[Long-Term Survival of a Patient with Triple-Negative Breast Cancer with Hormone Receptor Status Conversion between Primary and Metastatic Tumors].

Patients with triple-negative breast cancer have poor survival after recurrence. However, previous studies have shown that receptor conversion can occur between primary breast tumor and metastatic sites. Herein, we describe the case of a 54- year-old woman with advanced breast cancer, which showed receptor conversion from primary tumor(triple-negative)to distant metastases(Luminal type). The patient had undergone left radical mastectomy and left axillary lymph node dissection at another hospital(pT3N0M0, Stage ⅡB, ER-negative, PgR-negative, and HER2-negative). She was referred to our hospital for adjuvant chemotherapy with 3 courses of 5-fluorouracil, epirubicin, and cyclophosphamide and 3 courses of docetaxel. Around 26 months after the surgery, the follow-up CT scan showed multiple lung nodules. Another 9 months later, her left axillary and mediastinal lymph nodes were enlarged. She received several courses of anticancer chemotherapy. After paclitaxel and bevacizumab were administered as seventh-line chemotherapy, a vacuum-assisted biopsy of the left axillary lymph node was performed to confirm the presence of metastasis. Furthermore, immunohistochemistry results showed that the metastatic tumor was ER-positive, PgR-positive, and HER2-negative. Fulvestrant and palbociclib were then initiated as first-line endocrine therapy. She has been stable for more than 18 months since. It is essential to perform biopsies of metastatic sites for optimal management of patients with metastatic breast cancer.

Influence of Flap Thickness on Nipple Projection After Nipple Reconstruction Using a Modified Star Flap.

BACKGROUND: In nipple reconstruction, the width, length, and thickness of modified star flaps are concerns for long-term reconstructed nipple projection. However, the flap's projection has not been analyzed, based on its thickness. The aim of the present study was to investigate how flap thickness in a modified star flap influences the resulting reconstructed nipple and achieves an appropriate flap width in design. METHODS: Sixty-three patients who underwent nipple reconstruction using a modified star flap following implant-based breast reconstruction between August 2014 and July 2016 were included in this case-controlled study. The length of laterally diverging flaps was 1.5 times their width. The thickness of each flap was measured using ultrasonography, and the average thickness was defined as the flap thickness. We investigated the correlation between the resulting reconstructed nipple and flap thickness, and the difference of the change in the reconstructed nipple projection after using a thin or thick flap. RESULTS: The average flap thickness was 3.8 ± 1.7 (range 2.5-6.0) mm. There was a significant, linear correlation between the flap thickness and resulting reconstructed nipple projection (ß = 0.853, p < 0.01). Furthermore, the difference between the thin and thick flaps in the resulting reconstructed nipple projection was significant (p < 0.01). CONCLUSION: Measuring the flap thickness preoperatively may allow surgeons to achieve an appropriate flap width; otherwise, alternative methods for higher projection might be used. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.

This study investigated the clinical effect of metformin on breast cancer patients with preexisting type 2 diabetes mellitus (T2DM). We analyzed 177 patients with T2DM who underwent breast cancer surgery and assessed tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in patients who underwent tumor resection with or without metformin treatment using multiplex immunohistochemistry (IHC). Patients who received metformin either pre- or postoperatively exhibited reduced distant organ recurrence and improved postoperative recurrence-free survival compared to those of patients who did not. Additionally, in a subgroup of 40 patients receiving preoperative systemic therapy, metformin treatment was associated with increased rates of pathological complete response. IHC analysis revealed significantly lower levels of cluster of differentiation (CD) 68(+) CD163(+) M2-type TAMs (p < 0.01) but higher CD3(+) and CD8(+) TIL densities in the metformin-treated group compared with the same parameters in those without metformin treatment, with a significant difference in the CD8(+)/CD3(+) TIL ratio (p < 0.01). Despite the constraints posed by our small sample size, our findings suggest a potential role for metformin in modulating the immunological microenvironment, which may contribute to improved outcomes in diabetes patients with breast cancer.

Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

BACKGROUND: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. METHODS: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. RESULTS: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively. CONCLUSION: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Efficacy and safety of surgical energy devices for axillary node dissection: a systematic review and network meta-analysis.

Various surgical energy devices are used for axillary lymph-node dissection. However, those that reduce seroma during axillary lymph-node dissection are unknown. We aimed to determine the best surgical energy device for reducing seroma by performing a network meta-analysis to synthesize the current evidence on the effectiveness of surgical energy devices for axillary node dissection for breast cancer patients. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal. Two reviewers independently selected randomized controlled trials (RCTs) comparing electrosurgical bipolar vessel sealing (EBVS), ultrasonic coagulation shears (UCS), and conventional techniques for axillary node dissection. Primary outcomes were seroma, drained fluid volume (mL), and drainage duration (days). We analyzed random-effects and Bayesian network meta-analyses. We evaluated the confidence of each outcome using the CINeMA tool. We registered with PROSPERO (CRD42022335434). We included 34 RCTs with 2916 participants. Compared to the conventional techniques, UCS likely reduces seroma (risk ratio [RR], 0.61; 95% credible interval [CrI], 0.49-0.73), the drained fluid volume (mean difference [MD], - 313 mL; 95% CrI - 496 to - 130), and drainage duration (MD - 1.79 days; 95% CrI - 2.91 to - 0.66). EBVS might have little effect on seroma, the drained fluid volume, and drainage duration compared to conventional techniques. UCS likely reduce seroma (RR 0.44; 95% CrI 0.28-0.69) compared to EBVS. Confidence levels were low to moderate. In conclusion, UCS are likely the best surgical energy device for seroma reduction during axillary node dissection for breast cancer patients.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Peptides derived from human insulin-like growth factor-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells.

Insulin-like growth factor-II mRNA binding protein 3 (IMP-3) is an oncofetal protein expressed in various malignancies including lung cancer. This study aimed to identify immunogenic peptides derived from IMP-3 that can induce tumor-reactive and human leukocyte antigen (HLA)-A2 (A*02:01)-restricted cytotoxic T lymphocytes (CTL) for lung cancer immunotherapy. Forty human IMP-3-derived peptides predicted to bind to HLA-A2 were analyzed to determine their capacity to induce HLA-A2-restricted T cells in HLA-A2.1 (HHD) transgenic mice (Tgm). We found that three IMP-3 peptides primed HLA-A2-restricted CTL in the HLA-A2.1 Tgm. Among them, human CTL lines reactive to IMP-3 (515) NLSSAEVVV(523) were reproducibly established from HLA-A2-positive healthy donors and lung cancer patients. On the other hand, IMP-3 (199) RLLVPTQFV(207) reproducibly induced IMP-3-specific and HLA-A2-restricted CTL from healthy donors, but did not sensitize CTL in the HLA-A2.1 Tgm. Importantly, these two IMP-3 peptide-specific CTL generated from healthy donors and cancer patients effectively killed the cancer cells naturally expressing both IMP-3 and HLA-A2. Cytotoxicity was significantly inhibited by anti-HLA class I and anti-HLA-A2 monoclonal antibodies, but not by the anti-HLA-class II monoclonal antibody. In addition, natural processing of these two epitopes derived from the IMP-3 protein was confirmed by specific killing of HLA-A2-positive IMP-3-transfectants but not the parental IMP-negative cell line by peptide-induced CTL. This suggests that these two IMP-3-derived peptides represent highly immunogenic CTL epitopes that may be attractive targets for lung cancer immunotherapy.

Making the upper edge of a silicone breast implant invisible by fat onlay-grafting harvested from the affected inframammary fold.

BACKGROUND: In silicone breast implant (SBI)-based breast reconstructions, aesthetic outcomes are often low due to the visible upper edge of the SBI. To ameliorate this, grafting fat harvested from the SBI operative field has not been reported to date. Therefore, we aimed to develop a novel technique for fat onlay-grafting, harvested from the inframammary fold (IMF) of the reconstructed breast, and investigate its usefulness. METHODS: A total of 90 patients who underwent SBI-based breast reconstruction after a simple mastectomy were included in this study. The harvested fat was recorded by weight and grafted evenly to the medial and median upper edge of the SBI on the pectoralis major muscle. We applied this technique to 30 patients (fat onlay-grafting group) and compared them with the 60 patients (no-grafting group) who did not undergo our technique using the postoperative 1-year aesthetic outcome scores of the medial and median upper edge of the SBI. Furthermore, we investigated the correlation between the weight of harvested fat and body mass index. RESULTS: No postoperative wound complications occurred, and infection, hardened fat, and fat lysis were not found in the fat onlay-grafting group. The medial and total aesthetic outcome scores in the fat onlay-grafting group were significantly higher than those in the no-grafting group (P<0.05). The average weight of harvested fat was 11.9 [5-32] g. The correlation between the weight of the harvested fat and body mass index was significantly positive (R2=0.7119, P<0.05). CONCLUSIONS: Our technique made the upper edge of the SBI invisible. Further, it was simple and less invasive with safe augmentation. Therefore, we believe that this technique can contribute to better aesthetic outcomes in SBI-based breast reconstruction.

The forkhead box M1 transcription factor as a candidate of target for anti-cancer immunotherapy.

The present study attempted to identify a target antigen for immunotherapy for cholangiocarcinoma. Forkhead box M1 (FOXM1) was selected as a candidate antigen based on the data of previous cDNA microarray analysis of clinical samples of cholangiocarcinoma. The level of FOXM1 mRNA was more than 4 times higher in cancer cells in comparison to adjacent normal epithelial cells, in all of 24 samples of cholangiocarcinoma tissues. An immunohistochemical analysis also detected FOXM1 protein in the cancer cells but not in the normal cells. Twenty-three human FOXM1-derived peptides predicted to bind to HLA-A2 were analyzed to determine their ability to induce HLA-A2-restricted T cells in HLA-A2 transgenic mice. FOXM1(362-370) (YLVPIQFPV), FOXM1(373-382) (SLVLQPSVKV), and FOXM1(640-649) (GLMDLSTTPL) peptides primed HLA-A2-restricted cytotoxic T lymphocytes (CTLs) in the HLA-A2 transgenic mice. Human CTL lines reactive to these 3 peptides could also be established from HLA-A2-positive healthy donors and cancer patients. Natural processing of the 3 epitopes from FOXM1 protein was confirmed by specific killing of HLA-A2-positive FOXM1-transfectants by peptide-induced CTLs. FOXM1 is expressed in various types of cancers and it is also functionally involved in oncogenic transformation and the survival of cancer cells. Therefore, FOXM1 may be a suitable target for immunotherapy against various cancers including cholangiocarcinoma.

Identification of SPARC as a candidate target antigen for immunotherapy of various cancers.

To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2K(d)-restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2K(d)-binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1(143-151) (DYIGPCKYI) and SPARC-A24-4(225-234) (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy.

Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers.

PURPOSE: To establish cancer immunotherapy, it is important to identify the tumor-associated antigens (TAA) that are strongly expressed in the tumor cells but not in the normal cells. In this study, to establish an effective anticancer immunotherapy, we tried to identify the useful TAA of pancreatic cancer. EXPERIMENTAL DESIGN: Based on a previous genome-wide cDNA microarray analysis of pancreatic cancer, we focused on cadherin 3 (CDH3)/P-cadherin as a novel candidate TAA for anticancer immunotherapy. To identify the HLA-A2 (A*0201)-restricted CTL epitopes of CDH3, we used HLA-A2.1 (HHD) transgenic mice (Tgm). Furthermore, we examined the cytotoxicity against the tumor cells in vitro and in vivo of CTLs specific to CDH3 induced from HLA-A2-positive healthy donors and cancer patients. RESULTS: CDH3 was overexpressed in the majority of pancreatic cancer and various other malignancies, including gastric and colorectal cancers, but not in their noncancerous counterparts or in many normal adult tissues. In the experiment using HLA-A2.1 Tgm, we found that the CDH3-4(655-663) (FILPVLGAV) and CDH3-7(757-765) (FIIENLKAA) peptides could induce HLA-A2-restricted CTLs in Tgm. In addition, peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A2-positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both CDH3 and HLA-A2. Furthermore, the adoptive transfer of the CDH3-specific CTLs could inhibit the tumor growth of human cancer cells engrafted into nonobese diabetic/severe combined immunodeficiency mice. CONCLUSIONS: These results suggest that CDH3 is a novel TAA useful for immunotherapy against a broad spectrum of cancers, including pancreatic cancer.

Fusion of MRI and sonography image for breast cancer evaluation using real-time virtual sonography with magnetic navigation: first experience.

OBJECTIVE: We recently developed a real-time virtual sonography (RVS) system that enables simultaneous display of both sonography and magnetic resonance imaging (MRI) cutaway images of the same site in real time. The aim of this study was to evaluate the role of RVS in the management of enhancing lesions visualized with MRI. METHODS: Between June 2006 and April 2007, 65 patients underwent MRI for staging of known breast cancer at our hospital. All patients were examined using mammography, sonography, MRI and RVS before surgical resection. Results were correlated with histopathologic findings. MRI was obtained on a 1.5 T imager, with the patient in the supine position using a flexible body surface coil. Detection rate was determined for index tumors and incidental enhancing lesions (IELs), with or without RVS. RESULTS: Overall sensitivity for detecting index tumors was 85% (55/65) for mammography, 91% (59/65) for sonography, 97% (63/65) for MRI and 98% (64/65) for RVS. Notably, in one instance in which the cancer was not seen on MRI, RVS detected it with the supplementation of sonography. IELs were found in 26% (17/65) of the patients. Of 23 IELs that were detected by MRI, 30% (7/23) of IELs could be identified on repeated sonography alone, but 83% (19/23) of them were identified using the RVS system (P = 0.001). The RVS system was able to correctly project enhanced MRI information onto a body surface, as we checked sonography form images. CONCLUSIONS: Our results suggest that the RVS system can identify enhancing breast lesions with excellent accuracy.

Whole stomach and spleen preserving total pancreatectomy: a new surgical technique for pancreatic cancer.

Total pancreatectomy has been used to treat both benign and malignant diseases of the pancreas. The procedure of total pancreatectomy for invasive pancreatic cancer usually includes distal gastrectomy and splenectomy to prevent ischemic changes due to decreased blood supply. In this report, it was introduced a new technique of total pancreatectomy for invasive pancreatic cancer preserving both the whole stomach and spleen. The patient was a 61 year old man. Preoperative computed tomography (CT) showed a mass of tumor, measuring 23x18x25mm, located in the pancreatic head. It was tried, initially to perform pylorus-preserving pancreatoduodenectomy (PPPD). Repeated frozen section examination of the pancreatic stumps, however, revealed persistent cancer infiltration to the distal pancreas. Therefore, we altered the planned PPPD to total pancreatectomy preserving the whole stomach and spleen with severing both the splenic artery and vein at their origins. The postoperative course was uneventful. Enhanced CT following surgery showed sufficient blood supply to the whole stomach and spleen without any congestive changes of blood flow. This method is considered safe and useful for patients with both benign and malignant disease of the pancreas.

HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL.

Toward the development of a novel cancer immunotherapy, we have previously identified several tumor-associated antigens (TAAs) and the epitopes recognized by human histocompatibility leukocyte (HLA)-A2/A24-restricted cytotoxic T lymphocyte (CTL). In this study, we tried to identify a TAA of lung cancer (LC) and its HLA-A2 restricted CTL epitopes to provide a target antigen useful for cancer immunotherapy of LC. We identified a novel cancer testis antigen, cell division cycle associated gene 1 (CDCA1), overexpressed in nonsmall cell LC using a cDNA microarray analysis. The expression levels of CDCA1 were also increased in the majority of small cell LC, cholangiocellular cancer, urinary bladder cancer and renal cell cancers. We used HLA-A2.1 transgenic mice to identify the HLA-A2 (A*0201)-restricted CDCA1 epitopes recognized by mouse CTL, and we investigated whether these peptides could induce CDCA1-reactive CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A2-positive donors and a NSCLC patient. Consequently, we found that the CDCA1(65-73) (YMMPVNSEV) peptide and CDCA1(351-359) (KLATAQFKI) peptide could induce peptide-reactive CTLs in HLA-A2.1 transgenic mice. In HLA-A2(+) donors, in vitro stimulation of PBMC with these peptides could induce peptide-reactive CTLs which killed tumor cell lines endogenously expressing both HLA-A2 and CDCA1. As a result, CDCA1 is a novel cancer-testis antigen overexpressed in LC, cholangiocellular cancer, urinary bladder cancer and renal cell cancers, and CDCA1 may therefore be an ideal TAA useful for the diagnosis and immunotherapy of these cancers.

[The significance of combined treatment for hepatocellular carcinoma with partial splenic embolization and transcatheter arterial chemoembolization using IA call/lipiodol].

BACKGROUND AND AIM: Partial splenic embolization (PSE) is often performed to improve thrombocytopenia in liver cirrhotic patients. The aim of this study was to evaluate the efficacy and safety of PSE in combination with trans-catheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From January 2004 to December 2007, 8 HCC patients associated with hypersplenism caused by cirrhosis were synchronously treated with TACE and PSE. Fifteen patients with TACE alone at the same period were enrolled as a control. Follow-up examinations included a calculation of peripheral blood cells (leukocytes and platelets), liver damage, duration until recovery, and treatment-associated complications. RESULTS: Initially, there were no significant differences in sex, age, Child-Pugh grade and peripheral blood cell counts between two groups. After treatment, leukocyte and platelet counts were significantly higher in PSE combined with TACE group during the follow-up period than TACE group (p<0.01). Severe complications never occurred in both groups. CONCLUSION: PSE combined with TACE is more effective than TACE alone for patients with HCC associated with hypersplenism caused by cirrhosis.

Individual difference in pectoralis major muscle thickness and its effect on single-stage breast reconstruction using a tissue expander.

BACKGROUND: In breast reconstruction using a tissue expander (TE), sufficient coverage of the TE with the pectoralis major (PM) muscle, particularly with a musculofascial flap, is highly important for avoiding postoperative complications. In patients in whom the PM is thin, intraoperative trauma often occurs, leading to troublesome repair. The present study aimed to investigate the usefulness of preoperative measurement of PM thickness in planning of breast reconstruction using a TE. METHODS: In this case-control study, we identified 68 patients (70 breasts) with mammary carcinoma treated with simple mastectomy and TE insertion from April 2014 to December 2016. We measured average PM thickness at two specific points, sternocostal PM distance on the long axis and sternocostal PM area preoperatively using magnetic resonance imaging. Then, we analyzed the difference in PM thickness among individuals and its relationship to intraoperative trauma to the PM or surgical difficulty creating a muscular pocket (delicate PM). RESULTS: Average PM thickness was significantly larger in younger patients (p = 0.046) and those with larger breasts (p < 0.01). In addition, average PM thickness on the affected side was significantly smaller in patients with delicate PM (12 breasts) (p < 0.01). PM thickness had a significant influence on delicate or firm PM (odds ratio 27.40; 95% confidence interval 2.01-372.00; p = 0.013). CONCLUSION: These findings demonstrate the usefulness of preoperative measurement of PM thickness in planning of breast reconstruction using a TE. Dissection should be performed more carefully in patients with average PM thickness less than 2.9 mm.

Peritoneal cancer arising after total abdominal hysterectomy and bilateral salpingo-oophorectomy for cervical cancer in a patient with right breast cancer and germline mutation of BRCA1 gene: a case report and literature review.

Primary peritoneal carcinoma is usually advanced at diagnosis and curability is low unless the patient has a small tumor burden. Peritoneal carcinoma can occur in association with hereditary breast and ovarian cancer syndrome, which is thought to account for 5-6% of all breast cancer. Mutations of two breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for hereditary breast and ovarian cancer. Women with BRCA1/2 mutations often undergo risk-reducing salpingo-oophorectomy (RRSO) to prevent both ovarian and breast cancer. However, peritoneal carcinoma has been reported to develop after RRSO in patients with BRCA1/2 mutations. We experienced a patient with peritoneal carcinoma and inguinal lymph node metastasis after surgical resection of breast cancer and subsequent RRSO. This report describes the first case of peritoneal carcinoma arising after RRSO in a Japanese patient with BRCA1 mutation, including a review of the literature on peritoneal carcinoma associated with BRCA1/2 mutation.

Identification of HLA-A2- or HLA-A24-restricted CTL epitopes possibly useful for glypican-3-specific immunotherapy of hepatocellular carcinoma.

PURPOSE AND EXPERIMENTAL DESIGN: We previously reported that glypican-3 (GPC3) was overexpressed, specifically in hepatocellular carcinoma (HCC) and melanoma in humans, and it was useful as a novel tumor marker. We also reported that the preimmunization of BALB/c mice with dendritic cells pulsed with the H-2K(d)-restricted mouse GPC3(298-306) (EYILSLEEL) peptide prevented the growth of tumor-expressing mouse GPC3. Because of similarities in the peptide binding motifs between H-2K(d) and HLA-A24 (A*2402), the GPC3(298-306) peptide therefore seemed to be useful for the immunotherapy of HLA-A24+ patients with HCC and melanoma. In this report, we investigated whether the GPC3(298-306) peptide could induce GPC3-reactive CTLs from the peripheral blood mononuclear cells (PBMC) of HLA-A24 (A*2402)+ HCC patients. In addition, we used HLA-A2.1 (HHD) transgenic mice to identify the HLA-A2 (A*0201)-restricted GPC3 epitopes to expand the applications of GPC3-based immunotherapy to the HLA-A2+ HCC patients. RESULTS: We found that the GPC3(144-152) (FVGEFFTDV) peptide could induce peptide-reactive CTLs in HLA-A2.1 (HHD) transgenic mice without inducing autoimmunity. In five out of eight HLA-A2+ GPC3+ HCC patients, the GPC3(144-152) peptide-reactive CTLs were generated from PBMCs by in vitro stimulation with the peptide and the GPC3(298-306) peptide-reactive CTLs were also generated from PBMCs in four of six HLA-A24+ GPC3+ HCC patients. The inoculation of these CTLs reduced the human HCC tumor mass implanted into nonobese diabetic/severe combined immunodeficiency mice. CONCLUSION: Our study raises the possibility that these GPC3 peptides may therefore be applicable to cancer immunotherapy for a large number of HCC patients.

Breast reconstruction of an unusual configuration using two paranemic implants.

Implant-based breast reconstruction can be performed using a choice of various types of breast implants. However, cases where the breast shapes are unsuitable for implant-based reconstruction method are occasionally encountered. We present two patients with wide trunks who underwent breast reconstruction using an unusual configuration that involved a latissimus dorsi myocutaneous flap combined with two paranemic implants.

Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm3. The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully.