients with stage I to IIIA breast cancer using neoadjuvant epirubicin/cyclophosphamide (EC) or 5-fluorouracil/epirubicin/cyclophosphamide every 3 weeks (q3w) for 4 cycles, followed by nab-PTX (260 mg/m(2)) plus trastuzumab q3w for 4 cycles. The primary endpoint was the pCR rate. The secondary endpoints included the clinical response rate, disease-free survival, pathologic response rate (defined as pCR or minimal residual invasive disease only in the breast), breast-conserving surgery rate, and safety. RESULTS Forty-six patients were enrolled. One patient met the exclusion criteria because of the coexistence of another malignant disease; therefore, we evaluated 45 patients in the entire study. One patient experienced rapid disease progression during EC therapy, leaving 44 patients evaluable for nab-PTX treatment. Of the 45 patients, 49% achieved a pCR. The pCR rate was 36% and 71% in those with estrogen receptor-positive and -negative cancer, respectively. Of all the study treatments, the most frequent reason for delay or dose reduction was hematologic toxicity; only 1 patient required a dose reduction for nab-PTX because of peripheral neuropathy. CONCLUSION Neoadjuvant therapy using this combination appears to be effective and safe.

Safety of nanoparticle albumin‑bound paclitaxel administered to breast cancer patients with clinical contraindications to paclitaxel or docetaxel: Four case reports

Taxanes, including paclitaxel (PTX) and docetaxel (DOC), are poorly soluble in water due to their hydrophobic properties and thus, require solvents. However, use of these solvents has been associated with toxic responses, including a hypersensitivity reaction (HSR). Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel formulation of PTX, which allows reconstitution of the agent with a saline solution instead of solvents and administration without premedication for HSRs. The current study reports the safe administration of nab-PTX to four breast cancer patients considered clinically to have contraindications to PTX or DOC. Two of the patients had previously experienced HSRs to PTX or DOC and the other two patients had contraindications to steroids as a premedication for HSRs, since one patient suffered from diabetes and the other was a carrier of the hepatitis B virus. All 4 patients were safely administered nab-PTX. In conclusion, administration of nab-PTX appears to be effective for patients that have previously experienced HSRs to other taxanes or in those with contraindications to steroids.

Validation of online calculators to predict the non-sentinel lymph node status in sentinel lymph node-positive breast cancer patients

PurposeThis study evaluated and compared the predictive values of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Stanford nomogram for predicting non-sentinel lymph node (SLN) metastasis in patients with SLN metastasis, which were the only nomograms available online, and verified their usefulness in the macrometastasis or micrometastasis/isolated tumor cell (ITC) subgroups.MethodsEighty-nine patients with a positive SLN biopsy who underwent axillary lymph node dissection were analyzed. The predicted probability of non-SLN metastasis was calculated using a computerized model from the websites for each nomogram. The results were compared using the area under the curve (AUC) of the receiver operating characteristics curve for each model. The false-negative and false-positive rates were also calculated.ResultsThe AUC for the entire population was 0.701 with the MSKCC nomogram and 0.756 with the Stanford nomogram. The AUCs of macrometastasis and micrometastasis/ITC groups were 0.680 and 0.469 with the MSKCC nomogram, and were 0.676 and 0.574 with the Stanford nomogram, respectively. Although false-negative cases were not identified, the false-positive rates were high in both subgroups when using these nomograms.ConclusionsThis independent comparison found no significant difference between the two nomograms. In this study, these nomograms could not reliably predict positive non-SLN in patients with SLN micrometastasis/ITC.

Association between body mass index and breast cancer intrinsic subtypes in Japanese women

The purpose of this study was to examine the association between body mass index (BMI) and breast cancer intrinsic subtypes in Japanese women. A more complete understanding of the subtypes of breast cancer may elucidate the mechanisms affecting the etiology and mortality associated with each subtype. Tumor data on 531 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (Her2) status were obtained [luminal A, luminal B, triple-negative (TN) and Her2-type]. Demographics (age at diagnosis, menopausal status and BMI) were collected from medical records. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis. Of the 531 cases, 333 (62.7%) were luminal A, 85 (16.0%) were luminal B, 43 (8.1%) were Her2-type and 70 (13.2%) were TN. Compared with luminal A cases, premenopausal TN cases were more likely to be obese (OR, 4.11; 95% CI, 1.10–14.40), while postmenopausal TN cases were more likely to be underweight (OR, 3.14; 95% CI, 1.19–8.01). Premenopausal luminal B cases were likely to be underweight or obese, while luminal B and Her2-type cases were likely to be underweight. In the present study, significant heterogeneity of associations between BMI and tumor subtypes was observed. Breast cancer subtypes may have various etiologies associated with each subtype.

Comparative proteomic analysis of paclitaxel resistance‑related proteins in human breast cancer cell lines

Paclitaxel is widely used to treat various cancers; however, resistance to this drug is a major obstacle to breast cancer chemotherapy. To identify the proteins involved in paclitaxel resistance, the present study compared the proteomes of MCF-7 human breast cancer cells and its paclitaxel-resistant subclone MCF-7/PTX. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry, 11 upregulated and 12 downregulated proteins were identified in MCF-7/PTX cells compared with the parental cell line. These 23 proteins were functionally classified as stress-induced chaperones, metabolic enzymes and cytoskeletal proteins. The anti-apoptotic proteins, stress-70 protein, 78-kD glucose-regulated protein, peptidyl-prolyl cis-trans isomerase A (PPIA) and heterogeneous nuclear ribonucleoprotein H3, were also upregulated in MCF-7/PTX cells. Notably, knockdown of the stress-response chaperone PPIA using small interfering RNA in MCF-7/PTX cells restored their sensitivity to paclitaxel. These findings indicated that PPIA may have an important role in paclitaxel resistance in MCF-7/PTX cells.

Esthetic result of rhomboid flap repair after breast-conserving surgery for lower quadrant breast cancer lesion with skin invasion: Report of two cases

Breast-conserving surgery (BCS) has been increasingly performed as a standard operative strategy for patients with breast cancer. The primary purpose of BCS is to acquire both local control and good cosmetic results. An insignificant difference in cancer treatment results has been shown between BCS and total mastectomy. However, achieving sufficiently cosmetic results can be difficult, particularly in patients with tumors that are large or localized to the lower quadrant. To avoid breast deformities and asymmetries after BCS, immediate reconstruction using autologous tissue has been accepted as the standard option. Rhomboid skin and adipose flap repair is a simple, less invasive procedure than the myocutaneous flap, which has primarily been performed in patients with upper quadrant lesions. We herein report the cases of two patients with lower quadrant breast cancer with skin invasion, who underwent BCS with immediate breast repair using a rhomboid flap. This procedure is therefore worth considering as one of the first options for immediate repair after BCS.